4-1BB BINDING MOLECULES
The present disclosure provides isolated binding molecules that bind to human 4-1BB, nucleic acid molecules encoding an amino acid sequence of the binding molecules, vectors comprising the nucleic acid molecules, host cells containing the vectors, methods of making the binding molecules, pharmaceutical compositions containing the binding molecules, and methods of using the binding molecules or compositions.
1 - 7 . (canceled)
8 . An isolated antibody or an antigen-binding portion thereof wherein said antibody or antigen-binding portion binds human 4-1BB extracellular domain, and wherein said binding is abrogated by one or more mutations of SEQ ID NO: 68 selected from K115Q, C121R, R134Q, R154S, or V156A.
9 . The antibody or antigen-binding portion thereof according to claim 8 wherein the one or more mutations of SEQ ID NO: 68 comprise K115Q, C121R, R134Q, R154S, and V156A.
10 . A pharmaceutical composition comprising an antibody or antigen-binding portion thereof according to claim 8 and a pharmaceutically acceptable carrier.
11 . An isolated antibody, wherein said antibody comprises a V H and a V L region wherein the V H region amino acid sequence comprises the amino acid sequence set forth in SEQ ID NO: 43 and the V L region amino acid sequence comprises the amino acid sequence set forth in SEQ ID NO: 45, wherein the antibody isotype is IgG 1.
12 . The antibody according to claim 11 wherein said antibody comprises the human IgG 1 constant domain amino acid sequence comprising the amino acid sequence set forth in SEQ ID NO: 69, with the proviso that the C-terminal lysine residue of SEQ ID NO: 69 is optionally absent.
13 . A pharmaceutical composition comprising an antibody according to claim 11 and a pharmaceutically acceptable carrier.
14 . A method for reducing tumor growth in a subject in need thereof, comprising administering to the subject an effective amount of an antibody or antigen-binding portion thereof according to claim 8 .
15 . A method of treating cancer in a mammal, which comprises administering to the mammal in need of treatment a therapeutically effective amount of an antibody or antigen-binding portion thereof according to claim 8 .
16 . The method of claim 15 wherein said cancer is selected from the group consisting of colorectal cancer, non-Hodgkin's lymphoma, prostate cancer, or melanoma.
17 . The method of claim 15 further comprising administering an immunotherapeutic agent.
18 . The method of claim 17 wherein said immunotherapeutic agent is rituximab.
19 . A method for reducing tumor growth in a subject in need thereof, comprising administering to the subject an effective amount of an antibody according to claim 11 .
20 . A method of treating cancer in a mammal, which comprises administering to the mammal in need of treatment a therapeutically effective amount of an antibody according to claim 11 .
21 . The method of claim 20 wherein said cancer is selected from the group consisting of colorectal cancer, non-Hodgkin's lymphoma, prostate cancer, or melanoma.
22 . The method of claim 20 further comprising administering an immunotherapeutic agent.
23 . The method of claim 22 wherein said immunotherapeutic agent is rituximab.