Athersys, Inc.

Abt Holding Company

Other

John Joseph Harrington

Stephen Rundlett

Bruce Sherf

Paul David Jackson

Li Jiang

Michael J Robarge

Robert W Mays

Rakesh Ramachandran

Scott Cain

Benjamin Philip Faga

Chih-Lin Hsieh

Michelle Zawadski

John Mecom

Gregory B Foust

Pieter W Faber

Michael R Lieber

David Gerrish

Mike Robarge

George Mbella Ekema

P David Jackson

The present invention generally relates to a series of compounds, to pharmaceutical compositions containing the compounds, and to use of the compounds and compositions as therapeutic agents. More specifically, compounds of the present invention are thienylindole azepines. These compounds are serotonin receptor (5-HT) ligands and are useful for treating diseases, disorders, and conditions wherein modulation of the activity of serotonin receptors (5-HT) is desired (e.g. addiction, anxiety, depression, obesity, and others).

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The present invention generally relates to a series of compounds, to pharmaceutical compositions containing the compounds, and to use of the compounds and compositions as therapeutic agents. More specifically, compounds of the present invention are benzazepine compounds. These compounds are serotonin receptor (5-HT) ligands and are useful for treating diseases, disorders, and conditions wherein modulation of the activity of serotonin receptors (5-HT) is desired (e.g. addiction, anxiety, depression, obesity, and others).

The current disclosure provide a novel human calcium sensing receptor named CaR2 and the nucleotide sequence that encodes the receptor. The disclosure further provides antibodies specific for CaR2. Also disclosed are methods of identifying modulators of the receptor and methods of using the identified modulators to treat calcium receptor mediated conditions.

Calcium-sensing receptor 2 (CaR2) and methods for using

The present invention is directed generally to reduction or inactivation of gene function or gene expression in cells in vitro and in multicellular organisms. The invention encompasses methods for mutating cells using a combination of mutagens, particularly wherein at least one mutagen is an insertional mutagen, to achieve homozygous gene mutation or mutation of multiple genes required cumulatively to achieve a phenotype to create knock-outs, knock-downs, and other modifications in the same cell. The invention is also directed to cells (and libraries thereof) and organisms created by the methods of the invention, including those in which at least one of the genes created by insertional mutagenesis is tagged by means of the insertion sequences thereby allowing identification of the mutated gene(s). The invention is also directed to libraries of mutated cells and their uses. The invention is also directed to methods of identifying mutations with methods of the invention, in cells (and libraries thereof) and organisms, by means of the insertional tag.

Compositions and methods for making mutations in cell lines and animals

The present invention is directed generally to activating gene expression or causing over-expression of a gene by recombination methods in situ. The invention also is directed generally to methods for expressing an endogenous gene in a cell at levels higher than those normally found in the cell. In one embodiment of the invention, expression of an endogenous gene is activated or increased following integration into the cell, by non-homologous or illegitimate recombination, of a regulatory sequence that activates expression of the gene. In another embodiment, the expression of the endogenous gene may be further increased by co-integration of one or more amplifiable markers, and selecting for increased copies of the one or more amplifiable markers located on the integrated vector. The invention also provides methods for the identification, activation, isolation, and/or expression of genes undiscoverable by current methods since no target sequence is necessary for integration.

Compositions and methods for non-targeted activation of endogenous genes

The present invention is directed generally to activating gene expression or causing over-expression of a gene by recombination methods in situ. The invention also is directed generally to methods for expressing an endogenous gene in a cell at levels higher than those normally found in the cell. In one embodiment of the invention, expression of an endogenous gene is activated or increased following integration into the cell, by non-homologous or illegitimate recombination, of a regulatory sequence that activates expression of the gene. The invention also provides methods for the identification, activation, isolation, and/or expression of genes undiscoverable by current methods since no target sequence is necessary for integration. Thus, by the present invention, endogenous genes, including those associated with human disease and development, may be activated and isolated without prior knowledge of the sequence, structure, function, or expression profile of the genes.

The present invention is in the fields of molecular biology, cell biology, and genetics. The invention is directed generally to mutating genes in cells in vitro and in multi-cellular organisms. The invention encompasses methods for mutating genes in cells using polynucleotides that act as insertional mutagens. Such methods are used to achieve mutation of a single gene to achieve a desired phenotype as well as mutation of multiple genes, required cumulatively to achieve a desired phenotype, in a cell or in a multi-cellular organism. The invention is also directed to methods of identifying one or more mutated genes, made by the methods of the invention, in cells and in multi-cellular organisms, by means of a tagging property provided by the insertional mutagen(s). The insertional mutagen thus allows identification of one or more genes that are mutated by insertion of an insertional mutagen. The invention is also directed to methods for correlating a phenotype with a gene by screening or selecting cells that have been mutated by an insertional mutagen incorporated into one or more genes in a cell and identifying the gene or genes causing the phenotype by means of a tagging property in one or more of the insertional mutagens. The invention is also directed to cells and multi-cellular organisms created by the methods of the invention and uses of the cells and multicellular organisms. The invention is also directed to libraries of cells created by the methods of the invention and uses of the libraries.

Methods for mutating genes in cells using insertional mutagenesis

The present invention is directed generally to activating gene expression or causing over-expression of a gene by recombination methods in situ. The invention also is directed generally to methods for expressing an endogenous gene in a cell at levels higher than those normally found in the cell. In one embodiment of the invention, expression of an endogenous gene is activated or increased following integration into the cell, by non-homologous or illegitimate recombination, of a regulatory sequence that activates expression of the gene. The invention also provides methods for the identification, activation, isolation, and/or expression of genes undiscoverable by current methods since no target sequence is necessary for integration. The invention is specifically directed to methods of drug discovery using the activated gene products for compound testing.

The present invention relates to the identification of novel nucleic acid molecules and the proteins encoded by these nucleic acid molecules, as well as their production for use as therapeutics, diagnostics and for research purposes.

Nucleic acid and protein homologs and uses thereof

The present invention is directed generally to activating gene expression or causing over-expression of a gene by recombination methods in situ. The invention also is directed generally to methods for expressing an endogenous gene in a cell at levels higher than those normally found in the cell. In one embodiment of the invention, expression of an endogenous gene is activated or increased following integration into the cell, by non-homologous or illegitimate recombination, of a regulatory sequence that activates expression of the gene. In another embodiment, the expression of the endogenous gene may be further increased by co-integration of one or more amplifiable markers, and selecting for increased copies of the one or more amplifiable markers located on the integrated vector. In another embodiment, the invention is directed to activation of endogenous genes by non-targeted integration of specialized activation vectors, which are provided by the invention, into the genome of a host cell. The invention also provides methods for the identification, activation, isolation, and/or expression of genes undiscoverable by current methods since no target sequence is necessary for integration. The invention also provides methods for isolation of nucleic acid molecules (particularly cDNA molecules) encoding a variety of proteins, including transmembrane proteins, and for isolation of cells expressing such transmembrane proteins which may be heterologous transmembrane proteins. The invention also is directed to isolated genes, gene products, nucleic acid molecules, to compositions comprising such genes, gene products and nucleic acid molecules, and to vectors and host cells comprising such genes and nucleic acid molecules, that may be used in a variety of therapeutic and diagnostic applications. Thus, by the present invention, endogenous genes, including those associated with human disease and development, may be activated and isolated without prior knowledge of the sequence, structure, function, or expression profile of the genes.

The field of the invention is activating gene expression or causing over-expression of a gene by recombination methods in situ. The invention relates to expresssing an endogenous gene in a cell at levels higher than those normally found in the cell. Expression of the gene is activated or increased following integration, by non-homolgous or illegitimate recombination, of a regulatory sequence that activates expression of the gene. The method allows the identification and expression of gene undiscovered by current methods since no target sequence is necessary for integration. Thus, gene products associated with human disease and development are obtainable from gene that have not been sequenced and indeed, whose existence is unknown, as well as from well characterized genes. The methods provide gene products from such genes for therapeutic and diagnostic purposes. In one embodiment the vector comprises a promoter, an exon, and an unpaired splice donor sequence, the exon being derived from a eukaryotic gene.

The present invention is directed generally to activating gene expression or causing over-expression of a gene by recombination methods in situ. The invention also is directed generally to methods for expressing an endogenous gene in a cell at levels higher than those normally found in the cell. In one embodiment of the invention, expression of an endogenous gene is activated or increased following integration into the cell, by non-homologous or illegitimate recombination, of a regulatory sequence that activates expression of the gene. The invention also provides methods for the identification, activation, isolation, and/or expression of genes undiscoverable by current methods since no target sequence is necessary for integration. Thus, by the present invention, endogenous genes, including those associated with human disease and development, may be activated and isolated without prior knowledge of the, sequence, structure, function, or expression profile of the genes.

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Mentor, OH, United States of America

John Joseph Harrington