Regeneron Pharmaceuticals, Inc.

Nicholas W Gale

George D Yancopoulos

David M Valenzuela

Samuel H Davis

Rostislav Chernomorsky

Eric L Smith

Gavin Thurston

David Frendewey

Aris N Economides

Neil E Stahl

Wojtek Auerbach

Thomas H Aldrich

William Poueymirou

Sam Cichon

Mitchell Goldfarb

Irene Noguera-Troise

Peter C Maisonpierre

Eric Smith

Thomas M Dechiara

Irene Noguera

A system for processing samples by a robotic platform has a tray that defines a well defining a drain. The well has a bottom surface, an access port in fluid communication with the drain, and an insert adapted to be received in the well. The insert has a bottom wall and a side wall. At least one of the bottom wall and the side wall define a plurality of openings, such that an interior of the insert is in fluid communication with the well when the insert is inserted into the well.

Systems and trays for processing samples by a robotic platform

Disclosed is a therapeutic method for inhibiting development or growth of tumors that are resistant to the blockade of delta-like ligand 4 (Dll4), or vascular endothelial growth factor (VEGF), or to other therapeutic agents, by administering the combination of Dll4 antagonist and VEGF antagonist. The combined administration of these two agents, concurrently or sequentially, exhibits synergistic effects on blood vessel development and growth, thereby more effectively inhibiting the tumor growth than an administration of either agent alone. The Dll4 antagonist can be an anti-Dll4 antibody or antibody fragment capable of inhibiting the binding of Dll4 to a Notch receptor, or a fusion protein comprising the extracellular domain of Dll4 or a soluble Notch receptor, or a fragment thereof, fused to a multimerizing component. The VEGF antagonist can be a VEGF trap, anti-VEGF antibody or antibody fragment capable of inhibiting the binding of VEGF to a VEGF receptor.

Therapeutic methods for inhibiting tumor growth with combination of Dll4 antagonists and VEGF antagonists

Novel fusion polypeptide ligands that bind Eph family receptors or the Tie-2 receptor are identified, and methods for making the fusion polypeptide ligands in biologically active form are described. Nucleic acids encoding these novel fusion polypeptide ligands enable production of the fusion polypeptide ligands. The method of making the nucleic acids and the fusion polypeptide ligands is broadly applicable to the production of polypeptide ligands in general, resulting in improved affinity and/or increased activity of the ligand when compared to its native form.

Method of enhancing the biological activity of ligands

Methods for imaging and targeting tumor vasculature are provided. Specifically, the methods for imaging and targeting tumor vasculature relate to using ephrin-B2 to image developing tumor vasculature and to target therapeutic agents to developing tumor vasculature. Kits for imaging and targeting tumor vasculature are also provided. Also provided for are methods of delivering agents to vasculature.

Methods of imaging and targeting vasculature

A novel ligand (Efl-6) that binds the Elk subfamily of Eph receptors is identified, and methods for making the soluble Elf-6 ligand in biologically active form is described. A cDNA clone encoding this novel protein enables production of the recombinant protein, which is useful to support neuronal and other eph receptor-bearing cell populations.

Biologically active Eph family ligands

Novel ligands that bind Eph family receptors are identified, and methods for making the soluble ligands in biologically active form are described. cDNA clones encoding these novel proteins enable production of the recombinant proteins, which are useful to support neuronal and other receptor-bearing cell populations.

Method of enhancing the biological activity of Eph family ligands

Growing community of inventors

Tarrytown, NY, United States of America

Nicholas W Gale