Vertex Pharmaceuticals, Inc.

Exithera Pharmaceuticals, Inc.

Enclear Therapies, Inc.

Elixir Pharmaceuticals, Inc.

Pliva D.d.

Daimed

Manuel A Navia

Nancy L St Clair

Robert C Gadwood

Robert Alan Chrusciel

Michael Joesph Melnick

Neil J Hayward

Frans L Stassen

Catherine A Stewart

Toni J Poel

Jeffrey O Saunders

Jean-Francois Pons

Kasper Roet

Jay R Luly

Andrew Napper

Peter DiStefano

Rory A Curtis

Scott T Moe

Jonathan Fleming

Jian Lin

Emanuele Perola

Kerry Leigh Spear

Lei Jin

Amy Ripka

Thomas D Bannister

Cassandra Celatka

Russell Thomas

Patrick Raymond Connelly

Tsvetelina Ivanova Lazarova

Thomas Stephen Coulter

Hongfeng Deng

Kevin Eggan, Jr

Roger Xie

Anthony DePasqua

Alan D Watson

Michael Rynkiewicz

Zihong Guo

William X Siopes

Kevin Kalish

Gianna N Riccardi

Marcie Ann Glicksman

Nizal Chandrakumar

Ching-Hua Tseng

Andrew Magee

Salvatore Anthony Marchese

Carlos H Faerman

Paul Mortenson

Russell J Thomas

Pamela Nagafuji

James E Stickler

Paul J Ala

Janid A Ali

Jacob J Clement

Christopher Faraday

John V Gazzaniga

Paul Will

The present invention provides compounds and compositions that inhibit Factor XIa or kallikrein and methods of using these compounds and composition.

Therapeutic compounds and compositions

Disclosed is a method for treating a subject having a neurological disorder characterized by the presence of toxic proteins comprising contacting the cerebrospinal fluid (CSF) of the subject with an agent capable of removing or degrading the toxic protein.

Methods of treating neurological disorders

Disclosed is a method for treating a subject having a neurological disorder characterized by the presence of dipeptide repeat proteins comprising contacting the cerebrospinal fluid (CSF) of the subject with an agent capable of removing or degrading the toxic protein.

Cerebrospinal fluid (CSF) and other fluid amelioration systems completely or partially implantable within a mammalian subject and associated methods include a substrate and an agent for amelioration of a toxic biomolecule present in the CSF or fluid, wherein the agent is disposed on or within the substrate.

Methods of amelioration of cerebrospinal fluid and devices and systems therefor

Compounds of formula (I) are described herein  The compounds can be used, for example, to modulate growth hormone secretagogue receptor (GHS-R). In some instances, the compounds can be used to treat obesity.

Therapeutic compounds and uses thereof

Compounds that modulate GHS-R are described, for examples compounds formula (I) 

Sulfonamide compounds and uses thereof

Compounds of formula (I) are described herein The compounds can be used, for example, to modulate growth hormone secretagogue receptor (GHS-R). In some instances, the compounds can be used to treat obesity.

Compounds are provided which have the structure Wherein A, B, C, D, m, Y, Ra, Rc, Rd, and Rd' are as described herein, and which are useful as inhibitors of tryptase, thrombin, trypsin, Factor Xa, Factor VIIa, Factor XIa, and urokinase-type plasminogen activator and may be employed in preventing and/or treating asthma, chronic asthma, allergic rhinitis, and thrombotic disorders.

Substituted azetidinones

The invention relates to D-Ala-D-Ala ligase inhibitors having the formula: wherein Ris NH; Ris NH; Ris selected from hydrogen, alkyl, amino, hydroxy, alkoxy, and alkylamino; and Rand Rare each independently hydrogen or a substituted or unsubstituted, linear, branched, or cyclic, alkyl, alkenyl, alkynyl, aryl, acyl, aralkyl, or alkaryl group wherein one or more carbon or hydrogen atoms may be substituted by a substituent selected from amino, alkylamino, hydroxyl, alkoxyl, thio, halogen, nitro, and carbonyl; wherein NRRincorporates a substituted or unsubstituted naphthyl group, wherein the substituents are selected from alkoxy, halogen, alkyl, and alkylene, and wherein said naphthyl group in NRRis bonded to N through a substituted or unsubstituted alkylene moiety. These compounds have antibacterial properties based on their ability to bind and inhibit D-Ala-D-Ala ligase, a critical pathway enzyme in bacterial cell-wall synthesis, and are suitable for various antibacterial uses.

Heterocyclic compounds and uses thereof as D-alanyl-D-alanine ligase inhibitors

A protein such as an enzyme or antibody is immobilized by crosslinking crystals of the protein with a multifunctional crosslinking agent. The crosslinked protein crystals may be lyophilized for storage. A preferred protein is an enzyme such as thermolysin, elastase, asparaginase, lysozyme, lipase or urease. Crosslinked enzyme crystals preferably retain at least 91% activity after incubation for three hours in the presence of a concentration of Pronase.TM. that causes the soluble uncrosslinked form of the enzyme to lose at least 94% of its initial activity under the same conditions. A preferred enzyme:Pronase.TM. ratio is 40:1. Enzyme crystals that are crosslinked may be microcrystals having a cross-section of 10.sup.-1 mm or less. Crosslinked enzyme or antibody crystals may be used in an assay, diagnostic kit or biosensor for detecting an analyte, in an extracorporeal device for altering a component of a fluid, in producing a product such as using crosslinked thermolysin crystals to produce aspartame and in separating a substance from a mixture. Enzyme or non-enzyme protein therapy can be performed by administering orally crosslinked enzyme crystals or crosslinked non-enzyme protein crystals that have a therapeutic affect. The crosslinked crystals have improved stability to proteases in the gut. Crosslinked lipase crystals may be administered for treatment where there is pancreatic insufficiency and/or fat malabsorption conditions in which lipase secretion is abnormally low.

Method of protein therapy by orally administering crosslinked protein

Proteins such as enzymes and antibodies are immobilized by crosslinking crystals of the proteins such as microcrystals having a cross-section of 10.sup.-1 mm or less with a multifunctional crosslinking agent. The crosslinked protein crystals may be lyophilized for storage. Crystals of an enzyme such as thermolysin, elastase, asparaginase, lysozyme, lipase or urease may be crosslinked to provide crosslinked enzyme crystals that retain at least 91% activity after incubation for three hours in the presence of a concentration of Pronase.TM. that causes the soluble uncrosslinked form of the enzyme to lose at least 94% of its initial activity under the same conditions. A preferred Pronase.TM.:enzyme ratio is 1:40. Crosslinked enzyme or antibody crystals may be used in an assay, diagnostic kit or biosensor for detecting an analyte, in an extracorporeal device for altering a component of a fluid, in producing a product such as using crosslinked thermolysin crystals to produce aspartame, in separating a substance from a mixture, and in therapy.

Biosensors, extracorporeal devices and methods for detecting substances

Growing community of inventors

Lexington, MA, United States of America

Manuel A Navia