Protoxin-II variants and methods of use

Patent metadata

Field	Value
Publication number	US-10975129-B2
Application number	US-201715489714-A
Country	US
Kind code	B2
Filing date	Apr 17, 2017
Priority date	Oct 3, 2013
Publication date	Apr 13, 2021
Grant date	Apr 13, 2021

Abstract

The present invention relates to Protoxin-II variants, polynucleotides encoding them, and methods of making and using the foregoing.

First claim

We claim:

1. An isolated Protoxin-II variant comprising the sequence of SEQ ID NO: 56 or SEQ ID NO: 78.

2. The Protoxin-II variant of claim 1 , further comprising an N-terminal and/or C-terminal extension that is conjugated to the Protoxin-II variant via a linker.

3. The Protoxin-II variant of claim 2 , wherein the linker comprises the amino acid sequence of SEQ ID NOs: 383, 392, 398, 399, 400, 401 or 402.

4. The isolated Protoxin-II variant of claim 3 , having a free C-terminal carboxylic acid, amide, methylamide or butylamide group.

5. A pharmaceutical composition comprising the isolated Protoxin-II variant of claim 4 and a pharmaceutically acceptable excipient.

6. An isolated polynucleotide encoding the Protoxin-II variant of claim 3 .

7. A vector comprising the isolated polynucleotide of claim 6 .

8. A host cell comprising the vector of claim 7 .

9. A method of producing an isolated Protoxin-II variant, comprising culturing the host cell of claim 8 and recovering the Protoxin-II variant produced by the host cell.

10. A pharmaceutical composition comprising the isolated Protoxin-II variant of claim 3 and a pharmaceutically acceptable excipient.

11. The isolated Protoxin-II variant of claim 2 , having a free C-terminal carboxylic acid, amide, methylamide or butylamide group.

12. A pharmaceutical composition comprising the isolated Protoxin-II variant of claim 11 and a pharmaceutically acceptable excipient.

13. A pharmaceutical composition comprising the isolated Protoxin-II variant of claim 2 and a pharmaceutically acceptable excipient.

14. The isolated Protoxin-II variant of claim 1 , having a free C-terminal carboxylic acid, amide, methylamide or butylamide group.

15. A pharmaceutical composition comprising the isolated Protoxin-II variant of claim 14 and a pharmaceutically acceptable excipient.

16. An isolated fusion protein comprising the Protoxin-II variant of claim 1 that is conjugated to a half-life extending moiety.

17. The isolated fusion protein of claim 16 , wherein the half-life extending moiety is human serum albumin (HSA), albumin binding domain (ABD), Fc or polyethylene glycol (PEG).

18. A pharmaceutical composition comprising the isolated fusion protein of claim 17 and a pharmaceutically acceptable excipient.

19. A pharmaceutical composition comprising the isolated fusion protein of claim 16 and a pharmaceutically acceptable excipient.

20. A method of reducing the perception of pain in a subject, comprising administering to a subject in need thereof an effective amount of the fusion protein of claim 16 to treat the pain.

21. The method of claim 20 , wherein the pain is chronic pain, acute pain, neuropathic pain, nociceptive pain, visceral pain, back pain, post-operative pain, thermal pain, phantom limb pain, or pain associated with inflammatory conditions, primary erythemalgia (PE), paroxysmal extreme pain disorder (PEPD), osteoarthritis, rheumatoid arthritis, lumbar discectomy, pancreatitis, fibromyalgia, painful diabetic neuropathy (PDN), post-herpetic neuropathy (PHN), trigeminal neuralgia (TN), spinal cord injuries or multiple sclerosis.

22. The method of claim 20 , wherein the fusion protein is administered peripherally.

23. The method of claim 20 , wherein the fusion protein is administered locally to a joint, spinal cord, surgical wound, sites of injury or trauma, peripheral nerve fibers, urogenital organs, or inflamed tissues.

24. The method of claim 20 , wherein the subject is a human.

25. An isolated polynucleotide encoding the Protoxin-II variant of claim 1 .

26. A vector comprising the isolated polynucleotide of claim 25 .

27. A host cell comprising the vector of claim 26 .

28. A method of producing an isolated Protoxin-II variant, comprising culturing the host cell of claim 27 and recovering the Protoxin-II variant produced by the host cell.

29. A pharmaceutical composition comprising the isolated Protoxin-II variant of claim 1 and a pharmaceutically acceptable excipient.

30. A method of reducing the perception of pain in a subject, comprising administering to a subject in need thereof an effective amount of the Protoxin-II variant of claim 1 to treat the pain.

31. The method of claim 30 , wherein the pain is chronic pain, acute pain, neuropathic pain, nociceptive pain, visceral pain, back pain, post-operative pain, thermal pain, phantom limb pain, or pain associated with inflammatory conditions, primary erythemalgia (PE), paroxysmal extreme pain disorder (PEPD), osteoarthritis, rheumatoid arthritis, lumbar discectomy, pancreatitis, fibromyalgia, painful diabetic neuropathy (PDN), post-herpetic neuropathy (PHN), trigeminal neuralgia (TN), spinal cord injuries or multiple sclerosis.

32. The method of claim 30 , wherein the Protoxin-II variant is administered peripherally.

33. The method of claim 30 , wherein the Protoxin-II variant is administered locally to a joint, spinal cord, surgical wound, sites of injury or trauma, peripheral nerve fibers, urogenital organs, or inflamed tissues.

Assignees

• Janssen Biotech Inc

Inventors

• Flinspach Mack
• Wickenden Alan
• Fellows Ross
• Neff Robert
• Liu Yi
• Hagan Rebecca
• Xu Qinghao

Classifications

• C07K14/43518 Primary

  from spiders · CPC title

• C07K14/765

  Serum albumin, e.g. HSA · CPC title

• C07K2319/31

  fusions, other than Fc, for prolonged plasma life, e.g. albumin · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• 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