Merial Limited

Merck + Co., Inc.

Schering Corporation

Doris F Cully

Yingcong Zheng

Jeffrey W Warmke

Michel J Hamelin

Youfeng Yang

Joseph P Arena

Ken K Liu

Philip S Paress

Leonardus H T Van Der Ploeg

Andrew D Howard

Paul A Liberator

John W Hess

Scott D Feighner

Leonardus H Van Der Ploeg

Michael R Tota

Fang Chen

James M Schaeffer

Adrian Etter

Charles J Cohen

Richard Brochu

Steve W Ludmerer

Demetrios Vassilatis

Jeffrey Yuan

Birgit Priest

Sajjad A Qureshi

Charles I Rosenblum

Birgit Hirschberg

The present invention relates in part to isolated nucleic acid molecules (polynucleotides) which encodeligand gated ion channel proteins. The present invention also relates to recombinant vectors and recombinant hosts which contain a DNA fragment encodingLGIC/GluCl channels, substantially purified forms of associatedchannel proteins and recombinant membrane fractions comprising these proteins, associated mutant proteins, and methods associated with identifying compounds which modulate associatedLGIC/GluCl, which will be useful as insecticides and acaricides.

[object Object]

The present invention relates in part to isolated nucleic acid molecules (polynucleotides) which encodeglutamate gated chloride channels. The present invention also relates to recombinant vectors and recombinant hosts which contain a DNA fragment encodingglutamate gated chloride channels, substantially purified forms of associatedglutamate gated chloride channels and recombinant membrane fractions comprising these proteins, associated mutant proteins, and methods associated with identifying compounds which modulate associatedglutamate gated chloride channels, which will be useful as insecticides.

The present invention relates in part to isolated nucleic acid molecules (polynucleotides) which encodeligand gated ion channel proteins. The present invention also relates to recombinant vectors and recombinant hosts which contain a DNA fragment encodingLGIC/GluCl channels, substantially purified forms of associatedchannel proteins and recombinant membrane fractions comprising these proteins, associated mutant proteins, and methods associated with identifying compounds which modulate associatedLGIC/GluCl, which will be useful as insecticides and acaracides.

The present invention relates in part to isolated nucleic acid molecules (polynucleotides) which encodeligand-gated ion channel proteins. The present invention also relates to recombinant vectors and recombinant hosts which contain a DNA fragment encodingligand-gated ion channel proteins, substantially purified forms of associatedligand-gated ion channel proteins and recombinant membrane fractions comprising these proteins, associated mutant proteins, and methods associated with identifying compounds which modulate associatedligand-gated ion channel proteins, which will be useful as insecticides.

The present invention featuresGABA-gated chloride channel polypeptides and nucleic acids, and uses of such polypeptides and nucleic acids.is a widely distributed tick associated with different diseases. A preferred use of the present invention is to obtain compounds for preventing or treating a tick infestation.

Human, swine and rat growth hormone secretagogue receptors have been isolated, cloned and sequenced. Growth hormone secretagogue receptors are new members of the G-protein family of receptors. The growth hormone secretagogue receptors may be used to screen and identify compounds which bind to the growth hormone secretagogue receptor. Such compounds may be used in the treatment of conditions which occur when there is a shortage of growth hormone, such as observed in growth hormone deficient children, elderly patients with musculoskeletal impairment and recovering from hip fracture and osteoporosis.

Growth hormone secretagogue receptor family

To date, L-glutamate-gated chloride (GluCl) channels have been observed only in invertebrate organisms. Modulators of this channel (either agonists or antagoinists) will interfere with neurotransmission. For example, agents such as avermectins activate the GluCl, causing paralysis due to blocking of neurotranmitter release, resulting in death of the organism. Because GluCl channels are invertebreate specific, they are excellent targets for the discovery of novel insecticides, anthelminths and parasiticides that will display a marked safety profile because of the lack of mechanism based toxicity in vertebrate organisms. The present specification discloses isolation of a cDNA clone from the cat flea (CfGluCl-1) that encodes a L-glutamate-gated chloride channel. Heterologous expression of CfGluCl-1 cRNA in results in robust expression of a L-glutamate-gated chloride current and the channel is activated and potentiated by avermectins. The expression of CfGluCl-1 in a heterologous expression system if useful to screens for novel GluCl channel agonsts and antagonsits. Additionally, this specification disclose impoved methods of screening for GluCl channel modulators.

DNA molecules encoding Ctenocephalides felis glutamate gated chloride channels

A trans-activation assay for leptin is described. Leptin response elements are located proximal to a promoter, and the promoter region is operatively linked to a reporter gene. When leptin binds with the receptor, the reporter gene is transcribed.

Leptin assay

DNA encoding glutamate and avermectin-sensitive chloride channels have been cloned and characterized. The protein is capable of forming channels selectively opened with either avermectin or glutamate. The cDNA has been expressed in recombinant host cells which produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified. Receptor modulators active in the method disclosed herein are useful as ectoparasiticides, antiparasitic, anthelmenthic, acaracidal and insecticide agents.

DNA encoding glutamate gated chloride channels

DNAs encoding glutamate and avermectin-sensitive chloride channels have been cloned and characterized. The individual alpha and beta subunits are capable of forming homomeric and heteromeric channels selectively opened with either avermectin or glutamate. The cDNA's have been expressed in recombinant host cells which produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified. Receptor modulators are useful as insecticides and anthelminthic agents.

Growing community of inventors

Scotch Plains, NJ, United States of America

Doris F Cully