Regeneron Pharmaceuticals, Inc.

The University of North Carolina at Chapel Hill

Vesta Therapeutics Inc.

Incara Cell Technologies, Inc.

Mark E Furth

Stephen P Squinto

George D Yancopoulos

Samuel H Davis

Lola M Reid

Andrew T Bruce

John W Ludlow

Nancy Y Ip

Ronald M Lindsay

Eric M Shooter

Nicholas Moss

Ulrich Suter

Thomas H Aldrich

Nikos Panayotatos

David J Glass

Friedrich Lottspeich

Vivien Wong

Trevor Stitt

Hans Thoenen

Piotr J Masiakowski

Peter S DiStefano

Nancy P Ip

Kurt Stockli-Rippstein

Dan B Lindholm

Georg W Kreutzberg

Michael Sendtner

Yoshihiro Arakawa

Patrick Desmond Carroll

Rudolf Georg Gotz

Nicholas G Moss

Hepatic progenitors comprise two populations of human hepatic stem cells, primitive and proximal hepatic stem cells, and two populations of committed progenitors, one for biliary cells and one for hepatocytes. Human primitive hepatic stem cells are a very small fraction of the liver cell population and give rise to proximal hepatic stem cells constituting a much larger fraction of the liver. Human proximal hepatic stem cells give rise to biliary and hepatocyte committed progenitors. Primitive and proximal stem cells are the primary stem cells for the human liver. Human primitive hepatic stem cells may be isolated by immunoselection from human livers or culturing human liver cells under conditions which select for a human primitive hepatic stem cell. Proximal hepatic stem cells may be isolated by immunoselection, or by culturing human liver cells under conditions which include a developmental factor. Proximal hepatic stem cells may also be isolated by culturing colonies comprising a primitive hepatic stem cell under conditions which include a developmental factor. Resulting compositions may be used for treating liver disorders and for producing bioartificial organs.

Primitive and proximal hepatic stem cells

DNA encoding human ciliary neurotrophic factor and method for producing the protein encoded thereby

The present invention relates to the ciliary neurotrophic factor (CNTF) receptor, and provides for CNTF receptor nucleic acid and amino acid sequences. It also relates to (i) assay systems for detecting CNTF activity; (ii) experimental model systems for studying the physiologic role of CNTF; (ii) diagnostic techniques for identifying CNTF-related neurologic conditions; (iv) therapeutic techniques for the treatment of CNTF-related neurologic and muscular conditions, and (v) methods for identifying molecules homologous to CNTF and CNTFR.

Method for screening comprising cells expressing the CNTF receptor

The present invention relates to the ciliary neurotropic factor (CNTF) receptor, and provides for CNTF receptor antibodies. It also relates to diagnostic techniques for identifying CNTF-related neurologic conditions.

Ciliary neurotrophic factor receptor antibodies

Nucleic acid molecule encoding ciliary neurotrophic factor receptor

The present invention relates to a method of treatment of a neuromuscular or muscle disorder resulting from the loss of axonal contact with the muscle comprising administering an effective amount of ciliary neurotrophic factor. The invention also relates to a method of treatment of a disorder of a type of tissue or cell resulting from the loss of axonal contact with the cell comprising administering an effective amount of ciliary neurotrophic factor in which the type of tissue or cell expresses a CNTF receptor protein.

Methods of treatment using ciliary neurotrophic factor

The present invention provides for assay systems that may be used to detect and/or measure neurotrophin activity or to identify agents that exhibit neurotrophin-like activity, and for methods of using such assay systems. It is based, at least in part, on the discovery that the trkB protooncogene encodes a tyrosine kinase receptor that may serve as a functional binding protein for BDNF and NT-3. Such assay systems may be of particular value in identifying new neurotrophins or agents with neurotrophin-like activity. In various embodiments, the assay systems and methods of the invention may be used to detect and/or measure the binding of neurotrophin to trkB, either using direct binding studies or the detection of the secondary affects of trkB/neurotrophin binding. The present invention also has diagnostic and therapeutic utilities. In particular embodiments of the invention, methods of detecting aberrancies in trkB function or expression may be used in the diagnosis of neurological disorders. In other embodiments, manipulation of the trkB/neurotrophin interaction may be used in the treatment of neurological disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (Lou Gehrig's disease).

Assay systems for trkB neurotrophin activity

The present invention relates to chimeric neurotrophic factors which comprise at least a portion of a naturally occurring cellular factor and a portion of at least one other molecule such that the resulting chimeric molecule has neurotrophic activity. It is based, in part, on the discovery that chimeric molecules comprising portions of both NGF and BDNF are likely to possess neurotrotrophic activity, and in some cases exhibit a spectrum of activity larger than that of either parent molecule. It is further based on the discovery that chimeric molecules comprising neurotrophic factor sequences as well as additional peptide sequences may retain neurotrophic activity, and in some cases may exhibit a more potent activity than the parent factor. The chimeric neurotrophic factor molecules of the invention provide a number of advantages relative to naturally occurring neurotrophic factors. Chimeric neurotrophic factors may be used to provide, for example, the activity of two neurotrophic factors in a single molecule, or may serve as superagonists of an endogenous neurotrophic factor, thereby enabling an increased biological response at lower doses.

Multitrophic and multifunctional chimeric neurotrophic factors

Ciliary neurotrophic factor receptor

The present invention relates to chimeric neurotrophic factors which comprise at least a portion of a naturally occurring cellular factor and a portion of at least one other molecule such that the resulting chimeric molecule has neurotrophic activity. It is based, in part, on the discovery that chimeric molecules comprising portions of both NGF and BDNF are likely to possess neurotrotrophic activity, and in some cases exhibit a spectrum of activity larger than that of either parent molecule. It is further based on the discovery that chimeric molecules comprising neurotrophic factor sequences as well as additional peptide sequences may retain neurotrophic activity, and in some cases may exhibit a more potent activity than the parent factor. The chimeric neurotrophic factor molecules of the invention provide a number of advantages relative to naturally occurring neurotrophic factors. Chimeric neurotrophic factors may be used to provide, for example, the activity of two neurotrophic factors in a single molecule, or may serve as superagonists of an endogenous neurotrophic factor, thereby enabling an increased biological response at lower doses. Nucleic acids and plasmids encoding the chimeras are disclosed.

Multitrophic and multifunctional chimeric neurotrophic factors, and

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Pelham, NY, United States of America

Mark E Furth