Monoclonal antibodies against CD32b
View Patent ↗Isolated monoclonal antibodies which bind to human CD32b and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the antibodies, and therapeutic and diagnostic methods for using the antibodies.
1. A method for inhibiting growth and/or proliferation of a tumor cell expressing CD32b, comprising administration, to an individual in need thereof, of an anti-CD32b antibody which comprises:
a) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:2, 3 and 4, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 6, 7 and 8,
b) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:10, 11 and 12, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:14, 15 and 16,
c) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:18, 19 and 20, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:22, 23 and 24,
d) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:26, 27 and 28, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:30, 31 and 32,
e) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:34, 35 and 36, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:38, 39 and 40,
f) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:42, 43 and 44, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:14, 15 and 16,
g) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 46, 47 and 48, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 50, 51 and 52,
h) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 54, 55 and 56, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 58, 59 and 60,
i) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 62, 63 and 64, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 66, 67 and 68, or
j) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 70, 71 and 72, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 74, 75 and 76.
2. The method of claim 1 , wherein the tumor cell is a B-cell neoplasm.
3. The method of claim 2 , wherein the B-cell neoplasm is selected from the group consisting of: small lymphocytic lymphoma, B-cell prolymphocytic lymphoma, B-cell chronic lymphocytic leukemia, mantle cell lymphoma, Burkitt's lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, multiple myeloma, lymphoplasmacytic lymphoma, splenic margina zone lymphoma, plasma cell neoplasms, such as plasma cell myeloma, plasmacytoma, monoclonal immunoglobulin deposition disease, heavy chain disease, MALT lymphoma, nodal marginal B cell lymphoma, intravascular large B cell lymphoma, primary effusion lymphoma, lymphomatoid granulomatosis, non-Hodgkins lymphoma, Hodgkins lymphoma, hairy cell leukemia, primary effusion lymphoma and AIDS-related non-Hodgkins lymphoma.
4. The method of claim 1 , wherein the anti-CD32b antibody is administered in combination with a therapeutic antibody.
5. The method of claim 4 , wherein the therapeutic antibody is selected from the group consisting of an anti-CD20 therapeutic antibody and an anti-CD38 therapeutic antibody.
6. The method of claim 1 , wherein the antibody comprises:
a) a VH region comprising the sequence as set forth in SEQ ID NO:1 and a VL region comprising the sequence as set forth in SEQ ID NO: 5,
b) a VH region comprising the sequence as set forth in SEQ ID NO:9 and a VL region comprising the sequence as set forth in SEQ ID NO:13,
c) a VH region comprising the sequence as set forth in SEQ ID NO:17 and a VL region comprising the sequence as set forth in SEQ ID NO:21,
d) a VH region comprising the sequence as set forth in SEQ ID NO:25 and a VL region comprising the sequence as set forth in SEQ ID NO:29,
e) a VH region comprising the sequence as set forth in SEQ ID NO:33 and a VL region comprising the sequence as set forth in SEQ ID NO:37,
f) a VH region comprising the sequence as set forth in SEQ ID NO:41 and a VL region comprising the sequence as set forth in SEQ ID NO:21,
g) a VH region comprising the sequence as set forth in SEQ ID NO:45 and a VL region comprising the sequence as set forth in SEQ ID NO:49,
h) a VH region comprising the sequence as set forth in SEQ ID NO:61 and a VL region comprising the sequence as set forth in SEQ ID NO:65, or
i) a VH region comprising the sequence as set forth in SEQ ID NO:69 and a VL region comprising the sequence as set forth in SEQ ID NO:73.
7. The method of claim 1 , wherein the antibody is a bispecific molecule comprising an anti-CD32b antibody and a second binding specificity.
8. The method of claim 1 , wherein the tumor cell is involved in Acute myelogenous leukemia (AML); Chronic lymphocytic leukemia (CLL) or Chronic myelogenous leukemia (CML).
9. The method of claim 1 , wherein the tumor cell is involved in peripheral T-Cell lymphomas or cutaneous T-Cell lymphoma.
10. The method of claim 1 , the tumor cell is involved in melanoma.
11. The method of claim 1 , wherein the anti-CD32b antibody is administered in combination with a therapeutic agent.
12. The method of claim 11 , wherein the therapeutic agent is selected from the group consisting of a cytotoxic, chemotherapeutic or anti-angiogenic agent.
13. The method of claim 12 , wherein the chemotherapeutic agent is selected from the group of an antimetabolite, an alkylating agent, an anti-mitotic agent, a growth factor inhibitor, and a tyrosine kinase inhibitor.
14. A method for stimulating the immune system, comprising administering, to an individual in need thereof, an anti-CD32b antibody comprising:
a) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:2, 3 and 4, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 6, 7 and 8,
b) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:10, 11 and 12, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:14, 15 and 16,
c) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:18, 19 and 20, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:22, 23 and 24,
d) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:26, 27 and 28, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:30, 31 and 32,
e) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:34, 35 and 36, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:38, 39 and 40,
f) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:42, 43 and 44, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:14, 15 and 16,
g) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 46, 47 and 48, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 50, 51 and 52,
h) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 54, 55 and 56, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 58, 59 and 60,
i) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 62, 63 and 64, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 66, 67 and 68, or
j) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 70, 71 and 72, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 74, 75 and 76.
15. A method for stimulating the immune system, comprising administering, to an individual in need thereof, an anti-CD32b antibody comprising:
a) a VH region comprising the sequence as set forth in SEQ ID NO:1 and a VL region comprising the sequence as set forth in SEQ ID NO: 5,
b) a VH region comprising the sequence as set forth in SEQ ID NO:9 and a VL region comprising the sequence as set forth in SEQ ID NO:13,
c) a VH region comprising the sequence as set forth in SEQ ID NO:17 and a VL region comprising the sequence as set forth in SEQ ID NO:21,
d) a VH region comprising the sequence as set forth in SEQ ID NO:25 and a VL region comprising the sequence as set forth in SEQ ID NO:29,
e) a VH region comprising the sequence as set forth in SEQ ID NO:33 and a VL region comprising the sequence as set forth in SEQ ID NO:37,
f) a VH region comprising the sequence as set forth in SEQ ID NO:41 and a VL region comprising the sequence as set forth in SEQ ID NO:21,
g) a VH region comprising the sequence as set forth in SEQ ID NO:45 and a VL region comprising the sequence as set forth in SEQ ID NO:49,
h) a VH region comprising the sequence as set forth in SEQ ID NO:61 and a VL region comprising the sequence as set forth in SEQ ID NO:65, or
i) a VH region comprising the sequence as set forth in SEQ ID NO:69 and a VL region comprising the sequence as set forth in SEQ ID NO:73.
16. A method for stimulating the immune system, comprising administering, to an individual in need thereof, a bispecific molecule comprising an anti-CD32b antibody and a second binding specificity, wherein the anti-CD32b antibody comprises:
a) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:2, 3 and 4, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 6, 7 and 8,
b) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:10, 11 and 12, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:14, 15 and 16,
c) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:18, 19 and 20, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:22, 23 and 24,
d) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:26, 27 and 28, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:30, 31 and 32,
e) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:34, 35 and 36, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:38, 39 and 40,
f) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:42, 43 and 44, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO:14, 15 and 16,
g) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 46, 47 and 48, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 50, 51 and 52,
h) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 54, 55 and 56, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 58, 59 and 60,
i) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 62, 63 and 64, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 66, 67 and 68, or
j) a VH region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 70, 71 and 72, and a VL region comprising CDR1, 2 and 3 sequences as set forth in SEQ ID NO: 74, 75 and 76.