Novo Nordisk A/S
GLP-1 derivatives and uses thereof

Abstract:

The invention relates to a derivative of a GLP-1 analog of a general Formula I, which derivative comprises a side chain attached to a Lys residue at position 34, 35, 36, 37, 38, or 39 of the GLP-1 analog. The side chain comprises a Branched linker, a 1.sup.st and a 2.sup.nd Protractor and a Pre-linker. The Branched linker is connected to the Lys residue of the GLP-1 analog via the Pre-linker and to the 1.sup.st and the 2.sup.nd Protractor via a 1.sup.st and 2.sup.nd Post-linker, respectively. The Branched linker may, e.g., be a tri-radical of Lys. The 1.sup.st and the 2.sup.nd Protractor is C20 diacid. Various linker elements may be used in the Prelinker as well as the two Post-linkers. The invention also relates to novel GLP-analogs, novel side chain intermediates and their manufacture and use to prepare derivatives of biologically active peptides and proteins, as well as pharmaceutical compositions and medical uses of the analogs and derivatives. The derivatives have very long half-lives while maintaining a satisfactory potency, which makes them potentially suitable for once-monthly administration.