University of Connecticut

Beth Israel Deaconess Medical Center, Inc.

Kevin Patrick Claffey

Timothy Hla

Charan Devarakonda

Teresa Sanchez

Daniel Kita

Ji-Hye Paik

Michael Detmar

Donald R Senger

Described herein is an isolated antibody or antigen-binding fragment including a heavy chain variable region including three heavy chain complementary determining regions (HCDRs), wherein the sequence of HCDR1 is GYRLSELS (SEQ ID NO: 1), the sequence of HCDR2 is ISGWDGNT (SEQ ID NO: 2), and the sequence of HCDR3 is ARASGYNY (SEQ ID NO: 3), wherein the isolated antibody or antigen-binding fragment specifically binds human HSP90, specifically HSP90 beta. Also included are detection and therapeutic methods using the isolated antibodies or antigen-binding fragments.

Antibody and antigen-binding fragment compositions targeting cell surface antigens in tumors and methods of use thereof

Described herein is an isolated antibody or antigen-binding fragment including a heavy chain variable region including three heavy chain complementary determining regions (HCDRs), wherein the sequence of HCDR1 is GYRLSELS (SEQ ID NO: 1), the sequence of HCDR2 is ISGWDGNT (SEQ ID NO: 2), and the sequence of HCDR3 is ARASGYNY(SEQ ID NO: 3), wherein the isolated antibody or antigen-binding fragment specifically binds human HSP90, specifically HSP90 beta. Also included are detection and therapeutic methods using the isolated antibodies or antigen-binding fragments.

Agonists of vascular endothelial sphingosine-1-phosphate receptors are described. Compounds such as FTY720 can be phosphorylated by sphingosine kinase-2 into the phosphorylated forms which serve as sphingosine-1-phosphate receptor agonists. The vascular endothelial sphingosine-1-phosphate receptor agonists are employed in methods of treating a mammal for vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels. The sphingosine-1-phosphate receptor agonists can be used for the manufacture of a medicament for treating vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels.

Methods of inhibiting vascular permeability and apoptosis

Agonist of vascular endothelial sphingosine-1-phosphate receptors are described. Compounds such as FTY720 can be phosphorylated by sphingosine kinase-2 into the phosphorylated forms which serve as sphingosine-1-phosphate receptor agonists. The vascular endothelial sphingosine-1-phosphate receptor agonists are employed in methods of treating a mammal for vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels. The sphingosine-1-phosphate receptor agonists can be used for the manufacture of a medicament for treating vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels.

The present invention provides a method for inhibiting tumor angiogenesis in a living subject. The method relies upon tumor angiogenesis mediated by vascular endothelial growth factor and specified induced integrin cell surface receptors expressed on the endothelial cells of tumor-included and tumor-associated blood vessels. The methodology also administers at least one antagonistic preparation effective against specified induced and expressed integrin heterodimers on the endothelial cell surface of the living subjects, the consequence of which results in an effective inhibition of tumor angiogenesis in-vivo.

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Burlington, CT, United States of America

Kevin Patrick Claffey