Compositions comprising cross-species-specific antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-11925684-B2
Application number	US-201816116293-A
Country	US
Kind code	B2
Filing date	Aug 29, 2018
Priority date	Oct 11, 2005
Publication date	Mar 12, 2024
Grant date	Mar 12, 2024

Abstract

The present invention relates to uses of bispecific antibodies exhibiting cross-species specificity for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of the same in non-human species and humans. The present invention moreover relates to methods for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of said bispecific antibodies exhibiting cross-species specificity. The present invention also relates to methods of measuring the biological activity and/or efficacy of such bispecific antibodies exhibiting cross-species specificity. In addition, the present invention relates to pharmaceutical compositions comprising bispecific single chain antibodies exhibiting cross-species specificity and to methods for the preparation of pharmaceutical compositions comprising said bispecific single chain antibodies exhibiting cross-species specificity for the treatment of diseases.

First claim

The invention claimed is:

1. A bispecific single chain antibody comprising:
(i) a first binding domain which binds to primate CD3 comprising
CDR-L1 (SEQ ID NO: 118), CDR-L2 (SEQ ID NO: 117), and CDR-L3 (SEQ ID NO: 116) and CDR-H1 (SEQ ID NO: 115), CDR-H2 (SEQ ID NO: 114) and CDR-H3 (SEQ ID NO: 112) or (SEQ ID NO: 113),
wherein the first binding domain comprises a VH region comprising the amino acid sequence set forth in SEQ ID NO: 110 and/or a VL region comprising the amino acid sequence set forth in SEQ ID NO: 168; and

(ii) a second binding domain binding to a cell surface antigen.

2. The bispecific single chain antibody of claim 1 , wherein said first binding domain binds to an epitope of human and non-chimpanzee primate CD3 comprising the amino acid sequence of “FSEXE” (SEQ ID NO: 204), wherein “X” represents L (Leucine) or M (Methionine).

3. The bispecific single chain antibody of claim 1 , wherein said first binding domain is located C-terminally or N-terminally to the second binding domain.

4. The bispecific single chain antibody of claim 1 , wherein the second binding domain binds to a human cell surface antigen and to a non-chimpanzee primate homolog of the cell surface antigen.

5. The bispecific single chain antibody of claim 1 , wherein the cell surface antigen is a tumor antigen.

6. The bispecific single chain antibody of claim 1 , wherein the first binding domain comprises a VH region comprising the amino acid sequence set forth in SEQ ID NO: 110.

7. The bispecific single chain antibody of claim 1 , wherein the first binding domain comprises a VL region comprising the amino acid sequence set forth in SEQ ID NO: 168.

8. The bispecific single chain antibody of claim 1 , wherein the VH region of the first binding domain comprises or consists of the amino acid sequence set forth in SEQ ID NO: 110 and the VL region of the first binding domain comprises or consists of the amino acid sequence set forth in SEQ ID NO: 168.

9. The bispecific single chain antibody of claim 5 , wherein said tumor antigen is EpCAM, EGFR, EGFRvIII or Carboanhydrase IX (MN/CA IX).

10. The bispecific single chain antibody of claim 1 , wherein the primate is a baboon, marmoset or an old world monkey.

11. The bispecific single chain antibody of claim 10 , wherein the old world monkey is a monkey of the macaque genus.

12. The bispecific single chain antibody of claim 1 , wherein the primate CD3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 135, 136, 144 or 145.

13. The bispecific single chain antibody of claim 1 , wherein at least one of said first or second binding domains is human, humanized, CDR-grafted and/or deimmunized.

14. A composition comprising the bispecific single chain antibody of claim 1 and a carrier, stabilizer, and/or excipient.

15. The bispecific single chain antibody of claim 1 , wherein the first binding domain comprises a single chain antibody fragment (scFv) comprising:
(a) the amino acid sequence set forth in SEQ ID NO: 170; or
(b) an amino acid sequence encoded by the nucleotide sequence set forth in SEQ ID NO: 169.

16. A bispecific single chain antibody comprising:
(i) a first binding domain which binds to primate CD3 comprising CDR-L1 (SEQ ID NO: 118), CDR-L2 (SEQ ID NO: 117), and CDR-L3 (SEQ ID NO: 116) and CDR-H1 (SEQ ID NO: 115), CDR-H2 (SEQ ID NO: 114) and CDR-H3 (SEQ ID NO: 112) or (SEQ ID NO: 113),
wherein the first binding domain comprises a single chain antibody fragment (scFv) comprising:
(a) the amino acid sequence set forth in SEQ ID NO: 194; or
(b) an amino acid sequence encoded by the nucleotide sequence set forth in SEQ ID NO: 193; and

(ii) a second binding domain binding to a cell surface antigen.

Assignees

• Amgen Res Munich Gmbh

Inventors

• Kischel Roman
• Raum Tobias
• Schlereth Bernd
• Rau Doris
• Cierpka Ronny
• Kufer Peter

Classifications

• A61K39/39558 Primary

  against tumor tissues, cells, antigens · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07K16/2809 Primary

  against the T-cell receptor (TcR)-CD3 complex · CPC title

• C07K16/30

  from tumour cells · CPC title

• C07K16/40

  against enzymes · CPC title