Wyeth

Pfizer Corporation

Xiaotian Zhong

Ronald William Kriz

Amarnauth Shastrie Prashad

Leo J Letendre

Lidia Mosyak

Tao He

Wenge Wang

Zhijian Lu

Stephen H Herrmann

Yijie Gao

Will Somers

Nicole M Piche

Mei Geng

Ravindra Kumar

Phaik-Eng Sum

Edward R LaVallie

Mark L Stahl

Lisa Anne Collins-Racie

Christopher John Corcoran

William Stuart Somers

Stephane Olland

Thomas Saltmarsh Rush, Iii

Katy Evangelia Georgiadis

Thomas E McDonagh

Jose Manuel Gomes

James M Wilhelm

Stewart Andrews Mackie

Kaushik Dutta

Frank W Kotch

Vimalkumar B Patel

Renee L Procopio-melino

Brian Dwyer

Mark Johnson

Eleonora Presman

Tracy Hebert

Leo Joseph Letendre

Optimizing production of selectively capped, and uncapped, cysteines on antibodies by manipulation of cell growth conditions including the deliberate depletion of cysteine and/or cystine in the cell culture process by way of media components, batch duration, or cell density to achieve efficient production of proteins including antibody-drug-conjugates (ADCs).; conjugating a TNB-capped cysteine-containing protein by reacting it with a reducing agent capable of detaching the TNB-capping moieties from the protein without significantly reducing antibody inter-chain sulfur bonds, and conjugating reduced sulfur bonds on the protein to a payload through a reactive linking moiety.

Large scale production process for capped and un-capped antibody cysteines and their use in therapeutic protein conjugation

An antibody production process in mammalian cells in which engineered unpaired cysteine residues are post-translationally modified and capped with particular chemical entities, which capped antibodies are well suited to further site-specific conjugation steps to form antibody-drug conjugates (ADCs) or protein drug conjugates; ADCs produced using these capped antibodies including in particular ADCs formed by the selective reduction of the capped antibodies' cysteine residues, and ADCs formed using chemical handles such as aldehyde/azide/alkyne biorthogonal groups, which permit additional drug conjugation chemistry; and uncapped antibodies produced by cells in low cysteine, cysteine and glutathione media, and ADCs produced via direct conjugation to these uncapped antibodies.

Capped and uncapped antibody cysteines, and their use in antibody-drug conjugation

The invention relates to systems and methods for producing proteins of interest. The invention employs genetically-engineered animal or plant cells that have modified protein folding or processing capacities. In one aspect, the invention features genetically-engineered cells comprising one or more recombinant expression cassettes which encode (1) a protein of interest and (2) a polypeptide that is functional in the unfolded protein response (UPR) pathway of the cells. Co-expression of the polypeptide significantly increases the yield of the protein of interest in the genetically-engineered cells. In one example, the genetically-engineered cells are animal cells, and the co-expressed polypeptide is a component or modulator of an XB1- or ATF6-mediated UPR pathway.

Systems and methods for protein production

This disclosure relates to LINGO-1 polypeptides, LINGO-1 polypeptide/ligand complexes, crystals of LINGO-1 polypeptides, crystals of LINGO-1 polypeptide/ligand complexes, and related methods and software systems.

Method for identifying or designing a candidate agent that interacts with LINGO-1 polypeptide using a LINGO-1 three-dimensional structure

This invention relates to aggrecanase polypeptides and aggrecanase polypeptide/ligand complexes, crystals of aggrecanase and aggrecanase polypeptide/ligand complexes, and related methods and software systems.

Aggrecanase structure

The invention relates to systems and methods for producing proteins of interest. The invention employs genetically-engineered animal or plant cells that have modified protein folding or processing capacities. In one aspect, the invention features genetically-engineered cells comprising one or more recombinant expression cassettes which encode (1) a protein of interest and (2) a polypeptide that is functional in the unfolded protein response (UPR) pathway of the cells. Co-expression of the polypeptide significantly increases the yield of the protein of interest in the genetically-engineered cells. In one example, the genetically-engineered cells are animal cells, and the co-expressed polypeptide is a component or modulator of an XBP1- or ATF6-mediated UPR pathway.

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Wayland, MA, United States of America

Xiaotian Zhong