Xenon Pharmaceuticals Inc.

University of California

Novartis Pharma Ag

Teva Pharmaceuticals International Gmbh

Xenox Pharmaceuticals Inc.

Yigal Paul Goldberg

Rajender Kamboj

Marcia MacDonald

Mark E Samuels

Robin Sherrington

Michael D Winther

Tomas Ganz

Andreas Billich

Lan Lin

Michael J Lamson

Michael Fetell

Ofer Spiegelstein

Richard Malamut

Nicola Anne Price

Methods of treating postherpetic neuralgia in a mammal with a pharmaceutical composition comprising a spiro-oxindole compound of the formula: are disclosed. The methods provide excellent penetration of the spiro-oxindole compound into the affected skin area to effectively reduce the severity of the postherpetic neuralgia and/or to alleviate the postherpetic neuralgia with minimal or negligible systemic exposure of the spiro-oxindole compound.

Methods of treating postherpetic neuralgia with a topical formulation of a spiro-oxindole compound

The present invention relates to the discovery that mutations in SCN9A are causative of Congenital Indifference to Pain (CIP) in humans. The invention also relates to methods of using compounds small organic compounds to treat pain as well as to predict the effect of analgesic agents in patients, such as those possessing gain of function mutations.

Methods for identifying analgesic agents

The present invention relates to the discovery that mutations in SCN9A are causative of Congenital Indifference to Pain (CIP) in humans. The invention also relates to methods of utilizing the SCN9A gene and expression products thereof for the screening and identification of therapeutic agents, including small organic compounds, which are selective for SCN9A, and are useful in the treatment of pain and other disorders. The invention also relates to methods of using these compounds to treat or otherwise ameliorate such disorders.

Isolated fragments of the HFE2A protein able to bind and modulate HFE2A and other proteins, such as hepcidin, involved in the iron metabolism pathway are disclosed. Also disclosed are corresponding isolated polynucleotides encoding the fragments of the HFE2A protein. Methods for identifying modulators of HFE2A, comprising contacting a test compound with HFE2A and determining a change in HFE2A activity due to the compound, are provided. Also taught are methods of diagnosing an animal afflicted with or at risk of developing a disease of iron metabolism. Methods for treating and/or preventing a disorder in animals comprising administering to an animal afflicted therewith, or at risk of developing said disorder, a therapeutically effective amount of an HFE2A modulator are provided.

Juvenile hemochromatosis gene (HFE2A) cleavage products and uses thereof

Methods for treating pain by inhibition of the SCN9A channel

Isolated fragments of the HFE2A protein able to bind and modulate HFE2A and other proteins, such as hepcidin, involved in the iron metabolism pathway are disclosed, such fragments being of molecular weight of approximately 7 kDa to 43 kDa. Also disclosed are corresponding isolated polynucleotides encoding the fragments of the HFE2A protein. The invention includes derivatives and analogs of the polypeptide fragments of HFE2A, along with compositions of these, that are functionally active, i.e. capable of interacting with the HFE2A, as well as methods of production of the HFE2A cleavage products, derivatives and analogs, e.g. by recombinant means. Methods for identifying modulators of HFE2A, comprising contacting a test compound with HFE2A and determining a change in HFE2A activity due to the compound, are provided. Also taught are methods of diagnosing an animal afflicted with or at risk of developing a disease of iron metabolism comprising determining a change in the level, amount or activity of a fragment of an HFE2A obtained in a sample from said animal relative to the level, amount or activity of a fragment of an HFE2A obtained in a control sample from an unaffected animal, wherein a change identifies said individual as being affect by or at risk of developing a disease of iron metabolism. Methods for treating and/or preventing a disorder in animals comprising administering to an animal afflicted therewith, or at risk of developing said disorder, a therapeutically effective amount of an HFE2A modulator are provided.

Polynucleotide and polypeptide sequences for HFE2A, as well as mutations associated with juvenile hemochromatosis, and methods of utilizing these for the screening and identification of agents for the treatment of diseases of iron metabolism, including small organic compounds, are disclosed along with methods of treating and/or ameliorating diseases of iron metabolism, especially in human patients are disclosed. Diagnostic compounds, kits and methods using HFE2A are also described.

Juvenile hemochromatosis gene (HFE2A), expression products and uses thereof

Methods of treating an SCD-mediated skin disorder or condition in a mammal, preferably a human include administering to a mammal in need thereof a compound of formula (I): 

Pyridazine derivatives and their use as therapeutic agents

Isolated fragments of the HFE2A protein able to bind and modulate HFE2A and other proteins, such as hepcidin, involved in the iron metabolism pathway are disclosed, such fragments being of molecular weight of approximately 7 kDa to 43 kDa. Also disclosed are corresponding isolated polynucleotides encoding the fragments of the HFE2A protein. The invention includes derivatives and analogs of the polypeptide fragments of HFE2A, along with compositions of these, that are functionally active, i.e., capable of interacting with the HFE2A, as well as methods of production of the HFE2A cleavage products, derivatives and analogs, e.g., by recombinant means. Methods for identifying modulators of HFE2A are provided. Also taught are methods of diagnosing an animal afflicted with or at risk of developing a disease of iron metabolism. Methods for treating and/or preventing a disorder in animals comprising administering a therapeutically effective amount of an HFE2A modulator are provided.

Methods of treating an SCD-mediated skin disorder or condition in a mammal, preferably a human include administering to a mammal in need thereof a compound of formula (I): where x, y, W, V, R, R, R, R, R, R, R, R, R, R, Rand Rare defined herein.

Disclosed herein are hemojuvelin-specific siRNAs that vary hemojuvelin mRNA concentration. Also disclosed herein, GPI-hemojuvelin positively regulated hepcidin mRNA expression, independently of the IL-6 pathway, whereas soluble hemojuvelin (s-hemojuvelin) suppressed hepcidin mRNA expression in primary human hepatocytes in a log-linear dosedependent manner. Disclosed are compositions and methods for modulating diseases of iron metabolism and hepcidin expression or hepcidin levels.

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Vancouver, Canada

Yigal Paul Goldberg