Ludwig Institute for Cancer Research Limited

Acorda Therapeutics, Inc.

Cambridge Neuroscience, Inc.

Other

Cambridge Neuroscience Research Inc.

Ludwig Institute for Cancer Research and Cambridge Neuroscience

Ian D Hiles

Michael Derek Waterfield

Paul Stroobant

Andrew David Goodearl

Luisa Minghetti

Mark Marchioni

Mario Su Chen

Ivan Tarasovich Gout

Ritu Bala Dhand

Michael J Fry

Mark Andrew Marchionni

Peter J Parker

Masayuki Otsu

George Panayoutou

Stefano Volinia

Maio Su Chen

Peter End

Masato Kasuga

Kazuyoshi Yonezawa

George Panayotou

Disclosed is the characterization and purification of DNA encoding a numerous polypeptides useful for the stimulation of glial cell (particularly, Schwann cell) mitogenesis and treating glial cell tumors. Also disclosed are DNA sequences encoding novel polypeptides which may have use in stimulating glial cell mitogenesis and treating glial cell tumors. Methods for the synthesis, purification and testing of both known and novel polypeptides for their use as both therapeutic and diagnostic aids in the treatment of diseases involving glial cells are also provided. Methods are also provided for the use of these polypeptides for the preparation of antibody probes useful for both diagnostic and therapeutic use in diseases involving glial cells.

Glial mitogenic factors, their preparation and use

This invention relates to new polypeptides which exhibit kinase activity or, more specifically, which show phosphoinositide (PI) 3-kinase activity. Such polypeptides are involved in pathways responsible for cellular growth and differentiation. An isolated polypeptide which possesses PI3-kinase activity when produced by recombinant production in insect cells is disclosed.

Method for determining expression of a PI3 kinase gene

Disclosed is the characterization and purification of DNA encoding a numerous polypeptides useful for the stimulation of glial cell (particularly, Schwann cell) mitogenesis and treating glial cell tumors. Also disclosed are DNA sequences encoding novel polypeptides which may have use in stimulating glial cell mitogenesis and treating glial cell tumors. Methods for the synthesis, purification and testing of both known and novel polypeptides for their use as both therapeutic and diagnostic aids in the treatment of diseases involving glial cells are also provided. Also included is the mature GGF peptide and the DNA encoding said peptide, exclusive of the N-terminal signal sequence. The mature GGF peptide and DNA encoding the same are also useful for treatment of conditions of the central nervous system. Methods are also provided for the use of these polypeptides for the preparation of antibody probes useful for both diagnostic and therapeutic use in diseases involving glial cells.

Glial mitogenic factors lacking an N-terminal signal sequence

The invention involves prophylaxis or treatment of nervous system pathological conditions. This is accomplished by administering secretable glial growth factors, such as the molecule referred to as GGF-2.

Method for prophylaxis or treatment of a nervous system, pathophysiological condition involving a glial growth factor sensitive cell by administration of a glial growth factor

Disclosed is the characterization and purification of DNA encoding polypeptides useful for the stimulation of glial cell mitogenesis. Methods for the synthesis, purification and testing of both known and novel polypeptides for their use as both therapeutic and diagnostic aids in the treatment of diseases involving glial cells are also provided. Methods are also provided for the use of these polypeptides in the prevention or treatment of multiple sclerosis.

Methods for treating multiple sclerosis with GGF-related polypeptides

Disclosed is the characterization and purification of DNA encoding a numerous polypeptides useful for the stimulation of glial cell (particularly, Schwann cell) mitogenesis and treating glial cell tumors. Also disclosed are DNA sequences encoding novel polypeptides which may have use in stimulating glial cell mitogenesis and treating glial cell tumors. Methods for the synthesis, purification and testing of both known and novel polypeptides for their use as both therapeutic and diagnostic aids in the treatment of diseases involving glial cells are also provided. Methods are also provided for the use of these polypeptides for the preparation of antibody probes useful for both diagnostic and therapeutic use in diseases involving glial cells. The present invention is specifically directed to methods of using said polypeptides to induce myelination and to treat multiple sclerosis.

Disclosed are methods for inducing myelination of neural cells by glial cells, The methods involve contacting glial cells with polypeptides comprising epidermal growth factor-like domains encoded by the GGF/p185 erb B2 ligand gene provided as a feature of the invention.

Polypeptides having kinase activity, their preparation and use

The invention features methods for stimulating glial cell mitogenesis by contacting the glial cells with p185,ligand polypeptides, including glial growth factor (GGF), a GGF splice variant comprised of segments E, B, A, C, and C/D or C/D&prime;, a 35 kD polypeptide factor isolated from rat I-EJ transformed fibroblast cells, 75 kD polypeptide factor isolated from the LKBR-3 human breast cells, 44 kD polypeptide factor isolated from the rat I-EJ transformed fibroblast cells, 45 kD polypeptide factor isolated from MDA-MB 231 human breast cells, 7-14 kD polypeptide factor isolated from the ATL-2 human T-cells, 25 kD polypeptide factor isolated from activated mouse peritoneal macrophages, and 25 kD polypeptide factor isolated from bovine kidney.

Methods of stimulating mitogenesis in glial cells using glial mitogenic factors

Disclosed are methods for treating pathophysiological conditions of the mammalian nervous system. The methods involve administering an effective amount of a polypeptide comprising amino acids 51 to 422 of human GGF2.

Method for treating nervous system pathophysiologies using glial growth factors

Disclosed are methods for treating pathophysiological conditions of the mammalian nervous system. The methods involve administering pharmaceutically effective amounts of recombinant polypeptides comprising epidermal growth factor-like domains encoded by the GGF/p185erbB2 ligand gene.

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London, United Kingdom

Ian D Hiles