Novo Nordisk A/s

Birgit Wieczorek

Lars Linderoth

Kristian Sass-Oerum

Kilian Waldemar Conde Frieboes

Patrick William Garibay

Thomas Kruse

Jacob Kofoed

Tina Moeller Tagmose

Jane Spetzler

Birgitte Schjellerup Wulff

Soeren Oestergaard

Birgitte Andersen

Jens Kaalby Thomsen

Joergen Olsen

Jesper F Lau

Janos Tibor Kodra

Henning Thoegersen

Carsten Jessen

Yi Wang

Per Sauerberg

Xiang Gao

Hongtao Guan

Tina Møller Tagmose

Kristian Tage Hansen

Peter Kresten Nielsen

Lars Fogh Iversen

Jianhe Chen

Sebastian Beck Joergensen

Henning Thøgersen

János Tibor Kodra

Per Noergaard

Xujia Zhang

Kristian Sass-Ørum

Alice Ravn Madsen

Rita Slaaby

Bírgítte Andersen

Kristian Sass Bak-Jensen

Salka Elboel Rasmussen

Jørgen Olsen

Henning THØGERSEN

Jishu Wang

Jorgen Olsen

Kristian Sass-Orum

Søren ØStergaard

Salka Elbøl Rasmussen

Helle WÖLDIKE

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 compounds derived from the EGF(A) domain of LDL-R, in particular compounds comprising a peptide analogue of the wild-type EGF(A) (LDL-R(293-332)) sequence and at least one substituent comprising at least one fatty acid group. The invention also relates to a pharmaceutical composition thereof and use a medicament. The novel EGF(A) compounds of the invention are useful as treatment e.g. in the field of cholesterol lowering, dyslipidaemia and cardiovascular disease.

EGF(A) analogues with fatty acid substituents

The invention relates to PYY compounds having the amino acid in the position corresponding to position 35 of hPYY(1-36) substituted with beta-homoarginine and derivatives thereof with a modifying group attached to the position corresponding to position 7 of hPYY(1-36). The compounds of the invention are selective Y2 receptor agonists. The invention also relates to pharmaceutical compositions comprising such PYY compounds and pharmaceutically acceptable excipients, as well as the medical use of the PYY compounds.

HPYY(1-36) having a beta-homoarginine substitution at position 35

The invention relates to MIC-1 compounds. More specifically it relates to compounds comprising a MIC-1 polypeptide with an N-terminal amino acid extension and a protractor wherein the amino acid extension comprises 3 to 36 amino acid residues and where the MIC-1 polypeptide and the N-terminal amino acid extension together have a calculated pI lower than 6.5. The compounds of the invention have MIC-1 activity. The invention also relates to pharmaceutical compositions comprising such compounds and pharmaceutically acceptable excipients, as well as the medical use of the compounds.

MIC-1 compounds and uses thereof

The invention relates to PYY compounds having the amino acid in the position corresponding to position 30 of hPYY(1-36) substituted with tryptophan and derivatives thereof with a modifying group attached to the position corresponding to position 7 of hPYY(1-36). The compounds of the invention are selective Y2 receptor agonists. The invention also relates to pharmaceutical compositions comprising such PYY compounds and pharmaceutically acceptable excipients, as well as the medical use of the PYY compounds.

Selective PYY compounds and uses thereof

The invention relates to a derivative of a FGF21 protein having a cysteine residue at a position corresponding to position 167, 169, 170, 171, 172, 173, 174, 175 and in particular position 180 or position 181 of mature human FGF21 and derivatives thereof having a side chain attached to this cysteine. The FGF21 derivatives of the invention display high potency towards the FGF receptors. The invention also relates to pharmaceutical compositions comprising such FGF21 derivatives and pharmaceutically acceptable excipients, as well as the medical use of the FGF21 derivatives.

FGF21 derivatives and uses thereof

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 present invention relates to Fibroblast Growth Factor 21 (FGF21), more in particular to derivatives of FGF21 compounds having an albumin binder of the formula A-B-C-D-E- covalently attached. The invention also relates to novel FGF21 analogues, as well as to the pharmaceutical use of these FGF21 derivatives and analogues, in particular for the treatment of diabetes, dyslipidemia, obesity, cardiovascular diseases, metabolic syndrome, and/or Non Alcoholic Fatty Liver Disease (NAFLD). The derivatives of the invention are protracted, e.g. capable of maintaining a low blood glucose level for a longer period of time, capable of increasing the in vivo half-life of FGF21, and/or result in a lower clearance of FGF21. The derivatives of the invention are preferably furthermore of an improved oxidative stability.

FGF21 derivatives with albumin binder A-B-C-D-E- and their use

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.

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Koebenhavn N, Denmark

Birgit Wieczorek