Antibodies Directed To Alpha V Beta 6 And Uses Thereof

Abstract

Targeted binding agents, such antibodies directed to the antigen αVβ6 and uses of such agents are described. In particular, fully human monoclonal antibodies directed to the antigen αVβ6 are disclosed. Nucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3 are disclosed. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also disclosed.

1 . A targeted binding agent that specifically binds to αVβ6 and inhibits binding of ligands to αVβ6. 
     
     
         2 - 22 . (canceled) 
     
     
         23 . An isolated antibody that binds αVβ6, wherein the antibody comprises:
 a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences; and 
 a light chain variable region comprising CDR1, CDR2, and CDR3 sequences, wherein 
 the heavy chain variable region CDR3 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO.: 14, SEQ ID NO.: 22, SEQ ID NO.: 26, SEQ ID NO.: 30 or SEQ ID NO.: 38, SEQ ID NO:71, SEQ ID NO: 76, SEQ ID NO: 79 and conservative sequence modifications thereof, and 
 the light chain variable region CDR3 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: SEQ ID NO.: 16, SEQ ID NO.: 24, SEQ ID NO.: 28, SEQ ID NO.: 32 or SEQ ID NO.: 40, SEQ ID NO:85, SEQ ID NO: 93, and conservative sequence modifications thereof. 
 
     
     
         24 - 51 . (canceled) 
     
     
         52 . A method of inhibiting the interaction of αVβ6 with it's ligand, comprising contacting αVβ6 with an isolated antibody that binds αVβ6, wherein the antibody is selected from the group consisting of an antibody comprising
 (a) a light chain variable region selected from the group consisting of: a. a light chain sequence comprising the sequence of SEQ ID NO:77, b. a light chain sequence comprising the sequence of SEQ ID NO:24, c. a light chain sequence comprising the sequence of SEQ ID NO:40; and d. a light chain sequence comprising the sequence of SEQ ID NO:28; 
 (b) a heavy chain variable region selected from the group consisting of: a. a heavy chain sequence comprising the sequence of SEQ ID NO:75, b. a heavy chain sequence comprising the sequence of SEQ ID NO:22, c. a heavy chain sequence comprising the sequence of SEQ ID NO:38; and d. a heavy chain sequence comprising the sequence of SEQ ID NO:26; or 
 (c) a heavy chain variable region and a light chain variable region selected from the group consisting of: a. a light chain sequence comprising the sequence of SEQ ID NO:77 and a heavy chain sequence comprising the sequence of SEQ ID NO:75, b. a light chain sequence comprising the sequence of SEQ ID NO:24 and a heavy chain sequence comprising the sequence of SEQ ID NO:22, c. a light chain sequence comprising the sequence of SEQ ID NO:40 and a heavy chain sequence comprising the sequence of SEQ ID NO:38; and d. a light chain sequence comprising the sequence of SEQ ID NO:28 and a heavy chain sequence comprising the sequence of SEQ ID NO:26. 
 
     
     
         53 . A method of treating a malignant tumor in an animal, comprising administering to said animal in need thereof a therapeutically effective dose of an antibody of  claim 23 . 
     
     
         54 . A method of treating inflammation, comprising administering to an animal in need thereof a therapeutically effective dose of an antibody of  claim 23 . 
     
     
         55 - 59 . (canceled) 
     
     
         60 . A conjugate comprising an antibody of  claim 23 . 
     
     
         61 - 62 . (canceled) 
     
     
         63 . The method of  claim 52 , wherein the antibody comprises a light chain variable region selected from the group consisting of: a. a light chain sequence comprising the sequence of SEQ ID NO:77, b. a light chain sequence comprising the sequence of SEQ ID NO:24, c. a light chain sequence comprising the sequence of SEQ ID NO:40; and d. a light chain sequence comprising the sequence of SEQ ID NO:28. 
     
     
         64 . The method of  claim 52 , wherein the antibody comprises a heavy chain variable region selected from the group consisting of: a. a heavy chain sequence comprising the sequence of SEQ ID NO:75, b. a heavy chain sequence comprising the sequence of SEQ ID NO:22, c. a heavy chain sequence comprising the sequence of SEQ ID NO:38; and d. a heavy chain sequence comprising the sequence of SEQ ID NO:26. 
     
     
         65 . The method of  claim 52 , wherein the antibody comprises a heavy chain variable region and a light chain variable region selected from the group consisting of: a. a light chain sequence comprising the sequence of SEQ ID NO:77 and a heavy chain sequence comprising the sequence of SEQ ID NO:75, b. a light chain sequence comprising the sequence of SEQ ID NO:24 and a heavy chain sequence comprising the sequence of SEQ ID NO:22, c. a light chain sequence comprising the sequence of SEQ ID NO:40 and a heavy chain sequence comprising the sequence of SEQ ID NO:38; and d. a light chain sequence comprising the sequence of SEQ ID NO:28 and a heavy chain sequence comprising the sequence of SEQ ID NO:26. 
     
     
         66 . The method of  claim 63 , wherein the antibody comprises the light chain sequence comprising SEQ ID NO:77. 
     
     
         67 . The method of  claim 63 , wherein the antibody comprises the light chain sequence comprising SEQ ID NO:24. 
     
     
         68 . The method of  claim 64 , wherein the antibody comprises the light chain sequence comprising SEQ ID NO:75. 
     
     
         69 . The method of  claim 64 , wherein the antibody comprises the light chain sequence comprising SEQ ID NO:22. 
     
     
         70 . The method of  claim 65 , wherein the antibody comprises: a. a heavy chain variable region CDR1, CDR2, and CDR3 of SEQ ID NO:75; and b. a light chain variable region CDR1, CDR2 and CDR3 of SEQ ID NO:77.