Novo Nordisk A/s

Lauge Schaeffer

Thomas Kruse

Henning Thoegersen

Jesper F Lau

Jane Spetzler

Patrick William Garibay

Kirsten Dahl

Ingrid Pettersson

Steffen Reedtz-Runge

Kjeld Madsen

Kirsten Raun

Thomas Kruse Hansen

Janos Tibor Kodra

Jacob Kofoed

Lars Linderoth

Leif Hoejslet Christensen

Jakob Brandt

Christian Poulsen

Soeren Oestergaard

Rita Slaaby

Bo Falck Hansen

Grith Skytte Olsen

The present invention relates to novel insulin analogues and derivatives thereof, such as acylated insulin analogues, and their pharmaceutical use, in particular in the treatment or prevention of medical conditions relating to diabetes, obesity and cardiovascular diseases.

Acylated insulin analogues and uses thereof

The present invention relates to peptides comprising an amino acid sequence SEQ ID NO: 1 (EASELSTAALGRLSAELHELATLPRTETGPESP), analogs and derivatives thereof and pharmaceutical compositions comprising such peptides and derivatives. This invention further regards the use of these peptides according to SEQ ID NO: 1, analogs and derivatives thereof as medicaments.

Amylin and calcitonin receptor agonist

The invention relates to truncated GLP-1 analogs, in particular a GLP-1 analog which is a modified GLP-1(7-35) (SEQ ID No 1) having: i) a total of 2, 3, 4, 5 6, 7, 8, or 9 amino acid substitutions as compared to GLP-1(7-35), including a) a Glu residue at a position equivalent to position 22 of GLP-1(7-35), and b) an Arg residue at a position equivalent to position 26 of GLP-1(7-35); as well as derivatives thereof, and therapeutic uses and compositions. These analogs and derivatives are highly potent, have a good binding affinity to the GLP-1 receptor, also to the extracellular domain of the GLP-1 receptor, which is of potential relevance achieving long-acting, stable GLP-1 compounds with a potential for once weekly administration.

Truncated GLP-1 derivatives and their therapeutical use

The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 37 of GLP-1(7-37) (SEQ ID NO: 1), a second K residue at a position corresponding to position 26 of GLP-1(7-37), and a maximum of ten amino acid modifications as compared to GLP-1(7-37), wherein the first K residue is designated K, and the second K residue is designated K, which derivative comprises two albumin binding moieties attached to Kand K, respectively, wherein the albumin binding moiety comprises a protracting moiety selected from: Chem. 1, Chem. 2, Chem. 3 or Chem. 4; or a pharmaceutically acceptable salt, amide, or ester thereof.

Double-acylated GLP-1 derivatives

The invention relates to protracted Glucagon-Like Peptide-1 (GLP-1) derivatives and therapeutic uses thereof. The GLP-1 derivative of the invention comprises a modified GLP-1(7-37) sequence having a total of 2-12 amino acid modifications, including Glu22 and Arg26, and being derivatised with an albumin binding residue or pegylated in position 18, 20, 23, 30, 31, 34, 36, 37, or 39. These compounds are useful in the treatment or prevention of diabetes type 2 and related diseases. The compounds are potent, stable, have long half-lives, a high affinity of binding to albumin, and/or a high affinity of binding to the extracellular domain of the GLP-1 receptor (GLP-1R), all of which is of potential relevance for the overall aim of achieving long-acting, stable and active GLP-1 derivatives with a potential for once weekly administration.

Glucagon-like peptide-1 derivatives and their pharmaceutical use

The invention relates to protracted peptide derivatives such as Glucagon-Like Peptide-1 (GLP-1), exendin-4, and analogs thereof, as well as therapeutic uses thereof. The peptide derivative of the invention comprises a peptide wherein at least one amino acid residue is derivatized with A-B-C-, or A-B-C-D-. These compounds are useful in the treatment or prevention of diabetes type 2 and related diseases. The compounds are potent, have a low ratio of binding affinity to the GLP-1 receptor in the presence of high/low albumin concentrations, have long half-lives, and have a high affinity of binding to albumin, all of which is of potential relevance for the overall aim of achieving long-acting, stable and active GLP-1 derivatives with a potential for once weekly administration.

Peptides derivatized with A-B-C-D- and their therapeutical use

The invention relates to polypeptides comprising an amino acid sequence which is an analogue of pramlintide, pharmaceutical compositions comprising these polypeptides, and these polypeptides for use as medicaments.

Amylin analogues and pharmaceutical compositions thereof

The invention relates to polypeptides comprising an amino acid sequence which is an analog of human amylin, pharmaceutical compositions comprising these polypeptides, and these polypeptides for use as medicaments.

Amylin analogs and pharmaceutical compositions thereof

This invention provides Exendin-4 compounds derivatized at a lysine 14 residue to give an acylated lysine, pharmaceutical compositions comprising such compounds, and the use of such compositions for treating diabetes.

Acylated exendin-4 compounds

Polypeptides

The invention relates to polypeptides comprising an amino acid sequence which is an analogue of human amylin, pharmaceutical compositions comprising these polypeptides, and these polypeptides for use as medicaments.

Growing community of inventors

Lyngby, Denmark

Lauge Schaeffer