Genentech, Inc.

Kenneth C Olson

James A Wells

Germaine G Fuh

Brian C Cunningham

Ross G Clark

Henry Bernard Lowman

Rong-Chang Pai

Barry R Bochner

Steven J Shire

Andrew J Jones

Human growth hormone variants are disclosed having enhanced affinity for the growth hormone receptor. Also disclosed are human growth hormone variants conjugated to one or more chemical groups, such as poly(ethylene glycol), which is believed to prolong the in vivo half-life of the variants.

Human growth hormone variants comprising amino acid substitutions

Method for inhibiting growth hormone action

Human growth hormone variants, DNA encoding the variants, vectors, host cells, pegylated forms of the variants, as well as methods of making the variants are disclosed.

Human growth hormone variants

Periplasmic proteins are recovered from transformed gram negative bacteria by a process comprising freezing and thawing the cells. Advantages are obtained by culturing the cells in phosphate-limiting media and by killing the cells prior to separation of periplasmic proteins.

Periplasmic protein recovery

A process for isolating and purifying a precipitated heterologous protein from a host cell culture, including treating the host cell culture with a buffered solution of ionic strength suitable to solubilize most of the host protein but in which refractile heterologous protein is substantially insoluble, and disrupting the cells to form a supernatant and an insoluble fraction; treating the insoluble fraction with a strongly denaturing solution to solubilize the refractile heterologous protein; and recovering renatured heterologous protein.

Purification and activity assurance of precipitated heterologous proteins

A process for maintaining refractile proteins in solubilized form by replacing the strongly denaturing solution with a weakly denaturing solution.

A process for dissolving refractile proteins from their insoluble form by using a strongly denaturing solution.

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Burlingame, CA, United States of America

Kenneth C Olson