Regeneron Pharmaceuticals, Inc.

Regeneran Pharmaceuticals, Inc.

Xiaolin Tang

Daniel B Dix

Ravi Chari

Franco Tzul

Mary Kleppe

David Brett Ludwig

Ning Li

John Mattila

Hanne Bak

Mohammed Shameem

Chen Li

William Markis

Danya Spritzer

Mayank Patel

Stacy Wasinger

Jayant Arora

Alireza Tafazzol

Stable lyophilized therapeutic protein compositions and their methods of manufacture are provided. Specifically, the use of water as a solid cake plasticizer and protein stabilizer is described. Also, the inclusion of a multicomponent stabilizer comprising a larger molecular entity and a smaller molecular entity is described. Also, the inclusion of post-drying annealing under certain conditions improves protein stability. Proteins are predicted to remain stable over 24 months at 25° C.

Room temperature stable lyophilized protein

Lyophilization methods for preparing protein formulations for long-term storage at room temperature or improved stability at refrigeration storage are provided. Specifically, the present application provides lyophilization methods to obtain a target percentage of residual moisture of a lyophilized product, such as 3-5% residual moisture. The secondary drying of the lyophilization can be conducted under controlling rate of desorption under a temperature which is similar to the shelf temperature of the primary drying. Alternatively, the lyophilization can be conducted without a distinguished secondary drying step.

Target residual moisture content for lyophilized drug product

The present disclosure provides a stable protein composition containing a surfactant and having less than 400 subvisible particles of 10 microns or greater diameter per container, or less than 10,000 subvisible particles of 2 microns or greater per container. A method of manufacturing such a stable protein composition is disclosed, which includes a unit of operation that removes or decreases an esterase activity that degrades the surfactant. The unit of operation may be hydrophobic interaction chromatography or filtration, mixed mode chromatography, or the like.

Process for reducing subvisible particles in a pharmaceutical formulation

Biopharmaceutical compositions and drug products disclosed herein exhibit reduced amounts of subvisible particle formation. Compositions and drug products disclosed herein comprise a protein and a surfactant or stabilizer including high percentage amounts (e.g., at least 97%) of a long-chain fatty acid ester. Also disclosed herein are methods of preparing and storing such compositions and drug products.

Methods of reducing particle formation and compositions formed thereby

The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human interleukin-4 receptor (hIL-4R). The formulations may contain, in addition to an anti-hIL-4R antibody, at least one amino acid, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.

Stabilized formulations containing anti-interleukin-4 receptor (IL-4R) antibodies

Stable lyophilized therapeutic protein compositions and their methods of manufacture are provided. Specifically, the use of water as a solid cake plasticizer and protein stabilizer is described. Also, the inclusion of a multicomponent stabilizer comprising a larger molecular entity and a smaller molecular entity is described. Also, the inclusion of post-drying annealing under certain conditions improves protein stability. Proteins are predicted to remain stable over 24 months at 25&#xb0; C.

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Old Tappan, NJ, United States of America

Xiaolin Tang