Other

Arena Pharmaceuticals, Inc.

Clapp, Lucie H.

John W Adams

Daniel T Connolly

Dominic P Behan

Lucie H Clapp

Provided herein in some embodiments are pharmaceutical compositions comprising a prostacyclin (PGI2) receptor agonist selected from 2-(((1r,4r)-4-(((4-chlorophenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)methoxy)acetic acid (Compound 1) and pharmaceutically acceptable salts, solvates, and hydrates thereof, as disclosed herein. In some embodiments the pharmaceutical compositions comprise a compound selected from 2-(((1r,4r)-4-(((4-chlorophenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)methoxy)acetic acid (Compound 1), and pharmaceutically acceptable salts, solvates, and hydrates thereof, in an amount equivalent to a therapeutically effective amount of Compound 1, the composition having a release rate by weight of the compound in an aqueous medium that is one or more of release rates (a), (b) and (c) as disclosed herein. The compositions of the present invention are useful in the treatment of PGI2 related disorders, such as those disclosed herein.

Compositions comprising PGI2-receptor agonists and processes for the preparation thereof

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 methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In some embodiments, the GPCR is mammalian, preferably human. In some embodiments, the GPCR is expressed endogenously by cardiomyocytes. In some embodiments, the GPCR is coupled to Gq. In some embodiments, the GPCR increases the intracellular level of inositol 1,4,5-triphosphate (IP3). In some embodiments, a modulator of the GPCR is a modulator of cardiomyocyte hypertrophy. The present invention further relates to methods of using a modulator of the GPCR. Preferred modulators are inverse agonists and antagonists. Inverse agonists and antagonists of the invention are useful as therapeutic agents for the prevention or treatment of heart disease, including hypertrophic cardiomyopathy and congestive heart failure, in particular hypertrophic cardiomyopathy resulting from post-myocardial infarction remodeling, cardiac valve disease, sustained cardiac afterload, myocarditis, and familial hypertrophic cardiomyopathy.

Human G protein-coupled receptor and modulators thereof for the treatment of cardiovascular disorders

The present invention relates to methods of identifying whether a candidate compound is a modulator of an orphan G protein-coupled receptor (GPCR). Preferably the GPCR is human. In some embodiments, the GPCR is expressed endogenously by cardiomyocytes. In some embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In some embodiments, overexpression of the GPCR promotes survival of cardiomyocytes. In some embodiments, overexpression of the GPCR rescues cardiomyoctes from hypoxia/reoxygenation induced apoptosis. In some embodiments, the GPCR is down-regulated in individuals with congestive heart failure. Agonists of the invention are envisioned to be useful as therapeutic agents for the treatment of ischemic heart disease, including myocardial infarction, post-myocardial infarction remodeling, and congestive heart failure.

Human G protein-coupled receptor and modulators thereof for the treatment of ischemic heart disease and congestive heart failure

A method and apparatus for picking and collecting fruit from fruit trees comprising a fruit picking assembly including a water cannon to selectively impact fruit to be picked with a water slug to detach the fruit from the fruit tree and a fruit collecting assembly disposed beneath the fruit picking assembly to catch the fruit detatched from the fruit tree.

Fruit picking method and apparatus

The invention relates to a support stand including at least three outwardly extending and diverging legs. A distal end of each of the legs defines a notional perimeter having at least three corners. Each of the legs extends outwardly to a respective one of the corners. A distal support column is located at respective distal ends of the legs and provides an area of increased rigidity. The support column defines a respective corner of the notional perimeter.

Support stand

An exterior gas-fired water heater enclosure, comprising a base, sidewalls mounted on the base and defining an interior space for receiving a gas-fired water heater, a top positioned on the top of the sidewalls, a flue positioned in the top and communicating with the interior of the enclosure for discharging heated combustion air from the enclosure, vent means positioned adjacent the bottom of the sidewalls for permitting air flow into the enclosure from a point closely proximate a gas burner positioned in the bottom of the water heater, and baffle means positioned over the vent means for directing all of the air flow through the vent downwardly to a position below the gas burner of the water heater.

Exterior enclosure for gas-fired water heater

A pocket watch display kit comprising a hollow box like housing forming an open ended chamber, a lateral support shelf affixed with the housing dividing the open ended chamber and forming an upper chamber and a lower chamber, the lateral support shelf adapted to support a pocket watch, a semi-oblongitudinal notch in the free edge of the upper lateral portion of the housing, the crown of the pocket accommodated between the internal edges of the notch, a pendulum pivotally disposed within the lower chamber, a first door element hingedly affixed over the upper chamber, the door element having a first transparent window therein permitting display of the face of the pocket watch, a lower panel element fixedly secured to the housing adjacent the lower lateral portion thereof, and a second door element hingedly affixed by second hinge means over the opening in the lower chamber above the lower panel, the second door element having a second transparent window therein permitting the viewing of the pendulum element and the lower chamber.

Growing community of inventors

Charlotte, NC, United States of America

John W Adams