Transform Pharmaceuticals, Inc.

Mcneil-ppc, Inc.

Alkermes Pharma Ireland Limited

Modernatx, Inc.

University of South Florida

University of Michigan

Örn Almarsson

Julius F Remenar

Mark Tawa

Laura Cook Blumberg

Matthew Lynn Peterson

Magali Bourghol Hickey

Michael John Cima

Tarek A Zeidan

Douglas Adam Levinson

Staci Sabnis

Mark Oliveira

Antonin De Fougerolles

Noubar Boghos Afeyan

Stephen G Hoge

Michael John Zaworotko

Javier Gonzalez-Zugasti

Anthony Lemmo

Alasdair Y Johnson

Christopher McNulty

Kristy M Wood

Joseph Beene Bolen

Hongming Chen

John Podobinski

Hector Guzman

Divakar Ramakrishnan

Brian Moulton

Eugene Cheung

Tanise Shattock

Nair Rodriguez-Hornedo

Jin Lim

David D Hile

Ciarán Lawlor

Jaclyn Milton

Matthew Peterson

The present disclosure is based, at least in part, on the discovery that high-purity PEG lipids exhibit superior physical and biological properties, particularly when used in lipid nanoparticle (LNP) formulations. Therefore, the present disclosure provides PEG lipids at a recommended purity, e.g., for use in formulations, such as LNP formulations. The present disclosure also provides LNPs comprising the high-purity PEG lipids, and methods for delivering therapeutic agents to a subject using the same.

High-purity peg lipids and uses thereof

The present disclosure provides, inter alia, formulation compositions comprising modified nucleic acid molecules which may encode a protein, a protein precursor, or a partially or fully processed form of the protein or a protein precursor. The formulation composition may further include a modified nucleic acid molecule and a delivery agent. The present invention further provides nucleic acids useful for encoding polypeptides capable of modulating a cell's function and/or activity.

Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions

The present invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides formulations containing amino acids.

Polynucleotide compositions containing amino acids

The invention provides a method of sustained delivery of a tertiary amine-containing parent drug comprising administering to a patient an effective amount of a prodrug compound of the invention wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release. Prodrug compounds suitable for use in the methods of the invention are labile quaternary ammonium salts of tertiary amine-containing parent drugs (or tertiary imine-containing parent drugs) that are derivatized through aldehyde-linked prodrug moieties that reduce the solubility of the prodrug compound at a reference pH as compared to the parent drug. The physical, chemical and solubility properties of these derivatives can be further modulated by the choice of counterion X. In one embodiment, the present invention provides a prodrug compound of Formula I: where R-Rare defined in the written description of the invention. The prodrug compounds of the invention can be used to treat any condition for which the tertiary amine-containing parent drug or tertiary imine-containing parent drug is useful as a treatment.

Quaternary ammonium salt prodrugs

The present invention relates to prodrugs of parent drug compounds containing heteroaromatic NH groups.

Prodrugs of heteraromatic compounds

The invention provides a method of sustained delivery of a lactam, imide, amide, sulfonamide, carbamate or urea containing parent drug by administering to a patient an effective amount of a prodrug compound of the invention wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release. Prodrug compounds suitable for use in the methods of the invention are labile conjugates of parent drugs that are derivatized through carbonyl linked prodrug moieties. The prodrug compounds of the invention can be used to treat any condition for which the lactam, imide, amide, sulfonamide, carbamate or urea containing parent drug is useful as a treatment.

Prodrugs of NH-acidic compounds

Prodrugs of NH-acidic compounds: ester, carbonate, carbamate and phosphonate derivatives

The invention relates to pharmaceutical compositions comprising propylene glycol solvates of APIs.

Pharmaceutical propylene glycol solvate compositions

Crystalline salts, polymorphs, solvates, and hydrates of bicalutamide, 5-fluorouracil, donepezil, anastrozole, nelfinavir, mirtazapine, lansoprazole, and tamsulosin, or derivatives thereof are provided by the subject invention. Methods of making and using the same are also provided.

Pharmaceutical forms, and methods of making and using the same

The invention relates to methods of screening mixtures containing a pharmaceutical compound and an excipient to identify properties of the pharmaceutical compound/excipient combination that retard solid-state nucleation. The invention further relates to increasing the solubility, dissolution and bioavailability of a drug with low solubility in gastric fluids conditions by combining the drug with a precipitation retardant and an optional enhancer.

Pharmaceutical compositions with improved dissolution

The invention relates to pharmaceutical compositions comprising propylene glycol solvates of APIs. In particular a 2:1 complex of naproxen sodium to propylene glycol is disclosed which is a crystalline solid. The complex is prepared by crystallization of a mixture of naproxen sodium and propylene glycol from diethyl ether. It is identifiable by its X-ray powder diffraction pattern described herein.

Pharmaceutically acceptable propylene glycol solvate of naproxen

A pharmaceutical composition comprising a co-crystal of an API and a co-crystal former; wherein the API has at least one functional group selected from ether, thioether, alcohol, thiol, aldehyde, ketone, thioketone, nitrate ester, phosphate ester, thiophosphate ester, ester, thioester, sulfate ester, carboxylic acid, phosphonic acid, phosphinic acid, sulfonic acid, amide, primary amine, secondary amine, ammonia, tertiary amine, sp2 amine, thiocyanate, cyanamide, oxime, nitrile diazo, organohalide, nitro, s-heterocyclic ring, thiophene, n-heterocyclic ring, pyrrole, o-heterocyclic ring, furan, epoxide, peroxide, hydroxamic acid, imidazole, pyridine and the co-crystal former has at least one functional group selected from amine, amide, pyridine, imidazole, indole, pyrrolidine, carbonyl, carboxyl, hydroxyl, phenol, sulfone, sulfonyl, mercapto and methyl thio, such that the API and co-crystal former are capable of co-crystallizing from a solution phase under crystallization conditions.

Pharmaceutical co-crystal compositions

A mixed co-crystal comprising an API, a first co-crystal former, and a second co-crystal former which is isomorphically substitutable with said first co-crystal former is described. A pharmaceutical composition comprising a mixed co-crystal, methods of making mixed co-crystals, and methods of using mixed co-crystals are also described.

Mixed co-crystals and pharmaceutical compositions comprising the same

Systems and methods are described that allow the high-throughput preparation, processing, and study of arrays of samples, each of which comprises at least one compound. Particular embodiments of the invention allow a large number of experiments to be performed in parallel on samples that comprised of one or more compounds on the milligram or microgram quantities of compounds. Other embodiments of the invention encompass methods and devices for the rapid screening of the results of such experiments, as well as methods and devices for rapidly determining whether or not similarities exist among groups of samples in an array. Particular embodiments of the invention encompass methods and devices for the high-throughput preparation of different forms of compounds (e.g., different crystalline forms), for the discovery of new forms of old compounds, and for the discovery of new methods of producing such forms. Embodiments of the invention also allow for the high-throughput determination of how specific compounds or forms of compounds behave when exposed to other chemicals or environmental conditions.

Apparatus and method for high-throughput preparation and spectroscopic classification and characterization of compositions

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Shrewsbury, MA, United States of America

Örn Almarsson