US 11,858,991 B2
LAG-3-binding molecules and methods of use thereof
Ross La Motte-Mohs, Boyds, MD (US); Kalpana Shah, Boyds, MD (US); Douglas H. Smith, San Mateo, CA (US); Leslie S. Johnson, Rockville, MD (US); Paul A. Moore, North Potomac, MD (US); Ezio Bonvini, Potomac, MD (US); and Scott Koenig, Rockville, MD (US)
Assigned to MacroGenics, Inc., Rockville, MD (US)
Filed by MacroGenics, Inc., Rockville, MD (US)
Filed on Jan. 12, 2021, as Appl. No. 17/147,279.
Application 17/147,279 is a continuation of application No. 15/580,029, granted, now 11,072,653, previously published as PCT/US2016/036172, filed on Jun. 7, 2016.
Claims priority of provisional application 62/255,094, filed on Nov. 13, 2015.
Claims priority of provisional application 62/172,277, filed on Jun. 8, 2015.
Prior Publication US 2021/0206851 A1, Jul. 8, 2021
Int. Cl. C07K 16/28 (2006.01); A61P 31/04 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/2803 (2013.01) [A61P 31/04 (2018.01); C07K 16/2818 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/33 (2013.01); C07K 2317/35 (2013.01); C07K 2317/52 (2013.01); C07K 2317/522 (2013.01); C07K 2317/524 (2013.01); C07K 2317/526 (2013.01); C07K 2317/565 (2013.01); C07K 2317/626 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01); C07K 2319/21 (2013.01)] 18 Claims
 
1. A method of stimulating a T-cell-mediated immune response in a subject in need thereof comprising administering to said subject a therapeutically effective amount of 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 CDRH1 Domain, a CDRH2 Domain and a CDRH3 Domain, and said Variable Light Chain Domain comprises a CDRL1 Domain, a CDRL2 Domain, and a CDRL3 Domain, wherein:
(A) (1) the CDRH1 Domain, CDRH2 Domain, and CDRH3 Domain are the Heavy Chain CDRs of LAG-3 mAb 1, and respectively have the amino acid sequences: SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10; and
(2) the CDRL1 Domain, CDRL2 Domain, and CDRL3 Domain are the Light Chain CDRs of LAG-3 mAb 1, and respectively have the amino acid sequences: SEQ ID NO:13, SEQ ID NO:14, and SEQ ID NO:15;
or
(B) (1) the CDRH1 Domain, CDRH2 Domain, and CDRH3 Domain are the Heavy Chain CDRs of hLAG-3 mAb 1, and respectively have the amino acid sequences: SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10; and
(2) the CDRL1 Domain, CDRL2 Domain, and CDRL3 Domain are the Light Chain CDRs of hLAG-3 mAb 1, and respectively have the amino acid sequences: SEQ ID NO:28, SEQ ID NO:14, and SEQ ID NO:15;
or
(C) (1) the CDRH1 Domain, CDRH2 Domain, and CDRH3 Domain are the Heavy Chain CDRs of LAG-3 mAb 6 VH1, and respectively have the amino acid sequences: SEQ ID NO:71, SEQ ID NO:72, and SEQ ID NO:73; and
(2) the CDRL1 Domain, CDRL2 Domain, and CDRL3 Domain are the Light Chain CDRs of LAG-3 mAb 6, and, respectively have the amino acid sequences: SEQ ID NO:76, SEQ ID NO:77, and SEQ ID NO:78;
or
(D) (1) the CDRH1 Domain, CDRH2 Domain, and CDRH3 Domain are the Heavy Chain CDRs of LAG-3 mAb 6, and respectively have the amino acid sequences: SEQ ID NO:71, SEQ ID NO:72, and SEQ ID NO:73; and
(2) the CDRL1 Domain, CDRL2 Domain, and CDRL3 Domain are the Light Chain CDRs of hLAG-3 mAb 6, and respectively have the amino acid sequences: SEQ ID NO:87, SEQ ID NO:77, and SEQ ID NO:78.