Syntex (u.s.a.) Inc.

Pherin Pharmaceuticals, Inc.

Ronald Herman

Lakshmi Sangameswaran

Linda Marie Fish

Stephen Gregory Delgado

Douglas Kenneth Rabert

David L Berliner

Paul Shartzer Dietrich

The present invention relates to a voltage-gated sodium channel present in peripheral nerve tissue that is tetrodotoxin-resistant. One aspect of the present invention is purified and isolated DNA encoding this sodium channel. Another aspect of the present invention is the recombinant protein expressed by this DNA, expression vectors comprising the DNA sequence, and host cells transformed with these expression vectors. Another aspect of this invention is the use of this voltage-gated, tetrodotoxin-resistant sodium channel as a therapeutic target for compounds to treat disorders of the peripheral nervous system.

Method of modulating tetrotodoxin-resistant sodium channel

This invention relates to DNA libraries, in particular a human VNO cDNA library is described. Pheromone receptor cDNA once isolated is transfected into competent cells. The transfected cell lines provide a scaleable source of homogeneous material to develop efficient, automated high throughput screening assays for new vomeropherins, and thereby reduce the ongoing need for human volunteers in the preclinical phases of drug discovery. Identification and characterization of the human VNO receptor(s) will facilitate the development and commercialization of vomeropherins with improved specificity, and enhanced therapeutic efficacy in the treatment of the target diseases.

Human VNO cDNA libraries

Human peripheral nerve, tetrodotoxin-resistant sodium channel &agr;-subunit polypeptide

DNA encoding for a voltage-gated, TTX-sensitive sodium channel is isolated. Also disclosed are polypeptide products of recombinant expression of these DNA sequences, expression vectors comprising the DNA sequences, and host cells transformed with these expression vectors. Other aspects of this invention are peptides whose sequences are based on the amino acid sequences deduced from these DNA sequences, antibodies specific for such proteins and peptides, procedures for detection and quantitation of such proteins, and nucleic acids related thereto. Another aspect of this invention is the use of this voltage-gated, tetrodotoxin-sensitive sodium channel as a therapeutic target for compounds.

Cloned tetrodotoxin-sensitive sodium channel &agr;-subunit and a splice variant thereof

Cloned peripheral nerve, tetrodotoxin-resistant sodium channel &agr;-subunit

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Sunnyvale, CA, United States of America

Ronald Herman