IP Library › Granted Patent US 11,072,653
Granted Patent B2
US 11,072,653 · App. 15/580,029 · Granted Jul 27, 2021

LAG-3-binding molecules and methods of use thereof

Inventors: Ross La Motte-Mohs (Boyds, MD); Kalpana Shah (Boyds, MD); Douglas H. Smith (San Mateo, CA); Leslie S. Johnson (Darnestown, 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
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Quick Facts
Patent No.
US 11,072,653
App. No.
15/580,029
Granted
Jul 27, 2021
Kind
B2
Abstract

The present invention is directed to the anti-LAG-3 antibodies, LAG-3 mAb 1, LAG-3 mAb 2, LAG-3 mAb 4, LAG-3 mAb 5, and LAG-3 mAb 6, and to humanized and chimeric versions of such antibodies. The invention additionally pertains to LAG-3-binding molecules that comprise LAG-3 binding fragments of such anti-LAG-3 antibodies, immunocongugates, and to bispecific molecules, including diabodies, BiTEs, bispecific antibodies, etc., that comprise (i) such LAG-3-binding fragments, and (ii) a domain capable of binding an epitope of a molecule involved in regulating an immune check point present on the surface of an immune cells. The present invention also pertains to methods of detecting LAG-3, as well as methods of using molecules that bind LAG-3 for stimulating immune responses.

Claims (49)

1. A Lymphocyte Activation Gene 3 (LAG-3)-binding molecule that is capable of binding both to human LAG-3 and to cynomolgus monkey LAG-3, wherein said LAG-3-binding molecule comprises a Variable Heavy Chain Domain and a Variable Light Chain Domain, wherein:

said Variable Heavy Chain Domain comprises a CDR H 1 Domain, a CDR H 2 Domain and a CDR H 3 Domain, and said Variable Light Chain Domain comprises a CDR L 1 Domain, a CDR L 2 Domain, and a CDR L 3 Domain, wherein:

(A) (1) the CDR H 1 Domain, CDR H 2 Domain, and CDR H 3 Domain are the Heavy Chain CDRs of LAG-3 mAb 1, and respectively comprise the amino acid sequences: SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10; and

(2) the CDR L 1 Domain, CDR L 2 Domain, and CDR L 3 Domain are the Light Chain CDRs of LAG-3 mAb 1, and respectively comprise the amino acid sequences: SEQ ID NO:13, SEQ ID NO:14, and SEQ ID NO:15;

or

(B) (1) the CDR H 1 Domain, CDR H 2 Domain, and CDR H 3 Domain are the Heavy Chain CDRs of hLAG-3 mAb 1, and respectively comprise the amino acid sequences: SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10; and

(2) the CDR L 1 Domain, CDR L 2 Domain, and CDR L 3 Domain are the Light Chain CDRs of hLAG-3 mAb 1, and respectively comprise the amino acid sequences: SEQ ID NO:28, SEQ ID NO:14, and SEQ ID NO:15;

or

(C) (1) the CDR H 1 Domain, CDR H 2 Domain, and CDR H 3 Domain are the Heavy Chain CDRs of LAG-3 mAb 2, and respectively comprise the amino acid sequences: SEQ ID NO:31, SEQ ID NO:32, and SEQ ID NO:33; and

(2) the CDR L 1 Domain, CDR L 2 Domain, and CDR L 3 Domain are the Light Chain CDRs of LAG-3 mAb 2, and, respectively comprise the amino acid sequences: SEQ ID NO:36, SEQ ID NO:37, and SEQ ID NO:38;

or

(D) (1) the CDR H 1 Domain, CDR H 2 Domain, and CDR H 3 Domain are the Heavy Chain CDRs of LAG-3 mAb 3, and respectively comprise the amino acid sequences: SEQ ID NO:41, SEQ ID NO:42, and SEQ ID NO:43; and

(2) the CDR L 1 Domain, CDR L 2 Domain, and CDR L 3 Domain are the Light Chain CDRs of LAG-3 mAb 3, and, respectively comprise the amino acid sequences: SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48;

or

(E) (1) the CDR H 1 Domain, CDR H 2 Domain, and CDR H 3 Domain are the Heavy Chain CDRs of LAG-3 mAb 4, and respectively comprise the amino acid sequences: SEQ ID NO:51, SEQ ID NO:52, and SEQ ID NO:53; and

(2) the CDR L 1 Domain, CDR L 2 Domain, and CDR L 3 Domain are the Light Chain CDRs of LAG-3 mAb 4, and, respectively comprise the amino acid sequences: SEQ ID NO:56, SEQ ID NO:57, and SEQ ID NO:58;

or

(F) (1) the CDR H 1 Domain, CDR H 2 Domain, and CDR H 3 Domain are the Heavy Chain CDRs of LAG-3 mAb 5, and respectively comprise the amino acid sequences: SEQ ID NO:61, SEQ ID NO:62, and SEQ ID NO:63; and

(2) the CDR L 1 Domain, CDR L 2 Domain, and CDR L 3 Domain are the Light Chain CDRs of LAG-3 mAb 5, and, respectively comprise the amino acid sequences: SEQ ID NO:66, SEQ ID NO:67, and SEQ ID NO:68;

or

(G) (1) the CDR H 1 Domain, CDR H 2 Domain, and CDR H 3 Domain are the Heavy Chain CDRs of LAG-3 mAb 6, and respectively comprise the amino acid sequences: SEQ ID NO:71, SEQ ID NO:72, and SEQ ID NO:73; and

(2) the CDR L 1 Domain, CDR L 2 Domain, and CDR L 3 Domain are the Light Chain CDRs of LAG-3 mAb 6, and, respectively comprise the amino acid sequences: SEQ ID NO:76, SEQ ID NO:77, and SEQ ID NO:78;

or

(H) (1) the CDR H 1 Domain, CDR H 2 Domain, and CDR H 3 Domain are the Heavy Chain CDRs of hLAG-3 mAb 6, and respectively comprise the amino acid sequences: SEQ ID NO:71, SEQ ID NO:72, and SEQ ID NO:73; and

(2) the CDR L 1 Domain, CDR L 2 Domain, and CDR L 3 Domain are the Light Chain CDRs of hLAG-3 mAb 6, and respectively comprise the amino acid sequences: SEQ ID NO:87, SEQ ID NO:77, and SEQ ID NO:78.

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

3. The LAG-3-binding molecule of claim 2 , wherein said molecule is a chimeric antibody or a humanized antibody.

4. The LAG-3-binding molecule of claim 1 , wherein said molecule comprises a Heavy Chain Variable Domain comprising the amino acid sequence of SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO: 79, or SEQ ID NO: 81.

5. The LAG-3-binding molecule of claim 1 , wherein said molecule comprises a Light Chain Variable Domain comprising the amino acid sequence of SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:83, or SEQ ID NO:85.

6. A labeled LAG-3-binding molecule of claim 1 , wherein said LAG-3 binding molecule is labeled for the detection of LAG-3.

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

8. The LAG-3-binding molecule of claim 1 , wherein:

(1) the CDR H 1 Domain, CDR H 2 Domain, and CDR H 3 Domain are the Heavy Chain CDRs of LAG-3 mAb 1, and respectively comprise the amino acid sequences: SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10; and

(2) the CDR L 1 Domain, CDR L 2 Domain, and CDR L 3 Domain are the Light Chain CDRs of LAG-3 mAb 1, and respectively comprise the amino acid sequences: SEQ ID NO:13, SEQ ID NO:14, and SEQ ID NO:15.

9. The LAG-3-binding molecule of claim 8 , wherein said Variable Heavy Chain Domain comprises the amino acid sequence of SEQ ID NO:16, and said Variable Light Chain Domain comprises the amino acid sequence of SEQ ID NO:24.

10. A pharmaceutical composition comprising the LAG-3-binding molecule of claim 9 and a pharmaceutically acceptable carrier.

11. The LAG-3-binding molecule of claim 1 , wherein:

(1) the CDR H 1 Domain, CDR H 2 Domain, and CDR H 3 Domain are the Heavy Chain CDRs of hLAG-3 mAb 1, and respectively comprise the amino acid sequences: SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10; and

(2) the CDR L 1 Domain, CDR L 2 Domain, and CDR L 3 Domain are the Light Chain CDRs of hLAG-3 mAb 1, and respectively comprise the amino acid sequences: SEQ ID NO:28, SEQ ID NO:14, and SEQ ID NO:15.

12. The LAG-3-binding molecule of claim 11 , wherein said Variable Heavy Chain Domain comprises the amino acid sequence of SEQ ID NO:16, and said Variable Light Chain Domain comprises the amino acid sequence of SEQ ID NO:26.

13. A pharmaceutical composition comprising the LAG-3-binding molecule of claim 12 and a pharmaceutically acceptable carrier.

14. The LAG-3-binding molecule of claim 1 , wherein:

(1) the CDR H 1 Domain, CDR H 2 Domain, and CDR H 3 Domain are the Heavy Chain CDRs of LAG-3 mAb 6, and respectively comprise the amino acid sequences: SEQ ID NO:71, SEQ ID NO:72, and SEQ ID NO:73; and

(2) the CDR L 1 Domain, CDR L 2 Domain, and CDR L 3 Domain are the Light Chain CDRs of LAG-3 mAb 6, and respectively comprise the amino acid sequences: SEQ ID NO:76, SEQ ID NO:77, and SEQ ID NO:78.

15. The LAG-3-binding molecule of claim 1 , wherein:

(1) the CDR H 1 Domain, CDR H 2 Domain, and CDR H 3 Domain are the Heavy Chain CDRs of hLAG-3 mAb 6, and respectively comprise the amino acid sequences: SEQ ID NO:71, SEQ ID NO:72, and SEQ ID NO:73; and

(2) the CDR L 1 Domain, CDR L 2 Domain, and CDR L 3 Domain are the Light Chain CDRs of hLAG-3 mAb 6, and respectively comprise the amino acid sequences: SEQ ID NO:87, SEQ ID NO:77, and SEQ ID NO:78.

16. The LAG-3-binding molecule of claim 15 , wherein said Variable Heavy Chain Domain comprises the amino acid sequence of SEQ ID NO:79, and said Variable Light Chain Domain comprises the amino acid sequence of SEQ ID NO:83.

17. A pharmaceutical composition comprising the LAG-3-binding molecule of claim 16 and a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 18, 2018
From: LA MOTTE-MOHS, ROSS; SHAH, KALPANA; JOHNSON, LESLIE S.; MOORE, PAUL A.; BONVINI, EZIO; KOENIG, SCOTT; SMITH, DOUGLAS H.
To: MACROGENICS, INC.
Reel/Frame 046900/0023 →
Continuity (3)
Provisional Application 62255094 · Nov 13, 2015
Provisional Application 62172277 · Jun 8, 2015
Related Publication 20190085075A1 · Mar 21, 2019
Cited By (1)
US 12,600,779