Insmed Incorporated

Walter Perkins

Vladimir Malinin

Adam Plaunt

Donna M Konicek

Zhili Li

Franziska Leifer

Ryan Heckler

Michael Hahn

Roman Perez-Soler

Brian S Miller

Philipp Holzmann

Xingong Li

Yiyu Zou

Harald Schulz

Jin K Lee

Frank G Pilkiewicz

Jimin Zhang

Dominique Seidel

Keith Dipetrillo

Kuan-Ju Chen

Brian Miller

The present invention provides certain lipo-glycopeptide cleavable derivatives and methods for using the same for the treatment of bacterial infections, for example, pulmonary bacterial infections. The LGPC derivatives include a cleavable moiety that in certain embodiments, is designed to allow for cellular uptake and/or a more rapid clearance of the glycopeptide metabolite (i.e., the cleaved glycopeptide) from the site of administration (e.g., the lung) as compared to the uncleaved LGPC.

Lipo-glycopeptide cleavable derivatives and uses thereof

Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C-Calkyl, branched C-Calkyl, linear C-Calkenyl, branched C-Calkenyl, aryl, aryl-C-Calkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.

Prostacyclin compounds, compositions and methods of use thereof

Methods for making prodrugs of treprostinil and treprostinil derivatives are provided. Specifically, methods are provided herein for producing prostacyclin compounds comprising treprostinil covalently linked to a linear C-Calkyl, branched C-Calkyl, linear C-Calkenyl, branched C-Calkenyl, aryl, aryl-C-Calkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide). The linkage, in one embodiment, is via an amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. The compounds provided herein can be used to treat pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension.

Methods of manufacturing treprostinil and treprostinil derivative prodrugs

In one aspect, the invention provides a stabilized lipid-based glycopeptide antibiotic composition and a process for producing the same. In another aspect, the invention provides methods for treating a bacterial pulmonary infection by administering to a subject in need thereof a therapeutically effective amount of the stabilized lipid-based glycopeptide antibiotic composition.

Stabilized vancomycin formulations

Methods for making prodrugs of trepreostinil and treprostinil derivatives are provided. Specifically, methods are provided herein for producing prostacyclin compounds comprising treprostinil covalently linked to a linear C-Calkyl, branched C-Calkyl, linear C-Calkenyl, branched C-Calkenyl, aryl, aryl-C-Calkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide). The linkage, in one embodiment, is via an amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. The compounds provided herein can be used to treat pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension.

Provided herein are systems for treating a subject with a pulmonary infection, for example, a nontuberculous mycobacterial pulmonary infection, apulmonary infection, a pulmonary infection associated with bronchiectasis, or apulmonary infection. The system includes a pharmaceutical formulation comprising a liposomal aminoglycoside dispersion, and the lipid component of the liposomes consist essentially of electrically neutral lipids. The system also includes a nebulizer which generates an aerosol of the pharmaceutical formulation at a rate greater than about 0.53 gram per minute. The aerosol is delivered to the subject via inhalation for the treatment of the pulmonary infection.

Systems for treating pulmonary infections

One aspect of the invention relates to methods of treating cancer in a patient comprising administering intraperitoneally to a patient in need thereof a cancer treating effective amount of a composition comprising a lipid-complexed platinum compound wherein the concentration of the platinum compound of the lipid-complexed platinum compound composition is greater than about 1.2 mg/ml. Another aspect of the invention relates to lipid-complexed platinum compound compositions where the concentration of the platinum compound is greater than about 1.2 mg/ml.

Methods of treating cancer with high potency lipid-based platinum compound formulations administered intraperitoneally

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Pennington, NJ, United States of America

Walter Perkins