Anti-CD3 antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-10865251-B2
Application number	US-201816144452-A
Country	US
Kind code	B2
Filing date	Sep 27, 2018
Priority date	Dec 17, 2013
Publication date	Dec 15, 2020
Grant date	Dec 15, 2020

Abstract

The invention provides anti-cluster of differentiation 3 (CD3) antibodies and methods of using the same.

First claim

What is claimed is:

1. One or more isolated nucleic acids encoding a bispecific antibody that binds to CD20 and CD3, wherein the bispecific antibody comprises:
(a) an anti-CD20 arm comprising a first binding domain, the first binding domain comprising:
a hypervariable region (HVR)-H1 comprising the amino acid sequence of SEQ ID NO: 157,
an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 158,
an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 159,
an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 160,
an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 161, and
an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 162; and

(b) an anti-CD3 arm comprising a second binding domain, the second binding domain comprising:
an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1,
an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2,
an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3,
an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4,
an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and
an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

2. The one or more nucleic acids of claim 1 , wherein the first binding domain comprises:
(a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 266; (b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 267; or (c) a VH domain as in (a) and a VL domain as in (b),
and the second binding domain comprises:
(a) a VH domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 184; (b) a VL domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 185; or (c) a VH domain as in (a) and a VL domain as in (b).

3. The one or more nucleic acids of claim 1 , wherein the second binding domain binds to a human CD3ε polypeptide.

4. The one or more nucleic acids of claim 1 , wherein the second binding domain binds to a cynomolgus monkey (cyno) CD3ε polypeptide.

5. The one or more nucleic acids of claim 1 , wherein the bispecific antibody comprises a substitution mutation in the Fc region that reduces effector function.

6. The one or more nucleic acids of claim 5 , wherein the substitution mutation is an aglycosylation site mutation.

7. The one or more nucleic acids of claim 6 , wherein the aglycosylation site mutation is at amino acid residue N297, L234, L235, and/or D265 (EU numbering).

8. The one or more nucleic acids of claim 7 , wherein the aglycosylation site mutation is selected from the group consisting of N297G, N297A, L234A, L235A, and D265A.

9. The one or more nucleic acids of claim 1 , wherein the bispecific antibody is monoclonal, humanized, or chimeric.

10. The one or more nucleic acids of claim 9 , wherein the bispecific antibody is an antibody fragment that binds CD20 and CD3.

11. The one or more nucleic acids of claim 10 , wherein the antibody fragment is a Fab, Fab′-SH, Fv, scFv, or (Fab′) 2 fragment.

12. The one or more nucleic acids of claim 9 , wherein the bispecific antibody is a full-length antibody.

13. A vector comprising the one or more isolated nucleic acids of claim 1 .

14. A host cell comprising a vector, wherein the vector comprises the one or more isolated nucleic acids of claim 1 .

15. One or more isolated nucleic acids encoding a bispecific antibody that binds to CD20 and CD3, wherein the bispecific antibody comprises an anti-CD3 arm comprising a first binding domain comprising (a) a VH domain comprising the amino acid sequence of SEQ ID NO: 184 and (b) a VL domain comprising the amino acid sequence of SEQ ID NO: 185, and an anti-CD20 arm comprising a second binding domain comprising (a) a VH domain comprising the amino acid sequence of SEQ ID NO: 266 and (b) a VL domain comprising the amino acid sequence of SEQ ID NO: 267.

16. A vector comprising the one or more isolated nucleic acids of claim 15 .

17. A host cell comprising a vector, wherein the vector comprises the one or more isolated nucleic acids of claim 15 .

18. One or more isolated nucleic acids encoding a bispecific antibody that binds to CD20 and CD3, wherein the bispecific antibody comprises an anti-CD3 arm comprising a first binding domain comprising (a) a VH domain comprising the amino acid sequence of SEQ ID NO: 184 and (b) a VL domain comprising the amino acid sequence of SEQ ID NO: 185, and an anti-CD20 arm comprising a second binding domain comprising (a) a VH domain comprising the amino acid sequence of SEQ ID NO: 266 and (b) a VL domain comprising the amino acid sequence of SEQ ID NO: 267, wherein (a) the anti-CD3 arm comprises T366S, L368A, Y407V, and N297G substitution mutations and (b) the anti-CD20 arm comprises T366W and N297G substitution mutations.

19. A vector comprising the one or more isolated nucleic acids of claim 18 .

20. A host cell comprising a vector, wherein the vector comprises the one or more isolated nucleic acids of claim 18 .

Assignees

• Genentech Inc

Inventors

• Chen Xiaocheng
• Dennis Mark S
• Ebens Jr Allen J
• Kelley Robert F
• Mathieu Mary A
• Sun Liping L

Classifications

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K16/2809 Primary

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

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/31

  multispecific · CPC title

• A61P35/00

  Antineoplastic agents · CPC title