SG11201807885PA - Compositions and methods for making antibodies based on use of expression-enhancing loci - Google Patents

Abstract

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 111111101111 0 DOI 010111110101111 0 111 Iiv 1111 OEN Organization International Bureau (10) International Publication Number (43) International Publication Date ......0\" WO 2017/184832 Al 26 October 2017 (26.10.2017) WIPO I PCT (51) International Patent Classification: TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, C07K 16/00 (2006.01) C12N 15/90 (2006.01) KM, ML, MR, NE, SN, TD, TG). CO7K 16/46 (2006.01) (21) International Application Number: Declarations under Rule 4.17: PCT/US2017/028555 — as to applicant's entitlement to apply for and be granted a patent (Rule 4.1700) (22) International Filing Date: — as to the applicant's entitlement to claim the priority of the 20 April 2017 (20.04.2017) earlier application (Rule 4.17(iii)) — of inventorship (Rule 4.17(iv)) (25) Filing Language: English (26) Publication Language: English Published: — with international search report (Art. 21(3)) (30) Priority Data: — with sequence listing part of description (Rule 5.2(a)) 62/325,400 20 April 2016 (20.04.2016) US (71) Applicant: REGENERON PHARMACEUTICALS, INC. [US/US]; 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 (US). (72) Inventors: BABB, Robert; c/o Regeneron Pharmaceu- ticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 (US). BURAKOV, Darya; c/o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tar- rytown, NY 10591-6707 (US). CHEN, Gang; c/o Regen- eron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 (US). FANDL, James, P.; c/o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 (US). = — (74) Agent: GROLZ, Edward, W.; Scully, Scott, Murphy & Presser, 400 Garden City Plaza, Suite 300, Garden City, NY 11530 (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, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, 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, SA, 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 ARIPO GH, of regional protection available): (BW, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, - TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, .4 EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, N i MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, M co iv co 1-1 (54) Title: COMPOSITIONS AND METHODS FOR MAKING ANTIBODIES BASED ON USE OF EXPRESSION-ENHANCING IN LOCI 11 0 (57) : This invention relates to site-specific integration and expression of recombinant proteins in eukaryotic cells. In partic- \" ular, the invention includes compositions and methods for improved expression of antigen-binding proteins including monospecific C and bispecifc antibodies in eukaryotic cells, particularly Chinese hamster (Cricetulus griseus) cell lines, by employing multiple expres- sion-enhancing locus.