Patent SG-11201408780X-A (SG)
Title: Optimization of antibodies that bind lymphocyte activation gene-3 (lag-3), and uses thereof
Inventor: LONBERG NILS
IPC: C07K16/28
Filed: 2013-07-02
Abstract: (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 9 January 2014 (09.01.2014) WIPOIPCT (10) International Publication Number WO 2014/008218 A1 (51) International Patent Classification: C07K16/28 (2006.01) (21) International Application Number: (22) International Filing Date: (25) Filing Language: (26) Publication Language: PCT/US2013/048999 2 July 2013 (02.07.2013) English English (30) Priority Data: 61/667,058 2 July 2012 (02.07.2012) US (71) Applicant: BRISTOL-MYERS SQUIBB COMPANY [US/US]; P.O. Box 4000, Route 206 and ProvinceLine Road, Princeton, New Jersey 08543-4000 (US). (72) Inventors: LONBERG, Nils; c/o Bristol-Myers Squibb Company, 700 Bay Road, Redwood City, California 94063 (US). SRINIVASAN, Mohan; c/o Bristol-Myers Squibb Company, 700 Bay Road, Redwood City, California 94063 (US). (74) Agents: REMILLARD, Jane, E. et al.; Nelson Mullins Riley & Scarborough LLP, One Post Office Square, 30th Floor, Boston, MA 02109-2127 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available)'. AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available)'. ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(H)) — as to the applicant's entitlement to claim the priority of the earlier application (Rule 4.17(iii)) — of inventorship (Rule 4.17(iv)) Published: — with international search report (Art. 21(3)) — with sequence listing part of description (Rule 5.2(a)) (54) Title: OPTIMIZATION OF ANTIBODIES THAT BIND LYMPHOCYTE ACTIVATION GENE-3 (LAG-3), AND USES THEREOF 25- 20- 1 15- ig o 10- 4°C • Lag3.1 @ 4°C • Lag3.5 @ 4°C 00 i-H CJ 00 o o o CJ o & 12 Weeks (57) Abstract: The present invention provides isolated monoclonal antibodies that specifically bind LAG-3, and have optimized functional properties compared to previously described anti-LAG-3 antibodies, such as antibody 25F7 (US 2011/0150892 Al). These properties include reduced deamidation sites, while still retaining high affinity binding to human LAG-3, and physical (i.e., thermal and chemical) stability. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided, as well as immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies. The present invention also provides methods for detecting LAG-3, as well as methods for treating stimulating immune responses using an anti-LAG-3 antibody of the invention. Combination therapy, in which the antibodies are co-administered with at least one additional immunostimulatory antibody, also is provided.