US Patent No. 10,766,969

BINDING MOLECULES FOR BCMA AND CD3


Patent No. 10,766,969
Issue Date September 08, 2020
Title Binding Molecules For Bcma And Cd3
Inventorship Peter Kufer, Munich (DE)
Tobias Raum, Munich (DE)
Patrick Hoffmann, Munich (DE)
Roman Kischel, Munich (DE)
Ralf Lutterbuese, Munich (DE)
Doris Rau, Munich (DE)
Paul Adam, Ingelheim am Rhein (DE)
Eric Borges, Ingelheim am Rhein (DE)
Barbara Hebeis, Ingelheim am Rhein (DE)
Susanne Hipp, Ingelheim am Rhein (DE)
Assignee Amgen Inc., Thousand Oaks, CA (US)

Claim of US Patent No. 10,766,969

1. A binding molecule which is at least bispecific comprising a first and a second binding domain, wherein(a) the first binding domain comprises a variable heavy chain and a variable light chain and binds to B cell maturation antigen (BCMA), wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2, and CDR-H3 and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, and at least five of the six CDRs selected from the group consisting of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 have sequences as follows:
(i) CDR-H1 as depicted in SEQ ID NO: 1, SEQ ID NO: 161, or SEQ ID NO: 311;
(ii) CDR-H2 as depicted in SEQ ID NO: 2, SEQ ID NO: 12, SEQ ID NO: 162, SEQ ID NO: 212, SEQ ID NO: 312, SEQ ID NO: 322, SEQ ID NO: 352, SEQ ID NO: 362, SEQ ID NO: 582, SEQ ID NO: 622, or SEQ OD NO: 752;
(iii) CDR-H3 as depicted in SEQ ID NO: 3, SEQ ID NO: 163, SEQ ID NO: 313, SEQ ID NO: 323, or SEQ ID NO: 623;
(iv) CDR-L1 as depicted in SEQ ID NO: 4, SEQ ID NO: 164, SEQ ID NO: 314, SEQ ID NO: 624, SEQ ID NO: 774, SEQ ID NO: 974, or SEQ ID NO: 994;
(v) CDR-L2 as depicted in SEQ ID NO: 5, SEQ ID NO: 165, SEQ ID NO: 315, or SEQ ID NO: 625; and
(vi) CDR-L3 as depicted in SEQ ID NO: 6, SEQ ID NO: 166, SEQ ID NO: 176, SEQ ID NO: 316, SEQ ID NO: 626, SEQ ID NO: 656, SEQ ID NO: 676, SEQ ID NO: 776, SEQ ID NO: 816, SEQ ID NO: 966, or SEQ ID NO: 996, and
wherein not more than one of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 has a sequence as follows:
(i) CDR-H1 comprises amino acid sequence X1X2X3X4X5 which has 80% or greater identity to a sequence selected from the group consisting of NYDMA (SEQ ID NO:1), NFDMA (SEQ ID NO:161), and NHIIH (SEQ ID NO:311), and where X1 is N; X2 is Y, F, or H; X3 is D or I; X4 is M or I; and X5 is A or H;
(ii) CDR-H2 comprises amino acid sequence X6X7X8X9X10X11X12X13X14X15X16X17X18X19X20X21X22 which has 80% or greater identity to a sequence selected from the group consisting of: SIITSGDATYYRDSVKG (SEQ ID NO:2), SIITSGDMTYYRDSVKG (SEQ ID NO:12), SITTGADHAIYADSVKG (SEQ ID NO:162), SITTGADHAIYAESVKG (SEQ ID NO:212), SIITSGGDNYYRDSVKG (SEQ ID NO:582), SITTGGGDTYYADSVKG (SEQ ID NO:732), YINPYPGYHAYNEKFQG (SEQ ID NO:312), YINPYPGYHAYNQKFQG (SEQ ID NO:352), YINPYDGWGDYNEKFQG (SEQ ID NO:322), YINPYDGWGDYNQKFQG (SEQ ID NO:362), and SISTRGDITSYRDSVKG (SEQ ID NO: 622), and where X6 is S or Y; X7 is I; X8 is I, T, N, or S; X9 is T or P; X10 is S, Y, R, or G; is G, A, D, or P; X12 is D or G; X13 is A, M, H, D, Y, W or I; X14 is T, A, N, H, or G; X15 is Y, I, A, D or S; X16 is Y; X17 is R, A, or N; X18 is D, E, or Q; X19 is S or K; X20 is V or F; X21 is K or Q; and X22 is G;
(iii) CDR-H3 comprises amino acid sequence X23X24X25X26X27X28X29X30X31X32X33X34 which has 80% or greater identity to a sequence selected from the group consisting of: HDYYDGSYGFAY (SEQ ID NO:3), HGYYDGYHLFDY (SEQ ID NO:163), QDYYTDYMGFAY (SEQ ID NO:623), DGYYRDTDVLDY (SEQ ID NO:313), and DGYYRDADVLDY (SEQ ID NO:323), and where X23 is H, Q or D; X24 is D or G; X25 is Y; X26 is Y; X27 is D, T or R; X28 is G or D; X29 is S, Y, T or A; X30 is Y, H, M or D; X31 is G, L, or V; X32 is F or L; X33 is A or D; and X34 is Y;
(iv) CDR-L1 comprises amino acid sequence X35X36X37X38X39X40X41X42X43X44X45 which has 80% or greater identity to a sequence selected from the group consisting of: KASQSVGINVD (SEQ ID NO:4), RASQGISNYLN (SEQ ID NO:164), RASEDIYNGLA (SEQ ID NO:624), RASQGISNHLN (SEQ ID NO:774), RANQGISNNLN (SEQ ID NO:974), RASQGISNNLN (SEQ ID NO:994), and QASQDISNYLN (SEQ ID NO:314), and wherein X35 is K, R or Q; X36 is A; X37 is S or N; X38 is Q or E; X39 is S, G, or D; X40 is V or I; X41 is G, S, or Y; X42 is I or N; X43 is N, Y, G, or H; X44 is V or L; and X45 is D, N, or A;
(v) CDR-L2 comprises amino acid sequence X46X47X48X49X50X51X52 which has 80% or greater identity to a sequence selected from the group consisting of: GASNRHT (SEQ ID NO:5), YTSNLQS (SEQ ID NO:165), GASSLQD (SEQ ID NO:625), and YTSRLHT (SEQ ID NO:315), and wherein X46 is G or Y; X47 is A or T; X48 is S; X49 is N, S, or R; X50 is R or L; X51 is H or Q; and X52 is T, S, or D; or
(vi) CDR-L3 comprises amino acid sequence X53X54X55X56X57X58X59X60X61 which has 80% or greater identity to a sequence selected from the group consisting of: LQYGSIPFT (SEQ ID NO:6), QQYDISSYT (SEQ ID NO:166), MGQTISSYT (SEQ ID NO:176), QQGNTLPWT (SEQ ID NO:316), QQSYKYPLT (SEQ ID NO:626), AGPHKYPLT (SEQ ID NO:656), QQSRNYQQT (SEQ ID NO:676), QQYFDRPYT (SEQ ID NO:776), QQYSNLPYT (SEQ ID NO:816), QQFTSLPYT (SEQ ID NO:966), and QQFAHLPYT (SEQ ID NO:996), and wherein X53 is L, Q, M, or A; X54 is Q or G; X55 is G, P, Y, Q, S, or F; X56 is G, D, T, N, Y, H, R, F, S, or A; X57 is S, I, T, K, N, D, or H; X58 is I, S, L, Y, or R; X59 is P, S, or Q; X60 is F, Y, W, L, or Q and X61 is T; and
(b) the second binding domain comprises a variable heavy chain and a variable light chain and binds to the human T cell CD3 receptor complex.