Novo Nordisk A/s

Svend Ludvigsen

Frantisek Hubalek

Thomas Boerglum Kjeldsen

Peter Madsen

Niels Christian Kaarsholm

Morten Schlein

Thomas Borglum Kjeldsen

Svend Havelund

Helle Birk Olsen

Peter Kresten Nielsen

Ulla Ribel-Madsen

Tine Nygaard Vinther

Claude Bonde

Inger Lautrup-Larsen

Palle Jakobsen

Thomas Kruse Hansen

Per Balschmidt

Thomas Børglum Kjeldsen

Dorthe Kot Engelund

Tine Elisabeth Gottschalk Bøving

Lars Bohn Hansen

Anders Klarskov Petersen

Kristian Tage Hansen

Liselotte Bjerre Knudsen

Jeppe Sturis

Dorte Bjerre Steensgaard

Soren Ostergaard

Bjarne Rønfeldt Nielsen

Helle Naver

Per Nørgaard

Thomas B&oslash;rglum Kjeldsen

Anne-Mette Lilleøre

Ejvind Jensen

Tine Elisabeth Gottschalk BØVING

Ulla Ribel

Lars Hansen

Tine Elisabeth Gottschalk Boving

The present invention is related to insulin derivatives containing additional disulfide bonds and methods of making such.

Insulin derivatives containing additional disulfide bonds

The present invention relates to novel insulin analogs comprising mutations at position A14 in the A chain and at positions B27, B28, B29 and B30 in the B chain and exhibiting resistance towards protease; a method for the preparation of such insulin analogs; insulin preparations containing the insulin analogs of the invention; and, a method of treating diabetes mellitus using these insulin analogs.

Protease-stabilized insulin analogues

The present invention relates to novel insulin analogues exhibiting resistance towards protease, wherein at least two amino acids are substituted and/or deleted relative to the parent insulin molecule. A method for the preparation of such insulin analogues, insulin preparations containing the insulin analogues of the invention and a method of treating diabetes mellitus using these insulin analogues is also provided.

Protease resistant insulin analogues

The present invention is related to human insulin containing additional disulfide bonds and methods of making such.

Human insulin containing additional disulfide bonds

The present invention is related to insulin analogs containing additional disulfide bonds and methods of making such.

Insulin analogues containing additional disulfide bonds

Stable pharmaceutical composition comprising insulinotropic peptide.

Stable formulations of peptides

Insulin preparations comprising an insulin compound or a mixture of two or more insulin compounds, a nicotinic compound and an amino acid.

Preparation comprising insulin, nicotinamide and an amino acid

Pharmaceutical composition for parenteral administration comprising a meal related insulin peptide and an insulinotropic peptide.

Soluble pharmaceutical compositions for parenteral administration comprising a GLP-1 peptide and an insulin peptide of short time action for treatment of diabetes and bulimia

Novel insulin precursors and insulin precursor analogs comprising a connecting peptide (mini C-peptide) of preferably up to 15 amino acid residues and comprising at least one Gly are provided. The precursors can be converted into human insulin or a human insulin analog. The precursors will typically have a distance between B27 (atom CG2) and A1 (atom CA) of less than 5 &#x212b;.

Method for making insulin precursors and insulin precursor analogues having improved fermentation yield in yeast

The present invention relates to novel ligands for the HisZnsites of the R-state insulin hexamer having the formula A-B-C-D-X (III), wherein: A is a chemical group which reversibly binds to a HisZnsites of an insulin hexamer; B is a linker; C is a fragment consisting of 0 to 5 neutral amino acids; D is a fragment comprising 1 to 20 positively charged groups independently selected from amino or guanidino groups; and X is &#x2014;OH, &#x2014;NHor a diamino group. The present invention also relates to R-state insulin hexamers comprising such ligands, and aqueous insulin preparations comprising such R-state insulin hexamers.

[object Object]

Novel insulin precursors and insulin precursor analogs having a mini C-peptide comprising at least one aromatic amino acid residue have an increased folding stability. The novel insulin precursors and insulin precursor analogs can be expressed in yeast in high yields and are preferably not more 15 amino acid residues in length. Also provided are polynucleotide sequences encoding the claimed precursors or precursor analogs, and vectors and cell lines containing such polynucleotide sequences.

Method for making insulin precursors and insulin precursor analogs

Novel insulin precursors and insulin precursor analogs comprising a connecting peptide (mini C-peptide) of preferably up to 15 amino acid residues and comprising at least one Gly are provided. The precursors can be converted into human insulin or a human insulin analog. The precursors will typically have a distance between B27 (atom CG2) and A1 (atom CA) of less than 5 &angst;.

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Lynge, Denmark

Svend Ludvigsen