Targets for regulation of angiogenesis
The present invention relates to the identification of polynucleotides and polypeptides having increased expression in tumor blood vessels. The invention further relates to the use of the identified polynucleotides and polypeptides, and inhibitors of the polynucleotides and polypeptides, in the regulation of angiogenesis and the diagnosis and treatment of angiogenesis-related diseases such as cancer.
1. An isolated monoclonal antibody or an antigen binding fragment thereof which: (a) specifically binds an epitope comprised of amino acids selected from the group consisting of amino acids EITYINRDTKIILETKSKT-Cys (SEQ ID NO:6) and ITSVKRWQKGQREFKRISRSIRKLQC (SEQ ID NO:7); and (b) inhibits one or more of angiogenesis and tumor growth.
2. The monoclonal antibody or an antigen binding fragment thereof of claim 1 , which is a chimeric antibody.
3. The monoclonal antibody or an antigen binding fragment thereof of claim 1 , which is a humanized antibody.
4. The monoclonal antibody or an antigen binding fragment thereof of claim 1 , comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:13.
5. The monoclonal antibody or an antigen binding fragment thereof of claim 1 , comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO:15.
6. The monoclonal antibody or an antigen binding fragment thereof of claim 1 , comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:13 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:15.
7. The monoclonal antibody or an antigen binding fragment thereof of claim 1 , which specifically recognizes an epitope which is amino acids EITYINRDTKIILETKSKT-Cys (SEQ ID NO:6).
8. An isolated monoclonal antibody produced by hybridoma cell line UNC 68-80 (ATCC Deposit No. PTA-11762) or an antigen binding fragment thereof.
9. An isolated monoclonal antibody or an antigen binding fragment thereof which comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:13 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:15.