Macrogenics, Inc.

Immunogen, Inc.

Gundo Diedrich

Leslie Sydnor Johnson

Ezio Bonvini

Paul A Moore

Liqin Liu

Chia-Ying Kao Lam

Kalpana Shah

Deryk T Loo

Hua Watson Li

Bhaswati Barat

Juniper A Scribner

Nicholas C Yoder

Alexey Yevgenyevich Berezhnoy

Stuart William Hicks

The present invention is directed to binding molecules that possess one or more epitope-binding sites specific for an epitope of CD137, including antibodies, and molecules comprising epitope-binding fragments thereof. The invention is further directed to multispecific binding molecules comprising 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 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 possessing two epitope-binding sites each specific for an epitope of CD137 and one epitope-binding sites each specific for an epitope of a TA. The invention also provides novel Binding Molecules, as well as derivatives thereof and uses thereof. The invention is directed to pharmaceutical compositions that contain such CD137 molecules. The invention is additionally directed to methods for the use of such molecules in the treatment of cancer and other diseases and conditions.

CD137 binding molecules and uses thereof

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. The CD137×TA Binding Molecules of the invention are capable of simultaneous binding to CD137, and a TA. The invention is directed to pharmaceutical compositions that contain any such CD137×TA Binding Molecules. The invention is additionally directed to methods for the use of such molecules in the treatment of cancer and other diseases and conditions. The invention also provides novel CD137-binding molecules, and HER2/neu-binding molecules, as well as derivatives thereof and uses thereof.

Bispecific binding molecules that are capable of binding CD137 and tumor antigens, and uses thereof

The present invention is directed to molecules (e.g., an antibody, a diabody, an scFv, an antibody, a TandAb, etc.) capable of binding an epitope of human CD16 (a 'CD16 Binding Molecule'). The present invention is further directed to CD 16 Binding Molecules that are capable of binding an epitope of human CD16 and one or more epitope(s) of a Disease Antigen ('DA') (e.g., a &#x201c;CD16&#xd7;DA Binding Molecule&#x201d;). The present invention is particularly directed to such CD16&#xd7;DA Binding Molecules that are antibodies, or that comprise an Epitope Binding Domain thereof, or are diabodies (including DART&#xae; diabodies), bispecific antibodies, TandAbs, other multispecific binding molecules (e.g., trivalent TRIDENT&#x2122; molecules), etc. The invention particularly concerns CD16&#xd7;DA Binding Molecules that are capable of binding a Disease Antigen that is a Cancer Antigen or a Pathogen-Associated Antigen in addition to being able to bind CD 16. The invention particularly concerns the use of such CD16 and CD16&#xd7;DA Binding Molecules in the treatment of cancer and pathogen-associated diseases. The present invention is also directed to pharmaceutical compositions that comprise such molecule(s).

Bispecific CD16-binding molecules and their use in the treatment of disease

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&#xd7;TA Binding Molecule'). In one embodiment, such CD137&#xd7;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&#xd7;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. The CD137&#xd7;TA Binding Molecules of the invention are capable of simultaneous binding to CD137, and a TA. The invention is directed to pharmaceutical compositions that contain any such CD137&#xd7;TA Binding Molecules. The invention is additionally directed to methods for the use of such molecules in the treatment of cancer and other diseases and conditions. The invention also provides novel CD137-binding molecules, and HER2/neu-binding molecules, as well as derivatives thereof and uses thereof.

The present invention is directed to molecules, such as monospecific antibodies and bispecific, trispecific or multispecific binding molecules, including diabodies, BITE&#xae; 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. The invention is also directed to pharmaceutical compositions that contain any of such ADAM9-binding molecules, and to methods involving the use of any of such ADAM9-binding molecules in the treatment of cancer and other diseases and conditions.

ADAM9-binding molecules, and methods of use thereof

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North Potomac, MD, United States of America

Gundo Diedrich