Method of treating cancer comprising a vegf-b antagonist

Abstract

The present invention relates generally to the field of cancer therapy and prophylaxis. More particularly, the present invention provides growth factor antagonists which inhibit the growth of cancers including tumors and pre-cancerous tissue. Even more particularly, the present invention is directed to antagonists of vascular endothelial growth factor-B and their use to inhibit the growth of cancer including tumor tissue and pre-cancerous tissue.

1 . A method of treating cancer in a mammal the method comprising administering to a subject in need thereof an effective amount of a VEGF-B antagonist. 
     
     
         2 . The method of  claim 1  wherein the cancer is a tumor, a pre-cancerous condition, a myeloma or a lymphoma. 
     
     
         3 - 6 . (canceled) 
     
     
         7 . The method according to  claim 1  wherein the VEGF-B antagonist is an anti-VEGF-B antibody that inhibits binding of VEGF-B to VEGFR-I. 
     
     
         8 - 14 . (canceled) 
     
     
         15 . An isolated anti-VEGF-B antibody that inhibits binding of VEGF-B to VEGFR-I wherein the antibody binds human VEGF-B with a K D  value of 1×10 −7 M or less. 
     
     
         16 . (canceled) 
     
     
         17 . The antibody of  claim 16  wherein the antibody is human or humanized. 
     
     
         18 - 21 . (canceled) 
     
     
         22 . The antibody of  claim 15  wherein the antibody comprises four, five or all six CDR sequences from the heavy and light chain variable regions of mAb 2H10. 
     
     
         23 . The antibody of  claim 15  wherein the antibody comprises four, five or all six CDR sequences from the heavy and light chain variable regions of mAb 2F5. 
     
     
         24 . The antibody of  claim 15  wherein the antibody comprises four, five or all six CDR sequences from the heavy and light chain variable regions of mAb 1C6. 
     
     
         25 . A composition comprising an antibody of  claim 15 . 
     
     
         26 . A method of treating cancer in a mammal the method comprising administering to a subject in need thereof an effective amount of an antibody of  claim 22 . 
     
     
         27 . An isolated anti-VEGF-B antibody according to  claim 17  comprising a light chain with CDRs having the sequences shown in SEQ ID NOs: 5 to 7, or having at least about 80% identity to the sequences shown in SEQ ID NOs:5 to 7. 
     
     
         28 . An isolated anti-VEGF-B antibody according to  claim 17  comprising a heavy chain with CDRs having the sequences shown in SEQ ID NOs: 8 to 10, or having at least about 80% identity to the sequences shown in SEQ ID NOs:8 to 10. 
     
     
         29 . An isolated anti-VEGF-B antibody according to  claim 17  comprising CDRs having the sequences shown in SEQ ID NOs:5 to 10, or having at least about 80% identity to the sequences shown in SEQ ID NOs: 5 to 10. 
     
     
         30 . An isolated anti-VEGF-B antibody according to  claim 27  comprising a variable light chain sequence and a variable heavy chain having the sequences shown in SEQ ID NOs:29 and 30, or having at least about 80% identity to the sequences shown in SEQ ID NOs:29 and 30. 
     
     
         31 . An isolated anti-VEGF-B antibody which competes with the antibody produced by the hybridoma cell line, Accession No. ______, deposited at ATCC on 27 Jul. 2005. 
     
     
         32 . An isolated anti-VEGF-B antibody according to  claim 31  which binds to the same or substantially the same epitope as the antibody produced by the hybridoma cell line, Accession No. ______, deposited at ATCC on 27 Jul. 2005. 
     
     
         33 . A method of treating cancer in a mammal the method comprising administering to a subject in need thereof an effective amount of an antibody according to  claim 27 . 
     
     
         34 . A composition comprising an antibody according to  claim 27 . 
     
     
         35 . A nucleic acid encoding the light chain of an anti-VEGF-B antibody according to  claim 30  comprising the nucleotide sequences of SEQ ID NOs:31, 33 and 35, or having at least about 80% identity to the sequences shown in SEQ ID NOs:31, 33 and 35. 
     
     
         36 . A nucleic acid encoding the heavy chain of an anti-VEGF-B antibody according to  claim 30  comprising the nucleotide sequences of SEQ ID NOs:37, 39 and 41, or having at least about 80% identity to the sequences shown in SEQ ID NOs:37, 39 and 41. 
     
     
         37 . An expression vector comprising a nucleic acid encoding the light chain of an anti-VEGF-B antibody according to  claim 30  comprising the nucleotide sequences of SEQ ID NOs:31, 33 and 35, or having at least about 80% identity to the sequences shown in SEQ ID NOs:31, 33 and 35 and a nucleic acid encoding the heavy chain of an anti-VEGF-B antibody according to  claim 30  comprising the nucleotide sequences of SEQ ID NOs:37, 39 and 41, or having at least about 80% identity to the sequences shown in SEQ ID NOs:37, 39 and 41, wherein said expression vector is capable of expressing said nucleic acids in prokaryotic or eukaryotic host cell. 
     
     
         38 . A prokaryotic or eukaryotic host cell comprising an expression vector of  claim 37 . 
     
     
         39 . A method for producing an anti-VEGF-B antibody according to  claim 30  said method comprising (a) culturing a prokaryotic or eukaryotic host cell comprising an expression vector comprising a nucleic acid and a nucleic acid encoding the light chain of an anti-VEGF-B antibody according to  claim 30  comprising the nucleotide sequences of SEQ ID NOs:31, 33 and 35, or having at least about 80% identity to the sequences shown in SEQ ID NOs:31, 33 and 35, wherein said expression vector is capable of expressing said nucleic acids in prokaryotic or eukaryotic host cell for a period of time sufficient to allow for expression of the antibody and (b) purifying the expressed antibody.