Arena Pharmaceuticals, Inc.

The Salk Institute for Biological Studies

University of Reading

University of Glasgow

Neurocrine Biosciences, Inc.

Other

Tripos, Inc.

Clapp, Lucie H.

Dominic P Behan

Derek T Chalmers

Chen Wang Liaw

William J Thomsen

Joseph F Russo

Wylie W Vale, Jr

Philip J Lowry

Ruoping Chen

Wolfgang H Fischer

Qian Liu

Ellen Potter

Kevin P Lowitz

Robert C Glen

Richard J Foster

Michael S Lawless

Julian R Smith

Elizabeth A Linton

Brian Christopher Smith

James R McCarthy

Jeffrey Paul Whitten

James N Leonard

Charles Q Huang

David J Unett

Zhengyu Liu

Daniel T Connolly

Yaron Hakak

Graeme Milligan

Jeremy G Richman

Christina Bjenning

Philip E Erickson

Sonja Strah-Pleynet

Nigel R A Beeley

John W Adams

I-Lin Lin

Nigel R Beeley

Huong T Dang

Lucie H Clapp

Bryan J Choi

Michael R Lerner

I Lin-Lin

Daniel Ortuño

Dominique Maciejewski-Lenior

The present disclosure encompasses combinations of ralinepag with a cGMP-elevating agent or prostanoid such as riociguat, treprostinil, or iloprost for treating PAH. The disclosed combination therapy provides for advantages such as improved efficacy, improved safety, reduced doses and/or frequency of ralinepag and/or riociguat, reduced doses and/or frequency of ralinepag and/or treprostinil, and reduced doses and/or frequency of ralinepag and/or iloprost. In some embodiments, the clinical effectiveness of a reduced dose combination is additive or synergistic compared to that provided by the corresponding ralinepag, riociguat, treprostinil, and/or iloprost monotherapies.

Methods of treating PAH with combinations of ralinepag and other agents

The present invention relates to a composition comprising phentermine and a selective 5HT-2C receptor agonist. In addition, the invention relates to a composition comprising phentermine and a selective 5HT-2C receptor agonist having Formula (I): or a pharmaceutically acceptable salt, solvate or hydrate thereof. These compositions are useful in pharmaceutical compositions whose use includes the treatment of obesity.

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The invention disclosed in this patent document relates to transmembrane receptors, more particularly to a human G protein-coupled receptor for which the endogenous ligand is unknown ('orphan GPCR receptors'), and most particularly to mutated (non-endogenous) versions of the human GPCRs for evidence of constitutive activity.

Constitutively activated human G protein coupled receptors

The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In preferred embodiments, the GPCR is human. In other preferred embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In other preferred embodiments, the GPCR is expressed endogenously by adipocytes. In further preferred embodiments, the GPCR inhibits intracellular lipolysis. In other further preferred embodiments, the GPCR is a nicotinic acid receptor. The present invention also relates to methods of using a modulator of said GPCR. Preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, stroke, insulin resistance, and type 2 diabetes.

Human G protein-coupled receptors for metabolic-related disorders

Disclosed herein are non-endogenous, constitutively activated forms of the human 5-HTand human 5-HTreceptors and uses of such receptors to screen candidate compounds. Further disclosed herein are candidate compounds identified by the screening method which act at the 5HTreceptors. Yet further disclosed is a new class of compounds which act at the 5HTreceptors.

Non-endogenous, constitutively activated human serotonin receptors and small molecule modulators thereof

The invention provides materials and methods relating to G-protein coupled receptor (GPCR) oligomers. Complexes of two or more GPCRs associated with G-proteins are provided. Also provided are fusion proteins comprising a GPCR and a G-protein, nucleic acids, expression vectors and host cells. Methods of producing the complexes and fusion proteins of the invention are also provided.

Materials and methods relating to G-protein coupled receptor oligomers

Disclosed herein are constitutively activated, non-endogenous versions of endogenous human G protein-coupled receptors comprising (a) the following amino acid sequence region (C-terminus to N-terminus orientation) and/or (b) the following nucleic acid sequence region (3' to 5&#x2032; orientation) transversing the transmembrane-6 (TM6) and intracellular loop-3 (IC3) regions of the GPCR:

Non-endogenous, constitutively activated human G protein-coupled receptors

The invention disclosed in this patent document relates to transmembrane receptors, more particularly to a human G protein-coupled receptor and to mutated (non-endogenous) versions of the human GPCRs for evidence of constitutive activity.

Endogenous and non-endogenous versions of human G protein-coupled receptors

Human G protein-coupled receptors and modulators thereof for the treatment of metabolic-related disorders

Disclosed herein are techniques for directly identifying candidate compounds as agonists, partial agonists and/or, most preferably, inverse agonists, to endogenous, constitutively activated orphan G protein-coupled receptors. Such directly identified compounds can be utilized, most preferably, in pharmaceutical compositions

Endogenous constitutively activated G protein-coupled orphan receptors

Non-endogenous, constitutively activated human protein-coupled receptors

Growing community of inventors

San Diego, CA, United States of America

Dominic P Behan