Cetus Corporation

Schering Aktiengesellschaft

Terrance A Taforo

James W Thomson

Wolfgang H Hanisch

Pete M Fernandes

Thomas R Tice

Ze'ev Shaked

Richard M Gilley

Jack H Nunberg

Peter M Fernandes

Susan Hershenson

Jody Thomson

Tracy Stewart

Maninder Singh

Michael E Hudson

Highly stable, pharmaceutical compositions comprising a therapeutically effective amount of a biologically active recombinant lipophilic protein such as human .beta.-interferon and interleukin-2 dissolved in a non-toxic, inert, therapeutically compatible aqueous-based carrier at pH ranges of from about 6.8 to 7.8 and about 8.5 to 10, which formulations contain a stabilizer for the protein selected from the group comprising human serum album, human serum albumin and dextrose or human plasma protein fraction, and at a pH range of from about 2 to 4, which latter formulations optionally contain a carbohydrate and/or protein stabilizer, are disclosed. Further, preferred formulation processes to prepare said compositions are described which avoid highly alkaline conditions.

Formulation processes for lipophilic proteins

Stable pharmaceutical compositions suitable for parenteral administration to animals or humans are prepared comprising a therapeutically effective amount of a recombinant IFN-.beta. protein dissolved in an inert carrier medium comprising as solubilizer/stabilizer(s) one or more biocompatible non-ionic polymeric detergents or a combination of one or more biocompatible non-ionic polymeric detergents with an additional solubilizing and/or stabilizing agent, such as sodium dodecyl sulfate or glycerol. The compositions are in liquid form or lyophilized.

Formulation processes for pharmaceutical compositions of recombinant .beta.

Shipping fever, and other stress-related diseases in livestock, are treated by administration of a microencapsulated composition comprising IL-2 conjugated with a polyoxyethylene polymer, and mixed with a release-modulating amount of humen serum albumin. The microcapsules are administered parenterally, and release an effective amount of conjugated IL-2 continuously over a period of 14-30 days. These microcapsules are also effective in the treatment of cancer in mammals.

Controlled-release formulations of interleukin-2

An improved process for recovering and purifying lipophilic recombinant proteins such as human .beta.-interferon and interleukin-2 from their hosts yields a protein preparation which may be formulated into a stable pharmaceutical composition having a therapeutically effective amount of the biologically active recombinant lipophilic protein dissolved in a non-toxic, inert, therapeutically compatible aqueous-based carrier medium at a pH of 6.8 to 7.8 which medium also contains a stabilizer for the protein, such as human serum albumin, normal serum albumin and human plasma protein fraction.

Formulation for lipophilic IL-2 proteins

A sterile, stable lyophilized formulation of selectively oxidized microbially produced recombinant IL-2 in which the recombinant IL-2 is admixed with a water soluble carrier such as mannitol that provides bulk, and a sufficient amount of sodium dodecyl sulfate to ensure the solubility of the recombinant IL-2 in water. The formulation is suitable for reconstitution in aqueous injections for parenteral administration and it is stable and well tolerated in human patients. FIG. 1 illustrates a preferred method of purifying recombinant IL-2 suitable for use in preparing the formulations of the present invention.

Pharmaceutical compositions of microbially produced interleukin-2

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San Leandro, CA, United States of America

Terrance A Taforo