Fcgamma riib specific antibodies and methods of use thereof
AssigneeMacroGenics, Inc.
InventorsScott Koenig, Maria Veri
Life of this patent
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Abstract
The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.
Claims107
An isolated antibody or a fragment thereof that specifically binds native FcγRIIB with greater affinity than said antibody or fragment thereof binds native FcγRIIA.
A bispecific antibody comprising a first heavy chain-light chain pair that specifically binds FcγRIIB with greater affinity than said heavy chain-light chain pair binds FcγRIIA, and a second heavy chain-light chain pair that specifically binds a tumor antigen.
An isolated antibody or a fragment thereof that specifically binds native FcγRIIB with at least 2 times greater affinity than said antibody or fragment thereof binds native FcγRIIA.
A method for producing a monoclonal antibody that specifically binds FcγRIIB with greater affinity than said monoclonal antibody binds FcγRIIA, said method comprising:
- (a) immunizing FcγRIIA transgenic mice with purified FcγRIIB or an immunogenic fragment thereof;
- (b) producing hybridoma cells lines from spleen cells of said mice;
- (c) screening said hybridoma cell lines for one or more hybridoma cell lines that produce antibodies that specifically bind FcγRIIB with greater affinity than the antibodies bind FcγRIIA.
A mouse monoclonal antibody produced by clone 3H7, having ATCC accession number PTA-4592.
A mouse monoclonal antibody produced by clone 2B6, having ATCC accession number PTA-4591.
A hybridoma cell line 3H7, having ATCC accession number PTA-4592.
A hybridoma cell line 2B6, having ATCC accession number PTA-4591.
A method of treating cancer in a patient having a cancer characterized by a cancer antigen, said method comprising administering to said patient a therapeutically effective amount of a first antibody or fragment thereof that specifically binds FcγRIIB with greater affinity than said antibody or fragment thereof binds FcγRIIA, and a second antibody that specifically binds said cancer antigen and is cytotoxic.
A pharmaceutical composition comprising (i) a therapeutically effective amount of the antibody or fragment thereof that specifically binds FcγRIIB with greater affinity than said antibody or fragment thereof binds FcγRIIA;
- (ii) a cytotoxic antibody that specifically binds a cancer antigen;
- and (iii) a pharmaceutically acceptable carrier.
A method of enhancing an immune response to a vaccine composition in a subject, said method comprising administering to said subject an antibody or fragment thereof that specifically binds FcγRIIB with greater affinity than said antibody or fragment thereof binds FcγRIIA, and a vaccine composition, said antibody or fragment thereof being administered in an amount effective to enhance the immune response to said vaccine composition in said subject.
An isolated antibody or a fragment thereof that specifically binds FcγRIIB with 4 times greater affinity than said antibody or fragment thereof binds FcγRIIA.
An isolated antibody or a fragment thereof that specifically binds FcγRIIB with 6 times greater affinity than said antibody or fragment thereof binds FcγRIIA.
An isolated antibody or a fragment thereof that specifically binds FeγRIIB with 8 times greater affinity than said antibody or fragment thereof binds FcγRIIA.
An isolated antibody or a fragment thereof that specifically binds FcγRIIB with 10 times greater affinity than said antibody or fragment thereof binds FcγRIIA.
An isolated antibody or a fragment thereof that specifically binds FcγRIIB with 100 times greater affinity than said antibody or fragment thereof binds FcγRIIA.
An isolated antibody or a fragment thereof that specifically binds FcγRIIB with 1000 times greater affinity than said antibody or fragment thereof binds FcγRIIA.
An isolated antibody or a fragment thereof that specifically binds FcγRIIB with 104 times greater affinity than said antibody or fragment thereof binds FcγRIIA.
An isolated antibody or a fragment thereof that specifically binds FcγRIIB with 105 times greater affinity than said antibody or fragment thereof binds FcγRIIA.
An isolated antibody or a fragment thereof that specifically binds FcγRIIB with 106 times greater affinity than said antibody or fragment thereof binds FcγRIIA.
A pharmaceutical composition comprising (i) a therapeutically effective amount of the antibody or fragment thereof that specifically binds FcγRIIB with greater affinity than said antibody or fragment thereof binds FcγRIIA;
- and (ii) a pharmaceutically acceptable carrier.
A method for producing a monoclonal antibody that specifically binds FcγRIIB with greater affinity than said monoclonal antibody binds FcγRIIA, said method comprising:
- (a) immunizing FcγRIIA transgenic mice with purified FcγRIIB or an immunogenic fragment thereof;
- (b) booster immunizing said mice for a time sufficient to elicit an immune response;
- (c) producing hybridoma cells lines from spleen cells of said mice;
- (d) screening said hybridoma cell lines for one or more hybridoma cell lines that produce antibodies that specifically bind FcγRIIB with greater affinity than the antibodies bind FcγRIIA.
A method of treating cancer in a patient, said method comprising administering to said patient a therapeutically effective amount of an antibody or a fragment thereof that specifically binds FcγRIIB with greater affinity than said antibody or fragment thereof binds FcγRIIA.
A method of treating a B cell malignancy in a patient, said method comprising administering to said patient a therapeutically effective amount of an antibody or a fragment thereof that specifically binds FcγRIIB with greater affinity than said antibody or fragment thereof binds FcγRIIA.
A method of treating a disease in a patient comprising administering a therapeutically effective amount of a first antibody or fragment thereof that specifically binds FcγRIIB with a greater affinity than said antibody or fragment thereof binds FcγRIIA, and a second antibody, wherein said second antibody does not mediate its therapeutic effect by cell killing.
A method of treating a solid tumor in a patient having a tumor characterized by infiltration of a population of macrophages at the site of the tumor, said method comprising administering a therapeutically effective amount of a first antibody or fragment thereof that specifically binds FcγRIIB with a greater affinity than said antibody or fragment thereof binds FcγRIIA, wherein said antibody reduces the population of macrophages.
A method of treating cancer in a patient having a cancer characterized by a cancer antigen, said method comprising administering to said patient a therapeutically effective amount of a first antibody or fragment thereof that specifically binds FcγRIIB with a greater affinity than said antibody or fragment thereof binds FcγRIIIA, and a second antibody that does not bind said cancer antigen.
Dependencies are inferred from the claim text.