Antibody constructs for CD70 and CD3

Patent metadata

Field	Value
Publication number	US-10851170-B2
Application number	US-201615225282-A
Country	US
Kind code	B2
Filing date	Aug 1, 2016
Priority date	Jul 31, 2015
Publication date	Dec 1, 2020
Grant date	Dec 1, 2020

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

The invention claimed is:

1. 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, 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.

2. The antibody construct according to claim 1 , wherein the first binding domain comprises a VH region comprising the amino acid sequence of SEQ ID NO: 1148.

3. The antibody construct according to claim 1 , wherein the first binding domain comprises a VL region comprising the amino acid sequence of SEQ ID NO: 1149.

4. The antibody construct according to claim 1 , wherein the first binding domain comprises a VH region and a VL region comprising the pair of amino acid sequences, respectively, of SEQ ID NOs: 1148 and 1149.

5. The antibody construct according to claim 1 , wherein the first binding domain comprises a polypeptide comprising the amino acid sequence of SEQ ID NO: 1150.

6. The antibody construct according to claim 1 comprising a polypeptide comprising the amino acid sequence of SEQ ID NO: 1151.

7. The antibody construct according to claim 1 comprising a polypeptide comprising the amino acid sequence of SEQ ID NO: 1710.

8. The antibody construct according to claim 1 , wherein the first binding domain further binds to macaque CD70.

9. The antibody construct according to claim 1 , wherein the second binding domain binds to human CD3 epsilon and to Callithrix jacchus, Saguinus Oedipus or Saimiri sciureus CD3 epsilon.

10. The antibody construct according to claim 1 , wherein the antibody construct is in a format selected from the group consisting of (scFv) 2 , scFv-single domain mAb, diabodies and oligomers of the foregoing formats.

11. A polynucleotide encoding the antibody construct according to claim 1 .

12. A vector comprising the polynucleotide according to claim 11 .

13. A host cell transformed or transfected with the polynucleotide according to claim 11 .

14. A process for producing an 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, said process comprising culturing the host cell of claim 13 under conditions allowing the expression of said antibody construct, and recovering the produced antibody construct from the culture.

15. A pharmaceutical composition comprising the antibody construct according to claim 1 and a carrier, stabilizer, excipient, diluent, solubilizer, surfactant, emulsifier, preservative, or adjuvant.

16. A kit comprising the antibody construct according to claim 1 and a recipient and, optionally, directions for use.

17. The antibody construct according to claim 8 , wherein the macaque CD70 is Macaca fascicularis CD70.

18. The antibody construct according to claim 1 , wherein the second binding domain comprises an amino acid sequence selected from the group consisting of: SEQ ID NO: 835, SEQ ID NO: 844, SEQ ID NO: 853, SEQ ID NO: 862, SEQ ID NO: 871, SEQ ID NO: 880, SEQ ID NO: 889, SEQ ID NO: 898, SEQ ID NO: 907, SEQ ID NO: 916, and SEQ ID NO: 919.

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