Regeneron Pharmaceuticals, Inc.

Facebook, Inc.

Regeneran Pharmaceuticals, Inc.

Ning Li

Shunhai Wang

Hunter Chen

Amardeep Singh Bhupender Bhalla

Shawn M Lawrence

Amy S Johnson

Meghan E Casey

Thomas Daly

Erica Pyles

Andrew Tustian

Nisha Palackal

Ankit Vartak

Kent Schoen

Philip Zigoris

Jessica Gronski

Eric Michel Giovanola

Jordan Christopher Walke

Haibo Qiu

Jaimie Grapel

Robert Kang Xing Jin

Hongxia Wang

Robert Kang-Xing Jin

Matthew Franklin

Jikang Wu

Jaimie Mastrogiacomo

Daniel B Dix

Xiaolin Tang

John Mattila

Xiaobin Xu

Hanne Bak

Hui Xiao

Sook Yen E

William Markis

Chen Li

I-Hsuan Chen

Neville S Bowers

Philip Anastasios Zigoris

Phillip Anastasios Zigoris

Xiaojing Zheng

Tyler Greer

Reid O'Brien Johnson

Sisi Zhang

Xiaoxiao Huang

Milos Cejkov

Xueqing Zhao

Ming Huang

Robert Kang Jin

Jordan Walke

The present invention generally pertains to methods of quantifying free fatty acids in a pharmaceutical formulation. In particular, the present invention pertains to a method of quantifying free fatty acids released from polysorbate hydrolysis in a pharmaceutical formulation comprising a pharmaceutical product, polysorbate and free fatty acids, using liquid chromatography-mass spectrometry, without the use of an extraction step.

Monitoring polysorbate hydrolysis in pharmaceutical formulations using an ultrasensitive extraction-free fatty acid quantitation method

The present invention provides methods and systems for isotyping and quantification of antibodies based on immunocapture and/or Liquid Chromatography-Mass Spectrometry (LC-MS) analysis. These antibodies are induced by the administration of pharmaceutical products. The immunocapture method comprises contacting samples with a solid support, wherein the pharmaceutical product has been cross-linked directly to the solid support. The MS analysis includes conducting peptide mapping, selecting unique peptides and fragment ions to generate MRM (multiple reaction monitoring) transitions, optimizing collision energy, and determining a LLOQ (lower limit of quantification).

LC-MS methods for antibody isotyping and quantification

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

Disclosed are methods for improving compound detection and characterization. Methods for characterizing a sample are disclosed. The methods can include providing a sample to a liquid chromatography system capable of sample separation to generate sample components; analyzing sample components by multiplexed targeted selected ion monitoring (SIM) to generate an inclusion list; and performing iterative mass spectral data-dependent acquisition (DDA) from the inclusion list, to identify individual sample components thereby characterizing the sample. In one example, multiplexed targeted SIMs and iterative MS2 DDA acquisition is used to increase robust compound identification for cell culture medium analysis.

High confidence compound identification by liquid chromatography-mass spectrometry

The present disclosure pertains to compositions comprising aflibercept and methods for producing such compositions in chemically defined media and using chromatography to reduce certain aflibercept variants.

The present disclosure provides methods and compositions for the determining the abundance and/or concentration of protein biomarkers in a biological sample.

Use of LC-MS/MS to quantitate protein biomarkers

The present invention provides methods to quickly and efficiently assess the effect of antibody variants, including PTMs, e.g., glycosylation, oxidation, and deamidation variants, on the binding between the antibody and FcRn. In particular, the present invention is based, at least in part, on the development of an online, two dimension liquid chromatography (2D-LC) method for assessing binding between antibody variants and FcRn. In one aspect, the online 2D-LC is coupled with mass spectrometry (MS). The present invention allows for differentiation of antibody variants by peak pattern and retention time profile by affinity chromatography, and identification of these variants by mass spectrometry analysis.

Methods for assessing binding affinity of an antibody variant to the neonatal Fc receptor

Methods for detecting and/or discriminating between post-translational modification variants of an antibody of interest in a sample. The methods including: contacting a sample comprising one or more antibodies of interest with a protease to digest the sample into antibody fragments; separating antibody fragments by molecular weight and/or charge in one or more capillaries using capillary electrophoresis; eluting separated antibody fragments from the one or more capillaries; and determining the mass of the eluted antibody fragments by mass spec analysis, thereby detecting and/or discriminating between post-translational modification variants of the antibody of interest.

Native microfluidic CE-MS analysis of antibody charge heterogeneity

The present disclosure provides a method for accurately measuring post-translational modifications in proteins such as antibodies. In particular, the method pertains to the use of heavy isotopic standards to generate a calibration curve to allow for accurate quantitation of a modified peptide. The method may be used to accurately quantify C-terminal truncation in antibodies using mass spectrometry.

Heavy peptide approach to accurately measure unprocessed C-terminal lysine

Method of identifying host-cell proteins in a sample matrix are provided.

Identification of host cell proteins

The disclosure provides methods of characterizing a sample of oligonucleotides of interest using liquid chromatography and mass spectrometry.

Use of liquid chromatography and mass spectrometry to characterize oligonucleotides

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

The present disclosure pertains to methods for producing aflibercept from a host cell cultured in a chemically defined medium (CDM) including purification of aflibercept, wherein aflibercept following purification includes aflibercept variants that have at least one oxidized amino acid residue selected from the group consisting of tryptophan, histidine and a combination thereof.

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New Canaan, CT, United States of America

Ning Li