Anti- integrin antibodies, compositions, methods and uses

Abstract

The present invention relates to at least one novel anti-alpha-V subunit antibodies, including isolated nucleic acids that encode at least one anti-alpha-V subunit antibody, alpha-V subunit, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

1 . A method for modulating angiogenesis in a cell, tissue, organ or animal, comprising administering a composition comprising an effective amount of an isolated human anti-αV subunit antibody or antigen-binding fragment thereof, to said cell, tissue, organ or animal 
     
     
         2 . The method of  claim 1  wherein the isolated human antibody or antigen-binding fragment binds to human α v  integrin subunit with a Kd of 10 −8  M or less. 
     
     
         3 . The method of  claim 1  wherein the isolated human anti-αV subunit antibody or antigen-binding fragment thereof, wherein the heavy chain variable region sequences is derived from the heavy chain CNTO 95 variable region sequence of SEQ ID NO.7 and the light chain variable region sequences is derived from the light chain CNTO 95 variable region sequence of SEQ ID NO.8. 
     
     
         4 . The method of  claim 1  wherein the isolated human antibody or antigen-binding fragment comprises human heavy chain CDR sequences of SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3, and human light chain CDR sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6. 
     
     
         5 . The method of  claim 1  wherein the human anti-αV subunit antibody or antigen-binding fragment thereof completely inhibits M21 cell adhesion to vitronectin. 
     
     
         6 . The method of  claim 1  wherein the human anti-αV subunit antibody or antigen-binding fragment thereof comprises a human IgG heavy chain and a human kappa light chain. 
     
     
         7 . The method of  claim 1  wherein the human anti-αV subunit antibody or antigen-binding fragment thereof comprises an IgG1 or IgG3 heavy chain. 
     
     
         8 . A method for inhibiting microcapillary formation in a cell, tissue, organ or animal, comprising administering a composition comprising an effective amount of an isolated human anti-αV subunit antibody or antigen-binding fragment thereof, to said cell, tissue, organ or animal. 
     
     
         9 . The method of  claim 8  wherein the isolated human antibody or antigen-binding fragment binds to human α v  integrin subunit with a Kd of 10 −8  M or less. 
     
     
         10 . The method of  claim 8  wherein the isolated human anti-αV subunit antibody or antigen-binding fragment thereof, wherein the heavy chain variable region sequences is derived from the heavy chain CNTO 95 variable region sequence of SEQ ID NO.7 and the light chain variable region sequences is derived from the light chain CNTO 95 variable region sequence of SEQ ID NO.8. 
     
     
         11 . The method of  claim 8  wherein the isolated human antibody or antigen-binding fragment comprises human heavy chain CDR sequences of SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3, and human light chain CDR sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6. 
     
     
         12 . The method of  claim 8  wherein the human anti-αV subunit antibody or antigen-binding fragment thereof completely inhibits M21 cell adhesion to vitronectin. 
     
     
         13 . The method of  claim 8  wherein the human anti-αV subunit antibody or antigen-binding fragment thereof comprises a human IgG heavy chain and a human kappa light chain. 
     
     
         14 . The method of  claim 8  wherein the human anti-αV subunit antibody or antigen-binding fragment thereof comprises an IgG1 or IgG3 heavy chain. 
     
     
         15 . A method for treating malignant disease in an animal in need thereof, comprising administering a composition comprising an effective amount of an isolated human anti-αV subunit antibody or antigen-binding fragment thereof, to said cell, tissue, organ or animal 
     
     
         16 . The method of  claim 15  wherein the isolated human antibody or antigen-binding fragment binds to human α v  integrin subunit with a Kd of 10 −8  M or less. 
     
     
         17 . The method of  claim 15  wherein the isolated human antibody or antigen-binding fragment comprises human heavy chain CDR sequences of SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3, and human light chain CDR sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6. 
     
     
         18 . The method of  claim 15  wherein the human anti-αV subunit antibody or antigen-binding fragment thereof completely inhibits M21 cell adhesion to vitronectin. 
     
     
         19 . The method of  claim 15  wherein the human anti-αV subunit antibody or antigen-binding fragment thereof comprises a human IgG heavy chain and a human kappa light chain. 
     
     
         20 . The method of  claim 15  wherein the human anti-αV subunit antibody or antigen-binding fragment thereof comprises an IgG1 or IgG3 heavy chain.