Anti-FcRH5 antibodies
AssigneeGenentech, Inc.
InventorsAllen J. Ebens, Meredith C. Hazen, Jo-Anne Hongo, Jennifer W. Johnston, Teemu T. Junttila, Ji Li, Andrew G. Polson
Life of this patent
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Abstract
The invention provides anti-FcRH5 antibodies and immunoconjugates and methods of using the same.
Claims14
A method of treating an individual having an FcRH5-positive cancer, the method comprising administering to the individual an effective amount of an isolated anti-FcRH5 antibody that binds an isoform c-specific region of the extracellular domain of FcRH5c, wherein the isoform c-specific region comprises amino acids 745-850 of SEQ ID NO:1, and wherein the antibody comprises:
- (a) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:39, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:63, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:87, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:3, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:15, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:27;
- (b) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:38, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:62, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:86, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:2, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:14, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:26;
- (c) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:41, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:65, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:89, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:5, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:17, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:29;
- (d) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:42, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:66, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:90, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:6, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:18, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:30;
- (e) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:43, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:67, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:91, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:19, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:31;
- (f) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:44, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:68, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:92, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:20, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:32;
- (g) a heavy chain comprising 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:69, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:93, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:21, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:33;
- (h) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:46, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:70, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:94, and a light chain comprising 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:22, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:34;
- (i) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:48, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:72, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:96, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:12, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:24, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:36;
- or
- (j) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:49, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:73, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:97, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:25, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:37.
A method of inhibiting proliferation of an FcRH5-positive cell, the method comprising exposing the cell to an isolated anti-FcRH5 antibody that binds an isoform c-specific region of the extracellular domain of FcRH5c under conditions permissive for binding of the antibody to FcRH5 on the surface of the cell, thereby inhibiting proliferation of the cell, wherein the isoform c-specific region comprises amino acids 745-850 of SEQ ID NO:1, and wherein the antibody comprises:
- (a) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:39, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:63, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:87, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:3, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:15, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:27;
- (b) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:38, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:62, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:86, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:2, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:14, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:26;
- (c) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:41, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:65, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:89, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:5, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:17, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:29;
- (d) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:42, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:66, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:90, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:6, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:18, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:30;
- (e) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:43, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:67, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:91, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:19, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:31;
- (f) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:44, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:68, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:92, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:20, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:32;
- (g) a heavy chain comprising 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:69, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:93, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:21, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:33;
- (h) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:46, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:70, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:94, and a light chain comprising 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:22, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:34;
- (i) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:48, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:72, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:96, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:12, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:24, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:36;
- or
- (j) a heavy chain comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO:49, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:73, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:97, and a light chain comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO:13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:25, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:37.
Dependencies are inferred from the claim text.