Granted Patent
B2
US 12,344,645 · App. 15/940,626 · Granted Jul 1, 2025
Protein conjugates
Inventors:
Robert J. Almassy (Vista, CA); Elena Brin (San Diego, CA); Richard E. Showalter (El Cajon, CA); James A. Thomson (San Diego, CA)
Assignee:
POLARIS GROUP
C07K14/525A61K38/1761A61K38/50A61K47/60A61K47/642A61K47/6815A61P35/00C07K14/70575C12N9/78C12Y305/03006
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Abstract
Provided are conjugates of an arginine deiminase (ADI) and a Tumor Necrosis Factor (TNF) superfamily ligand, and related compositions and methods of use thereof. Also provided are conjugates of a hexameric polypeptide and a trimeric polypeptide, conjugates of a first and second trimeric polypeptide, and related compositions and methods of use thereof.
Claims (21)
1. A conjugate protein, wherein said conjugate protein is a single protein comprising a first polypeptide that is at least 95% identical to SEQ ID NO: 9, 37, 38, 50, or 57-68, that is covalently linked to a second polypeptide, wherein the second polypeptide comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 69 or SEQ ID NO: 70.
2. The conjugate protein of claim 1 , wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO: 9, 37, 38, 50, or 57-68 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 69 or SEQ ID NO: 70.
3. The conjugate protein of claim 1 , wherein the first polypeptide is a hexameric polypeptide.
4. The conjugate protein of claim 1 , wherein the second polypeptide is a trimeric polypeptide.
5. The conjugate protein of claim 1 , wherein the first polypeptide and the second polypeptide are separated by a linker.
6. The conjugate protein of claim 5 , wherein the linker is a peptide linker.
7. The conjugate protein of claim 6 , wherein the peptide linker is 1-100 amino acids in length.
8. The conjugate protein of claim 6 , wherein the peptide linker is selected from [G] x , [S] x , [N] x , [GS] x , [GGS] x , [GSS] x , [GSGS (SEQ ID NO: 73)] x , [GGSG (SEQ ID NO: 74)] x , [GGGS (SEQ ID NO: 75)] x , [GGGGS (SEQ ID NO: 76)] x , [GN] x , [GNN] x , [GNGN (SEQ ID NO: 77)] x , [GGNG (SEQ ID NO: 78)] x , [GGGN (SEQ ID NO: 79)] x , [GGGGN (SEQ ID NO: 80)] x , A(EAAAK) x A (SEQ ID NO: 81), AEAAAAKA (SEQ ID NO: 81), AEAAAKEAAAKA (SEQ ID NO: 82), (XP) x , APAPKP (SEQ ID NO: 83), APAPKPEPAPKP (SEQ ID NO: 94), GGGGS (SEQ ID NO: 76), GGGGSGGGGS (SEQ ID NO: 85), DGGGS (SEQ ID N: 86), TGEKP (SEQ ID NO: 87), GGRR (SEQ ID NO: 88), EGKSSGSGSESKVD (SEQ ID NO: 89), KESGSVSSEQLAQFRSLD (SEQ ID NO: 90), GGRRGGGS (SEQ ID NO: 91), LRQRDGERP (SEQ ID NO: 92), LRQKDGGGSERP (SEQ ID NO: 93), LRQKD (GGGS) 2 , ERP (SEQ ID NO: 94)
wherein x is 1-50, 60, 70, 80, 90, or 100.
9. The conjugate protein of claim 1 , wherein the conjugate protein is a fusion polypeptide.
10. The conjugate protein of claim 9 , wherein the first polypeptide is fused to the N-terminus of the second polypeptide.
11. The conjugate protein of claim 1 , wherein the first polypeptide is covalently bonded via a linking group to at least one polyethylene glycol (PEG) molecule.
12. An isolated polynucleotide which encodes a conjugate protein of claim 1 , wherein the conjugate protein is a fusion protein, or an expression vector that comprises the isolated polynucleotide, or an isolated host cell that comprises the isolated polynucleotide or the expression vector.
13. A therapeutic composition, comprising a conjugate protein of claim 1 and a pharmaceutically acceptable carrier or excipient.
14. The therapeutic composition of claim 13 , wherein the conjugate protein forms a protein complex of one hexamer of six first polypeptides and two trimers of three second polypeptides.
15. The therapeutic composition of claim 13 , where the conjugate protein as is at least 95% pure and less than 5% aggregated, and wherein the composition is substantially endotoxin-free.
16. The conjugate protein of claim 5 , wherein the linker is a physiologically-stable linker.
17. The conjugate protein of claim 6 , wherein the peptide linker is a flexible peptide linker or a rigid peptide linker.
18. The conjugate protein of claim 10 , wherein the first polypeptide is separated from the second polypeptide by a linker.
19. The conjugate protein of claim 11 , wherein the second polypeptide is not covalently bonded to a PEG molecule.
20. The conjugate protein of claim 4 , wherein the trimeric polypeptide is a homotrimeric polypeptide.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 26, 2018
From: BRIN, ELENA; ALMASSY, ROBERT J.; SHOWALTER, RICHARD E.; THOMSON, JAMES A.
To: TDW GROUP
Reel/Frame 046204/0835 →
Continuity (2)
Provisional Application
62478398
· Mar 29, 2017
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