IP Library › Granted Patent US 12,703,747
Granted Patent B2
US 12,703,747 · App. 18/058,364 · Granted Aug 11, 2026

Fusion constructs and methods of using thereof

Inventors: Helen Sabzevari (Germantown, MD); Simon Metenou (Germantown, MD); ChangHung Chen (Germantown, MD); Rutul R. Shah (Germantown, MD)
Assignee: PRECIGEN, INC.
C07K16/2818A61K40/11A61K40/31A61K40/36A61K40/4202A61K40/421A61K40/4211A61K40/4214A61K40/4229A61K40/4276A61P35/00C07K14/71C07K16/22A61K2039/505A61K2239/50A61K2239/59C07K2317/56C07K2317/92C07K2319/00
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Quick Facts
Patent No.
US 12,703,747
App. No.
18/058,364
Filed
Nov 23, 2022
Granted
Aug 11, 2026
Kind
B2
Art Unit
1674
USPC
424/134.1
Abstract

Provided herein is a composition comprising a fusion protein or a fragment or a variant thereof comprising an anti-PD1 antibody or a fragment/variant thereof and a TGF-β trap. Provided herein is a composition comprising a fusion protein or a fragment thereof or a variant thereof comprising an anti-PD1 antibody or a fragment/variant thereof and a ADA2 polypeptide. Also provided herein are methods of using the composition in treating cancer.

Claims (28)

1 . A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a fusion protein comprising:

(a) an antibody, or an antigen-binding fragment or variant thereof, that specifically binds to programmed cell death protein-1 (PD-1) and comprises either:

(1) a VH region having the sequence of SEQ ID NO: 6 and a VL region having the sequence of SEQ ID NO: 12; or

(ii) a VH region having the sequence of SEQ ID NO: 7 and a VL region having the sequence of SEQ ID NO: 13;

and

(b) a transforming growth factor beta (TGF-β) cytokine trap having the sequence of SEQ ID NO: 14;

wherein the components of (a) and (b) are connected by a peptide linker and the cancer is colorectal cancer, head and neck cancer, or ovarian cancer.

2 . The method of claim 1 , wherein the peptide linker comprises the sequence of any one of SEQ ID NOs: 17-34.

3 . The method of claim 1 , wherein the antibody is an immunoglobulin G (IgG) antibody.

4 . The method of claim 3 , wherein the IgG antibody comprises a mutation at position 108 of SEQ ID NO: 146 or 292.

5 . The method of claim 4 , wherein the mutation is S108P mutation.

6 . The method of claim 1 , wherein the peptide linker connects the VH region with the TGF-β cytokine trap.

7 . The method of claim 1 , wherein the antibody, or antigen-binding fragment or variant thereof, comprises

a VH region having the sequence of SEQ ID NO: 6 and a VL region having the sequence of SEQ ID NO: 12.

8 . The method of claim 1 , wherein the antibody, or antigen-binding fragment or variant thereof, comprises

a VH region having the sequence of SEQ ID NO: 7 and a VL region having the sequence of SEQ ID NO: 13.

9 . The method of claim 1 , wherein the subject is a human.

10 . The method of claim 1 , further comprising administering to the subject an effective amount of T cells engineered to express an exogenous receptor.

11 . The method of claim 10 , wherein the exogenous receptor is a chimeric antigen receptor comprising an antigen-binding domain that binds to an epitope on CD19, BCMA, CD44, α-Folate receptor, CAIX, CD30, ROR1, CEA, EGP-2, EGP-40, HER2, HER3, Folate-binding Protein, GD2, GD3, IL-13R-a2, KDR, EDB-F, mesothelin, CD22, EGFR, Folate receptor α, MUC-1, MUC-4, MUC-16, MAGE-A1, h5T4, PSMA, TAG-72, EGFR, CD20, EGFRVIII, CD123, or VEGF-R2.

12 . The method of claim 10 , wherein the exogenous receptor is a chimeric antigen receptor and the engineered T cells further express a fusion protein comprising IL-15 and IL-15Rα.

13 . The method of claim 1 , wherein the fusion protein comprises either:

(a) the amino acid sequences of SEQ ID NO: 15 and SEQ ID NO: 294; or

(b) the amino acid sequences of SEQ ID NO: 296 and SEQ ID NO: 144.

14 . The method of claim 1 , wherein the cancer is colorectal cancer.

15 . The method of claim 11 , wherein the chimeric antigen receptor comprises an antigen-binding domain that binds to an epitope on CD33.

16 . The method of claim 1 , wherein the fusion protein comprises either:

(a) (i) the amino acid sequence of SEQ ID NO: 15, and (ii) the sequence of SEQ ID NO: 16, 143, or 294; or (b) (i) the amino acid sequence of SEQ ID NO: 296, and (ii) the amino acid sequence of SEQ ID NO: 144, 145, or 295.

17 . The method of claim 1 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 296 and the amino acid sequence of SEQ ID NO: 144.

Assignments (1)
PATENT SECURITY AGREEMENT Recorded Sep 3, 2025
From: PRECIGEN, INC.; GENVEC LLC; PRECIGEN ACTOBIO, INC.; EXEMPLAR GENETICS, LLC
To: BIOPHARMA CREDIT PLC, AS COLLATERAL AGENT
Reel/Frame 072828/0564 →
Continuity (7)
Division 16506981 · Jul 9, 2019
Provisional Application 62866420 · Jun 25, 2019
Provisional Application 62864367 · Jun 20, 2019
Provisional Application 62863710 · Jun 19, 2019
Provisional Application 62695623 · Jul 9, 2018
Provisional Application 62695627 · Jul 9, 2018
Related Publication 20240141045A1 · May 2, 2024
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