Regeneron Pharmaceuticals, Inc.

Regeneran Pharmaceuticals, Inc.

Hunter Chen

Shunhai Wang

Ning Li

Amardeep Singh Bhupender Bhalla

Shawn M Lawrence

Amy S Johnson

Meghan E Casey

Jaimie Grapel

Yiming Zhao

Erica Schlesinger

Scott M Walsh

James Feindt

Timothy Riehlman

Gabriel Carreau

Ying Wang

Shao-Chun Wang

Philip Brudnicki

The present disclosure is directed to methods for tuning the release profile of a biologic disposed in a hydrogel. Parameters that can be used for the tuning include a molar ratio of a nucleophilic group to an electrophilic group, the number of the nucleophilic groups in the first precursor, the number of the electrophilic groups in the second precursor, the molecular weight of the first precursor, the molecular weight of the second precursor, a weight ratio of the biologic and excipient to the hydrogel, a weight percentage of the biologic in a solid state formulation, and a ratio of surface area to volume of the hydrogel. The methods described herein allow the formation of hydrogel with different release profiles suitable for different therapeutic applications.

Tuning of release kinetics in hydrogels

The present invention provides methods for fabricating protein-encapsulating microgels using hydrocarbon-in-fluorocarbon emulsions. The non-aqueous emulsion-based microgel fabrication methods can be used for the encapsulation of a wide range of proteins and peptides, including antibodies and antibody-fusion proteins, for therapeutic use with ease of administration.

Fabrication of protein-encapsulating microgels

The present disclosure pertains to compositions comprising anti-VEGF proteins and methods for producing such compositions.

Anti-VEGF protein compositions and methods for producing the same

Non-aqueous membrane emulsion methods for producing polymeric and polymer-coated microparticles are provided. Some embodiments provide methods for producing a sustained release or controlled release microparticle by combining micronized protein powder and a polymer into a hydrocarbon solvent to form a non-aqueous first solution, agitating the first non-aqueous solution to form a suspension, feeding the suspension into a dispersion pump, wherein the suspension is infused through a porous membrane into a continuous phase comprising a fluorocarbon liquid and a fluorosurfactant to form a hydrocarbon-in-fluorocarbon emulsion. The hydrocarbon solvent, the fluorocarbon liquid, and the fluorosurfactant are removed, and the microparticles are collected.

Sustained release formulations using non-aqueous membrane emulsification

The present invention pertains to compositions and methods of making high concentration protein formulations of a therapeutic protein.

High concentration protein formulation

The present disclosure pertains to compositions comprising anti-VEGF proteins.

Microparticles containing a core of therapeutic protein and a cortex of a biocompatible and biodegradable polymer, and methods of making and using the microparticles are provided. The extended release of a therapeutic protein from the microparticles in a physiological solution is demonstrated over an extended period of time.

Polymer protein microparticles

The disclosure relates to methods of analyzing a post-translationally modified protein of interest using electrophoresis, the methods comprising deglycosylating the protein of interest after labeling.

Deglycosylation methods for electrophoresis of glycosylated proteins

Non-aqueous emulsion methods for producing polymeric or polymer-coated microparticles are provided. One method produces a sustained release microparticle composition by combining protein powder and a polymer into a hydrocarbon solvent to form a non-aqueous first solution and adding the first solution to a second solution, wherein the second solution comprises a fluorocarbon liquid and a fluorosurfactant to form a non-aqueous emulsion comprising multiple emulsion hydrocarbon droplets in the fluorocarbon liquid. The subsequent microparticle hardening process includes the steps of removing the hydrocarbon solvent from the formed emulsion droplets, which can be achieved through evaporation the hydrocarbon at ambient condition under stirring, or accelerated hardening through vacuum, or through adding hydrofluoroester into the fluorocarbon as a cosolvent. Removing the fluorocarbon liquid and washing with extra fluorocarbon liquid to isolate the sustained release microparticles, wherein the sustained release microparticles comprise one or more cores of protein and a cortex of polymer.

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New York, NY, United States of America

Hunter Chen