IP Library › Granted Patent US 12,599,663
Granted Patent B2
US 12,599,663 · App. 16/977,636 · Granted Apr 14, 2026

Multivalent peptide conjugates for sustained intra-articular treatment of joint inflammation

Inventors: Wesley M. Jackson (Berkeley, CA); Mavish Mahomed (Berkeley, CA); Livia W. Brier (Berkeley, CA); Kevin E. Healy (Berkeley, CA)
Assignee: VALITOR, INC.
A61K39/3955A61K31/728A61K47/22A61K47/61A61K47/68A61P19/02
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Quick Facts
Patent No.
US 12,599,663
App. No.
16/977,636
Granted
Apr 14, 2026
Kind
B2
Abstract

The present disclosure is directed to peptide-polymer conjugates, and to their use in treating intra-articular diseases or disorders.

Claims (38)

1 . A method of treating a disease or disorder in an articular joint, the method comprising injecting into the articular joint an effective amount of a conjugate comprising: a biocompatible polymer having a molecular weight of from about 0.8 MDa to about 3 MDa; and a plurality of peptides, wherein the peptide has a molecular weight of from about 5 kDa to about 150 kDa;

wherein

the biocompatible polymer is hyaluronic acid,

each peptide is covalently linked to the polymer,

the peptide is covalently linked to the polymer via a sulfide bond and a linker having a molecular weight of from about 100 Da to about 500 Da,

the peptide is a monoclonal IgG antibody, an IgG antibody fragment, a single-chain variable region antibody, a single-domain heavy chain antibody, an adnectin, an affibody, an anticalin, a DARPin, a Kunitz-type inhibitor, or a receptor decoy,

the peptide has an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10 and SEQ ID NO:11,

the molar ratio of the peptide to the polymer in the conjugate is at least about 5:1, and

the disease or disorder is rheumatoid arthritis, wear-related osteoarthritis, age-related osteoarthritis, post-traumatic osteoarthritis, psoriatic arthritis, aseptic implant loosening, joint effusion, ankylosing spondylitis, bursitis, gout, reactive arthritis, synovitis, or avascular necrosis.

2 . The method of claim 1 , wherein

the biocompatible polymer has a molecular weight of from about 0.8 MDa to about 2 MDa; and a plurality of peptides, wherein the peptide has a molecular weight of from about 5 kDa to about 100 kDa;

wherein

the molecular weight of the polymer is from about 5 kDa to about 50 kDa per peptide.

3 . The method of claim 1 , wherein the biocompatible polymer has a molecular weight of from about 0.8 MDa to about 1.5 MDa.

4 . The method of claim 1 , wherein the biocompatible polymer has a molecular weight of about 0.9 MDa.

5 . The method of claim 1 , wherein the biocompatible polymer has a molecular weight of about 2 MDa.

6 . The method of claim 1 , wherein the peptide modulates the activity of immune cell function.

7 . The method of claim 1 , wherein the peptide inhibits tumor necrosis factor-α, interleukin-1β, interleukin-6, or interferon-γ.

8 . The method of claim 1 , wherein the peptide inhibits tumor necrosis factor-α.

9 . The method of claim 1 , wherein the peptide has a molecular weight of from about 5 kDa to about 30 kDa.

10 . The method of claim 1 , wherein the peptide has a molecular weight of from about 10 kDa to about 20 kDa.

11 . The method of claim 1 , wherein the peptide has an amino acid sequence according to SEQ ID NO:1:

(SEQ ID NO: 1)

QVQLQESGGGLVQPGGSLRLSCAASGRTFSDHSGYTYTIGWFRQAPGKE

REFVARIYWSSGNTYYADSVKGRFAISRDIAKNTVDLTMNNLEPEDTAV

YYCAARDGIPTSRSVESYNYWGQGTQVTVSS.

12 . The method of claim 1 , wherein the molar ratio of the peptide to the polymer is from about 5:1 to about 400:1.

13 . The method of claim 1 , wherein the molar ratio of the peptide to the polymer is from about 10:1 to about 100:1.

14 . The method of claim 1 , wherein the molar ratio of the peptide to the polymer is from about 30:1 to about 50:1.

15 . The method of claim 1 , wherein the linker has a molecular weight of from about 100 Da to about 300 Da.

16 . The method of claim 1 , wherein the linker comprises a succinimide.

17 . The method of claim 1 , wherein the diffusion half-life of the conjugate is at least about 2 times longer than the diffusion half-life of the peptide.

18 . The method of claim 1 , wherein the diffusion half-life of the conjugate is from about 2 to about 100 times longer than the diffusion half-life of the peptide.

19 . The method of claim 1 , wherein the intra-articular half-life of the conjugate is at least about 20% longer than intra-articular half-life of the peptide.

20 . The method of claim 1 , wherein the intra-articular half-life of the conjugate is from about 20% to about 1000% longer than the intra-articular half-life of the peptide.

21 . The method of claim 1 , wherein the conjugate is injected into the articular joint no more than about once a month.

22 . The method of claim 1 , wherein the conjugate is injected into the articular joint from about once a month to once every 6 months.

23 . The method of claim 1 , wherein the conjugate is injected into the articular joint once every 2 months or once every 3 months.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 13, 2020
From: JACKSON, WESLEY M.; MAHOMED, MAVISH; BRIER, LIVIA W.; HEALY, KEVIN E.
To: VALITOR, INC.
Reel/Frame 054036/0470 →
Continuity (2)
Provisional Application 62640749 · Mar 9, 2018
Related Publication 20210046181A1 · Feb 18, 2021
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