HUMANIZED AND AFFINITY MATURED ANTIBODIES TO FcRH5 AND METHODS OF USE
AssigneeGenentech, Inc.
InventorsIsidro HOTZEL, Teemu T. JUNTTILA, Ji LI, Justin SCHEER, Danielle DICARA, Diego ELLERMAN, Christoph SPIESS, Paul J. CARTER
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Abstract
The present invention relates to anti-FcRH5 antibodies, including anti-FcRH5 antibodies comprising an FcRH5 binding domain and a CD3 binding domain (e.g., FcRH5 T cell-dependent bispecific (TDB) antibodies), and methods of using the same.
Claims39
1-335. (canceled)
One or more isolated nucleic acids encoding an anti-FcRH5 antibody, wherein the anti-FcRH5 antibody comprises a binding domain that binds to FcRH5, the binding domain comprising the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 1;
- (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 8;
- (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 9;
- (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 12;
- (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 16;
- and
- (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 23.
One or more isolated nucleic acids encoding an anti-FcRH5 antibody, wherein the anti-FcRH5 antibody comprises a binding domain that binds to FcRH5, the binding domain comprising a binding domain comprising (a) a VH domain comprising the amino acid sequence of SEQ ID NO:
- 104 and (b) a VL domain comprising the amino acid sequence of SEQ ID NO:
- 105.
One or more isolated nucleic acids encoding an anti-FcRH5 antibody that binds to FcRH5 and CD3, wherein the anti-FcRH5 antibody comprises an anti-FcRH5 arm comprising a first binding domain comprising the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 1;
- (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 8;
- (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 9;
- (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 12;
- (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 16;
- and
- (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 23;
- and
- an anti-CD3 arm comprising a second binding domain comprising the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 115;
- (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 116;
- (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 121;
- (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 118;
- (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 119;
- and
- (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 123.
One or more isolated nucleic acids encoding an anti-FcRH5 antibody that binds to FcRH5 and CD3, wherein the anti-FcRH5 antibody comprises an anti-FcRH5 arm comprising a first binding domain comprising the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 1;
- (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 8;
- (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 9;
- (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 12;
- (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 16;
- and
- (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 23;
- and
- an anti-CD3 arm comprising a second binding domain comprising the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 115;
- (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 116;
- (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 121;
- (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 118;
- (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 119;
- and
- (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 123;
- and
- wherein the anti-FcRH5 arm and the anti-CD3 arm each comprise an N297G substitution mutation (EU numbering);
- and
- wherein the anti-FcRH5 arm comprises a T366W substitution mutation (EU numbering) and the anti-CD3 arm comprises T366S, L368A, and Y407V substitution mutations (EU numbering).
Dependencies are inferred from the claim text.