Abstract: The present invention is directed to bi-specific monovalent diabodies that comprise an immunoglobulin Fc Domain (“bi-specific monovalent Fc diabodies”) and are composed of three polypeptide chains and which possess at least one binding site specific for an epitope of CD32B and one binding site specific for an epitope of CD79b (i.e., a “CD32B×CD79b bi-specific monovalent Fc diabody”). The bi-specific monovalent Fc diabodies of the present invention are capable of simultaneous binding to CD32B and CD79b. The invention is directed to such compositions, to pharmaceutical compositions that contain such bi-specific monovalent Fc diabodies and to methods for their use in the treatment of inflammatory diseases or conditions, and in particular, systemic lupus erythematosus (SLE) and graft vs. host disease.

Abstract: The present invention is directed to stable aqueous pharmaceutical formulations that comprise a bispecific monovalent diabody (“Diabody formulation”), and to aqueous stabilizer solutions for stabilizing and administering said diabody. The invention particularly concerns such pharmaceutical formulations that comprise a diabody drug product (DART-A DP formulations) that comprise a sequence-optimized CD 123×CDS bispecific diabody (DART-A) that is capable of simultaneously binding to CD 123 and CDS. The invention further concerns the use of such DART-A DP formulations in the treatment of hematologic malignancies such as acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in patients.

Abstract: The present invention is directed to molecules, such as monospecific antibodies and bispecific, trispecific or multispecific binding molecules, including diabodies, BITE® molecules, and antibodies that are capable of specifically binding to “Disintegrin and Metalloproteinase Domain-containing Protein 9” (“ADAM9”). The invention particularly concerns such binding molecules that are capable of exhibiting high affinity binding to human and non-human ADAM9. The invention further particularly relates to such molecules that are thereby cross-reactive with human ADAM9 and the ADAM9 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to all such ADAM9-binding molecules that comprise a Light Chain Variable (VL) Domain and/or a Heavy Chain Variable (VH) Domain that has been humanized and/or deimmunized so as to exhibit reduced immunogenicity upon administration of such ADAM9-binding molecule to a recipient subject.

Abstract: The present invention is directed to binding molecules that possess one or more epitope-binding sites specific for an epitope of CD137 and one or more epitope-binding sites specific for an epitope of a tumor antigen (“TA”) (e.g., a “CD137×TA Binding Molecule”). In one embodiment, such CD137×TA Binding Molecules will be bispecific molecules, especially bispecific tetravalent diabodies, that are composed of two, three, four or more than four polypeptide chains and possessing two epitope-binding sites each specific for an epitope of CD137 and two epitope-binding sites each specific for an epitope of a TA. Alternatively, such CD137×TA Binding Molecules will be bispecific molecules, especially bispecific trivalent binding molecules composed of three or more polypeptide chains and possessing one or two epitope-binding sites each specific for an epitope of CD137 and one or two epitope-binding sites each specific for an epitope of a TA.

Abstract: The present invention is directed in part to pharmaceutical compositions for storage and administration comprising a) a HER2/neu antibody (“margetuximab”), b) buffering agents, and c) stabilizers, wherein said margetuximab is stable. The invention in part provides, containers and kits comprising such pharmaceutical compositions. The invention is directed in part to the use of such pharmaceutical compositions, containers, and kits containing margetuximab in the treatment of HER2/neu-positive cancer (i.e., a cancer that expresses HER2), including breast cancer or gastric cancer or GEJ cancer.

Abstract: The present invention is directed to diabody molecules and uses thereof in the treatment of a variety of diseases and disorders, including immunological disorders, infectious disease, intoxication and cancers. The diabody molecules of the invention comprise two polypeptide chains that associate to form at least two epitope binding sites, which may recognize the same or different epitopes on the same or differing antigens. Additionally, the antigens may be from the same or different molecules. The individual polypeptide chains of the diabody molecule may be covalently bound through non-peptide bond covalent bonds, such as, but not limited to, disulfide bonding of cysteine residues located within each polypeptide chain. In particular embodiments, the diabody molecules of the present invention further comprise an Fc region, which allows antibody-like functionality to engineered into the molecule.

Abstract: The present invention relates to bispecific molecules that are capable of localizing an immune effector cell that expresses an activating receptor to a virally infected cell, so as to thereby facilitate the killing of the virally infected cell. In a preferred embodiment, such localization is accomplished using bispecific molecules that are immunoreactive with an activating receptor of an immune effector cell and to an antigen expressed by a cell infected with a virus wherein the antigen is detectably present on the cell infected with the virus at a level that is greater than the level at which the antigen is detected on the virus by the bispecific molecules, and to the use of such bispecific molecules in the treatment of latent viral infections.

Abstract: The present invention is directed to bi-specific monovalent diabodies that comprise an immunoglobulin Fc Domain (“bi-specific monovalent Fc diabodies”) and are composed of three polypeptide chains and which possess at least one binding site specific for an epitope of CD32B and one binding site specific for an epitope of CD79b (i.e., a “CD32B×CD79b bi-specific monovalent Fc diabody”). The bi-specific monovalent Fc diabodies of the present invention are capable of simultaneous binding to CD32B and CD79b. The invention is directed to such compositions, to pharmaceutical compositions that contain such bi-specific monovalent Fc diabodies and to methods for their use in the treatment of inflammatory diseases or conditions, and in particular, systemic lupus erythematosus (SLE) and graft vs. host disease.

Abstract: The present invention is directed to a dosing regimen for administering a CD 123×CDS bispecific diabody to patients with a hematologic malignancy such as acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The present invention is also directed to a dosing regimen for administering a CD 123×CDS bispecific diabody in combination with a molecule capable of binding PD-1 or a natural ligand of PD-1 (a “PD-1 or PD-1 ligand binding molecule”) to patients with a hematologic malignancy such as acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The invention particularly concerns the use of such regimens for administering the sequence-optimized CD 123×CDS bispecific diabody, “DART-A,” which is capable of simultaneous binding to CD 123 and CDS.

Abstract: The present invention is directed to a combination therapy involving the administration of a first molecule that specifically binds to human B7-H3 and a second molecule that that specifically binds to human PD-1 to a subject for the treatment of cancer and/or inflammation. The invention also concerns pharmaceutical compositions that comprise a first molecule that specifically binds to human B7-H3 and a second molecule that specifically binds to human PD-1 that are capable of mediating, and more preferably enhancing, the activation of the immune system against cancer cells that are associated with any of a variety of human cancers. The invention also relates to the use of such pharmaceutical compositions to treat cancer and other diseases in recipient subjects.

Abstract: The present invention is directed in part to pharmaceutical compositions for storage and administration comprising a) a HER2/neu antibody (“margetuximab”), b) buffering agents, and c) stabilizers, wherein said margetuximab is stable. The invention in part provides, containers and kits comprising such pharmaceutical compositions. The invention is directed in part to the use of such pharmaceutical compositions, containers, and kits containing margetuximab in the treatment of HER2/neu-positive cancer (i.e., a cancer that expresses HER2), including breast cancer or gastric cancer or GEJ cancer.

Abstract: The present invention relates to antibodies or fragments thereof that specifically bind Fc?RIIB, particularly human Fc?RIIB, with greater affinity than the antibodies or fragments thereof bind Fc?RIIA, particularly human Fc?RIIA. The present invention also provides the use of an anti-Fc?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 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.

Abstract: Disclosed herein, in one aspect, is a method of treating B cell driven autoimmune and allergic diseases, such as lupus, comprising administering to a patient in need thereof an effective amount of B cell inhibitor that is non-depletional.

Abstract: 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.

Abstract: The present invention relates to CD3-binding molecules capable of binding to human and non-human CD3, and in particular to such molecules that are cross-reactive with CD3 of a non-human mammal (e.g., a cynomolgus monkey). The invention also pertains to uses of such antibodies and antigen-binding fragments in the treatment of cancer, autoimmune and/or inflammatory diseases and other conditions.

Abstract: The present invention is directed to diabody molecules and uses thereof in the treatment of a variety of diseases and disorders, including immunological disorders, infectious disease, intoxication and cancers. The diabody molecules of the invention comprise two polypeptide chains that associate to form at least two epitope binding sites, which may recognize the same or different epitopes on the same or differing antigens. Additionally, the antigens may be from the same or different molecules. The individual polypeptide chains of the diabody molecule may be covalently bound through nonpeptide bond covalent bonds, such as, but not limited to, disulfide bonding of cysteine residues located within each polypeptide chain. In particular embodiments, the diabody molecules of the present invention further comprise an Fc region, which allows antibody like functionality to engineered into the molecule.

Abstract: The present invention is directed to diabody molecules and uses thereof in the treatment of a variety of diseases and disorders, including immunological disorders, infectious disease, intoxication and cancers. The diabody molecules of the invention comprise two polypeptide chains that associate to form at least two epitope binding sites, which may recognize the same or different epitopes on the same or differing antigens. Additionally, the antigens may be from the same or different molecules. The individual polypeptide chains of the diabody molecule may be covalently bound through non-peptide bond covalent bonds, such as, but not limited to, disulfide bonding of cysteine residues located within each polypeptide chain. In particular embodiments, the diabody molecules of the present invention further comprise an Fc region, which allows antibody-like functionality to engineered into the molecule.

Abstract: The present invention is directed to bi-specific diabodies that comprise two or more polypeptide chains and which possess at least one Epitope-Binding Site that is immunospecific for an epitope of PD-1 and at least one Epitope-Binding Site that is immunospecific for an epitope of LAG-3 (i.e., a “PD-1×LAG-3 bi-specific diabody”). More preferably, the present invention is directed to bi-specific diabodies that comprise four polypeptide chains and which possess two Epitope-Binding Sites that are immunospecific for one (or two) epitope(s) of PD-1 and two Epitope-Binding Site that are immunospecific for one (or two) epitope(s) of LAG-3 (i.e., a “PD-1×LAG-3 bi-specific, tetra-valent diabody”). The present invention also is directed to such diabodies that additionally comprise an immunoglobulin Fc Domain (“bi-specific Fc diabodies and bi-specific, tetra-valent, Fc diabodies”).

Abstract: This invention relates to a pharmaceutical composition that comprises a first molecule that specifically binds HER2/neu and a second molecule that specifically binds a cell-surface receptor (or its ligand) that is involved in regulating an immune checkpoint (or the ligand thereof). The invention particularly relates to the embodiment wherein the second molecule binds to PD-1. The invention also relates to the use of such pharmaceutical compositions to treat cancer and other diseases.

Abstract: The present invention is directed to molecules, such as monospecific antibodies and bispecific, trispecific or multispecific binding molecules, including diabodies, BITE® molecules, and antibodies that are capable of specifically binding to “Disintegrin and Metalloproteinase Domain-containing Protein 9” (“ADAM9”). The invention particularly concerns such binding molecules that are capable of exhibiting high affinity binding to human and non-human ADAM9. The invention further particularly relates to such molecules that are thereby cross-reactive with human ADAM9 and the ADAM9 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to all such ADAM9-binding molecules that comprise a Light Chain Variable (VL) Domain and/or a Heavy Chain Variable (VH) Domain that has been humanized and/or deimmunized so as to exhibit reduced immunogenicity upon administration of such ADAM9-binding molecule to a recipient subject.