Granted Patent B2

US 12,600,779 · App. 18/515,530 · Granted Apr 14, 2026

Inventors: Ross La Motte-Mohs (Boyds, MD); Kalpana Shah (Boyds, MD); Douglas H. Smith (San Mateo, CA); Leslie S. Johnson (Rockville, MD); Paul A. Moore (North Potomac, MD); Ezio Bonvini (Potomac, MD); Scott Koenig (Rockville, MD)

Assignee: MACROGENICS, INC.

C07K16/2803A61P31/04C07K16/2818A61K2039/505C07K2317/24C07K2317/31C07K2317/33C07K2317/35C07K2317/52C07K2317/522C07K2317/524C07K2317/526C07K2317/565C07K2317/626C07K2317/76C07K2317/92C07K2317/94C07K2319/21

Abstract

Claims (30)

1 . A Lymphocyte Activation Gene 3 (LAG-3)-binding molecule that binds to both to human LAG-3 and to cynomolgus monkey LAG-3, wherein said LAG-3-binding molecule comprises an epitope-binding domain and an Fc region of an antibody, wherein said epitope-binding domain comprises:

(A) an antibody Heavy Chain Variable Domain comprising the amino acid sequence: SEQ ID NO:69, and an antibody Light Chain Variable Domain comprising the amino acid sequence: SEQ ID NO:74;

or

(B) an antibody Heavy Chain Variable Domain comprising the amino acid sequence: SEQ ID NO:79 or SEQ ID NO:81, and an antibody Light Chain Variable Domain comprising the amino acid sequence: SEQ ID NO:83 or SEQ ID NO: 85.

2 . The LAG-3-binding molecule of claim 1 , wherein said molecule comprises said Heavy Chain Variable Domain having the amino acid sequence of SEQ ID NO: 69, and said Light Chain Variable Domain having the amino acid sequence of SEQ ID NO: 74.

3 . The LAG-3-binding molecule of claim 1 , wherein said molecule comprises said Heavy Chain Variable Domain comprising the amino acid sequence of SEQ ID NO: 79, and said Light Chain Variable Domain comprising the amino acid sequence of SEQ ID NO:85.

4 . The LAG-3-binding molecule of claim 1 , wherein said molecule comprises said Heavy Chain Variable Domain comprising the amino acid sequence of SEQ ID NO: 79, and said Light Chain Variable Domain comprising the amino acid sequence of SEQ ID NO:83.

5 . The LAG-3-binding molecule of claim 1 , wherein said molecule comprises said Heavy Chain Variable Domain comprising the amino acid sequence of SEQ ID NO: 81, and said Light Chain Variable Domain comprising the amino acid sequence of SEQ ID NO:83.

6 . The LAG-3-binding molecule of claim 1 , wherein said molecule comprises said Heavy Chain Variable Domain comprising the amino acid sequence of SEQ ID NO: 81, and said Light Chain Variable Domain comprising the amino acid sequence of SEQ ID NO:85.

7 . The LAG-3-binding molecule of claim 1 , wherein said molecule is an antibody.

8 . The LAG-3-binding molecule of claim 7 , wherein said antibody is a chimeric antibody or a humanized antibody.

9 . The LAG-3-binding molecule of claim 1 , wherein said molecule is a bispecific binding molecule that simultaneously binds to human LAG-3 and to a second epitope, wherein said second epitope is an epitope of Programmed Death-1 (PD-1), wherein said bispecific binding molecule comprises second epitope-binding domain, wherein said second epitope-binding domain comprises:

(A) an antibody Heavy Chain Variable Domain comprising the amino acid sequence: SEQ ID NO:131, and an antibody Light Chain Variable Domain comprising the amino acid sequence: SEQ ID NO:132;

(B) an antibody Heavy Chain Variable Domain comprising the amino acid sequence: SEQ ID NO:133, and an antibody Light Chain Variable Domain comprising the amino acid sequence: SEQ ID NO:134;

(C) an antibody Heavy Chain Variable Domain comprising the amino acid sequence: SEQ ID NO:135, and an antibody Light Chain Variable Domain comprising the amino acid sequence: SEQ ID NO:136; or

(D) an antibody Heavy Chain Variable Domain comprising the amino acid sequence: SEQ ID NO:137, and an antibody Light Chain Variable Domain comprising the amino acid sequence: SEQ ID NO:138.

10 . The LAG-3-binding molecule of claim 1 , wherein said Fc Region is a variant Fc Region that comprises:

(a) one or more amino acid modifications that reduce(s) the affinity of said variant Fc Region for an FcγR, wherein said modifications comprise the substitutions:

(1) L234A;

(2) L235A; or

(3) L234A and L235A; and/or

(b) one or more amino acid modifications that enhance(s) the serum half-life of said variant Fc Region, wherein said modifications comprise the substitutions:

(1) M252Y and S254T;

(2) M252Y and T256E;

(3) M252Y, S254T and T256E; or

(4) K288D and H435K;

wherein said numbering is that of the EU index according to Kabat.

11 . A pharmaceutical composition comprising the LAG-3-binding molecule of claim 1 , and a pharmaceutically acceptable carrier.

12 . The LAG-3-binding molecule of claim 1 , for use in stimulating a T-cell-mediated immune response of a subject in need thereof.

13 . The LAG-3-binding molecule of claim 1 , wherein said molecule is detectably labeled and for use in the detection of LAG-3.

Assignments (1)

Continuity (5)

References Cited (400)