Humanized or chimeric cd3 antibodies

Patent metadata

Field	Value
Publication number	US-2016333095-A1
Application number	US-201515110414-A
Country	US
Kind code	A1
Filing date	Jan 8, 2015
Priority date	Jan 9, 2014
Publication date	Nov 17, 2016
Grant date	—

Abstract

The present invention relates to humanized or chimeric antibodies binding CD3. It furthermore relates to bispecific antibodies, compositions, pharmaceutical compositions, use of said antibodies in the treatment of a disease, and method of treatment.

First claim

1 . A humanized or chimeric antibody binding to human CD3, wherein said antibody comprises a binding region comprising heavy chain variable (VH) region CDR1, CDR2, and CDR3 having the sequences as set forth in SEQ ID NOs: 1, 2, and 3, respectively, and light chain variable (VL) region CDR1, CDR2, and CDR3 having the sequences as set forth in SEQ ID NO: 4, the sequence GTN, and the sequence as set forth in SEQ ID NO: 5 or SEQ ID NO:60, respectively.

2 . The antibody according to claim 1 , wherein said VH region has at least 90%, at least 95%, at least 97%, or at least 99% amino acid sequence identity to the amino acid sequence as set forth in the VH sequences selected from the group consisting of;
a) a VH sequence as set forth in SEQ ID NO:6; b) a VH sequence as set forth in SEQ ID NO:8; c) a VH sequence as set forth in SEQ ID NO:7; and d) a VH sequence as set forth in SEQ ID NO:9.

3 . The antibody according to any one of the preceding claims, wherein said VL region has at least 90%, at least 95%, at least 97%, or at least 99% amino acid sequence identity to the amino acid sequence as set forth in the VL sequences selected from the group consisting of;
a) a VL sequence as set forth in SEQ ID NO:10; b) a VL sequence as set forth in SEQ ID NO:11; and c) a VL sequence as set forth in SEQ ID NO:12.

4 . The antibody according to any one of the preceding claims, wherein said VH region is selected from the group consisting of;
a) a VH sequence as set forth in SEQ ID NO:6; b) a VH sequence as set forth in SEQ ID NO:8; c) a VH sequence as set forth in SEQ ID NO:7; and d) a VH sequence as set forth in SEQ ID NO:9.

5 . The antibody according to any one of the preceding claims, wherein said VL region is selected from the group consisting of;
a) a VL sequence as set forth in SEQ ID NO:10; b) a VL sequence as set forth in SEQ ID NO:11; and c) a VL sequence as set forth in SEQ ID NO:12.

6 . The antibody according to any one of the preceding claims, wherein said VH and VL regions are selected from the group consisting of;
a) a VH sequence as set forth in SEQ ID NO:6, and a VL sequence as set forth in SEQ ID NO:10; b) a VH sequence as set forth in SEQ ID NO:8, and a VL sequence as set forth in SEQ ID NO:10; c) a VH sequence as set forth in SEQ ID NO:9, and a VL sequence as set forth in SEQ ID NO:10; d) a VH sequence as set forth in SEQ ID NO:6, and a VL sequence as set forth in SEQ ID NO:11; e) a VH sequence as set forth in SEQ ID NO:6, and a VL sequence as set forth in SEQ ID NO:12; f) a VH sequence as set forth in SEQ ID NO:7, and a VL sequence as set forth in SEQ ID NO:10; g) a VH sequence as set forth in SEQ ID NO:7, and a VL sequence as set forth in SEQ ID NO:11; h) a VH sequence as set forth in SEQ ID NO:7, and a VL sequence as set forth in SEQ ID NO:12; i) a VH sequence as set forth in SEQ ID NO:8, and a VL sequence as set forth in SEQ ID NO:11; j) a VH sequence as set forth in SEQ ID NO:8, and a VL sequence as set forth in SEQ ID NO:12; k) a VH sequence as set forth in SEQ ID NO:9, and a VL sequence as set forth in SEQ ID NO:11; and l) a VH sequence as set forth in SEQ ID NO:9, and a VL sequence as set forth in SEQ ID NO:12.

7 . The antibody according to any one of the preceding claims, wherein said binding region comprises a VH sequence and a VL sequence selected from the group consisting of;
a) a VH sequence as set forth in SEQ ID NO:6, and a VL sequence as set forth in SEQ ID NO:10; b) a VH sequence as set forth in SEQ ID NO:8, and a VL sequence as set forth in SEQ ID NO:10; and c) a VH sequence as set forth in SEQ ID NO:9, and a VL sequence as set forth in SEQ ID NO:10.

8 . The antibody according to any one of the preceding claims, wherein the antibody is a humanized antibody.

9 . The antibody according to claim 1 , wherein the antibody is a chimeric antibody.

10 . The antibody according to any one of the preceding claims, wherein the antibody is a full-length antibody.

11 . The antibody according to any one of the preceding claims, wherein said antibody comprises an Fc region comprising a first and a second immunoglobulin heavy chain.

12 . The antibody according to any one of the preceding claims, wherein said first and said second heavy chains are of an isotype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.

13 . The antibody according to any one of the preceding claims, wherein said antibody comprises an Fc region which has been modified so that binding of C1q to said antibody is reduced compared to a wild-type antibody by at least 70%, at least 80%, at least 90%, at least 95%, at least 97%, or 100%, wherein C1q binding is determined by ELISA.

14 . The antibody according to any one of the preceding claims, wherein said antibody comprises an Fc region which has been modified so that said antibody mediates reduced Fc-mediated T-cell proliferation compared to a wild-type antibody by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 99% or 100%, wherein said T-cell proliferation is measured in a peripheral blood mononuclear cell (PBMC)-based functional assay.

15 . The antibody according to any one of the preceding claims, wherein said antibody comprises an Fc region which has been modified so that said antibody reduces Fc-mediated CD69 expression by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 99% or 100% when compared to a wild-type antibody wherein said Fc-mediated CD69 expression is determined in a PBMC-based functional assay.

16 . The antibody according to any one of the preceding claims, wherein said antibody comprises a first and a second immunoglobulin heavy chain, wherein in at least one of said first and second immunoglobulin heavy chains one or more amino acids in the positions corresponding to positions L234, L235, D265, N297, and P331 in a human IgG1 heavy chain, are not L, L, D, N, and P, respectively.

17 . The antibody according to claim 16 , wherein in at least one of said first and second heavy chains the amino acid in the position corresponding to position D265 in a human IgG1 heavy chain, is not D.

18 . The antibody according to claim 16 , wherein in at least one of said first and second heavy chains the amino acid in the position corresponding to position N297 in a human IgG1 heavy chain, is not N.

19 . The antibody according to claim 16 , wherein in at least one of said first and second heavy chains the amino acids in the positions corresponding to positions L234 and L235 in a human IgG1 heavy chain, are not L and L, respectively.

20 . The antibody according to any of claims 16 and 19 , wherein in at least one of said first and second heavy chains the amino acids in the positions corresponding to positions L234 and L235 in a human IgG1 heavy chain, are F and E; or A and A, respectively.

21 . The antibody according to claim 20 , wherein in at least one of said first and second heavy chains the amino acids in the positions corresponding to positions L234 and L235 in a human IgG1 heavy chain, are F and E, respectively.

22 . The antibody according to claim 20 , wherein in at least one of said first and second heavy chains at least the amino acids in the positions corresponding to positions L234 and L235 in a human IgG1 heavy chain, are A and A, respectively.

23 . The antibody according to any of claims 1 to 16 , wherein in at least one of said first and second heavy chains the amino acids in the positions corr

Assignees

• Genmab As

Inventors

• Van Den Brink Edward Norbert
• Neijssen Joost J
• Labrijn Aran Frank
• Meesters Joyce
• Schuurman Janine
• Altintas Isil
• Parren Paul
• Rademaker Rik

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• C07K16/1145

  Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site · CPC title

• C07K2317/75

  Agonist effect on antigen · CPC title