Bristol-myers Squibb Compnay

Kirk J Leister

Ronald Charles Bates

Jeffrey Schrimsher

Pallaiah Thammana

Ajoy Velayudhan

Lee K Tay

Joyce Patricia Whitehead

Eugene J Schaefer

Robert Donaldson

Elizabeth A Bramhall

Alan R Flesher

David Edward Smolin

John Malcolm Tabor

Helen Gray Haggerty

Reb J Russell

David Henry Kirkley

Thomas James Vanden Boom

David Michael Didio

Dean Woodrow Brownell

Jonathan D Basch

Bernhard M Schilling

Linda Matlock

Stephen G Zegarelli

Christoph E Joosten

Sivakesava Sakhamuri

Steven S Lee

Scott Gangloff

Dharti Kothari

Jonathan O Basch

The invention provides for mammalian cells capable of producing recombinant CTLA4-Ig and variants thereof. The invention also provides for compositions comprising CTLA4-Ig and formulations thereof. The invention further provides for methods for mass-producing CTLA4-Ig from mammalian cells capable of producing this recombinant protein, and for purifying the CTLA4-Ig.

Compositions and methods for producing a composition

Carbohydrate content of CTLA4 molecules

The present invention describes methods and processes for the production of proteins, particularly glycoproteins, by animal cell or mammalian cell culture, illustratively, but not limited to, fed-batch cell cultures. The methods comprise feeding the cells with D-galactose, preferably with feed medium containing D-galactose, preferably daily, to sustain a sialylation effective level of D-galactose in the culture for its duration, thus increasing sialylation of the produced proteins. The methods can also comprise at least two temperature shifts performed during the culturing period, in which the temperature is lower at the end of the culturing period than at the time of initial cell culture. The cell culture processes of the invention involving two or more temperature shifts sustain a high cell viability, and can allow for an extended protein production phase. The methods can also comprise the delayed addition of polyanionic compound at a time after innoculation. Supplementation of the cultures with D-galactose, preferably in a feed medium, to sustain galactose at sialylation effective levels in the cultures until the end of a culture run reverses a decline in sialylation that accompanies culture scale up, and is advantageous for large scale culturing processes.

Product quality enhancement in mammalian cell culture processes for protein production

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Fayetteville, NY, United States of America

Kirk J Leister