Granted Patent
B2
US 12,329,801 · App. 18/662,443 · Granted Jun 17, 2025
Regenerative polypeptides and uses thereof
Inventors:
Hanadie Yousef (Palo Alto, CA); Jeremy O'Connell (Palo Alto, CA); Thach Mai (South San Francisco, CA); Zhihua Li (San Jose, CA)
Assignee:
JUVENA THERAPEUTICS, INC.
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Abstract
Described herein are polypeptides with an IGF2 amino acid sequence and an amino acid sequence from a heterologous polypeptide for treatment of soft-tissue and muscle diseases, disorders, and injuries. Mutations within the IGF2 amino acid sequence improved stability by reducing backbone cleavage. Synergistic combinations of an Insulin-like Growth Factor 1 Receptor (IGF1R) agonist and a short chain fatty acid are also described. Methods of treating muscle and soft-tissue diseases comprising administering the polypeptides and/or synergistic compositions are provided herein.
Claims (14)
1. A fusion protein comprising an insulin-like growth factor 2 (IGF2) polypeptide fused to an N-terminal human serum albumin (HSA) polypeptide, wherein the IGF2 polypeptide comprises the amino acid sequence of SEQ ID NO: 29 and an R61A mutation in the amino acid sequence of SEQ ID NO: 32, wherein the R61A mutation resides within an IGF2 C-domain, and wherein the fusion protein exhibits reduced cleavage within the IGF2 C-domain.
2. The fusion protein of claim 1 , wherein the HSA polypeptide of the fusion protein comprises the amino acid sequence of SEQ ID NO: 58.
3. The fusion protein of claim 1 , further comprising a glycine-rich linker that couples the N-terminal HSA polypeptide to the IGF2 polypeptide.
4. The fusion protein of claim 3 , wherein the glycine-rich linker is a glycine-serine linker.
5. The fusion protein of claim 4 , wherein the glycine-serine linker comprises the amino acid sequence of SEQ ID NO: 63.
6. The fusion protein of claim 4 , wherein the glycine-serine linker comprises a multimer of the 4GS linker of SEQ ID NO: 63, with repeats of 2, 3, 4, or 5 4GS linkers.
7. The fusion protein of claim 4 , wherein the glycine-serine linker comprises the amino acid sequence of SEQ ID NO: 53.
8. The fusion protein of claim 7 , comprising an amino acid sequence at least 98% identical to SEQ ID NO: 59.
9. The fusion protein of claim 7 , comprising an amino acid sequence at least 99% identical to SEQ ID NO: 59.
10. The fusion protein of claim 7 , comprising the amino acid sequence of SEQ ID NO: 59.
11. The fusion protein of claim 7 , consisting essentially of the amino acid sequence of SEQ ID NO: 59.
12. A pharmaceutical composition comprising:
a fusion protein comprising an insulin-like growth factor 2 (IGF2) polypeptide fused to an N-terminal human serum albumin (HSA) polypeptide, wherein the IGF2 polypeptide comprises the amino acid sequence of SEQ ID NO: 29 and an R61A mutation in the amino acid sequence of SEQ ID NO: 32, wherein the R61A mutation resides within an IGF2 C-domain, and wherein the fusion protein exhibits reduced cleavage within the IGF2 C-domain; and
a pharmaceutically acceptable excipient, carrier, or diluent.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 24, 2024
From: YOUSEF, HANADIE; O'CONNELL, JEREMY; MAI, THACH; LI, ZHIHUA
To: JUVENA THERAPEUTICS, INC.
Reel/Frame 069267/0969 →
Continuity (3)
Continuation
18572740
Provisional Application
63259088
· Jun 21, 2021
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