Polypeptides and Antibodies

Abstract

Polypeptides are provided. Antibodies or antigen binding domains are provided which bind such polypeptides. Also provided are methods of obtaining an antibody that binds tumor necrosis factor (TNF)-related apoptosis-inducing ligand (“TRAIL”) Receptor-2 (TR-2) comprising administering at least one of such polypeptides to an animal and obtaining an antibody that binds TR-2 from the animal. Antibodies reactive with TR-2 are provided. Also provided are cells producing antibodies reactive with TR-2, pharmaceutical compositions comprising antibodies reactive with TR-2, methods using antibodies reactive with TR-2, and kits comprising antibodies reactive with TR-2. Also provided are methods of decreasing or preventing binding of an antibody to TR-2 by administering such a polypeptide.

1 - 113 . (canceled) 
     
     
         114 . An isolated antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises:
 a) CDR1, CDR2, and CDR3 of SEQ ID NO: 2;   b) CDR1, CDR2, and CDR3 of SEQ ID NO: 4;   c) CDR1, CDR2, and CDR3 of SEQ ID NO: 6;   d) CDR1, CDR2, and CDR3 of SEQ ID NO: 8;   e) CDR1, CDR2, and CDR3 of SEQ ID NO: 10;   f) CDR1, CDR2, and CDR3 of SEQ ID NO: 12;   g) CDR1, CDR2, and CDR3 of SEQ ID NO: 14;   h) CDR1, CDR2, and CDR3 of SEQ ID NO: 16;   i) CDR1, CDR2, and CDR3 of SEQ ID NO: 18;   j) CDR1, CDR2, and CDR3 of SEQ ID NO: 20;   k) CDR1, CDR2, and CDR3 of SEQ ID NO: 22;   l) CDR1, CDR2, and CDR3 of SEQ ID NO: 24;   m) CDR1, CDR2, and CDR3 of SEQ ID NO: 26;   n) CDR1, CDR2, and CDR3 of SEQ ID NO: 28;   o) CDR1, CDR2, and CDR3 of SEQ ID NO: 30;   p) CDR1, CDR2, and CDR3 of SEQ ID NO: 32; or   q) CDR1, CDR2, and CDR3 of SEQ ID NO: 34; and   
       wherein the antibody binds TRAIL receptor-2 (TR-2). 
     
     
         115 . The isolated antibody of  claim 114 , wherein the heavy chain comprises an amino acid sequence of any of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, and 34. 
     
     
         116 . The isolated antibody of  claim 114 , wherein the antibody is a fully human antibody. 
     
     
         117 . The isolated antibody of  claim 114 , wherein the antibody is linked to polyethylene glycol. 
     
     
         118 . The isolated antibody of  claim 114 , wherein the antibody is glycosylated. 
     
     
         119 . An isolated antibody comprising a heavy chain and a light chain, wherein the light chain comprises:
 a) CDR1, CDR2, and CDR3 of SEQ ID NO: 36;   b) CDR1, CDR2, and CDR3 of SEQ ID NO: 38;   c) CDR1, CDR2, and CDR3 of SEQ ID NO: 40;   d) CDR1, CDR2, and CDR3 of SEQ ID NO: 42;   e) CDR1, CDR2, and CDR3 of SEQ ID NO: 44;   f) CDR1, CDR2, and CDR3 of SEQ ID NO: 46;   g) CDR1, CDR2, and CDR3 of SEQ ID NO: 48;   h) CDR1, CDR2, and CDR3 of SEQ ID NO: 50;   i) CDR1, CDR2, and CDR3 of SEQ ID NO: 52;   j) CDR1, CDR2, and CDR3 of SEQ ID NO: 54;   k) CDR1, CDR2, and CDR3 of SEQ ID NO: 56;   l) CDR1, CDR2, and CDR3 of SEQ ID NO: 58;   m) CDR1, CDR2, and CDR3 of SEQ ID NO: 60;   n) CDR1, CDR2, and CDR3 of SEQ ID NO: 62;   o) CDR1, CDR2, and CDR3 of SEQ ID NO: 64;   p) CDR1, CDR2, and CDR3 of SEQ ID NO: 66; or   q) CDR1, CDR2, and CDR3 of SEQ ID NO: 68; and   
       wherein the antibody binds TRAIL receptor-2 (TR-2). 
     
     
         120 . The isolated antibody of  claim 119 , wherein the light chain comprises an amino acid sequence of any of SEQ ID NOs: 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, and 68. 
     
     
         121 . The isolated antibody of  claim 119 , wherein the antibody is a fully human antibody. 
     
     
         122 . The isolated antibody of  claim 119 , wherein the antibody is linked to polyethylene glycol. 
     
     
         123 . The isolated antibody of  claim 119 , wherein the antibody is glycosylated. 
     
     
         124 . An isolated antibody that specifically binds to an epitope that is specifically bound by at least one antibody selected from: Ab A, Ab B, Ab C, Ab D, Ab E, Ab F, Ab G, Ab H, Ab I, Ab J, Ab K, Ab L, Ab M, Ab N, Ab O, Ab P, and Ab Q, wherein the antibody induces apoptosis in at least one cell line selected from COLO 205 cells, MDA-231 cells, WM35 cells, and WM793 cells. 
     
     
         125 . The isolated antibody of  claim 124 , wherein the antibody binds to an epitope that is specifically bound by Ab O. 
     
     
         126 . The isolated antibody of  claim 124 , wherein the antibody binds to an epitope within at least one amino acid sequence selected from SEQ ID NO: 94, SEQ ID NO: 95, and SEQ ID NO: 96. 
     
     
         127 . The isolated antibody of  claim 124 , wherein the antibody binds to a polypeptide having the amino acid sequence of SEQ ID NO: 71. 
     
     
         128 . A pharmaceutical composition comprising the isolated antibody of  claims 114  and a pharmaceutically acceptable carrier. 
     
     
         129 . A pharmaceutical composition comprising the isolated antibody of  claims 119  and a pharmaceutically acceptable carrier. 
     
     
         130 . A pharmaceutical composition comprising the isolated antibody of  claims 124  and a pharmaceutically acceptable carrier. 
     
     
         131 . A method of treating cancer in a patient comprising administering a therapeutically effective amount of the antibody of  claim 114 . 
     
     
         132 . A method of treating cancer in a patient comprising administering a therapeutically effective amount of the antibody of  claim 119 . 
     
     
         133 . A method of treating cancer in a patient comprising administering a therapeutically effective amount of the antibody of  claim 124 .