IP Library › Granted Patent US 12,435,124
Granted Patent B2
US 12,435,124 · App. 17/814,434 · Granted Oct 7, 2025

Compositions and methods for treating CEACAM positive cancers

Inventors: Xueyin Wang (Agoura Hills, CA); Carl Alexander Kamb (Agoura Hills, CA); Han Xu (Agoura Hills, CA); Mark L. Sandberg (Agoura Hills, CA); Dora Toledo Warshaviak (Agoura Hills, CA)
Assignee: A2 Biotherapeutics, Inc.
C07K14/70578A61K40/11A61K40/31A61K40/32A61K40/4266A61P35/00C07K14/7051C07K14/70517C07K14/70521A61K2239/50
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Quick Facts
Patent No.
US 12,435,124
App. No.
17/814,434
Granted
Oct 7, 2025
Kind
B2
Abstract

The disclosure provides immune cells comprising a first activator receptor specific to CEA, and a second inhibitory receptor, and methods of making and using same for the treatment of cancer.

Claims (31)

1. A polynucleotide comprising one or more polynucleotide sequences encoding:

a. a first receptor polypeptide, comprising an extracellular ligand binding domain specific to CEA cell adhesion molecule 5 (CEA); and

b. a second receptor polypeptide, comprising an extracellular ligand binding domain specific to HLA-A*02,

wherein the first receptor is an activator receptor responsive to CEA; and wherein the second receptor is an inhibitory receptor responsive to HLA-A*02;

wherein the extracellular ligand binding domain of the first receptor comprises a variable heavy (VH) portion comprising complementarity determining regions (CDRs) CDR-H1, CDR-H2, and CDR-H3 of SEQ ID NOS: 55, 56, and 57, respectively, and a variable light (VL) portion comprising CDRs CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NOS: 59, 61, and 63, respectively;

and

wherein the extracellular ligand binding domain of the second receptor comprises a VH portion comprising CDRs CDR-H1, CDR-H2, and CDR-H3 of SEQ ID NOS: 106, 107, and 108, respectively, and a VL portion comprising CDRs CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NOS: 103, 104, and 105, respectively.

2. The polynucleotide of claim 1 , wherein the extracellular ligand binding domain of the first receptor comprises a VH portion comprising SEQ ID NO: 144 or a sequence having at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity thereto, and a VL portion comprising SEQ ID NO: 148 or a sequence having 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity thereto.

3. The polynucleotide of claim 1 , wherein the extracellular ligand binding domain of the second receptor comprises a VH portion comprising SEQ ID NO: 981 or a sequence having at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity thereto, and a VL portion comprising SEQ ID NO: 166 or a sequence having 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity thereto.

4. The polynucleotide of claim 1 , wherein the extracellular ligand binding domain of the first receptor comprises an scFv sequence of SEQ ID NO: 68 or a sequence having at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity thereto.

5. The polynucleotide of claim 1 , wherein the extracellular ligand binding domain of the second receptor comprises an scFv sequence of SEQ ID NO: 91 or a sequence having at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity thereto.

6. The polynucleotide of claim 1 , wherein the first receptor is a chimeric antigen receptor (CAR) comprising a hinge domain, a transmembrane domain and an intracellular domain.

7. The polynucleotide of claim 1 , wherein the first receptor comprises a sequence of SEQ ID NO: 52, or a sequence having at least 90%, at least 95%, at least 97% or at least 99% identity thereto.

8. The polynucleotide of claim 1 , wherein the second receptor comprises a LILRB1 intracellular domain or a functional variant thereof.

9. The polynucleotide of claim 8 , wherein the LILRB1 intracellular domain comprises a sequence at least 90%, at least 95%, at least 97%, at least 99%, or is identical to SEQ ID NO: 131.

10. The polynucleotide of claim 1 , wherein the second receptor comprises a LILRB1 transmembrane domain comprising a sequence at least 90%, at least 95%, at least 97%, at least 99% or is identical to SEQ ID NO: 135.

11. The polynucleotide of claim 1 , wherein the second receptor comprises a LILRB1 hinge domain comprising a sequence at least 90%, at least 95%, at least 97%, at least 99% or is identical to SEQ ID NO: 134.

12. The polynucleotide of claim 1 , wherein the second receptor comprises a sequence of SEQ ID NO: 164, or a sequence having at least 90%, at least 95%, at least 97%, or at least 99% identity thereto.

13. A pharmaceutical composition, comprising a therapeutically effective amount of the polynucleotide of claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.

14. The polynucleotide of claim 1 , wherein the second receptor comprises a LILRB1 intracellular domain, a LILRB1 transmembrane domain, a LILRB1 hinge domain, a functional variant of any of these, or combinations thereof.

15. The polynucleotide of claim 1 , wherein the second receptor comprises a LILRB1 intracellular domain, a LILRB1 transmembrane domain, and a LILRB1 hinge domain.

16. The polynucleotide of claim 15 , wherein the second receptor comprises a sequence of SEQ ID NO: 164.

17. A polynucleotide system, comprising one or more polynucleotide sequences comprising:

a. a first polynucleotide encoding a first receptor polypeptide, comprising an extracellular ligand binding domain specific to CEA cell adhesion molecule 5 positive (CEA); and

b. a second polynucleotide encoding a second receptor polypeptide, comprising an extracellular ligand binding domain specific to HLA-A*02,

wherein the first receptor is an activator receptor responsive to CEA on the CEA+ cancer cell; and wherein the second receptor is an inhibitory receptor responsive to HLA-A*02;

wherein the extracellular ligand binding domain of the first receptor comprises a variable heavy (VH) portion comprising complementarity determining regions (CDRs) CDR-H1, CDR-H2, and CDR-H3 of SEQ ID NOS: 55, 56, and 57, respectively, and a variable light (VL) portion comprising CDRs CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NOS: 59, 61, and 63, respectively;

and

wherein the extracellular ligand binding domain of the second receptor comprises a VH portion comprising CDRs CDR-H1, CDR-H2, and CDR-H3 of SEQ ID NOS: 106, 107, and 108, respectively, and a VL portion comprising CDRs CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NOS: 103, 104, and 105, respectively.

18. A vector comprising the polynucleotide system of claim 17 .

19. The vector of claim 18 , wherein the vector is a lentiviral vector.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 22, 2022
From: WANG, XUEYIN; KAMB, CARL ALEXANDER; XU, HAN; SANDBERG, MARK L.; WARSHAVIAK, DORA TOLEDO
To: A2 BIOTHERAPEUTICS, INC.
Reel/Frame 060598/0357 →
Continuity (4)
Division 17517559 · Nov 2, 2021
Continuation PCTUS2021046774 · Aug 19, 2021
Provisional Application 63068244 · Aug 20, 2020
Related Publication 20230172983A1 · Jun 8, 2023
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