Compositions And Methods For Treating Angiogenesis-Related Disorders

Abstract

Provided herein are anti-angiogenic monoclonal antibodies and antigen-binding antibody fragments that selectively and specifically bind to an epitope in both fibronectin and either fibrinogen or fibrin fragment E, compositions containing these antibodies and antibody fragments, and methods of using these antibodies and antibody fragments.

1 .- 57 . (canceled) 
     
     
         58 . A method of inhibiting solid tumor growth in a subject, the method comprising
 identifying a subject having a solid tumor; and   administering to the subject a composition comprising an effective amount of a monoclonal antibody or antigen-binding fragment thereof that binds to human fibronectin, and human fibrinogen, and human fibrin fragment E.   
     
     
         59 . The method of  claim 58 , wherein the monoclonal antibody or antigen-binding fragment thereof is produced by a hybridoma deposited at the American Type Culture Collection (ATCC) and designated as PTA-120972. 
     
     
         60 . The method of  claim 58 , wherein the isolated monoclonal antibody or antigen-binding fragment thereof is a humanized antibody or a fully human antibody. 
     
     
         61 . The method of  claim 58 , wherein the antigen-binding fragment is selected from the group consisting of a Fab fragment, a F(ab′)2 fragment, a scFv fragment, and a sc(Fv)2 diabody. 
     
     
         62 . The method of  claim 58 , wherein the solid tumor is a sarcoma, a carcinoma, or a lymphoma. 
     
     
         63 . The method of  claim 58 , further comprising administering to the subject a chemotherapeutic agent. 
     
     
         64 . The method of  claim 58 , further comprising administering to the subject one or more angiogenesis inhibitors selected from the group consisting of bevacizumab, sorafenib, sunitinib, pazopanib, axitinib, cabozantinib, regorafenib, vandetanib, temsirolimus, everolimus, lenalidomide, erlotinib, angiostatin, endostatin, tumstatin, canstatin, restin, and arresten. 
     
     
         65 . The method of  claim 58 , wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3 wherein:
 (i) the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:20,   (ii) the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:22,   (iii) the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:24,   (iv) the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:28,   (v) the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:30, and   (vi) the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:32.   
     
     
         66 . The method of  claim 65 , wherein the isolated monoclonal antibody or antigen-binding fragment thereof is a humanized antibody or a fully human antibody. 
     
     
         67 . The method of  claim 65 , wherein the antigen-binding fragment is selected from the group consisting of a Fab fragment, a F(ab′)2 fragment, a scFv fragment, and a sc(Fv)2 diabody. 
     
     
         68 . The method of  claim 65 , wherein the solid tumor is a sarcoma, a carcinoma, or a lymphoma. 
     
     
         69 . The method of  claim 65 , further comprising administering to the subject a chemotherapeutic agent. 
     
     
         70 . The method of  claim 65 , further comprising administering to the subject one or more angiogenesis inhibitors selected from the group consisting of bevacizumab, sorafenib, sunitinib, pazopanib, axitinib, cabozantinib, regorafenib, vandetanib, temsirolimus, everolimus, lenalidomide, erlotinib, angiostatin, endostatin, tumstatin, canstatin, restin, and arresten. 
     
     
         71 . The method of  claim 58 , wherein the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3, wherein:
 (i) the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4,   (ii) the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:6,   (iii) the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:8,   (iv) the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:12,   (v) the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:14, and   (vi) the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:16.   
     
     
         72 . The method of  claim 71 , wherein the isolated monoclonal antibody or antigen-binding fragment thereof is a humanized antibody or a fully human antibody. 
     
     
         73 . The method of  claim 71 , wherein the antigen-binding fragment is selected from the group consisting of a Fab fragment, a F(ab′)2 fragment, a scFv fragment, and a sc(Fv)2 diabody. 
     
     
         74 . The method of  claim 71 , wherein the solid tumor is a sarcoma, a carcinoma, or a lymphoma. 
     
     
         75 . The method of  claim 71 , further comprising administering to the subject a chemotherapeutic agent. 
     
     
         76 . The method of  claim 71 , further comprising administering to the subject one or more angiogenesis inhibitors selected from the group consisting of bevacizumab, sorafenib, sunitinib, pazopanib, axitinib, cabozantinib, regorafenib, vandetanib, temsirolimus, everolimus, lenalidomide, erlotinib, angiostatin, endostatin, tumstatin, canstatin, restin, and arresten.