Endostatin mutants with mutations at ATP binding sites

Patent metadata

Field	Value
Publication number	US-10647968-B2
Application number	US-201214343694-A
Country	US
Kind code	B2
Filing date	Sep 10, 2012
Priority date	Sep 9, 2011
Publication date	May 12, 2020
Grant date	May 12, 2020

Abstract

The present invention discloses a new anti-tumor medicament comprising a mutant of endostatin. The mutant comprises a mutation in the ATP-binding site of endostatin and has a decreased ATPase activity and an increased anti-angiogenesis activity.

First claim

The invention claimed is:

1. A method of tumor therapy comprising administering to a subject having a tumor a mutant of human endostatin having the amino acid sequence set forth in SEQ ID NO:1 or of a human endostatin variant having the amino acid sequence set forth in SEQ ID No:2, 3 or 4, wherein said mutant has increased anti-angiogenesis activity as compared with the corresponding wild type endostatin or a variant thereof, wherein said mutant has decreased ATPase activity as compared with the corresponding wild type endostatin or a variant thereof, and wherein said mutant is selected from the group consisting of
a) a mutant having the amino acid sequence set forth in SEQ ID NO:6,
b) a mutant having the amino acid sequence set forth in SEQ ID NO:10,
c) a mutant having the amino acid sequence set forth in SEQ ID NO:27, and
d) a mutant having the amino acid sequence set forth in SEQ ID NO:30.

2. The method of claim 1 , wherein said mutant is further covalently linked to a PEG molecule.

3. The method of claim 2 , wherein the molecular weight of said PEG is 5-40 kD.

4. The method of claim 3 , wherein said PEG is covalently linked to the α amino group at N-terminal of said mutant.

5. The method of claim 4 , wherein said PEG is Monomethoxy Poly(ethylene glycol).

6. The method of claim 5 , wherein said Monomethoxy Poly(ethylene glycol) is Monomethoxy Poly(ethylene glycol)-Aldehyde (mPEG-ALD).

Assignees

• Luo Yongzhang
• Liu Peng
• Lu Xinan
• Chen Yang
• Fu Yan
• Chang Guodong
• Zhou Daifu
• Univ Tsinghua
• Beijing Protgen Ltd

Inventors

• Luo Yongzhang
• Liu Peng
• Lu Xinan
• Chen Yang
• Fu Yan
• Chang Guodong
• Zhou Daifu

Classifications

• C07K14/475

  Growth factors; Growth regulators · CPC title

• C12N9/14 Primary

  Hydrolases (3) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• C12Q1/00

  Measuring or testing processes involving enzymes, nucleic acids or microorganisms (measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34); Compositions therefor; Processes of preparing such compositions · CPC title