IP Library › Granted Patent US 11,433,100
Granted Patent B2
US 11,433,100 · App. 17/517,559 · Granted Sep 6, 2022

Compositions and methods for treating ceacam positive cancers

Inventors: Xueyin Wang (Agoura Hills, CA); Carl Alexander Kamb (Westlake Village, CA); Han Xu (Agoura Hills, CA); Mark L. Sandberg (Agoura Hills, CA); Dora Toledo Warshaviak (Agoura Hills, CA)
Assignee: A2 Biotherapeutics, Inc.
A61K35/17A61P35/00C07K14/7051C07K14/70517C07K14/70521C07K14/70578
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Quick Facts
Patent No.
US 11,433,100
App. No.
17/517,559
Granted
Sep 6, 2022
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 (35)

1. An immune cell comprising:

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

b. a second receptor, 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 immune cell 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% identity thereto, and a VL portion comprising SEQ ID NO: 148 or a sequence having at least 85% identity thereto.

3. The immune cell 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% identity thereto, and a VL portion comprising SEQ ID NO: 166 or a sequence having at least 85% identity thereto.

4. The immune cell 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% identity thereto.

5. The immune cell 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% identity thereto.

6. The immune cell 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 immune cell of claim 6 , wherein the hinge domain of the first receptor comprises a CD8α hinge domain.

8. The immune cell of claim 7 , wherein the CD8α hinge domain of the first receptor comprises a sequence of SEQ ID NO: 71, or a sequence having at least 85% identity thereto.

9. The immune cell of claim 6 , wherein the transmembrane domain of the first receptor comprises a CD28 transmembrane domain.

10. The immune cell of claim 9 , wherein the CD28 transmembrane domain of the first receptor comprises a sequence of SEQ ID NO: 75, or a sequence having at least 85% identity thereto.

11. The immune cell of claim 6 , wherein the intracellular domain of the first receptor comprises a CD28 co-stimulatory domain, a 4-1BB co-stimulatory domain, and a CD3ζ activation domain.

12. The immune cell of claim 11 , wherein the intracellular domain of the first receptor comprises a sequence of SEQ ID NO: 158, or a sequence having at least 85% identity thereto.

13. The immune cell of claim 1 , wherein the first receptor comprises a sequence of SEQ ID NO: 52, or a sequence having at least 90% identity thereto.

14. The immune cell of claim 1 , wherein the second receptor comprises a LILRB1 intracellular domain.

15. The immune cell of claim 14 , wherein the LILRB1 intracellular domain comprises a sequence at least 90%, or is identical to SEQ ID NO: 131.

16. The immune cell of claim 1 , wherein the second receptor comprises a LILRB1 transmembrane domain.

17. The immune cell of claim 16 , wherein the LILRB1 transmembrane domain comprises a sequence at least 90% or is identical to SEQ ID NO: 135.

18. The immune cell of claim 1 , wherein the second receptor comprises a LILRB1 hinge domain.

19. The immune cell of claim 18 , wherein the LILRB1 hinge domain comprises a sequence at least 90% or is identical to SEQ ID NO: 134.

20. The immune cell of claim 1 , wherein the second receptor comprises a sequence of SEQ ID NO: 164, or a sequence having at least 90% identity thereto.

21. The immune cell of claim 1 , wherein the immune cell is a T cell, an NK cell or a macrophage.

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

23. The immune cell 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 at least 95% thereto, and a VL portion comprising SEQ ID NO: 166 or a sequence having at least 95% identity thereto.

24. The immune cell of claim 23 , 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 95% thereto, and a VL portion comprising SEQ ID NO: 148 or a sequence at least 95% identity thereto.

25. The immune cell of claim 23 , wherein the extracellular ligand binding domain of the first receptor comprises an scFv sequence of SEQ ID NO: 68 or at least 95% identity thereto.

26. The immune cell 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 95% identity thereto.

27. The immune cell of claim 1 , wherein the extracellular ligand binding domain of the second receptor comprises a VH portion comprising SEQ ID NO: 981, and a VL portion comprising SEQ ID NO: 166.

28. The immune cell of claim 27 , wherein the extracellular ligand binding domain of the first receptor comprises a VH portion comprising SEQ ID NO: 144, and a VL portion comprising SEQ ID NO: 148.

29. The immune cell of claim 1 , wherein the extracellular ligand binding domain of the first receptor comprises an scFv sequence of SEQ ID NO: 68; and wherein the extracellular ligand binding domain of the second receptor comprises an scFv sequence of SEQ ID NO: 91.

30. The immune cell of claim 1 , wherein the immune cell is a T cell.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 28, 2022
From: WANG, XUEYIN; KAMB, CARL ALEXANDER; XU, HAN; SANDBERG, MARK L.; WARSHAVIAK, DORA TOLEDO
To: A2 BIOTHERAPEUTICS, INC.
Reel/Frame 060336/0980 →
Continuity (3)
Continuation PCTUS2021046774 · Aug 19, 2021
Provisional Application 63068244 · Aug 20, 2020
Related Publication 20220054551A1 · Feb 24, 2022