Patent SG-11201806594Q-A (SG)
Title: Specific conjugation linkers, specific immunoconjugates thereof, methods of making and uses such conjugates thereof
Inventor: YANG QINGLIANG
IPC: C07D417/14
Filed: 2016-02-04
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property -, Organization M1111101110101011111 OH 110101011111110111011101011101 11111131011 11 International Bureau ... .... ..Yjd (10) International Publication Number ..... ....!;,„. (43) International Publication Date WO 2016/059622 A2 21 April 2016 (21.04.2016) WI P0 I P CT (51) International Patent Classification: Not classified (CN). HUANG, Yuanyuan; Room 2007, Building 2, No 452 Sixth St., Hangzhou Economic & Technological De- (21) International Application Number: velopment Area, Hangzhou, Zhejiang 310018 (CN). GM, PCT/IB2016/050580 Shun; Room 2015, Building 2, No 452 Sixth St., Hang- (22) International Filing Date: zhou Economic & Technological Development Area, 4 February 2016 (04.02.2016) Hangzhou City, Zhejiang 310018 (CN). ZHAO, Linyao; Room 2007, Building 2, No 452 Sixth St., Hangzhou Eco - (25) Filing Language: English nomic & Technological Development Area, Hangzhou (26) Publication Language: English City, Zhejiang 310018 (CN). YE, Hangbo; Room 2009, Building 2, No 452 Sixth St., Hangzhou Economic & (71) Applicants: SUZHOU M-CONJ BIOTECH CO., LTD. Technological Development Area, Hangzhou City, Zheji- [CN/CN]; Room 1108, Building 99, No. 999 Xinghu ang 310018 (CN). GUO, Huihui; Room 2001, Building 2, Street, Suzhou Industrial Park, Suzhou City, Jiangsu No 452 Sixth St., Hangzhou Economic & Technological 215123 (CN). HANGZHOU DAC BIOTECH CO, LTD Development Area, Hangzhou City, Zhejiang 310018 [CN/CN]; Building 12, No 260 Sixth Street, Zhongzi (CN). TONG, qianqian; Room 2016, Building 2, No 452 Technology Park, Hangzhou Economic & Technological Sixth St., Hangzhou Economy Development Area, Hang- Development Area, Hangzhou City, Zhejiang 310018 zhou City, Zhejiang 310018 (CN). CAO, Minjun; Room (CN). 2002, Building 2, No 452 Sixth St., Hangzhou Economic (72) Inventor; and & Technological Development Area, Hangzhou City, (71) Applicant : ZHAO, Robert Yongxin [US/US]; 7 Loring Zhejiang 310018 (CN). JIA, Junxiang; Room 2010, Road, Lexington, MA 02421 (US). Building 2, No 452 Sixth St., Hangzhou Economic & Technological Development Area, Hangzhou City, Zheji- (72) Inventors: YANG, Qingliang; Room 2009, Building 2, ang Room 2005, Buil (CN). YANG, Chengyu; Room No 452 Sixth St., Hangzhou Economic & Technological 2009, Building 2, No 452 Sixth St., Hangzhou Economic = Development Area, Hangzhou City, Zhejiang 310018 & Technological Development Area, Hangzhou City, [Continued on next page] = (54) Title: SPECIFIC CONJUGATION LINKERS, SPECIFIC IMMUNOCONJUGATES THEREOF, METHODS OF MAKING USES SUCH CONJUGATES THEREOF AND = (57) : The present invention relates to novel linkers containing a Nc ..,,, tor m im.,, , i. in . IT 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted n- i , N„.„,r. , . \" 'H' H ry'VV - Drag 63 FH\"''\" 0 64 ' 0 65 fumaric or maleic (trans (E)- or cis (Z)- butenedioic), or acetylenedicarboxyl N116/Mu( fU, o z , 04 ,,,, ,.th group for conjugation of a cytotoxic agent, and/or one or more different func- = -1 \" Dr\": g - 0 7=‘ Ell r '' 1 ; DD PIT FP tional molecules per linker to a cell-binding molecule, through bridge linking 66 6.5-8 5 - Tio - 1,°4 - . -: i s T ° s pairs of thiols on the cell-binding molecule specifically. The invention also ,,,,,A „ ki s_ i s mlb . i._30, 0_,. relates to methods of making such linkers, and of using such linkers in mak- = IT 0 \" 67 ing homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders. N =;. kl y^ , 44\".„ , ? k, ° 10TI - = FlO Y ; , . -- 7-( 91 / 4 „ , 11-4^04, 7 -- v i Dr 27 68 O = Antibody HO (\") Cil T( TP Drog 0 = pH 6.5-8.5 Zi N S 69 „D -l i t- its s 0 )-; 4 10H Drug 4 kl e,•^2 r- jj \",,kv ( VOIT Br ° 34 T‘ITS/F'DC ' 0 Br H 71 H0-7 -1 :Y\"\POH 65 Dr .,( 4 1 f.,\"4 . 5L y: N('N/V011 fi i TI = 35 72 --(\"Cisi 11 y TCEP „ el pH 6.5-8.5 -\"Byok.,.....,NA n=1-30, m = 0-100 69 0 4 4 ...,,,„ .. ,.., HO J.; OH Dm( g Q. , el N - i ,T1 v - i i 7 ,, 7 0 „ 28 , ,tD 0 C7 krody . D0 ,...4,0 st , kin ICEP pIT 6 5 , 8 5 Bru g , ,..k ... „.„A n'A n = I-30.m = 0-100 © H 0 69 \.... ,tD Figure E Il © N O WO 2016/059622 A2IMIOHOIIIMIHOHIC0 0 WIIINH0IR11101 IIII Zhejiang 310018 (CN). LI, Wenjun; Room 2017, Build- ing 2, No 452 Sixth St., Hangzhou Economic & Techno- logical Development Area, Hangzhou City, Zhejiang 310018 (CN). ZHOU, Xiaomai; Room 2015, Building 2, No 452 Sixth St., Hangzhou Economic & Technological Development Area, Hangzhou City, Zhejiang 310018 KP, KR, 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. (CN). XIE, Hongsheng; Room 2006, Building 2, No 452 (84) Sixth St., Hangzhou Economic & Technological Develop - ment Area, Hangzhou City, Zhejiang 310018 (CN). LIN, Chen; Room 2012, Building 2, No 452 Sixth St., Hang- zhou Economic & Technological Development Area, 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, Han zhou City Zhejian 310018 C GUO Zhixian , g (N). , g; Room 2014, Building 2, No 452 Sixth St., Hangzhou Economic & Technological Development Area, Hang- zhou City, Zhejiang 310018 (CN). YE, Zhicang; Room TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IF, 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). 2013, Building 2, No 452 Sixth St., Hangzhou Economic & Technological Development Area, Hangzhou City, Declarations under Rule 4.17: Zhejiang 310018 (CN). — as to the identity of the inventor (Rule 4.17(i)) (74) Common Representative: HANGZHOU DAC BI- OTECH CO, LTD; Zhao, Yongxin, Building 12, No 260 Sixth Street, Zhongzi Technology Park, Hangzhou Eco- nomic & Technological Development Area, Hangzhou — as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(ii)) of inventorship (Rule 4.17(iv)) City, Zhejiang 310018 (CN). Published: (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, IR, IS, JP, KE, KG, KN, upon request of the applicant, before the expiration of the time limit referred to in Article 21(2)(a) without international search report and to be republished upon receipt of that report (Rule 48.2(g))