IP Library › Granted Patent US 12,435,142
Granted Patent B2
US 12,435,142 · App. 17/417,244 · Granted Oct 7, 2025

Anti-CTLA4 antibodies and methods of use thereof

Inventor: Margaret Karow (Waltham, MA)
Assignee: Xilio Development, Inc.
C07K16/2818A61K47/6849A61P35/00A61K2039/505C07K2317/24C07K2317/31C07K2317/40C07K2317/52C07K2317/55C07K2317/565C07K2317/72C07K2317/732C07K2317/76C07K2317/92C07K2319/50
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Quick Facts
Patent No.
US 12,435,142
App. No.
17/417,244
Granted
Oct 7, 2025
Kind
B2
Abstract

The invention provides anti-CTLA4 binding proteins (e.g., antibodies, bispecific antibodies, and chimeric receptors) and their use in treating and preventing cancer, as well as compositions and kits comprising the anti-CTLA4 binding proteins.

Claims (24)

1. An anti-CTLA4 antibody comprising a light chain variable (VL) domain and a heavy chain variable (VH) domain, wherein:

the VL domain comprises (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 19, (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 20, and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 21; and the VH domain comprises (1) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 22, (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 23, and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 24; and

wherein the antibody comprises a heavy chain constant region (CH) comprising substitutions S239D and I332E, wherein the amino acid residues are numbered according to EU index as in Kabat.

2. The anti-CTLA4 antibody of claim 1 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO: 30, and the VH domain comprises the amino acid sequence of SEQ ID NO: 31.

3. The anti-CTLA4 antibody of claim 1 , wherein the antibody comprises a CH sequence of SEQ ID NO: 38.

4. The anti-CTLA4 antibody claim 1 , wherein the antibody comprises a CL sequence of SEQ ID NO: 39.

5. The anti-CTLA4 antibody of claim 1 , wherein the light chain comprises the amino acid sequence of SEQ ID NO: 32, and the heavy chain comprises the amino acid sequence of SEQ ID NO: 34.

6. The anti-CTLA4 antibody of claim 1 , wherein the antibody is afucosylated or fucose-deficient.

7. A bispecific antibody comprising:

1) a light chain and a heavy chain of a first pair that specifically binds to CTLA4;

2) a light chain and a heavy chain of a second pair that specifically binds to an antigen; wherein the light chain of the first pair comprises a VL domain, and the heavy chain of the first pair comprises a VH domain and wherein:

the VL domain comprises (1) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 19, (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 20, and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 21; and the VH domain comprises (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 22, (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 23, and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 24

wherein the heavy chain of the first pair comprises a heavy chain constant region (CH) comprising substitutions S239D and I332E, wherein the amino acid residues are numbered according to EU index as in Kabat.

8. The bispecific antibody of claim 7 , wherein:

the VL domain comprises the amino acid sequence of SEQ ID NO: 30, and the VH domain comprises the amino acid sequence of SEQ ID NO: 31.

9. The bispecific antibody of claim 7 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO: 25, and the VH domain comprises the amino acid sequence of SEQ ID NO: 26.

10. The bispecific antibody of claim 7 , wherein the bispecific antibody comprises a CH sequence of SEQ ID NO: 38.

11. The bispecific antibody of claim 7 , wherein the bispecific antibody comprises a CL sequence of SEQ ID NO: 39.

12. The bispecific antibody of claim 7 , wherein:

the light chain of the first pair comprises the amino acid sequence of SEQ ID NO: 32, and the heavy chain of the first pair comprises the amino acid sequence of SEQ ID NO: 34.

13. A nucleic acid encoding the anti-CTLA4 antibody of claim 1 .

14. A host cell comprising the anti-CTLA4 antibody of the nucleic acid of claim 13 .

15. The host cell of claim 14 , wherein the host cell has an alpha 1,6-fucosyltransferase (Fut8) knockout.

16. A method of treating or preventing a neoplastic disease in a subject, the method comprising administering to a subject an effective amount of the anti-CTLA4 antibody or antigen-binding fragment thereof of claim 1 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 7, 2021
From: KAROW, MARGARET
To: XILIO DEVELOPMENT, INC.
Reel/Frame 057401/0080 →
Continuity (2)
Provisional Application 62785111 · Dec 26, 2018
Related Publication 20220064301A1 · Mar 3, 2022
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