Health Research, Inc.

Tracon Pharmaceuticals, Inc.

Ben K Seon

Hirofumi Toi

Provided are compositions and methods that relate to prophylaxis and therapy of angiogenesis associated disease and includes novel knockin mice which express novel human/mouse chimeric endoglin, vectors for use in making such mice, and murine embryonic stem cells comprising the novel human/mouse transgene. Also provided are anti-human endoglin monoclonal antibodies (mAbs) which can be used as antiangiogenic agents for prophylaxis or therapy of human tumor angiogenesis and human angiogenesis-associated diseases having excessive vascularization. The mAbs do not cross react with murine endoglin. Also provides are methods for using the anti-human endoglin mAbs for prophylaxis or therapy of human tumor angiogenesis and for angiogenesis-associated diseases having excessive vascularization.

Anti-endoglin antibodies and knockin mice expressing novel human/mouse chimeric endoglin

The present invention provides a method for enhancing the efficacy of chemotherapeutic agents for therapy of cancer including tumors and other angiogenesis-associated diseases such as rheumatoid arthritis. The method comprises the steps of administering to an individual in need of treatment, a combination of an anti-endoglin antibody and a chemotherapeutic agent. The anti-endoglin antibody and the chemotherapeutic agent may be administered sequentially or concurrently.

Method for increasing the efficacy of anti-tumor agents by anti-endoglin antibody

The present invention provides a method for enhancing the efficacy of chemotherapeutic agents for therapy of cancer and other angiogenesis-associated diseases such as rheumatoid arthritis. The method comprises the steps of administering to an individual in need of treatment, a combination of an anti-endoglin antibody and a chemotherapeutic agent. The anti-endoglin antibody and the chemotherapeutic agent may be administered sequentially or concurrently.

A monoclonal antibody, or fragments thereof, having binding specificity for both endoglin expressed on human vascular endothelial cells and on murine endothelial cells. Antiangiogenic therapy in mammals can be effected by administering to the mammalian host a therapeutically effective amount of an anti-endoglin monoclonal antibody, or fragment thereof, which is conjugated to at least one angiogenesis inhibitor or antitumor agent. The composition is useful for treating tumor and angiogenesis-associated diseases.

Anti-endoglin monoclonal antibodies and their use in antiangiogenic therapy

A monoclonal antibody, or fragments thereof, having binding specificity for both endoglin expressed on human vascular endothelial cells and on murine endothelial cells. Antiangiogenic therapy in mammals can be effected by administering to the mammalian host a therapeutically effective amount of an anti-endoglin monoclonal antibody, or fragment thereof, either unconjugated or conjugated to at least one angiogenesis inhibitor or antitumor agent. The composition is useful for treating tumor and angiogenesis-associated diseases.

Anti-endoglin monoclonal antibodies and their use in antiangiogenic

Three monoclonal antibodies defining extracellular epitopes of a unique heterodimeric glycoprotein complex consisting of the human mb-1 protein and the human B29 protein which react with one or more leukemia lymphoma cell specimens selected from the group consisting of B prolymphocytic leukemia cells, B non-Hodgkin's lymphoma cells, B chronic lymphocytic leukemia cells, B hairy cell leukemia cells, and B acute lymphoblastic leukemia cells. The three monoclonal antibodies also react with human non-malignant B cells. The invention also provides a method for producing the new monoclonal antibodies and for diagnostic procedures using the monoclonal antibodies and for the treatment of leukemia-lymphoma patients and patients with immunological diseases. The invention also relates to the isolation and chemical identification of the human B29 and mb-1 proteins of B cell antigen receptor complex. The amino-terminal amino acid sequences of the mb-1 and B29 gene products were determined.

Monoclonal antibodies that define a unique antigen of human B cell

A leukemia lymphoma reactive monoclonal antibody which, relative to normal peripheral blood cells, strongly reacts with one or more leukemia lymphoma cell specimens selected from the group consisting of B non-Hodgkin's lymphoma cells, B chronic lymphocytic leukemia cells, B prolymphocytic leukemia cells, B hairy cell leukemia cells, and B acute lymphoblastic leukemia cells. More specifically, a novel hybrid cell line, designated 2B-4G9, for production of monoclonal antibody specific for a unique cell surface epitope associated with a wide variety of human lymphomas and leukemias is provided. This invention also provides a method for producing the new monoclonal antibody and to diagnostic procedures using the new monoclonal antibody to detect various leukemias and lymphomas. Also disclosed are methods of using the antibody or reactive fragments of the antibody for the treatment of leukemia-lymphoma patients.

Monoclonal antibody reactive to human leukemia and lymphoma cells and

A novel hybrid cell line, designated T6-1G9, for production of monoclonal antibodies specific for a unique cell surface epitope associated with a wide variety of human lymphomas and leukemias. Hybridoma T6-1G9 was generated by fusing mouse myeloma cells with spleen cells from a BALB/c mouse that was immunized with a human leukemia antigen preparation isolated from the cell membranes of acute lymphoblastic leukemia cells. This invention also provides a method for producing the new monoclonal antibody designated SN7 and to diagnostic procedures using SN7 to detect various leukemias and lymphomas. Also disclosed are methods of using SN7 or reactive fragments of SN7 for the treatment of leukemia-lymphoma patients.

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Williamsville, NY, United States of America

Ben K Seon