Novo Nordisk A/s

Beijing University of Technology

Thorkild Christensen

Henrik Dalbo Slashedge

John Pedersen

Jo Slashedrli Ringsted

Torben E Jessen

Ole Hvilsted Olsen

Per Balschmidt

Lars Thim

Hans Holmegaard So Slashedrensen

Peter Becker

Wei Jiang

Therese Jane Mooney

Bimbil Graham

Jan Anton Enoksen

Hans Holmegaard S&oslash;rensen

William Milton Thomas Hearn

Giorgio Meyn

Leone Spiccia

A method for reducing or substantially preventing formation of a trisulfide derivative of a polypeptide in a liquid medium containing the polypeptide ijn question comprises stripping the liquid medium with a gas, suitably a chemically unreactive gas such as nitrogen or argon.

Method for preventing formation of trisulfide derivatives of polypeptides

Provided are new methods for precipitating proteins comprising (a) providing a protein solution, (b) adding a salt to the solution, (c) either (i) adjusting pH of the composition to below the pI of the protein (in cases where the method is directed towards precipitation of most or all proteins in the solution) or (ii) adjusting the pH of the composition to above the pI of the protein (in cases where keeping the target protein in solution is desired), and (d) adding an organic compound to the solution, wherein (I) in the case where the method comprises step (c)(i) a two phase solution is formed wherein at least about 75% of the protein is contained in the protein phase or (II) in the case where the method comprises step (c)(ii) the method further comprises removing precipitated impurities from the protein solution.

Two-phase precipitation of proteins

A polymer substrate functionalized with a functionality comprising at least one cyclic, metal ion coordinating ligand group, the cyclic ligand group comprising at least 3 metal ion coordinating donor atoms independently selected from the group consisting of N, O and S.

Peptide purification by means of metal ion affinity chromatography

A readily-soluble freeze-dried solid preparation of hGH with a minimal content of degradation products in terms of deamidation, dimers, polymers, and sulphoxide forms, obtainable by a method comprising a single lyophilization of an aqueous slurry of an amorphous hGH isoprecipitate, the slurry having a pH of from about 4.7 to 5.0 and being essentially free of buffer components other than acetate.

Freeze-dried preparation of human growth hormone

A pharmaceutical formulation comprising a growth hormone and Leu-His-Leu as additive or buffering substance shows a very high stability against deamidation, oxidation and cleavage of peptide bonds. The stability of the product allows for the storing and shipment thereof in a lyophilized state or in the form of a dissolved or re-dissolved formulation at ambient temperature.

Pharmaceutical formulation

Process for preparing a desired protein

Amino-terminally extended human growth hormone (HGH)

Biosynthetic human growth hormone

A process for producing ripe human growth hormone is described which comprises introducing into bacteria a recombinant DNA vector comprising a DNA sequence encoding an amino-terminal extended human growth hormone which amino-terminal extension has a negatively charged amino acid sequence and has an even number of amino acids, growing the bacteria such that the amino-terminal extended human growth is expressed, separating the amino-terminal extended human grown hormone from contaminants, cleaving the amino-terminal extension with dipeptidyl aminopeptidase I to obtain ripe human growth hormone and isolating the ripe human growth hormone produced.

A pharmaceutical formulation comprising a growth hormone and Lys-Gly-Asp-Ser (SEQ ID No: 1) as additive or buffering substance shows a very high stability against deamidation, oxidation and cleavage of peptide bonds. The stability of the product allows for the storing and shipment thereof in a lyophilized state or in the form of a dissolved or re-dissolved formulation at ambient temperature.

Growing community of inventors

Aller.o slashed.d, Denmark

Thorkild Christensen