Compositions and methods for increasing vascularization

• US 9,138,461 B2
• Filed: 11/16/2012
• Issued: 09/22/2015
• Est. Priority Date: 05/01/2007
• Status: Active Grant

• Current Assignee: Inserm (institut national de la sant et de la recherche mdicale, Sinfonia Biotherapeutics AB
• Original Assignee: Institut National De La Sante Et De La Recherche Medicale (Inserm) (Allianz Global Investors GmbH), Biogen MA Inc. (Biogen, Inc.)
• Inventors: Rossomando, Anthony, Silvestre, Jean-Sebastien, Tamarat, Radia
• Primary Examiner(s): HOWARD, ZACHARY C
• Application Number:
  US13/679,529
• Publication Number:
  US 20130237477A1
• Time in Patent Office: 1,040 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 14/475 Growth factors; Growth regulators

Abstract

Disclosed are methods of increasing vascularization in a tissue by administering a neublastin polypeptide to a mammal exhibiting impaired or inadequate blood flow in the tissue. The methods can be used to in the treatment or prevention of a disorder characterized by impaired or inadequate blood flow or to increase vascularization in an organ that has been transplanted into a subject.

Claims

1. A method of increasing vascularization in a tissue, the method comprising:

selecting a human exhibiting impaired or inadequate blood flow in a tissue; and

administering to the human an amount of a polypeptide effective to increase vascularization in the tissue, wherein the polypeptide comprises an amino acid sequence that is at least 80% identical to amino acids 15-113 of SEQ ID NO;

1, wherein the polypeptide, when dimerized, binds to a complex containing GFRalpha3 and RET, and wherein the human has received a transplanted organ and administration of the polypeptide increases vascularization in the transplanted organ.

2. The method of claim 1, wherein the transplanted organ is a heart.

3. The method of claim 1, wherein the transplanted organ is dermis.

4. The method of claim 1, further comprising determining whether increased vascularization has occurred subsequent to administration of the polypeptide.

5. The method of claim 1, wherein the polypeptide is administered to the human via systemic administration.

6. The method of claim 1, wherein the polypeptide is administered to the human via subcutaneous administration.

7. The method of claim 1, wherein herein the polypeptide is administered to the human via local administration.

8. The method of claim 1, wherein the amino acid sequence is at least 90% identical to amino acids 15-113 of SEQ ID NO:

1.

9. The method of claim 1, wherein the amino acid sequence is at least 95% identical to amino acids 15-113 of SEQ ID NO:

1.

10. The method of claim 1, wherein the amino acid sequence is at least 98% identical to amino acids 15-113 of SEQ ID NO:

1.

11. The method of claim 1, wherein the polypeptide comprises amino acids 15-113 of SEQ ID NO:

1, amino acids 15-113 of SEQ ID NO;

2, amino acids 15-113 of SEQ ID NO;

3, amino acids 15-113 of SEQ ID NO;

4, amino acids 15-113 of SEQ ID NO;

5, amino acids 15-113 of SEQ ID NO;

8, or amino acids 15-113 of SEQ ID NO;

9.

12. The method of claim 1, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:

1, the amino acid sequence of SEQ ID NO;

2, the amino acid sequence of SEQ ID NO;

3, the amino acid sequence of SEQ ID NO;

4, the amino acid sequence of SEQ ID NO;

5, the amino acid sequence of SEQ ID NO;

8, or the amino acid sequence of SEQ ID NO;

9.

13. The method of claim 1, wherein the polypeptide comprises amino acids 10-113 of SEQ ID NO:

1.

14. The method of claim 1, wherein the human has not been diagnosed with a neurological disorder.

15. The method of claim 1, wherein the human has not been diagnosed with an ocular disorder.