Patent SG-11201902857S-A (SG)
Title: Activatable anti-ctla-4 antibodies and uses thereof
Inventor: TIPTON KIMBERLY ANN
IPC: C07K19/00
Filed: 2017-11-02
Abstract: 40 60 Days Post Implantation 'gr ' E 2500- 10/10 TF nE 2500 E 2000- E 2000 E 1500- E 1500 7 , 1000- 0 1000 500- 0 E 500 0 0 20 40 60 Days Post Implantation 8/10 TF 20 40 60 Days Post Implantation rTe E E 0 0 2500 2000 1500 1000 500 0 FIG. 9D YV23 2001 9/10 TF 20 40 60 Days Post Implantation FIG. 9E YV24 2001 2500 2000 1500 1000 500 0 FIG. 9F YV39 2001 2500 2000 1500 1000 500 0 Fsi E E E E C . 7 2500 E 2000 E 1500 0 1000 8 500 E 0 7/10 TF 20 40 60 Days Post Implantation E ‘ E ) o 0 E I- 10/101T 20 40 60 Days Post Implantation (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) CORRECTED VERSION (19) World Intellectual Property Organization International Bureau (43) International Publication Date 1111111111110110101011111011110 100111MIONOITEREMOVIO# (10) International Publication Number WO 2018/085555 A8 11 May 2018 (11.05.2018) WIPO I PCT (51) International Patent Classification: CO7K 16/28 (2006.01) A61K 39/395 (2006.01) C07K 19/00 (2006.01) A61P 35/00 (2006.01) (21) International Application Number: PCT/US2017/059740 (22) International Filing Date: 02 November 2017 (02.11.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/417,212 03 November 2016 (03.11.2016) US (71) Applicants: BRISTOL-MYERS SQUIBB COMPANY [US/US]; Rt. 206 & Province Line Road, Princeton, New Jersey 08543 (US). CYTOMX THERAPEUTICS, INC. [US/US]; 151 Oyster Point Boulevard, Suite 400, South San Francisco, California 94080 (US). (72) Inventors: TIPTON, Kimberly Ann; c/o CytomX Thera- peutics, Inc., 151 Oyster Point Boulevard, Suite 400, South San Francisco, California 94080 (US). WEST, James William; c/o CytomX Therapeutics, Inc., 151 Oyster Point Boulevard, Suite 400, South San Francisco, California 94080 (US). DESHPANDE, Shrikant; c/o Bristol-Myers Squibb Company, 700 Bay Road, Redwood City, California 94063 (US). ENGELHARDT, John J.; c/o Bristol-Myers Squibb Company, 700 Bay Road, Redwood City, California 94063 (US). (74) Agent: CALVO, Paul A. et al.; Sterne, Kessler, Goldstein & Fox P.L.L.C., 1100 New York Avenue, NW, Washing- ton, District of Columbia 20005 (US). (54) Title: ACTIVATABLE ANTI-CTLA-4 ANTIBODIES AND USES THEREOF FIG. 9A Control mg2a FIG. 9B !pi mg2a (YV1) FIG. 9C YV04 2001 (57) : Provided herein are activatable anti-human CTLA-4 antibodies comprising a heavy chain comprising a VH domain and a light chain comprising a masking moiety (MM), a cleavable moiety (CM), and a VL domain. Such activatable anti-human CTLA-4 00 antibodies have CTLA-4 binding activity in the tumor microenvironment, where the masking moiety is removed by proteolytic cleavage O of the cleavable moiety by tumor-specific proteases, but exhibit greatly reduced binding to CTLA-4 outside the tumor. In this way, the 00 activatable anti-human CTLA-4 antibodies of the present invention retain anti-tumor activity while reducing the side effects associated O with anti-CTLA-4 activity outside the tumor. O [Continued on next page] WO 2018/085555 A8 MIDEDIM01101 DIDIRE10111011111111111HHH11111111101111111111 (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, 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: — of inventorship (Rule 4.17(iv)) Published: with international search report (Art. 21(3)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) with sequence listing part of description (Rule 5.2(a)) (48) Date of publication of this corrected version: 31 May 2018 (31.05.2018) (15) Information about Correction: see Notice of 31 May 2018 (31.05.2018)