Cetus Corporation

Cetus Oncology Corporation

Robert J Goodson

Nandini Katre

Danute E Nitecki

Lois Aldwin

Robert F Halenbeck

Will Bloch

Patrick J Sheridan

Michael J Knauf

Peter C McCabe

Muteins of IL-2 in which one of the amino acids of the mature native sequence of IL-2 is replaced by a cysteine residue are prepared and conjugated through the replaced cysteine residue to a polymer selected from polyethylene glycol homopolymers or polyoxyethylated polyols, wherein said homopolymers are unsubstituted or substituted at one end with an alkyl group. These muteins are made via host expression of mutant genes encoding the muteins that have been changed from the genes for the parent proteins by site-directed mutagenesis. In addition, other species of IL-2 may be conjugated via the cysteine residue at position 125 of the mature IL-2 protein that is not necessary for the biological activity of the IL-2.

Interleukin-2 muteins and polymer conjugation thereof

The present invention is a process for preparing a pharmaceutical composition comprising a biologically active conjugated protein. It comprises a polyethylene glycol or a polyoxyethylated polyol conjugated to IL-2. This protein is conjugated to reduce its immunogenicity, and increase its solubility, and increase its circulating in vivo half-life.

Preparation of a polymer/interleukin-2 conjugate

The present invention is a process for preparing a pharmaceutical composition comprising a biologically active conjugated protein. It comprises a polyethylene glycol or a polyoxyethylated polyol conjugated to IL-2. This protein is conjugated to reduce its immunogenicity, and increase it solubility, and increase its circulating in vivo half-life.

Useful for visualizing biological materials in a solid phase, on a gel, or in a liquid phase is a solid salt of the meriquinone of benzidine or a substituted benzidine. An immobilized or dissolved complex of a polymeric anion and the meriquinone of benzidine or a substituted benzidine having controllable solubility may also be employed. Preferred are meriquinone salts and complexes of 3,3,5,5'-tetramethylbenzidine. For visualization, the benzidine or substituted benzidine is oxidized to its meriquinone at pH 3 to 7 in the presence of an effective anion or polymeric anion, an oxidation catalyst, and an effective amount of oxidant to form a solid salt or immobilized complex of the meriquinone under conditions where the meriquinone solubility lies below about 10.sup.-5 M.

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Albany, CA, United States of America

Robert J Goodson