Rigel Pharmaceuticals, Incorporated

Rigel, Inc.

Rigel Pharmaceuticlas, Inc.

James B Lorens

Ying Luo

Jakob Maria Bogenberger

Pei Wen Yu

Joseph Fisher

Donald G Payan

Alexander B Rossi

Weiduan Xu

Sacha Holland

Esteban Masuda

Todd M Kinsella

David C Anderson

Yasumichi Hitoshi

Mary Shen

X Charlene Liao

Robert E Atchison

Peter Chu

Denise Pearsall

Annabelle Freiro

Chao Bai (Betty) Huang

The invention relates to novel methods of detecting alterations in cell cycle regulation in a cell or a cell population and screening for agents capable of modulating cell cycle regulation through the use of multiparameter assays and a fluorescence-activated cell sorter (FACS) machine.

Multiparameter FACS assays to detect alterations in cellular parameters and to screen small molecule libraries

The present invention relates to regulation of angiogenesis. More particularly, the present invention is directed to nucleic acids encoding 'angiogenesis regulatory proteins and nucleic acids' which are involved in modulation of angiogenesis. The invention further relates to methods for identifying and using agents, including small organic molecules, antibodies, peptides, cyclic peptides, nucleic acids, antisense nucleic acids, RNAi, and ribozymes, that modulate angiogenesis via modulation of angiogenesis regulatory proteins and nucleic acids; as well as to the use of expression profiles and compositions in diagnosis and therapy of diseases related to angiogenesis.

Modulators of angiogenesis

The present invention relates to regulation of angiogenesis. More particularly, the present invention is directed to nucleic acids encoding C1-angiogenesis protein, also called integrin-linked kinase associated protein ('ILKAP') and ILKAP protein, which is involved in modulation of angiogenesis. The invention further relates to methods for identifying and using agents, including small organic molecules, antibodies, peptides, cyclic peptides, nucleic acids, antisense nucleic acids, and ribozymes, that modulate angiogenesis via modulation of ILKAP and ILKAP-related cascades; as well as to the use of expression profiles and compositions in diagnosis and therapy of angiogenesis.

The present invention provides random cDNA expression vector libraries, comprising expression vectors which comprise random cDNAs positioned in sense and antisense orientation, which are useful for the delivery and expression of a combination of genetic effector types to host cells. Methods for producing these libraries through bi-directional cloning of random cDNAs are also provided. Also provided herein are methods of using these libraries to screen for agents capable of modulating cell phenotype in desirable ways.

Bi-directionally cloned random cDNA expression vector libraries, compositions and methods of use

The invention relates to methods and compositions useful for screening for altered cellular phenotypes using an inducible expression system to enrich for and detect the altered phenotypes and, more particularly, relates to screening libraries of candidate bioactive agents, for example, nucleic acids and peptides, in cells using an regulatable expression system to enrich for a subpopulation of cells having an altered phenotype due to the presence of a candidate bioactive agent.

Methods and compositions for screening for altered cellular phenotypes

Described is a method for screening for alterations in exocytosis of a population of cells. The cells are sorted by a FACS machine by assaying for alterations in at least three of the properties selected from the group consisting of light scattering, fluorescent dye uptake, fluorescent dye release, annexin granule binding, surface granule enzyme activity, and the quantity of granule specific proteins. Methods for screening for bioactive agents capable of modulating exocytosis in a cell are also described. The methods provide for reduced background and increased specificity without increasing the time or steps involved in assaying for exocytosis.

Multiparameter FACS assays to detect alterations in exocytosis

The invention provides shuttle vectors, and methods of using shuttle vectors, capable of expression in, at least, a mammalian cell. Furthermore, the shuttle vectors are capable of replication in at least yeast, and optionally, bacterial cells. Also provided is a method wherein yeast are transformed with a shuttle vector as provided herein. Heterologous nucleic acids flanked by 5&prime; and 3&prime; ends identical to a homologous recombination site within the shuttle vector are introduced to the transformed yeast and allowed to homologously recombine with the shuttle vector such that they are inserted into the vector by the yeast organism. The shuttle vector is then recovered and transferred to a mammalian cell for expression.

Shuttle vectors

The present invention is directed to novel exocytotic polypeptides, such as Exo1 and Exo2 polypeptides and related molecules, which have an inhibitory effect on exocytosis and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided by the present invention are method for identifying novel compositions which mediate exocytotic polypeptide bioactivity, and the use of such compositions in diagnosis and treatment of disease.

Exo1 and Exo2, exocytotic proteins

The invention related to novel methods of detecting alterations in cell cycle regulation in a cell or a cell population and screening for agents capable of modulating cell cycle regulation through the use of multiparameter assays and a fluorescence-activated cell sorter (FACS) machine.

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Portola Valley, CA, United States of America

James B Lorens