Anti-CD3 antibodies and methods of use
The invention provides anti-cluster of differentiation 3 (CD3) antibodies and methods of using the same.
1. 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 bispecific antibody 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 bispecific antibody of claim 1 , wherein the second binding domain binds to a human CD3ε polypeptide or a cynomolgus monkey (cyno) CD3ε polypeptide.
4. The bispecific antibody of claim 1 , wherein the bispecific antibody comprises a substitution mutation in the Fc region that reduces effector function.
5. The bispecific antibody of claim 4 , wherein the substitution mutation is an aglycosylation site mutation.
6. The bispecific antibody of claim 5 , wherein the aglycosylation site mutation is at amino acid residue N297, L234, L235, and/or D265 (EU numbering).
7. The bispecific antibody of claim 6 , wherein the aglycosylation site mutation is selected from the group consisting of N297G, N297A, L234A, L235A, and D265A.
8. The bispecific antibody of claim 1 , wherein the bispecific antibody is monoclonal, humanized, or chimeric.
9. The bispecific antibody of claim 8 , wherein the bispecific antibody is an antibody fragment that binds CD20 and CD3.
10. The bispecific antibody of claim 8 , wherein the bispecific antibody is a full-length antibody.
11. A composition comprising the bispecific antibody of claim 1 .
12. A kit comprising:
(a) the composition of claim 11 ; and
(b) a package insert comprising instructions for administering the composition to a subject to treat or delay progression of a cell proliferative disorder or an autoimmune disorder.
13. 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.
14. 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.