Macrogenics, Inc.

Nadine Tuaillon

Leslie Sydnor Johnson

Ling Ling Huang

Ezio Bonvini

Scott Koenig

Christopher Rankin

Maria Concetta Veri

Hua Watson Li

Jeffrey B Stavenhagen

Sergey Gorlatov

Jeffery Stavenhagen

Jeffrey Stavenhagen

This invention relates to antibodies that specifically bind HER2/neu, and particularly chimeric 4D5 antibodies to HER2/neu, which have reduced glycosylation as compared to known 4D5 antibodies. The invention also relates to methods of using the 4D5 antibodies and compositions comprising them in the diagnosis, prognosis and therapy of diseases such as cancer, autoimmune diseases, inflammatory disorders, and infectious disease.

HER2/neu-specific antibodies and methods of using same

The present invention relates to methods of treatment, prevention, management or amelioration of one or more symptoms of diseases or disorders associated with CD20 expression that encompass administration of a combination of: (A) one or more antibodies that specifically bind Fc&#x3b3;RIIB, particularly human Fc&#x3b3;RIIB, with greater affinity than said antibodies bind Fc&#x3b3;RIIA, and (B) one or more antibodies that specifically bind to CD20. Such methods include methods of treating, preventing, managing or ameliorating one or more symptoms of a B cell related disease or disorder or an inflammatory disorder. The invention also provides pharmaceutical compositions comprising an anti-Fc&#x3b3;RIIB antibody and an anti-CD20 antibody.

Combination of Fc&#x3b3;RIIB-specific antibodies and CD20-specific antibodies and methods of use thereof

HER2/neu-specific antibodies and methods of using the same

The present invention relates to antibodies or fragments thereof that specifically bind the extracellular domain of Fc&#x3b3;RIIB, particularly human Fc&#x3b3;RIIB, and block the Fc binding site of human Fc&#x3b3;RIIB. The invention provides methods of treating cancer and/or regulating immune complex-mediated cell activation by administering the antibodies of the invention to enhance an immune response. The invention also provides methods of breaking tolerance to an antigen by administering an antigen-antibody complex and an antibody of the invention.

Fc&#x3b3;RIIB specific antibodies and methods of use thereof

The present invention relates to antibodies or fragments thereof that specifically bind Fc&#x3b3;RIIB, particularly human Fc&#x3b3;RIIB, more particularly the extracellular domain of Fc&#x3b3;RIIB with greater affinity than said antibodies or fragments thereof bind Fc&#x3b3;RIIA, particularly human Fc&#x3b3;RIIA, and block the Fc binding site of Fc&#x3b3;RIIB. The present invention also encompasses the use of an anti-Fc&#x3b3;RIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The present invention also encompasses the use of an anti-Fc&#x3b3;RIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies. The present invention provides pharmaceutical compositions comprising an anti-Fc&#x3b3;RIIB antibody or an antigen-binding fragment thereof, in amounts effective to prevent, treat, manage, or ameliorate a cancer, such as a B-cell malignancy, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The invention further 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 with a vaccine composition. The invention further provides methods of treating cancer and/or regulating immune complex-mediated cell activation by administering the antibodies of the invention to enhance an immune response. The invention also provides methods of breaking tolerance to an antigen by administering an antigen-antibody complex and an antibody of the invention.

The present invention relates to molecules comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds Fc&#x3b3;RIIIA and/or Fc&#x3b3;RIIA with a greater affinity relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are useful in preventing, treating, or ameliorating symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function mediated by Fc&#x3b3;R is desired, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

Identification and engineering of antibodies with variant Fc regions and methods of using same

The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds Fc&#x3b3;RIIIA and/or Fc&#x3b3;RIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by Fc&#x3b3;R is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

The present invention relates to antibodies or fragments thereof that specifically bind Fc&#x3b3;RIIB with greater affinity than said antibodies or fragments thereof bind Fc&#x3b3;RIIA. The present invention also encompasses the use of an anti-Fc&#x3b3;RIIB antibody or an antigen-binding fragment thereof for the treatment, prevention, management, or amelioration of a disease or disorder. The invention further 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 with a vaccine composition. The invention also provides methods of breaking tolerance to an antigen by administering an antigen-antibody complex and an antibody of the invention.

The present invention relates to antibodies or fragments thereof that specifically bind Fc&#x3b3;RIIB, particularly human Fc&#x3b3;RIIB, with greater affinity than said antibodies or fragments thereof bind Fc&#x3b3;RIIA, particularly human Fc&#x3b3;RIIA. The present invention also encompasses the use of an anti-Fc&#x3b3;RIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The present invention also encompasses the use of an anti-Fc&#x3b3;RIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies. The present invention provides pharmaceutical compositions comprising an anti-Fc&#x3b3;RIIB antibody or an antigen-binding fragment thereof, in amounts effective to prevent, treat, manage, or ameliorate a cancer, such as a B-cell malignancy, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The invention further 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 with a vaccine composition.

CD16A binding proteins useful for the reduction of a deleterious immune response are described. In one aspect, humanized anti-cd16A antibodies, optionally lacking effector function, are used for the treatment of immune disorders such as idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia.

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Gettysburg, PA, United States of America

Nadine Tuaillon