Gen-probe, Inc.

Genta Incorporated

Loxo Oncology, Inc.

Other

Isis Pharmaceuticals, Inc.

Array Biopharma Inc.

Incyte Genomics, Inc.

Genentech, Inc.

Curis, Inc.

Biosite Incorporated

Mark A Reynolds

Lyle J Arnold, Jr

Lyle J Arnold

David Aaron Schwartz

Charles Todd Eary

Timothy Andrew Riley

Ram S Bhatt

Steven A Smith

Michael McClellan Becker

Mehrdad R Majlessi

Reinhold B Pollner

Richard I Hogrefe

Susan K Yamagata

Cristina Giachetti

Morteza M Vaghefi

Amara Siva

Steven Wade Andrews

Bob Dale Brown

Kenneth Francis Buechler

Norman C Nelson

Yutong Jiang

Julia Haas

Paul Polakis

Daniel P Sutherlin

Georgette M Castanedo

Shumei Wang

Brian Patrick Dwyer

Janet Gunzner

Michael F T Koehler

Stacey Spencer

Thomas H Adams

Kimberly Malesky

Nisha Nanda

Robert E Klem

William J Daily

Derrick Juengst

Bruno P Hache

Liang Bao

Michael S Dina

Rebecca L Lalonde

Michael Cox

Scott Savage

Alexander A Waldrop, Iii

Michael Ruvolo

Alexandre V Lebedev

Lloyd Robert Snyder

Mark Stanley

Michael F Koehler

Michael Whittaker

Christopher A Scott

6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile, or a pharmaceutically acceptable salt, amorphous form, polymorph form, or pharmaceutical composition (including solid formulations or liquid formulations) thereof and the use thereof for treating diseases and disorders which can be treated with a RET kinase inhibitor, such as RET-associated diseases and disorders, e.g., proliferative disorders such as cancers, including hematological cancers and solid tumors, and gastrointestinal disorders such as IBS are disclosed.

Formulations of 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile

Formulations of 6-(2-hydroxy-methylpropoxy-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile

A liquid formulation of (S)&#x2014;N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutically acceptable salts thereof, or a combination thereof and the use of the liquid formulation in the treatment of pain, cancer, inflammation, and certain infectious diseases are disclosed.

Liquid formulations of (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-a] pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide

Process for preparing (S)&#x2014;N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a] pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide (formula I) or a salt thereof by reacting phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate or a similar derivative (formula 13) with (S)-pyrrolidin-3-ol (formula 14). Process for preparing phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate (formula 13) or a similar derivative by reduction of (R)-5-(2-(2,5-difluorophenyl) pyrrolidin-1-yl)-3-nitropyrazolo[1,5-a]pyrimidine (formula 11) to (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (formula 12). Process for preparing (R)-2-(2,5-difluorophenyl)pyrrolidine(R)-2-hydroxysuccinate (formula 10) by treating (R)&#x2014;N&#x2014;((R)-1-(2,5-difluorophenyl)-3-(1,3-dioxan-2-yl)propyl)-2-methylpropane-2-sulfinamide (formula 19) with an acid and a reducing agent. (S)&#x2014;N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, is a tyrosin kinase (TRK) inhibitor for trearing e.g. cancer. 

Process for the preparation of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide and salts thereof

The invention provides chimeric capture probes immobilizable via an L-nucleic acid tail that can bind to a complementary L-nucleic acid in an immobilized probe. The capture probes are useful for capturing a target nucleic acid from a sample. The L-nucleic acid in the tail of the capture probe bind to the complementary L-nucleic acid in the immobilized probe with similar affinity as would otherwise equivalent D-nucleic acids. However, the L-nucleic acid of the capture probe tail and immobilized probes do not form stable duplexes with D-nucleic acids present in the in the sample containing the target nucleic acid. Binding of nucleic acids in the sample directly to immobilized probe or to the tail of the capture probe is reduced or eliminated increasing the sensitivity and/or specificity of the assay.

Capture probes immobilizable via L-nucleotide tail

Formulations of 6-(2-hydroxy-2-methylpropxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-A]pyridine-3-carbonitrile

Liquid formulations of (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide

Liquid formulations of (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-A]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide

The invention provides chimeric capture probes immobilizable via an L-nucleic acid tail that can bind to a complementary L-nucleic acid in an immobilized probe. The capture probes are useful for capturing a target nucleic acid from a sample. The L-nucleic acid in the tail of the capture probe bind to the complementary L-nucleic acid in the immobilized probe with similar affinity as would otherwise equivalent D-nucleic acids. However, the L-nucleic acid of the capture probe tail and immobilized probes do not form stable duplexes with D-nucleic acids present in the sample containing the target nucleic acid. Binding of nucleic acids in the sample directly to immobilized probe or to the tail of the capture probe is reduced or eliminated increasing the sensitivity and/or specificity of the assay.

A snow plow blade with integrated multiple horizontal slats in lieu of one solid curved blade comprises a plurality of thin blades stacked upon one another in a staggered retreating arrangement from the bottom up. Should any blade damage occur, just the section damaged can be replaced by simply unbolting it and bolting on a new one. The slat structure allows air to flow through the blade while moving down the road and not plowing snow, enabling air to enter the radiator section of the vehicle to cool the radiator more efficiently. Finally, the slat structure is envisioned to create lift, in much the same manner as an airplane wing, thus making the blade appear lighter than its actual static weight when moving down the road and not plowing snow. This feature is envisioned to reduce wear and tear on suspension components, steering components, tires, and other similar items.

Louvered snow plow

Compositions and reaction mixtures are provided for the detection of small RNA target nucleic acids, preferably miRNA target nucleic acids, wherein the compositions and reaction mixtures provide for sensitive and specific detection of the target nucleic acids. The compositions and reaction mixtures include one or more of a first amplification oligomer that is preferably an extender primer, a target capture oligomer that is preferably at least partially double stranded, a promoter primer/provider, a reverse primer that is preferably a universal primer and a detection probe. The compositions and reaction mixtures are useful for diagnostics, prognostics, monitoring the effectiveness of treatment and/or determining a treatment.

Compositions for detecting small RNAs

Compositions and methods are provided for the detection of small RNA target nucleic acids, preferably miRNA target nucleic acids, wherein the compositions and methods provide for sensitive and specific detection of the target nucleic acids. The compositions and methods include using one or more of a first amplification oligomer that is preferably an extender primer, a target capture oligomer that is preferably at least partially double stranded, a promoter primer/provider, a reverse primer that is preferably a universal primer and a detection probe. The compositions and methods are useful for diagnostics, prognostics, monitoring the effectiveness of treatment and/or determining a treatment.

Compositions and methods for detecting small RNAs, and uses thereof

Compositions, formulations and methods for inhibiting messenger RNA translation using anti-sense oligonucleosides containing 5&prime;-cap cleavage moieties are described.

Metal complex containing oligonucleoside cleavage compounds and therapies

Methods are provide for determining the relative amounts of individual polynucleotides in a complex mixture. The polynucleotides, after fluorescent labeling, are contacted under hybridization conditions with an array having element disposed at discrete locations on a substrate. The elements comprise two or more distinct polynucleotides that are combined prior to arraying. The level of fluorescence associated with each element provides a measure of its relative amount in the mixture.

Combined polynucleotide sequence as discrete assay endpoints

Growing community of inventors

San Diego, CA, United States of America

Mark A Reynolds