Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The invention relates to a polypeptide of formula I:R.sup.1 -A.sup.1 -A.sup.2 -A.sup.3 -A.sup.3 -A.sup.4 -A.sup.5 -A.sup.6 -A.sup.7 -A.sup.9 -Qwherein each of the generic terms is disclosed in full in the specification and includes: R.sup.1 is (2-6C)alkanoyl or (1-4C)alkoxycarbonyl; A.sup.1 is a direct link to A.sup.2, or is Gly or Arg; A.sup.2 is a direct link to A.sup.3, or is Gly or Pro; A.sup.3 is a direct link to A.sup.4, or is Lys or Lys(Z); A.sup.4 is His or D-His; A.sup.5 is Trp or MeTrp; A.sup.6 is Ala or MeAla; A.sup.7 is Val or MeVal; A.sup.8 is Gly or Sar; A.sup.9 is His or MeHis; and Q is a group of the formula -A.sup.10.R.sup.2 in which A.sup.10 is Leu or D-Leu and R.sup.2 is hydroxy, amino, (1-3C)alkylamino or (1-3C)alkoxy; or Q is (1-6C)alkoxy or (1-10C)alkylamino; provided that when R.sup.1 is acetyl and -A.sup.4 -A.sup.5 -A.sup.6 -A.sup.7 -A.sup.8 -A.sup.9 -Q is -His-Trp-Ala-Val-Gly-His-Leu-NH.sub.2 then -A.sup.1 -A.sup.2 -A.sup.3 - is not a direct link to His.