Granted Patent B2

US 12,729,236 · App. 17/622,467 · Granted Sep 8, 2026

Inventors: Wesley M. Jackson (Berkley, CA); Amy A. Twite (Berkeley, CA); Livia Wilz Brier (Berkeley, CA)

Assignee: VALITOR, INC.

C07K16/241A61K9/0019A61K47/61A61P29/00A61P35/00A61K39/00C07K2317/94C07K2319/31

Abstract

Claims (43)

1 . A conjugate of Formula I:

(

X

-

Y

)

n

-

Z

Formula

⁢

(

I

)

wherein

each X is independently a peptide, wherein the peptide is an antibody or a DARPin;

each Y is independently a hydrophilic linker, wherein the hydrophilic linker corresponds to any one of the following:

1-[3-({[2-(3-Hydrazino-3-oxopropoxy)ethoxy]methyl}amino)-3-oxopropyl]-1H-pyrrole-2,5-dione,

1-(3-{2-[2-(3-Hydrazino-3-oxopropoxy)ethoxy]ethylamino}-3-oxopropyl)-1H-pyrrole-2,5-dione, or

1-[3-(2-{2-[2-(2-Aminoethoxy)ethoxy]ethoxy}ethylamino)-3-oxopropyl]-1H-pyrrole-2,5-dione;

Z is a biocompatible polymer having a molecular weight of from about 0.8 MDa to about 3 MDa, wherein the biocompatible polymer is hyaluronic acid; and

subscript n is an integer from 10 to 1000.

2 . The conjugate of claim 1 , wherein the peptide is an inhibitor of angiogenesis.

3 . The conjugate of claim 2 , wherein the peptide is an antibody specific for VEGF- or a DARPin specific for VEGF.

4 . The conjugate of claim 2 , wherein the peptide inhibits VEGF-A, VEGF-B, VEGF-C, VEGF-D, Ang-1, Ang-2, PDGF, or PlGF.

5 . The conjugate of claim 2 , wherein the peptide is a monoclonal IgG antibody, an IgG antibody fragment, a single-chain variable region antibody, a single-domain heavy chain antibody, or a DARPin.

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

7 . The conjugate of claim 6 , wherein the peptide inhibits tumor necrosis factor-α.

8 . The conjugate of claim 6 , wherein the peptide is a monoclonal IgG antibody, an IgG antibody fragment, a single-chain variable region antibody, a single-domain heavy chain antibody, or a DARPin.

9 . The conjugate of claim 6 , wherein 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, and SEQ ID NO:10.

10 . The conjugate of claim 6 , wherein the peptide has a sequence:

(SEQ ID NO: 1)

QVQLQESGGGLVQPGGSLRLSCAASGRTFSDHSGYTYTIGWFRQAPGKER

EFVARIYWSSGNTYYADSVKGRFAISRDIAKNTVDLTMNNLEPEDTAVYY

CAARDGIPTSRSVESYNYWGQGTQVTVSS.

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

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

13 . The conjugate of claim 1 , wherein subscript n is an integer of from 10 to 400.

14 . The conjugate of claim 1 , wherein subscript n is an integer of from 10 to 100.

15 . The conjugate of claim 1 , wherein subscript n is an integer of from 50 to 100.

16 . A pharmaceutical composition comprising the conjugate of claim 1 , and a pharmaceutically acceptable carrier.

17 . The conjugate of claim 1 , wherein the hydrophilic linker corresponds to 1-(3-{2-[2-(3-Hydrazino-3-oxopropoxy)ethoxy]ethylamino}-3-oxopropyl)-1H-pyrrole-2,5-dione.

18 . The conjugate of claim 1 , wherein the hydrophilic linker is

Assignments (1)

Continuity (3)

References Cited (118)