Novo Nordisk A/S
Double-acylated GLP-1 derivatives

Abstract:

The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 27 of GLP-1(7-37) (SEQ ID NO: 1); a second K residue at a position corresponding to position T of GLP-1(7-37), where T is an integer in the range of 7-37 except 18 and 27; and a maximum of ten amino acid changes as compared to GLP-1(7-37); wherein the first K residue is designated K.sup.27, and the second K residue is designated K.sup.T; which derivative comprises two albumin binding moieties attached to K.sup.27 and K.sup.T, respectively, via a linker, wherein the albumin binding moiety comprises a protracting moiety selected from HOOC--(CH.sub.2).sub.x--CO-- and HOOC--C.sub.6H.sub.4--O--(CH.sub.2).sub.y--CO--; in which x is an integer in the range of 6-16, and y is an integer in the range of 3-17; wherein the linker comprises an element of the formula --NH--(CH.sub.2).sub.2--(O--(CH.sub.2).sub.2).sub.k--O--(CH.sub.2).sub.n-- -CO--, wherein k is an integer in the range of 1-5, and n is an integer in the range of 1-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel GLP-1 analogues. The derivatives are suitable for oral administration.