Patent SG-11201907288R-A (SG)
Title: Cysteine mutated antibodies for conjugation
Inventor: WAIGHT ANDREW
IPC: A61K39/395
Filed: 2018-02-28
Abstract: eINTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 07 September 2018 (07.09.2018) WIP0 I PCT Iiiimmomiolollmonolomomioolioluflionovoiml (10) International Publication Number WO 2018/160683 Al (51) International Patent Classification: A61K 39/395 (2006.01) C07K 16/46 (2006.01) A61K 38/02 (2006.01) Cl 2N 15/09 (2006.01) A61K 47/64 (2017.01) Cl 2P 21/02 (2006.01) A61K 47/68 (2017.01) (21) International Application Number: PCT/US2018/020206 (22) International Filing Date: 28 February 2018 (28.02.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/465,129 28 February 2017 (28.02.2017) US 62/561,151 20 September 2017 (20.09.2017) US (71) Applicant: SEATTLE GENETICS, INC. [US/US]; 21823 30th Drive SE, Bothell, Washington 98021 (US). (72) Inventors: WAIGHT, Andrew; 21823 30th Drive SE, Bothell, Washington 98021 (US). LEISKE, Chris; 21823 30th Drive SE, Bothell, Washington 98021 (US). BIECHELE, Travis; 21823 30th Drive SE, Bothell, Wash- ington 98021 (US). SUSSMAN, Django; 21823 30th Dri- ye SE, Bothell, Washington 98021 (US). BURKE, Patrick; 21823 30th Drive SE, Bothell, Washington 98021 (US). LEISKE, Jocelyn; 21823 30th Drive SE, Bothell, Wash- ington 98021 (US). (74) Agent: LIEBESCHUETZ, Joe et al.; Alston & Bird LLP, 101 South Tryon Street, Bank of America Plaza, Suite 4000, Charlotte, North Carolina 28280-4000 (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, 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 of regional protection available): ARIPO (BW, GH, 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, W O 20 18/ 160683 Al (54) Title: CYSTEINE MUTATED ANTIBODIES FOR CONJUGATION 100 - -e- e e e e SINGLE MUTATION e DOUBLE MUTATION (+S239C) 0 C-, 0, co FIG. 6 (57) : The invention provides modified heavy chain constant regions including a cysteine at position 295 by EU numbering and optionally at position 239 by EU numbering. These cysteine residues provide sites for conjugation to a drug or label. When both cysteines are present in a normal heterodimeric antibody format, there are four such sites per molecule of antibody allowing a stoichiometry of one molecule of antibody to four of drug or label. Selection of the cysteine at position 295 with or without cysteine at position 239 is advantageous over cysteines at many other positions due to ease of expression, stability and cytotoxicity. [Continued on next page] 80 - % INTAC T TU BU LYS IN 60 - 40 - 20 - Co) Cr) Cr) WO 2018/160683 Al MIDEDIM011010EIREEM0MOH1001111111111111111111111110111111111111 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 the identity of the inventor (Rule 4.17(0) as to the applicant's entitlement to claim the priority of the earlier application (Rule 4.17(iii)) Published: — with international search report (Art. 21(3)) with sequence listing part of description (Rule 5.2(a))