Peptide antagonists of vascular endothelial growth factor and methods of use thereof
The present invention provides isolated polypeptides having VEGF antagonist activity, pharmaceutical compositions and methods of treatment of subjects having a disease or disorder associated with VEGF activity or subjects having tumors expressing a VEGF receptor. The polypeptides of the invention include polypeptides comprising a portion of SEQ ID NO: 1 having VEGF antagonist activity, polypeptides comprising SEQ ID NO: 2 or a portion thereof having VEGF antagonist activity, and a polypeptide having the structure of formula (I), set forth above. The present invention further includes analogs and derivatives of these polypeptides having VEGF antagonist activity.
1. A method of treating a subject having a disease or disorder associated with VEGF-induced neovascularization or angiogenesis, which comprises administering to the subject a pharmaceutical composition comprising an isolated polypeptide:
(i) comprising a portion of SEQ ID NO:1 having VEGF antagonist activity;
(ii) comprising SEQ ID NO:2 or a portion thereof having VEGF antagonist activity; or
(iii) comprising a peptide having the structure of the following formula (I):
(X 1 -(CSCKNTDSRCKARQLELNERT(SEQ ID NO:3))X 2 I
wherein X 1 is H, or any portion of amino acids 2-21 of SEQ ID NO:1, and X 2 is H or C, CR, RC, or CRC;
and a pharmaceutically acceptable carrier.
2. The method of claim 1 , wherein said disease or disorder associated with VEGF-induced neovascularization or angiogenesis is selected from the group consisting of metastasis, inappropriate angiogenesis, and chronic inflammation.
3. The method of claim 1 , wherein the disease or disorder is a solid tumor.
4. A method for treating a subject having a tumor expressing a VEGF165R/NP-1 receptor comprising administering to the subject a pharmaceutical composition comprising an isolated polypeptide:
(i) comprising a portion of SEQ ID NO:1 having VEGF antagonist activity;
(ii) comprising SEQ ID NO:2 or a portion thereof having VEGF antagonist activity; or
(iii) comprising a peptide having the structure of the following formula (I):
(X 1 -(CSCKNTDSRCKARQLELNERT(SEQ ID NO:3))X 2 I
wherein X 1 is H, or any portion of amino acids 2-21 of SEQ ID NO:1, and X 2 is H or C, CR, RC, or CRC;
and a pharmaceutically acceptable carrier.