CD19 binding agents and uses thereof

Patent metadata

Field	Value
Publication number	US-11331394-B2
Application number	US-201815897063-A
Country	US
Kind code	B2
Filing date	Feb 14, 2018
Priority date	Oct 19, 2007
Publication date	May 17, 2022
Grant date	May 17, 2022

Abstract

This invention, among other things, relates to CD19 binding agents and methods of using such CD binding agents for treating disease.

First claim

What is claimed:

1. An antibody that specifically binds to human CD19, the antibody comprising a heavy chain variable region comprising CDRs comprising the amino acid sequences set forth in SEQ ID NOS:46, 47, and 48, wherein the amino acid sequence of the heavy chain variable region is at least 90% identical to SEQ ID NO:2, and a light chain variable region comprising CDRs comprising the amino acid sequences set forth in SEQ ID NOS:49, 50 and 51, wherein the amino acid sequence of the light chain variable region is at least 90% identical to SEQ ID NO:17 or SEQ ID NO:26.

2. The antibody of claim 1 , further comprising a human IgG constant region joined to the heavy chain variable region.

3. The antibody of claim 2 , wherein the isotype of IgG constant region is human IgG1, IgG2, or IgG1V1.

4. The antibody of claim 2 , further comprising a light chain constant domain joined to the light chain variable region, wherein the light chain constant domain is a kappa constant domain.

5. The antibody of claim 1 that is a humanized antibody.

6. An antibody-drug conjugate comprising the antibody of claim 1 conjugated to a cytotoxic agent.

7. The antibody-drug conjugate of claim 6 according to the following formula:
L-(LU-D) p   (I)

or a pharmaceutically acceptable salt or solvate thereof;
wherein:
L is a ligand unit wherein the ligand unit is a CD19 binding agent of claim 1 ; and
(LU-D) is a Linker unit-Drug unit moiety, wherein:
LU— is a Linker unit, and
-D is a Drug unit having cytostatic or cytotoxic activity against the target cells; and
p is an integer from 1 to about 20.

8. The antibody-drug conjugate of claim 7 , wherein the antibody-drug conjugate has the formula:

or a pharmaceutically acceptable salt or solvate form thereof, wherein mAb-S— is the antibody specifically binding to CD19 and p is from 1 to 8.

9. A pharmaceutical composition comprising the antibody-drug conjugate compound of claim 1 , and a pharmaceutically acceptable carrier or excipient.

10. The humanized antibody of claim 5 , wherein any heavy chain variable region framework positions that differ from SEQ ID NO:2 are occupied by the amino acids occupying the corresponding positions of SEQ ID NO:8 or SEQ ID NO:32; and wherein any light chain variable region framework positions that differ from SEQ ID NO:17 are occupied by the amino acids occupying the corresponding position of SEQ ID NO:25 or SEQ ID NO:34.

11. The humanized antibody of claim 10 , wherein any heavy chain variable region framework positions that differ from SEQ ID NO:2 and the amino acids occupying those positions are selected from the group consisting of positions H75, H79, H81, H82, H82A, H82B, H82C, and H89 occupied by S, F, K, I, A, S, V, and A respectively; and any light chain variable region framework positions that differ from SEQ ID NO.17 and the amino acids occupying those positions are selected from the group consisting of positions L2, L40, L41, L42, L69, L70, L71, L72 and L83 occupied by N, S, S, T, N, S, H, F, and V respectively.

12. The humanized antibody of claim 11 , wherein the light chain variable region framework position L83 is occupied by V.

13. The humanized antibody of claim 5 , wherein at least one of the heavy chain variable region positions H75, H79, H81, H82, H82A, H82B, H82C and H89 is occupied by S, F, K, I, A, S, V, and A respectively.

14. The humanized antibody of claim 5 , wherein at least one of the light chain variable region positions L2, L69, L71, L72 and L83 is occupied by N, N, H, F and V respectively.

15. The humanized antibody of claim 5 , wherein no more than three amino acids in the heavy chain variable region framework differ from SEQ ID NO:2, and no more than three amino acids in the light chain variable region framework differ from SEQ ID NO:17.

16. The humanized antibody of claim 5 , wherein the mature heavy chain variable region comprises the amino acid sequence of any of SEQ ID NOS:2 and 4-7 and the mature light chain variable region comprises the amino acid sequence of any of SEQ ID NOS:17 and 19-24.

17. The antibody-drug conjugate of claim 6 , wherein the antibody is conjugated to a DNA minor groove binding agent or an anti-tubulin.

18. The antibody-drug conjugate of claim 17 , wherein the anti-tubulin is an auristatin.

19. The antibody-drug conjugate of claim 18 , wherein the auristatin is MMAE or MMAF.

20. The antibody-drug conjugate of claim 6 , wherein p is 1-8.

21. The antibody-drug conjugate of claim 6 , wherein p is 4.

Assignees

• Seagen Inc

Inventors

• Mcdonagh Charlotte
• Cerveny Charles G
• Benjamin Dennis
• Carter Paul

Classifications

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title

• A61K47/68031

  the drug being an auristatin · CPC title

• C07K16/3061

  Blood cells · CPC title

• C07K16/30 Primary

  from tumour cells · CPC title

• A61K38/05

  Dipeptides · CPC title