Senomyx, Inc.

Firmenich Incorporated

Amgen Inc.

Ucb Pharma, S.a.

Senumyx, Inc.

Lucent Technologies Inc.

Xiaodong Li

Hong Xu

Jon Elliot Adler

Lena Staszewski

Sergey Zozulya

Shawn O'Connell

Mark Zoller

Fernando Echeverri

Catherine Tachdjian

Guy Servant

Qing Li

Qing Chen

Vincent Darmohusodo

Feng Zhang

Xiao-Qing Tang

Alexey Pronin

Marketa Rinnova

Huixian Tang

Lena Luukkonen

Donald Karanewsky

Hong Zhang

Andrew P Patron

Sara L Adamski-Werner

Victor Selchau

Ming Qi

David Mark Wallace

Albert Zlotnik

Richard Masten Fine

Farid Bakir

Boris Klebansky

Amy Xing

Timothy Davis

Daniel Harry Rogers

Stephen Terrence Hobson

Klaus Gubernator

Haitian Liu

Xinshan Kang

Melissa Sue Wong

Xiao Qing Tang

Lan Zhang

Sara Werner

Wen Zhao

Harish Viswanathan

Joseph R Fotsing

Paul Brust

Chad Priest

Shankar Narayanaswamy

Rajeev Krishnamoorthy

Thomas P Brady

Jeffrey Robert Hammaker

Melissa Arellano

Goran Petrovic

Jon Elliott Adler

Brett Weylan Ching

Jing Ling

Rachel D A Kimmich

Jeffrey Yamamoto

Femando Echeverri

Shawn O'connell

Hua Zhu Ke

Hanghui Liu

Melissa S Wong

Donald S Karanewsky

Markus Rupp

Martyn Kim Robinson

Michael Stuart Ominsky

Jon Elliot Alder

Hubdan Tang

Hulxian Tang

Keping Wu

Rachel Da Kimmich

Sara Adamski-Werner

Mark T Zoller

Rachel DA Kimmich

Shawn M O'Connell

The invention relates to the treatment of bone disorders. In particular, the invention provides an approach involving administration of a high initial dose or doses of an sclerostin antibody to bring about a rapid increase in bone formation, followed by administration of lowers doses of the antibody to give a sustained lower rate of bone formation after the initial burst of bone formation. The invention also provides an approach involving decreasing dosing frequency with such an antibody to control bone formation. The approaches may be used in particular in those subjects who would benefit most from such an initial rapid burst of bone formation. Examples of such subjects include subjects who have been recently diagnosed or are experiencing severe symptoms of the disorder, as well as those subjects who have been administered a different treatment for the bone disorder which is proving ineffective. The approaches may be used in combination with each other.

Anti-sclerostin antibodies and their use to treat bone disorders as part of a regimen

The present invention relates to the discovery that certain non-naturally occurring, non-peptide amide compounds and amide derivatives, such as oxalamides, ureas, and acrylamides, are useful flavor or taste modifiers, such as a flavoring or flavoring agents and flavor or taste enhancer, more particularly, savory (the 'umami' taste of monosodium glutamate) or sweet taste modifiers, savory or sweet flavoring agents and savory or sweet flavor enhancers, for food, beverages, and other comestible or orally administered medicinal products or compositions.

Flavors, flavor modifiers, tastants, taste enhancers, umami or sweet tastants, and/or enhancers and use thereof

The present invention relates to the discovery that the T1R receptors assemble to form functional taste receptors. Particularly, it has been discovered that co-expression of T1R1 and T1R3 results in a taste receptor that responds to umami taste stimuli, including monosodium glutamate. Also, it has been discovered that co-expression of the T1R2 and T1R3 receptors results in a taste receptor that responds to sweet taste stimuli including naturally occurring and artificial sweeteners. Also the present invention relates to the use of hetero-oligomeric taste receptors comprising T1R1/T1R3 and T1R2/T1R3 in assays to identify compounds that respectively respond to umami taste stimuli and sweet taste stimuli. Further, the invention relates to the constitutive of cell lines that stably or transiently co-express a combination of T1R1 and T1R3; or T1R2 and T1R3; under constitutive or inducible conditions. The use of these cells lines in cell-based assays to identify umami and sweet taste modulatory compounds is also provided, particularly high throughput screening assays that detect receptor activity by use of fluorometric imaging. Finally, the invention relates to the discovery that some compounds, e.g., lactisole, inhibit both the activities of human T1R2/T1R3 and T1R1/T1R3 receptors, and accordingly the sweet and umami taste, suggesting that these receptors may be the only sweet and umami receptors.

In vitro methods of detecting heteroligomeric T1R2/T2R3-expressing cells that are potentially sensitive to sweet tastants

Newly identified mammalian taste-cell-specific G protein-coupled receptors, and the genes and cDNA encoding said receptors are described. Specifically, T1R G protein-coupled receptors active in taste signaling, and the genes and cDNA encoding the same, are described, along with methods for isolating such genes and for isolating and expressing such receptors. Methods for representing taste perception of a particular taste stimulus in a mammal are also described, as are methods for generating novel molecules or combinations of molecules that elicit a predetermined taste perception in a mammal, and methods for simulating one or more tastes. Further, methods for stimulating or blocking taste perception in a mammal are also disclosed.

T1R taste receptors and genes encoding same

Newly identified mammalian taste-cell-specific G protein-coupled receptors which function as hetero-oligomeric complexes in the sweet taste transduction pathway, and the genes and cDNA encoding said receptors are described. Specifically, T1R G protein-coupled receptors active in sweet taste signaling as hetero-oligomeric complexes, and the genes and cDNA encoding the same, are described, along with methods for isolating such genes and for isolating and expressing such receptors. Methods for identifying putative taste modulating compounds using such hetero-oligomeric complexes also described, as is a novel surface expression facilitating peptide useful for targeting integral plasma membrane proteins to the surface of a cell.

Methods of using T1R hetero-oligomeric taste receptors to screen for compounds which modulate sweet or umami taste signaling

The present invention relates to the discovery that certain non-naturally occurring, non-peptide amide compounds and amide derivatives, such as oxalamides, ureas, and acrylamides, are useful flavor or taste modifiers, such as a flavoring or flavoring agents and flavor or taste enhancer, more particularly, savory (the 'umami' taste of monosodium glutamate) or sweet taste modifiers,&#x2014;savory or sweet flavoring agents and savory or sweet flavor enhancers, for food, beverages, and other comestible or orally administered medicinal products or compositions.

The invention relates to the identification of taste receptors and cells which express these taste receptors which are involved in sweet and umami taste transduction. Also, the invention relates to the use of these taste receptors and cells which express these taste receptors in assays for the identification of taste modulatory compounds.

TIR taste receptors and genes encoding same

The invention provides a method of enhancing bone gap defect healing involving administering a sclerostin inhibitor.

Methods for treating bone gap defects

The present invention relates to the discovery that specific human taste receptors in the T2R taste receptor family respond to particular bitter compounds. Also, the invention relates to the discovery of specific hT2R9 alleles and their disparate activity in functional assays with the same biter ligands. The invention further relates to the use of these T2R receptors in assays for identifying ligands that modulate the activation of these taste receptors by specific bitter ligands and related compounds. These compounds may be used as additives and/or removed from foods, beverages, cosmetics and medicinals in order to modify (block) T2R-associated bitter taste. Also T2R ligands may be used as therapeutics to treat and modulate T2R associated gastrointestinal and metabolic functions as well as treat gastrointestinal and metabolic diseases such as eating disorders, food sensing, fod absorption, obesity, diabetes, Crohn's disease, celiac disease, et al.

Identification of bitter ligands that specifically activate human T2R receptors and related assays for identifying human bitter taste modulators

The invention relates to compounds that specifically bind a T1R1/T1R3 or T1R2/T1R3 receptor or fragments or sub-units thereof. The present invention also relates to the use of hetero-oligomeric and chimeric taste receptors comprising T1R1/T1R3 and T1R2/T1R3 in assays to identify compounds that respectively respond to umami taste stimuli and sweet taste stimuli. Further, the invention relates to the constitutive of cell lines that stably or transiently co-express a combination of T1R1 and T1R3; or T1R2 and T1R3; under constitutive or inducible conditions. The use of these cells lines in cell-based assays to identify umami and sweet taste modulatory compounds is also provided, particularly high throughput screening assays that detect receptor activity by use of fluorometric imaging.

T1R hetero-oligomeric taste receptors, cell lines that express said receptors, and taste compounds

The present invention relates to the discovery that the T1R receptors assemble to form functional taste receptors. Particularly, it has been discovered that co-expression of T1R1 and T1R3 results in a taste receptor that responds to umami taste stimuli, including monosodium glutamate. Also, it has been discovered that co-expression of the T1R2 and T1R3 receptors results in a taste receptor that responds to sweet taste stimuli including naturally occurring and artificial sweeteners. Also the present invention relates to the use of hetero-oligomeric taste receptors comprising T1R1/T1R3 and T1R2/T1R3 in assays to identify compounds that respectively respond to umami taste stimuli and sweet taste stimuli.

Methods of detecting T1R hetero-oligomeric taste receptor expression to identify cells that are potentially sensitive to sweet tastants

Methods are provided for identifying human and non-human primate cells which respond to sweet tastants. These methods screen for human or non-human primate cells which express a polypeptide which binds to or responds to sweet tastants. These cells may be used in binding and functional assays to screen for compounds which modulate sweet taste.

Methods of using TIR hetero-oligomeric receptors for screening compounds that modulate sweet or umami taste

The present invention includes compounds having structural formula (I), or pharmaceutically acceptable salts, solvate, and/or ester thereof. These compounds are useful as sweet flavor modifiers. The present invention also includes compositions comprising the present compounds and methods of enhancing the sweet taste of ingestible compositions. Furthermore, the present invention provides methods for preparing the compounds.

Sweet flavor modifier

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San Diego, CA, United States of America

Xiaodong Li