Abstract: The present invention relates to Fibroblast Growth Factor 21 (FGF21), more in particular to derivatives of FGF21 compounds having an albumin binder of the formula A-B-C-D-E- covalently attached. The invention also relates to novel FGF21 analogues, as well as to the pharmaceutical use of these FGF21 derivatives and analogues, in particular for the treatment of diabetes, dyslipidemia, obesity, cardiovascular diseases, metabolic syndrome, and/or Non Alcoholic Fatty Liver Disease (NAFLD). The derivatives of the invention are protracted, e.g. capable of maintaining a low blood glucose level for a longer period of time, capable of increasing the in vivo half-life of FGF21, and/or result in a lower clearance of FGF21. The derivatives of the invention are preferably furthermore of an improved oxidative stability.

Abstract: Insulin albumin conjugates consisting of an insulin analogue, a bifunctional linker and albumin can efficiently be used to treat diabetic patients.

Abstract: An acylated insulin analogue wherein the insulin analogue comprises a lysine residue connected C-terminally to the A21 amino acid residue or a peptide residue of up to 4 amino acid residues comprising a lysine residue which peptide residue is connected C-terminally to the A21 amino acid residue, characterized in that an acyl moiety comprising an alkylene glycol moiety is attached to the lysine residue in the A22 position or attached to a lysine residue present in the peptide residue that is attached to the C terminal end of the A21 amino acid residue and wherein there is only one lysine (K, Lys) in the insulin analogue, can conveniently be administered pulmonary.

Abstract: Novel PEGylated insulin analogs exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogs contain B25H and A14E or A14H. The PEGylation is at B29K.

Abstract: The present invention relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have a side chain attached either to the ?-amino group of the N-terminal amino acid residue of the B chain or to the ?-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula: —W—X—Y—Z wherein W, X, Y and Z are as defined in the disclosure.

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: 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 regular insulin and are in particular suited for pulmonary administration and can, conveniently, be used to treat diabetes.

Abstract: A method has for selectively acylating an amino group in a peptide or protein which has two or more reactive nucleophilic functional groups is described.

Abstract: The present invention relates to insulin derivatives having a side chain attached either to the ?-amino group of the N-terminal amino acid residue of the B chain or to the ?-amino group of a Lys residue present in the B chain of the parent insulin via an amide bond which side chain comprises at least one aromatic group; at least one free carboxylic acid group or a group which is negatively charged at neutral pH, a fatty acid moiety with 4 to 22 carbon atoms in the carbon chain; and possible linkers which link the individual components in the side chain together via amide bonds.

Abstract: Novel PEGylated insulin analogues exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogues contain B25H and A14E or A14H. The PEGylation is at B29K.

Abstract: Derivatives of Fibroblast Growth Factor 21 which have improved properties for treating diabetes can be prepared by a recombinant process.

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 regular insulin and are in particular suited for pulmonary administration and can, conveniently, be used to treat diabetes.

Abstract: A method has for selectively acylating an amino group in a peptide or protein which has two or more reactive nucleophilic functional groups is described.

Abstract: Novel acylated insulin analogues exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogues contain B25H and A14E or A14H.

Abstract: Insulin albumin conjugates consisting of an insulin analogue, a bifunctional linker and albumin can efficiently be used to treat diabetic patients.

Abstract: The present invention relates to Fibroblast Growth Factor 21 (FGF21), more in particular to derivatives of FGF21 compounds having an albumin binder of the formula A-B-C-D-E- covalently attached. The invention also relates to novel FGF21 analogues, as well as to the pharmaceutical use of these FGF21 derivatives and analogues, in particular for the treatment of diabetes, dyslipidemia, obesity, cardiovascular diseases, metabolic syndrome, and/or Non Alcoholic Fatty Liver Disease (NAFLD). The derivatives of the invention are protracted, e.g. capable of maintaining a low blood glucose level for a longer period of time, capable of increasing the in vivo half-life of FGF21, and/or result in a lower clearance of FGF21. The derivatives of the invention are preferably furthermore of an improved oxidative stability.

Abstract: The present invention relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have a side chain attached either to the ?-amino group of the N-terminal amino acid residue of the B chain or to the ?-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula: —W—X—Y—Z wherein W, X, Y and Z are as defined in the disclosure.

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 relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have a side chain attached either to the ?-amino group of the N-terminal amino acid residue of the B chain or to the ?-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula: -W-X—Y-Z wherein W, X, Y and Z are as defined in the disclosure.

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.