Anti-CD79b antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-10941199-B2
Application number	US-201815957157-A
Country	US
Kind code	B2
Filing date	Apr 19, 2018
Priority date	Dec 5, 2014
Publication date	Mar 9, 2021
Grant date	Mar 9, 2021

Abstract

The invention provides anti-CD79b antibodies and methods of using the same.

First claim

What is claimed is:

1. A bispecific antibody that binds to CD79b and CD3,
wherein the bispecific antibody comprises:
(a) a CD79b binding domain comprising the following six hypervariable regions (HVRs):
an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 5,
an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 8,
an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 9,
an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10,
an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and
an HVR-L3 comprising the amino acid sequence of SEQ ID NO, 12;

and
(b) a CD3 binding domain.

2. The bispecific antibody of claim 1 , wherein CD3 binding domain comprises the following six HVRs:
an HVR-H1 comprising the amino acid sequence of SEQ ID NO:45,
an HVR-H2 comprising the amino acid sequence of SEQ ID NO:46,
an HVR-H3 comprising the amino acid sequence of SEQ ID NO:47,
an HVR-L1 comprising the amino acid sequence of SEQ ID NO:48,
an HVR-L2 comprising the amino acid sequence of SEQ ID NO:49, and
an HVR-L3 comprising the amino acid sequence of SEQ ID NO:50.

3. The bispecific antibody of claim 2 , wherein the CD3 binding domain comprises
(a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:59;
(b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:60; or
(c) a VH sequence as in (a) and a VL sequence as in (b).

4. The bispecific antibody of claim 1 , wherein the CD3 binding domain comprises a VH sequence of SEQ ID NO:59 and a VL sequence of SEQ ID NO:60.

5. A bispecific antibody that binds to CD79b and CD3,
wherein the bispecific antibody comprises:
(a) a CD79b binding domain comprising the following six hypervariable regions (HVRs):
an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 3,
an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 6,
an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 9,
an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10,
an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and
an HVR-L3 comprising the amino acid sequence of SEQ ID NO, 12;

and
(b) a CD3 binding domain comprising the following six HVRs:
an HVR-H1 comprising the amino acid sequence of SEQ ID NO:45,
an HVR-H2 comprising the amino acid sequence of SEQ ID NO:46,
an HVR-H3 comprising the amino acid sequence of SEQ ID NO:47,
an HVR-L1 comprising the amino acid sequence of SEQ ID NO:48,
an HVR-L2 comprising the amino acid sequence of SEQ ID NO:49, and
an HVR-L3 comprising the amino acid sequence of SEQ ID NO:50.

6. The bispecific antibody of claim 5 , wherein the CD3 binding domain comprises
(a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:59;
(b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:60; or
(c) a VH sequence as in (a) and a VL sequence as in (b).

7. The bispecific antibody of claim 5 , wherein the CD3 binding domain comprises a VH sequence of SEQ ID NO:59 and a VL sequence of SEQ ID NO:60.

8. A bispecific antibody that binds to CD79b and CD3, wherein the bispecific antibody comprises:
(a) a CD79b binding domain comprising the following six hypervariable regions (HVRs):
an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 4,
an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 7,
an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 9,
an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10,
an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and
an HVR-L3 comprising the amino acid sequence of SEQ ID NO, 12;

and
(b) a CD3 binding domain comprising the following six HVRs:
an HVR-H1 comprising the amino acid sequence of SEQ ID NO:45,
an HVR-H2 comprising the amino acid sequence of SEQ ID NO:46,
an HVR-H3 comprising the amino acid sequence of SEQ ID NO:47,
an HVR-L1 comprising the amino acid sequence of SEQ ID NO:48,
an HVR-L2 comprising the amino acid sequence of SEQ ID NO:49, and
an HVR-L3 comprising the amino acid sequence of SEQ ID NO:50.

9. The bispecific antibody of claim 8 , wherein the CD3 binding domain comprises
(a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:59;
(b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:60; or
(c) a VH sequence as in (a) and a VL sequence as in (b).

10. The bispecific antibody of claim 8 , wherein the CD3 binding domain comprises a VH sequence of SEQ ID NO:59 and a VL sequence of SEQ ID NO:60.

11. The bispecific antibody of claim 8 , wherein the CD79b binding domain comprises
(a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 19;
(b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:20; or
(c) a VH sequence as in (a) and a VL sequence as in (b).

12. The bispecific antibody of claim 8 , wherein the CD79b binding domain comprises a VH sequence of SEQ ID NO: 19 and a VL sequence of SEQ ID NO:20.

13. A bispecific antibody that binds to CD79b and CD3, wherein the bispecific antibody comprises:
(a) a CD79b binding domain comprising a VH sequence of SEQ ID NO: 19 and a VL sequence of SEQ ID NO:20, and
(b) a CD3 binding domain comprising a VH sequence of SEQ ID NO:59 and a VL sequence of SEQ ID NO:60.

14. The bispecific antibody of claim 8 , wherein the bispecific antibody has a B cell killing EC50 of less than about 100 ng/mL.

15. The bispecific antibody of claim 14 , wherein the B cell killing is endogenous B cell killing.

16. The bispecific antibody of claim 8 , wherein the bispecific antibody has a cytotoxic T cell activation EC50 is less than about any of 50 ng/mL.

17. The bispecific antibody of claim 1 , wherein (a) the CD3 binding domain comprises a Fc domain, wherein the Fc domain comprises T366S, L368A, Y407V, and N297G substitution mutations according EU numbering and (b) the CD79b binding domain comprises a Fc domain, wherein the Fc domain comprises T366W and N297G substitution mutations according EU numbering.

18. An isolated nucleic acid encoding the bispecific antibody of claim 1 .

19. A vector comprising the isolated nucleic acid of claim 18 .

20. A host cell comprising the vector of claim 19 .

21. A method of producing a bispecific antibody, the method comprising culturing the host cell of claim 20 in a culture medium.

22. A pharmaceutical composition comprising the bispecific antibody of claim 1 .

23. The bispecific antibody of claim 15 , wherein the B cell killing is cell line B cell killing using a cell line selected from the group consisting of BJAB cell line, WSU-CLCL2 cell line, and OCI-Ly-19 cell line.

Assignees

• Genentech Inc

Inventors

• Sun Liping L
• Chen Yvonne Man-Yee
• Dennis Mark S
• Ebens Jr Allen J
• Polson Andrew

Classifications

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• A61K47/6803

  Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2317/31

  multispecific · CPC title