Yale University

New York University

Isis Pharmaceuticals, Inc.

Cambridge Enterprise Limited

Genetics Indtitute LLC

Alexion Pharmaceuticals, Inc.

Jordan S Pober

C Frank Bennett

Yi Wang

W Mark Saltzman

Shohei Koide

Akiko Koide

Peter Petzelbauer

Thomas P Condon

Joseph M Carroll

James Keith

Shin Cheng Flournoy

Martin Kluger

Wang Min

Paul Clark

John Bradley

Philip W Askenase

Allan G Murray

Christopher C Hughes

Weillie Ma

Claire Albert

Gregory T Tietjen

Laura Bracaglia

Lingfeng Qin

Daniel Jane-Wit

A platform technology provides particle and nucleic acid conjugates, and compositions thereof, with enhanced targeting to cells, tissues, organs. The particles and nucleic acids and other deliverables contain a synthetic binding protein such as a polypeptide monobody covalently conjugated to the surface of the particle or the nucleic acid, for linking a targeting agent to the particle's surface or the nucleic acid. The particles and nucleic acids and other deliverables optionally contain an antibody non-covalently conjugated to the binding protein, via an Fc domain of the antibody. The particles can include therapeutic agents, diagnostic agents, prophylactic agents, or a combination thereof, to be delivered to desired cells, tissues, and/or organs. The particles and nucleic acids and other deliverables can be used in a wide array of applications including, but not limited to, ex vivo perfusion of mammalian organs and in vivo disease treatment.

Enhanced targeting platform

This invention relates to the identification and characterization of specific cellular responses which are associated with tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 1 (TNFR2). Selective modulation of these tumor necrosis factor receptors (TNFRs) Selective modulations of these responses may be useful in the promotion or inhibition of cell growth, for example, in the treatment of disease conditions, including cardiovascular and kidney diseases. Therapeutic methods employed selective TNFR1 and TNFR2 modulators are provided, along with screening methods for the identification of selective TNFR1 and TNFR2 modulators useful in such methods.

Methods for identifying modulators of tumor necrosis factor receptors

The use of interleukin-11 to prevent, to ameliorate, and to treat an immune-mediated disease in a mammal in need of such treatment is disclosed.

Use of interleukin-11 to prevent immune-mediated cytotoxicity

Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a nucleic acid encoding a lymphocyte function associated antigen 3 (LFA-3; also known as CD58) protein are provided.

Antisense modulation of LFA-3

The present invention describes a novel immunodeficient rodent model comprising an organ graft, such as a human skin graft, said graft containing microvessels lined by endothelial cells, human T lymphocytes and, optionally, at least one agent capable of substantially depleting the rodent's Natural Killer cells. The human T lymphocytes are engrafted and circulating in the animal's blood, enabling interaction with the endothelial cells which can be allogenic to the donor for the skin graft. The immunodeficient rodent used can be a SCID mouse. Preferably, the endothelial cells are provided by grafting said human skin with an intact dermal superficial vascular plexus. This immunodeficient rodent can be used as a model for studying inflammatory human immune responses of the engrafted T lymphocytes to foreign antigen as well as for studying human allograft rejection, e.g. human microvessel destruction and the T cell-endothelial cell in vivo interactions associated with a human allograft rejection.

Immunodeficient animal model for studying T cell-mediated immune

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Guilford, CT, United States of America

Jordan S Pober