Novo Nordisk A/s

Antyra Inc.

Dgi Biotechnologies, Inc.

Jane Spetzler

Jesper F Lau

Thomas Kruse

Patrick William Garibay

Jacob Kofoed

Lars Linderoth

Lauge Schaeffer

Steffen Reedtz-Runge

Ingrid Pettersson

Henning Thoegersen

Birgit Wieczorek

Janos Tibor Kodra

Kjeld Madsen

Per Sauerberg

Peter Madsen

Thomas Kruse Hansen

Thomas Hoeg-Jensen

James Beasley

Tina Moeller Tagmose

Leif Hoejslet Christensen

Ulrich Sensfuss

Jakob Brandt

Henning Thøgersen

Soeren Oestergaard

Arthur J Blume

Per Hertz Hansen

Christian Wenzel Tornoee

János Tibor Kodra

Renee Brissette

Soren Ostergaard

Lauge Schaffer

Lauge Schäffer

Renuka Pillutla

Søren Østergaard

Alice Ravn Madsen

Christoph Kalthoff

Sören Östergaard

Wlodek S Mandecki

Ku-Chuan Hsiao

Mark Ravera

Weiqing Cheng

Ida Heise Stenfeldt Mathiasen

Paul Fletcher

Steffen Runge

Birgit Wiezorek

Christian Wenzel TORNØE

Neil L Goldstein

Renuta Pillutla

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, and the second K residue is designated K; which derivative comprises two albumin binding moieties attached to Kand K, respectively, via a linker, wherein the albumin binding moiety comprises a protracting moiety selected from HOOC&#x2014;(CH)&#x2014;CO&#x2014; and HOOC&#x2014;CH&#x2014;O&#x2014;(CH)&#x2014;CO&#x2014;; 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 &#x2014;NH&#x2014;(CH)&#x2014;(O&#x2014;(CH))&#x2014;O&#x2014;(CH)&#x2014;CO&#x2014;, 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.

Double-acylated GLP-1 derivatives

The invention relates to a derivative of a GLP-1 analog, which analog 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, and the second K residue is designated K; which derivative comprises two albumin binding moieties attached to Kand K, respectively, via a linker, wherein the albumin binding moiety comprises a protracting moiety selected from HOOC&#x2014;(CH)&#x2014;CO&#x2014; and HOOC&#x2014;CH&#x2014;O&#x2014;(CH)&#x2014;CO&#x2014;; 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 &#x2014;NH&#x2014;(CH)&#x2014;(O&#x2014;(CH))&#x2014;O&#x2014;(CH)&#x2014;CO&#x2014;, 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 analogs. The derivatives are suitable for oral administration.

New GLP-1 derivatives, compositions thereof and their use in medicine.

Stable GLP-1 based GLP-1/glucagon receptor co-agonists

The invention relates to a derivative of a GLP-1 analog, which analog comprises a first K residue at a position corresponding to position 18 of GLP-1(7-37) (SEQ ID NO: 1), a second K residue at another position, and a maximum of twelve 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, Chem. 2, and Chem. 3:HOOC&#x2014;(CH)&#x2014;CO&#x2014;*&#x2003;&#x2003;Chem. 1:HOOC&#x2014;CH&#x2014;O&#x2014;(CH)&#x2014;CO&#x2014;*&#x2003;&#x2003;Chem. 2:R&#x2014;CH&#x2014;(CH)&#x2014;CO&#x2014;*,&#x2003;&#x2003;Chem. 3: 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 peptides and side chain intermediates. The derivatives are suitable for oral administration.

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.

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 present invention regards an insulin derivative comprising at least 2 albumin binding moieties, wherein said albumin binding moieties comprise fatty diacid substitutions and a method for preparing such an insulin derivative by acylation and/or reductive alkylation. The present invention also concern a pharmaceutical comprising such an insulin derivative.

Multi-substituted insulins

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

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

Glucagon-Like Peptide-1 derivatives and their pharmaceutical use

The invention relates to a GLP-1 analog which comprises a histidine (H) residue at a position corresponding to position 31 of GLP-1(7-37) (SEQ ID NO: 1), a glutamine (Q) residue at a position corresponding to position 34 of GLP-1 (7-37) (SEQ ID NO: 1), and a maximum of ten amino acid modifications as compared to GLP-1 (7-37) (SEQ ID NO: 1); wherein the H residue is designated H, and the Q residue is designated Q; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to derivatives thereof, as well as the pharmaceutical use of these analogs and derivatives, for example in the treatment and/or prevention of all forms of diabetes and related diseases. The invention furthermore relates to corresponding novel side chain intermediates. The derivatives are suitable for oral administration.

GLP-1 analogues and derivatives

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Broenshoej, Denmark

Jane Spetzler