US2013129735A1PendingUtilityA1

Antibodies to egfl7 and methods for their use

Assignee: GENENTECH INCPriority: Mar 16, 2006Filed: Jan 31, 2013Published: May 23, 2013
Est. expiryMar 16, 2026(expired)· nominal 20-yr term from priority
A61P 35/04A61P 9/10A61P 35/00A61P 43/00A61P 37/06A61P 9/00A61P 27/00A61P 27/02A61P 27/06C07K 2317/73A61P 19/02C07K 2317/565A61K 2039/505A61K 2039/507A61P 17/06C07K 2317/56C07K 16/22
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Claims

Abstract

The invention provides anti-EGFL7 antibodies, and compositions comprising and methods of using these antibodies.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . An antibody produced by a hybridoma selected from the group consisting of: anti-EGFL7 mumab 4F11.1.8, anti-EGFL7 mumab 10G9.1.6, and anti-EGFL7 mumab 18F7.1.8. 
     
     
         2 . An anti-EGFL7 antibody comprising one or more complementarity determining regions (CDRs) selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 5) 
                 
                     
                   (a) 4F11 CDR-L1 sequence KASQSVDYDGDSYMS; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   (b) 4F11 CDR-L2 sequence GASNLES; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   (c) 4F11 CDR-L3 sequence QQNNEDPYT; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   (d) 4F11 CDR-H1 sequence TYGMS; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   (e) 4F11 CDR-H2 sequence WINTHSGVPTYADDFKG; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 10) 
                 
                     
                   (f) 4F11 CDR-H3 sequence LGSSA. 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         3 . The anti-EGFL7 antibody of  claim 2 , wherein the light chain of said antibody comprises at least one, at least two or all three of the CDR sequences selected from: KASQSVDYDGDSYMS (SEQ ID NO: 5), GASNLES (SEQ ID NO: 6), and QQNNEDPYT (SEQ ID NO: 7). 
     
     
         4 . The anti-EGFL7 antibody of  claim 2 , wherein the heavy chain of said antibody comprises at least one, at least two or all three of the CDR sequences selected from: TYGMS (SEQ ID NO: 8), WINTHSGVPTYADDFKG (SEQ ID NO: 9), and LGSSA (SEQ ID NO: 10). 
     
     
         5 . The anti-EGFL7 antibody of  claim 2 , wherein the light chain of said antibody comprises at least one, at least two or all three of the CDR sequences selected from: KASQSVDYDGDSYMS (SEQ ID NO: 5), GASNLES (SEQ ID NO: 6), and QQNNEDPYT (SEQ ID NO: 7); and
 wherein the heavy chain of said antibody comprises at least one, at least two or all three of the CDR sequences selected from: TYGMS (SEQ ID NO: 8), WINTHSGVPTYADDFKG (SEQ ID NO: 9), and LGSSA (SEQ ID NO: 10).   
     
     
         6 . The anti-EGFL7 antibody of  claim 2 , wherein the light chain of said antibody comprises the sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 1) 
                 
                   DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMSWYQQKPGQPPKL 
                 
                     
                 
                   LIYGASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQNNEDPY 
                 
                     
                 
                   TFGGGTKVEIKR. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         7 . The anti-EGFL7 antibody of  claim 2 , wherein the heavy chain of said antibody comprises the sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 2) 
                 
                   QIQLVQSGPELKKPGETVKISCKASGHTFTTYGMSWVKQAPGKGLKWMGW 
                 
                     
                 
                   INTHSGVPTYADDFKGRFAFSLETSASTAHLQINNLKNEDTATYFCARLG 
                 
                     
                 
                   SSAVDYWGQGTTVTVSS. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         8 . An anti-EGFL7 antibody comprising one or more complementarity determining regions (CDRs) selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 11) 
                 
                     
                   (a) 10G9 CDR-L1 sequence RSSQSLVHTNGITYLH; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 12) 
                 
                     
                   (b) 10G9 CDR-L2 sequence KVSNRFS; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 13) 
                 
                     
                   (c) 10G9 CDR-L3 sequence SQSTHVPLT; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 14) 
                 
                     
                   (d) 10G9 CDR-H1 sequence DYYMNSDYYMN; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 15) 
                 
                     
                   (e) 10G9 CDR-H2 sequence DINPKNGGTTYNQKFKG; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 16) 
                 
                     
                   (f) 10G9 CDR-H3 sequence ALGVFDY. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         9 . The anti-EGFL7 antibody of  claim 8 , wherein the light chain of said antibody comprises at least one, at least two or all three of the CDR sequences selected from: RSSQSLVHTNGITYLH (SEQ ID NO: 11), KVSNRFS (SEQ ID NO: 12), and SQSTHVPLT (SEQ ID NO: 13). 
     
     
         10 . The anti-EGFL7 antibody of  claim 8 , wherein the heavy chain of said antibody comprises at least one, at least two or all three of the CDR sequences selected from: DYYMNSDYYMN (SEQ ID NO: 14), DINPKNGGTTYNQKFKG (SEQ ID NO: 15), and ALGVFDY (SEQ ID NO: 16). 
     
     
         11 . The anti-EGFL7 antibody of  claim 8 , wherein the light chain of said antibody comprises at least one, at least two or all three of the CDR sequences selected from: RSSQSLVHTNGITYLH (SEQ ID NO: 11), KVSNRFS (SEQ ID NO: 12), and SQSTHVPLT (SEQ ID NO: 13); and
 wherein the heavy chain of said antibody comprises at least one, at least two or all three of the CDR sequences selected from: DYYMNSDYYMN (SEQ ID NO: 14), DINPKNGGTTYNQKFKG (SEQ ID NO: 15), and ALGVFDY (SEQ ID NO: 16).   
     
     
         12 . The anti-EGFL7 antibody of  claim 8 , wherein the light chain of said antibody comprises the sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 3) 
                 
                   DIVMTQTPLSLPVSLGDQASISCRSSQSLVHTNGITYLHWYLQKPGQSPK 
                 
                     
                 
                   LLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVP 
                 
                     
                 
                   LTFGAGTKVEIKR. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         13 . The anti-EGFL7 antibody of  claim 8 , wherein the heavy chain of said antibody comprises the sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 4) 
                 
                   EVQLQQSGPELVKPGASVKISCKASGYTFSDYYMNSDYYMNWVKQSHGKS 
                 
                     
                 
                   LEWIGDINPKNGGTTYNQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVY 
                 
                     
                 
                   YCAREADYDPIYYAMDYWGQGTTLTVSA. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         14 . An anti-EGFL7 antibody that specifically binds to a polypeptide comprising an amino acid sequence selected from the group consisting of: CCP, RTIY (SEQ ID NO 33). 
     
     
         15 . An isolated antibody that binds to the same epitope on human EGFL7 as the antibody of any one of  claims 1  to  14 . 
     
     
         16 . An isolated antibody that competes for EGFL7 binding with the antibody of any one of  claims 1  to  14 . 
     
     
         17 . The antibody of any one of  claims 1  to  16 , wherein the antibody is a monoclonal antibody. 
     
     
         18 . The antibody of any one of  claims 1  to  17 , wherein the antibody is selected from the group consisting of a chimeric antibody, a humanized antibody, an affinity matured antibody, a human antibody, and a bispecific antibody. 
     
     
         19 . The antibody of any one of  claims 1  to  18 , wherein the antibody is an antibody fragment. 
     
     
         20 . A pharmaceutical composition comprising an anti-EGFL7 antibody of any of  claims 1  to  19 . 
     
     
         21 . The pharmaceutical composition of  claim 20 , further comprising and anti-angiogenic agent. 
     
     
         22 . The pharmaceutical composition of  claim 21 , wherein the anti-angiogenic agent is selected from the group consisting of bevacizumab and ranibizumab. 
     
     
         23 . A polynucleotide encoding an antibody of any of  claims 1  to  19 . 
     
     
         24 . A vector comprising the polynucleotide of  claim 23 . 
     
     
         25 . The vector of  claim 24 , wherein the vector is an expression vector. 
     
     
         26 . A host cell comprising a vector of  claim 24  or  25 . 
     
     
         27 . The host cell of  claim 26 , wherein the host cell is prokaryotic. 
     
     
         28 . The host cell of  claim 26 , wherein the host cell is eukaryotic. 
     
     
         29 . The host cell of  claim 26 , wherein the host cell is mammalian. 
     
     
         30 . A method for making an anti-EGFL7 antibody, said method comprising (a) expressing a vector of  claim 25  in a suitable host cell, and (b) recovering the antibody. 
     
     
         31 . The method of  claim 30 , wherein the host cell is prokaryotic. 
     
     
         32 . The method of  claim 30 , wherein the host cell is eukaryotic. 
     
     
         33 . A method for reducing or inhibiting angiogenesis in a subject having a pathological condition associated with angiogenesis, comprising administering to the subject an effective amount of the anti-EGFL7 antibody of any one of  claims 1  to  19  or the pharmaceutical composition of  claim 20 . 
     
     
         34 . The method of  claim 33 , wherein the pathological condition is a neoplasm. 
     
     
         35 . The method of  claim 34 , wherein the neoplasm is a carcinoma. 
     
     
         36 . The method of  claim 33 , wherein the pathological condition is associated with the eye. 
     
     
         37 . The method of  claim 36 , wherein the pathological condition is an intraocular neovascular disease. 
     
     
         38 . The method of any one of  claims 33  to  35 , further comprising administering to the subject an anti-angiogenic agent. 
     
     
         39 . The method of  claim 38 , wherein the anti-angiogenic agent is an antagonist of vascular endothelial growth factor (VEGF). 
     
     
         40 . The method of  claim 39 , wherein the antagonist is an anti-VEGF antibody. 
     
     
         41 . The method of  claim 40 , wherein the anti-VEGF antibody is bevacizumab. 
     
     
         42 . The method of  claim 36  or  37 , further comprising administering to the subject an anti-angiogenic agent. 
     
     
         43 . The method of  claim 42 , wherein the anti-angiogenic agent is an antagonist of vascular endothelial growth factor (VEGF). 
     
     
         44 . The method of  claim 43 , wherein the antagonist is an anti-VEGF antibody. 
     
     
         45 . The method of  claim 44 , wherein the anti-VEGF antibody is ranibizumab. 
     
     
         46 . The method of any one of  claims 38  to  45 , wherein the anti-angiogenic agent is administered prior to or subsequent to the administration of the anti-EGFL7 antibody. 
     
     
         47 . The method of any one of  claims 38  to  45 , wherein the anti-angiogenic agent is administered concurrently with the anti-EGFL7 antibody. 
     
     
         48 . A method of enhancing the efficacy of an anti-angiogenic agent in a subject having a pathological condition associated with angiogenesis, comprising administering to the subject the antibody of any one of  claims 1  to  19  or the pharmaceutical composition of  claim 20  or  21 . 
     
     
         49 . The method of  claim 38 , wherein the pathological condition is a neoplasm. 
     
     
         50 . The method of  claim 39 , wherein the neoplasm is a carcinoma. 
     
     
         51 . The method of any one of  claims 48  to  50 , wherein the anti-antigenic agent is bevacizumab. 
     
     
         52 . The method of any one of  claims 48  to  51 , further comprising administering a chemotherapeutic agent. 
     
     
         53 . The method of  claim 48 , wherein the pathological condition is associated with the eye. 
     
     
         54 . The method of  claim 53 , wherein the pathological condition is an intraocular neovascular disease. 
     
     
         55 . The method of  claim 53  or  54 , wherein the anti-angiogenic agent is ranibizumab. 
     
     
         56 . The method of any one of  claims 53  to  55 , further comprising administering a corticosteroid. 
     
     
         57 . The method of any one of  claims 53  to  55 , further comprising administering photodynamic therapy.

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