NOPE for treatment of pathological muscle loss and weakness

Patent metadata

Field	Value
Publication number	US-10799559-B2
Application number	US-201716095974-A
Country	US
Kind code	B2
Filing date	Apr 24, 2017
Priority date	Apr 25, 2016
Publication date	Oct 13, 2020
Grant date	Oct 13, 2020

Abstract

Methods of treating muscle wasting and other disorders with NOPE extracellular domain (ECD) polypeptides and NOPE ECD fusion molecules are provided.

First claim

The invention claimed is:

1. A NOPE ECD fusion molecule comprising the sequence of SEQ ID NO: 17.

2. A polynucleotide encoding the NOPE ECD fusion molecule of claim 1 .

3. A vector comprising the polynucleotide of claim 2 .

4. A host cell comprising the vector of claim 3 .

5. A method for treating a muscle degenerative disorder, wherein the muscle degenerative disorder is selected from muscular dystrophy, myotonic dystrophy, polymyositis, and dermatomyositis in a subject in need of such treatment, the method comprising administering to the subject an effective amount of a NOPE extracellular domain (ECD) polypeptide or a NOPE ECD fusion molecule, wherein the NOPE ECD or NOPE ECD fusion molecule comprises amino acids 26 to 620 of SEQ ID NO: 1.

6. The method of claim 5 , wherein the muscle degenerative disorder is muscular dystrophy.

7. The method of claim 6 , wherein the muscular dystrophy is selected from Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophy, Fukuyama muscular dystrophy, Emery Dreifuss muscular dystrophy, limb girdle muscular dystrophy, and fascioscapulohumeral muscular dystrophy.

8. The method of claim 5 , wherein the muscle degenerative disorder is myotonic dystrophy.

9. The method of claim 8 , wherein the myotonic dystrophy is selected from myotonic dystrophy type I, myotonic dystrophy type II, and congenital myotonia.

10. The method of claim 5 , wherein the method comprises administering to the subject an effective amount of the NOPE ECD fusion molecule.

11. The method of claim 5 , wherein the NOPE ECD polypeptide or NOPE ECD fusion molecule is capable of binding myostatin with a K D of less than 100 nM and/or inhibiting myostatin-mediated activation of SMAD2/3.

12. The method of claim 10 , wherein the NOPE ECD fusion molecule comprises a NOPE ECD polypeptide and an Fc.

13. The method of claim 12 , wherein the NOPE ECD fusion molecule comprises the sequence of SEQ ID NO: 17.

14. A method of treating amyotrophic lateral sclerosis (ALS), comprising administering to a subject with ALS an effective amount of a NOPE extracellular domain (ECD) polypeptide or a NOPE ECD fusion molecule, wherein the NOPE ECD or NOPE ECD fusion molecule comprises amino acids 26 to 620 of SEQ ID NO: 1.

15. The method of claim 14 , wherein the treatment delays progression of ALS by having at least one effect selected from the group consisting of: reducing physical decline, improving forced vital capacity, slowing the decline in forced vital capacity, slowing the decline in the subject's score on the ALS functional rating scale (ALSFRS), improving the subject's score on the ALSFRS, delaying occurrence of life-changing events, improving the subject's time of survival, delaying a tracheostomy and delaying placement of a percutaneous endoscopic gastrostomy (PEG).

16. The method of claim 14 , wherein the method comprises administering to the subject an effective amount of the NOPE ECD fusion molecule.

17. The method of claim 14 , wherein the NOPE ECD polypeptide or NOPE ECD fusion molecule is capable of binding myostatin with a KD of less than 100 nM and/or inhibiting myostatin-mediated activation of SMAD2/3.

18. The method of claim 16 , wherein the NOPE ECD fusion molecule comprises a NOPE ECD polypeptide and an Fc.

19. The method of claim 18 , wherein the NOPE ECD fusion molecule comprises the sequence of SEQ ID NO: 17.

20. A method for increasing type I slow muscle mass or decreasing fat mass, the method comprising administering to a subject an effective amount of a NOPE extracellular domain (ECD) fusion molecule comprising the sequence of SEQ ID NO: 17.

Assignees

• Five Prime Therapeutics Inc
• Glaxosmithkline Ip Dev Ltd

Inventors

• Hinken Aaron Curtis
• Hsu Amy W
• Powers Janine
• Rocque Warren James
• Russell Alan James

Classifications

• C07K14/70503

  Immunoglobulin superfamily · CPC title

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61K38/1774 Primary

  Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules) · CPC title