Patent application title: ANTI-SERUM ALBUMIN BIDING VARIABLE DOMAINS
Inventors:
Edward Coulstock (Cambridge, GB)
Elena De Angelis (Cambridge, GB)
Haiqun Liu (Cambridge, GB)
Haiqun Liu (Cambridge, GB)
Oliver Schon (Cambridge, GB)
Oliver Schon (Cambridge, GB)
Assignees:
GLAXO GROUP LIMITED
IPC8 Class: AC07K1618FI
USPC Class:
4241341
Class name: Immunoglobulin, antiserum, antibody, or antibody fragment, except conjugate or complex of the same with nonimmunoglobulin material structurally-modified antibody, immunoglobulin, or fragment thereof (e.g., chimeric, humanized, cdr-grafted, mutated, etc.) antibody, immunoglobulin, or fragment thereof fused via peptide linkage to nonimmunoglobulin protein, polypeptide, or fragment thereof (i.e., antibody or immunoglobulin fusion protein or polypeptide)
Publication date: 2014-05-22
Patent application number: 20140140996
Abstract:
The invention relates to improved anti-serum albumin immunoglobulin
single variable domains, as well as ligands and drug conjugates
comprising such variable domains, compositions, nucleic acids, vectors
and hosts.Claims:
1. An anti-serum albumin (SA) immunoglobulin single variable domain
comprising an amino acid sequence that is at least 80% identical to an
amino acid sequence selected from SEQ ID NOs: 97 to 191 and 198 to 203.
2. An anti-serum albumin (SA) immunoglobulin single variable domain comprising an amino acid sequence having up to 4 amino acid changes compared to an amino acid sequence selected from SEQ ID NOs: 97 to 191 and 198 to 203.
3. An anti-serum albumin (SA) immunoglobulin single variable domain comprising an amino acid sequence that is encoded by a nucleotide sequence which is at least 80% identical to a sequence selected from SEQ ID NOs 1 to 96 and 192 to 197.
4. The variable domain of claim 1, wherein the variable domain comprises the amino acid sequence of any one of SEQ ID NOs: 97 to 103 and 198 to 203.
5. The variable domain of claim 1, comprising a binding site that specifically binds human SA with a dissociation constant (KD) of from about 0.1 to about 10000 nM, optionally from about 1 to about 6000 nM, as determined by surface plasmon resonance.
6. The variable domain of claim 1, comprising a binding site that specifically binds human SA with an off-rate constant (Kd) of from about 1.5.times.10.sup.-4 to about 0.1 sec-1, optionally from about 3.times.10.sup.-4 to about 0.1 sec as determined by surface plasmon resonance.
7. The variable domain of claim 1, comprising a binding site that specifically binds human SA with an on-rate constant (Ka) of from about 2.times.10.sup.6 to about 1.times.10.sup.4 M-1sec-1, optionally from about 1.times.10.sup.6 to about 2.times.10.sup.4M-1sec-1 as determined by surface plasmon resonance.
8. The variable domain of claim 1, comprising a binding site that specifically binds Cynomolgus monkey SA with a dissociation constant (KD) of from about 0.1 to about 10000 nM, optionally from about 1 to about 6000 nM, as determined by surface plasmon resonance.
9. The variable domain of claim 1, comprising a binding site that specifically binds Cynomolgus monkey SA with an off-rate constant (Kd) of from about 1.5.times.10.sup.-4 to about 0.1 sec-1, optionally from about 3.times.10.sup.-4 to about 0.1 sec-1 as determined by surface plasmon resonance.
10. The variable domain of claim 1, comprising a binding site that specifically binds Cynomolgus monkey SA with an on-rate constant (Ka) of from about 2.times.10.sup.6 to about 1.times.10.sup.4M-1sec-1, optionally from about 1.times.10.sup.6 to about 5.times.10.sup.3M-1sec-1 as determined by surface plasmon resonance.
11. The variable domain of claim 1, wherein the variable domain has a melting temperature (Tm) of at least 55 degrees centigrade, optionally 55.ltoreq.Tm≦75 degrees centigrade, as determined by DSC (differential scanning calorimetry).
12. The variable domain of claim 1, wherein the variable domain is substantially monomeric as determined by SEC-MALLS (size exclusion chromatography with multi-angle-LASER-light-scattering).
13. A multispecific ligand comprising an anti-SA variable domain of claim 1 and a binding moiety that specifically binds a target antigen other than SA, optionally wherein the binding moiety is an TNFR1 antagonist.
14. An anti-SA single variable domain of claim 1, wherein the variable domain is conjugated to a drug (optionally an NCE drug).
15. A fusion protein comprising a polypeptide or peptide drug fused to a variable domain according to claim 1.
16. A composition comprising a variable domain, fusion protein or ligand of claim 1 and a pharmaceutically acceptable diluent, carrier, excipient or vehicle.
17. A nucleic acid comprising a nucleotide sequence encoding a variable domain according to claim 1.
18. A vector comprising the nucleic acid of claim 17.
19. An isolated host cell comprising the vector of claim 18.
20. A method of treating or preventing a disease or disorder in a patient, comprising administering at least one dose of a variable domain according to claim 1.
Description:
[0001] This application is a continuation of U.S. application Ser. No.
13/384,316, filed Jan. 16, 2012, which is a 371 of International
Application No. PCT/EP2010/060112, filed 14 Jul. 2010, which claims the
benefit of U.S. Provisional Application Nos. 61/226,028, filed 16 Jul.
2009 and 61/307,554 filed 24 Feb. 2010, which are incorporated by
reference in their entireties.
[0002] The invention relates to improved anti-serum albumin immunoglobulin single variable domains, as well as ligands and drug conjugates comprising such domains, compositions, nucleic acids, vectors and hosts.
BACKGROUND OF THE INVENTION
[0003] WO04003019 and WO2008/096158 disclose anti-serum albumin (SA) binding moieties, such as anti-SA immunoglobulin single variable domains (dAbs), which have therapeutically-useful half-lives. These documents disclose monomer anti-SA dAbs as well as multi-specific ligands comprising such dAbs, eg, ligands comprising an anti-SA dAb and a dAb that specifically binds a target antigen, such as TNFR1. Binding moieties are disclosed that specifically bind serum albumins from more than one species, eg human/mouse cross-reactive anti-SA dAbs.
[0004] WO05118642 and WO2006/059106 disclose the concept of conjugating or associating an anti-SA binding moiety, such as an anti-SA immunoglobulin single variable domain, to a drug, in order to increase the half-life of the drug. Protein, peptide and NCE (chemical entity) drugs are disclosed and exemplified. WO2006/059106 discloses the use of this concept to increase the half-life of insulintropic agents, eg, incretin hormones such as glucagon-like peptide (GLP)-1.
[0005] Reference is also made to Holt et al, "Anti-Serum albumin domain antibodies for extending the half-lives of short lived drugs", Protein Engineering, Design & Selection, vol 21, no 5, pp 283-288, 2008.
[0006] It would be desirable to provide improved heavy chain variable domain dAbs that specifically bind serum albumin, preferably albumins from human and non-human species, which would provide utility in animal models of disease as well as for human therapy and/or diagnosis. It would also be desirable to provide for the choice between relatively modest- and high-affinity anti-SA binding moieties (dAbs). Such moieties could be linked to drugs, the anti-SA binding moiety being chosen according to the contemplated end-application. This would allow the drug to be better tailored to treating and/or preventing chronic or acute indications, depending upon the choice of anti-SA binding moiety. It would also be desirable to provide anti-SA dAbs that are monomeric or substantially so in solution. This would especially be advantageous when the anti-SA dAb is linked to a binding moiety, eg, a dAb, that specifically binds a cell-surface receptor, such as TNFR1, with the aim of antagonizing the receptor. The monomeric state of the anti-SA dAb is useful in reducing the chance of receptor cross-linking, since multimers are less likely to form which could bind and cross-link receptors (eg, TNFR1) on the cell surface, thus increasing the likelihood of receptor agonism and detrimental receptor signaling. It would also be desirable to provide anti-SA dAbs that have relatively high melting temperatures. This is useful for providing stable formulations, eg, storage-stable formulations and variable domains that have a good shelf-life.
SUMMARY OF THE INVENTION
[0007] Aspects of the present invention solve these problems.
[0008] In one aspect the invention, therefore, there is provided an anti-serum albumin (SA) immunoglobulin single variable domain comprising an amino acid sequence that is at least 80% identical to an amino acid sequence selected from SEQ ID NOs: 97 to 191 and 198 to 203.
[0009] An aspect of the invention provides an anti-serum albumin (SA) immunoglobulin single variable domain comprising an amino acid sequence having up to 4 amino acid changes compared to an amino acid sequence selected from SEQ ID NOs: 97 to 191 and 198 to 203.
[0010] An aspect of the invention provides an anti-serum albumin (SA) immunoglobulin single variable domain comprising an amino acid sequence that is encoded by a nucleotide sequence which is at least 80% identical to a sequence selected from SEQ ID NOs 1 to 96 and 192-197.
[0011] An aspect of the invention provides a multispecific ligand comprising an anti-SA variable domain of the invention and a binding moiety that specifically binds a target antigen other than SA.
[0012] An aspect of the invention provides an anti-SA single variable domain of the invention, wherein the variable domain is conjugated to a drug (optionally an NCE drug).
[0013] An aspect of the invention provides a fusion product, eg, a fusion protein or fusion with a peptide or NCE (new chemical entity) drug, comprising a polypeptide, protein, peptide or NCE drug fused or conjugated (for an NCE) to any anti-SA variable domain of the invention. For example, the variable domain comprises or consists of the amino acid sequence of any one of SEQ ID NOs: 97 to 103 and 198 to 203 (or an amino acid sequence that is at least 95, 96, 97, 98 or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 97 to 103 and 198 to 203).
[0014] An aspect of the invention provides a composition comprising a variable domain, fusion protein or ligand of the invention and a pharmaceutically acceptable diluent, carrier, excipient or vehicle.
[0015] An aspect of the invention provides a nucleic acid comprising a nucleotide sequence encoding a variable domain, or a multispecific ligand or fusion protein of the invention.
[0016] An aspect of the invention provides a nucleic acid comprising a nucleotide sequence that is at least 80% identical to a sequence selected from SEQ ID NOs 1 to 96 and 192-197.
[0017] An aspect of the invention provides a vector comprising the nucleic acid of the invention.
[0018] An aspect of the invention provides an isolated host cell comprising the vector of the invention.
[0019] An aspect of the invention provides a method of treating or preventing a disease or disorder in a patient, comprising administering at least one dose of a variable domain, or a multispecific ligand or fusion protein of the invention to said patient.
[0020] Embodiments of any aspect of the invention provide anti-serum albumin single variable domains of good anti-serum albumin affinities. The choice of variable domain can allow for tailoring of half-life according to the desired therapeutic and/or prophylactic setting. For example, in one embodiment, the affinity of the variable domain for serum albumin is relatively high, such that the variable domain would be useful for inclusion in products that find utility in treating and/or preventing chronic or persistent diseases, conditions, toxicity or other chronic indications. In one embodiment, the affinity of the variable domain for serum albumin is relatively modest, such that the variable domain would be useful for inclusion in products that find utility in treating and/or preventing acute diseases, conditions, toxicity or other acute indications. In one embodiment, the affinity of the variable domain for serum albumin is intermediate, such that the variable domain would be useful for inclusion in products that find utility in treating and/or preventing acute or chronic diseases, conditions, toxicity or other acute or chronic indications.
[0021] It is conceivable that a molecule with an appropriately high affinity and specificity for serum albumin would stay in circulation long enough to have the desired therapeutic effect. (Tomlinson, Nature Biotechnology 22, 521-522 (2004)). Here, a high affinity anti-SA variable domain would stay in serum circulation matching that of the species' serum albumin (WO2008096158). Once in circulation, any fused therapeutic agent to the AlbudAb variable domain, be it NCE, peptide or protein, consequently would be able to act longer on its target and exhibit a longer lasting therapeutic effect. This would allow for targeting chronic or persisitent diseases without the need of frequent dosing.
[0022] A variable domain with moderate affinity, (but specificity to SA) would only stay in serum circulation for a short time (eg, for a few hours or a few days) allowing for the specific targeting of therapeutic targets involved in acute diseases by the fused therapeutic agent.
[0023] This way it is possible to tailor the anti-SA-containing product to the therapeutic disease area by choosing an anti-SA variable domain with the appropriate albumin binding affinity and/or serum half-life.
DETAILED DESCRIPTION OF THE INVENTION
[0024] Within this specification the invention has been described, with reference to embodiments, in a way which enables a clear and concise specification to be written. It is intended and should be appreciated that embodiments may be variously combined or separated without parting from the invention.
[0025] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art (e.g., in cell culture, molecular genetics, nucleic acid chemistry, hybridization techniques and biochemistry). Standard techniques are used for molecular, genetic and biochemical methods (see generally, Sambrook et al., Molecular Cloning: A Laboratory Manual, 2d ed. (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. and Ausubel et al., Short Protocols in Molecular Biology (1999) 4th Ed, John Wiley & Sons, Inc. which are incorporated herein by reference) and chemical methods.
[0026] As used herein, the term "antagonist of Tumor Necrosis Factor Receptor 1 (TNFR1)" or "anti-TNFR1 antagonist" or the like refers to an agent (e.g., a molecule, a compound) which binds TNFR1 and can inhibit a (i.e., one or more) function of TNFR1. For example, an antagonist of TNFR1 can inhibit the binding of TNFα to TNFR1 and/or inhibit signal transduction mediated through TNFR1. Accordingly, TNFR1-mediated processes and cellular responses (e.g., TNFα-induced cell death in a standard L929 cytotoxicity assay) can be inhibited with an antagonist of TNFR1.
[0027] A "patient" is any animal, eg, a mammal, eg, a non-human primate (such as a baboon, rhesus monkey or Cynomolgus monkey), mouse, human, rabbit, rat, dog, cat or pig. In one embodiment, the patient is a human.
[0028] As used herein, "peptide" refers to about two to about 50 amino acids that are joined together via peptide bonds.
[0029] As used herein, "polypeptide" refers to at least about 50 amino acids that are joined together by peptide bonds. Polypeptides generally comprise tertiary structure and fold into functional domains.
[0030] As used herein an antibody refers to IgG, IgM, IgA, IgD or IgE or a fragment (such as a Fab, F(ab')2, Fv, disulphide linked Fv, scFv, closed conformation multispecific antibody, disulphide-linked scFv, diabody) whether derived from any species naturally producing an antibody, or created by recombinant DNA technology; whether isolated from serum, B-cells, hybridomas, transfectomas, yeast or bacteria.
[0031] As used herein, "antibody format" refers to any suitable polypeptide structure in which one or more antibody variable domains can be incorporated so as to confer binding specificity for antigen on the structure. A variety of suitable antibody formats are known in the art, such as, chimeric antibodies, humanized antibodies, human antibodies, single chain antibodies, bispecific antibodies, antibody heavy chains, antibody light chains, homodimers and heterodimers of antibody heavy chains and/or light chains, antigen-binding fragments of any of the foregoing (e.g., a Fv fragment (e.g., single chain Fv (scFv), a disulfide bonded Fv), a Fab fragment, a Fab' fragment, a F(ab')2 fragment), a single antibody variable domain (e.g., a dAb, VH, VHH, VL), and modified versions of any of the foregoing (e.g., modified by the covalent attachment of polyethylene glycol or other suitable polymer or a humanized VHH).
[0032] The phrase "immunoglobulin single variable domain" refers to an antibody variable domain (VH, VHH, VL) that specifically binds an antigen or epitope independently of different V regions or domains. An immunoglobulin single variable domain can be present in a format (e.g., homo- or hetero-multimer) with other variable regions or variable domains where the other regions or domains are not required for antigen binding by the single immunoglobulin variable domain (i.e., where the immunoglobulin single variable domain binds antigen independently of the additional variable domains). A "domain antibody" or "dAb" is the same as an "immunoglobulin single variable domain" as the term is used herein. A "single immunoglobulin variable domain" is the same as an "immunoglobulin single variable domain" as the term is used herein. A "single antibody variable domain" or an "antibody single variable domain" is the same as an "immunoglobulin single variable domain" as the term is used herein. An immunoglobulin single variable domain is in one embodiment a human antibody variable domain, but also includes single antibody variable domains from other species such as rodent (for example, as disclosed in WO 00/29004, the contents of which are incorporated herein by reference in their entirety), nurse shark and Camelid VHH dAbs. Camelid VHH are immunoglobulin single variable domain polypeptides that are derived from species including camel, llama, alpaca, dromedary, and guanaco, which produce heavy chain antibodies naturally devoid of light chains. The VHH may be humanized.
[0033] A "domain" is a folded protein structure which has tertiary structure independent of the rest of the protein. Generally, domains are responsible for discrete functional properties of proteins, and in many cases may be added, removed or transferred to other proteins without loss of function of the remainder of the protein and/or of the domain. A "single antibody variable domain" is a folded polypeptide domain comprising sequences characteristic of antibody variable domains. It therefore includes complete antibody variable domains and modified variable domains, for example, in which one or more loops have been replaced by sequences which are not characteristic of antibody variable domains, or antibody variable domains which have been truncated or comprise N- or C-terminal extensions, as well as folded fragments of variable domains which retain at least the binding activity and specificity of the full-length domain.
[0034] In the instant application, the term "prevention" and "preventing" involves administration of the protective composition prior to the induction of the disease or condition. "Treatment" and "treating" involves administration of the protective composition after disease or condition symptoms become manifest. "Suppression" or "suppressing" refers to administration of the composition after an inductive event, but prior to the clinical appearance of the disease or condition.
[0035] As used herein, the term "dose" refers to the quantity of ligand administered to a subject all at one time (unit dose), or in two or more administrations over a defined time interval. For example, dose can refer to the quantity of ligand (e.g., ligand comprising an immunoglobulin single variable domain that binds target antigen) administered to a subject over the course of one day (24 hours) (daily dose), two days, one week, two weeks, three weeks or one or more months (e.g., by a single administration, or by two or more administrations). The interval between doses can be any desired amount of time. The term "pharmaceutically effective" when referring to a dose means sufficient amount of the ligand, domain or pharmaceutically active agent to provide the desired effect. The amount that is "effective" will vary from subject to subject, depending on the age and general condition of the individual, the particular drug or pharmaceutically active agent and the like. Thus, it is not always possible to specify an exact "effective" amount applicable for all patients. However, an appropriate "effective" dose in any individual case may be determined by one of ordinary skill in the art using routine experimentation.
[0036] Methods for pharmacokinetic analysis and determination of ligand (eg, single variable domain, fusion protein or multi-specific ligand) half-life will be familiar to those skilled in the art. Details may be found in Kenneth, A et al: Chemical Stability of Pharmaceuticals: A Handbook for Pharmacists and in Peters et al, Pharmacokinetc analysis: A Practical Approach (1996). Reference is also made to "Pharmacokinetics", M Gibaldi & D Perron, published by Marcel Dekker, 2nd Rev. ex edition (1982), which describes pharmacokinetic parameters such as t alpha and t beta half lives and area under the curve (AUC). Optionally, all pharmacokinetic parameters and values quoted herein are to be read as being values in a human. Optionally, all pharmacokinetic parameters and values quoted herein are to be read as being values in a mouse or rat or Cynomolgus monkey.
[0037] Half lives (t1/2 alpha and t1/2 beta) and AUC can be determined from a curve of serum concentration of ligand against time. The WinNonlin analysis package, eg version 5.1 (available from Pharsight Corp., Mountain View, Calif. 94040, USA) can be used, for example, to model the curve. When two-compartment modeling is used, in a first phase (the alpha phase) the ligand is undergoing mainly distribution in the patient, with some elimination. A second phase (beta phase) is the phase when the ligand has been distributed and the serum concentration is decreasing as the ligand is cleared from the patient. The t alpha half life is the half life of the first phase and the t beta half life is the half life of the second phase. Thus, in one embodiment, in the context of the present invention, the variable domain, fusion protein or ligand has a tα half-life in the range of (or of about) 15 minutes or more. In one embodiment, the lower end of the range is (or is about) 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 10 hours, 11 hours or 12 hours. In addition, or alternatively, the variable domain, fusion protein or ligand according to the invention will have a ta half life in the range of up to and including 12 hours (or about 12 hours). In one embodiment, the upper end of the range is (or is about) 11, 10, 9, 8, 7, 6 or 5 hours. An example of a suitable range is (or is about) 1 to 6 hours, 2 to 5 hours or 3 to 4 hours.
[0038] In one embodiment, the present invention provides the variable domain, fusion protein or ligand according to the invention has a tβ half-life in the range of (or of about) 2.5 hours or more. In one embodiment, the lower end of the range is (or is about) 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 10 hours, 11 hours, or 12 hours. In addition, or alternatively, the tβ half-life is (or is about) up to and including 21 or 25 days. In one embodiment, the upper end of the range is (or is about) 12 hours, 24 hours, 2 days, 3 days, 5 days, 10 days, 15 days, 19 days 20 days, 21 days or 22 days. For example, the variable domain, fusion protein or ligand according to the invention will have a tβ half life in the range 12 to 60 hours (or about 12 to 60 hours). In a further embodiment, it will be in the range 12 to 48 hours (or about 12 to 48 hours). In a further embodiment still, it will be in the range 12 to 26 hours (or about 12 to 26 hours).
[0039] As an alternative to using two-compartment modeling, the skilled person will be familiar with the use of non-compartmental modeling, which can be used to determine terminal half-lives (in this respect, the term "terminal half-life" as used herein means a terminal half-life determined using non-compartmental modeling). The WinNonlin analysis package, eg version 5.1 (available from Pharsight Corp., Mountain View, Calif. 94040, USA) can be used, for example, to model the curve in this way. In this instance, in one embodiment the single variable domain, fusion protein or ligand has a terminal half life of at least (or at least about) 8 hours, 10 hours, 12 hours, 15 hours, 28 hours, 20 hours, 1 day, 2 days, 3 days, 7 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days or 25 days. In one embodiment, the upper end of this range is (or is about) 24 hours, 48 hours, 60 hours or 72 hours or 120 hours. For example, the terminal half-life is (or is about) from 8 hours to 60 hours, or 8 hours to 48 hours or 12 to 120 hours, eg, in man.
[0040] In addition, or alternatively to the above criteria, the variable domain, fusion protein or ligand according to the invention has an AUC value (area under the curve) in the range of (or of about) 1 mg.min/ml or more. In one embodiment, the lower end of the range is (or is about) 5, 10, 15, 20, 30, 100, 200 or 300 mg.min/ml. In addition, or alternatively, the variable domain, fusion protein or ligand according to the invention has an AUC in the range of (or of about) up to 600 mg.min/ml. In one embodiment, the upper end of the range is (or is about) 500, 400, 300, 200, 150, 100, 75 or 50 mg.min/ml. Advantageously the variable domain, fusion protein or ligand will have an AUC in (or about in) the range selected from the group consisting of the following: 15 to 150 mg.min/ml, 15 to 100 mg.min/ml, 15 to 75 mg.min/ml, and 15 to 50 mg.min/ml.
[0041] "Surface Plasmon Resonance": Competition assays can be used to determine if a specific antigen or epitope, such as human serum albumin, competes with another antigen or epitope, such as cynomolgus serum albumin, for binding to a serum albumin binding ligand described herein, such as a specific dAb. Similarly competition assays can be used to determine if a first ligand such as dAb, competes with a second ligand such as a dAb for binding to a target antigen or epitope. The term "competes" as used herein refers to substance, such as a molecule, compound, preferably a protein, which is able to interfere to any extent with the specific binding interaction between two or more molecules. The phrase "does not competitively inhibit" means that substance, such as a molecule, compound, preferably a protein, does not interfere to any measurable or significant extent with the specific binding interaction between two or more molecules. The specific binding interaction between two or more molecules preferably includes the specific binding interaction between a single variable domain and its cognate partner or target. The interfering or competing molecule can be another single variable domain or it can be a molecule that that is structurally and/or functionally similar to a cognate partner or target.
[0042] The term "binding moiety" refers to a domain that specifically binds an antigen or epitope independently of a different epitope or antigen binding domain. A binding moiety may be a domain antibody (dAb) or may be a domain which is a derivative of a non-immunoglobulin protein scaffold, eg, a scaffold selected from the group consisting of CTLA-4, lipocalin, SpA, an adnectin, affibody, an avimer, GroEl, transferrin, GroES and fibronectin, which binds to a ligand other than the natural ligand (in the case of the present invention, the moiety binds serum albumin). See WO2008/096158, which discloses examples of protein scaffolds and methods for selecting antigen or epitope-specific binding domains from repertoires (see Examples 17 to 25). These specific disclosures of WO2008/096158 are expressly incorporated herein by reference as though explicitly written herein and for use with the present invention, and it is contemplated that any part of such disclosure can be incorporated into one or more claims herein).
[0043] In one embodiment, a variable domain of the invention comprises one or more of the following kinetic characteristics:--
[0044] (a) The variable domain comprises a binding site that specifically binds human SA with a dissociation constant (KD) from (or from about) 0.1 to (or to about) 10000 nM, optionally from (or from about) 1 to (or to about) 6000 nM, as determined by surface plasmon resonance;
[0045] (b) The variable domain comprises a binding site that specifically binds human SA with an off-rate constant (Kd) from (or from about) 1.5×10-4 to (or to about) 0.1 sec-1, optionally from (or from about) 3×10-4 to (or to about) 0.1 sec as determined by surface plasmon resonance;
[0046] (c) The variable domain comprises a binding site that specifically binds human SA with an on-rate constant (Ka) from (or from about) 2×106 to (or to about) 1×104 M-1sec-1, optionally from (or from about) 1×106 to (or to about) 2×104 M-1sec-1 as determined by surface plasmon resonance;
[0047] (d) The variable domain comprises a binding site that specifically binds Cynomolgus monkey SA with a dissociation constant (KD) from (or from about) 0.1 to (or to about) 10000 nM, optionally from (or from about) 1 to (or to about) 6000 nM, as determined by surface plasmon resonance;
[0048] (e) The variable domain of any preceding claim, wherein the variable domain comprises a binding site that specifically binds Cynomolgus monkey SA with an off-rate constant (Kd) from (or from about) 1.5×10-4 to (or to about) 0.1 sec-1, optionally from (or from about) 3×10-4 to (or to about) 0.1 sec-1 as determined by surface plasmon resonance;
[0049] (f) The variable domain of any preceding claim, wherein the variable domain comprises a binding site that specifically binds Cynomolgus monkey SA with an on-rate constant (Ka) from (or from about) 2×106 to (or to about) 1×104M-1sec-1, optionally from (or from about) 1×106 to (or to about) 5×103 M-1sec-1 as determined by surface plasmon resonance;
[0050] (g) The variable domain comprises a binding site that specifically binds rat SA with a dissociation constant (KD) from (or from about) 1 to (or to about) 10000 nM, optionally from (or from about) 20 to (or to about) 6000 nM, as determined by surface plasmon resonance;
[0051] (h) The variable domain comprises a binding site that specifically binds rat SA with an off-rate constant (Ka) from (or from about) 2×10-3 to (or to about) 0.15 sec-1, optionally from (or from about) 9×10-3 to (or to about) 0.14 sec-1 as determined by surface plasmon resonance;
[0052] (i) The variable domain comprises a binding site that specifically binds rat SA with an on-rate constant (Ka) from (or from about) 2×106 to (or to about) 1×104M-1sec-1, optionally from (or from about) 1×106 to (or to about) 3×104 M-1sec-1 as determined by surface plasmon resonance;
[0053] (j) The variable domain comprises a binding site that specifically binds mouse SA with a dissociation constant (KD) from (or from about) 1 to (or to about) 10000 nM as determined by surface plasmon resonance;
[0054] (k) The variable domain comprises a binding site that specifically binds mouse SA with an off-rate constant (Kd) from (or from about) 2×10-3 to (or to about) 0.15 sec-1 as determined by surface plasmon resonance; and/or
[0055] (l) The variable domain comprises a binding site that specifically binds mouse SA with an on-rate constant (Ka) from (or from about) 2×106 to (or to about) 1×104 M-1sec-1, optionally from (or from about) 2×106 to (or to about) 1.5×104 M-1sec-1 as determined by surface plasmon resonance.
[0056] Optionally, the variable domain has
[0057] I: a KD according to (a) and (d), a Kd according to (b) and (e), and a Ka according to (c) and (f); or
[0058] II: a KD according to (a) and (g), a Kd according to (b) and (h), and a Ka according to (c) and (i); or
[0059] III: a KD according to (a) and (j), a Kd according to (b) and (k), and a Ka according to (c) and (l); or
[0060] IV. kinetics according to I and II; or
[0061] V: kinetics according to I and III; or
[0062] VI: kinetics according to I, II and III.
[0063] The invention also provides a ligand comprising a variable domain of any preceding aspect or embodiment of the invention. For example, the ligand can be a dual-specific ligand (see WO04003019 for examples of dual-specific ligands). In one aspect, the invention provides a multispecific ligand comprising an anti-SA variable domain of any preceding aspect or embodiment of the invention and a binding moiety that specifically binds a target antigen other than SA. The binding moiety can be any binding moiety that specifically binds a target, eg, the moiety is an antibody, antibody fragment, scFv, Fab, dAb or a binding moiety comprising a non-immunoglobulin protein scaffold. Such moieties are disclosed in detail in WO2008/096158 (see examples 17 to 25, which disclosure is incorporated herein by reference). Examples of non-immunoglobulin scaffolds are CTLA-4, lipocallin, staphylococcal protein A (spA), Affibody®, Avimers®, adnectins, GroEL and fibronectin.
[0064] In one embodiment, a linker is provided between the anti-target binding moiety and the anti-SA variable domain, the linker comprising the amino acid sequence AST, optionally ASTSGPS. Alternative linkers are described in WO2007085814 (incorporated herein by reference) and WO2008/096158 (see the passage at page 135, line 12 to page 140, line 14, which disclosure and all sequences of linkers are expressly incorporated herein by reference as though explicitly written herein and for use with the present invention, and it is contemplated that any part of such disclosure can be incorporated into one or more claims herein).
[0065] In one embodiment of the multispecific ligand, the target antigen may be, or be part of, polypeptides, proteins or nucleic acids, which may be naturally occurring or synthetic. In this respect, the ligand of the invention may bind the target antigen and act as an antagonist or agonist (e.g., EPO receptor agonist). One skilled in the art will appreciate that the choice is large and varied. They may be for instance, human or animal proteins, cytokines, cytokine receptors, where cytokine receptors include receptors for cytokines, enzymes, co-factors for enzymes or DNA binding proteins. Suitable cytokines and growth factors include, but are preferably not limited to: ApoE, Apo-SAA, BDNF, Cardiotrophin-1, EGF, EGF receptor, ENA-78, Eotaxin, Eotaxin-2, Exodus-2, EpoR, FGF-acidic, FGF-basic, fibroblast growth factor-10, FLT3 ligand, Fractalkine (CX3C), GDNF, G-CSF, GM-CSF, GF-131, insulin, IFN-γ, IGF-I, IGF-II, IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8 (72 a.a.), IL-8 (77 a.a.), IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, IL-16, IL-17, IL-18 (IGIF), Inhibin α, Inhibin β, IP-10, keratinocyte growth factor-2 (KGF-2), KGF, Leptin, LIF, Lymphotactin, Mullerian inhibitory substance, monocyte colony inhibitory factor, monocyte attractant protein, M-CSF, MDC (67 a.a.), MDC (69 a.a.), MCP-1 (MCAF), MCP-2, MCP-3, MCP-4, MDC (67 a.a.), MDC (69 a.a.), MIG, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-4, myeloid progenitor inhibitor factor-1 (MPIF-1), NAP-2, Neurturin, Nerve growth factor, β-NGF, NT-3, NT-4, Oncostatin M, PDGF-AA, PDGF-AB, PDGF-BB, PF-4, RANTES, SDF1α, SDF1β, SCF, SCGF, stem cell factor (SCF), TARC, TGF-α, TGF-β, TGF-β2, TGF-β3, tumour necrosis factor (TNF), TNF-α, TNF-β, TNF receptor I, TNF receptor II, TNIL-1, TPO, VEGF, VEGF receptor 1, VEGF receptor 2, VEGF receptor 3, GCP-2, GRO/MGSA, GRO-β, GRO-γ, HCC1, 1-309, HER 1, HER 2, HER 3 and HER 4, CD4, human chemokine receptors CXCR4 or CCR5, non-structural protein type 3 (NS3) from the hepatitis C virus, TNF-alpha, IgE, IFN-gamma, MMP-12, CEA, H. pylori, TB, influenza, Hepatitis E, MMP-12, internalizing receptors that are over-expressed on certain cells, such as the epidermal growth factor receptor (EGFR), ErBb2 receptor on tumor cells, an internalising cellular receptor, LDL receptor, FGF2 receptor, ErbB2 receptor, transferrin receptor, PDGF receptor, VEGF receptor, PsmAr, an extracellular matrix protein, elastin, fibronectin, laminin, a 1-antitrypsin, tissue factor protease inhibitor, PDK1, GSK1, Bad, caspase-9, Forkhead, an antigen of Helicobacter pylori, an antigen of Mycobacterium tuberculosis, and an antigen of influenza virus. It will be appreciated that this list is by no means exhaustive.
[0066] In one embodiment, the multispecific ligand comprises an anti-SA dAb variable domain of the invention and an anti-TNFR1 binding moiety, e.g., an anti-TNFR1 dAb. Optionally, the ligand has only one anti-TNFR1 binding moiety (e.g., dAb) to reduce the chance of receptor cross-linking. In one embodiment, the anti-SA dAb comprises or consists of the amino acid sequence of any one of SEQ ID NOs: 97 to 103 and 198 to 203 (or an amino acid sequence that is at least 95, 96, 97, 98 or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 97 to 103 and 198 to 203).
[0067] In one embodiment, the anti-TNFR1 binding moiety is DOM1h-131-206 disclosed in WO2008149148 (the amino acid sequence of which and the nucleotide sequence of which, as disclosed in that PCT application, are expressly incorporated herein by reference as though explicitly written herein and for use with the present invention, and it is contemplated that any part of such disclosure can be incorporated into one or more claims herein). In one embodiment, the multispecific ligand comprises or consists of the amino acid sequence of DOM1h-131-206 and the amino acid sequence of any one of SEQ ID NOs: 97 to 103 and 198 to 203 (or an amino acid sequence that is at least 95, 96, 97, 98 or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 97 to 103 and 198 to 203).
[0068] In one embodiment, the anti-TNFR1 binding moiety or dAb is any such moiety or dAb disclosed in co-pending application U.S. Ser. No. 61/153,746, the disclosure of which is incorporated herein by reference. In one embodiment, the anti-TNFR1 binding moiety comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of DOM1h-574-156, DOM1h-574-72, DOM1h-574-109, DOM1h-574-138, DOM1h-574-162 or DOM1h-574-180 or the amino acid sequence of any anti-TNFR1 dAb disclosed herein. In one embodiment, the multispecific ligand comprises or consists of the amino acid sequence of DOM1h-574-156 and the amino acid sequence of any one of SEQ ID NOs: 97 to 103 and 198 to 203 (or an amino acid sequence that is at least 95, 96, 97, 98 or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 97 to 103 and 198 to 203).
[0069] In one embodiment, the ligand of the invention is a fusion protein comprising a variable domain of the invention fused directly or indirectly to one or more polypeptides. For example, the fusion protein can be a "drug fusion" as disclosed in WO2005/118642 (the disclosure of which is incorporated herein by reference), comprising a variable domain of the invention and a polypeptide drug as defined in that PCT application.
[0070] As used herein, "drug" refers to any compound (e.g., small organic molecule, nucleic acid, polypeptide) that can be administered to an individual to produce a beneficial, therapeutic or diagnostic effect through binding to and/or altering the function of a biological target molecule in the individual. The target molecule can be an endogenous target molecule encoded by the individual's genome (e.g. an enzyme, receptor, growth factor, cytokine encoded by the individual's genome) or an exogenous target molecule encoded by the genome of a pathogen (e.g. an enzyme encoded by the genome of a virus, bacterium, fungus, nematode or other pathogen). Suitable drugs for use in fusion proteins and conjugates comprising an anti-SA dAb domain of the invention are disclosed in WO2005/118642 and WO2006/059106 (the entire disclosures of which are incorporated herein by reference, and including the entire list of specific drugs as though this list were expressly written herein, and it is contemplated that such incorporation provides disclosure of specific drugs for inclusion in claims herein). For example, the drug can be glucagon-like peptide 1 (GLP-1) or a variant, interferon alpha 2b or a variant or exendin-4 or a variant.
[0071] In one embodiment, the invention provides a drug conjugate as defined and disclosed in WO2005/118642 and WO2006/059106, wherein the conjugate comprises a variable domain of the invention. In one example, the drug is covalently linked to the variable domain (eg, the variable domain and the drug are expressed as part of a single polypeptide). Alternatively, in an example, the drug is non-covalently bonded or associated with the variable domain. The drug can be covalently or noncovalently bonded to the variable domain directly or indirectly (e.g., through a suitable linker and/or noncovalent binding of complementary binding partners (e.g., biotin and avidin)). When complementary binding partners are employed, one of the binding partners can be covalently bonded to the drug directly or through a suitable linker moiety, and the complementary binding partner can be covalently bonded to the variable domain directly or through a suitable linker moiety. When the drug is a polypeptide or peptide, the drug composition can be a fusion protein, wherein the polypeptide or peptide, drug and the polypeptide binding moiety are discrete parts (moieties) of a continuous polypeptide chain. As described herein, the polypeptide binding moieties and polypeptide drug moieties can be directly bonded to each other through a peptide bond, or linked through a suitable amino acid, or peptide or polypeptide linker.
[0072] A ligand which contains one single variable domain (eg, monomer) of the invention or more than one single variable domain (multimer, fusion protein, conjugate, and dual specific ligand as defined herein) which specifically binds to serum albumin, can further comprise one or more entities selected from, but preferably not limited to a label, a tag, an additional single variable domain, a dAb, an antibody, and antibody fragment, a marker and a drug. One or more of these entities can be located at either the COOH terminus or at the N terminus or at both the N terminus and the COOH terminus of the ligand comprising the single variable domain, (either immunoglobulin or non-immunoglobulin single variable domain). One or more of these entities can be located at either the COOH terminus, or the N terminus, or both the N terminus and the COOH terminus of the single variable domain which specifically binds serum albumin of the ligand which contains one single variable domain (monomer) or more than one single variable domains (multimer, fusion protein, conjugate, and dual specific ligand as defined herein). Non-limiting examples of tags which can be positioned at one or both of these termini include a HA, his or a myc tag. The entities, including one or more tags, labels and drugs, can be bound to the ligand which contains one single variable domain (monomer) or more than one single variable domain (multimer, fusion protein, conjugate, and dual specific ligand as defined herein), which binds serum albumin, either directly or through linkers as described above.
[0073] An aspect of the invention provides a fusion product, eg, a fusion protein or fusion with a peptide or conjugate with an NCE (new chemical entity) drug, comprising a polypeptide drug fused or conjugated (for an NCE) to any variable domain as described above, optionally wherein the variable domain comprises or consists of the amino acid sequence of any one of SEQ ID NOs: 97 to 103 and 198 to 203 (or an amino acid sequence that is at least 95, 96, 97, 98 or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 97 to 103 and 198 to 203).
[0074] The invention provides a composition comprising a variable domain, fusion protein, conjugate or ligand of any aspect of the invention and a pharmaceutically acceptable diluent, carrier, exipient or vehicle.
[0075] Also encompassed herein is an isolated nucleic acid encoding any of the variable domain, fusion proteins, conjugates or ligands described herein, e.g., a ligand which contains one single variable domain (eg, monomer) of the invention or more than one single variable domain (e.g., multimer, fusion protein, conjugate, and dual specific ligand as defined herein) which specifically binds to serum albumin, or which specifically binds both human serum albumin and at least one non-human serum albumin, or functionally active fragments thereof. Also encompassed herein is a vector and/or an expression vector, a host cell (eg, a non-human host cell or a host cell that is not isolated from a human or human embryo) comprising the vector, e.g., a plant or animal cell and/or cell line transformed with a vector, a method of expressing and/or producing one or more variable domains, fusion proteins or ligands which contains one single variable domain (monomer) or more than one single variable domains (e.g., multimer, fusion protein, conjugate, and dual specific ligand as defined herein) which specifically binds to serum albumin, or fragment(s) thereof encoded by said vectors, including in some instances culturing the host cell so that the one or more variable domains, fusion proteins or ligands or fragments thereof are expressed and optionally recovering the ligand which contains one single variable domain (monomer) or more than one single variable domain (e.g., multimer, fusion protein, conjugate, and dual specific ligand as defined herein) which specifically binds to serum albumin, from the host cell culture medium. Also encompassed are methods of contacting a ligand described herein with serum albumin, including serum albumin and/or non-human serum albumin(s), and/or one or more targets other than serum albumin, where the targets include biologically active molecules, and include animal proteins, cytokines as listed above, and include methods where the contacting is in vitro as well as administering any of the variable domains, fusion proteins or ligands described herein to an individual host animal or cell in vivo and/or ex vivo. Preferably, administering ligands described herein which comprises a single variable domain (immunoglobulin or non-immunoglobulin) directed to serum albumin and/or non-human serum albumin(s), and one or more domains directed to one or more targets other than serum albumin, will increase the half life, including the T beta and/or terminal half life, of the anti-target ligand. Nucleic acid molecules encoding the domains, fusion proteins or single domain containing ligands or fragments thereof, including functional fragments thereof, are contemplated herein. Vectors encoding the nucleic acid molecules, including but preferably not limited to expression vectors, are contemplated herein, as are host cells from a cell line or organism containing one or more of these expression vectors. Also contemplated are methods of producing any domain, fusion protein or ligand, including, but preferably not limited to any of the aforementioned nucleic acids, vectors and host cells.
[0076] An aspect of the invention provides a nucleic acid comprising a nucleotide sequence encoding a variable domain according to the invention or a multispecific ligand of the invention or fusion protein of the invention.
[0077] An aspect of the invention provides a nucleic acid comprising the nucleotide sequence selected from any one of SEQ ID NOs: 1 to 96 and 192-197, or a nucleotide sequence that is at least 70, 75, 80, 85, 90, 95, 96, 97, 98 or 99% identical to said selected sequence.
[0078] An aspect of the invention provides a vector comprising the nucleic acid of the invention. An aspect of the invention provides an isolated host cell comprising the vector.
[0079] Reference is made to WO2008/096158 for details of library vector systems, combining single variable domains, characterization of dual specific ligands, structure of dual specific ligands, scaffolds for use in constructing dual specific ligands, uses of anti-serum albumin dAbs and multispecific ligands and half-life-enhanced ligands, and compositions and formulations of comprising anti-serum albumin dAbs. These disclosures are incorporated herein by reference to provide guidance for use with the present invention, including for domains, ligands, fusion proteins, conjugates, nucleic acids, vectors, hosts and compositions of the present invention.
TABLE-US-00001 SEQUENCES OF ANTI-SERUM ALBUMIN VH SINGLE VARIABLE DOMAINS All variable domains bind at least one species of serum albumin as determined by SPR . . . Nucleotide sequences: DOM7h-112 SEQ ID NO: 1 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGGGGGTATGTGATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGCTATTAATAGGTTTGGTTCGTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGTAGTTTGCGGCATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAG C DOM7h-98 SEQ ID NO: 2 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGTAATTATGCGATGGCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCGATTGATATGGTTGGTATTAAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGTTTTCGTATTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7r-29 SEQ ID NO: 3 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAAGGATTATGATATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAATGATTTCTTCGTCGGGTCTTTGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGTTTTAGGCTGTTTCCTCGGACTTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGCG DOM7r-35 SEQ ID NO: 4 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTTCGCTGTATAGGATGGTGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAATGATTTCTCAGTTTGGTAATCAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGTTAGGTCTTGGGATCAGACTGGTGGTCGTCGTACTTTTGACTACTGGGGTCAGGG AACCCTGGTCACCGTCTCGAGC DOM7r-36 SEQ ID NO: 5 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAATCATTATACGATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATTGATTCATCCGAGTGGTACGGTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATGGAGTTCGAGGGCGTTTGACTACTG GGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7r-38 SEQ ID NO: 6 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATAATAATGCGATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTAGTGCGAATGGTAATGCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGGACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGGTTTCGTCGGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7r31 SEQ ID NO: 7 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAG CCTCCGGATTCACCTTTAGGCATTATCGTATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATGGATTCGTCCGGATGGTACGTTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATCTTATATGGGTGATAGGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTC GAGCG DOM7h-32 SEQ ID NO: 8 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGCGCAG CCTCCGGATTCACCTTTGGTAATTATCCGATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTG GGTCTCAACTATTAGTTATGGTGGTCTTGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAATGGCGATTAATGGTGTTAGGCCTAGGCGGTTTGACTACTGGGGTCAGGGAACCCT GGTCACCGTCTCGAGC DOM7h-33 SEQ ID NO: 9 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTATGGCGTATCAGATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTCATCAGACGGGTTTTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTAT ATTACTGTGCGAAAGTGCGTTCTATGCGTCCTTATAAGTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7h-34 SEQ ID NO: 10 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGTGATAAGGCAATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACGATTAGTGCTCCTGGTAACCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGTTTTCGGAATTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7h-83 SEQ ID NO: 11 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATGGGATGCGTATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGCTATTGAGGTGAATGGTCAGCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAATGGCTCATCCTCAGTCGGGGGTGGCTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7h-84 SEQ ID NO: 12 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTACGCCTGATGCTATGGCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCGATTGGTGTGAATGGTTCTCCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAGGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAATGGCTCATCCTCAGTCGGGGGTGGCTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7h-85 SEQ ID NO: 13 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTTATCAGTCGGATATGTCTTGGGTCCGCCAGGCTCCAGGGAAAGGTCTAGAGTG GGTCTCATCTATTTCTTCTCAGGGTCGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAATGGCTCATCCTCAGTCGGGGGTGGCTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7h-86 SEQ ID NO: 14 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAG CCTCCGGATTCACCTTTGCGGCGAGGGATATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTG GGTCTCAAGTATTTCTGCTCAGGGTGCTCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACGATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTAT ATTACTGTGCGAAACCTCGGCATCCTCAGGGGGGGGTTACTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7h-87 SEQ ID NO: 15 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATAATGGGGATATGGTTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGGGATTGCGCATAATGGTCGTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAAATTTGGGTCAGGGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAG C DOM7h-88 SEQ ID NO: 16 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCACCTGTGCAG CCTCCGGATTCACCTTGAATGGTACGTCGATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGATCTAGAGTG GGTCTCATCTATTATGCCTGTGGGTTCTCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAATGGCTCATCCTCAGTCGGGGGTGGCTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7h-89 SEQ ID NO: 17 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATCATGCGCCTATGAAGTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATATATTGGGTCGGCGGGTAATATGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGATGAGGGGCCGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7h-90 SEQ ID NO: 18 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTACAG CCTCCGGATTCACCTTTGATGGGATGGATATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAAGTATTTCTACGACTGGTGGGACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACCTCGGCATCCTCAGGGGGGGGTTACTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7h-91
SEQ ID NO: 19 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGGCGGAGACGATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTCATTCGGAGGGTTCTCGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACCTCGGCATCCTCAGGGGGGGGTTACTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7h-92 SEQ ID NO: 20 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAGTACTGGGGAGATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCTATTAGTTCGAGTGGTGCTACGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACCTCGGCATCCTCAGGGGGGGGTTACTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7h-93 SEQ ID NO: 21 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCCTAGTGCTGATATGGTTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCACGTATTTCGCCTGAGGGTAATCATACATACTACGCAGACTCCGTGAAGGGTCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTAT ATTACTGTGCGGAACGGCCTCCTTCGGATTATGTTTCTTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7h-94 SEQ ID NO: 22 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGCGAATGCGACTATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGATATTGATCAGGTGGGTCATGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATATTCGTGGCATCCGGATCTGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGT CTCGAGC DOM7h-95 SEQ ID NO: 23 GAGGTGCGGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAAGGATTATGGGATGAATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCACGGATTAGTAGGAATGGTACTGTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAACTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATTGGCTGCTCCGGTTCGTCAGAAGGGGATGGATTTTGACTACTGGGGTCAGGGAAC CCTGGTCACCGTCTCGAGC DOM7h-96 SEQ ID NO: 24 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGTGGTATAATATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGATCTGGAGTG GGTCTCATCGATTTCTCATGATGGTTGGAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGGATGATTGGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7h-97 SEQ ID NO: 25 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATATTTATACGATGCATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTGTTCCGCAGGGTACTCCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATCTAAGCGTAGGTTTCTTAAGAGGTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7h-99 SEQ ID NO: 26 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGCTAGGTATGATATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCGATTAAGAGTAATGGTATGAAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGCTAGTATGTGGACGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAA C DOM7h-100 SEQ ID NO: 27 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTATGTTGTATCATATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGCTATTACCGGGGGGGGTTATCCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACTGGGGCTTCGGGGTGTGCTGTGGCGGAGGAGGTTTGACTACTGGGGTCAGGGAAC CCTGGTCACCGTCTCGAGC DOM7h-101 SEQ ID NO: 28 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGTGCTTATTCTATGATGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCACGGATTAGTAGGAATGGTACTGTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAATTAGGTGGAATACTGCTCAGGTGCCTGTGTTTGACTACTGGGGTCAGGGAACTCT GGTCACCGTCTCGAGC DOM7h-102 SEQ ID NO: 29 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGTCCGTATTGGATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACGATTACGCCTTCGGGTCGTGGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTAT ATTACTGTGCGAAAGGGCGTCCTCGTGTTGGTTTGTGGAGGTCGGGGTTTGACTACTGGGGTCAGGGAAC CCTGGTCACCGTCTCGAGC DOM7h-103 SEQ ID NO: 30 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGGCAGTATGCTATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCTATTAATATTACTGGTTCTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAGATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGTTTTAGGTCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7h-106 SEQ ID NO: 31 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGCTGGTTATACGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACGATTTCGGGTTTTGGTTGGACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTAT ATTACTGTGCGAAAAGGCTGGGGATGCGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAG C DOM7h-109 SEQ ID NO: 33 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGTCCGTATTCGATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATTTATTCATTCTGATGGTCGTCATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAAAGACGCCTTATAGGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAG C DOM7h-111 SEQ ID NO: 34 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGGCAGTATGCTATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCTATTAATATTACTGGTTCTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAGATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGTTTTAGGTCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7h-114 SEQ ID NO: 35 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAGGCGGTATGCGATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACGATTTCGCCTTATGGTCCTGTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGCTTATTATGGTGGGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAG C DOM7r-34 SEQ ID NO: 36 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATGCTTATGCTATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAAAGATTGATTCTCCTGGTTGGAGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATCGGCTCGGATGCGTTCTCGGCATTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7r-37 SEQ ID NO: 37 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAAGGATTATGGGATGAATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCACGGATTAGTAGGAATGGTACTGTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAATTAGGTGGAATACTGCTCAGGTGCCTGTGTTTGACTACTGGGGTCAGGGAACTCT GGTCACCGTCTCGAGC DOM7r-39 SEQ ID NO: 38 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAA CCTCCGGATTCACCTTTCCGTCTTATACGATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG
GGTCTCACGTATTTCTCGTACTGGGAATTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTAT ATTACTGTGCGAAACCTATGTATAATAGGGGGTCTTCGTATTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7r-40 SEQ ID NO: 39 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTTCGCAGTATCAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCGATTTCGCCTACGGGTATTCAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAAGGCTTATTGGGATGCCGTATGTTGAGGATACTTTTGACTACTGGGGTCAGGGAAC CCTGGTCACCGTCTCGAGC DOM7r-41 SEQ ID NO: 40 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTATGGAGTATGAGATGGAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGGTATTACTAATTCTGGTTCTGGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAACTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGATAATGCAGCATCCTCAGGCGACTGGGGGGAGGGTTGGGTTTGACTACTGGGGTCAGGG AACCCTGGTCACCGTCTCGAGC DOM7r-42 SEQ ID NO: 41 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCCGAGGTATACTATGAAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCGATTGATAGGACGGGTCGTAAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTAT ATTACTGTGCGAAAGAGTCGTTGGTTTCGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAG C DOM7r-43 SEQ ID NO: 42 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGTGGTTATACGATGCCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTTCTCGTGATGGTAATTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGATATTGGTATGGGTTTTGACTACGGGGGGCGGGGAACCCTGGTCACCGTCTCGAG C DOM7r-44 SEQ ID NO: 43 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGATTTATGCGATGCATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACGATTAGTTCGGGTGGTAAGGGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATCGCGTACTATGTATTTTCGTGTTAGGGAGGCTTTTGACTACTGGGGTCAGGGAAC CCTGGTCACCGTCTCGAGC DOM7r-45 SEQ ID NO: 44 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCGTGCTTATAGGATGATGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTG GGTCTCATCTATTGATCCTGATGGTGCGGTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGGAACATTTTGATCTTGCGATGCCGAATCCGAATGCGAAGTTTGACTACTGGGGTCAGGG AACCCTGGTCACCGTCTCGAGC DOM7r-46 SEQ ID NO: 45 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGCCTCTCCTGTGCAG CCTCCGGATTCACCTTTTCTCGTTATCAGATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTG GGTCTCATCTATTAAGTCGAATGGTTCTTCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACCTAGTCGGCAGAGTTTTCAGTATCCGAGTTTTGACTACTGGGGTCAGGGAACCCT GGTCACCGTCTCGAGC DOM7r-47 SEQ ID NO: 46 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGGCGTTATAAGATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCTATTTCGCCTACGGGTTCGTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAACTGGGTATGTTATGGTTGAGCATTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7r-48 SEQ ID NO: 47 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAGTGATTATCCGATGAAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTG GGTCTCAACTATTAATTCTTCGGGTACGATTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACCGTTGTTGCCGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7r-49 SEQ ID NO: 48 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGCTAGGTATAGGATGTGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATGTATTCGGGATCCGGGTTTTCCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATGTTCGCCGTCTTCTACGCAGTGTACGGGGCTTTTTGACTACTGGGGTCAGGGAAC CCTGGTCACCGTCTCGAGC DOM7r-50 SEQ ID NO: 49 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAGGTTTTATGGGATGGCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCACTTATTGATCCTCCTGGTGGGGCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAATGGAGAGGCGGCATCTTAAGAGTGGTCATAAGGGGTTTGACTACTGGGGTCAGGG AACCCTGGTCACCGTCTCGAGC DOM7r-51 SEQ ID NO: 50 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTACGGAGTATGATATGATGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCTATTAGTCATAGGGGTGAGAAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGATAAGCGTTATCGGGGGTCTCAGCATTATTTTGACTACTGGGGTCAGGGAACCCT GGTCACCGTCTCGAGC DOM7r-52 SEQ ID NO: 51 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCGGAGTTATGATATGGGTTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTGGGTCGAATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACTTATGGGTATGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7r-53 SEQ ID NO: 52 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGCGTTATTCTATGAGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACGATTGGTTCGACGGGTAAGTGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGGCGTGGGTTGGTTTCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTC GAGC DOM7r-54 SEQ ID NO: 53 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAGGCGTTATTCGATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCTATTGATCGGTCTGGTAGGATGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATCTCGGCTGTCTTCGACGGGTTCTGAGGGTCATAATTTTGACTACTGGGGTCAGGG AACCCTGGTCACCGTCTCGAGC DOM7r-55 SEQ ID NO: 54 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAAGTGGTATCCGATGAAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTGCTTATGATGGTGTTCAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATTGGGTCCGACTAGTCGTGTGTTTGCTGCTACTGATTTTGACTACTGGGGTCAGGG AACCCTGGTCACCGTCTCGAGC DOM7r-56 SEQ ID NO: 55 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCCGAATTATGCGATGAAGTGGGGCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTGATACGAGTGGTAGTACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACTTACTCATCCTATGGCGCCGCGTCCGGCTTTTGACTACTGGGGTCAGGGAACCCT GGTCACCGTCTCGAGC DOM7r-57 SEQ ID NO: 56 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATCTTACGGAGATGGAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTG GGTCTCATCGATTGGGCCTTGGGGTACTCCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT
ATTACTGTGCGAAAATTTCGCATCCTCAGGCGATGTATCATACGTTTGACTACTGGGGTCAGGGAACCCT GGTCACCGTCTCGAGC DOM7r-58 SEQ ID NO: 57 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGCGCATCAGGATATGACGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGATATTGATCATTCGGGTTCGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATGGTGGCATCCGCAGGGGGGGACTTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7r-59 SEQ ID NO: 58 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGTTCTAAGGATATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACGATTGGGGCGAATGGTAAGGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGGAAGCGGGTCATCCTCAGGCGCCGTCTTTTAAGAGTTTTGACTACTGGGGTCAGGGAAC CCTGGTCACCGTCTCGAGC DOM7r-60 SEQ ID NO: 59 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCTGAATGCGGAGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTGATCGGGATGGTGCTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACTTCCTCCGCCGATGTCGCCGAAGAAGTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7r-61 SEQ ID NO: 60 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGAGGGAGGGTATGATGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTTTCAACTATTGATCGTATGGGTAGGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAAGGGATTCGCATCCTATGGGGTTTGACTACCGGGGTCAGGGAACCCTGGTCACCGT CTCGAGC DOM7r-62 SEQ ID NO: 61 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGGTTCACCTTTGAGAATGAGAAGATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCGATTGGTCCTACGGGTAGTGGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAACTCCTCATCCGCAGGTTTCTAGTTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7r-63 SEQ ID NO: 62 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGATTGATCATATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGAGATTGCGCCTTCGGGTGATCGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTAT ATTACTGTGCGAAAGTGATTTGTCAGAATCAGTGTCTGTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7r-64 SEQ ID NO: 63 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAGGGATTCTGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATTTATTACTTCTGATGGTCGGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACCTAGTCTGCCTCATGTTACGGCTTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7r-65 SEQ ID NO: 64 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGGATGAGACGATGAGTTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCGATTGGGGATGCTGGTATGCCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGGGAGCCGATTTATGTTCATACGACTCATTTTGACTACTGGGGTCAGGGAACCCT GGTCACCGTCTCGAGC DOM7r-66 SEQ ID NO: 65 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCCGCATGGTAAGATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATGGATTGCTGGGTCTGGTGATATGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATTGGGTCATCCTCAGCGGGGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGT CTCGAGC DOM7r-67 SEQ ID NO: 66 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGGACTTCTGATATGTCGTGGGTCCGCCAGGCCCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTGATTCTGGGGGTAGTTTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACCTCGGCATCCTCAGGGGGGGGTTACTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7r-68 SEQ ID NO: 68 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGCATGTTCCTATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCACGGATTAGTGAGCAGGGTAGTAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGTGCAGCATCCTATGTCTCCGCATGAGTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7r-69 SEQ ID NO: 69 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGCAGGGTATGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCGATTAATCCTGGTGGTCAGTTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAGGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGGAAGATCTGGGGCCGGGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAG C DOM7r-70 SEQ ID NO: 70 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGCGTTGGCCTATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTGATAGGTCTGGTAATACTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTAT ATTACTGTGCGAAAGTTTTGCATCCTCAGGCGGGGTCTGCTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7r-71 SEQ ID NO: 71 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTCGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGGGGTAGTGATATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATATATTGATAATCAGGGTTATAATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATATAAGCTTCTGGGTCCGTCTACTGAGTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7r-72 SEQ ID NO: 72 GAGGTGCAGCTGTTGGAGTCAGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAGTAGTGATGTTATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAAGTATTACGAGGTCGGGTATGCAGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATATGCGCATCCTCAGTCGGCTGTTGAGTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7r-73 SEQ ID NO: 73 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCGTAATGAGCCGATGAGTTGGGTGCGCCAGGCTCCAGTGAAGGGTCTAGAGTG GGTCTCAACTATTTCGCCTGATGGTAGTGGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACATGGTCATCCTCAGGGGGCTCGTTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7r-74 SEQ ID NO: 74 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTTTGAATAGTGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTG GGTCTCAACTATTGGGTATGCGGGTACTCCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACCTCGGCATCCTCAGGGGGGGGTTACTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7r-75 SEQ ID NO: 75 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGCTCGGGGGCCTATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTACGAATGATGGTACGTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC
TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGGAACCGCCTCATAGTGGTAGGCCTATGTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7r-76 SEQ ID NO: 76 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCAGCGGACTGCTATGTCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTTGAGTG GGTCTCATCTATTGAGGCTTCGGGTCGGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACAGTCGCATCCTCAGAATGGTCGTTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7r-77 SEQ ID NO: 77 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATGCGTCGGAGATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAAGTATTACGGTTTATGGTGATAGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACCTCGGCATCCTCAGGGGGGGGTTACTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7r-78 SEQ ID NO: 78 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATGATTCGCATATGGCTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAAGGATTTCGAGGGAGGGTAAGGCGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGGCACCGAATGATCAGTCGGCGGCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGT CTCGAGC DOM7r-79 SEQ ID NO: 79 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATATGAGTGAGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGCTATTACTTCGGATGGTAGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACCTAGTCTGCCTCATGTTACGGCTTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7r-80 SEQ ID NO: 80 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGAGGTCTACTATGCATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGAGATTGATGCTCTGGGTACGGATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATCGTCTGATCATCCTCAGAATAGTTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7r-81 SEQ ID NO: 81 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGCCTCGTGAGATGTATTGGGCCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCGCACGGATTGGTTGGGATGGTCATACGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACAGCTGGGTCAGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7r-82 SEQ ID NO: 82 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATGCTTATAGTATGATGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTGGTAGGTGGGGTGAGATTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTAT ATTACTGTGCGAAACGTCGTTATATTGGGCCTTATATGCTTTCGGGTCGTTTTGACTACTGGGGTCAGGG AACCCTGGTCACCGTCTCGAGC DOM7r-83 SEQ ID NO: 83 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTATGCGGTATCCTATGGTGTGGGTCCGCCAGGCTCCAGGGAGGGGTCTAGAGTG GGTCTCATCTATTTCTCCTGCTGGTTATGGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGTCATGAGATTAGTCGGTTTTCTCGTTGGTCTTCTTTTGACTACTGGGGTCAGGG AACCCTGGTCACCGTCTCGAGC DOM7r-84 SEQ ID NO: 84 GAGGTGCAGCTGTTGGAGTCTGGGGGGGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCGGAAGTATAGGATGTCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCTATTGCGAGGAATGGTCGTTCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAACTACGTCTGGGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7r-85 SEQ ID NO: 85 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAATAAGAAGGAGATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCTATTGATGTGAGTGGTAATGTTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAATGGCTCATCCTCAGTCGGGGGTGGCTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7r-88 SEQ ID NO: 86 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCGGATGTATGATATGGCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAAAGTG GGTCTCAACTATTCTGTCTTCTGGTAAGGGTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATTGGCTCATCCTCAGAAGGGTAGTATTTTTGACTACCGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7r-89 SEQ ID NO: 87 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCATCAGGGTCCTATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATGGATTCAGGCTACGGGTGGTGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGGATGCATCCTCAGAGTGGTACTCTTTTTGACTACTGGGGTCAGGGAACCCTGGT CACCGTCTCGAGC DOM7r-90 SEQ ID NO: 88 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATGTTGCGGATATGGATTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGGGATTTCGTCGTCGGGTGGTTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGATACCGCGGTAT ATTACTGTGCGAAAAATTTGGGTCAGGGTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAG C DOM7r-92 SEQ ID NO: 89 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGATACGAGTAGTATGTTGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGTTATTCATCAGAGTGGTACGCCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATTTCCGTTTACTCATGGTAAGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGT CTCGAGC DOM7r-93 SEQ ID NO: 90 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAATAATTATACGATGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATTGATTCATACGAGTGGTACGGTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATGGAGTTCGAGGGCGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAG C DOM7r-94 SEQ ID NO: 91 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGGAATTATAGGATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAACTATTTCTCCTTTGGGTACGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGGGCGTTGGTCGATTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAG C DOM7r-95 SEQ ID NO: 92 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGGTAGTTATCCTATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTGGAGTG GGTCTCATGGATTCGTGGGAGGGGTCTTGCTACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATATTTTCATGGTAAGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAG C DOM7r-96 SEQ ID NO: 93 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTAGTGCTTATGTGATGGGTTGGGTACGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCATCGATTCGGATGCCGGGTTATCTGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAACGTACTCCTTTTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC
DOM7r-97 SEQ ID NO: 94 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTGAGCATTATTCGATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGAGATTGATCCGGATGGTATTATGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGCGCCGGGGGTTCTTGAGATGTGGATTACGCATTTTGACTACTGGGGTCAGGGAAC CCTGGTCACCGTCTCGAGC DOM7r-98 SEQ ID NO: 95 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTCGTCATTATGTGATGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGCTATTTCTGCGCATGGTAATCGGACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAATCTTATAGCCTTGCTCTGACTCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCAC CGTCTCGAGC DOM7r-99 SEQ ID NO: 96 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTCTCTCCTGTGCAG CCTCCGGATTCACCTTTACTGTGTATGAGATGAAGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTG GGTCTCAGCGATTTCTGCTGGGGGTAAGTATACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATC TCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTAT ATTACTGTGCGAAAGAGATTCGGCATCTTGATAATGCGGTTGAGTTTGACTACTGGGGTCAGGGAACCCT GGTCACCGTCTCGAGC Amino acid sequences: DOM7h-112 SEQ ID NO: 97 EVQLLESGGGLVQPGGSLRLSCAASGFTFGGYVMGWVRQAPGKGLEWVSAINRFGSSTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGSLRHFDYWGQGTLVTVSS DOM7h-98 SEQ ID NO: 98 EVQLLESGGGLVQPGGSLRLSCAASGFTFGNYAMAWVRQAPGKGLEWVSSIDMVGIKTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGFRIFDYWGQGTLVTVSS DOM7r-29 SEQ ID NO: 99 EVQLLESGGGLVQPGGSLRLSCAASGFTFKDYDMTWVRQAPGKGLEWVSMISSSGLWTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGFRLFPRTFDYWGQGTLVTVSS DOM7r-35 SEQ ID NO: 100 EVQLLESGGGLVQPGGSLRLSCAASGFTFSLYRMVWVRQAPGKGLEWVSMISQFGNQTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKVRSWDQTGGRRTFDYWGQGTLVTVSS DOM7r-36 SEQ ID NO: 101 EVQLLESGGGLVQPGGSLRLSCAASGFTFNHYTMGWVRQAPGKGLEWVSLIHPSGTVTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKWSSRAFDYWGQGTLVTVSS DOM7r-38 SEQ ID NO: 102 EVQLLESGGGLVQPGGSLRLSCAASGFTFDNNAMGWVRQAPGKGLEWVSTISANGNATYYADSVKGRFTI SRDNSKDTLYLQMNSLRAEDTAVYYCAKGFRRFDYWGQGTLVTVSS DOM7r31 SEQ ID NO: 103 EVQLLESGGGLVQPGGSLRLSCTASGFTFRHYRMGWVRQAPGKGLEWVSWIRPDGTFTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKSYMGDRFDYWGQGTLVTVSS DOM7h-32 SEQ ID NO: 104 EVQLLESGGGLVQPGGSLRLSCAASGFTFGNYPMTWVRQAPGKGLEWVSTISYGGLATYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKMAINGVRPRRFDYWGQGTLVTVSS DOM7h-33 SEQ ID NO: 105 EVQLLESGGGLVQPGGSLRLSCAASGFTFMAYQMAWVRQAPGKGLEWVSTIHQTGFSTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKVRSMRPYKFDYWGQGTLVTVSS DOM7h-34 SEQ ID NO: 106 EVQLLESGGGLVQPGGSLRLSCAASGFTFGDKAMGWVRQAPGKGLEWVSTISAPGNRTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGFRNFDYWGQGTLVTVSS DOM7h-83 SEQ ID NO: 107 EVQLLESGGGLVQPGGSLRLSCAASGFTFDGMRMGWVRQAPGKGLEWVSAIEVNGQHTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKMAHPQSGVAFDYWGQGTLVTVSS DOM7h-84 SEQ ID NO: 108 EVQLLESGGGLVQPGGSLRLSCAASGFTFTPDAMAWVRQAPGKGLEWVSSIGVNGSPTYYADSVKGRFTI SRDNSRNTLYLQMNSLRAEDTAVYYCAKMAHPQSGVAFDYWGQGTLVTVSS DOM7h-85 SEQ ID NO: 109 EVQLLESGGGLVQPGGSLRLSCAASGFTFYQSDMSWVRQAPGKGLEWVSSISSQGRSTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKMAHPQSGVAFDYWGQGTLVTVSS DOM7h-86 SEQ ID NO: 110 EVQLLESGGGLVQPGGSLRLSCTASGFTFAARDMSWVRQAPGKGLEWVSSISAQGAHTYYADSVKGRFTI SRDDSKNTLYLQMNSLRAEDTAVYYCAKPRHPQGGVTFDYWGQGTLVTVSS DOM7h-87 SEQ ID NO: 111 EVQLLESGGGLVQPGGSLRLSCAASGFTFDNGDMVWVRQAPGKGLEWVSGIAHNGRNTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKNLGQGFDYWGQGTLVTVSS DOM7h-88 SEQ ID NO: 112 EVQLLESGGGLVQPGGSLRLTCAASGFTLNGTSMGWVRQAPGKDLEWVSSIMPVGSHTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKMAHPQSGVAFDYWGQGTLVTVSS DOM7h-89 SEQ ID NO: 113 EVQLLESGGGLVQPGGSLRLSCAASGFTFDHAPMKWARQAPGKGLEWVSYIGSAGNMTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKDEGPFDYWGQGTLVTVSS DOM7h-90 SEQ ID NO: 114 EVQLLESGGGLVQPGGSLRLSCTASGFTFDGMDMSWVRQAPGKGLEWVSSISTTGGTTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKPRHPQGGVTFDYWGQGTLVTVSS DOM7h-91 SEQ ID NO: 115 EVQLLESGGGLVQPGGSLRLSCAASGFTFEAETMAWVRQAPGKGLEWVSTIHSEGSRTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKPRHPQGGVTFDYWGQGTLVTVSS DOM7h-92 SEQ ID NO: 116 EVQLLESGGGLVQPGGSLRLSCAASGFTFSTGEMAWVRQAPGKGLEWVSSISSSGATTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKPRHPQGGVTFDYWGQGTLVTVSS DOM7h-93 SEQ ID NO: 117 EVQLLESGGGLVQPGGSLRLSCAASGFTFPSADMVWVRQAPGKGLEWVSRISPEGNHTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAERPPSDYVSFDYWGQGTLVTVSS DOM7h-94 SEQ ID NO: 118 EVQLLESGGGLVQPGGSLRLSCAASGFTFANATMSWVRQAPGKGLEWVSDIDQVGHATYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKYSWHPDLFDYWGQGTLVTVSS DOM7h-95 SEQ ID NO: 119 EVRLLESGGGLVQPGGSLRLSCAASGFTFKDYGMNWVRQAPGKGLEWVSRISRNGTVTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKLAAPVRQKGMDFDYWGQGTLVTVSS DOM7h-96 SEQ ID NO: 120 EVQLLESGGGLVQPGGSLRLSCAASGFTFEWYNMSWVRQAPGKDLEWVSSISHDGWNTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGMIGFDYWGQGTLVTVSS DOM7h-97 SEQ ID NO: 121 VQLLESGGGLVQPGGSLRLSCAASGFTFDIYTMHWVRQAPGKGLEWVSTIVPQGTPTYYADSVKGRFTIS RDNSKNTLYLQMNSLRAEDTAVYYCAKSKRRFLKRFDYWGQGTLVTVSS DOM7h-99 SEQ ID NO: 122 EVQLLESGGGLVQPGGSLRLSCAASGFTFARYDMQWVRQAPGKGLEWVSSIKSNGMKTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKASMWTFDYWGQGTLVTVSN DOM7h-100 SEQ ID NO: 123 EVQLLESGGGLVQPGGSLRLSCAASGFTFMLYHMGWVRQAPGKGLEWVSAITGGGYPTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKLGLRGVLWRRRFDYWGQGTLVTVSS DOM7h-101 SEQ ID NO: 124 EVQLLESGGGLVQPGGSLRLSCAASGFTFGAYSMMWVRQAPGKGLEWVSRISRNGTVTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKIRWNTAQVPVFDYWGQGTLVTVSS DOM7h-102 SEQ ID NO: 125 EVQLLESGGGLVQPGGSLRLSCAASGFTFGPYWMAWVRQAPGKGLEWVSTITPSGRGTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGRPRVGLWRSGFDYWGQGTLVTVSS DOM7h-103 SEQ ID NO: 126 EVQLLESGGGLVQPGGSLRLSCAASGFTFGQYAMQWVRQAPGKGLEWVSSINITGSTTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGFRSFDYWGQGTLVTVSS DOM7h-106 SEQ ID NO: 127 VQLLESGGGLVQPGGSLRLSCAASGFTFAGYTMSWVRQAPGKGLEWVSTISGFGWTTYYADSVKGRFTIS RDNSKNTLYLQMNSLRAEDTAVYYCAKRLGMRFDYWGQGTLVTVSS DOM7h-109 SEQ ID NO: 129 EVQLLESGGGLVQPGGSLRLSCAASGFTFGPYSMGWVRQAPGKGLEWVSFIHSDGRHTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKKTPYRFDYWGQGTLVTVSS DOM7h-111 SEQ ID NO: 130 EVQLLESGGGLVQPGGSLRLSCAASGFTFGQYAMQWVRQAPGKGLEWVSSINITGSTTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGFRSFDYWGQGTLVTVSS DOM7h-114 SEQ ID NO: 131 EVQLLESGGGLVQPGGSLRLSCAASGFTFRRYAMSWVRQAPGKGLEWVSTISPYGPVTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKAYYGGFDYWGQGTLVTVSS DOM7r-34 SEQ ID NO: 132 EVQLLESGGGLVQPGGSLRLSCAASGFTFDAYAMGWVRQAPGKGLEWVSKIDSPGWRTYYADSVKGRFTI
SRDNSKNTLYLQMNSLRAEDTAVYYCAKSARMRSRHFDYWGQGTLVTVSS DOM7r-37 SEQ ID NO: 133 EVQLLESGGGLVQPGGSLRLSCAASGFTFKDYGMNWVRQAPGKGLEWVSRISRNGTVTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKIRWNTAQVPVFDYWGQGTLVTVSS DOM7r-39 SEQ ID NO: 134 EVQLLESGGGLVQPGGSLRLSCATSGFTFPSYTMGWVRQAPGKGLEWVSRISRTGNYTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKPMYNRGSSYFDYWGQGTLVTVSS DOM7r-40 SEQ ID NO: 135 EVQLLESGGGLVQPGGSLRLSCAASGFTFSQYQMSWVRQAPGKGLEWVSSISPTGIQTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKRLIGMPYVEDTFDYWGQGTLVTVSS DOM7r-41 SEQ ID NO: 136 EVQLLESGGGLVQPGGSLRLSCAASGFTFMEYEMEWVRQAPGKGLEWVSGITNSGSGTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAIMQHPQATGGRVGFDYWGQGTLVTVSS DOM7r-42 SEQ ID NO: 137 EVQLLESGGGLVQPGGSLRLSCAASGFTFPRYTMKWVRQAPGKGLEWVSSIDRTGRKTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKESLVSFDYWGQGTLVTVSS DOM7r-43 SEQ ID NO: 138 EVQLLESGGGLVQPGGSLRLSCAASGFTFGGYTMPWVRQAPGKGLEWVSTISRDGNYTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKDIGMGFDYGGRGTLVTVSS DOM7r-44 SEQ ID NO: 139 EVQLLESGGGLVQPGGSLRLSCAASGFTFEIYAMHWVRQAPGKGLEWVSTISSGGKGTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKSRTMYFRVREAFDYWGQGTLVTVSS DOM7r-45 SEQ ID NO: 140 EVQLLESGGGLVQPGGSLRLSCAASGFTFRAYRMMWVRQAPGKGLEWVSSIDPDGAVTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAEHFDLAMPNPNAKFDYWGQGTLVTVSS DOM7r-46 SEQ ID NO: 141 EVQLLESGGGLVQPGGSLRLSCAASGFTFSRYQMSWVRQAPGKGLEWVSSIKSNGSSTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKPSRQSFQYPSFDYWGQGTLVTVSS DOM7r-47 SEQ ID NO: 142 EVQLLESGGGLVQPGGSLRLSCAASGFTFGRYKMGWVRQAPGKGLEWVSSISPTGSSTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKTGYVMVEHFDYWGQGTLVTVSS DOM7r-48 SEQ ID NO: 143 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYPMKWVRQAPGKGLEWVSTINSSGTITYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKPLLPFDYWGQGTLVTVSS DOM7r-49 SEQ ID NO: 144 EVQLLESGGGLVQPGGSLRLSCAASGFTFARYRMCWVRQAPGKGLEWVSCIRDPGFPTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKCSPSSTQCTGLFDYWGQGTLVTVSS DOM7r-50 SEQ ID NO: 145 VQLLESGGGLVQPGGSLRLSCAASGFTFRFYGMAWVRQAPGKGLEWVSLIDPPGGATYYADSVKGRFTIS RDNSKNTLYLQMNSLRAEDTAVYYCAKMERRHLKSGHKGFDYWGQGTLVTVSS DOM7r-51 SEQ ID NO: 146 EVQLLESGGGLVQPGGSLRLSCAASGFTFTEYDMMWVRQAPGKGLEWVSSISHRGEKTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKDKRYRGSQHYFDYWGQGTLVTVSS DOM7r-52 SEQ ID NO: 147 VQLLESGGGLVQPGGSLRLSCAASGFTFRSYDMGWARQAPGKGLEWVSTIGSNGANTYYADSVKGRFTIS RDNSKNTLYLQMNSLRAEDTAVYYCAKLMGMFDYWGQGTLVTVSS DOM7r-53 SEQ ID NO: 148 EVQLLESGGGLVQPGGSLRLSCAASGFTFERYSMRWVRQAPGKGLEWVSTIGSTGKWTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGRGLVSFDYWGQGTLVTVSS DOM7r-54 SEQ ID NO: 149 EVQLLESGGGLVQPGGSLRLSCAASGFTFRRYSMSWVRQAPGKGLEWVSSIDRSGRMTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKSRLSSTGSEGHNFDYWGQGTLVTVSS DOM7r-55 SEQ ID NO: 150 VQLLESGGGLVQPGGSLRLSCAASGFTFKWYPMKWVRQAPGKGLEWVSTIAYDGVQTYYADSVKGRFTIS RDNSKNTLYLQMNSLRAEDTAVYYCAKLGPTSRVFAATDFDYWGQGTLVTVSS DOM7r-56 SEQ ID NO: 151 EVQLLESGGGLVQPGGSLRLSCAASGFTFPNYAMKWGRQAPGKGLEWVSTIDTSGSTTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKLTHPMAPRPAFDYWGQGTLVTVSS DOM7r-57 SEQ ID NO: 152 EVQLLESGGGLVQPGGSLRLSCAASGFTFDLTEMEWVRQAPGKGLEWVSSIGPWGTPTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKISHPQAMYHTFDYWGQGTLVTVSS DOM7r-58 SEQ ID NO: 153 EVQLLESGGGLVQPGGSLRLSCAASGFTFAHQDMTWVRQAPGKGLEWVSDIDHSGSYTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKWWHPQGGTFDYWGQGTLVTVSS DOM7r-59 SEQ ID NO: 154 EVQLLESGGGLVQPGGSLRLSCAASGFTFGSKDMSWVRQAPGKGLEWVSTIGANGKATYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAEAGHPQAPSFKSFDYWGQGTLVTVSS DOM7r-60 SEQ ID NO: 155 EVQLLESGGGLVQPGGSLRLSCAASGFTFLNAEMSWVRQAPGKGLEWVSTIDRDGANTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKLPPPMSPKKFDYWGQGTLVTVSS DOM7r-61 SEQ ID NO: 156 EVQLLESGGGLVQPGGSLRLSCAASGFTFEREGMMWVRQAPGKGLEWVSTIDRMGRYTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKRDSHPMGFDYRGQGTLVTVSS DOM7r-62 SEQ ID NO: 157 EVQLLESGGGLVQPGGSLRLSCAASGFTFENEKMSWVRQAPGKGLEWVSSIGPTGSGTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKTPHPQVSSFDYWGQGTLVTVSS DOM7r-63 SEQ ID NO: 158 EVQLLESGGGLVQPGGSLRLSCAASGFTFEIDHMGWVRQAPGKGLEWVSEIAPSGDRTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKVICQNQCLFDYWGQGTLVTVSS DOM7r-64 SEQ ID NO: 159 EVQLLESGGGLVQPGGSLRLSCAASGFTFRDSEMSWVRQAPGKGLEWVSFITSDGRDTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKPSLPHVTAFDYWGQGTLVTVSS DOM7r-65 SEQ ID NO: 160 EVQLLESGGGLVQPGGSLRLSCAASGFTFEDETMSWARQAPGKGLEWVSSIGDAGMPTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGEPIYVHTTHFDYWGQGTLVTVSS DOM7r-66 SEQ ID NO: 161 EVQLLESGGGLVQPGGSLRLSCAASGFTFPHGKMGWVRQAPGKGLEWVSWIAGSGDMTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKLGHPQRGFDYWGQGTLVTVSS DOM7r-67 SEQ ID NO: 162 EVQLLESGGGLVQPGGSLRLSCAASGFTFGTSDMSWVRQAPGKGLEWVSTIDSGGSFTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKPRHPQGGVTFDYWGQGTLVTVSS DOM7r-68 SEQ ID NO: 163 EVQLLESGGGLVQPGGSLRLSCAASGFTFEHVPMAWVRQAPGKGLEWVSRISEQGSNTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKVQHPMSPHEFDYWGQGTLVTVSS DOM7r-69 SEQ ID NO: 164 EVQLLESGGGLVQPGGSLRLSCAASGFTFEQGMMSWVRQAPGKGLEWVSSINPGGQFTYYADSVKGRFTI SRDNSRNTLYLQMNSLRAEDTAVYYCAEDLGPGFDYWGQGTLVTVSS DOM7r-70 SEQ ID NO: 165 EVQLLESGGGLVQPGGSLRLSCAASGFTFERWPMSWVRQAPGKGLEWVSTIDRSGNTTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKVLHPQAGSAFDYWGQGTLVTVSS DOM7r-71 SEQ ID NO: 166 EVQLLESGGGSVQPGGSLRLSCAASGFTFGGSDMGWVRQAPGKGLEWVSYIDNQGYNTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKYKLLGPSTEFDYWGQGTLVTVSS DOM7r-72 SEQ ID NO: 167 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSDVMSWVRQAPGKGLEWVSSITRSGMQTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKYAHPQSAVEFDYWGQGTLVTVSS DOM7r-73 SEQ ID NO: 168 EVQLLESGGGLVQPGGSLRLSCAASGFTFRNEPMSWVRQAPVKGLEWVSTISPDGSGTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKHGHPQGARFDYWGQGTLVTVSS DOM7r-74 SEQ ID NO: 169 EVQLLESGGGLVQPGGSLRLSCAASGFTFLNSEMSWVRQAPGKGLEWVSTIGYAGTPTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKPRHPQGGVTFDYWGQGTLVTVSS DOM7r-75 SEQ ID NO: 170 EVQLLESGGGLVQPGGSLRLSCAASGFTFARGPMSWVRQAPGKGLEWVSTITNDGTSTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAEPPHSGRPMFDYWGQGTLVTVSS DOM7r-76 SEQ ID NO: 171 EVQLLESGGGLVQPGGSLRLSCAASGFTFQRTAMSWVRQAPGKGLEWVSSIEASGRYTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKQSHPQNGRFDYWGQGTLVTVSS DOM7r-77 SEQ ID NO: 172 EVQLLESGGGLVQPGGSLRLSCAASGFTFDASEMAWVRQAPGKGLEWVSSITVYGDRTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKPRHPQGGVTFDYWGQGTLVTVSS DOM7r-78 SEQ ID NO: 173 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDSHMAWVRQAPGKGLEWVSRISREGKATYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAAPNDQSAAFDYWGQGTLVTVSS DOM7r-79 SEQ ID NO: 174
EVQLLESGGGLVQPGGSLRLSCAASGFTFDMSEMSWVRQAPGKGLEWVSAITSDGSSTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKPSLPHVTAFDYWGQGTLVTVSS DOM7r-80 SEQ ID NO: 175 EVQLLESGGGLVQPGGSLRLSCAASGFTFERSTMHWVRQAPGKGLEWVSEIDALGTDTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKSSDHPQNSFDYWGQGTLVTVSS DOM7r-81 SEQ ID NO: 176 EVQLLESGGGLVQPGGSLRLSCAASGFTFEPREMYWARQAPGKGLEWVARIGWDGHTTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKQLGQFDYWGQGTLVTVSS DOM7r-82 SEQ ID NO: 177 EVQLLESGGGLVQPGGSLRLSCAASGFTFDAYSMMWVRQAPGKGLEWVSTIGRWGEITYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKRRYIGPYMLSGRFDYWGQGTLVTVSS DOM7r-83 SEQ ID NO: 178 EVQLLESGGGLVQPGGSLRLSCAASGFTFMRYPMVWVRQAPGRGLEWVSSISPAGYGTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGHEISRFSRWSSFDYWGQGTLVTVSS DOM7r-84 SEQ ID NO: 179 EVQLLESGGGLVQPGGSLRLSCAASGFTFRKYRMSWVRQAPGKGLEWVSSIARNGRSTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKTTSGFDYWGQGTLVTVSS DOM7r-85 SEQ ID NO: 180 EVQLLESGGGLVQPGGSLRLSCAASGFTFNKKEMGWVRQAPGKGLEWVSSIDVSGNVTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKMAHPQSGVAFDYWGQGTLVTVSS DOM7r-88 SEQ ID NO: 181 EVQLLESGGGLVQPGGSLRLSCAASGFTFRMYDMAWVRQAPGKGLKWVSTILSSGKGTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKLAHPQKGSIFDYRGQGTLVTVSS DOM7r-89 SEQ ID NO: 182 EVQLLESGGGLVQPGGSLRLSCAASGFTFHQGPMGWVRQAPGKGLEWVSWIQATGGATYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGMHPQSGTLFDYWGQGTLVTVSS DOM7r-90 SEQ ID NO: 183 EVQLLESGGGLVQPGGSLRLSCAASGFTFDVADMDWVRQAPGKGLEWVSGISSSGGYTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKNLGQGFDYWGQGTLVTVSS DOM7r-92 SEQ ID NO: 184 EVQLLESGGGLVQPGGSLRLSCAASGFTFDTSSMLWVRQAPGKGLEWVSVIHQSGTPTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKFPFTHGKFDYWGQGTLVTVSS DOM7r-93 SEQ ID NO: 185 EVQLLESGGGLVQPGGSLRLSCAASGFTFNNYTMGWVRQAPGKGLEWVSLIHTSGTVTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKWSSRAFDYWGQGTLVTVSS DOM7r-94 SEQ ID NO: 186 EVQLLESGGGLVQPGGSLRLSCAASGFTFGNYRMTWVRQAPGKGLEWVSTISPLGTYTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKGRWSIFDYWGQGTLVTVSS DOM7r-95 SEQ ID NO: 187 EVQLLESGGGLVQPGGSLRLSCAASGFTFGSYPMGWVRQAPGKGLEWVSWIRGRGLATYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKYFHGKFDYWGQGTLVTVSS DOM7r-96 SEQ ID NO: 188 EVQLLESGGGLVQPGGSLRLSCAASGFTFSAYVMGWVRQAPGKGLEWVSSIRMPGYLTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKRTPFFDYWGQGTLVTVSS DOM7r-97 SEQ ID NO: 189 EVQLLESGGGLVQPGGSLRLSCAASGFTFEHYSMGWVRQAPGKGLEWVSEIDPDGIMTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKAPGVLEMWITHFDYWGQGTLVTVSS DOM7r-98 SEQ ID NO: 190 EVQLLESGGGLVQPGGSLRLSCAASGFTFRHYVMGWVRQAPGKGLEWVSAISAHGNRTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKSYSLALTPFDYWGQGTLVTVSS DOM7r-99 SEQ ID NO: 191 EVQLLESGGGLVQPGGSLRLSCAASGFTFTVYEMKWVRQAPGKGLEWVSAISAGGKYTYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCAKEIRHLDNAVEFDYWGQGTLVTVSS
EXEMPLIFICATION
Example 1
Biophysical Characterisation
[0080] The routine bacterial expression level in 2.5 L shake flasks was determined following culture in Onex media at 30° C. for 48 hrs at 250 rpm. The biophysical characteristics were determined by SEC MALLS and DSC.
[0081] SEC MALLS (size exclusion chromatography with multi-angle-LASER-light-scattering) is a non-invasive technique for the characterizing of macromolecules in solution. Briefly, proteins (at concentration of 1 mg/mL in buffer Dulbecco's PBS) are separated according to their hydrodynamic properties by size exclusion chromatography (column: TSK3000; S200). Following separation, the propensity of the protein to scatter light is measured using a multi-angle-LASER-light-scattering (MALLS) detector. The intensity of the scattered light while protein passes through the detector is measured as a function of angle. This measurement taken together with the protein concentration determined using the refractive index (R1) detector allows calculation of the molar mass using appropriate equations (integral part of the analysis software Astra v.5.3.4.12). The highest concentration at the mid-point of the eluting peak is about 8-10 uM and this consequently is the concentration at which MALLS determines the in-solution state of the protein.
[0082] DSC (Differential Scanning calorimetry): briefly, the protein is heated at a constant rate of 180 degrees C./hrs (at 1 mg/mL in PBS) and a detectable heat change associated with thermal denaturation measured. The transition midpoint (appTm) is determined, which is described as the temperature where 50% of the protein is in its native conformation and the other 50% is denatured. Here, DSC determined the apparent transition midpoint (appTm) as most of the proteins examined do not fully refold. The higher the Tm, the more stable the molecule. The software package used was OriginR v7.0383.
[0083] Characteristics of the VH dAbs are summarised in Table 1 below. Cross-reactivity of the AlbudAbs® (i.e., anti-serum albumin dAbs) was determined against human, Cynomolgus monkey (cyno), rat and mouse serum albumin ("4AGs" in the table) using surface plasmon resonance (SPR). In this case, Biacore® was used. The epitope mapping to domain 1, 2 and/or 3 (D1,2,3) of human serum albumin (HSA) was performed using SPR and purified individual domains of HSA (in-house) covalently coupled to a CM5 chip (amine coupling). The expression was in 2.5 L baffled glass flasks in a volume of 500 mL in OverNight Express® at 30 C, 250 rpm.
[0084] MALLS results: A single VH AlbudAb is 14 kDa in size. Any value between 14 and 28 kDa as determined by MALLS is indicative of varying degrees of self-association or dimer formation (i.e. 16 kDa predominately monomeric under the conditions tested whereas 22 kDa indicates a strong propensity to dimerise under MALLS conditions).
[0085] DSC results: The concentration of protein in a DSC experiment is much higher at 1 mg/mL in the actual reaction cell compared to MALLS. This higher concentration could explain in part the presence of two appTms for some AlbudAbs as seen in tablel; the first Tm constitutes the dissociation of the dimeric complex, whereas the second Tm represents the unfolding of the actual AlbudAb protein.
TABLE-US-00002 TABLE 1 Binding to Expression (E. coli) D1/2/3 of x-reactivity MALLS DSC [° C.] mg/L HSA *Clone Name (4AGs) [kDa] appTm1 appTm2 in shake flasks SPR DOM7h-112 no human; 16 62 66 46.6 No binding yes other 3 antigens DOM7h-98 yes 14.7 65 28.3 D2 DOM7r-29 yes 16.9 62.5 21 D2 DOM7r-35 yes 21.8 58.7 61.8 33.5 D2 DOM7r-36 yes 98/45/16 67.4 69.9 31.5 D2 DOM7r-38 yes 14.8 61.3 64.5 61.5 D2 DOM7r-31 yes 15 67.9 74.5 25 D2 *precise in-solution affinities of the leads will be determine by ITC, equilibrium dialysis or fluorescence polarisation
Apart from DOM7h-112, all above AlbudAbs leads are fully cross-reactive between the four species of serum albumin. All identified AlbudAbs bind Domain2 of HSA and express reasonably well in shake flasks under non-optimised conditions. 5 out of 7 AlbudAbs are monomeric as determined by MALLS, whereas DOM7r-35 shows a significant propensity to dimerise under the MALLS conditions. Monomeric state is advantageous because it avoids dimerisation and the risk of products that may cross-link targets such as cell-surface receptors.
[0086] DOM7r-36 shows some degree of aggregate formation (less than 10% when quantified on MALLS). For 5 out of 7 AlbudAbs, 2 appTms can be determined. This is due to the higher experimental concentration in DSC experiments and slightly different in-solution state of the dAb at this elevated concentration (for details, see explanation also above).
Example 2
Determination of Serum Half Life in Rat
[0087] AlbudAbs were cloned into the pDOM5 vector. The pDOM5 vector is a pUC 119-based expression vector where protein expression is driven by the LacZ promoter. A GAS 1 leader sequence (see WO 2005/093074) ensures secretion of isolated, soluble dAbs into the periplasm and culture supernatant of E. coli. dAbs are cloned SalI/NotI in this vector, which appends a myc tag at the C-terminus of the dAb. For each AlbudAb, 20-50 mg quantities were expressed in E. coli and purified from bacterial culture supernatant using protein A affinity resin and eluted with 100 mM glycine pH2. The proteins were concentrated to greater than 1 mg/ml, buffer exchanged into PBS and endotoxin depleted using Q spin columns (Vivascience). For Rat pharmacokinetic (PK) analysis, AlbudAbs were dosed as single i.v injections at 2.5 mg/kg using 3 rats per compound. Serum samples were taken at 0.16, 1, 4, 12, 24, 48, 72, 96, 120, 168 hrs. Analysis of serum levels was by anti-myc capture followed by anti-VH detection ELISA as per the method described below.
[0088] Results are shown in table 2. All tested AlbudAbs show a serum-half life extending ability (negative control HEL4 dAb with T1/2 of 20mins in rat) to varying degrees; this trend can also be seen in the calculated AUC being the highest value for the longest t1/2. The longest serum half-life with 34.5 hrs approximates the serum half-life of rat serm albumin.
[0089] The specific affinities of the AlbudAbs to RSA will need to be determined.
TABLE-US-00003 TABLE 2 T 1/2* AUC 0-inf VH dAb [hr] [hr*ug/mL)] DOM7h-98 13.5 577.5 DOM7r-29 21.9 697.6 DOM7r-35 34.4 1249.6 DOM7r-36 26.5 910.8 DOM7r-38 8.8 203.4 DOM7r-31 11 239 *The serum half-life of rat serum albumin is 35 hrs. T 1/2 is a measure of the circulation time of the molecule in the subjects. AUC = area under the curve, which is a PK profile parameter
Anti-Myc ELISA Method Using MSD
[0090] The AlbudAb concentration in serum was measured by anti-myc ELISA. Briefly, goat anti-myc polyclonal antibody (1:500; Abcam, catalogue number ab9132) was coated overnight onto Nunc 96-well Maxisorp plates and blocked with 5% BSA/PBS+1% TWEEN®. Serum samples were added at a range of dilutions alongside a standard at known concentrations. Bound myc-tagged AlbudAb was then detected using a rabbit polyclonal anti-VH directly labelled with the MSD sulfo-tag. Each dAb was diluted in assay buffer containing 10% control rat serum (1:1000; in-house reagent) (method DM222). MSD (MesoScaleDiscovery; MesoScale.com) utilizes electrochemiluminescence detection of the sulfo-tag after electrochemical stimulus.
[0091] From the raw ELISA data, the concentration of unknown samples was established by interpolation against the standard curve taking into account dilution factors. The mean concentration result from each time point was determined from replicate values and entered into WinNonLin analysis package (eg version 5.1 (available from Pharsight Corp., Mountain View, Calif. 94040, USA). The data was fitted using a non-compartmental model, where PK parameters were estimated by the software to give terminal half-lives. Dosing information and time points were selected to reflect the terminal phase of each PK profile.
Example 3
Affinity Maturation of Naive VH AlbudAbs®
[0092] 12 VH AlbudAb leads isolated from naive selection were taken forward for affinity maturation. Individual error prone libraries (EP) of DOM7r-36, DOM7r-35, DOM7r-31, DOM7h-98, DOM7h-112, DOM7r-38 and DOM7r-29 were made, whereas the following parental clones were pooled and combined in a single EP library and screened together: DOM7r-83, DOM7r-85, DOM7r-92, DOM7r-94 and DOM7r-95. All libraries were greater than 2×109 CFU/mL. Selections were performed in 4 rounds on soluble antigen (biotin-HSA; biotin-RSA; blocking with 2% Marvel) by cross over-selection with decreasing concentration of antigen: Round1 at 1 μM (HSA or RSA), Round 2 at 1 μM (RSA or HSA), followed by 2 further rounds of selection at 100 nM and 10 nM, respectively, with the same antigen as in Round2. Ca. 3000 samples from both, R3 and R4 outputs were screened by supernatant BIAcore and clones ranked according to their off-rate only. Eight-point dilution kinetic affinity measurements were performed on improved clones (data below).
TABLE-US-00004 TABLE 3 Improved clone From round DOM7r-31-14 R4 DOM7r-201 R3 DOM7r-36-2 R4 DOM7r-36-8 R4 DOM7r-92-4 R4 DOM7h-98-4 R3
TABLE-US-00005 TABLE 4 Kinetic data: RSA HSA CSA MSA KD (M) KD (M) KD (M) KD (M) DOM7r-201 2.4E-07 6.0E-08 5.8E-08 2.8E-07 DOM7r-36-2 1.9E-07 1.5E-07 1.8E-07 5.2E-07 DOM7r-36-8 2.1E-07 6.7E-08 9.2E-08 5.2E-07 DOM7r-92-4 2.6E-07 1.3E-07 9.8E-08 1.1E-07 DOM7h-98-4 5.8E-07 2.0E-06 3.6E-06 8.1E-07 DOM7r-31-14 4.6E-08 5.8E-08 3.1E-05 6.0E-09
TABLE-US-00006 TABLE 5 Sequence alignment: 5 15 25 35 45 55 A EVQLLESGGG LVQPGGSLRL SCAASGFTFS SYAMSWVRQA PGKGLEWVSA ISGSGGSTYY B EVQLLESGGG LVQPGGSLRL SCAASGFTFN HYTMGWVRQA PGKGLEWVSL IHPSGTVIYY C EVQLLESGGG LVQPGGSLRL SCAASGFTFN HYTMGWVRQA PGKGREWVSL IHPSGTVTYY D EVQLLESGGG LVQPGGSLRL SCAASGFTFN HYTMGWVRQA PGKGLEWVSL IHPSGTVIYY E EVQLLESGGG LVQPGGSLRL SCAASGFTFD TSSMLWVRQA PGKGLEWVSV IHQSGTPTYY F EVQLLESGGG LVQPGGSLRL SCAASGFTFG NYAMAWVRQA PGKGLEWVSS IDMVGIKTYY G EVQLLESGGG LVQPGGSLRL SCTASGFTFR HYRMGWVRQA PGKGLEWVSW IRPDGTFTYY 65 75 85 95 105 115 A ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKSY GA~~~FDYWG QGTLVTVSS B ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKWS SRA~~FDYWG QGTLVTVSS C ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKWS SRA~~FDYWG QGTLVTVSS D ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARWS SRA~~FDYWG QGTLVTVSS E ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKFP STHGKFDYWG QGTLVTVSS F ADSVKGRFTN SRDNSKNTLY LQMNSLRAED TAVYYCARGF RI~~~FDYWG QGTLVTVSS G ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKSY MADR~FDYWG QGTLVTVSS A = VH dummy B = DOM7r-201 C = DOM7r-36-2 D = DOM7r-36-8 E = DOM7r-92-4 F = DOM7h-98-4 G = DOM7r-31-1
The CDRs are underlined; sequences are shown N- to C-terminus; "˜" denote gaps introduced for alignment
TABLE-US-00007 Nucleotide sequences DOM7r-201 SEQ ID NO: 192 GAGGTGCAACTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTC CCTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTTAATCATTATACGA TGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATTG ATTCATCCGAGTGGTACGGTGATATACTACGCAGACTCCGTGAAGGGCCG GTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGA ACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATGGAGT TCGAGGGCATTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCTAG C DOM7r-36-2 SEQ ID NO: 193 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTC CCTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTTAATCATTATACGA TGGGGTGGGTCCGCCAGGCTCCAGGGAAGGGTCGAGAGTGGGTCTCATTG ATTCATCCGAGTGGTACGGTGACATACTACGCAGACTCCGTGAAGGGCCG GTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGA ACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATGGAGT TCGAGGGCGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAG C DOM7r-36-8 SEQ ID NO: 194 GAGGTGCAACTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTC CCTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTTAATCATTATACGA TGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATTG ATTCATCCGAGTGGTACGGTGATATACTACGCAGACTCCGTGAAGGGCCG GTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGA ACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAGATGGAGT TCGAGGGCGTTTGACTACTGGGGTCAGGGGACCCTGGTCACCGTCTCGAG C DOM7r-92-4 SEQ ID NO: 195 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTC CCTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTTGATACGAGTAGTA TGTTGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCAGTT ATTCATCAGAGTGGTACGCCTACATACTACGCAGACTCCGTGAAGGGCCG GTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGA ACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATTTCCG TCTACTCATGGTAAGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGT CTCGAGC DOM7h-98-4 SEQ ID NO: 196 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTC CCTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTTGGTAATTATGCGA TGGCGTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCG ATTGATATGGTTGGTATTAAGACATACTACGCAGACTCCGTGAAGGGCCG GTTCACCAATTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGA ACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAGAGGTTTT CGTATTTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTCGAGC DOM7r-31-14 SEQ ID NO: 197 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTC CCTGCGTCTCTCCTGTACAGCCTCCGGATTCACCTTTAGGCATTATCGTA TGGGTTGGGTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATGG ATTCGTCCGGATGGTACGTTTACATACTACGCAGACTCCGTGAAGGGCCG GTTCACCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGA ACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGCGAAATCTTAT ATGGCTGATAGGTTTGACTACTGGGGTCAGGGAACCCTGGTCACCGTCTC GAGC Amino Acid Sequences DOM7r-201 SEQ ID NO: 198 EVQLLESGGGLVQPGGSLRLSCAASGFTFNHYTMGWVRQAPGKGLEWVSL IHPSGTVIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKWS SRAFDYWGQGTLVTVSS DOM7r-36-2 SEQ ID NO: 199 EVQLLESGGGLVQPGGSLRLSCAASGFTFNHYTMGWVRQAPGKGREWVSL IHPSGTVTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKWS SRAFDYWGQGTLVTVSS DOM7r-36-8 SEQ ID NO: 200 EVQLLESGGGLVQPGGSLRLSCAASGFTFNHYTMGWVRQAPGKGLEWVSL IHPSGTVIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWS SRAFDYWGQGTLVTVSS DOM7r-92-4 SEQ ID NO: 201 EVQLLESGGGLVQPGGSLRLSCAASGFTFDTSSMLWVRQAPGKGLEWVSV IHQSGTPTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKFP STHGKFDYWGQGTLVTVSS DOM7h-98-4 SEQ ID NO: 202 EVQLLESGGGLVQPGGSLRLSCAASGFTFGNYAMAWVRQAPGKGLEWVSS IDMVGIKTYYADSVKGRFTNSRDNSKNTLYLQMNSLRAEDTAVYYCARGF RIFDYWGQGTLVTVSS DOM7r-31-14 SEQ ID NO: 203 EVQLLESGGGLVQPGGSLRLSCTASGFTFRHYRMGWVRQAPGKGLEWVSW IRPDGTFTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSY MADRFDYWGQGTLVTVSS
Sequence CWU
1
1
2001351DNAArtificial SequenceDerived from a Human germline sequence
1gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggg gggtatgtga tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagct attaataggt ttggttcgtc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaggtagt
300ttgcggcatt ttgactactg gggtcaggga accctggtca ccgtctcgag c
3512348DNAArtificial SequenceDerived from a Human germline sequence
2gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggt aattatgcga tggcgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatcg attgatatgg ttggtattaa gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaggtttt
300cgtatttttg actactgggg tcagggaacc ctggtcaccg tctcgagc
3483361DNAArtificial SequenceDerived from a Human germline sequence
3gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttaag gattatgata tgacttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaatg atttcttcgt cgggtctttg gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaggtttt
300aggctgtttc ctcggacttt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
360g
3614372DNAArtificial SequenceDerived from a Human germline sequence
4gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt caccttttcg ctgtatagga tggtgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaatg atttctcagt ttggtaatca gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagttagg
300tcttgggatc agactggtgg tcgtcgtact tttgactact ggggtcaggg aaccctggtc
360accgtctcga gc
3725351DNAArtificial SequenceDerived from a Human germline sequence
5gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttaat cattatacga tggggtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcattg attcatccga gtggtacggt gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatggagt
300tcgagggcgt ttgactactg gggtcaggga accctggtca ccgtctcgag c
3516348DNAArtificial SequenceDerived from a Human germline sequence
6gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat aataatgcga tggggtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact attagtgcga atggtaatgc gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagga cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagggttt
300cgtcggtttg actactgggg tcagggaacc ctggtcaccg tctcgagc
3487355DNAArtificial SequenceDerived from a Human germline sequence
7gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtacag cctccggatt cacctttagg cattatcgta tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatgg attcgtccgg atggtacgtt tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatcttat
300atgggtgata ggtttgacta ctggggtcag ggaaccctgg tcaccgtctc gagcg
3558366DNAArtificial SequenceDerived from a Human germline sequence
8gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgcgcag cctccggatt cacctttggt aattatccga tgacgtgggt ccgccaggct
120ccagggaagg gtctggagtg ggtctcaact attagttatg gtggtcttgc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaatggcg
300attaatggtg ttaggcctag gcggtttgac tactggggtc agggaaccct ggtcaccgtc
360tcgagc
3669360DNAArtificial SequenceDerived from a Human germline sequence
9gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttatg gcgtatcaga tggcttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact attcatcaga cgggtttttc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggat accgcggtat attactgtgc gaaagtgcgt
300tctatgcgtc cttataagtt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36010348DNAArtificial SequenceDerived from a Human germline sequence
10gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggt gataaggcaa tggggtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaacg attagtgctc ctggtaaccg tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaggtttt
300cggaattttg actactgggg tcagggaacc ctggtcaccg tctcgagc
34811363DNAArtificial SequenceDerived from a Human germline sequence
11gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat gggatgcgta tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagct attgaggtga atggtcagca tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaatggct
300catcctcagt cgggggtggc ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36312363DNAArtificial SequenceDerived from a Human germline sequence
12gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttacg cctgatgcta tggcgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatcg attggtgtga atggttctcc gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaggaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaatggct
300catcctcagt cgggggtggc ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36313363DNAArtificial SequenceDerived from a Human germline sequence
13gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt caccttttat cagtcggata tgtcttgggt ccgccaggct
120ccagggaaag gtctagagtg ggtctcatct atttcttctc agggtcgttc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaatggct
300catcctcagt cgggggtggc ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36314363DNAArtificial SequenceDerived from a Human germline sequence
14gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtacag cctccggatt cacctttgcg gcgagggata tgagttgggt ccgccaggct
120ccagggaagg gtctggagtg ggtctcaagt atttctgctc agggtgctca tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgacg attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggat accgcggtat attactgtgc gaaacctcgg
300catcctcagg ggggggttac ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36315351DNAArtificial SequenceDerived from a Human germline sequence
15gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat aatggggata tggtttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaggg attgcgcata atggtcgtaa tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaaatttg
300ggtcagggtt ttgactactg gggtcaggga accctggtca ccgtctcgag c
35116363DNAArtificial SequenceDerived from a Human germline sequence
16gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60acctgtgcag cctccggatt caccttgaat ggtacgtcga tggggtgggt ccgccaggct
120ccagggaagg atctagagtg ggtctcatct attatgcctg tgggttctca tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaatggct
300catcctcagt cgggggtggc ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36317348DNAArtificial SequenceDerived from a Human germline sequence
17gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat catgcgccta tgaagtgggc ccgccaggct
120ccagggaagg gtctagagtg ggtctcatat attgggtcgg cgggtaatat gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagatgag
300gggccgtttg actactgggg tcagggaacc ctggtcaccg tctcgagc
34818363DNAArtificial SequenceDerived from a Human germline sequence
18gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtacag cctccggatt cacctttgat gggatggata tgagttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaagt atttctacga ctggtgggac tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacctcgg
300catcctcagg ggggggttac ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36319363DNAArtificial SequenceDerived from a Human germline sequence
19gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag gcggagacga tggcttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact attcattcgg agggttctcg gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacctcgg
300catcctcagg ggggggttac ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36320363DNAArtificial SequenceDerived from a Human germline sequence
20gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttagt actggggaga tggcttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatct attagttcga gtggtgctac gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacctcgg
300catcctcagg ggggggttac ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36321360DNAArtificial SequenceDerived from a Human germline sequence
21gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttcct agtgctgata tggtttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcacgt atttcgcctg agggtaatca tacatactac
180gcagactccg tgaagggtcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggat accgcggtat attactgtgc ggaacggcct
300ccttcggatt atgtttcttt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36022357DNAArtificial SequenceDerived from a Human germline sequence
22gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgcg aatgcgacta tgtcgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagat attgatcagg tgggtcatgc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatattcg
300tggcatccgg atctgtttga ctactggggt cagggaaccc tggtcaccgt ctcgagc
35723369DNAArtificial SequenceDerived from a Human germline sequence
23gaggtgcggc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttaag gattatggga tgaattgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcacgg attagtagga atggtactgt tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca actccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaattggct
300gctccggttc gtcagaaggg gatggatttt gactactggg gtcagggaac cctggtcacc
360gtctcgagc
36924348DNAArtificial SequenceDerived from a Human germline sequence
24gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag tggtataata tgtcgtgggt ccgccaggct
120ccagggaagg atctggagtg ggtctcatcg atttctcatg atggttggaa tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagggatg
300attggttttg actactgggg tcagggaacc ctggtcaccg tctcgagc
34825360DNAArtificial SequenceDerived from a Human germline sequence
25gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat atttatacga tgcattgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact attgttccgc agggtactcc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatctaag
300cgtaggtttc ttaagaggtt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36026351DNAArtificial SequenceDerived from a Human germline sequence
26gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgct aggtatgata tgcagtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatcg attaagagta atggtatgaa gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagctagt
300atgtggacgt ttgactactg gggtcaggga accctggtca ccgtctcgaa c
35127369DNAArtificial SequenceDerived from a Human germline sequence
27gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttatg ttgtatcata tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagct attaccgggg ggggttatcc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaactgggg
300cttcggggtg tgctgtggcg gaggaggttt gactactggg gtcagggaac cctggtcacc
360gtctcgagc
36928366DNAArtificial SequenceDerived from a Human germline sequence
28gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggt gcttattcta tgatgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcacgg attagtagga atggtactgt tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaattagg
300tggaatactg ctcaggtgcc tgtgtttgac tactggggtc agggaactct ggtcaccgtc
360tcgagc
36629369DNAArtificial SequenceDerived from a Human germline sequence
29gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggt ccgtattgga tggcttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaacg attacgcctt cgggtcgtgg gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggat accgcggtat attactgtgc gaaagggcgt
300cctcgtgttg gtttgtggag gtcggggttt gactactggg gtcagggaac cctggtcacc
360gtctcgagc
36930348DNAArtificial SequenceDerived from a Human germline sequence
30gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggg cagtatgcta tgcagtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatct attaatatta ctggttctac tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcagatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaggtttt
300aggtcttttg actactgggg tcagggaacc ctggtcaccg tctcgagc
34831351DNAArtificial SequenceDerived from a Human germline sequence
31gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgct ggttatacga tgtcgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaacg atttcgggtt ttggttggac tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggat accgcggtat attactgtgc gaaaaggctg
300gggatgcgtt ttgactactg gggtcaggga accctggtca ccgtctcgag c
35132351DNAArtificial SequenceDerived from a Human germline sequence
32gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggt ccgtattcga tggggtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcattt attcattctg atggtcgtca tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaaagacg
300ccttataggt ttgactactg gggtcaggga accctggtca ccgtctcgag c
35133348DNAArtificial SequenceDerived from a Human germline sequence
33gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggg cagtatgcta tgcagtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatct attaatatta ctggttctac tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcagatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaggtttt
300aggtcttttg actactgggg tcagggaacc ctggtcaccg tctcgagc
34834351DNAArtificial SequenceDerived from a Human germline sequence
34gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttagg cggtatgcga tgtcttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaacg atttcgcctt atggtcctgt tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga atagcctgcg tgccgaggac accgcggtat attactgtgc gaaagcttat
300tatggtgggt ttgactactg gggtcaggga accctggtca ccgtctcgag c
35135360DNAArtificial SequenceDerived from a Human germline sequence
35gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat gcttatgcta tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaaag attgattctc ctggttggag gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatcggct
300cggatgcgtt ctcggcattt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36036366DNAArtificial SequenceDerived from a Human germline sequence
36gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttaag gattatggga tgaattgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcacgg attagtagga atggtactgt tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaattagg
300tggaatactg ctcaggtgcc tgtgtttgac tactggggtc agggaactct ggtcaccgtc
360tcgagc
36637363DNAArtificial SequenceDerived from a Human germline sequence
37gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcaa cctccggatt cacctttccg tcttatacga tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcacgt atttctcgta ctgggaatta tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggat accgcggtat attactgtgc gaaacctatg
300tataataggg ggtcttcgta ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36338369DNAArtificial SequenceDerived from a Human germline sequence
38gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt caccttttcg cagtatcaga tgtcgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatcg atttcgccta cgggtattca gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaaggctt
300attgggatgc cgtatgttga ggatactttt gactactggg gtcagggaac cctggtcacc
360gtctcgagc
36939372DNAArtificial SequenceDerived from a Human germline sequence
39gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttatg gagtatgaga tggagtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaggt attactaatt ctggttctgg gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca actccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gataatgcag
300catcctcagg cgactggggg gagggttggg tttgactact ggggtcaggg aaccctggtc
360accgtctcga gc
37240351DNAArtificial SequenceDerived from a Human germline sequence
40gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttccg aggtatacta tgaagtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatcg attgatagga cgggtcgtaa gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggat accgcggtat attactgtgc gaaagagtcg
300ttggtttcgt ttgactactg gggtcaggga accctggtca ccgtctcgag c
35141351DNAArtificial SequenceDerived from a Human germline sequence
41gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggt ggttatacga tgccttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact atttctcgtg atggtaatta tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagatatt
300ggtatgggtt ttgactacgg ggggcgggga accctggtca ccgtctcgag c
35142369DNAArtificial SequenceDerived from a Human germline sequence
42gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag atttatgcga tgcattgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaacg attagttcgg gtggtaaggg gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatcgcgt
300actatgtatt ttcgtgttag ggaggctttt gactactggg gtcagggaac cctggtcacc
360gtctcgagc
36943372DNAArtificial SequenceDerived from a Human germline sequence
43gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttcgt gcttatagga tgatgtgggt ccgccaggct
120ccagggaagg gtctggagtg ggtctcatct attgatcctg atggtgcggt tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc ggaacatttt
300gatcttgcga tgccgaatcc gaatgcgaag tttgactact ggggtcaggg aaccctggtc
360accgtctcga gc
37244366DNAArtificial SequenceDerived from a Human germline sequence
44gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgcctc
60tcctgtgcag cctccggatt caccttttct cgttatcaga tgtcttgggt ccgccaggct
120ccagggaagg gtctggagtg ggtctcatct attaagtcga atggttcttc gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacctagt
300cggcagagtt ttcagtatcc gagttttgac tactggggtc agggaaccct ggtcaccgtc
360tcgagc
36645360DNAArtificial SequenceDerived from a Human germline sequence
45gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggg cgttataaga tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatct atttcgccta cgggttcgtc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaactggg
300tatgttatgg ttgagcattt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36046348DNAArtificial SequenceDerived from a Human germline sequence
46gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttagt gattatccga tgaagtgggt ccgccaggct
120ccagggaagg gtctggagtg ggtctcaact attaattctt cgggtacgat tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaccgttg
300ttgccgtttg actactgggg tcagggaacc ctggtcaccg tctcgagc
34847369DNAArtificial SequenceDerived from a Human germline sequence
47gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgct aggtatagga tgtgttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatgt attcgggatc cgggttttcc gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatgttcg
300ccgtcttcta cgcagtgtac ggggcttttt gactactggg gtcagggaac cctggtcacc
360gtctcgagc
36948372DNAArtificial SequenceDerived from a Human germline sequence
48gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttagg ttttatggga tggcgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcactt attgatcctc ctggtggggc gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaatggag
300aggcggcatc ttaagagtgg tcataagggg tttgactact ggggtcaggg aaccctggtc
360accgtctcga gc
37249366DNAArtificial SequenceDerived from a Human germline sequence
49gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttacg gagtatgata tgatgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatct attagtcata ggggtgagaa gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagataag
300cgttatcggg ggtctcagca ttattttgac tactggggtc agggaaccct ggtcaccgtc
360tcgagc
36650348DNAArtificial SequenceDerived from a Human germline sequence
50gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttcgg agttatgata tgggttgggc ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact attgggtcga atggtgctaa tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacttatg
300ggtatgtttg actactgggg tcagggaacc ctggtcaccg tctcgagc
34851354DNAArtificial SequenceDerived from a Human germline sequence
51gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag cgttattcta tgaggtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaacg attggttcga cgggtaagtg gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagggcgt
300gggttggttt cttttgacta ctggggtcag ggaaccctgg tcaccgtctc gagc
35452372DNAArtificial SequenceDerived from a Human germline sequence
52gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttagg cgttattcga tgtcttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatct attgatcggt ctggtaggat gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatctcgg
300ctgtcttcga cgggttctga gggtcataat tttgactact ggggtcaggg aaccctggtc
360accgtctcga gc
37253372DNAArtificial SequenceDerived from a Human germline sequence
53gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttaag tggtatccga tgaagtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact attgcttatg atggtgttca gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaattgggt
300ccgactagtc gtgtgtttgc tgctactgat tttgactact ggggtcaggg aaccctggtc
360accgtctcga gc
37254366DNAArtificial SequenceDerived from a Human germline sequence
54gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttccg aattatgcga tgaagtgggg ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact attgatacga gtggtagtac tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacttact
300catcctatgg cgccgcgtcc ggcttttgac tactggggtc agggaaccct ggtcaccgtc
360tcgagc
36655366DNAArtificial SequenceDerived from a Human germline sequence
55gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat cttacggaga tggagtgggt ccgccaggct
120ccagggaagg gtctggagtg ggtctcatcg attgggcctt ggggtactcc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaatttcg
300catcctcagg cgatgtatca tacgtttgac tactggggtc agggaaccct ggtcaccgtc
360tcgagc
36656360DNAArtificial SequenceDerived from a Human germline sequence
56gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgcg catcaggata tgacgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagat attgatcatt cgggttcgta tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatggtgg
300catccgcagg gggggacttt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36057369DNAArtificial SequenceDerived from a Human germline sequence
57gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggt tctaaggata tgtcgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaacg attggggcga atggtaaggc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc ggaagcgggt
300catcctcagg cgccgtcttt taagagtttt gactactggg gtcagggaac cctggtcacc
360gtctcgagc
36958363DNAArtificial SequenceDerived from a Human germline sequence
58gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttctg aatgcggaga tgagttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact attgatcggg atggtgctaa tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacttcct
300ccgccgatgt cgccgaagaa gtttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36359357DNAArtificial SequenceDerived from a Human germline sequence
59gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag agggagggta tgatgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtttcaact attgatcgta tgggtaggta tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaagggat
300tcgcatccta tggggtttga ctaccggggt cagggaaccc tggtcaccgt ctcgagc
35760360DNAArtificial SequenceDerived from a Human germline sequence
60gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccgggtt cacctttgag aatgagaaga tgagttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatcg attggtccta cgggtagtgg tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaactcct
300catccgcagg tttctagttt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36061360DNAArtificial SequenceDerived from a Human germline sequence
61gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag attgatcata tggggtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagag attgcgcctt cgggtgatcg tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggat accgcggtat attactgtgc gaaagtgatt
300tgtcagaatc agtgtctgtt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36062360DNAArtificial SequenceDerived from a Human germline sequence
62gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttagg gattctgaga tgtcgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcattt attacttctg atggtcggga tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacctagt
300ctgcctcatg ttacggcttt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36063366DNAArtificial SequenceDerived from a Human germline sequence
63gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag gatgagacga tgagttgggc ccgccaggct
120ccagggaagg gtctagagtg ggtctcatcg attggggatg ctggtatgcc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaggggag
300ccgatttatg ttcatacgac tcattttgac tactggggtc agggaaccct ggtcaccgtc
360tcgagc
36664357DNAArtificial SequenceDerived from a Human germline sequence
64gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttccg catggtaaga tggggtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatgg attgctgggt ctggtgatat gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaattgggt
300catcctcagc ggggttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc
35765363DNAArtificial SequenceDerived from a Human germline sequence
65gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggg acttctgata tgtcgtgggt ccgccaggcc
120ccagggaagg gtctagagtg ggtctcaact attgattctg ggggtagttt tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacctcgg
300catcctcagg ggggggttac ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36366363DNAArtificial SequenceDerived from a Human germline sequence
66gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag catgttccta tggcttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcacgg attagtgagc agggtagtaa tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagtgcag
300catcctatgt ctccgcatga gtttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36367351DNAArtificial SequenceDerived from a Human germline sequence
67gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag cagggtatga tgtcgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatcg attaatcctg gtggtcagtt tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaggaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc ggaagatctg
300gggccgggtt ttgactactg gggtcaggga accctggtca ccgtctcgag c
35168363DNAArtificial SequenceDerived from a Human germline sequence
68gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag cgttggccta tgtcttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact attgataggt ctggtaatac tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggat accgcggtat attactgtgc gaaagttttg
300catcctcagg cggggtctgc ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36369363DNAArtificial SequenceDerived from a Human germline sequence
69gaggtgcagc tgttggagtc tgggggaggc tcggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggg ggtagtgata tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatat attgataatc agggttataa tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatataag
300cttctgggtc cgtctactga gtttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36370363DNAArtificial SequenceDerived from a Human germline sequence
70gaggtgcagc tgttggagtc agggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttagt agtgatgtta tgtcttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaagt attacgaggt cgggtatgca gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatatgcg
300catcctcagt cggctgttga gtttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36371360DNAArtificial SequenceDerived from a Human germline sequence
71gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttcgt aatgagccga tgagttgggt gcgccaggct
120ccagtgaagg gtctagagtg ggtctcaact atttcgcctg atggtagtgg gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacatggt
300catcctcagg gggctcgttt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36072363DNAArtificial SequenceDerived from a Human germline sequence
72gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttttg aatagtgaga tgtcgtgggt ccgccaggct
120ccagggaagg gtctggagtg ggtctcaact attgggtatg cgggtactcc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacctcgg
300catcctcagg ggggggttac ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36373360DNAArtificial SequenceDerived from a Human germline sequence
73gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgct cgggggccta tgtcttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact attacgaatg atggtacgtc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc ggaaccgcct
300catagtggta ggcctatgtt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36074360DNAArtificial SequenceDerived from a Human germline sequence
74gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttcag cggactgcta tgtcttgggt ccgccaggct
120ccagggaagg gtcttgagtg ggtctcatct attgaggctt cgggtcggta tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacagtcg
300catcctcaga atggtcgttt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36075363DNAArtificial SequenceDerived from a Human germline sequence
75gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat gcgtcggaga tggcttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaagt attacggttt atggtgatag gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacctcgg
300catcctcagg ggggggttac ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36376357DNAArtificial SequenceDerived from a Human germline sequence
76gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat gattcgcata tggcttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaagg atttcgaggg agggtaaggc gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc ggcaccgaat
300gatcagtcgg cggcttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc
35777360DNAArtificial SequenceDerived from a Human germline sequence
77gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat atgagtgaga tgtcgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagct attacttcgg atggtagttc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacctagt
300ctgcctcatg ttacggcttt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36078360DNAArtificial SequenceDerived from a Human germline sequence
78gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag aggtctacta tgcattgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagag attgatgctc tgggtacgga tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatcgtct
300gatcatcctc agaatagttt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36079348DNAArtificial SequenceDerived from a Human germline sequence
79gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag cctcgtgaga tgtattgggc ccgccaggct
120ccagggaagg gtctagagtg ggtcgcacgg attggttggg atggtcatac gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacagctg
300ggtcagtttg actactgggg tcagggaacc ctggtcaccg tctcgagc
34880372DNAArtificial SequenceDerived from a Human germline sequence
80gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat gcttatagta tgatgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact attggtaggt ggggtgagat tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggat accgcggtat attactgtgc gaaacgtcgt
300tatattgggc cttatatgct ttcgggtcgt tttgactact ggggtcaggg aaccctggtc
360accgtctcga gc
37281372DNAArtificial SequenceDerived from a Human germline sequence
81gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttatg cggtatccta tggtgtgggt ccgccaggct
120ccagggaggg gtctagagtg ggtctcatct atttctcctg ctggttatgg tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaggtcat
300gagattagtc ggttttctcg ttggtcttct tttgactact ggggtcaggg aaccctggtc
360accgtctcga gc
37282348DNAArtificial SequenceDerived from a Human germline sequence
82gaggtgcagc tgttggagtc tggggggggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttcgg aagtatagga tgtcgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatct attgcgagga atggtcgttc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaactacg
300tctgggtttg actactgggg tcagggaacc ctggtcaccg tctcgagc
34883363DNAArtificial SequenceDerived from a Human germline sequence
83gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttaat aagaaggaga tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatct attgatgtga gtggtaatgt tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaaatggct
300catcctcagt cgggggtggc ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36384363DNAArtificial SequenceDerived from a Human germline sequence
84gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttcgg atgtatgata tggcgtgggt ccgccaggct
120ccagggaagg gtctaaagtg ggtctcaact attctgtctt ctggtaaggg tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaattggct
300catcctcaga agggtagtat ttttgactac cggggtcagg gaaccctggt caccgtctcg
360agc
36385363DNAArtificial SequenceDerived from a Human germline sequence
85gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttcat cagggtccta tggggtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatgg attcaggcta cgggtggtgc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagggatg
300catcctcaga gtggtactct ttttgactac tggggtcagg gaaccctggt caccgtctcg
360agc
36386351DNAArtificial SequenceDerived from a Human germline sequence
86gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat gttgcggata tggattgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaggg atttcgtcgt cgggtggtta tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggat accgcggtat attactgtgc gaaaaatttg
300ggtcagggtt ttgactactg gggtcaggga accctggtca ccgtctcgag c
35187357DNAArtificial SequenceDerived from a Human germline sequence
87gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat acgagtagta tgttgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagtt attcatcaga gtggtacgcc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatttccg
300tttactcatg gtaagtttga ctactggggt cagggaaccc tggtcaccgt ctcgagc
35788351DNAArtificial SequenceDerived from a Human germline sequence
88gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttaat aattatacga tggggtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcattg attcatacga gtggtacggt gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatggagt
300tcgagggcgt ttgactactg gggtcaggga accctggtca ccgtctcgag c
35189351DNAArtificial SequenceDerived from a Human germline sequence
89gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggg aattatagga tgacttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcaact atttctcctt tgggtacgta tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagggcgt
300tggtcgattt ttgactactg gggtcaggga accctggtca ccgtctcgag c
35190351DNAArtificial SequenceDerived from a Human germline sequence
90gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggt agttatccta tgggttgggt ccgccaggct
120ccagggaagg gtctggagtg ggtctcatgg attcgtggga ggggtcttgc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatatttt
300catggtaagt ttgactactg gggtcaggga accctggtca ccgtctcgag c
35191348DNAArtificial SequenceDerived from a Human germline sequence
91gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttagt gcttatgtga tgggttgggt acgccaggct
120ccagggaagg gtctagagtg ggtctcatcg attcggatgc cgggttatct gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacgtact
300cctttttttg actactgggg tcagggaacc ctggtcaccg tctcgagc
34892369DNAArtificial SequenceDerived from a Human germline sequence
92gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgag cattattcga tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagag attgatccgg atggtattat gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagcgccg
300ggggttcttg agatgtggat tacgcatttt gactactggg gtcagggaac cctggtcacc
360gtctcgagc
36993360DNAArtificial SequenceDerived from a Human germline sequence
93gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttcgt cattatgtga tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagct atttctgcgc atggtaatcg gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatcttat
300agccttgctc tgactccttt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc
36094366DNAArtificial SequenceDerived from a Human germline sequence
94gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttact gtgtatgaga tgaagtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagcg atttctgctg ggggtaagta tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagagatt
300cggcatcttg ataatgcggt tgagtttgac tactggggtc agggaaccct ggtcaccgtc
360tcgagc
36695117PRTArtificial SequenceDerived from a Human germline sequence
95Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu
Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Gly Tyr 20
25 30 Val Met Gly Trp Val Arg Gln Ala Pro
Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Ala Ile Asn Arg Phe Gly Ser Ser Thr Tyr Tyr Ala Asp
Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65
70 75 80 Leu Gln Met Asn Ser
Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85
90 95 Ala Lys Gly Ser Leu Arg His Phe Asp Tyr
Trp Gly Gln Gly Thr Leu 100 105
110 Val Thr Val Ser Ser 115 96116PRTArtificial
SequenceDerived from a Human germline sequence 96Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Gly Asn Tyr 20 25 30
Ala Met Ala Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Ser Ile
Asp Met Val Gly Ile Lys Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Gly Phe Arg Ile Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110 Thr Val Ser Ser
115 97120PRTArtificial SequenceDerived from a Human germline
sequence 97Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
Gly1 5 10 15 Ser
Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Lys Asp Tyr 20
25 30 Asp Met Thr Trp Val Arg
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Met Ile Ser Ser Ser Gly Leu Trp Thr Tyr
Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Gly Phe Arg Leu
Phe Pro Arg Thr Phe Asp Tyr Trp Gly Gln 100
105 110 Gly Thr Leu Val Thr Val Ser Ser
115 120 98124PRTArtificial SequenceDerived from a Human
germline sequence 98Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Leu Tyr
20 25 30 Arg Met Val Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Met Ile Ser Gln Phe Gly Asn Gln Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Val Arg Ser Trp
Asp Gln Thr Gly Gly Arg Arg Thr Phe Asp 100
105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
Ser Ser 115 120 99117PRTArtificial
SequenceDerived from a Human germline sequence 99Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Asn His Tyr 20 25 30
Thr Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Leu Ile
His Pro Ser Gly Thr Val Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Trp Ser Ser Arg Ala Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110 Val Thr Val Ser Ser
115 100116PRTArtificial SequenceDerived from a Human
germline sequence 100Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asn Asn
20 25 30 Ala Met Gly Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Thr Ile Ser Ala Asn Gly Asn Ala Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asp Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Gly Phe Arg Arg
Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 100
105 110 Thr Val Ser Ser 115
101118PRTArtificial SequenceDerived from a Human germline sequence 101Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Thr Ala Ser Gly Phe Thr Phe Arg His Tyr 20 25
30 Arg Met Gly Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Trp Ile Arg Pro Asp Gly Thr Phe Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Ser Tyr Met Gly Asp Arg Phe Asp Tyr Trp Gly
Gln Gly Thr 100 105 110
Leu Val Thr Val Ser Ser 115 102122PRTArtificial
SequenceDerived from a Human germline sequence 102Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Gly Asn Tyr 20 25 30
Pro Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Thr Ile
Ser Tyr Gly Gly Leu Ala Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Met Ala Ile Asn Gly Val Arg Pro Arg Arg Phe Asp Tyr Trp
100 105 110 Gly Gln Gly Thr Leu
Val Thr Val Ser Ser 115 120
103120PRTArtificial SequenceDerived from a Human germline sequence 103Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Met Ala Tyr 20 25
30 Gln Met Ala Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Thr Ile His Gln Thr Gly Phe Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Val Arg Ser Met Arg Pro Tyr Lys Phe Asp Tyr
Trp Gly Gln 100 105 110
Gly Thr Leu Val Thr Val Ser Ser 115 120
104116PRTArtificial SequenceDerived from a Human germline sequence 104Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Gly Asp Lys 20 25
30 Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Thr Ile Ser Ala Pro Gly Asn Arg Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Gly Phe Arg Asn Phe Asp Tyr Trp Gly Gln Gly
Thr Leu Val 100 105 110
Thr Val Ser Ser 115 105121PRTArtificial SequenceDerived from
a Human germline sequence 105Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Gly Met
20 25 30 Arg Met Gly
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Ala Ile Glu Val Asn Gly Gln
His Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Met Ala His
Pro Gln Ser Gly Val Ala Phe Asp Tyr Trp Gly 100
105 110 Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 106121PRTArtificial SequenceDerived from a
Human germline sequence 106Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Pro Asp
20 25 30 Ala Met Ala
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Ser Ile Gly Val Asn Gly Ser
Pro Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Met Ala His
Pro Gln Ser Gly Val Ala Phe Asp Tyr Trp Gly 100
105 110 Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 107121PRTArtificial SequenceDerived from a
Human germline sequence 107Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Tyr Gln Ser
20 25 30 Asp Met Ser
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Ser Ile Ser Ser Gln Gly Arg
Ser Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Met Ala His
Pro Gln Ser Gly Val Ala Phe Asp Tyr Trp Gly 100
105 110 Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 108121PRTArtificial SequenceDerived from a
Human germline sequence 108Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Ala Ala Arg
20 25 30 Asp Met Ser
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Ser Ile Ser Ala Gln Gly Ala
His Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Pro Arg His
Pro Gln Gly Gly Val Thr Phe Asp Tyr Trp Gly 100
105 110 Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 109117PRTArtificial SequenceDerived from a
Human germline sequence 109Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asn Gly
20 25 30 Asp Met Val
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Gly Ile Ala His Asn Gly Arg
Asn Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Asn Leu Gly
Gln Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu 100
105 110 Val Thr Val Ser Ser 115
110121PRTArtificial SequenceDerived from a Human germline sequence 110Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Thr Cys
Ala Ala Ser Gly Phe Thr Leu Asn Gly Thr 20 25
30 Ser Met Gly Trp Val Arg Gln Ala Pro Gly Lys
Asp Leu Glu Trp Val 35 40 45
Ser Ser Ile Met Pro Val Gly Ser His Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Met Ala His Pro Gln Ser Gly Val Ala Phe Asp
Tyr Trp Gly 100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser 115 120
111116PRTArtificial SequenceDerived from a Human germline sequence 111Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Asp His Ala 20 25
30 Pro Met Lys Trp Ala Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Tyr Ile Gly Ser Ala Gly Asn Met Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Asp Glu Gly Pro Phe Asp Tyr Trp Gly Gln Gly
Thr Leu Val 100 105 110
Thr Val Ser Ser 115 112121PRTArtificial SequenceDerived from
a Human germline sequence 112Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Asp Gly Met
20 25 30 Asp Met Ser
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Ser Ile Ser Thr Thr Gly Gly
Thr Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Pro Arg His
Pro Gln Gly Gly Val Thr Phe Asp Tyr Trp Gly 100
105 110 Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 113121PRTArtificial SequenceDerived from a
Human germline sequence 113Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Glu Ala Glu
20 25 30 Thr Met Ala
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Thr Ile His Ser Glu Gly Ser
Arg Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Pro Arg His
Pro Gln Gly Gly Val Thr Phe Asp Tyr Trp Gly 100
105 110 Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 114121PRTArtificial SequenceDerived from a
Human germline sequence 114Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Gly
20 25 30 Glu Met Ala
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Ser Ile Ser Ser Ser Gly Ala
Thr Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Pro Arg His
Pro Gln Gly Gly Val Thr Phe Asp Tyr Trp Gly 100
105 110 Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 115120PRTArtificial SequenceDerived from a
Human germline sequence 115Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Pro Ser Ala
20 25 30 Asp Met Val
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Arg Ile Ser Pro Glu Gly Asn
His Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Glu Arg Pro Pro
Ser Asp Tyr Val Ser Phe Asp Tyr Trp Gly Gln 100
105 110 Gly Thr Leu Val Thr Val Ser Ser
115 120 116119PRTArtificial SequenceDerived from a Human
germline sequence 116Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ala Asn Ala
20 25 30 Thr Met Ser Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Asp Ile Asp Gln Val Gly His Ala Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Tyr Ser Trp His
Pro Asp Leu Phe Asp Tyr Trp Gly Gln Gly 100
105 110 Thr Leu Val Thr Val Ser Ser 115
117123PRTArtificial SequenceDerived from a Human germline
sequence 117Glu Val Arg Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
Gly1 5 10 15 Ser
Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Lys Asp Tyr 20
25 30 Gly Met Asn Trp Val Arg
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Arg Ile Ser Arg Asn Gly Thr Val Thr Tyr
Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Leu Ala Ala Pro
Val Arg Gln Lys Gly Met Asp Phe Asp Tyr 100
105 110 Trp Gly Gln Gly Thr Leu Val Thr Val Ser
Ser 115 120 118116PRTArtificial
SequenceDerived from a Human germline sequence 118Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Glu Trp Tyr 20 25 30
Asn Met Ser Trp Val Arg Gln Ala Pro Gly Lys Asp Leu Glu Trp Val
35 40 45 Ser Ser Ile
Ser His Asp Gly Trp Asn Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Gly Met Ile Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110 Thr Val Ser Ser
115 119119PRTArtificial SequenceDerived from a Human germline
sequence 119Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
Ser1 5 10 15 Leu
Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Ile Tyr Thr 20
25 30 Met His Trp Val Arg Gln
Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 35 40
45 Thr Ile Val Pro Gln Gly Thr Pro Thr Tyr Tyr
Ala Asp Ser Val Lys 50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
Leu65 70 75 80 Gln
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95 Lys Ser Lys Arg Arg Phe
Leu Lys Arg Phe Asp Tyr Trp Gly Gln Gly 100
105 110 Thr Leu Val Thr Val Ser Ser 115
120117PRTArtificial SequenceDerived from a Human germline
sequence 120Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
Gly1 5 10 15 Ser
Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ala Arg Tyr 20
25 30 Asp Met Gln Trp Val Arg
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Ser Ile Lys Ser Asn Gly Met Lys Thr Tyr
Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Ala Ser Met Trp
Thr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 100
105 110 Val Thr Val Ser Asn 115
121123PRTArtificial SequenceDerived from a Human germline sequence 121Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Met Leu Tyr 20 25
30 His Met Gly Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Ala Ile Thr Gly Gly Gly Tyr Pro Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Leu Gly Leu Arg Gly Val Leu Trp Arg Arg Arg
Phe Asp Tyr 100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115
120 122122PRTArtificial SequenceDerived from a Human germline
sequence 122Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
Gly1 5 10 15 Ser
Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Ala Tyr 20
25 30 Ser Met Met Trp Val Arg
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Arg Ile Ser Arg Asn Gly Thr Val Thr Tyr
Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Ile Arg Trp Asn
Thr Ala Gln Val Pro Val Phe Asp Tyr Trp 100
105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 123123PRTArtificial SequenceDerived
from a Human germline sequence 123Glu Val Gln Leu Leu Glu Ser Gly Gly Gly
Leu Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Pro
Tyr 20 25 30 Trp
Met Ala Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Thr Ile Thr Pro Ser
Gly Arg Gly Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser
Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Gly
Arg Pro Arg Val Gly Leu Trp Arg Ser Gly Phe Asp Tyr 100
105 110 Trp Gly Gln Gly Thr Leu Val Thr
Val Ser Ser 115 120
124116PRTArtificial SequenceDerived from a Human germline sequence 124Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Gly Gln Tyr 20 25
30 Ala Met Gln Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Ser Ile Asn Ile Thr Gly Ser Thr Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Gly Phe Arg Ser Phe Asp Tyr Trp Gly Gln Gly
Thr Leu Val 100 105 110
Thr Val Ser Ser 115 125116PRTArtificial SequenceDerived from
a Human germline sequence 125Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val
Gln Pro Gly Gly Ser1 5 10
15 Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ala Gly Tyr Thr
20 25 30 Met Ser Trp
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 35
40 45 Thr Ile Ser Gly Phe Gly Trp Thr
Thr Tyr Tyr Ala Asp Ser Val Lys 50 55
60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
Leu Tyr Leu65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95 Lys Arg Leu Gly Met
Arg Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 100
105 110 Thr Val Ser Ser 115
126117PRTArtificial SequenceDerived from a Human germline sequence 126Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Gly Pro Tyr 20 25
30 Ser Met Gly Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Phe Ile His Ser Asp Gly Arg His Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Lys Thr Pro Tyr Arg Phe Asp Tyr Trp Gly Gln
Gly Thr Leu 100 105 110
Val Thr Val Ser Ser 115 127116PRTArtificial
SequenceDerived from a Human germline sequence 127Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Gly Gln Tyr 20 25 30
Ala Met Gln Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Ser Ile
Asn Ile Thr Gly Ser Thr Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Gly Phe Arg Ser Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110 Thr Val Ser Ser
115 128117PRTArtificial SequenceDerived from a Human germline
sequence 128Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
Gly1 5 10 15 Ser
Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Arg Arg Tyr 20
25 30 Ala Met Ser Trp Val Arg
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Thr Ile Ser Pro Tyr Gly Pro Val Thr Tyr
Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Ala Tyr Tyr Gly
Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu 100
105 110 Val Thr Val Ser Ser 115
129120PRTArtificial SequenceDerived from a Human germline sequence 129Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Asp Ala Tyr 20 25
30 Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Lys Ile Asp Ser Pro Gly Trp Arg Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Ser Ala Arg Met Arg Ser Arg His Phe Asp Tyr
Trp Gly Gln 100 105 110
Gly Thr Leu Val Thr Val Ser Ser 115 120
130122PRTArtificial SequenceDerived from a Human germline sequence 130Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Lys Asp Tyr 20 25
30 Gly Met Asn Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Arg Ile Ser Arg Asn Gly Thr Val Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Ile Arg Trp Asn Thr Ala Gln Val Pro Val Phe
Asp Tyr Trp 100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120
131121PRTArtificial SequenceDerived from a Human germline sequence
131Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu
Ser Cys Ala Thr Ser Gly Phe Thr Phe Pro Ser Tyr 20
25 30 Thr Met Gly Trp Val Arg Gln Ala Pro
Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Arg Ile Ser Arg Thr Gly Asn Tyr Thr Tyr Tyr Ala Asp
Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65
70 75 80 Leu Gln Met Asn Ser
Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85
90 95 Ala Lys Pro Met Tyr Asn Arg Gly Ser Ser
Tyr Phe Asp Tyr Trp Gly 100 105
110 Gln Gly Thr Leu Val Thr Val Ser Ser 115
120 132123PRTArtificial SequenceDerived from a Human germline
sequence 132Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
Gly1 5 10 15 Ser
Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Gln Tyr 20
25 30 Gln Met Ser Trp Val Arg
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Ser Ile Ser Pro Thr Gly Ile Gln Thr Tyr
Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Arg Leu Ile Gly
Met Pro Tyr Val Glu Asp Thr Phe Asp Tyr 100
105 110 Trp Gly Gln Gly Thr Leu Val Thr Val Ser
Ser 115 120 133124PRTArtificial
SequenceDerived from a Human germline sequence 133Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Met Glu Tyr 20 25 30
Glu Met Glu Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Gly Ile
Thr Asn Ser Gly Ser Gly Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Ile Met Gln His Pro Gln Ala Thr Gly Gly Arg Val Gly Phe Asp
100 105 110 Tyr Trp Gly Gln Gly
Thr Leu Val Thr Val Ser Ser 115 120
134117PRTArtificial SequenceDerived from a Human germline sequence
134Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu
Ser Cys Ala Ala Ser Gly Phe Thr Phe Pro Arg Tyr 20
25 30 Thr Met Lys Trp Val Arg Gln Ala Pro
Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Ser Ile Asp Arg Thr Gly Arg Lys Thr Tyr Tyr Ala Asp
Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65
70 75 80 Leu Gln Met Asn Ser
Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85
90 95 Ala Lys Glu Ser Leu Val Ser Phe Asp Tyr
Trp Gly Gln Gly Thr Leu 100 105
110 Val Thr Val Ser Ser 115 135117PRTArtificial
SequenceDerived from a Human germline sequence 135Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Gly Gly Tyr 20 25 30
Thr Met Pro Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Thr Ile
Ser Arg Asp Gly Asn Tyr Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Asp Ile Gly Met Gly Phe Asp Tyr Gly Gly Arg Gly Thr Leu
100 105 110 Val Thr Val Ser Ser
115 136123PRTArtificial SequenceDerived from a Human
germline sequence 136Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Glu Ile Tyr
20 25 30 Ala Met His Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Thr Ile Ser Ser Gly Gly Lys Gly Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Ser Arg Thr Met
Tyr Phe Arg Val Arg Glu Ala Phe Asp Tyr 100
105 110 Trp Gly Gln Gly Thr Leu Val Thr Val Ser
Ser 115 120 137124PRTArtificial
SequenceDerived from a Human germline sequence 137Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Arg Ala Tyr 20 25 30
Arg Met Met Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Ser Ile
Asp Pro Asp Gly Ala Val Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Glu His Phe Asp Leu Ala Met Pro Asn Pro Asn Ala Lys Phe Asp
100 105 110 Tyr Trp Gly Gln Gly
Thr Leu Val Thr Val Ser Ser 115 120
138122PRTArtificial SequenceDerived from a Human germline sequence
138Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu
Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Arg Tyr 20
25 30 Gln Met Ser Trp Val Arg Gln Ala Pro
Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Ser Ile Lys Ser Asn Gly Ser Ser Thr Tyr Tyr Ala Asp
Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65
70 75 80 Leu Gln Met Asn Ser
Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85
90 95 Ala Lys Pro Ser Arg Gln Ser Phe Gln Tyr
Pro Ser Phe Asp Tyr Trp 100 105
110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115
120 139120PRTArtificial SequenceDerived from a Human
germline sequence 139Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Arg Tyr
20 25 30 Lys Met Gly Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Ser Ile Ser Pro Thr Gly Ser Ser Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Thr Gly Tyr Val
Met Val Glu His Phe Asp Tyr Trp Gly Gln 100
105 110 Gly Thr Leu Val Thr Val Ser Ser
115 120 140116PRTArtificial SequenceDerived from a Human
germline sequence 140Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr
20 25 30 Pro Met Lys Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Thr Ile Asn Ser Ser Gly Thr Ile Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Pro Leu Leu Pro
Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 100
105 110 Thr Val Ser Ser 115
141123PRTArtificial SequenceDerived from a Human germline sequence 141Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Ala Arg Tyr 20 25
30 Arg Met Cys Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Cys Ile Arg Asp Pro Gly Phe Pro Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Cys Ser Pro Ser Ser Thr Gln Cys Thr Gly Leu
Phe Asp Tyr 100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115
120 142123PRTArtificial SequenceDerived from a Human germline
sequence 142Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
Ser1 5 10 15 Leu
Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Arg Phe Tyr Gly 20
25 30 Met Ala Trp Val Arg Gln
Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 35 40
45 Leu Ile Asp Pro Pro Gly Gly Ala Thr Tyr Tyr
Ala Asp Ser Val Lys 50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
Leu65 70 75 80 Gln
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95 Lys Met Glu Arg Arg His
Leu Lys Ser Gly His Lys Gly Phe Asp Tyr 100
105 110 Trp Gly Gln Gly Thr Leu Val Thr Val Ser
Ser 115 120 143122PRTArtificial
SequenceDerived from a Human germline sequence 143Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Thr Glu Tyr 20 25 30
Asp Met Met Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Ser Ile
Ser His Arg Gly Glu Lys Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Asp Lys Arg Tyr Arg Gly Ser Gln His Tyr Phe Asp Tyr Trp
100 105 110 Gly Gln Gly Thr Leu
Val Thr Val Ser Ser 115 120
144115PRTArtificial SequenceDerived from a Human germline sequence 144Val
Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser1
5 10 15 Leu Arg Leu Ser Cys Ala
Ala Ser Gly Phe Thr Phe Arg Ser Tyr Asp 20 25
30 Met Gly Trp Ala Arg Gln Ala Pro Gly Lys Gly
Leu Glu Trp Val Ser 35 40 45
Thr Ile Gly Ser Asn Gly Ala Asn Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60 Gly Arg Phe
Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu65 70
75 80 Gln Met Asn Ser Leu Arg Ala Glu
Asp Thr Ala Val Tyr Tyr Cys Ala 85 90
95 Lys Leu Met Gly Met Phe Asp Tyr Trp Gly Gln Gly Thr
Leu Val Thr 100 105 110
Val Ser Ser 115 145118PRTArtificial SequenceDerived from a Human
germline sequence 145Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Glu Arg Tyr
20 25 30 Ser Met Arg Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Thr Ile Gly Ser Thr Gly Lys Trp Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Gly Arg Gly Leu
Val Ser Phe Asp Tyr Trp Gly Gln Gly Thr 100
105 110 Leu Val Thr Val Ser Ser 115
146124PRTArtificial SequenceDerived from a Human germline sequence
146Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu
Ser Cys Ala Ala Ser Gly Phe Thr Phe Arg Arg Tyr 20
25 30 Ser Met Ser Trp Val Arg Gln Ala Pro
Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Ser Ile Asp Arg Ser Gly Arg Met Thr Tyr Tyr Ala Asp
Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65
70 75 80 Leu Gln Met Asn Ser
Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85
90 95 Ala Lys Ser Arg Leu Ser Ser Thr Gly Ser
Glu Gly His Asn Phe Asp 100 105
110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115
120 147123PRTArtificial SequenceDerived
from a Human germline sequence 147Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly Ser1 5 10
15 Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Lys Trp Tyr
Pro 20 25 30 Met
Lys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 35
40 45 Thr Ile Ala Tyr Asp Gly
Val Gln Thr Tyr Tyr Ala Asp Ser Val Lys 50 55
60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys
Asn Thr Leu Tyr Leu65 70 75
80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95 Lys Leu Gly
Pro Thr Ser Arg Val Phe Ala Ala Thr Asp Phe Asp Tyr 100
105 110 Trp Gly Gln Gly Thr Leu Val Thr
Val Ser Ser 115 120
148122PRTArtificial SequenceDerived from a Human germline sequence 148Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Pro Asn Tyr 20 25
30 Ala Met Lys Trp Gly Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Thr Ile Asp Thr Ser Gly Ser Thr Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Leu Thr His Pro Met Ala Pro Arg Pro Ala Phe
Asp Tyr Trp 100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120
149122PRTArtificial SequenceDerived from a Human germline sequence
149Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu
Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Leu Thr 20
25 30 Glu Met Glu Trp Val Arg Gln Ala Pro
Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Ser Ile Gly Pro Trp Gly Thr Pro Thr Tyr Tyr Ala Asp
Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65
70 75 80 Leu Gln Met Asn Ser
Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85
90 95 Ala Lys Ile Ser His Pro Gln Ala Met Tyr
His Thr Phe Asp Tyr Trp 100 105
110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115
120 150120PRTArtificial SequenceDerived from a Human
germline sequence 150Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ala His Gln
20 25 30 Asp Met Thr Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Asp Ile Asp His Ser Gly Ser Tyr Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Trp Trp His Pro
Gln Gly Gly Thr Phe Asp Tyr Trp Gly Gln 100
105 110 Gly Thr Leu Val Thr Val Ser Ser
115 120 151123PRTArtificial SequenceDerived from a Human
germline sequence 151Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Ser Lys
20 25 30 Asp Met Ser Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Thr Ile Gly Ala Asn Gly Lys Ala Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Glu Ala Gly His Pro
Gln Ala Pro Ser Phe Lys Ser Phe Asp Tyr 100
105 110 Trp Gly Gln Gly Thr Leu Val Thr Val Ser
Ser 115 120 152121PRTArtificial
SequenceDerived from a Human germline sequence 152Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Leu Asn Ala 20 25 30
Glu Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Thr Ile
Asp Arg Asp Gly Ala Asn Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Leu Pro Pro Pro Met Ser Pro Lys Lys Phe Asp Tyr Trp Gly
100 105 110 Gln Gly Thr Leu Val
Thr Val Ser Ser 115 120 153119PRTArtificial
SequenceDerived from a Human germline sequence 153Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Glu Arg Glu 20 25 30
Gly Met Met Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Thr Ile
Asp Arg Met Gly Arg Tyr Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Arg Asp Ser His Pro Met Gly Phe Asp Tyr Arg Gly Gln Gly
100 105 110 Thr Leu Val Thr Val
Ser Ser 115 154120PRTArtificial SequenceDerived
from a Human germline sequence 154Glu Val Gln Leu Leu Glu Ser Gly Gly Gly
Leu Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Glu Asn
Glu 20 25 30 Lys
Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Ser Ile Gly Pro Thr
Gly Ser Gly Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser
Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Thr
Pro His Pro Gln Val Ser Ser Phe Asp Tyr Trp Gly Gln 100
105 110 Gly Thr Leu Val Thr Val Ser Ser
115 120 155120PRTArtificial SequenceDerived from a
Human germline sequence 155Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Glu Ile Asp
20 25 30 His Met Gly
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Glu Ile Ala Pro Ser Gly Asp
Arg Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Val Ile Cys
Gln Asn Gln Cys Leu Phe Asp Tyr Trp Gly Gln 100
105 110 Gly Thr Leu Val Thr Val Ser Ser 115
120 156120PRTArtificial SequenceDerived from a Human
germline sequence 156Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Arg Asp Ser
20 25 30 Glu Met Ser Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Phe Ile Thr Ser Asp Gly Arg Asp Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Pro Ser Leu Pro
His Val Thr Ala Phe Asp Tyr Trp Gly Gln 100
105 110 Gly Thr Leu Val Thr Val Ser Ser
115 120 157122PRTArtificial SequenceDerived from a Human
germline sequence 157Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Glu Asp Glu
20 25 30 Thr Met Ser Trp Ala
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Ser Ile Gly Asp Ala Gly Met Pro Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Gly Glu Pro Ile
Tyr Val His Thr Thr His Phe Asp Tyr Trp 100
105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 158119PRTArtificial SequenceDerived
from a Human germline sequence 158Glu Val Gln Leu Leu Glu Ser Gly Gly Gly
Leu Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Pro His
Gly 20 25 30 Lys
Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Trp Ile Ala Gly Ser
Gly Asp Met Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser
Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Leu
Gly His Pro Gln Arg Gly Phe Asp Tyr Trp Gly Gln Gly 100
105 110 Thr Leu Val Thr Val Ser Ser
115 159121PRTArtificial SequenceDerived from a Human
germline sequence 159Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Thr Ser
20 25 30 Asp Met Ser Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Thr Ile Asp Ser Gly Gly Ser Phe Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Pro Arg His Pro
Gln Gly Gly Val Thr Phe Asp Tyr Trp Gly 100
105 110 Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 160119PRTArtificial SequenceDerived from a
Human germline sequence 160Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Glu His Val
20 25 30 Pro Met Ala
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Arg Ile Ser Glu Gln Gly Ser
Asn Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Val Gln His
Pro Met Ser Phe Phe Asp Tyr Trp Gly Gln Gly 100
105 110 Thr Leu Val Thr Val Ser Ser 115
161117PRTArtificial SequenceDerived from a Human germline
sequence 161Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
Gly1 5 10 15 Ser
Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Glu Gln Gly 20
25 30 Met Met Ser Trp Val Arg
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Ser Ile Asn Pro Gly Gly Gln Phe Thr Tyr
Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Glu Asp Leu Gly Pro
Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu 100
105 110 Val Thr Val Ser Ser 115
162121PRTArtificial SequenceDerived from a Human germline sequence 162Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Glu Arg Trp 20 25
30 Pro Met Ser Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Thr Ile Asp Arg Ser Gly Asn Thr Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Val Leu His Pro Gln Ala Gly Ser Ala Phe Asp
Tyr Trp Gly 100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser 115 120
163121PRTArtificial SequenceDerived from a Human germline sequence 163Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Ser Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Gly Gly Ser 20 25
30 Asp Met Gly Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Tyr Ile Asp Asn Gln Gly Tyr Asn Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Tyr Lys Leu Leu Gly Pro Ser Thr Glu Phe Asp
Tyr Trp Gly 100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser 115 120
164121PRTArtificial SequenceDerived from a Human germline sequence 164Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Ser Ser Asp 20 25
30 Val Met Ser Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Ser Ile Thr Arg Ser Gly Met Gln Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Tyr Ala His Pro Gln Ser Ala Val Glu Phe Asp
Tyr Trp Gly 100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser 115 120
165120PRTArtificial SequenceDerived from a Human germline sequence 165Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Arg Asn Glu 20 25
30 Pro Met Ser Trp Val Arg Gln Ala Pro Val Lys
Gly Leu Glu Trp Val 35 40 45
Ser Thr Ile Ser Pro Asp Gly Ser Gly Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys His Gly His Pro Gln Gly Ala Arg Phe Asp Tyr
Trp Gly Gln 100 105 110
Gly Thr Leu Val Thr Val Ser Ser 115 120
166121PRTArtificial SequenceDerived from a Human germline sequence 166Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Leu Asn Ser 20 25
30 Glu Met Ser Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Thr Ile Gly Tyr Ala Gly Thr Pro Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Pro Arg His Pro Gln Gly Gly Val Thr Phe Asp
Tyr Trp Gly 100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser 115 120
167118PRTArtificial SequenceDerived from a Human germline sequence 167Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Arg Pro Met 20 25
30 Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
Glu Trp Val Ser Thr 35 40 45
Ile Thr Asn Asp Gly Thr Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly
50 55 60 Arg Phe Thr
Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln65 70
75 80 Met Asn Ser Leu Arg Ala Glu Asp
Thr Ala Val Tyr Tyr Cys Ala Glu 85 90
95 Pro Pro His Ser Gly Arg Pro Met Phe Asp Tyr Trp Gly
Gln Gly Thr 100 105 110
Leu Val Thr Val Ser Ser 115 168120PRTArtificial
SequenceDerived from a Human germline sequence 168Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Gln Arg Thr 20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Ser Ile
Glu Ala Ser Gly Arg Tyr Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Gln Ser His Pro Gln Asn Gly Arg Phe Asp Tyr Trp Gly Gln
100 105 110 Gly Thr Leu Val Thr
Val Ser Ser 115 120 169121PRTArtificial
SequenceDerived from a Human germline sequence 169Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Asp Ala Ser 20 25 30
Glu Met Ala Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Ser Ile
Thr Val Tyr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Pro Arg His Pro Gln Gly Gly Val Thr Phe Asp Tyr Trp Gly
100 105 110 Gln Gly Thr Leu Val
Thr Val Ser Ser 115 120 170119PRTArtificial
SequenceDerived from a Human germline sequence 170Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Asp Asp Ser 20 25 30
His Met Ala Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Arg Ile
Ser Arg Glu Gly Lys Ala Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Ala Pro Asn Asp Gln Ser Ala Ala Phe Asp Tyr Trp Gly Gln Gly
100 105 110 Thr Leu Val Thr Val
Ser Ser 115 171120PRTArtificial SequenceDerived
from a Human germline sequence 171Glu Val Gln Leu Leu Glu Ser Gly Gly Gly
Leu Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Met
Ser 20 25 30 Glu
Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Ala Ile Thr Ser Asp
Gly Ser Ser Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser
Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Pro
Ser Leu Pro His Val Thr Ala Phe Asp Tyr Trp Gly Gln 100
105 110 Gly Thr Leu Val Thr Val Ser Ser
115 120 172120PRTArtificial SequenceDerived from a
Human germline sequence 172Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Glu Arg Ser
20 25 30 Thr Met His
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Glu Ile Asp Ala Leu Gly Thr
Asp Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Ser Ser Asp
His Pro Gln Asn Ser Phe Asp Tyr Trp Gly Gln 100
105 110 Gly Thr Leu Val Thr Val Ser Ser
115 120 173116PRTArtificial SequenceDerived from a Human
germline sequence 173Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Glu Pro Arg
20 25 30 Glu Met Tyr Trp Ala
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ala Arg Ile Gly Trp Asp Gly His Thr Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Gln Leu Gly Gln
Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 100
105 110 Thr Val Ser Ser 115
174124PRTArtificial SequenceDerived from a Human germline sequence 174Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Asp Ala Tyr 20 25
30 Ser Met Met Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Thr Ile Gly Arg Trp Gly Glu Ile Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Arg Arg Tyr Ile Gly Pro Tyr Met Leu Ser Gly
Arg Phe Asp 100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115
120 175124PRTArtificial SequenceDerived from a Human
germline sequence 175Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Met Arg Tyr
20 25 30 Pro Met Val Trp Val
Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40
45 Ser Ser Ile Ser Pro Ala Gly Tyr Gly Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Gly His Glu Ile
Ser Arg Phe Ser Arg Trp Ser Ser Phe Asp 100
105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
Ser Ser 115 120
176116PRTArtificial SequenceDerived from a Human germline sequence 176Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Arg Lys Tyr 20 25
30 Arg Met Ser Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Ser Ile Ala Arg Asn Gly Arg Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Thr Thr Ser Gly Phe Asp Tyr Trp Gly Gln Gly
Thr Leu Val 100 105 110
Thr Val Ser Ser 115 177121PRTArtificial SequenceDerived from
a Human germline sequence 177Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Lys
20 25 30 Glu Met Gly
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Ser Ile Asp Val Ser Gly Asn
Val Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Met Ala His
Pro Gln Ser Gly Val Ala Phe Asp Tyr Trp Gly 100
105 110 Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 178121PRTArtificial SequenceDerived from a
Human germline sequence 178Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Arg Met Tyr
20 25 30 Asp Met Ala
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Lys Trp Val 35
40 45 Ser Thr Ile Leu Ser Ser Gly Lys
Gly Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Leu Ala His
Pro Gln Lys Gly Ser Ile Phe Asp Tyr Arg Gly 100
105 110 Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 179121PRTArtificial SequenceDerived from a
Human germline sequence 179Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Gln Gly
20 25 30 Pro Met Gly
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Trp Ile Gln Ala Thr Gly Gly
Ala Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Gly Met His
Pro Gln Ser Gly Thr Leu Phe Asp Tyr Trp Gly 100
105 110 Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 180117PRTArtificial SequenceDerived from a
Human germline sequence 180Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Val Ala
20 25 30 Asp Met Asp
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Gly Ile Ser Ser Ser Gly Gly
Tyr Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Asn Leu Gly
Gln Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu 100
105 110 Val Thr Val Ser Ser 115
181119PRTArtificial SequenceDerived from a Human germline sequence 181Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Asp Thr Ser 20 25
30 Ser Met Leu Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Val Ile His Gln Ser Gly Thr Pro Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Phe Pro Phe Thr His Gly Lys Phe Asp Tyr Trp
Gly Gln Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
182117PRTArtificial SequenceDerived from a Human germline sequence 182Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Asn Asn Tyr 20 25
30 Thr Met Gly Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Leu Ile His Thr Ser Gly Thr Val Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Trp Ser Ser Arg Ala Phe Asp Tyr Trp Gly Gln
Gly Thr Leu 100 105 110
Val Thr Val Ser Ser 115 183117PRTArtificial
SequenceDerived from a Human germline sequence 183Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Gly Asn Tyr 20 25 30
Arg Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Thr Ile
Ser Pro Leu Gly Thr Tyr Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Gly Arg Trp Ser Ile Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110 Val Thr Val Ser Ser
115 184117PRTArtificial SequenceDerived from a Human
germline sequence 184Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Ser Tyr
20 25 30 Pro Met Gly Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Trp Ile Arg Gly Arg Gly Leu Ala Thr
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Tyr Phe His Gly
Lys Phe Asp Tyr Trp Gly Gln Gly Thr Leu 100
105 110 Val Thr Val Ser Ser 115
185116PRTArtificial SequenceDerived from a Human germline sequence 185Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Ser Ala Tyr 20 25
30 Val Met Gly Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Ser Ile Arg Met Pro Gly Tyr Leu Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Arg Thr Pro Phe Phe Asp Tyr Trp Gly Gln Gly
Thr Leu Val 100 105 110
Thr Val Ser Ser 115 186123PRTArtificial SequenceDerived from
a Human germline sequence 186Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu
Val Gln Pro Gly Gly1 5 10
15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Glu His Tyr
20 25 30 Ser Met Gly
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35
40 45 Ser Glu Ile Asp Pro Asp Gly Ile
Met Thr Tyr Tyr Ala Asp Ser Val 50 55
60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
Thr Leu Tyr65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Lys Ala Pro Gly
Val Leu Glu Met Trp Ile Thr His Phe Asp Tyr 100
105 110 Trp Gly Gln Gly Thr Leu Val Thr Val Ser
Ser 115 120 187120PRTArtificial
SequenceDerived from a Human germline sequence 187Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Arg His Tyr 20 25 30
Val Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Ala Ile
Ser Ala His Gly Asn Arg Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Ser Tyr Ser Leu Ala Leu Thr Pro Phe Asp Tyr Trp Gly Gln
100 105 110 Gly Thr Leu Val Thr
Val Ser Ser 115 120 188122PRTArtificial
SequenceDerived from a Human germline sequence 188Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Thr Val Tyr 20 25 30
Glu Met Lys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45 Ser Ala Ile
Ser Ala Gly Gly Lys Tyr Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Glu Ile Arg His Leu Asp Asn Ala Val Glu Phe Asp Tyr Trp
100 105 110 Gly Gln Gly Thr Leu
Val Thr Val Ser Ser 115 120
189351DNAArtificial SequenceDerived from a Human germline sequence
189gaggtgcaac tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttaat cattatacga tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcattg attcatccga gtggtacggt gatatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatggagt
300tcgagggcat ttgactactg gggtcaggga accctggtca ccgtctctag c
351190351DNAArtificial SequenceDerived from a Human germline sequence
190gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttaat cattatacga tggggtgggt ccgccaggct
120ccagggaagg gtcgagagtg ggtctcattg attcatccga gtggtacggt gacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatggagt
300tcgagggcgt ttgactactg gggtcaggga accctggtca ccgtctcgag c
351191351DNAArtificial SequenceDerived from a Human germline sequence
191gaggtgcaac tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttaat cattatacga tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcattg attcatccga gtggtacggt gatatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gagatggagt
300tcgagggcgt ttgactactg gggtcagggg accctggtca ccgtctcgag c
351192357DNAArtificial SequenceDerived from a Human germline sequence
192gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttgat acgagtagta tgttgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcagtt attcatcaga gtggtacgcc tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatttccg
300tctactcatg gtaagtttga ctactggggt cagggaaccc tggtcaccgt ctcgagc
357193348DNAArtificial SequenceDerived from a Human germline sequence
193gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtgcag cctccggatt cacctttggt aattatgcga tggcgtgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatcg attgatatgg ttggtattaa gacatactac
180gcagactccg tgaagggccg gttcaccaat tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gagaggtttt
300cgtatttttg actactgggg tcagggaacc ctggtcaccg tctcgagc
348194354DNAArtificial SequenceDerived from a Human germline sequence
194gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc
60tcctgtacag cctccggatt cacctttagg cattatcgta tgggttgggt ccgccaggct
120ccagggaagg gtctagagtg ggtctcatgg attcgtccgg atggtacgtt tacatactac
180gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat
240ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatcttat
300atggctgata ggtttgacta ctggggtcag ggaaccctgg tcaccgtctc gagc
354195117PRTArtificial SequenceDerived from a Human germline sequence
195Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu
Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn His Tyr 20
25 30 Thr Met Gly Trp Val Arg Gln Ala Pro
Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Leu Ile His Pro Ser Gly Thr Val Ile Tyr Tyr Ala Asp
Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65
70 75 80 Leu Gln Met Asn Ser
Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85
90 95 Ala Lys Trp Ser Ser Arg Ala Phe Asp Tyr
Trp Gly Gln Gly Thr Leu 100 105
110 Val Thr Val Ser Ser 115 196117PRTArtificial
SequenceDerived from a Human germline sequence 196Glu Val Gln Leu Leu Glu
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1 5
10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
Thr Phe Asn His Tyr 20 25 30
Thr Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Arg Glu Trp Val
35 40 45 Ser Leu Ile
His Pro Ser Gly Thr Val Thr Tyr Tyr Ala Asp Ser Val 50
55 60 Lys Gly Arg Phe Thr Ile Ser Arg
Asp Asn Ser Lys Asn Thr Leu Tyr65 70 75
80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
Tyr Tyr Cys 85 90 95
Ala Lys Trp Ser Ser Arg Ala Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110 Val Thr Val Ser Ser
115 197117PRTArtificial SequenceDerived from a Human
germline sequence 197Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
Pro Gly Gly1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn His Tyr
20 25 30 Thr Met Gly Trp Val
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Leu Ile His Pro Ser Gly Thr Val Ile
Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
Tyr65 70 75 80 Leu
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95 Ala Arg Trp Ser Ser Arg
Ala Phe Asp Tyr Trp Gly Gln Gly Thr Leu 100 105
110 Val Thr Val Ser Ser 115
198119PRTArtificial SequenceDerived from a Human germline sequence 198Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Asp Thr Ser 20 25
30 Ser Met Leu Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Val Ile His Gln Ser Gly Thr Pro Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Ala Lys Phe Pro Ser Thr His Gly Lys Phe Asp Tyr Trp
Gly Gln Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
199114PRTArtificial SequenceDerived from a Human germline sequence 199Glu
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly1
5 10 15 Ser Leu Arg Leu Ser Cys
Ala Ala Ser Gly Phe Thr Phe Gly Asn Tyr 20 25
30 Ala Met Ala Trp Val Arg Gln Ala Pro Gly Lys
Gly Leu Glu Trp Val 35 40 45
Ser Ser Ile Asp Met Val Gly Ile Lys Thr Tyr Tyr Ala Asp Ser Val
50 55 60 Lys Gly Arg
Phe Thr Asn Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr65 70
75 80 Leu Gln Met Asn Ser Leu Arg Ala
Glu Asp Thr Ala Val Tyr Tyr Cys 85 90
95 Arg Phe Arg Ile Phe Asp Tyr Trp Gly Gln Gly Thr Leu
Val Thr Val 100 105 110
Ser Ser200117PRTArtificial SequenceDerived from a Human germline
sequence 200Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
Gly1 5 10 15 Ser
Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Arg His Tyr 20
25 30 Arg Met Gly Trp Val Arg
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40
45 Ser Trp Arg Pro Asp Gly Thr Phe Thr Tyr Tyr
Ala Asp Ser Val Lys 50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
Leu65 70 75 80 Gln
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95 Lys Ser Tyr Met Ala Asp
Arg Phe Asp Tyr Trp Gly Gln Gly Thr Leu 100
105 110 Val Thr Val Ser Ser 115
User Contributions:
Comment about this patent or add new information about this topic: