ANTI-PACAP ANTIBODIES

Abstract

The present invention is directed to antagonistic antibodies and antigen binding fragments thereof having binding specificity for PACAP. These antibodies inhibit, block or neutralize at least one biological effect associated with PACAP, e.g., vasodilation. In exemplary embodiments these antibodies and antigen binding fragments thereof may comprise specific V.sub.H, V.sub.L, and CDR polypeptides described herein. In some embodiments these antibodies and antigen binding fragments thereof bind to and/or compete for binding to specific epitope(s) on human PACAP. The invention is further directed to using these antagonistic anti-PACAP antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with PACAP and conditions where antagonism of PACAP-related activities, such as vasodilation, mast cell degranulation, and/or neuronal activation, are therapeutically beneficial, e.g., headache and migraine indications.

Claims

1. An antibody or antibody fragment selected from the following: (a) a human, humanized or chimerized anti-human Pituitary Adenylate Cyclase-Activating Polypeptide ("PACAP") antibody or antibody fragment that antagonizes, inhibits, neutralizes or blocks at least one biological effect associated with human PACAP; (b) a human, humanized or chimerized anti-PACAP antibody or antibody fragment that specifically competes for binding to human PACAP with an antibody selected from the group consisting of Ab1, Ab2, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab1.H, Ab5, Ab7, Ab1, Ab12, Ab4, Ab3, Ab6, Ab8, and Ab9 or an antigen-binding fragment of any one of the foregoing; (c) a human, humanized or chimerized anti-PACAP antibody or antibody fragment that specifically binds to at least one linear or conformational epitope bound by an anti-PACAP antibody selected from the group consisting of Ab1, Ab2, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab1.H, Ab5, Ab7, Ab11, Ab12, Ab4, Ab3, Ab6, Ab8, and Ab9 or an antigen-binding fragment of any one of the foregoing; (d) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing claims which binds to the identical epitopes as any one of Ab1, Ab2, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab1.H, Ab5, Ab7, Ab11, Ab12, Ab4, Ab3, Ab6, Ab8, and Ab9 or an antigen-binding fragment of any one of the foregoing; (e) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing claims that specifically binds to an epitope on human PACAP or a fragment or variant thereof containing the corresponding amino acid residues wherein said epitope is selected from the group consisting of: (i) at least one of residues 7, 10, 13, and 14 of a human PACAP; (ii) at least one of residues 5, 6, 8, 10, and 13 of a human PACAP; (iii) at least one of residues 6, 8, 9, 10, and 13 of a human PACAP; (iv) at least one of residues 5, 6, 8, 9, 10, and 13 of a human PACAP; (v) at least one of residues 7, 10, 12, 13, 14, and 17 of a human PACAP; (vi) at least one of residues 5, 6, 8, 9, 10, 12, and 13 of a human PACAP; (vii) at least one of residues 5, 6, 8, 9, 10, 13, and 14 of a human PACAP; (viii) at least one of residues 6, 8, 10, 11, 13, 14, and 18 of a human PACAP; (ix) at least one of residues 8, 9, 10, 13, 14, 17, and 18 of a human PACAP; (x) at least one of residues 3, 4, 5, 6, 7, 10, 13, and 14 of a human PACAP; (xi) at least one of residues 5, 6, 8, 9, 10, 12, 13, and 14 of a human PACAP; (xii) at least one of residues 5, 6, 9, 10, 12, 13, 14, and 17 of a human PACAP; (xiii) at least one of residues 6, 8, 10, 11, 13, 14, 18, and 22 of a human PACAP; (xiv) at least one of residues 8, 9, 10, 11, 12, 13, 14, 17, and 21 of a human PACAP; (xv) at least one of residues 4, 5, 6, 8, 9, 10, 12, 13, 14, and 17 of a human PACAP; (xvi) at least two of the residues of any one of (i)-(xv); (xvii) at least three of the residues of any one of (i)-(xv); (xviii) at least four of the residues of any one of (i)-(xv); (xix) at least five of the residues of any one of (ii)-(xv); (xx) at least six of the residues of any one of (iv)-(xv); (xxi) at least seven of the residues of any one of (vi)-(xv); (xxii) at least eight of the residues of any one of (x)-(xv); (xxiii) at least nine of the residues of (xiv) or (xv); (xxiv) all ten residues of (xv); (f) a human, humanized or chimerized anti-PACAP human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which specifically binds to an epitope on human PACAP, or a fragment or variant thereof containing the corresponding amino acid residues that includes residues 8 and/or 14 of human PACAP; (g) human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing, which specifically binds to an epitope on human PACAP or a fragment or variant thereof containing the corresponding amino acid residues, wherein said epitope consists of the residues of any one of (i)-(xv) as set forth in claim (e); (h) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing, which specifically binds to an epitope on human PACAP (or a fragment or variant thereof containing the corresponding amino acid residues) that is present in human wild-type PACAP38 and in human wild-type human PACAP27; (i) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing wherein said epitope is identified by alanine scanning, e.g., as disclosed in Example 12; (j) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which does not bind to or does not appreciably bind to human Vasoactive Intestinal Peptide ("VIP"); (k) The human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which has a K.sub.D for human PACAP which is at least 10, 100, 1000, 10,000 or 100,000 fold lower (stronger) than the K.sub.D of said antibody or antibody fragment to human VI; (l) human, humanized or chimerized anti-PACAP antibody or antibody fragment of any of the foregoing which inhibits or neutralizes at least one biological effect elicited by human PACAP; (m) The human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which comprises one or more of the following: (1) inhibits, blocks or prevents PACAP activation of at least one of PAC1 receptor ("PAC1-R"), vasoactive intestinal peptide receptor type 1 ("VPAC1-R"), and/or vasoactive intestinal peptide receptor type 2 ("VPAC2-R"); (2) inhibits, blocks or prevents PACAP activation of each of PAC1-R, VPAC1-R, and VPAC2-R; (3) inhibits, blocks or prevents PACAP activation of PAC1-R; (4) is capable of inhibiting PACAP binding to at least one of PAC1-R, VPAC1-R, and/or VPAC2-R; (5) is capable of inhibiting PACAP binding to each of PAC1-R, VPAC1-R, and/or VPAC2-R; (6) is capable of inhibiting PACAP binding to PAC1-R-expressing cells; (7) is capable of inhibiting PACAP binding to VPAC1-R-expressing cells; (8) is capable of inhibiting PACAP binding to VPAC2-R-expressing cells; (9) inhibits PACAP binding to the cell surface, e.g. via a glycosaminoglycan ("GAG"); (10) does not inhibit PACAP-mediated binding of such antibody to the cell surface, e.g., via a GAG; (11) inhibits, blocks or prevents PACAP-induced cAMP production; and/or (12) when administered to a subject reduces PACAP-induced vasodilation; (n) human, humanized or chimerized anti-PACAP antibody or antibody fragment of any of the foregoing which inhibits or neutralizes at least one biological effect elicited by human PACAP; (o) a human, humanized or chimerized anti-PACAP antibody or antibody fragment of any of the foregoing which is substantially non-immunogenic in human subjects; (p) a human, humanized or chimerized anti-PACAP antibody or antibody fragment of any of the foregoing which is suitable for treating a human subject having an acute, episodic or chronic condition associated with increased vasodilation, mast cell degranulation and/or neuronal activation; (q) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising at least 2 complementarity determining regions ("CDRs") of an anti-PACAP antibody selected from Ab1, Ab2, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab1.H, Ab5, Ab7, Ab11, Ab12, Ab4, Ab3, Ab6, Ab8, or Ab9, preferably the V.sub.H CDR3 and/or the V.sub.L CDR3; (r) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing, comprising at least 3 CDRs of an anti-PACAP antibody selected from Ab1, Ab2, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab1.H, Ab5, Ab7, Ab11, Ab12, Ab4, Ab3, Ab6, Ab8, or Ab9; (s) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing, comprising at least 4 CDRs of an anti-PACAP antibody selected from Ab1, Ab2, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab1.H, Ab5, Ab7, Ab11, Ab12, Ab4, Ab3, Ab6, Ab8, or Ab9; (t) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising at least 5 CDRs of an anti-PACAP antibody selected from Ab1, Ab2, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab1.H, Ab5, Ab7, Ab11, Ab12, Ab4, Ab3, Ab6, Ab8, or Ab9; (u) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising all 6 CDRs of an anti-PACAP antibody selected from Ab1, Ab2, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab1.H, Ab5, Ab7, Ab11, Ab12, Ab4, Ab3, Ab6, Ab8, or Ab9; (v) a a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 4; a CDR2 sequence consisting of SEQ ID NO: 6; and a CDR3 sequence consisting of SEQ ID NO: 8; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 24; a CDR2 sequence consisting of SEQ ID NO: 26; and a CDR3 sequence consisting of SEQ ID NO: 28; (w) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any one of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 2, and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 22; (x) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any one of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 2, and/or (1) a variable light chain having the amino acid sequence of SEQ ID NO: 22; (y) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any one of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 1, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 21; (z) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any one of the foregoing comprising: comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 44; a CDR2 sequence consisting of SEQ ID NO: 46; and a CDR3 sequence consisting of SEQ ID NO: 48; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 64; a CDR2 sequence consisting of SEQ ID NO: 66; and a CDR3 sequence consisting of SEQ ID NO: 68; (aa) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any one of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 42, and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 62; (bb) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any one of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 42, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 62; (cc) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any one of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 41, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 61; (dd) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any one of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 84; a CDR2 sequence consisting of SEQ ID NO: 86; and a CDR3 sequence consisting of SEQ ID NO: 88; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 104; a CDR2 sequence consisting of SEQ ID NO: 106; and a CDR3 sequence consisting of SEQ ID NO: 108; (ee) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any one of the foregoing comprising: comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 82 and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 102; (ff) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 82, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 102; (gg) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 81, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 101; (hh) human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 124; a CDR2 sequence consisting of SEQ ID NO: 126; and a CDR3 sequence consisting of SEQ ID NO: 128; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 144; a CDR2 sequence consisting of SEQ ID NO: 146; and a CDR3 sequence consisting of SEQ ID NO: 148; (ii) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 122 and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 142; (jj) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 122, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 142; (kk) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 121, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 141; (ll) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 164; a CDR2 sequence consisting of SEQ ID NO: 166; and a CDR3 sequence consisting of SEQ ID NO: 168; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 184; a CDR2 sequence consisting of SEQ ID NO: 186; and a CDR3 sequence consisting of SEQ ID NO: 188; (mm) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 162, and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 182; (nn) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 162, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 182; (oo) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 161, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 181; (pp) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 204; a CDR2 sequence consisting of SEQ ID NO: 206; and a CDR3 sequence consisting of SEQ ID NO: 208; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 224; a CDR2 sequence consisting of SEQ ID NO: 226; and a CDR3 sequence consisting of SEQ ID NO: 228; (qq) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 202 and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 222; (rr) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 202, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 222; (ss) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 201, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 221; (tt) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1

sequence consisting of SEQ ID NO: 244; a CDR2 sequence consisting of SEQ ID NO: 246; and a CDR3 sequence consisting of SEQ ID NO: 248; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 264; a CDR2 sequence consisting of SEQ ID NO: 266; and a CDR3 sequence consisting of SEQ ID NO: 268; (uu) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 242, and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 262; (vv) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 242, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 262; (ww) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 241, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 261; (xx) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 284; a CDR2 sequence consisting of SEQ ID NO: 286; and a CDR3 sequence consisting of SEQ ID NO: 288; and/or (2) the variable light chain comprising a CDR1 sequence consisting of SEQ ID NO: 304; a CDR2 sequence consisting of SEQ ID NO: 306; and a CDR3 sequence consisting of SEQ ID NO: 308; (yy) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 282, and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 302; (zz) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 282, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 302; (aaa) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 281, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 301; (bbb) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 324; a CDR2 sequence consisting of SEQ ID NO: 326; and a CDR3 sequence consisting of SEQ ID NO: 328; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 344; a CDR2 sequence consisting of SEQ ID NO: 346; and a CDR3 sequence consisting of SEQ ID NO: 348; (ccc) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 322, and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 342; (ddd) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 322, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 342; (eee) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 321, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 341; (fff) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 364; a CDR2 sequence consisting of SEQ ID NO: 366; and a CDR3 sequence consisting of SEQ ID NO: 368; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 384; a CDR2 sequence consisting of SEQ ID NO: 386; and a CDR3 sequence consisting of SEQ ID NO: 388; (ggg) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 362, and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 382; (hhh) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 362, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 382; (iii) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 361, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 381; (jjj) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) the variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 484; the CDR2 sequence consisting of SEQ ID NO: 486; and the CDR3 sequence consisting of SEQ ID NO: 488; and/or (2) the variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 504; the CDR2 sequence consisting of SEQ ID NO: 506; and the CDR3 sequence consisting of SEQ ID NO: 508; (kkk) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 482, and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 502; (lll) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 482, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 502; (mmm) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 481, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 501; (nnn) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 524; a CDR2 sequence consisting of SEQ ID NO: 526; and a CDR3 sequence consisting of SEQ ID NO: 528; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 544; a CDR2 sequence consisting of SEQ ID NO: 546; and a CDR3 sequence consisting of SEQ ID NO: 548; (ooo) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 522, and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 542; (ppp) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 522, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 542; (qqq) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 521, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 541; (rrr) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 564; a CDR2 sequence consisting of SEQ ID NO: 566; and a CDR3 sequence consisting of SEQ ID NO: 568; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 584; a CDR2 sequence consisting of SEQ ID NO: 586; and a CDR3 sequence consisting of SEQ ID NO: 588; (sss) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (a) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 562, and/or (b) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 582; (ttt) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (a) a variable heavy chain having the amino acid sequence of SEQ ID NO: 562, and/or (b) a variable light chain having the amino acid sequence of SEQ ID NO: 582; (uuu) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 561, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 581; (vvv) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 604; a CDR2 sequence consisting of SEQ ID NO: 606; and a CDR3 sequence consisting of SEQ ID NO: 608; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 624; a CDR2 sequence consisting of SEQ ID NO: 626; and a CDR3 sequence consisting of SEQ ID NO: 628; (www) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 602 and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 622; (xxx) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 602, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 622; (yyy) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 601, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 621; (zzz) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) the variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 644; the CDR2 sequence consisting of SEQ ID NO: 646; and the CDR3 sequence consisting of SEQ ID NO: 648; and/or (2) the variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 664; the CDR2 sequence consisting of SEQ ID NO: 666; and the CDR3 sequence consisting of SEQ ID NO: 668; (aaaa) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 642, and/or

(2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 662; (bbbb) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 642, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 662, (cccc) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 641, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 661; (dddd) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) the variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 684; the CDR2 sequence consisting of SEQ ID NO: 686; and the CDR3 sequence consisting of SEQ ID NO: 688; and/or (2) the variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 704; the CDR2 sequence consisting of SEQ ID NO: 706; and the CDR3 sequence consisting of SEQ ID NO: 708; (eeee) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 682, and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 702; (ffff) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 682, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 702; (gggg) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 681, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 701; (hhhh) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 724; a CDR2 sequence consisting of SEQ ID NO: 726; and a CDR3 sequence consisting of SEQ ID NO: 728; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 744; a CDR2 sequence consisting of SEQ ID NO: 746; and a CDR3 sequence consisting of SEQ ID NO: 748; (iiii) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 722 and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 742; (jjjj) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 722, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 742; (kkkk) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 721, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 741; (llll) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 764; a CDR2 sequence consisting of SEQ ID NO: 766; and a CDR3 sequence consisting of SEQ ID NO: 768; and/or (2) a variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 784; a CDR2 sequence consisting of SEQ ID NO: 786; and a CDR3 sequence consisting of SEQ ID NO: 788; (mmmm) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 762, and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 782; (nnnn) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 762, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 782; (oooo) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a heavy chain having the amino acid sequence of SEQ ID NO: 761, and/or (2) a light chain having the amino acid sequence of SEQ ID NO: 781; (pppp) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) the variable heavy chain comprising the CDR1 sequence consisting of SEQ ID NO: 804; the CDR2 sequence consisting of SEQ ID NO: 806; and the CDR3 sequence consisting of SEQ ID NO: 808; and/or (2) the variable light chain comprising the CDR1 sequence consisting of SEQ ID NO: 824; the CDR2 sequence consisting of SEQ ID NO: 826; and the CDR3 sequence consisting of SEQ ID NO: 828; (qqqq) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 802, and/or (2) a variable light chain comprising an amino acid sequence with at least 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 822; (rrrr) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (1) a variable heavy chain having the amino acid sequence of SEQ ID NO: 802, and/or (2) a variable light chain having the amino acid sequence of SEQ ID NO: 822; (ssss) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising: (a) a heavy chain having the amino acid sequence of SEQ ID NO: 801, and/or (b) a light chain having the amino acid sequence of SEQ ID NO: 821; (tttt) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing selected from the group consisting of scFvs, camelbodies, nanobodies, Immunoglobulin New Antigen Receptor ("IgNAR"), fragment antigen binding ("Fab") fragments, Fab' fragments, MetMab like antibodies, monovalent antibody fragments, and F(ab')2 fragments; (uuuu) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising, wherein the antibody or antibody fragment substantially or entirely lacks N-glycosylation and/or O-glycosylation; (vvvv) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising wherein the antibody or antibody fragment comprises a human constant domain; (wwww) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising an IgG1, IgG2, IgG3, or IgG4 antibody; (xxxx) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising an Fc region that has been modified to alter at least one of effector function, half-life, proteolysis, or glycosylation; (yyyy) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising an Fc region which contains one or more mutations that alters or eliminates N- and/or O-glycosylation; (zzzz) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing wherein the antibody or antibody fragment binds to PACAP with a binding affinity (K.sub.D) of less than or equal to 5.times.10.sup.-5 M, 10.sup.-5 M, 5.times.10.sup.-6 M, 10.sup.-6 M, 5.times.10.sup.-7 M, 10.sup.-7 M, 5.times.10.sup.-8 M, 10.sup.-8 M, 5.times.10.sup.-9 M, 10.sup.-9 M, 5.times..sup.10-10 M, 10.sup.-10 M, 5.times.10.sup.-11 M, 10.sup.-11 M, 5.times.10.sup.-12 M, 10.sup.-12 M, 5.times.10.sup.-13 M, or 10.sup.-13 M, e.g., as determined by ELISA, bio-layer interferometry ("BLI"), KINEXA or surface plasmon resonance at 25.degree. or 37.degree. C.; (aaaaa) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing wherein the antibody or antibody fragment binds to PACAP with a binding affinity (K.sub.D) of less than or equal to 5.times.10.sup.-10 M, 10.sup.-10 M, 5.times.10.sup.-11 M, 10.sup.-11 M, 5.times.10.sup.-12 M, or 10.sup.-12 M; (bbbbb) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing comprising, which binds to PACAP with an off-rate (k.sub.off) of less than or equal to 5.times.10.sup.-4 s.sup.-1, 10.sup.-4 s.sup.-1, 5.times.10.sup.-5 s.sup.-1, or 10.sup.-5 s.sup.-1; (ccccc) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing wherein the antibody or antibody fragment is directly or indirectly attached to a detectable label or therapeutic agent; (ddddd) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which when administered to a subject inhibits or neutralizes at least one biological effect elicited by PACAP; (eeeee) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which neutralizes or inhibits PACAP activation of at least one of PAC1-R, VPAC1-R, or VPAC2-R; (fffff) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which neutralizes or inhibits PACAP activation of each of PAC1-R, VPAC1-R, and VPAC2-R; (ggggg) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which neutralizes or inhibits PACAP activation of PAC1-R; (hhhhh) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which is capable of inhibiting or preventing PACAP binding to at least one of PAC1-R, VPAC1-R, or VPAC2-R; (iiiii) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which is capable of inhibiting or preventing PACAP binding to each of PAC1-R, VPAC1-R, and VPAC2-R; (jjjjj) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which is capable of inhibiting or preventing PACAP binding to PAC1-R-expressing cells, VPAC1-R-expressing cells, and/or VPAC2-R-expressing cells; (kkkkk) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which inhibits or blocks PACAP-induced cAMP production; (lllll) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which when administered to a subject reduces PACAP-induced vasodilation, mast cell degranulation and/or neuronal activation; (mmmmm) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing wherein the antibody or antibody fragment binds to PACAP with a K.sub.D that is less than about 100 nM; (nnnnn) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing wherein the antibody or antibody fragment binds to PACAP with a K.sub.D that is less than about 40 nM; (ooooo) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing wherein the antibody or antibody fragment binds to PACAP with a K.sub.D that is less than about 100 pM; (ppppp) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing, wherein the antibody or antibody fragment binds to PACAP with a K.sub.D that is less than about 50 pM; (qqqqq) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing wherein the antibody or antibody fragment binds to PACAP with a K.sub.D that is less than about 25 pM; (rrrrr) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing wherein the antibody or antibody fragment binds to PACAP with a K.sub.D that is between about 10 pM and about 100 pM; (sssss) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing which has stronger affinity for PACAP as compared to VIP and/or does not bind to VIP, wherein the affinity of said antibody or antibody fragment to PACAP optionally is at least 10-fold, 30-fold, 100-fold, 300-fold, 1000-fold, 3000-fold, 10000-fold, 30000-fold, 100000-fold, 300000-fold, 1000000-fold, 3000000-fold, 10000000-fold, 30000000-fold or more stronger than the affinity of said antibody or antibody fragment to VIP; (ttttt) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing wherein the antibody or antibody fragment is attached to at least one effector moiety optionally wherein said effector moiety comprises a chemical linker; (uuuuu) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing wherein the antibody or antibody fragment is attached to one or more detectable moieties; optionally wherein said detectable moiety comprises a fluorescent dye, enzyme, substrate, bioluminescent material, radioactive material, chemiluminescent moiety, or mixtures thereof; or (wwwww) a human, humanized or chimerized anti-PACAP antibody or antibody fragment according to any of the foregoing wherein the antibody or antibody fragment is attached to one or more functional moieties:

2-128. (canceled)

129. An anti-idiotypic antibody produced against an anti-PACAP antibody or antibody fragment according claim 1, which optionally, neutralizes one or more biological effects of the anti-PACAP antibody to which it binds.

130. A method of using the anti-idiotypic antibody of claim 129 to monitor the in vivo levels of said anti-PACAP antibody or antibody fragment in a subject or to neutralize the in vivo effects of said anti-PACAP antibody in a subject.

131. A composition suitable for therapeutic, prophylactic, or a diagnostic use comprising a therapeutically, prophylactically or diagnostically effective amount of at least one anti-PACAP antibody or antibody fragment or anti-idiotypic antibody according to claim 1 or 129.

132. The composition of claim 131, which is (i) suitable for subcutaneous, intravenous, intramuscular, topical, oral, inhalatory, intranasal, intrabuccal, vaginal, anal, transdermal, intraperitoneal, or intrathecal administration; (ii) suitable for subcutaneous intravenous or intramuscular administration; (iii) is lyophilized; (iv) further comprising a pharmaceutically acceptable diluent, carrier, solubilizer, emulsifier, preservative, or mixture thereof; (v) further comprising at least one other active agent, optionally selected from the group consisting of a chemotherapeutic, an analgesic, an anti-inflammatory, an immunosuppressant, a cytokine, an antiproliferative, an antiemetic and a cytotoxin; (vi) is lyophilized, stabilized, and/or formulated for administration by injection.

133-138. (canceled)

139. An isolated nucleic acid sequence or nucleic acid sequences encoding an anti-PACAP antibody or antibody fragment or anti-idiotypic antibody according claim 1 or a vector or vectors containing the isolated nucleic acid sequence or sequences or a host cell containing the isolated nucleic acid sequence or sequences or vector or vectors.

140-141. (canceled)

142. The host cell of claim 139, which is a mammalian, bacterial, fungal, yeast, avian, amphibian, plant or insect cell, e.g., a filamentous fungus or a CHO cell or a yeast selected from the following genera: Arxiozyma; Ascobotryozyma; Citeromyces; Debaryomyces; Dekkera; Eremothecium; Issatchenkia; Kazachstania; Kluyveromyces; Kodamaea; Lodderomyces; Pachysolen; Pichia, Saccharomyces; Saturnispora; Tetrapisispora; Torulaspora; Williopsis; and Zygosaccharomyces, optionally Pichia, and further optionally a Pichia selected from Pichia pastoris, Pichia methanolica and Hansenula polymorpha (Pichia angusta).

143-146. (canceled)

147. A method of expressing an anti-PACAP antibody or antibody fragment comprising culturing the host cell according to claim 139 or 142 under conditions that provide for expression of said antibody or antibody fragment, optionally a polyploid yeast cell or CHO cell that stably expresses and secretes said antibody or antibody fragment, optionally made by a method that comprises: (i) introducing at least one expression vector containing one or more heterologous polynucleotides encoding said antibody operably linked to a promoter and a signal sequence into a haploid yeast cell; (ii) producing by mating or spheroplast fusion a polyploid yeast from said first and/or second haploid yeast cell; (iii) selecting polyploid yeast cells, optionally Pichia, that stably express said antibody; and (iv) producing stable polyploid yeast cultures from said polyploid yeast cells that stably express said antibody into the culture medium.

148-150. (canceled)

151. A method selected from the following: (i) blocking, inhibiting, blocking or neutralizing one or more biological effects associated with PACAP in a subject comprising administering to said subject a therapeutically or prophylactically effective amount of a human, humanized or chimerized anti-PACAP antibody or antibody fragment that antagonizes, inhibits, neutralizes or blocks at least one biological effect associated with human PACAP; (ii) blocking, inhibiting, or neutralizing one or more biological effects associated with pituitary adenylate cyclase-activating peptide ("PACAP") in a subject comprising administering to a subject a therapeutically or prophylactically effective amount of a human, humanized or chimerized anti-PACAP antibody or antibody fragment that antagonizes, inhibits, neutralizes or blocks at least one biological effect associated with human PACAP and that does not substantially interact with (bind) Vasoactive Intestinal Peptide ("VIP"); (iii) blocking, inhibiting, or neutralizing one or more biological effects, e.g., vasomotor effects, associated with pituitary adenylate cyclase-activating peptide ("PACAP") in a subject comprising administering to a subject a therapeutically or prophylactically effective amount of a human, humanized or chimerized anti-PACAP antibody or antibody fragment that comprises one or more of the following: (a) inhibits, blocks or neutralizes at least one biological effect elicited by PACAP; (b) neutralizes or inhibits PACAP activation of at least one of PAC1 receptor ("PAC1-R"), vasoactive intestinal peptide receptor type 1 ("VPAC1-R"), and/or vasoactive intestinal peptide receptor type 2 ("VPAC2-R"); (c) inhibits, blocks or neutralizes PACAP activation of each of PAC1-R, VPAC1-R, and VPAC2-R; (d) neutralizes or inhibits PACAP activation of PAC1-R; (d) is capable of inhibiting PACAP binding to at least one of PAC1-R, VPAC1-R, and/or VPAC2-R; (e) is capable of inhibiting PACAP binding to each of PAC1-R, VPAC1-R, and/or VPAC2-R; (f) is capable of inhibiting PACAP binding to PAC1-R-expressing cells; (g) is capable of inhibiting PACAP binding to VPAC1-R and/or VPAC2-R-expressing cells; (h) does not inhibit PACAP-mediated binding of such antibody to the cell surface, e.g., via a glycosaminoglvcan ("GAG"); (i) inhibits PACAP binding to the cell surface, e.g. via a glycosaminoglycan ("GAG"); (j) inhibits PACAP-induced cyclic adenosine monophosphate ("cAMP") production; and/or (k) when administered to a subject reduces PACAP-induced vasodilation, mast cell degranulation and/or neuronal activation: (iv) blocking, inhibiting, or neutralizing vasodilation, e.g., vasodilation of the dural arteries, which is associated with or elicited by pituitary adenylate cyclase-activating peptide ("PACAP") in a subject comprising administering to a subject a therapeutically or prophylactically effective amount of a human, humanized or chimerized anti-PACAP antibody or antibody fragment that blocks, inhibits, or neutralizes vasodilation associated with, or elicited by PACAP; (v) treating or preventing the onset, frequency, severity or duration of headache or migraine in a subject comprising administering to a subject in need thereof an effective amount of a human, humanized or chimerized anti-human Pituitary Adenylate Cyclase-Activating Polypeptide ("PACAP") antibody or antibody fragment that elicits one or more of the following effects: (a) inhibits or neutralizes at least one biological effect elicited by PACAP; (b) neutralizes or inhibits PACAP activation of at least one of PAC1 receptor ("PAC1-R"), vasoactive intestinal peptide receptor type 1 ("VPAC1-R"), and/or vasoactive intestinal peptide receptor type 2 ("VPAC2-R"); (c) neutralizes or inhibits PACAP activation of each of PAC1-R, VPAC1-R, and VPAC2-R; (d) neutralizes or inhibits PACAP activation of PAC1-R; (e) is capable of inhibiting PACAP binding to at least one of PAC1-R, VPAC1-R, and/or VPAC2-R; (f) is capable of inhibiting PACAP binding to each of PAC1-R, VPAC1-R, and/or VPAC2-R; (e) is capable of inhibiting PACAP binding to PAC1-R-expressing cells; (f) is capable of inhibiting PACAP binding to VPAC1-R and/or VPAC2-R-expressing cells; (g) does not inhibit PACAP-mediated binding of such antibody to the cell surface, e.g., via a GAG; (h) inhibits PACAP binding to the cell surface, e.g. via a glycosaminoglycan ("GAG"); (i) inhibits PACAP-induced cyclic adenosine monophosphate ("cAMP") production; and/or (j) when administered to a subject reduces PACAP-induced vasodilation, mast cell degranulation and/or neuronal activation; wherein the headache or migraine is optionally selected from migraine with aura, migraine without aura, hemiplegic migraine, cluster headache, migrainous neuralgia, chronic headache, chronic migraine, medication overuse headache, and tension headache; (vi) treating a human subject having an acute, episodic or chronic condition associated with at least one of increased vasodilation, mast cell degranulation and neuronal activation or a combination of any of the foregoing comprising administering to a subject in need thereof an effective amount of an antagonistic human, humanized or chimerized anti-human Pituitary Adenylate Cyclase-Activating Polypeptide ("PACAP") antibody or antibody fragment; (vii) The method of any one of (i)-(vi), which is effected by the administration of a therapeutically or prophylactically effective amount of at least one human, humanized or chimerized anti-PACAP antibody or antibody fragment according to claim 1 (viii) The method of any one of (i)-(vii), wherein the anti-PACAP antibody is a human antibody or antibody fragment; (ix) The method of any one of (i)-(vii), wherein the anti-PACAP antibody is a humanized antibody or antibody fragment; (x). The method of any one of (i)-(vii), wherein the anti-PACAP antibody is a chimeric antibody or antibody fragment; (xi) The method of any one of (i)-(x), wherein the anti-PACAP antibody or antibody fragment binds to PACAP27 and/or PACAP38 and blocks PACAP27 and/or PACAP38 binding to PAC1-R, VPAC1-R, and/or VPAC2-R; (xii) the method of any one of (i)-(vi), wherein the anti-PACAP antibody or antibody fragment binds to PACAP27 and/or PACAP38 and blocks PACAP27 and/or PACAP38 binding to each of PAC1-R, VPAC1-R, and VPAC2-R; (xiii) the method of any one of (i)-(vi), wherein the anti-PACAP antibody or antibody fragment binds to PACAP27 and/or PACAP38 and blocks PACAP27 and/or PACAP38 binding to PAC1-R-expressing cells; (xiv) the method of any one of (i)-(vi), wherein the affinity of said antibody or antibody fragment to PACAP is at least 10-fold, 30-fold, 100-fold, 300-fold, 1000-fold, 3000-fold, 10000-fold, 30000-fold, 100000-fold, 300000-fold, 1000000-fold, 3000000-fold, 10000000-fold, 30000000-fold or more stronger than the affinity of said antibody or antibody fragment to VIP; (xv) the method of any one of (i)-(xiv), wherein the subject has a condition selected from the group consisting of migraine with aura, migraine without aura, hemiplegic migraines, cluster headaches, migrainous neuralgia, chronic headaches, tension headaches, general headaches, hot flush, chronic paroxysmal hemicrania, secondary headaches due to an underlying structural problem in the head, secondary headaches due to an underlying structural problem in the neck, cranial neuralgia, sinus headaches, headache associated with sinusitis, allergy-induced headaches, allergy-induced migraines, trigeminal neuralgia, post-herpetic neuralgia, phantom limb pain, fibromyalgia, reflex sympathetic dystrophy, pain, chronic pain, inflammatory pain, post-operative incision pain, post-surgical pain, trauma-related pain, lower back pain, eye pain, tooth pain, complex regional pain syndrome, cancer pain, primary or metastatic bone cancer pain, fracture pain, osteoporotic fracture pain, pain resulting from burn, gout joint pain, pain associated with sickle cell crises, pain associated with temporomandibular disorders, cirrhosis, hepatitis, neurogenic pain, neuropathic pain, nociceptic pain, visceral pain, menstrual pain, ovarialgia, osteoarthritis pain, rheumatoid arthritis pain, diabetic neuropathy, sciatica, dyspepsia, irritable bowel syndrome, inflammatory bowel disease, Crohn's disease, ileitis, ulcerative colitis, renal colic, dysmenorrhea, cystitis, interstitial cystitis, menstrual period, labor, menopause, pancreatitis, schizophrenia, depression, post-traumatic stress disorder ("PTSD"), anxiety disorders, autoimmune diabetes, Sjogren's syndrome, multiple sclerosis, overactive bladder, bronchial hyperreactivity, asthma, stroke, bronchitis, bronchodilation, emphysema, chronic obstructive pulmonary disease ("COPD"), inflammatory dermatitis, adenocarcinoma in glandular tissue, blastoma in embryonic tissue of organs, carcinoma in epithelial tissue, leukemia in tissues that form blood cells, lymphoma in lymphatic tissue, myeloma in bone marrow, sarcoma in connective or supportive tissue, adrenal cancer, AIDS-related lymphoma, anemia, bladder cancer, bone cancer, brain cancer, breast cancer, carcinoid tumors, cervical cancer, chemotherapy, colon cancer, cytopenia, endometrial cancer, esophageal cancer, gastric cancer, head cancer, neck cancer, hepatobiliary cancer, kidney cancer, leukemia, liver cancer, lung cancer, lymphoma, Hodgkin's disease, non-Hodgkin's, nervous system tumors, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, skin cancer, stomach cancer, testicular cancer, thyroid cancer, urethral cancer, cancer of bone marrow, multiple myeloma, tumors that metastasize to the bone, tumors infiltrating the nerve and hollow viscus, tumors near neural structures; optionally the cancer pain comprises visceral pain, preferably visceral pain which arises from pancreatic cancer and/or metastases in the abdomen, optionally the cancer pain comprises somatic pain, preferably somatic pain due to one or more of metastasis in the bone, postsurgical pain, sarcomas cancer of the connective tissue, cancer of bone tissue, cancer of blood-forming cells of the bone marrow, multiple myeloma, leukemia, primary or secondary bone cancer, acne vulgaris, atopic dermatitis, urticaria, keloids, hypertrophic scars and rosacea, endothelial dysfunction, Raynaud's syndrome, coronary heart disease ("CHD"), coronary artery disease ("CAD"), heart failure, peripheral arterial disease ("PAD"), diabetes, pulmonary hypertension ("PH"), connective tissue disorder, allergic dermatitis, psoriasis, pruritus, neurogenic cutaneous redness, erythema, sarcoidosis, shock, sepsis, opiate withdrawal syndrome, morphine tolerance, and epilepsy; (xvi) the method of any one of (i)-(xv), wherein the subject has a condition selected from the group consisting of migraine, headache and a pain associated disease or condition, optionally a headache or migraine is selected from the group consisting of migraine with aura, migraine without aura, hemiplegic migraine, cluster headache, migrainous neuralgia, chronic headache, chronic migraine, medication overuse headache, and tension headache; (xvii) the method of any one of (i)-(xv), wherein the subject has a ocular disorder associated with photophobia selected from the group consisting of achromatopsia, aniridia, photophobia caused by an anticholinergic drug, aphakia, buphthalmos, cataracts, cone dystrophy, congenital abnormalities of the eye, viral conjunctivitis, corneal abrasion, corneal dystrophy, corneal ulcer, disruption of the corneal epithelium, ectopia lentis, endophthalmitis, eye trauma caused by disease, eye trauma caused by injury, eye trauma caused by infection, chalazion, episcleritis, glaucoma, keratoconus, optic nerve hypoplasia, hydrophthalmos, congenital glaucoma iritis, optic neuritis, pigment dispersion syndrome, pupillary dilation, retinal detachment, scarring of the cornea, sclera and uveitis; (xviii) the method of any one of (i)-(xv), wherein the subject has a nervous system-related or neurological condition associated with photophobia selected from the group consisting of autism spectrum disorders, Chiari malformation, dyslexia, encephalitis, meningitis, subarachnoid hemorrhage, tumor of the posterior cranial fossa, ankylosing spondylitis, albinism, ariboflavinosis, benzodiazepines, chemotherapy, chikungunya, cvstinosis, Ehlers-Danlos syndrome, hangover, influenza, infectious mononucleosis, magnesium deficiency, mercury poisoning, migraine, rabies, and tvrosinemia type II; (xix) the method of any one of (i)-(xviii), wherein the subject has a photophobia associated disorder selected from the group consisting of migraine with aura, migraine without aura, iritis, uveitis, meningitis, depression, bipolar disorder, cluster headache or anther trigeminal autonomic cephalalgia ("TAC") or blepharospasm, depression, agoraphobia and bipolar disorder; (xx) the method of any one of (i)-(xix), wherein the antibody is a human, humanized, or chimerized anti-PACAP antibody or antibody fragment; or (xxi) the method of any one of (i)-(xx), wherein the anti-PACAP antibody or antibody fragment is a human, humanized, or chimerized anti-PACAP antibody or antibody fragment according to claim 1.

152-261. (canceled)

262. Any of the methods of claim 151, wherein: (i) the anti-PACAP antibody or antibody fragment binds to PACAP with a K.sub.D that is between about 10 pM and about 100 pM; (ii) the method further comprises administering separately or co-administering another agent, optionally selected from a chemotherapeutic, an analgesic, an anti-inflammatory, an immunosuppressant, a cytokine, an antiproliferative, an antiemetic or a cytotoxin or a non-steroidal anti-inflammatory drug ("NSAID"), an opioid analgesic, another antibody or a non-antibody biologic or an anti-NGF antibody or antibody fragment or an anti-Calcitonin Gene-Related Peptide ("CGRP") antibody or antibody fragment and/or an anti-CGRP receptor antibody or antibody fragment or is a cyclooxygenase 1 and/or cyclooxygenase 2 inhibitor or is a NSAID is selected from the group consisting of (1) propionic acid derivatives including ibuprofen, naproxen, naprosyn, diclofenac, and ketoprofen; (2) acetic acid derivatives including tolmetin and sulindac: (3) fenamic acid derivatives including mefenamic acid and meclofenamic acid; (4) biphenylcarboxylic acid derivatives including diflunisal and flufenisal; and (5) oxicams including piroxim, sudoxicam, and isoxicam or ia an opioid analgesic selected from the group consisting of codeine, dihydrocodeine, diacetylmorphine, hydrocodone, hydromorphone, levorphanol, oxymorphone, alfentanil, buprenorphine, butorphanol, fentanyl, sufentanil, meperidine, methadone, nalbuphine, propoxyphene, pentazocine, and pharmaceutically acceptable salts thereof or is morphine or a morphine derivative or pharmaceutically acceptable salt thereof; (iii) the method comprises the combined administration of the opioid analgesic and the anti-PACAP antibody or antigen binding fragment which increase the analgesic effect as compared to either the opioid analgesic or the anti-PACAP antibody or antigen binding fragment administered alone; (iv) the treated subject has previously received an anti-CGRP antibody or antibody fragment and/or an anti-CGRP receptor antibody or antibody fragment; (v) the treated subject is a migraineur who did not adequately respond to anti-CGRP antibody and/or an anti-CGRP receptor antibody or antibody fragment treatment; (vi) the subject has previously received at least one anti-CGRP antibody or antibody fragment and/or an anti-CGRP receptor antibody or antibody fragment administration and has elicited an immune response to the anti-CGRP antibody or antibody fragment and/or the anti-CGRP receptor antibody or antibody fragment; or (vii) the method of any of the foregoing wherein the antibody or antigen binding fragment thereof ameliorates or treats one or more conditions associated with PACAP expression in a subject in need thereof, said condition selected from the group consisting of: migraine with aura, migraine without aura, hemiplegic migraines, cluster headaches, migrainous neuralgia, chronic headaches, tension headaches, general headaches, hot flush, chronic paroxysmal hemicrania, secondary headaches due to an underlying structural problem in the head, secondary headaches due to an underlying structural problem in the neck, cranial neuralgia, sinus headaches, headache associated with sinusitis, allergy-induced headaches, allergy-induced migraines, trigeminal neuralgia, post-herpetic neuralgia, phantom limb pain, fibromyalgia, reflex sympathetic dystrophy, pain, chronic pain, inflammatory pain, post-operative incision pain, post-surgical pain, trauma-related pain, lower back pain, eye pain, tooth pain, complex regional pain syndrome, cancer pain, primary or metastatic bone cancer pain, fracture pain, osteoporotic fracture pain, pain resulting from burn, gout joint pain, pain associated with sickle cell crises, pain associated with temporomandibular disorders, cirrhosis, hepatitis, neurogenic pain, neuropathic pain, nociceptic pain, visceral pain, menstrual pain, ovarialgia, osteoarthritis pain, rheumatoid arthritis pain, diabetic neuropathy, sciatica, dyspepsia, irritable bowel syndrome, inflammatory bowel disease, Crohn's disease, ileitis, ulcerative colitis, renal colic, dysmenorrhea, cystitis, interstitial cystitis, menstrual period, labor, menopause, pancreatitis, schizophrenia, depression, post-traumatic stress disorder, anxiety disorders, autoimmune diabetes, Sjogren's syndrome, multiple sclerosis, overactive bladder, bronchial hyperreactivity, asthma, stroke, bronchitis, bronchodilation, emphysema, chronic obstructive pulmonary disease ("COPD"), inflammatory dermatitis, adenocarcinoma in glandular tissue, blastoma in embryonic tissue of organs, carcinoma in epithelial tissue, leukemia in tissues that form blood cells, lymphoma in lymphatic tissue, myeloma in bone marrow, sarcoma in connective or supportive tissue, adrenal cancer, AIDS-related lymphoma, anemia, bladder cancer, bone cancer, brain cancer, breast cancer, carcinoid tumors, cervical cancer, chemotherapy, colon cancer, cytopenia, endometrial cancer, esophageal cancer, gastric cancer, head cancer, neck cancer, hepatobiliary cancer, kidney cancer, leukemia, liver cancer, lung cancer, lymphoma, Hodgkin's disease, non-Hodgkin's, nervous system tumors, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, skin cancer, stomach cancer, testicular cancer, thyroid cancer, urethral cancer, cancer of bone marrow, multiple myeloma, tumors that metastasize to the bone, tumors infiltrating the nerve and hollow viscus, tumors near neural structures, acne vulgaris, atopic dermatitis, urticaria, keloids, hypertrophic scars and rosacea, endothelial dysfunction, Raynaud's syndrome, coronary heart disease ("CHD"), coronary artery disease ("CAD"), heart failure, peripheral arterial disease ("PAD"), diabetes, pulmonary hypertension ("PH"), connective tissue disorder, allergic dermatitis, psoriasis, pruritus, neurogenic cutaneous redness, erythema, sarcoidosis, shock, sepsis, opiate withdrawal syndrome, morphine tolerance, and epilepsy.

263-277. (canceled)

278. An anti-PACAP antibody or antibody fragment or a method according to claim 1 or 262 which: (i) inhibits the effects of PACAP on vasodilation; (ii) inhibits the effects of PACAP on cAMP production; (iii) inhibits the effects of PACAP on PLC resulting in reduced Ca.sup.++ and PLD levels; (v) inhibits the effects of PACAP on adenylate cyclase activity; (vi) inhibits the effects of PACAP on its binding to any or all of PAC1-R, VPAC1-R or VPAC2-R; (vii) inhibits the effects of PACAP on neurodevelopment; (viii) inhibits the effects of PACAP on neuroprotection; (ix) inhibits the effects of PACAP on neuromodulation; (x) inhibits the effects of PACAP on neurogenic inflammation; (xi) inhibits the effects of PACAP on nociception; (xii) modulates the interaction of PACAP with binding the cell surface, e.g. via at least one glycosaminoglycan ("GAG"); optionally wherein said at least one GAG comprises one or more of heparin, chondroitin, keratin, and hyaluronic acid; (xiii) blocks or inhibits receptor-independent cellular uptake of PACAP38 and/or PACAP27; or it (xiv) inhibits or blocks GAG-dependent uptake of PACAP38 and/or PACAP27 by cells.

279-291. (canceled)

292. A method of therapy or prophylaxis which comprises the administration of an anti-PACAP antibody or antibody fragment according to claim 1.

293. A composition for use in human therapy containing an anti-PACAP antibody or antibody fragment according to claim 1.

294. The composition of claim 293, which: (i) contains another active agent, e.g., selected from a chemotherapeutic, an analgesic, an anti-inflammatory, an immunosuppressant, a cytokine, an antiproliferative, an antiemetic or a cytotoxin, optionally the analgesic is a non-steroidal anti-inflammatory drug ("NSAID"), an opioid analgesic, another antibody or a non-antibody biologic, the other antibody is an anti-NGF antibody or antibody fragment, the other antibody is an anti-Calcitonin Gene-Related Peptide ("CGRP") antibody or antibody fragment and/or an anti-CGRP receptor antibody or antibody fragment, optionally the NSAID is a cyclooxygenase 1 and/or cyclooxygenase 2 inhibitor, the NSAID is selected from the group consisting of (1) propionic acid derivatives including ibuprofen, naproxen, naprosyn, diclofenac, and ketoprofen; (2) acetic acid derivatives including tolmetin and sulindac: (3) fenamic acid derivatives including mefenamic acid and meclofenamic acid; (4) biphenylcarboxylic acid derivatives including diflunisal and flufenisal; and (5) oxicams including piroxim, sudoxicam, and isoxicam, the opioid analgesic is selected from the group consisting of codeine, dihydrocodeine, diacetylmorphine, hydrocodone, hydromorphone, levorphanol, oxymorphone, alfentanil, buprenorphine, butorphanol, fentanyl, sufentanil, meperidine, methadone, nalbuphine, propoxyphene, pentazocine, and pharmaceutically acceptable salts thereof, the opioid analgesic is morphine or a morphine derivative or pharmaceutically acceptable salt thereof, the opioid analgesic and the anti-PACAP antibody or antigen binding fragment increase the analgesic effect as compared to either the opioid analgesic or the anti-PACAP antibody or antigen binding fragment administered alone, the anti-PACAP antibody or fragment and another active agent combined therewith or administered in combination elicit a synergistic or additive effect on the treatment or prevention of a PACAP associated effect, e.g., migraine or on pain.

295-311. (canceled)

312. A composition for use in human therapy containing an anti-PACAP antibody or antibody fragment according to claim 278.