INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 11111111111111111111111111111111111111111111111111111111111111111111111111111 Organization International Bureau (10) International Publication Number (43) International Publication Date ......0\' WO 2018/128691 Al 12 July 2018 (12.07.2018) WIP0 1 PCT (51) International Patent Classification: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, A01K 67/027 (2006.01) C12N 15/85 (2006.01) SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, C12N 15/90 (2006.01) CO7K 16/00 (2006.01) TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (21) International Application Number: (84) Designated States (unless otherwise indicated, for every PCT/US2017/060006 kind of regional protection available): ARIPO (BW, GH, (22) International Filing Date: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, 03 November 2017 (03.11.2017) UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (25) Filing Language: English EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, (26) Publication Language: English 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, (30) Priority Data: KM, ML, MR, NE, SN, TD, TG). 62/417,845 04 November 2016 (04.11.2016) US 62/567,932 04 October 2017 (04.10.2017) US Declarations under Rule 4.17: — (71) Applicant: REGENERON PHARMACEUTICALS, of inventorship (Rule 4.17(iv)) INC. [US/US]; 777 Old Saw Mill Rover Road, Tarrytown, Published: NY 10591-6706 (US). — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the (72) Inventors: GUO, Chunguang; c/o Regeneron Pharmaceu- claims and to be republished in the event of receipt of ticals, Inc., 777 Old Saw Mill Rover Road, Tarrytown, NY amendments (Rule 48.2(h)) 10591 (US). HARRIS, Faith; c/o Regeneron Pharmaceuti- cals, Inc., 777 Old Saw Mill Rover Road, Tarrytown, NY = 10591 (US). VORONINA, Vera; c/o Regeneron Pharma- _ ceuticals, Inc., 777 Old Saw Mill Rover Road, Tarrytown, NY 10591 (US). MCWHIRTER, John; c/o Regeneron =_ — Pharmaceuticals, Inc., 777 Old Saw Mill Rover Road, Tar- rytown, NY 10591 (US). LEVENKONA, Natasha; c/o Re- generon Pharmaceuticals, Inc., 777 Old Saw Mill Rover = Road, Tarrytown, NY 10591 (US). MACDONALD, Lynn; c/o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill Rover Road, Tarrytown, NY 10591 (US). TU, Naxin; c/o = _ Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill Rover = Road, Tarrytown, NY 10591 (US). MURPHY, Andrew, _ J.; c/o Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill = = Rover Road, Tarrytown, NY 10591 (US). Agent: SCHONEWALD, Stephanie, L.; Choate, Hall & (74) Stewart LLP, Two International Place, Boston, MA 02110 = (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, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, = — 1-1 MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, Il ON (54) Title: NON-HUMAN ANIMALS HAVING AN ENGINEERED IMMUNOGLOBULIN LAMBDA LIGHT CHAIN LOCUS GO (57) : Non-human animals (and/or non-human cells) and methods of using and making the same are provided, which non- e\'' human animals (and/or non-human cells) have a genome comprising human antibody-encoding sequences (i.e., immunoglobulin genes). 1-1 —. Non-human animals described herein express antibodies that contain human Igk light chains, in whole or in part. In particular, non- GO human animals provided herein are, in some embodiments, characterized by expression of antibodies that contain human Ig?. light 1-1 © chains, in whole or in part, that are encoded by human Igk light chain-encoding sequences inserted into an endogenous Igk light chain f'1 locus of said non-human animals. Methods for producing antibodies from non-human animals are also provided. 0
NON-HUMAN ANIMALS HAVING AN ENGINEERED IMMUNOGLOBULIN LAMBDA LIGHT CHAIN LOCUS