TIMP3 as VEGF inhibitor

Patent metadata

Field	Value
Publication number	US-9498509-B2
Application number	US-65364707-A
Country	US
Kind code	B2
Filing date	Jan 16, 2007
Priority date	Mar 21, 2003
Publication date	Nov 22, 2016
Grant date	Nov 22, 2016

Abstract

Polypeptides or proteins comprising tissue inhibitor of mettaloproteinases-3 (TIMP3) or variants of TIMP3 can be used to substantially inhibit vascular endothelial growth factor (VEGF) binding to VEGF receptor-2 (VEGFR2/KDR/Flk-1)) without substantially inhibiting VEGF binding to VEGF receptor 1 (VEGFR1/Flt-1).

First claim

Having described the invention, I claim the following:

1. A method of inhibiting VEGF induced endothelial cell proliferation and/or migration in a population of VEGFR2 expressing endothelial cells in the presence of VEGF, the method comprising:
administering to the VEGFR2 expressing endothelial cells a polypeptide comprising a fragment of TIMP3 that includes SEQ ID NO: 9, wherein the polypeptide is effective to inhibit endothelial cell proliferation and/or migration in the population of VEGFR2 expressing endothelial cells and wherein the polypeptide is free of metalloproteinase inhibiting activity.

2. The method of claim 1 , wherein administering the polypeptide comprises affecting at least one cell of the population of VEGF2 expressing endothelial cells to express the polypeptide.

3. The method of claim 2 , the at least one cell of the population of VEGF2 expressing endothelial cells being affected to express the polypeptide by administering to the at least one cell a nucleotide sequence encoding the polypeptide.

4. The method of claim 2 , the at least one cell of the population of VEGF2 expressing endothelial cells being affected to express the polypeptide by transfecting the at least one cell with a vector, the vector including a nucleotide sequence encoding the polypeptide.

5. The method of claim 1 , wherein administering the polypeptide to the population of VEGF2 expressing endothelial cells comprises delivering a composition that includes the polypeptide to the population of VEGF2 expressing endothelial cells.

6. The method of claim 1 , the polypeptide being free of SEQ ID NO: 3.

7. The method of claim 1 , the fragment of TIMP3 that includes SEQ ID NO: 9 being linked to a therapeutic agent.

8. The method of claim 7 , the therapeutic agent comprising at least one of a chemotherapeutic agent, a radiotherapeutic agent, cytotoxic agent, anti-angiogenic agent, coagulent, or anti-tubulin drug.

Assignees

• Anand-Apte Bela
• Cleveland Clinic Found

Inventors

• Anand-Apte Bela

Classifications

• A61K38/00 Primary

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K14/8146 Primary

  Metalloprotease (E.C. 3.4.24) inhibitors, e.g. tissue inhibitor of metallo proteinase, TIMP · CPC title

• A61K47/66

  the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title