University of California

University of Florida Research Foundation Inc

Biomolecular Research Institute Ltd.

Kineta One, LLC

Bachem Americas, Inc.

Bachem Bioscience, Ing.

Bachem Biosciences, Inc.

K George Chandy

Heike Wulff

J Jay Gargus

George A Gutman

Emmanuelle Fantino

Katarin Kalman

Christine Beeton

William Michael Pennington

Ping Wang

Shawn P Iadonato

William Reade Kem

Michael William Pennington

Hiroaki Tomita

Raymond Stanley Norton

Katalin Kalman

Julia Vennekamp

M Reza Mirbolooki

Stephan Grissmer

Sanjeev Kumar Upadhayay

Wolfram Hansel

Paolo Sassone-Corsi

Vikram Shakkottai

Kristin Lynn Eckel-Mahan

Ralf Koehler

Jogesh Mukherjee

Joachim Hoyer

Activation of brown adipose tissue, treatment of obesity and/or treatment of obesity-related disorders in human or non-human animal subjects by administering to the subject a potassium channel inhibiting agent. The potassium channel inhibiting agent may comprise ShK toxin or a modified ShK toxin. Examples of modified ShK toxins include ShK-186.

Treatment of obesity and obesity related disorders by pharmalogical targeting of Kv1.3 potassium channels

Analogs of ShK toxin and methods for using such ShK analogs. The ShK analogs generally comprise ShK toxin attached to a chemical entity (e.g. an atom, molecule, group, residue, compound, moiety, etc.) that has an anionic charge. In some embodiments the chemical entity attached to the ShK toxin may comprise an amino acid residue. The ShK analogs may be administered to human or non-human animal subjects to cause inhibition of potassium channels or to otherwise treat diseases or disorders. In some embodiments, the chemical entity to which the ShK toxin is attached may be chosen to provide selective inhibition of certain potassium channels (e.g., Kv1.3 channels) over other potassium channels (e.g., Kv1.1 channels). In come embodiments, the chemical entity to which the ShK toxin is attached may include a fluorophore, thereby providing a fluorophore tagged ShK analog. Such fluorophore tagged ShK analogs may be used in flow cytometry alone, or in conjunction with class II tetramers that can detect autoreactive cells.

Analogs of ShK toxin and their uses in selective inhibition of Kv1.3 potassium channels

Analogs of ShK toxin and methods for using such ShK analogs. The ShK analogs generally comprise ShK toxin attached to a chemical entity (e.g. an atom, molecule, group, residue, compound, moiety, etc.) that has an anionic charge. The ShK analogs may be administered to human or non-human animal subjects to cause inhibition of potassium channels or to otherwise treat diseases or disorders. In some embodiments, the chemical entity to which the ShK toxin is attached may be chosen to provide selective inhibition of certain potassium channels (e.g., Kv 1.3 channels) over other potassium channels (e.g., Kv 1.1 channels). In come embodiments, the chemical entity to which the ShK toxin is attached may include a fluorophore and such fluorophore-tagged ShK analogs may be used in flow cytometry alone, or in conjunction with class II tetramers that can detect autoreactive cells.

Methods, compositions and devices for inhibiting neoproliferative changes in blood vessel walls or other anatomical structures. One or more compounds of Formula I or I-A set forth herein are administered systemically and/or locally to human or veterinary patients to deter or prevent unwanted proliferative changes in blood vessels or other anatomical structures. The invention may be used to deter or prevent stenosis or restenosis of arteries following angioplasty and/or stent placement. In one embodiment, there is provided an implantable stent or stent graft from which one or more compounds of the present invention will elute or otherwise be delivered into an affected blood vessel wall.

Methods for inhibiting neoproliferative changes in blood vessel walls

Compositions of matter comprising 5-phenylalkoxypsoralen compounds and their method of synthesis and use. The compounds are useable to treat diseases or disorders in human or veterinary patients, including autoimmune diseases such as multiple sclerosis. The compounds inhibit potassium channels, including the Kv1.3 channel and at least some of the therapeutic effects of such compounds may be due at least in part to potassium channel inhibition.

Substituted 5-alkoxypsoralens as inhibitors of potassium channel activity in lymphocytes and other cells

The present invention is based on the discovery and cloning of the human small conductance calcium activated potassium channel type 3 (hKCa3/KCNN3) gene, which is expressed in neuronal cells, skeletal muscle, heart, and lymphocytes. Alterations in the hKCa3/KCNN3 gene or its protein product may enhance susceptibility to schizophrenia and/or bipolar disorder. hKCa3/KCNN3 may be involved in neuropsychiatric, neurological, neuromuscular, and immunological disorders. Substantially purified hKCa3/KCNN3 polypeptides and polynucleotides are provided. Antibodies which bind to hKCa3/KCNN3 polypeptides are also disclosed. A method for identifying a compound which affects hKCa3/KCNN3 polynucleotide or polypeptide is provided. A method for diagnosis and determining the prognosis and treatment regimen of a subject having or at risk of having a hKCa3/KCNN3-associated disorder is also provided. A method of treating a subject having or at risk of having an hKCa3/KCNN3-associated disorder by administering a therapeutically effective amount of a polynucleotide encoding SEQ ID NO:2 is also provided. A formulation for administration of hKCa3/KCNN3 to a patient of a therapeutically effective amount of hKCa3/KCNN3 polypeptide is provided. Kits useful for detecting the presence of hKCa3/KCNN3 polypeptide or polynucleotide in a sample from a subject having a hKCa3/KCNN3-associated disorder are provided. Transgenic nonhuman animals having a transgene encoding hKCa3/KCNN3 are also described.

hKCa3/KCNN3 small conductance calcium activated potassium channel: a diagnostic marker and therapeutic target

Compounds, preparations and methods for immunosuppressive treatment of autoimmune disorders, graft rejection and/or graft/host disease. Therapeutically effective amounts of certain substituted triarylmethane compounds, such as 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole, are administered to mammalian patients to selectively inhibit the calcium-activated Kchannel (IKCa1) in lymphocytes, monocytes, macrophages, platelets or endothelial cells without concomitant inhibition of P450-dependent enzyme systems, resulting in reduction of antigen-, cytokine-, or mitogen-induced calcium entry through store operated calcium channels in these cells, suppression of cytokine production by these cells, and inhibition of activation of these cells. Such inhibition of the Caactivated Kchannel (IKCa1) prevents the pre-Castage of cell activation and thus causes immunosuppression and an anti-inflammatory response.

Non-peptide inhibition of T-lymphocyte activation and therapies related thereto

The present invention is based on the discovery and cloning of two variants of the small conductance calcium activated potassium channel type 3 (hKCa3/KCNN3) gene. The isoform variants are identical to the structure of the SKCa3-1a transcript with regard to exons 2&#x2013;8, but differ in that one variant, SKCa3-1b, contains exon 1b in place of exon 1a and in that the other variant, SKCa3-1c, contains exon 1c in place of exon 1a. When expressed simultaneously with SKCa3-1a, the variants will independently dominantly negatively suppress SKCa3-1a and other functional members of the SKchannel family. Accordingly, the present invention provides the novel gene variants, methods for the detection of the variants and treatment of disorders related to the activity of these variants. Kits employing the methods of the invention are also described.

Exons of the hSKCa3/KCNN3 gene

Compounds, preparations and methods for immunosuppressive treatment of autoimmune disorders, graft rejection and/or graft/host disease. Therapeutically effective amounts of certain substituted triarylmethane compounds, such as 1-&lsqb;(2-chlorophenyl)diphenylmethyl&rsqb;-1H-pyrazole, are administered to mammalian patients to selectively inhibit the calcium-activated K channel (IKCa1) in lymphocytes, monocytes, macrophages, platelets or endothelial cells without concomitant inhibition of P450-dependent enzyme systems, resulting in reduction of antigen-, cytokine-, or mitogen-induced calcium entry through store operated calcium channels in these cells, suppression of cytokine production by these cells, and inhibition of activation of these cells. Such inhibition of the Ca activated K channel (IKCa1) prevents the pre-Ca stage of cell activation and thus causes immunosuppression and an anti-inflammatory response.

hKCa3/KCNN3 small conductance calcium activated potassium channel: A diagnostic marker and therapeutic target

The present invention is based on the discovery and cloning of the human small conductance calcium activated potassium channel type 3 (hKCa3/KCNN3) gene, which is expressed in neuronal cells, skeletal muscle, heart, and lymphocytes. Alterations in the hKCa3/KCNN3 gene or its protein product may enhance susceptibility to schizophrenia and/or bipolar disorder. hKCa3/KCNN3 may be involved in neuropsychiatric, neurological, neuromuscular, and immunological disorders. Substantially purified hKCa3/KNN3 polypeptides and polynucleotides are provided. Antibodies which bind to hKCa3/KCNN3 polypeptides are also disclosed. A method for identifying a compound which affects hKCa3/KCNN3 polynucleotide or polypeptide is provided. A method for diagnosis and determining the prognosis and treatment regimen of a subject having or at risk of having a hKCa3/KCNN3-associated disorder is also provided. A method of treating a subject having or at risk of having an hKCa3/KCNN3-associated disorder by administering a therapeutically effective amount of a polynucleotide encoding SEQ ID NO:2 is also provided. A formulation for administration of hKCa3/KCNN3 to a patient of a therapeutically effective amount of hKCa3/KCNN3 polypeptide is provided. Kits useful for detecting the presence of hKCa3/KCNN3 polypeptide or polynucleotide in a sample from a subject having a hKCa3/KCNN3-associated disorder are provided. Transgenic nonhuman animals having a transgene encoding hKCa3/KCNN3 are also described.

hKCa3/KCNN3 small conductance calcium activated potassium channel: a

Disclosed are methods and compositions comprising DNA segments, and proteins derived from sea anemone species. More particularly, it concerns the novel ShK toxin, ShK toxin analogs, chemically-modified toxin analogs, and nucleic acid segments encoding the ShK toxin from Stichodactyla helianthus. Various methods for making and using these DNA segments, DNA segments encoding synthetically-modified ShK toxins, and native and synthetic ShK peptides are disclosed, such as, for example, the use of DNA segments as diagnostic probes and templates for protein production, and the use of proteins, fusion protein carriers and peptides in various immunological and diagnostic applications.

Growing community of inventors

Laguna Beach, CA, United States of America

K George Chandy