Regeneron Pharmaceuticals, Inc.

Columbia University

John Rudge

George D Yancopoulos

Eric L Smith

Thomas Nittoli

Jessica Kirshner

Frank Delfino

Lauric Haber

Alison Crawford

Jocelyn Holash

Neil E Stahl

Jesse M Cedarbaum

Jessica Kandel

Darrell Yamashiro

Jianzhong Huang

Yuping Xia

The protein known as six-transmembrane epithelial antigen of prostate 2 (STEAP2) is highly expressed in prostate cancer and is associated with the expression of other prostate cancer-associated genes. The present invention provides novel full-length human IgG antibodies that bind to human STEAP2 (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both STEAP2 and CD3 and activate T cells via the CD3 complex in the presence of STEAP2-expressing tumors. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human and monkey CD3, and a second antigen-binding molecule that specifically binds humanSTEAP2. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing STEAP2. The bispecific antigen-binding molecules of the invention are useful for the treatment of prostate diseases and disorders in which an upregulated or induced STEAP2-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of prostate cancers, including castrate-resistant prostate cancer. The present invention also includes anti-STEAP2 antibody drug conjugates which inhibit tumor growth in vivo.

Anti-STEAP2 antibodies, antibody-drug conjugates, and bispecific antigen-binding molecules that bind STEAP2 and CD3, and uses thereof

The protein known as six-transmembrane epithelial antigen of prostate 2 (STEAP2) is highly expressed in prostate cancer and is associated with the expression of other prostate cancer-associated genes. The present invention provides novel full-length human IgG antibodies that bind to human STEAP2 (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both STEAP2 and CD3 and activate T cells via the CD3 complex in the presence of STEAP2-expressing tumors. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human and monkey CD3, and a second antigen-binding molecule that specifically binds human STEAP2. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing STEAP2. The bispecific antigen-binding molecules of the invention are useful for the treatment of prostate diseases and disorders in which an upregulated or induced STEAP2-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of prostate cancers, including castrate-resistant prostate cancer. The present invention also includes anti-STEAP2 antibody drug conjugates which inhibit tumor growth in vivo.

Anti-STEAP2 antibody drug conjugates, and compositions and uses thereof

Methods of regressing or inhibiting a tumor in a subject by administering an agent capable of blocking, inhibiting, or ameliorating vascular endothelial growth factor (VEGF)-mediated activity to a subject in need thereof such that the tumor is regressed or inhibited. The method of the invention results in a reduction of tumor size and inhibition of tumor metastases. This method is particularly useful for patients suffering from bulky, metastatic cancers.

Method of tumor regression with VEGF inhibitors

Methods of treating anemic disorders in human subjects comprising administering a VEGF antagonist comprising a fusion polypeptide having an immunoglobulin-like (Ig) domain 2 of the VEGF receptor Flt1 and Ig domain 3 of the VEGF receptor Flk1 or Flt4, and a multimerizing component. Further included are methods of preventing anemia, increasing hematocrit levels, and increasing or stimulating erythropoietin, particularly in subjects being treated for cancer with chemotherapeutic agents and/or radiation.

Methods of treating anemia by inhibition of vascular endothelial growth factor (VEGF)

Modified chimeric polypeptides with improved pharmacokinetics are disclosed. Specifically, modified chimeric Flt1 receptor polypeptides that have been modified in such a way as to improve their pharmacokinetic profile are disclosed. Also disclosed are methods of making and using the modified polypeptides including but not limited to using the modified polypeptides to decrease or inhibit plasma leakage and/or vascular permeability in a mammal. Also disclosed are methods of treating diseases in which plasma leakage and/or vascular permeability occurs, for example, inflammatory skin diseases.

Methods of treating inflammatory skin diseases

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Mahopac, NY, United States of America

John Rudge