Abstract: The present invention is related to a single-chain insulin comprising the B- and the A-chain of human insulin or analogues thereof connected by a connecting peptide having from 3-35 amino acid residues, wherein the single-chain insulin comprises at least one PEG group attached to at least one lysine residue in the single-chain insulin molecule and/or to the B1 N terminal amino acid residue. The PEGylated single-chain insulins may comprise up to 4 PEG groups which may be the same or different.

Abstract: Insulins to which there is connected an amino acid oligomer have satisfactory properties.

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: PEGylated, extended insulins are insulins which, compared with human insulin, has one or more extensions extended from the A1, B1, A21 and/or B30 position(s), said extension(s) consist(s) of amino acid residue(s) and wherein a PEG moiety, via a linker, is attached to one or more of the amino acid residues in the extension(s). PEG is polyethyleneglycol. Such PEGylated, extended insulins have higher bioavailability and a longer time-action profile than regulär insulin and are in particular suited for pulmonary administration and can, conveniently, be used to treat diabetes.

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 is related to single-chain insulin having insulin activity comprising a B- and an A-chain or a modified B- and A-chain connected by a connecting peptide of from 6-11 amino acids. The single-chain insulins will have biological insulin activity and an IGF-1 receptor affinity similar to or lower than that of human insulin and a high physical stability. The single-chain insulin may contain at least one basic amino acid residues in the connecting peptide. The single-chain insulins may also be acylated in one or more Lys residues.

Abstract: The present invention is related to insulin derivatives having a side chain attached to an ?-amino group of a Lys residue present in the A-chain or to an ?-amino group of a Lys residue in the B-chain.

Abstract: The invention is related to an acylated, single-chain insulin comprising the B- and the A-chain of human insulin or an analogue thereof connected by a connecting peptide, wherein a lysine residue being substituted for the natural amino acid residue in one of the positions A12-A23 in the human insulin A-chain has been chemically modified by acylation.

Abstract: The present invention is related to fast acting single-chain insulin comprising a modified B-chain and the A-chain of human insulin or an analogue thereof connected by a connecting peptide wherein one or more of the amino acid residues in position B25, B26 or B27 in the human B-chain are Glu or Asp or are deleted and/or B28 is Glu, Asp, Lys or is deleted, and the amino acid residue in position B10 in the human insulin B-chain is Gln, Ala, Val, Thr or Ser. The invention is also related to pharmaceutical compositions being a mixture of the rapid acting single-chain insulin and the protracted acylated insulin.

Abstract: The invention is related to an acylated, single-chain insulin comprising the B- and the A-chain of human insulin or an analogue thereof connected by a connecting peptide, wherein a lysine residue being substituted for the natural amino acid residue in at least one of the positions B20, B21 or B22 in the human insulin B-chain is chemically modified by acylation.

Abstract: 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 ?.

Abstract: A method is provided which allows high yields of acylated insulin. The method comprises expressing a singe-chain insulin precursor, preferably in yeast, cleaving the single-chain insulin precursor with a suitable protease which will open the peptide bond between the C-terminal amino group in the B-chain and a connecting peptide connecting the B chain with the A-chain, acylating the two-chain insulin intermediate in the ?-amino group in LysB29 and subjecting the acylated two-chain insulin intermediate to a proteolytic enzyme which will cleave of the N-terminal extension on the B- and A-chains on the precursor molecule.

Abstract: 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 ?.

Abstract: Novel insulin precursors comprising a connecting peptide (mini C-peptide) of preferably up to 6 amino acid residues and comprising at least one Pro are provided. The precursors can be converted into human insulin or desB30 human insulin.

Abstract: 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.

Abstract: 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 Å.

Abstract: 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.

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 &egr;-amino groups.

Abstract: 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.

Abstract: The present invention relates to polypeptides expressed and processed in yeast, a DNA construct comprising a DNA sequence encoding such polypeptides, vectors carrying such DNA fragments and yeast cells transformed with the vectors, as well as a process of producing heterologous proteins in yeast.