Peptides and compositions for treatment of joint damage

Patent metadata

Field	Value
Publication number	US-9868771-B2
Application number	US-201615052029-A
Country	US
Kind code	B2
Filing date	Feb 24, 2016
Priority date	Mar 8, 2013
Publication date	Jan 16, 2018
Grant date	Jan 16, 2018

Abstract

The present invention provides new protease resistant polypeptides, as well as compositions and methods for treating, ameliorating or preventing conditions related to joint damage, including acute joint injury and arthritis.

First claim

What is claimed is:

1. A method of treating or ameliorating arthritis or articular cartilage damage in a subject, the method comprising administering to a joint of the subject a therapeutically effective amount of a polypeptide comprising an amino acid sequence that has at least 95% amino acid sequence identity to an amino acid sequence selected from the group of sequences of TABLE 1, wherein the polypeptide comprises an amino acid that is a polar amino acid other than K or R at position 423, as determined with reference to SEQ ID NO:1, and wherein the polypeptide has chondrogenic activity.

2. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that has at least 95% sequence identity to an amino acid sequence selected from any one of SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, or SEQ ID NO:29.

3. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence selected from any one of SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, or SEQ ID NO:29.

4. The method of claim 1 , wherein the polypeptide consists of an amino acid sequence that has at least 95% sequence identity to an amino acid sequence selected from any one of SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, or SEQ ID NO:41, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, or SEQ ID NO:29.

5. The method of claim 1 , wherein the polypeptide consists of an amino acid sequence selected from any one of SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, or SEQ ID NO:41, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, or SEQ ID NO:29.

6. The method of claim 1 , wherein the amino acid at position 423 of the polypeptide is Q or S.

7. The method of claim 1 , wherein the amino acid at position 423 of the polypeptide is Q.

8. The method of claim 1 , wherein the amino acid at position 423 of the polypeptide is S.

9. The method of claim 1 , wherein the polypeptide is PEGylated.

10. The method of claim 1 , wherein the polypeptide is fused to a heterologous peptide selected from any of human serum albumin (HSA), an immunoglobulin heavy chain constant region (Fc), a polyhistidine, a glutathione S transferase (GST), a thioredoxin, a protein A, a protein G, or a maltose binding protein (MBP), or a fragment thereof.

11. The method of claim 1 , wherein the subject has arthritis.

12. The method of claim 1 , wherein the subject has articular cartilage damage.

13. The method of claim 1 , wherein the arthritis is osteoarthritis, trauma arthritis, or autoimmune arthritis.

14. The method of claim 1 , further comprising administering to the subject one or more additional chondrogenic factors.

15. The method of claim 1 , further comprising administering to the subject hyaluronic acid or a derivative thereof.

16. The method of claim 1 , further comprising administering to the subject an agent selected from the group consisting of oral salmon calcitonin, SD-6010 (iNOS inhibitor), vitamin D3 (choliecalciferol), collagen hydrolyzate, FGF18, BMP7, rusalatide acetate, avocado soy unsaponifiables (ASU), kartogenin, a steroid, and a non-steroidal anti-inflammatory agent (NSAID).

17. The method of claim 1 , further comprising performing a surgical procedure to an affected joint in the subject.

18. The method of claim 17 , wherein administering the polypeptide occurs during or after the surgical procedure.

19. The method of claim 1 , wherein administering the polypeptide occurs in conjunction with any one of bone marrow stimulation, cartilage replacement, autologous chondrocyte implantation (ACI), matrix-induced autologous chondrocyte implantation (MACI).

20. The method of claim 1 , wherein the polypeptide is administered in a matrix or biocompatible scaffold.

21. The method of claim 1 , wherein the arthritis is osteoarthritis.

Assignees

• Johnson Kristen
• Shi Jian
• Novartis Ag

Inventors

• Johnson Kristen
• Shi Jian

Classifications

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title

• A61K38/45

  Transferases (2) · CPC title

• A61K31/728

  Hyaluronic acid · CPC title

• A61K38/1891

  Angiogenesic factors; Angiogenin · CPC title

• C12Q1/6883

  for diseases caused by alterations of genetic material · CPC title