Molecular design of recombinant protein drug

Patent metadata

Field	Value
Publication number	US-10869910-B2
Application number	US-201615550751-A
Country	US
Kind code	B2
Filing date	Feb 14, 2016
Priority date	Feb 13, 2015
Publication date	Dec 22, 2020
Grant date	Dec 22, 2020

Abstract

Provided is a mutant of an endostatin. The mutant has improved ATPase activity and improved activity of inhibiting angiogenesis and inhibiting tumors. Further provided is use of the mutant in treatment of angiogenesis related diseases such as tumors.

First claim

The invention claimed is:

1. A method for increasing the anti-angiogenesis activity of an endostatin or variant thereof, comprising genetically engineering the A motif of the endostatin or variant thereof, to obtain an endostatin mutant with increased ATPase activity compared to the endostatin or variant thereof, wherein said endostatin mutant comprises the sequence set forth in SEQ ID NO: 3.

2. The method of claim 1 , further comprising covalently linking said mutant to a PEG molecule.

3. The method of claim 2 , wherein said PEG molecule has a molecular weight of 5-40 kD.

4. The method of claim 2 , wherein said PEG molecule is covalently linked to the α-amino group at the N-terminal of said mutant.

5. The method of claim 2 , wherein said PEG molecule is monomethoxypolyethylene glycol.

6. The method of claim 2 , wherein said PEG molecule is monomethoxypolyethylene glycol propionaldehyde (mPEG-ALD).

7. The method of claim 1 , further comprising administering said mutant to a subject in need thereof for inhibiting endothelial cell migration in the subject.

Assignees

• Univ Tsinghua
• Beijing Protgen Ltd

Inventors

• Luo Yongzhang
• Liu Peng
• Lu Xinan

Classifications

• A61K38/00

  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

• C07K14/78 Primary

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · CPC title

• A61K47/50

  the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates · CPC title

• C07K14/435

  from animals; from humans · CPC title

• A61K38/17

  from animals; from humans {(enzyme inhibitors A61K38/005)} · CPC title