Peptides and compositions for treatment of joint damage

Patent metadata

Field	Value
Publication number	US-10328126-B2
Application number	US-201715457656-A
Country	US
Kind code	B2
Filing date	Mar 13, 2017
Priority date	Mar 8, 2013
Publication date	Jun 25, 2019
Grant date	Jun 25, 2019

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 inducing differentiation of mesenchymal stem cells into chondrocytes, the method comprising contacting mesenchymal stem cells in the joint of a subject suffering from arthritis or cartilage damage with an 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 any one of SEQ ID NOs: 58-70, wherein the amino acid at position 423, as determined with reference to SEQ ID NO: 1, is deleted, to induce differentiation of the mesenchymal stem cells into chondrocytes, wherein said contacting is achieved by intra-articular delivery of the polypeptide to said subject.

2. The method of claim 1 , wherein the subject is a human subject.

3. The method of claim 2 , wherein the arthritis is osteoarthritis, traumatic arthritis, or autoimmune arthritis.

4. The method of claim 2 , wherein the polypeptide comprises an amino acid sequence selected from any one of SEQ ID NOs: 58-70.

5. The method of claim 2 , wherein the polypeptide consists of an amino acid sequence selected from any one of SEQ ID NOs: 58-70.

6. The method of claim 2 , wherein the polypeptide is PEGylated.

7. The method of claim 2 , wherein the polypeptide is fused to a heterologous peptide selected from any of human serum albumin (HSA), immunoglobulin heavy chain constant region (Fc), polyhistidine, glutathione S transferase (GST), thioredoxin, protein A, protein G, or maltose binding protein (MBP), or a fragment thereof, wherein the heterologous peptide is fused at either the amino-terminal end or the carboxy-terminal end of the polypeptide.

8. The method of claim 2 , further comprising administering one or more additional chondrogenic factors to the subject.

9. The method of claim 2 , further comprising performing a surgical procedure on an affected joint of the subject.

10. A method of treating or ameliorating arthritis or cartilage damage in a joint of a subject in need thereof comprising administering to the subject at a site in need of treatment or by intra-articular delivery 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 any one of SEQ ID NOs: 58-70, wherein the amino acid at position 423, as determined with reference to SEQ ID NO: 1, is deleted.

11. The method of claim 10 , wherein the subject is a human.

12. The method of claim 10 , wherein the arthritis is osteoarthritis, trauma traumatic arthritis, or autoimmune arthritis.

13. The method of claim 10 , wherein the polypeptide comprises an amino acid sequence selected from any one of SEQ ID NOs: 58-70.

14. The method of claim 10 , wherein the polypeptide consists of an amino acid sequence selected from any one of SEQ ID NOs: 58-70.

15. The method of claim 10 , wherein the polypeptide is PEGylated.

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

17. The method of claim 10 , wherein the polypeptide is administered in a matrix or biocompatible scaffold.

18. The method of claim 10 , further comprising administering one or more additional chondrogenic factors to the subject.

19. The method of claim 10 , further comprising performing a surgical procedure on an affected joint of the subject.

20. The method of claim 10 , further comprising performing one or more of the following procedure to the subject: bone marrow stimulation, cartilage replacement, autologous chondrocyte implantation (ACI), matrix-induced autologous chondrocyte implantation (MACI).

Assignees

• Novartis Ag

Inventors

• Johnson Kristen
• Shi Jian

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P19/02

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