ALK7 antagonists and uses thereof

Patent metadata

Field	Value
Publication number	US-12024563-B2
Application number	US-202117505124-A
Country	US
Kind code	B2
Filing date	Oct 19, 2021
Priority date	Apr 6, 2016
Publication date	Jul 2, 2024
Grant date	Jul 2, 2024

Abstract

In certain aspects, the disclosure provides ALK7 antagonists. In certain aspects, these ALK7 antagonists are can be used to improve metabolic parameters in a patient in need thereof. In certain aspects, these ALK7 antagonists can be used to treat or prevent one or more kidney-associated disease or condition in a patient in need thereof. In certain aspects, these ALK7 antagonists can be used to treat or prevent cancer.

First claim

We claim:

1. A method for reducing kidney inflammation or kidney fibrosis, or reducing kidney damage resulting therefrom, comprising administering to a patient in need thereof an effective amount of an ALK7 antagonist, wherein the ALK7 antagonist is a heteromeric complex that binds to one or more of activin B, activin C and/or activin AC comprising an ALK7 polypeptide and an ActRIIB polypeptide in which the ALK7 polypeptide comprises an amino acid sequence with at least 90% identity to the amino acid sequence set forth in SEQ ID NO: 74, 76, 79, or 80 and the ActRIIB polypeptide comprises an amino acid sequence with at least 90% identity to the amino acid sequence set forth in SEQ ID NO: 71, 73, 77, or 78.

2. The method of claim 1 , wherein the method reduces kidney inflammation.

3. The method of claim 1 , wherein the method reduces kidney tissue damage resulting from kidney inflammation or kidney fibrosis.

4. The method of claim 1 , wherein the method reduces kidney fibrosis.

5. The method of claim 1 , wherein the ALK7 polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 76 or 80 and the ACRIIB polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 73 or 78.

6. The method of claim 1 , wherein the ALK7 polypeptide further comprises a C-terminal lysine.

7. The method of claim 1 , wherein the ActRIIB polypeptide further lacks a C-terminal lysine.

8. The method of claim 1 , wherein the ActRIIB polypeptide does not comprise an acidic amino acid at the position corresponding to L79 of SEQ ID NO: 1.

9. The method of claim 1 , wherein the ALK7 polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 73 and the ActRIIB polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 76.

10. The method of claim 1 , wherein the ALK7 polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 78 and the ActRIIB polypeptide-comprises the amino acid sequence set forth in SEQ ID NO: 80.

11. The method of claim 1 , wherein the ALK7 polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 74 and the ActRIIB polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 71.

12. The method of claim 1 , wherein the ALK7 polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 79 and the ActRIIB polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 77.

Assignees

• Acceleron Pharma Inc

Inventors

• Knopf John
• Kumar Ravindra
• Grinberg Asya
• Pearsall Robert Scott
• Sako Dianne S
• Castonguay Roselyne
• Li Gang
• Dagon Yossi

Classifications

• A61K38/1796 Primary

  for hormones (for neuromediators A61K38/1787) · CPC title

• C07K2319/74

  containing a fusion for binding to a cell surface receptor · CPC title

• C07K2319/35

  containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin · 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

• C07K2319/10

  containing a tag for extracellular membrane crossing, e.g. TAT or VP22 · CPC title