Patent application number | Description | Published |
20080221032 | Factor VIIa-Polysialic Acid Conjugate Having Prolonged In Vivo Half-Life - The present invention relates to a proteinaceous construct comprising plasmatic or recombinant factor VIIa (FVIIa) or biologically active derivatives thereof, which are bound to a carbohydrate moiety comprising 1-4 sialic acid units, wherein the in vivo half-life of the proteinaceous construct is substantially prolonged in the blood of a mammal, as compared to the in vivo half-life of a FVIIa molecule not bound to a carbohydrate moiety. The invention also provides a method for controlling bleeding in a mammal having a bleeding disorder due to functional defects or deficiencies of FVIIa, FVIII, or FIX. The invention also provides a method for controlling bleeding in a mammal during surgery or trauma. | 09-11-2008 |
20080234193 | Von Willebrand factor-and factor VIII-polymer conjugates having a releasable linkage - The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided. | 09-25-2008 |
20090005542 | Hydrolysable polymeric FMOC- linker - The invention relates to Fmoc (9-fluorenyl-methoxycarbonyl)-based polymeric conjugates. These conjugates are useful for extending the in-vivo circulation of protein and peptide drugs. | 01-01-2009 |
20090017467 | COMPOSITION EXHIBITING A VON WILLEBRAND FACTOR (vWF) PROTEASE ACTIVITY COMPRISING A POLYPEPTIDE CHAIN WITH THE AMINO ACID SEQUENCE AAGGILHLELLV - The invention relates to vWF cleaving entities having a molecular weight of 180 kD, 170 kD, 160 kD, 120 kD or 110 kD and an N-terminal amino acid sequence of AAGGILHLELLV, vWF cleaving complexes and methods for their production. | 01-15-2009 |
20090076237 | Factor VIII Polymer Conjugates - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 03-19-2009 |
20090176708 | CHEMICALLY MODIFIED FACTOR IX - The present invention discloses a chemically modified FIX, wherein the activation peptide region contains a covalently coupled water-soluble hydrophilic polymer. | 07-09-2009 |
20090192076 | RECOMBINANT VWF FORMULATIONS - The present invention provides long-term stable pharmaceutical formulations of recombinant von-Willebrand Factor (rVWF) and methods for making and administering said formulations. | 07-30-2009 |
20090203110 | COMPOSITION EXHIBITING A VON WILLEBRAND FACTOR (vWF) PROTEASE ACTIVITY COMPRISING A POLYPEPTIDE CHAIN WITH THE AMINO ACID SEQUENCE AAGGILHLELLV - The invention relates to vWF cleaving entities having a molecular weight of 180 kD, 170 kD, 160 kD, 120 kD or 110 kD and an N-terminal amino acid sequence of AAGGILHLELLV, vWF cleaving complexes and methods for their production. | 08-13-2009 |
20090220993 | Method and Compositions for Specifically Detecting Physiologically Acceptable Polymer Molecules - The present invention relates to a method for determining the amount of a physiologically acceptable polymer molecule bound to a protein, an antibody or other composition being capable of specifically binding to a physiologically acceptable polymer molecule, and a kit containing said antibody or composition. | 09-03-2009 |
20090221100 | METHODS FOR DIFFERENTIATING PLASMA-DERIVED PROTEIN FROM RECOMBINANT PROTEIN IN A SAMPLE - The present invention relates, in general, to methods for detecting and quantitating plasma-derived protein and recombinant protein in a sample based on the difference in protein glycosylation, when the plasma protein and the recombinant protein are essentially the same protein. | 09-03-2009 |
20090247459 | MODIFIED RECOMBINANT FACTOR VIII AND VON WILLEBRAND FACTOR AND METHODS OF USE - The present invention provides novel methods of increasing the survival of a coagulation protein by inhibiting the interaction with a clearance receptor. The invention also provides methods of preparing compositions that inhibit coagulation protein clearance receptors. Conjugated coagulation proteins, including compositions and formulations thereof, are also provided by the present invention. | 10-01-2009 |
20090304669 | PREPARATIVE PURIFICATION PROCESS FOR HUMAN FURIN - Recombinant truncated human furin was expressed in CHO cells and concentrated approximately 50-fold by ultrafiltration and diafiltration. The concentrate was purified by column chromatography on Capto-MMC™ resulting in a 30-50 fold purification factor and a yield of at least 60%. The at least 20% pure preparation obtained after Capto-MMC™ chromatography had already a purification degree allowing on-column maturation of pro-VWF. Then an additional Arginine Sepharose chromatography purification was carried out. This two column process for purification of truncated human furin resulted in an almost pure furin preparation with a specific activity of approximately 290,000 U furin/mg protein and a yield of about 50%. | 12-10-2009 |
20100099603 | LYOPHILIZED RECOMBINANT VWF FORMULATIONS - The present invention provides long-term stable pharmaceutical formulations of lyophilized recombinant von-Willebrand Factor (rVWF) and methods for making and administering said formulations. | 04-22-2010 |
20100099616 | MODIFIED BLOOD FACTORS COMPRISING A LOW DEGREE OF WATER SOLUBLE POLYMER - The present invention relates, in general, to materials and methods for the preparation of modified blood factors which have low levels of water soluble polymer molecules conjugated to the blood factor but exhibit biological activity similar to or better than molecules having a higher number of water soluble polymer moieties. | 04-22-2010 |
20100112607 | METHODS FOR DETERMINING ACTIVE INGREDIENTS IN PRO-DRUG PEG PROTEIN CONJUGATES WITH RELEASABLE PEG REAGENTS (IN VITRO DE-PEGYLATION) - The invention relates to the development of in vitro assay systems that force the release of a water-soluble polymer, such as polyethylene glycol (PEG) and polysialic acid (PSA), from proteins modified with a reversibly-linked water-soluble polymer. The invention includes methods for analyzing the release of the water-soluble polymer and measuring regained protein activity. The invention further includes methods appropriate for the quality control of proteins modified with releasable water-soluble polymers, including polymers like PEG and PSA. | 05-06-2010 |
20100113364 | FACTOR VIII POLYMER CONJUGATES - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 05-06-2010 |
20100113365 | FACTOR VIII POLYMER CONJUGATES - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 05-06-2010 |
20100115637 | MODELS OF THROMBOTIC THROMBOCYTOPENIC PURPURA AND METHODS OF USE THEREOF - The invention relates to the development of an animal model for testing various agents in the treatment of a clotting disorder. More specifically, the invention relates to the use of ultra-large molecular weight multimers of von Willebrand factor (VWF) in various mouse strains to induce thrombotic thrombocytopenic purpura (TTP)-like symptoms for the development of a mouse model of TTP. The invention also provides methods for generating such animal disease models and screening methods for identifying biologically active compounds which are effective in the treatment of TTP. | 05-06-2010 |
20100121028 | Hydrolysable Polymeric FMOC- Linker - The invention relates to Fmoc (9-fluorenyl-methoxycarbonyl)-based polymeric conjugates. These conjugates are useful for extending the in-vivo circulation of protein and peptide drugs. | 05-13-2010 |
20100121034 | Hydrolysable Polymeric FMOC-Linker - The invention relates to Fmoc (9-fluorenyl-methoxycarbonyl)-based polymeric conjugates. These conjugates are useful for extending the in-vivo circulation of protein and peptide drugs. | 05-13-2010 |
20100126866 | METHODS OF DETERMINING POLYDISPERSITY AND/OR MOLECULAR WEIGHT DISTRIBUTION OF A POLYETHYLENE GLYCOL SAMPLE - Disclosed herein are methods of determining polydispersity (PDI) and molecular mass distribution (MMD) of reactive PEG samples using mass spectrometry. More specifically, a mass spectrometry method called GEMMA is used to determine PDI and MMD of PEG samples which provides more accurate measurements for high molecular weight PEG samples than prior known MALDI-TOF analysis. | 05-27-2010 |
20100143957 | METHODS OF MEASURING ADAMTS13-MEDIATED IN VIVO CLEAVAGE OF VON WILLEBRAND FACTOR AND USES THEREOF - The invention generally relates to methods of measuring cleaved von Willebrand factor (VWF) fragments. More specifically, the invention relates to methods of measuring the ability of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) to cleave VWF in vivo. The invention also relates to methods of using various animal models which demonstrate ADAMTS13 activity similar to that of a human. The invention further relates to methods of measuring the cleavage products of rVWF in mammals, particularly in humans and in human plasma. | 06-10-2010 |
20100152115 | DETECTION OF PHYSIOLOGICALLY ACCEPTABLE POLYMER MOLECULES USING NEAR INFRARED SPECTROSCOPY - The present invention relates, in general, to methods for detecting the amount of a polymer on a protein using near-infrared spectroscopy. Measurement of the number of polymer moieties per protein molecule allows for production of molecules having a uniform number of polymer moieties, which is useful in the production of pharmaceutical compositions. | 06-17-2010 |
20100155588 | RECOMBINANT VON WILLEBRAND FACTOR AS MOLECULAR WEIGHT MARKER FOR MASS SPECTROMETRY ANALYSES - Methods for determining molecular mass of at least 150 kDa of an analyte of interest using MALDI mass spectrometry in combination with a recombinant von Willebrand factor (rVWF) molecular weight marker are disclosed. More specifically, monomeric and multimeric rVWF are used for external and internal calibration of mass spectra applied for analytes having high molecular weights above 150 kDa. | 06-24-2010 |
20100168391 | Pegylated Factor VIII - The invention is a proteinaceous construct comprising a Factor VIII molecule having at least a portion of the B domain intact, which is conjugated to a water-soluble polymer such as polyethylene glycol having a molecular weight of greater than 10,000 Daltons. The construct has a biological activity of at least 80% of the biological activity of native Factor VIII, and the in vivo half-life of the construct is increased by at least 1.5 fold as compared to the in vivo half-life of native factor FVIII. | 07-01-2010 |
20100173830 | FACTOR VIII POLYMER CONJUGATES - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 07-08-2010 |
20100173831 | FACTOR VIII POLYMER CONJUGATES - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 07-08-2010 |
20110027350 | GLYCOPOLYSIALYLATION OF NON-BLOOD COAGULATION PROTEINS - A water soluble polymer, in particular polysialic acid (PSA) or a modified PSA (mPSA), is conjugated to an oxidized carbohydrate moiety of a glycoprotein other than a blood coagulation protein or to a ganglioside or drug delivery system by contacting the oxidized carbohydrate moiety with the water soluble polymer, wherein said water soluble polymer contains an aminooxy group and an oxime linkage is formed between the oxidized carbohydrate moiety and the aminooxy group on the water soluble polymer or wherein said water soluble polymer contains a hydrazide group and a hydrazone linkage is formed between the oxidized carbohydrate moiety and the hydrazide group on the water soluble polymer. Conjugates of aminooxy- or hydrazide-water soluble polymer, such as PSA and mPSA, are thus obtained in which the PSA or mPSA is attached via a carbohydrate moiety. | 02-03-2011 |
20110028693 | BLOOD COAGULATION PROTEIN CONJUGATES - The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a blood coagulation protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer. In one embodiment of the invention the conjugation is carried out in the presence of the nucleophilic catalyst aniline. In addition the generated oxime linkage can be stabilized by reduction with NaCNBH | 02-03-2011 |
20110072524 | Transgenic Mouse Lacking Endogenous FVIII and VWF - A Model of Hemophilia A - The present invention relates, generally, to a transgenic non-human animal model of hemophilia A, wherein the transgenic animal is deficient in endogenous Factor VIII and endogenous von Willebrand Factor, and methods to treat hereditary or acquired hemophilia A or von Willebrand Disease (VWD) by administration of exogenous human VWF. | 03-24-2011 |
20110110921 | Methods for Treating Bleeding Disorders - A method of factor XI-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject. A method of factor XI-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising: (i) selecting a subject that is not deficient for factor XI; and (ii) administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject, wherein the NASP enhances blood coagulation in a factor XI-dependent manner. A method of identifying a non-anticoagulant sulfated polysaccharide (NASP) which is capable of enhancing blood coagulation in dependence on FXI, the method comprising: a) combining a blood or plasma sample comprising activation competent FXI with a composition comprising a sulfated polysaccharide and measuring the clotting or thrombin generation parameters of the blood or plasma sample; b) combining a corresponding blood or plasma sample deficient in activation competent FXI with a composition comprising the sulfated polysaccharide and measuring the clotting or thrombin generation parameters of the blood or plasma sample; and c) comparing the clotting or thrombin generation parameters of the blood or plasma samples as determined in steps (a) and (b) with each other, wherein a decrease in the clotting time of the blood sample or an increase in peak thrombin or decrease in peak time of the plasma sample comprising activation competent FXI compared to the clotting time of the blood sample or peak thrombin or peak time of the plasma sample deficient in activation competent FXI is indicative of a NASP which is capable of enhancing blood coagulation in dependence on FXI. | 05-12-2011 |
20110111455 | Polymer-Von Willebrand Factor-Conjugates - The present invention relates to a proteinaceous construct (also designated as polymer-VWF-conjugate) comprising plasmatic and/or recombinant von Willebrand factor (VWF), said VWF being bound to at least one physiologically acceptable polymer molecule, as well as to a complex between said proteinaceous construct and at least one factor VIII (FVIII) protein. The physiologically acceptable polymer molecule can be, for instance, polyethylene glycol (PEG) or polysialic acid (PSA). Further the present invention relates to methods for prolonging the in vivo-half-life of VWF or FVIII in the blood of a mammal having a bleeding disorder associated with functional defects of or deficiencies of at least one of FVIII or VWF. | 05-12-2011 |
20110112024 | FACTOR VIII POLYMER CONJUGATES - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 05-12-2011 |
20110112025 | FACTOR VIII POLYMER CONJUGATES - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 05-12-2011 |
20110112026 | FACTOR VIII POLYMER CONJUGATES - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 05-12-2011 |
20110112027 | FACTOR VIII POLYMER CONJUGATES - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 05-12-2011 |
20110112028 | FACTOR VIII POLYMER CONJUGATES - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 05-12-2011 |
20110118188 | FACTOR VIII POLYPEPTIDE HAVING FACTOR VIII:C ACTIVITY - Factor VIII polypeptides having FVIII:C activity that contain modifications in the A3 and/or C1 and/or C2 domains of the sequence of the light chain of Factor VIII, characterized by the binding affinity to low density lipoprotein receptor protein, and methods for producing the same. | 05-19-2011 |
20110206554 | METHODS FOR THE INACTIVATION OF MICROORGANISMS IN BIOLOGICAL FLUIDS, FLOW THROUGH REACTORS AND METHODS OF CONTROLLING THE LIGHT SUM DOSE TO EFFECTIVELY INACTIVATE MICROORGANISMS IN BATCH REACTORS - The present invention relates to a method for determining an effective dose of monochromatic or polychromatic light from one or more light sources to inactivate microorganisms present in a biological fluid, preferably a non-transparent fluid. Moreover, there is provided a method for the inactivation of microorganism in a biological fluid in a flow-through-reactor. Moreover, the invention advantageously provides a flow-through-reactor with one or more thermostated light sources. The invention further provides a method of controlling the light sum dose of monochromatic or polychromatic light emitted from one or more light sources to effectively inactivate microorganisms present in a biological fluid in a batch reactor. | 08-25-2011 |
20110206651 | FACTOR VIII POLYMER CONJUGATES - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 08-25-2011 |
20120035344 | NUCLEOPHILIC CATALYSTS FOR OXIME LINKAGE - The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst. | 02-09-2012 |
20120040379 | METHODS FOR DIFFERENTIATING PLASMA- DERIVED PROTEIN FROM RECOMBINANT PROTEIN IN A SAMPLE - The present invention relates, in general, to methods for detecting and quantitating plasma-derived protein and recombinant protein in a sample based on the difference in protein glycosylation, when the plasma protein and the recombinant protein are essentially the same protein. | 02-16-2012 |
20120076749 | Modified Blood Factors Comprising a Low Degree of Water Soluble Polymer - The present invention relates, in general, to materials and methods for the preparation of modified blood factors which have low levels of water soluble polymer molecules conjugated to the blood factor but exhibit biological activity similar to or better than molecules having a higher number of water soluble polymer moieties. | 03-29-2012 |
20120135462 | Polymer-Von Willebrand Factor-Conjugates - The present invention relates to a proteinaceous construct (also designated as polymer-VWF-conjugate) comprising plasmatic and/or recombinant von Willebrand factor (VWF), said VWF being bound to at least one physiologically acceptable polymer molecule, as well as to a complex between said proteinaceous construct and at least one factor VIII (FVIII) protein. The physiologically acceptable polymer molecule can be, for instance, polyethylene glycol (PEG) or polysialic acid (PSA). Further the present invention relates to methods for prolonging the in vivo-half-life of VWF or FVIII in the blood of a mammal having a bleeding disorder associated with functional defects of or deficiencies of at least one of FVIII or VWF. | 05-31-2012 |
20120142594 | Von Willebrand Factor- and Factor VIII-Polymer Conjugates Having a Releasable Linkage - The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided. | 06-07-2012 |
20120177625 | CHEMICALLY MODIFIED FACTOR IX - The present invention discloses a chemically modified FIX, wherein the activation peptide region contains a covalently coupled water-soluble hydrophilic polymer. | 07-12-2012 |
20120190096 | MATERIALS AND METHODS FOR CONJUGATING A WATER SOLUBLE FATTY ACID DERIVATIVE TO A PROTEIN - The invention relates to materials and methods of conjugating a water soluble fatty acid derivative to a therapeutic protein comprising contacting the therapeutic protein with an activated water soluble fatty acid derivative under conditions that allow conjugation. | 07-26-2012 |
20120232252 | FACTOR VIII POLYMER CONJUGATES - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 09-13-2012 |
20120316116 | TREATMENT OF COAGULATION DISEASE BY ADMINISTRATION OF RECOMBINANT VWF - The present invention provides methods of treating coagulation disease, including hemophilia and von Willebrand disease by administering recombinant von Willebrand Factor alone or in combination with Factor VIII. | 12-13-2012 |
20120322737 | MODIFIED RECOMBINANT FACTOR VIII AND VON WILLEBRAND FACTOR AND METHODS OF USE - The present invention provides novel methods of increasing the survival of a coagulation protein by inhibiting the interaction with a clearance receptor. The invention also provides methods of preparing compositions that inhibit coagulation protein clearance receptors. Conjugated coagulation proteins, including compositions and formulations thereof, are also provided by the present invention. | 12-20-2012 |
20120329127 | THERAPEUTIC PROTEINS WITH INCREASED HALF-LIFE AND METHODS OF PREPARING SAME - The present disclosure relates to materials and methods of conjugating a water soluble polymer to a therapeutic protein. | 12-27-2012 |
20130011900 | NUCLEOPHILIC CATALYSTS FOR OXIME LINKAGE - The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst. | 01-10-2013 |
20130012442 | VON WILLEBRAND FACTOR- AND FACTOR VIII-POLYMER CONJUGATES HAVING A RELEASABLE LINKAGE - The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided. | 01-10-2013 |
20130035288 | Resorption Enhancers As Additives To Improve The Oral Formulation Of Non-Anticoagulant Sulfated Polysaccharides - Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) in combination with a gastrointestinal epithelial barrier permeation enhancer is orally administered to a subject in a manner sufficient to enhance blood coagulation in the subject. Compositions and kits for practicing methods of the invention are also described. | 02-07-2013 |
20130043383 | Methods of Determining Polydispersity and/or Molecular Weight Distribution of a Polyethylene Glycol Sample - Disclosed herein are methods of determining polydispersity (PDI) and molecular mass distribution (MMD) of reactive PEG samples using mass spectrometry. More specifically, a mass spectrometry method called GEMMA is used to determine PDI and MMD of PEG samples which provides more accurate measurements for high molecular weight PEG samples than prior known MALDI-TOF analysis. | 02-21-2013 |
20130052672 | KIT FOR MEASURING THE THROMBIN GENERATION IN A SAMPLE OF A SAMPLE OF A PATIENT'S BLOOD OR PLASMA - The invention provides a kit for measuring the thrombin generation in a sample of a patient's blood or plasma, or in a sample of clotting factors. The kit contains lyophilized tissue factor/phospholipid-complex and a lyophilized mixture containing a thrombin-substrate and CaCl | 02-28-2013 |
20130115204 | PREPARATIVE PURIFICATION PROCESS FOR HUMAN FURIN - Recombinant truncated human furin was expressed in CHO cells and concentrated approximately 50-fold by ultrafiltration and diafiltration. The concentrate was purified by column chromatography on Capto-MMC™ resulting in a 30-50 fold purification factor and a yield of at least 60%. The at least 20% pure preparation obtained after Capto-MMC™ chromatography had already a purification degree allowing on-column maturation of pro-VWF. Then an additional Arginine Sepharose chromatography purification was carried out. This two column process for purification of truncated human furin resulted in an almost pure furin preparation with a specific activity of approximately 290,000 U furin/mg protein and a yield of about 50%. | 05-09-2013 |
20130119265 | METHODS FOR THE INACTIVATION OF MIRCROORGANISMS IN BIOLOGICAL FLUIDS, FLOW THROUGH REACTORS AND METHODS OF CONTROLLING THE LIGHT SUM DOSE TO EFFECTIVELY INACTIVATE MICROORGANISMS IN BATCH REACTORS - The present invention relates to a method for determining an effective dose of monochromatic or polychromatic light from one or more light sources to inactivate microorganisms present in a biological fluid, preferably a non-transparent fluid. Moreover, there is provided a method for the inactivation of microorganism in a biological fluid in a flow-through-reactor. Moreover, the invention advantageously provides a flow-through-reactor with one or more thermostated light sources. The invention further provides a method of controlling the light sum dose of monochromatic or polychromatic light emitted from one or more light sources to effectively inactivate microorganisms present in a biological fluid in a batch reactor. | 05-16-2013 |
20130172269 | LYOPHILIZED RECOMBINANT VWF FORMULATIONS - The present invention provides long-term stable pharmaceutical formulations of lyophilized recombinant von-Willebrand Factor (rVWF) and methods for making and administering said formulations. | 07-04-2013 |
20130190242 | Polymer-Von Willebrand Factor-Conjugates - The present invention relates to a proteinaceous construct (also designated as polymer-VWF-conjugate) comprising plasmatic and/or recombinant von Willebrand factor (VWF), said VWF being bound to at least one physiologically acceptable polymer molecule, as well as to a complex between said proteinaceous construct and at least one factor VIII (FVIII) protein. The physiologically acceptable polymer molecule can be, for instance, polyethylene glycol (PEG) or polysialic acid (PSA). Further the present invention relates to methods for prolonging the in vivo-half-life of VWF or FVIII in the blood of a mammal having a bleeding disorder associated with functional defects of or deficiencies of at least one of FVIII or VWF. | 07-25-2013 |
20130252263 | METHODS OF MEASURING ADAMTS 13-MEDIATED IN VIVO CLEAVAGE OF VON WILLEBRAND FACTOR AND USES THEREOF - The invention generally relates to methods of measuring cleaved von Willebrand factor (VWF) fragments. More specifically, the invention relates to methods of measuring the ability of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) to cleave VWF in vivo. The invention also relates to methods of using various animal models which demonstrate ADAMTS13 activity similar to that of a human. The invention further relates to methods of measuring the cleavage products of rVWF in mammals, particularly in humans and in human plasma. | 09-26-2013 |
20130296243 | MODIFIED RECOMBINANT FACTOR VIII AND VON WILLEBRAND FACTOR AND METHODS OF USE - The present invention provides novel methods of increasing the survival of a coagulation protein by inhibiting the interaction with a clearance receptor. The invention also provides methods of preparing compositions that inhibit coagulation protein clearance receptors. Conjugated coagulation proteins, including compositions and formulations thereof, are also provided by the present invention. | 11-07-2013 |
20140024808 | FACTOR VIII POLYMER CONJUGATES - The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same. | 01-23-2014 |
20140050717 | Methods for Treating Bleeding Disorders - A method of factor X1-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject. A method of factor X1-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising: (i) selecting a subject that is not deficient for factor X1; and (ii) administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject, wherein the NASP enhances blood coagulation in a factor X1-dependent manner. A method of identifying a non-anticoagulant sulfated polysaccharide (NASP) which is capable of enhancing blood coagulation in dependence on FXI, the method comprising: a) combining a blood or plasma sample comprising activation competent FXI with a composition comprising a sulfated polysaccharide and measuring the clotting or thrombin generation parameters of the blood or plasma sample; b) combining a corresponding blood or plasma sample deficient in activation competent FXI with a composition comprising the sulfated polysaccharide and measuring the clotting or thrombin generation parameters of the blood or plasma sample; and c) comparing the clotting or thrombin generation parameters of the blood or plasma samples as determined in steps (a) and (b) with each other, wherein a decrease in the clotting time of the blood sample or an increase in peak thrombin or decrease in peak time of the plasma sample comprising activation competent FXI compared to the clotting time of the blood sample or peak thrombin or peak time of the plasma sample deficient in activation competent FXI is indicative of a NASP which is capable of enhancing blood coagulation in dependence on FXI. | 02-20-2014 |
20140051094 | Method and Compositions for Specifically Detecting Physiologically Acceptable Polymer Molecules - The present invention relates to a method for determining the amount of a physiologically acceptable polymer molecule bound to a protein, an antibody or other composition being capable of specifically binding to a physiologically acceptable polymer molecule, and a kit containing said antibody or composition. | 02-20-2014 |
20140107320 | BLOOD COAGULATION PROTEIN CONJUGATES - The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a blood coagulation protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer. In one embodiment of the invention the conjugation is carried out in the presence of the nucleophilic catalyst aniline. In addition the generated oxime linkage can be stabilized by reduction with NaCNBH | 04-17-2014 |
20140121351 | NUCLEOPHILIC CATALYSTS FOR OXIME LINKAGE - The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst. | 05-01-2014 |
20140154709 | METHODS OF MEASURING ADAMTS 13-MEDIATED IN VIVO CLEAVAGE OF VON WILLEBRAND FACTOR AND USES THEREOF - The invention generally relates to methods of measuring cleaved von Willebrand factor (VWF) fragments. More specifically, the invention relates to methods of measuring the ability of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) to cleave VWF in vivo. The invention also relates to methods of using various animal models which demonstrate ADAMTS13 activity similar to that of a human. The invention further relates to methods of measuring the cleavage products of rVWF in mammals, particularly in humans and in human plasma. | 06-05-2014 |
20140186323 | FACTOR VIIA-POLYSIALIC ACID CONJUGATES HAVING PROLONGED IN VIVO HALF-LIFE - The present invention relates to a proteinaceous construct comprising plasmatic or recombinant factor VIIa (FVIIa) or biologically active derivatives thereof, which are bound to a carbohydrate moiety comprising 1-4 sialic acid units, wherein the in vivo half-life of the proteinaceous construct is substantially prolonged in the blood of a mammal, as compared to the in vivo half-life of a FVIIa molecule not bound to a carbohydrate moiety. The invention also provides a method for controlling bleeding in a mammal having a bleeding disorder due to functional defects or deficiencies of FVIIa, FVIII, or FIX. The invention also provides a method for controlling bleeding in a mammal during surgery or trauma. | 07-03-2014 |
20140232029 | KIT FOR MEASURING THE THROMBIN GENERATION IN A SAMPLE OF A PATIENT'S BLOOD OR PLASMA - The invention provides a kit for measuring the thrombin generation in a sample of a patient's blood or plasma, or in a sample of clotting factors. The kit contains lyophilized tissue factor/phospholipid-complex and a lyophilized mixture containing a thrombin-substrate and CaCl | 08-21-2014 |
20140271608 | RESORPTION ENHANCERS AS ADDITIVES TO IMPROVE THE ORAL FORMULATION OF LOW MOLECULAR WEIGHT HEPARINS - Aspects of the invention include methods for treating or preventing a thromboembolic disease in a subject. In practicing methods according to certain embodiments, an amount of a low molecular weight heparin (LMWH) and a synergistically effective combination of two or more gastrointestinal epithelial barrier permeation enhancers is orally administered to a subject in a manner sufficient to treat the thromboembolic disease in the subject. Compositions and kits for practicing methods of the invention are also described. | 09-18-2014 |
20140309176 | ETHANOL DEPENDENCE OF ALPHA1 ANTITRYPSIN C-TERMINAL LYS TRUNCATION BY BASIC CARBOXYPEPTIDASES - The present invention provides methods of preparing alpha-1-antiproteinase inhibitor and controlling the amount of des-lys alpha-1-antiproteinase inhibitor in the preparation, and compositions comprising the same, as well as methods of treatment using the same. | 10-16-2014 |
20140335071 | Composition Exhibiting a von Willebrand Factor (vWF) Protease Activity Comprising a Polypeptide Chain with the Amino Acid Sequence AAGGILHLELLV - The invention relates to vWF cleaving entities having a molecular weight of 180 kD, 170 kD, 160 kD, 120 kD or 110 kD and an N-terminal amino acid sequence of AAGGILHLELLV, vWF cleaving complexes and methods for their production. | 11-13-2014 |
20150024455 | NUCLEOPHILIC CATALYSTS FOR OXIME LINKAGE - The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst. | 01-22-2015 |