US 2016/0108102 A1Published application

Novel GLP-1 Derivatives

AssigneeNovo Nordisk A/S

InventorsJesper Lau, Thomas K. Hansen, Kjeld Madsen, Paw Bloch, Florencio Z. Dorwald, Niels L. Johansen

Life of this patent

Estimating the term…

Abstract

Novel polypeptide derivatives having protracted profile of action.

Claims21

Dependent claims

A compound which has the formula (I):

A-W-B-Y-therapeutic polypeptide (I)
wherein:
the therapeutic polypeptide is a GLP-1 peptide comprising the amino acid sequence of formula (V):
Xaa7-Xaa8-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Xaa18-Tyr-Leu-Glu-Xaa22-Xaa23-Ala-Ala-Xaa26-Glu-Phe-Ile-Xaa30-Trp-Leu-Val-Xaa34-Xaa35-Xaa36-Xaa37-Xaa38 Formula (V) (SEQ ID No:
3)
wherein
Xaa7 is L-histidine or desamino-histidine;
Xaa8 is Ala, Gly or Aib;
Xaa18 is Ser or Arg;
Xaa22 is Gly, Glu or Aib;
Xaa23 is Gln or Glu;
Xaa26 is Lys or Arg;
Xaa30 is Ala or Glu;
Xaa34 is Lys or Arg;
Xaa35 is Gly or Aib;
Xaa36 is Arg or Lys;
Xaa37 is Gly, Ala or Lys;
Xaa38 is Lys, amide or is absent;
A is an albumin binding residue selected from the group consisting of:
where the chiral carbon atom is either R or S,
where the chiral carbon atom is either R or S,
where the two chiral carbon atoms independently are either R or S,
where the two chiral carbon atoms independently are either R or S,
B is —(CH2)l—O—[(CH2)n—O]m—(CH2)p—[C(O)NH—(CH2)l—O—[(CH2)n—O]m—(CH2)p]q—,
where l, m, n, and p independently are 1-5, and q is 0-5,
Y is a chemical group linking B and the therapeutic polypeptide, selected from the group consisting of —C(O)NH—, —NHC(O)—, —C(O)NHCH2—, —CH2NHC(O)—, —OC(O)NH—, —NHC(O)O—, —C(O)NHCH2—, CH2NHC(O)—, —C(O)CH2—, —CH2C(O)—, —C(O)CH═CH—, —CH═CHC(O)—, —(CH2)s—, —C(O)—, —C(O)O—, —OC(O)—, —NHC(O)— and —C(O)NH—, wherein s is 0 or 1, and
W is a chemical group linking A and B, selected from the group consisting of —C(O)NH—, —NHC(O)—, —C(O)NHCH2—, —CH2NHC(O)—, —OC(O)NH—, —NHC(O)O—, —C(O)CH2—, —CH2C(O)—, —C(O)CH═CH—, —CH═CHC(O)—, —(CH2)s—, —C(O)—, —C(O)O—, —OC(O)—, —NHC(O)— and —C(O)NH—, wherein s is 0 or 1;
and said GLP-1 peptide is attached to A-W-B-Y via the amino acid residue in positions 26, 37 or 38 in SEQ ID NO:3;
or a pharmaceutically acceptable salt or prodrug thereof.

26 more elements

A compound selected from the group consisting of:

Nε37-{2-[2-(2-(15-carboxypentadecanoylamino)ethoxy)ethoxy]acetyl}-[Aib8,22,35,Lys37]GLP-1(7-37)amide
Nε37-(2-(2-(2-(17-carboxyheptadecanoylamino)ethoxy)ethoxy)acetyl)[Aib8,22,35,Lys37]GLP-1(7-37)amide
Nε37-(2-(2-(2-(19-carboxynonadecanoylamino)ethoxy)ethoxy)acetyl)[Aib8,22,35,Lys37]GLP-1(7-37)amide
[Aib8,22,35]GLP-1(7-37)Lys(({2-[2-(2-{2-[2-(2-{2-[2-(15-carboxypentadecanoylamino)ethoxy]ethoxy}acetylamino)ethoxy]ethoxy}acetyl amino)ethoxy]ethoxy}acetyl))amide
Nε37-[2-(2-{3-[2,5-dioxo-3-(15-carboxypentadecylsulfanyl)-pyrrolidin-1-yl]propionylamino}ethoxy)ethoxy)acetyl]-[D-Ala8,Lys37]-GLP-1-[7-37]amide
[Aib8,22,35Ala37]GLP-1(7-37)Lys((2-(2-(2-(11-(oxalylamino)undecanoylamino)ethoxy)ethoxy)acetyl-)))amide
[Aib8,22,35,Ala37]-GLP-1(7-37)Lys({2-[2-(2-{2-[2-(2-(15-carboxy-pentadecanoylamino)ethoxy]ethoxy}acetylamino)ethoxy]ethoxy}acetyl)amide
[Aib8,Arg26,34]GLP-1(7-37)Lys{2-(2-(2-(2-[2-(2-(17-carboxyheptanoylamino)ethoxy)ethoxy]acetylamino)ethoxy)ethoxy)acetyl)}-OH
[Gly8,Arg26,34]GLP1-(7-37)Lys{2-(2-(2-(2-[2-(2-(17-carboxyheptadecanoylamino)ethoxy)ethoxy]acetyl)ethoxy)ethoxy)acetyl)}-OH
[Ala8,Arg26,34]GLP-1(7-37)Lys((2-[2-((2-oxalylamino-3-carboxy-2-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl-acetylamino))ethoxy]ethoxyacetyl)amide
[Gly8,Arg26,34]GLP-1(7-37)Lys(2-(2-(19-(carboxy)nonadecanoylamino)ethoxy)ethoxy)acetyl)-OH
[Gly8,Arg26,34]GLP-1(7-37)Lys((2-(2-(17-(carboxy)heptadecanoylamino)ethoxy)ethoxy)acetyl))-OH
[Gly8,Arg26,34]GLP-1(7-37)Lys(2-(2-(2-(4-(19-(carboxy)nonadecanoylamino)-4-carboxybutyrylamino)ethoxy)ethoxy)acetyl)-OH
[Gly8,Arg26,34]GLP-1(7-37)Lys((2-(2-(2-(2-(2-(2-(2-(2-(2- (hexadecanoylamino)ethoxy)ethoxy)acetyl)ethoxy)ethoxy)acetylamino)ethoxy)ethoxy)acetyl)-OH
Nε26-(2-[2-(2-[2-(2-[2-(17-Carboxyheptadecanoylamino)ethoxy]ethoxy)acetylamino]ethoxy)ethoxy]acetyl)[Arg34]GLP-1-(7-37)-OH
Nε26-[2-(2-[2-(2-[2-(2-[4-(17-Carboxyheptadecanoylamino)-4(S)-carboxybutyrylamino]ethoxy)ethoxy]acetylamino)ethoxy]ethoxy)acetyl][Arg34]GLP-1-(7-37)-OH
and
[Gly8,Glu22,23,30,Arg18,26,34]GLP1(7-37)Lys(2-(2-(2-(2-(2-(2-(17- carboxyheptadecanoylamino)ethoxy)ethoxy)acetylamino)ethoxy))ethoxy)acetyl)-NH2

15 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/750,095Filed 25 Jun 2015
Priority: DK PA 2003 0136719 Sep 2003
Published: 21 Apr 2016
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07K 14/605
Hormones: glucagons
A61K 38/26
Hormones: glucagons
A61K 47/54
The non-active ingredient being a modifying agent: the modifying agent being an organic compound
A61K 47/542
The modifying agent being an organic compound: carboxylic acids, e.g. a fatty acid or an amino acid

Family

Application60/505,739Us provisional application · filed 25 Sep 2003
Application60/526,847Us provisional application · filed 4 Dec 2003
Application10/572,348Continuation · filed 18 Dec 2006
Application12/774,131Continuation · filed 5 May 2010
Application13/427,791Continuation · filed 22 Mar 2012
Application13/903,662Continuation · filed 28 May 2013
Application14/750,095Continuation
US 2007/0203058 A1Published application
US 2010/0305032 A1Published application
US 2013/0053315 A1Published application
US 2013/0244931 A1Published application
US 2016/0108102 A1This patent

From the US filing history. Foreign family members aren’t listed.

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A compound which has the formula (I):

A-W-B-Y-therapeutic polypeptide (I)
wherein:
the therapeutic polypeptide is a GLP-1 peptide comprising the amino acid sequence of formula (V):
Xaa7-Xaa8-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Xaa18-Tyr-Leu-Glu-Xaa22-Xaa23-Ala-Ala-Xaa26-Glu-Phe-Ile-Xaa30-Trp-Leu-Val-Xaa34-Xaa35-Xaa36-Xaa37-Xaa38 Formula (V) (SEQ ID No:
3)
wherein
Xaa7 is L-histidine or desamino-histidine;
Xaa8 is Ala, Gly or Aib;
Xaa18 is Ser or Arg;
Xaa22 is Gly, Glu or Aib;
Xaa23 is Gln or Glu;
Xaa26 is Lys or Arg;
Xaa30 is Ala or Glu;
Xaa34 is Lys or Arg;
Xaa35 is Gly or Aib;
Xaa36 is Arg or Lys;
Xaa37 is Gly, Ala or Lys;
Xaa38 is Lys, amide or is absent;
A is an albumin binding residue selected from the group consisting of:
where the chiral carbon atom is either R or S,
where the chiral carbon atom is either R or S,
where the two chiral carbon atoms independently are either R or S,
where the two chiral carbon atoms independently are either R or S,
B is —(CH2)l—O—[(CH2)n—O]m—(CH2)p—[C(O)NH—(CH2)l—O—[(CH2)n—O]m—(CH2)p]q—,
where l, m, n, and p independently are 1-5, and q is 0-5,
Y is a chemical group linking B and the therapeutic polypeptide, selected from the group consisting of —C(O)NH—, —NHC(O)—, —C(O)NHCH2—, —CH2NHC(O)—, —OC(O)NH—, —NHC(O)O—, —C(O)NHCH2—, CH2NHC(O)—, —C(O)CH2—, —CH2C(O)—, —C(O)CH═CH—, —CH═CHC(O)—, —(CH2)s—, —C(O)—, —C(O)O—, —OC(O)—, —NHC(O)— and —C(O)NH—, wherein s is 0 or 1, and
W is a chemical group linking A and B, selected from the group consisting of —C(O)NH—, —NHC(O)—, —C(O)NHCH2—, —CH2NHC(O)—, —OC(O)NH—, —NHC(O)O—, —C(O)CH2—, —CH2C(O)—, —C(O)CH═CH—, —CH═CHC(O)—, —(CH2)s—, —C(O)—, —C(O)O—, —OC(O)—, —NHC(O)— and —C(O)NH—, wherein s is 0 or 1;
and said GLP-1 peptide is attached to A-W-B-Y via the amino acid residue in positions 26, 37 or 38 in SEQ ID NO:3;
or a pharmaceutically acceptable salt or prodrug thereof.

26 more elements

Facts

Application

14/750,095Filed 25 Jun 2015

Priority

DK PA 2003 0136719 Sep 2003

Published

21 Apr 2016

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07K 14/605
Hormones: glucagons
A61K 38/26
Hormones: glucagons
A61K 47/54
The non-active ingredient being a modifying agent: the modifying agent being an organic compound
A61K 47/542
The modifying agent being an organic compound: carboxylic acids, e.g. a fatty acid or an amino acid

Family

Application60/505,739Us provisional application · filed 25 Sep 2003

Application60/526,847Us provisional application · filed 4 Dec 2003

Application10/572,348Continuation · filed 18 Dec 2006

Application12/774,131Continuation · filed 5 May 2010

Application13/427,791Continuation · filed 22 Mar 2012

Application13/903,662Continuation · filed 28 May 2013

Application14/750,095Continuation

US 2007/0203058 A1Published application

US 2010/0305032 A1Published application

US 2013/0053315 A1Published application

US 2013/0244931 A1Published application

US 2016/0108102 A1This patent

From the US filing history. Foreign family members aren’t listed.