Antibody constructs for cd70 and cd3

Patent metadata

Field	Value
Publication number	US-2021284748-A1
Application number	US-202017084088-A
Country	US
Kind code	A1
Filing date	Oct 29, 2020
Priority date	Jul 31, 2015
Publication date	Sep 16, 2021
Grant date	—

Abstract

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human CD70 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

First claim

1 - 21 . (canceled)

22 . A method of treating or ameliorating a tumor or cancer in a subject having a tumor or cancer expressing CD70 comprising administering to the subject an effective amount of a bispecific antibody construct comprising a first binding domain which binds to human CD70 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell and at least macaque CD3.

23 - 24 . (canceled)

25 . The method of claim 22 , 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, wherein
said CDR-H1 has the amino acid sequence X 1 YX 2 MX 3 (SEQ ID NO: 1869), wherein X 1 is S, T or V, X 2 is A or S, and X 3 is S or N; said CDR-H2 has the amino acid sequence X 1 ISX 2 SGGX 3 X 4 X 5 X 6 AESVX 7 G (SEQ ID NO: 1870), wherein X 1 is A, Y, V, L, or T, X 2 is G or S, X 3 is R, Y, S, G or I, X 4 is T, I, P, or A, X 5 is F, Y, N, Q or D, X 6 is Y or F, and X 7 is E, K or Q; said CDR-H3 has the amino acid sequence X 1 DYSNYX 2 X 3 FDY (SEQ ID NO: 1871), wherein X 1 is H, G or V, X 2 is P, A, L or F, and X 3 is Y or F; said CDR-L1 has the amino acid sequence RAX 1 QX 2 X 3 X 4 X 5 X 6 X 7 LX 8 (SEQ ID NO: 1872), wherein X 1 is S or G, X 2 is S or G, X 3 is I or V, X 4 is R, S or no amino acid, X 5 is S or G, X 6 is S, N, T or D, X 7 is Y or no amino acid, and X 8 is A or G; said CDR-L2 has the amino acid sequence X 1 X 2 SX 3 X 4 X 5 X 6 (SEQ ID NO: 1873), wherein X, is G or A, X 2 is A or S, X 3 is S, T, N or I, X 4 is R or L, X 5 is A or Q, and X 6 is T or S; and said CDR-L3 has the amino acid sequence QQYX 1 X 2 X 3 PX 4 X 5 (SEQ ID NO: 1874), wherein X 1 is G, Y or F, X 2 is D, S, Y, I or A, X 3 is L, T, S or Y, X 4 is F, L, P or I, and X 5 is T or P.

26 . The method of claim 22 , 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, wherein
said CDR-H1 has the amino acid sequence SYSMN (SEQ ID NO: 1422) or X1YAMS (SEQ ID NO: 1875), wherein X1 is S, T or V; said CDR-H2 has an amino acid sequence selected from the group consisting of yisssggyiyyaesvkg (SEQ ID NO: 1423), visgsggitdfaesvkg (SEQ ID NO: 1367) and X1ISGSGGX2X3X4YAESVX5G (SEQ ID NO: 1876), wherein X1 is A, V, L or T, X2 is R, S, or G, X3 is T, P or A, X4 is F, N, Y or Q, and X5 is E, K, or Q; said CDR-H3 has an amino acid sequence selected from the group consisting of gdysnyayfdy (SEQ ID NO: 1424), hdysnyfffdy (SEQ ID NO: 1368), and X1 DYSNYX2X3FDY (SEQ ID NO: 1877), wherein X1 is H or V, X2 is P, L or A, and X3 is Y or F; said CDR-L1 has the amino acid sequence RASQGISNYLA (SEQ ID NO: 1425) or RAX1QX2X3X4X5X6YLX7 (SEQ ID NO: 1878), wherein X1 is S or G, X2 is S or G, X3 is I or V, X4 is R or S, X5 is S or G, X6 is S, T, N or D, and X7 is A or G; said CDR-L2 has the amino acid sequence AASXLQS (SEQ ID NO: 1879), wherein X is T or I, or GX1SX2RAT (SEQ ID NO: 1880), wherein X1 is A or S, and X2 is S or N; and said CDR-L3 has an amino acid sequence selected from the group consisting of qqyystplt (SEQ ID NO: 1427), qqyfaypit (SEQ ID NO: 1371), and QQYGX1X2PX3X4 (SEQ ID NO: 1881), wherein X1 is D, Y, S or I, X2 is L, S or T, X3 is F or P, and X4 is T or P.

27 . The method of claim 22 , 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, wherein
said CDR-H1 has the amino acid sequence X1YAMS (SEQ ID NO: 1875), wherein X1 is S, T or V; said CDR-H2 has the amino acid sequence X1 ISGSGGX2X3X4YAESVX5G (SEQ ID NO: 1876), wherein X1 is A, V, L or T, X2 is R, S, or G, X3 is T, P or A, X4 is F, N, Y or Q, and X5 is E, K, or Q; said CDR-H3 has the amino acid sequence X1 DYSNYX2X3FDY (SEQ ID NO: 1877), wherein X1 is H or V, X2 is P, L or A, and X3 is Y or F; said CDR-L1 has the amino acid sequence RAX1QX2X3X4X5X6YLX7 (SEQ ID NO: 1878), wherein X1 is S or G, X2 is S or G, X3 is I or V, X4 is R or S, X5 is S or G, X6 is S, T, N or D, and X7 is A or G; said CDR-L2 has the amino acid sequence GX1SX2RAT (SEQ ID NO: 1880), wherein X1 is A or S, and X2 is S or N; and said CDR-L3 has the amino acid sequence QQYGX1X2PX3X4 (SEQ ID NO: 1881), wherein X1 is D, Y, S or I, X2 is L, S or T, X3 is F or P, and X4 is T or P.

28 . The method of claim 22 , 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, wherein
said CDR-H1 has an amino acid sequence selected from the group consisting of SYAMS (SEQ ID NO: 1044), TYAMS (SEQ ID NO: 1142), VYAMS (SEQ ID NO: 1436), and SYSMN (SEQ ID NO: 1422); said CDR-H2 has an amino acid sequence selected from the group consisting of aisgsggrtfyaesveg (SEQ ID NO: 1087), visgsggrpnyaesvkg (SEQ ID NO: 1045), aisgsggstfyaesvkg (SEQ ID NO: 1171), aisgsggstfyaesvqg (SEQ ID NO: 1213), aisgsgggtfyaesvkg (SEQ ID NO: 1227), Iisgsggrtyyaesvkg (SEQ ID NO: 1241), aisgsggraqyaesvqg (SEQ ID NO: 1255), tisgsggstfyaesvkg (SEQ ID NO: 1437), yisssggyiyyaesvkg (SEQ ID NO: 1423), and visgsggitdfaesvkg (SEQ ID NO: 1367); said CDR-H3 has an amino acid sequence selected from the group consisting of hdysnypyfdy (SEQ ID NO: 1088), vdysnylffdy (SEQ ID NO: 1046), hdysnyayfdy (SEQ ID NO: 1438), gdysnyayfdy (SEQ ID NO: 1424), and hdysnyfffdy (SEQ ID NO: 1368); said CDR-L1 has an amino acid sequence selected from the group consisting of rasqsirssyla (SEQ ID NO: 1089), rasqsvrstyla (SEQ ID NO: 1145), ragqsvrssylg (SEQ ID NO: 1047), rasqsvrssyla (SEQ ID NO: 1173), rasqsvrsnyla (SEQ ID NO: 1187), rasqsvrgnyla (SEQ ID NO: 1215), rasqsirsnyla (SEQ ID NO: 1229), rasqsvssnla (SEQ ID NO: 1257), rasqgvrsdyla (SEQ ID NO: 1271), rasqgvrssyla (SEQ ID NO: 1341), and rasqgisnyla (SEQ ID NO: 1369); said CDR-L2 has an amino acid sequence selected from the group consisting of GASSRAT (SEQ ID NO: 1048), GASNRAT (SEQ ID NO: 1244), GSSSRAT (SEQ ID NO: 1258), AASTLQS (SEQ ID NO: 1426), and AASILQS (SEQ ID NO: 1370); and said CDR-L3 has an amino acid sequence selected from the group consisting of qqygdlpft (SEQ ID NO: 1091); qqygysppt (SEQ ID NO: 1049), qqygyspft (SEQ ID NO: 1217), qqygsspft (SEQ ID NO: 1231), qqygisppt (SEQ ID NO: 1245), qqygssppp (SEQ ID NO: 1259), qqygstppt (SEQ ID NO: 1273), qqygssppt (SEQ ID NO: 1343), qqyystplt (SEQ ID NO: 1427), and qqyfaypit (SEQ ID NO: 1371).

29 . The method of claim 22 , 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, wherein said CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2 and CDR-L3 are selected from the group consisting of: SEQ: ID NOs: 1044-1049; SEQ: ID NOs: 1086-1091; SEQ: ID NOs: 1142-1147; SEQ: ID NOs: 1170-1175; SEQ: ID NOs: 1184-1189; SEQ: ID NOs: 1212-1217; SEQ: ID NOs: 1226-1231; SEQ: ID NOs: 1240-1245; SEQ: ID NOs: 1254-1259; SEQ: ID NOs: 1268-1273; SEQ: ID NOs: 1338-1343; SEQ: ID NOs: 1352-1357; SEQ: ID NOs: 1366-1371; SEQ: ID NOs: 1422-1427; and SEQ: ID NOs: 1436-1441.

30 . The method of claim 22 , 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, wherein
said CDR-H1 comprises the amino acid sequence of SEQ ID NO: 1142; said CDR-H2 comprises the amino acid sequence of SEQ ID NO: 1143; said CDR-H3 comprises the amino acid sequence of SEQ ID NO: 1144; said CDR-L1 comprises the amino acid sequence of SEQ ID NO: 1145; said CDR-L2 comprises the amino acid sequence of SEQ ID NO: 1146; and said CDR-L3 comprises the amino acid sequence of SEQ ID NO: 1147.

31 . The method of claim 22 , wherein the first

Assignees

• Amgen Res Munich Gmbh
• Amgen Inc

Inventors

• Raum Tobias
• Blümel Claudia
• Deisting Wibke
• Hoffmann Patrick
• LUTTERBÜSE Ralf
• Nahrwold Elisabeth
• Nolan-Stevaux Olivier
• Panzer Marc

Classifications

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/90

  characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin · CPC title

• C07K2317/64

  comprising a combination of variable region and constant region components · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title