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    HUMANIZED ANTI-PSMA ANTIBODY
    10.
    发明申请
    HUMANIZED ANTI-PSMA ANTIBODY 审中-公开

    公开(公告)号：WO2022238522A1

    公开(公告)日：2022-11-17

    申请号：PCT/EP2022/062868

    申请日：2022-05-12

    申请人： TECHNISCHE UNIVERSITÄT MÜNCHEN ,  INSTITUTE OF BIOTECHNOLOGY CAS, V.V.I.

    发明人： NOVÁKOVÁ, Zora ,  BARINKA, Cyril ,  SKERRA, Arne ,  PĚCHOUČKOVÁ, Šárka

    IPC分类号： C07K16/30 ,  A61K39/00 ,  A61K2039/505 ,  C07K16/3069 ,  C07K2317/24 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/92

    摘要： The present invention relates to an antibody binding to prostate-specific membrane antigen (PSMA), wherein the antibody comprises the VH region determined by the amino acid sequence of EVQLVESGGGLVQPGGSLRLSCAASGYAF(X1)(X2)(X3)W(X4)NWVRQAPGKGLEWISRIYPG(X5)(X6)(X7)(X8)NY(X9)(X10)KFKGKATISADKSKNTLYLQMNSLRAEDTAVYYCARGEWYLYYFDYWGQGTLVT VSS (SEQ ID NO: 30), wherein for (X1) to (X3) at least one applies: (X1) is G, A, V, L, I, Y, H, K, R, Q, N, E, D, S or T, preferably G, A, Y, H, K, R, Q, N, E, D, S or T, more preferably N or Q, and most preferably Q, (X2) is P or T, and (X3) is G, A, V, L, I, Y, H, K, R, Q, N, E, D, T or S and is preferably S, with the proviso that (X1) to (X3) are not N-(Z)-S/T, wherein (Z) can be any amino acid but not P, or wherein (X1) to (X3) are N-T-S; (X4) is M, I or L and preferably M; for (X5) and (X6) at least one applies: (X5) is G, A, V, L, I, Y, H, Q, N, E, D, S or T and preferably D or E, and (X6) is G, A, V, L, I, H, K, R, Q, N, E, D, S or T, preferably G or A, with the proviso that (X5)-(X6) are not D-S, N-G or N-S; for (X7) and (X8) at least one applies: (X7) is G, A, V, L, I, Y, H, Q, N, E, D, S or T, preferably D, E or S, and (Xs) is G, A, V, L, H, Q, N, E, D, S or T and preferably T or A, with the proviso that (X7)-(X8) are not D-G, D-S, N-G or N-S; for (X9) and (X10) at least one applies: (X9) is G, A, V, L, I, Y, H, K, R, Q, N, E, D, S or T and preferably N, E or Q, and (X10) is G, A, V, L, I, Y, H, K, R, Q, N, E, D, S or T, preferably G or A, with the proviso that (X9)-(X10) are not D-G, D-S or N-S; or an amino acid sequence being at least 90%, preferably at least 95% identical thereto; and the VL region determined by the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCSASQGI(XII)(XI2)FLTWYQQKPGKALKLLIYYTSSLHSGVPSRFSG SGSGTDYTLTISSLQPEDFATYYCQQYSNLPFTFGQGTKVEIK (SEQ ID NO: 31), wherein for (X11) and (X12) at least one applies: (X11) is G, A, V, L, I, Y, H, K, R, Q, N, E, D, S or T, preferably N, D, E or Q, and (X12) is G, A, V, L, I, Y, H, K, R, Q, N, E, D, S or T and preferably N, with the proviso that (X11)-(X12) are not D-G, D-S, N-G or N-S; or an amino acid sequence being at least 90%, preferably at least 95% identical thereto, provided that the three CDRs of the VH region are determined by the amino acid sequences of GYAF(X1)(X2)(X3)W(X4)N (SEQ ID NO: 32), wherein for (X1) to (X3) at least one applies: (X1) is G, A, V, L, I, Y, H, K, R, Q, N, E, D, S or T, preferably G, A, Y, H, K, R, Q, N, E, D, S or T, more preferably N or Q, and most preferably Q, (X2) is P or T, and (X3) is G, A, V, L, I, Y, H, K, R, Q, N, E, D, T or S and is preferably S, with the proviso that (X1) to (X3) are not N-(Z)-S/T, wherein (Z) can be any amino acid but not P, or wherein (X1) to (X3) are N-T-S; and (X4) is M, I or L and preferably M, RIYPG(X5)(X6)(X7)(X8)NY(X9)(X10)KFK (SEQ ID NO: 33), wherein for (X5) and (X6) at least one applies: (X5) is G, A, V, L, I, Y, H, Q, N, E, D, S or T and preferably D or E, and (X6) is G, A, V, L, I, H, K, R, Q, N, E, D, S or T, preferably G or A, with the proviso that (X5)-(X6) are not D-S, N-G or N-S; for (X7) and (X8) at least one applies: (X7) is G, A, V, L, I, Y, H, Q, N, E, D, S or T, preferably D, E or S, and (X8) is G, A, V, L, H, Q, N, E, D, S or T and preferably T or A, with the proviso that (X7)-(X8) are not D-G, D-S, N-G or N-S; for (X9) and (X10) at least one applies: (X9) is G, A, V, L, I, Y, H, K, R, Q, N, E, D, S or T and preferably N, E or Q, and (X10) is G, A, V, L, I, Y, H, K, R, Q, N, E, D, S or T, preferably G or A, with the proviso that (X9)-(X10) are not D-G, D-S or N-S; and SEQ ID NO: 5, and the three CDRs of the VL region are determined by the amino acid sequences of SASQGI(X11)(X12)FLT (SEQ ID NO: 34), wherein for (X11) and (X12) at least one applies: (X11) is G, A, V, L, I, Y, H, K, R, Q, N, E, D, S or T, preferably N, D, E or Q, and (X12) is G, A, V, L, I, Y, H, K, R, Q, N, E, D, S or T and preferably N, with the proviso that (X11)-(X12) are not D-G, D-S, N-G or N-S; SEQ ID NO: 7, and SEQ ID NO: 8.