Cetus Corporation

Cetus Oncology Corporation

Nandini Katre

Michael J Knauf

Danute E Nitecki

Lois Aldwin

Robert J Goodson

Kirston E Koths

Margaret Moreland

Paula J Shadle

Robert F Halenbeck

Walter J Laird

Maninder Singh Hora

John D Young

Kenneth A Laderman

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

Conjugation of polymer to colony stimulating factor-1

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 pharmaceutical composition for proteins which are not stably soluble. The preferred protein is IL-2 and the preferred composition includes amino acids, vitamins, polymers, fatty acids or low molecular weight acids.

Pharmaceutical composition for interleukin-2 containing physiologically

A pharmaceutical composition is prepared wherein biologically active conjugated interleukin-2 is dissolved in an aqueous carrier medium without the presence of a solubilizing agent. The unconjugated IL-2, which is not water soluble or not readily soluble in water at pH 6-8 without such solubilizing agent, is selectively conjugated to one or more succinyl groups by reaction with succinic anhydride.

Succinylated interleukin-2 for pharmaceutical compositions

A pharmaceutical composition is prepared wherein a biologically active conjugated protein which is .beta.-interferon, interleukin-2, or an immunotoxin is dissolved in an aqueous carrier medium without the presence of a solubilizing agent. The unconjugated protein, which is not water-soluble or not readily soluble in water at pH 6-8 without such solubilizing agent, is selectively conjugated to a water-soluble polymer selected from polyethylene glycol homopolymers or polyoxyethylated polyols.

Solubilization of immunotoxins for pharmaceutical compositions using

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.

A biologically active CSF-1 protein is selectively conjugated via certain amino acid residues or carbohydrate moieties to a water-soluble polymer selected from polyethylene glycol or polypropylene glycol homopolymers, polyoxyethylated polyols, or polyvinyl alcohol. The resulting conjugated CSF-1 is biologically active and has increased circulating half-life in mammals, compared to that of the unconjugated protein. The conjugated CSF-1 may be used to stimulate the immune response or to provide more cells to be stimulated.

Growing community of inventors

El Cerrito, CA, United States of America

Nandini Katre