Abstract: 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.

Abstract: 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.

Abstract: The invention is related to novel N-terminally modified insulin derivatives, pharmaceutical compositions comprising such and methods of making such.

Abstract: The present invention related to a method of producing polypeptides in transformed host cells by expressing a precursor molecule of the desired polypeptide which are to be acylated in a subsequent in vitro step. The invention is also related to DNA-sequences, vectors and transformed host cells for use in the claimed method. Further, the present invention is related to certain precursors of the desired polypeptides and certain acylation methods. The invention provides a method for making polypeptides being preferentially acylated in certain lysine ?-amino groups.

Abstract: The present invention relates to pharmaceutical compositions comprising a GLP-1 compound, a divalent metal and a polycationic compound. The invention is characterised in that the GLP-1:divalent metal molar ratio is 1:>2. The compositions of the invention are particularly useful in the treatment of diabetes.

Abstract: The present invention relates to compositions and particles comprising a GLP-1 compound, a divalent metal and a polycationic compound. The invention is characterised that the particle comprises a core and a surrounding layer, the core comprising the GLP-1 compound and the divalent metal, and the surrounding layer comprising the polycationic compound. The invention is particularly useful for the treatment of metabolic diseases, including diabetes.

Abstract: The invention is related to fast acting insulin analogues which can form soluble mix-tures (pre-mixed or self-mixed) with long acting insulin analogues. The fast action is achieved through monomerizing substitutions/deletions in the C-terminus of the B-chain of human insulin and the mixability with long acting insulin analogues is achieved through a substitution of the Zn-binding His in position B10 of human insulin with a Gln amino acid residue. In one embodiment the invention is related to fast acting insulin analogues in which at least one of the natural amino acid residues in position B22-B30 in the human B-chain has been substituted with another amino acid residue having the effect of promoting formation of the monomeric form of insulin, the His amino acid residue in position 10 in the B-chain is substituted with a Gln and wherein further one or more of the amino acid residues in position B22-B30 optionally have been deleted.

Abstract: The present invention relates to pharmaceutical formulations comprising insulin, an insulin analog, an insulin derivative, or a combination of any of the foregoing, and a salt of protamine, to methods of preparing such formulations, and to uses of such formulations in the treatment of diseases and conditions for which use of the insulin peptide(s) contained in such formulations is indicated. The present invention further relates to methods for increasing the stability and/or solubility of insulin in insulin-containing formulations at a pH less than 7.0 by adding a salt of protamine to the insulin-containing formulations.

Abstract: The present invention relates to novel insulin analogues 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 analogues; insulin preparations containing the insulin analogues of the invention; and, a method of treating diabetes mellitus using these insulin analogues.

Abstract: The present invention relates to pharmaceutical formulations comprising insulin, an insulin analog, an insulin derivative, or a combination of any of the foregoing, and a salt of protamine, to methods of preparing such formulations, and to uses of such formulations in the treatment of diseases and conditions for which use of the insulin peptide(s) contained in such formulations is indicated. The present invention further relates to methods for increasing the stability and/or solubility of insulin in insulin-containing formulations at a pH less than 7.0 by adding a salt of protamine to the insulin-containing formulations.

Abstract: The invention is related to fast acting insulin analogues which can form soluble mix-tures (pre-mixed or self-mixed) with long acting insulin analogues. The fast action is achieved through monomerizing substitutions/deletions in the C-terminus of the B-chain of human insulin and the mixability with long acting insulin analogues is achieved through a substitution of the Zn-binding His in position B10 of human insulin with a Gln amino acid residue. In one embodiment the invention is related to fast acting insulin analogues in which at least one of the natural amino acid residues in position B22-B30 in the human B-chain has been substituted with another amino acid residue having the effect of promoting formation of the monomeric form of insulin, the His amino acid residue in position 10 in the B-chain is substituted with a Gln and wherein further one or more of the amino acid residues in position B22-B30 optionally have been deleted.

Abstract: Highly concentrated insulin solutions and pharmaceutical compositions are described as are methods of their preparation and uses thereof.

Abstract: The present invention related to a method of producing polypeptides in transformed host cells by expressing a precursor molecule of the desired polypeptide which are to be acylated in a subsequent in vitro step. The invention is also related to DNA-sequences, vectors and transformed host cells for use in the claimed method. Further, the present invention is related to certain precursors of the desired polypeptides and certain acylation methods. The invention provides a method for making polypeptides being preferentially acylated in certain lysine ?-amino groups.

Abstract: 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.

Abstract: The present invention related to a method of producing polypeptides in transformed host cells by expressing a precursor molecule of the desired polypeptide which are to be acylated in a subsequent in vitro step. The invention is also related to DNA-sequences, vectors and transformed host cells for use in the claimed method. Further, the present invention is related to certain precursors of the desired polypeptides and certain acylation methods. The invention provides a method for making polypeptides being preferentially acylated in certain lysine ?-amino groups.

Abstract: The present invention related to a method of producing polypeptides in transformed host cells by expressing a precursor molecule of the desired polypeptide which are to be acylated in a subsequent in vitro step. The invention is also related to DNA-sequences, vectors and transformed host cells for use in the claimed method. Further, the present invention is related to certain precursors of the desired polypeptides and certain acylation methods. The invention provides a method for making polypeptides being preferentially acylated in certain lysine ?-amino groups.

Abstract: A preferred way of converting insulin precursors into insulin compounds is to perform an enzymatic peptide cleavage in an aqueous medium and, thereafter, without removal of the intermediate product formed, to add an amino acid ester or a peptide ester and an organic solvent so that the desired coupling takes place.

Abstract: Insulin derivatives having a built-in glucose sensor, capable of delivering insulin from a depot as a function of the glucose concentration in the surrounding medium (e.g. tissue), such that the rate of insulin release from the depot increases with an increased glucose concentration and decreases with a decreased glucose concentration.

Abstract: This invention relates to sustained release preparations of insulin comprising poly-amino acid particles, insulin and one or more preservative agents, and a method of preparing such preparations.

Abstract: This invention relates to NPH-insulin (crystalline preparations) that are prepared in the presence of certain high-affinity ligands for the HisB10 Zn2+-sites of the R-state insulin hexamer. Preparation of NPH-insulin in the presence of high-affinity ligand results in crystalline NPH-insulin suspensions that are absorbed more slowly from subcutis than regular NPH-insulin.