Imperial Chemical Industries Limited

Zeneca Limited

Roger Camble

David Timms

Anthony J Wilkinson

Ronald Cotton

Anand Swaroop Dutta

Christopher F Hayward

Heather Carr

The present invention provides a conjugate of a solution stable G-CSF derivative and a water soluble polymer which is an acid stable physiologically active substance derived from naturally occurring G-CSF.

Conjugate of a solution stable G-CSF derivative and a water-soluble

Derivatives of naturally occurring G-CSF having at least one of the biological properties of naturally occurring G-CSF, and a solution stability of at least 35% at 5 mg/ml are disclosed in which the derivative has at least Cys.sup.17 of the native sequence replaced by a Ser.sup.17 residue and Asp.sup.27 of the native sequence replaced by a Ser.sup.17 residue. Nucleotide sequences coding for part or all of the amino acid sequence of the derivatives of the invention may be incorporated into autonomously replicating plasmid or viral vectors employed to transform or transfect suitable procaryotic or eucaryotic host cells such as bacteria, yeast or vertebrate cells in culture.

Polypeptide derivatives of granulocyte colony stimulating factor

Pharmaceutical compositions for continuous release of a physiologically active substance in which the physiologically active substance comprises a polypeptide covalently conjugated to a water soluble polymer show particularly desirable release characteristics. Polypeptides for use in the pharmaceutical compositions include G-CSF and solution stable derivatives thereof, human calcitonin and interleukin-2. The material of the composition may be a polylactide or biodegradable hydrogel derived from an amphipathic block copolymer. The compositions enable a therapeutically effective polypeptide to be continuously released over a prolonged period of time following a single administration of the pharmaceutical composition to a patient.

Continuous release pharmaceutical compositions

The invention relates to a polypeptide of formula I:

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Macclesfield, United Kingdom

Roger Camble