Humanized or chimeric CD3 antibodies

Patent metadata

Field	Value
Publication number	US-10407501-B2
Application number	US-201515110414-A
Country	US
Kind code	B2
Filing date	Jan 8, 2015
Priority date	Jan 9, 2014
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

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

The invention claimed is:

1. A humanized or chimeric antibody which binds to human CD3 and comprises heavy chain variable region CDR1, CDR2, and CDR3 domains comprising the amino acid sequences set forth in SEQ ID NOs: 1, 2, and 3, respectively, and a light chain comprising the amino acid sequence of SEQ ID NO: 10, wherein the amino acid in the position corresponding to position T41 in SEQ ID NO: 10 is not T.

2. A humanized or chimeric antibody which binds to human CD3 and comprises heavy chain variable region CDR1, CDR2, and CDR3 domains comprising the amino acid sequences set forth in SEQ ID NOs: 1, 2, and 3, respectively, and a light chain comprising the amino acid sequence of SEQ ID NO: 10, wherein the amino acid in the position corresponding to position F10 in SEQ ID NO: 10 is not F, and wherein one or more of the amino acid positions corresponding to the positions T41, K55, and L97 in SEQ ID NO: 10 are not T, K, and L, respectively.

3. The antibody according to claim 2 , wherein the amino acids in the positions corresponding to positions F10, T41, K55, and L97 in SEQ ID NO: 10 are not F, T, K, and L, respectively.

4. A humanized or chimeric antibody which binds to human CD3 and comprises heavy chain variable region CDR1, CDR2, and CDR3 domains comprising the amino acid sequences set forth in SEQ ID NOs: 1, 2, and 3, respectively, and a light chain comprising the amino acid sequence of SEQ ID NO: 10, wherein the amino acids in the positions corresponding to positions R23 and A35 in SEQ ID NO: 10 are not R and A, respectively.

5. The antibody according to claim 4 , wherein the amino acids in the positions corresponding to positions F10, R23, A35, R47, D71, A82, D83, S86, 187, and F89 in SEQ ID NO: 10 are not F, R, A, R, D, A, D, S, I, and F, respectively.

6. The antibody according to claim 5 , wherein
i. the amino acid in the position corresponding to position F10 in SEQ ID NO: 10 is not F, or
ii. the amino acid in the position corresponding to position K55 in SEQ ID NO: 10 is not K, or
iii. the amino acid in the position corresponding to position F10 in SEQ ID NO: 10 is not F, and the amino acid in the position corresponding to position K55 in SEQ ID NO: 10 is not K.

7. The antibody according to claim 6 , wherein
(i) the amino acid in the position corresponding to position F10 in SEQ ID NO: 10 is L, or
(ii) the amino acid in the position corresponding to position K55 in SEQ ID NO: 10 is N, or
(iii) the amino acid in the position corresponding to position F10 in SEQ ID NO: 10 is L, and the amino acid in the position corresponding to position K55 in the lambda light chain of SEQ ID NO: 10 is N.

8. A humanized or chimeric antibody which binds to human CD3 and comprises heavy chain variable region CDR1, CDR2, and CDR3 domains comprising the amino acid sequences set forth in SEQ ID NOs: 1, 2, and 3, respectively, and light chain variable region CDR1, CDR2, and CDR3 domains comprising the amino acid sequences set forth in SEQ ID NO: 4, GTN, and SEQ ID NO: 5 or 60, respectively, wherein said antibody comprises a constant heavy chain and a constant light chain, wherein the positions corresponding to positions L234, L235, and D265 in the human IgG1 heavy chain of SEQ ID NO: 15 are F, E, and A, respectively, and wherein the position corresponding to F405 in the human IgG1 heavy chain of SEQ ID NO: 15 is L, and wherein (i) the positions corresponding to positions F10, T41, K55, and L97 in the lambda light chain of SEQ ID NO: 10 are L, K, N, and H, respectively, or (ii) the position corresponding to position T41 in the lambda light chain of SEQ ID NO: 10 is K.

9. A composition comprising the antibody of claim 1 and a carrier.

10. The antibody of claim 1 , wherein the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 6-9.

11. The antibody of claim 2 , wherein the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 6-9.

12. The antibody of claim 4 , wherein the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 6-9.

13. The antibody of claim 8 , wherein the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 6-9.

14. The antibody of claim 1 , which is a full length antibody.

15. The antibody of claim 2 , which is a full length antibody.

16. The antibody of claim 4 , which is a full length antibody.

17. A composition comprising the antibody of claim 2 and a carrier.

18. A composition comprising the antibody of claim 4 and a carrier.

19. A composition comprising the antibody of claim 8 and a carrier.

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

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title