The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue and a second K residue, at positions corresponding to position 26, and 37, respectively, of GLP-1(7-37) (SEQ ID NO: 1), and a maximum of eight amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1: HOOC—(CH.sub.2).sub.x—CO—*, and Chem. 2: HOOC—C.sub.6H.sub.4—O—(CH.sub.2).sub.y—CO—*, in which x is an integer in the range of 8-16, and y is an integer in the range of 6-13; and the linker comprises Chem. 3: *—NH—(CH.sub.2).sub.q—CH[(CH.sub.2).sub.w—NR.sub.1R.sub.2]—CO—*, which is connected at its CO—* end to the epsilon amino group of the first or the second K residue of the GLP-1 analogue, and wherein q is an integer in the range of 0-5, R.sub.1 and R.sub.2 independently represent *—H or *—CH.sub.3, and w is an integer in the range of 0-5; 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 peptide and linker intermediates. The derivatives are potent, stable, protracted, and suitable for oral administration.

The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue and a second K residue, at positions corresponding to position 26, and 37, respectively, of GLP-1(7-37) (SEQ ID NO: 1), and a maximum of eight amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1: HOOC—(CH.sub.2).sub.x—CO—*, and Chem. 2: HOOC—C.sub.6H.sub.4—O—(CH.sub.2).sub.y—CO—*, in which x is an integer in the range of 8-16, and y is an integer in the range of 6-13; and the linker comprises Chem. 3: *—NH—(CH.sub.2).sub.q—CH[(CH.sub.2).sub.w—NR.sub.1R.sub.2]—CO—*, which is connected at its CO—* end to the epsilon amino group of the first or the second K residue of the GLP-1 analogue, and wherein q is an integer in the range of 0-5, R.sub.1 and R.sub.2 independently represent *—H or *—CH.sub.3, and w is an integer in the range of 0-5; 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 peptide and linker intermediates. The derivatives are potent, stable, protracted, and suitable for oral administration.

Long-acting co-agonists of the glucagon and GLP-1 receptors are described.

Long-acting co-agonists of the glucagon and GLP-1 receptors are described.

The present invention provides an improved process for the preparation of high purity glucagon comprising the use of Xmb-protected amino acids, wherein may Xmb include, e.g., 2,4,6-trimethoxybenzyl, 2,4-dimethoxybenzyl, or 2-hydroxy-4-methoxybenzyl. The process also comprises the use of building blocks such as pseudoprolines to avoid aggregation and obtain the product in high yield and purity.

The present invention provides an improved process for the preparation of high purity glucagon comprising the use of Xmb-protected amino acids, wherein may Xmb include, e.g., 2,4,6-trimethoxybenzyl, 2,4-dimethoxybenzyl, or 2-hydroxy-4-methoxybenzyl. The process also comprises the use of building blocks such as pseudoprolines to avoid aggregation and obtain the product in high yield and purity.

Provided herein are GLP1-GDF15 fusion proteins comprising a GLP1 or GLP1 variant peptide, a first linker peptide, a serum albumin protein, a second linker peptide, and a GDF15 protein.

Provided herein are GLP1-GDF15 fusion proteins comprising a GLP1 or GLP1 variant peptide, a first linker peptide, a serum albumin protein, a second linker peptide, and a GDF15 protein.

Certain aspects of the present invention are directed to a method for making a protein blocking assembly reversibly linking a therapeutic protein to a blocking group via a linker moiety. Additional aspects of the invention are directed to the protein blocking assembly, and to methods of administering the protein blocking assembly to a subject, where the protein is cleaved from the protein blocking assembly.

Certain aspects of the present invention are directed to a method for making a protein blocking assembly reversibly linking a therapeutic protein to a blocking group via a linker moiety. Additional aspects of the invention are directed to the protein blocking assembly, and to methods of administering the protein blocking assembly to a subject, where the protein is cleaved from the protein blocking assembly.