WO2016034604A1 - Novel amylin and calcitonin receptor agonist - Google Patents

Novel amylin and calcitonin receptor agonist Download PDF

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Publication number
WO2016034604A1
WO2016034604A1 PCT/EP2015/069996 EP2015069996W WO2016034604A1 WO 2016034604 A1 WO2016034604 A1 WO 2016034604A1 EP 2015069996 W EP2015069996 W EP 2015069996W WO 2016034604 A1 WO2016034604 A1 WO 2016034604A1
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Prior art keywords
mimylin
peptide
preceding aspects
seq
sequence
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PCT/EP2015/069996
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English (en)
French (fr)
Inventor
Thomas Kruse
Lauge SCHÄFFER
Kirsten Dahl
Christian Poulsen
Kirsten Raun
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Novo Nordisk AS
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Novo Nordisk AS
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Priority to EP15766071.3A priority Critical patent/EP3189071B1/en
Priority to CN201580046850.8A priority patent/CN106687474A/zh
Priority to ES15766071T priority patent/ES2887370T3/es
Priority to JP2017512822A priority patent/JP6728141B2/ja
Publication of WO2016034604A1 publication Critical patent/WO2016034604A1/en
Priority to US15/151,093 priority patent/US9593149B2/en
Priority to US15/417,671 priority patent/US10174082B2/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention relates to peptides comprising an amino acid sequence SEQ ID NO : 1 (EASELSTAALGRLSAELHELATLPRTETGPESP). BACKGROUND
  • Type 2 diabetes is generally treated in the early phases with diet and exercise. As the condition progresses, various oral anti-diabetic agents are added. Novel hormone-based therapies for type 2 diabetes are now emerging resembling an endogenous mode of action, such as glucagon like peptide (GLP)-l and amylin analogues. These agents do not only improve glucose homeostasis but also very promisingly exert beneficial effects on body weight.
  • GLP glucagon like peptide
  • amylin In obese individuals, fasting amylin concentrations are elevated in conjunction with hyperinsulinemia and in patients with type 2 diabetes, amylin, like insulin, is relatively deficient depending on the severity of ⁇ - cell secretory failure.
  • Amylin receptor agonists are useful in reducing food intake and treating obesity.
  • Human amylin is a 37 amino acid long polypeptide which has physico- chemical properties that make its use as a drug troublesome. In particular, it has a tendency for fibrillogenesis, i.e. the formation of fibrils, in vitro and/or ex vivo and becomes ineffective due to precipitation.
  • Pramlintide is a drug product marketed by Amylin Pharmaceuticals as Symlin® and a human amylin analogue and receptor agonist used in the treatment of diabetes as an add-on to insulin.
  • Pramlintide is chemically unstable at neutral pH and it is therefore provided in an acidic solution.
  • the calcitonin receptor is found in many tissues throughout the body and it is believed to be involved in regulation of bone metabolism. Salmon calcitonin is currently sold under the tradename Miacalcic®. The product is used against hypercalcaemia, osteoporosis (including post-menopausal osteoporosis and glucocorticoid-related osteoporosis), ostitis deformans (Pagets disease) and is administered once daily either by injection or nasally.
  • the calcitonin is bound to specific receptors in the membrane of the skeleton, the kidneys and in the central nervous system (CNS). Calcitonin is chemically unstable at neutral pH and it is therefore provided in an acidic solution.
  • Polypeptides with activity at both the amylin and calcitonin receptor and the amylin receptor may be advantageous; however increased half-life of amylin and calcitonin receptor agonists would highly increase the usability and convenience for the use as a medicament in treating the above mentioned diseases.
  • a further drawback of the currently known pool of calcitonin and amylin peptides is that they are only chemically stable in solution when handled in a narrow acidic pH range, which makes them bothersome to handle under circumstances were a broader range of pH is desired.
  • polypeptides which are amylin and/or calcitonin receptor agonists with more flexible solubility profiles would increase the usability in medicinal products.
  • the invention relates to peptides comprising an amino acid sequence SEQ ID NO : 1 (EASELSTAALGRLSAELHELATLPRTETGPESP), analogues and derivatives thereof and pharmaceutical compositions comprising SEQ ID NO : 1, analogues or derivatives thereof.
  • this invention relates to derivatives, pharmaceutical formulations, co- formulations and co-treatments of such mimylin peptides or derivatives in combination with GLP-1 compounds and the use thereof as medicaments in the treatment of diabetes, overweight, obesity or neuropathic pain.
  • the present invention relates to a mimylin peptide comprising a sequence having at least 66% sequence identity to SEQ ID NO : 1.
  • a mimylin peptide according to the present invention comprises up to 11 amino acid modifications relative to SEQ ID NO: 1.
  • a mimylin peptide according to the present invention comprises up to 11 amino acid modifications in one or more of the positions 1, 2, 3, 4, 5, 6, 8, 9, 10, 12, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 27, 28, 30, 31, 32 relative to SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • the present invention relates to a mimylin peptide comprising a sequence having at least 66% sequence identity to SEQ ID NO : 1 and c- terminal amide group.
  • the present invention relates to a mimylin peptide comprising a sequence having at least 66% sequence identity to SEQ ID NO : 1 and no disulfide bridge. In some embodiments the present invention relates to a mimylin peptide comprising a sequence having at least 66% sequence identity to SEQ ID NO: 1 and comprises no cysteins in certain positions, preferably no cysteins in position 2 and/or 8, wherein the amino acid numbering corresponds to SEQ ID NO : 1. In some embodiments the mimylin peptides of the present invention have less than 60% sequence identity to known amylin and calcitonin receptor agonists.
  • mimylin peptides are agonists to the amylin and calcitonin receptors and show a favourable solubility profile throughout the complete pH scale, especially at neutral pH and above, i.e. from about pH 6.0 and above, preferably from about pH 7.0 and above.
  • the peptides of the present invention are very stable peptides and thus potentially very useful for use in medicaments.
  • mimylin has a low Immunogenicity Risk Score (IRS). It was surprisingly found that the mimylin compounds of this invention are able to be combined with GLP-1 compounds in co-formulations wherein both remain stable.
  • the mimylin compounds of this invention are able to be combined with GLP-1 compounds in formulations at pH between about 7.0 and 8.5 wherein both remain stable. It was further surprisingly found that co-administration in DIO rats of a compound according to this invention and liraglutatide enhanced the weightloss achieved by the liraglutide treatment alone, surpassing an add-on effect. Further studies are ongoing. It was surprisingly found that compounds of this invention do not affect the PK profile of liraglutide, and liraglutide does surprisingly not affect the PK profile of compounds of this invention when administered as co-formulations to LYD pigs. It was surprisingly found that Ex. compound 2 or 46 of this invention do not affect the PK profile of liraglutide and liraglutide does surprisingly not affect the PK profile of Ex. compound 2 or 46 of this invention when administered as co-formulations to LYD pigs.
  • the invention may also solve further problems that will be apparent from the disclosure of the exemplary embodiments and aspects.
  • the invention relates to mimylin peptides comprising an amino acid sequence which is a mimylin analogue (EASELSTAALGRLSAELHELATLPRTETGPESP) or analogues or derivatives thereof which all show agonist effects on the amylin receptor. Further this invention relates to derivatives, pharmaceutical compositions comprising of such mimylin peptides and the use of such mimylin peptides as medicaments.
  • mimylin peptides comprising an amino acid sequence which is a mimylin analogue (EASELSTAALGRLSAELHELATLPRTETGPESP) or analogues or derivatives thereof which all show agonist effects on the amylin receptor.
  • derivatives, pharmaceutical compositions comprising of such mimylin peptides and the use of such mimylin peptides as medicaments.
  • the mimylin peptides of the present invention are agonists to the calcitonin receptor. In some embodiments the mimylin peptide of the present invention agonises the human amylin and human calcitonin receptors and shows solubility throughout the complete pH scale, preferably neutral pH and above.
  • a mimylin peptide according to the present invention comprises up to 11 amino acid modifications relative to SEQ ID NO : 1. In some embodiments a mimylin peptide according to the present invention comprises up to 11 amino acid modifications relative to SEQ ID NO : 1, wherein in one or more of the positions 1, 2, 3, 4, 5, 6, 8, 9, 10, 12, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 27, 28, 30, 31, 32, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • the present invention relates to a mimylin peptide comprising a sequence having at least 66% sequence identity to SEQ ID NO: 1 and a c- terminal amide group.
  • the present invention relates to a mimylin peptide comprising a sequence having at least 66% sequence identity to SEQ ID NO : 1 and no disulfide bridge. In some embodiments the present invention relates to a mimylin peptide comprising a sequence having at least 66% sequence identity to SEQ ID NO: 1 and comprises no cysteins, preferably in position 2 and/or 8, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about 50pM or less. In some embodiments a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about 20pM or less. In some embodiments a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about 19pM or less.
  • a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about 18pM or less. In some embodiments a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about 17pM or less. In some embodiments a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about 16pM or less.
  • a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about 15pM or less. In some embodiments a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about 14pM or less. In some embodiments a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about 13pM or less.
  • a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about 12pM or less. In some embodiments a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about l lpM or less. In some embodiments a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about ⁇ or less. In some embodiments a mimylin peptide according to the present invention has an EC 50 in a human amylin receptor functional assay (tested as disclosed in Assay lib) of about 5pM or less.
  • a mimylin peptide according to the present invention is a peptide comprising SEQ ID NO : 1A;
  • X(-l) is E or no amino acid
  • XI is selected from the group consisting of E or A or no amino acid
  • X2 is selected from the group consisting of L, A or P,
  • X3 is selected from the group consisting of S or P
  • X4 is selected from the group consisting of E, P, K, Q or G
  • X5 is selected from the group consisting of L, V, or I,
  • X6 is S, T or H
  • X8 is selected from the group consisting of L or A,
  • X9 is selected from the group consisting of A, V, I, S or T,
  • X10 is selected from the group consisting of L, A, I, H or V,
  • X12 is selected from the group consisting of R, H or K,
  • X14 is selected from the group consisting of S, T or E,
  • X15 is selected from the group consisting of A, Q, E, e or T,
  • X16 is selected from the group consisting of R, E, K or Q,
  • X17 is selected from the group consisting of L or I,
  • X18 is selected from the group consisting of H or A,
  • X19 is selected from the group consisting of E, R or K,
  • X20 is selected from the group consisting of L, I or V
  • X21 is selected from the group consisting of A, Q, S, E or T
  • X23 is selected from the group consisting of T, Y or L,
  • X25 is selected from the group consisting of R, P, H or K,
  • X27 is selected from the group consisting of E, Q, G or K,
  • X28 is selected from the group consisting of T or P,
  • X30 is selected from the group consisting of P, S or T,
  • X31 is selected from the group consisting of E, Q, G, A, P or K,
  • X32 is selected from the group consisting of T, S, H, P or A and
  • X33 is P, Y, H, F, L, S, G or A and
  • X34 is G or no amino acid
  • a mimylin peptide according to the present invention is a peptide comprising SEQ ID NO : IB;
  • XI is selected from the group consisting of E or A or no amino acid
  • X2 is selected from the group consisting of L, A or P,
  • X3 is selected from the group consisting of S or P
  • X4 is selected from the group consisting of E, P, K, Q or G
  • X5 is selected from the group consisting of L, V, or I,
  • X6 is S, T or H
  • X8 is selected from the group consisting of L or A,
  • X9 is selected from the group consisting of A, V, I, S or T,
  • X10 is selected from the group consisting of L, A, I, H or V,
  • X12 is selected from the group consisting of R, H or K,
  • X14 is selected from the group consisting of S, T or E,
  • X15 is selected from the group consisting of A, Q, E, e or T,
  • X16 is selected from the group consisting of R, E, K or Q,
  • X17 is selected from the group consisting of L or I
  • X18 is selected from the group consisting of H or A
  • X19 is selected from the group consisting of E, R or K,
  • X20 is selected from the group consisting of L, I or V,
  • X21 is selected from the group consisting of A, Q, S, E or T,
  • X23 is selected from the group consisting of T, Y or L,
  • X25 is selected from the group consisting of R, P, H or K,
  • X27 is selected from the group consisting of E, Q, G or K,
  • X28 is selected from the group consisting of T or P,
  • X30 is selected from the group consisting of P, S or T,
  • X31 is selected from the group consisting of E, Q, G, A, P or
  • X32 is selected from the group consisting of T, S, H, P or A,
  • X33 is P, Y, H, F, L, S, G or A
  • X34 is G or no amino acid
  • X35 is T or no amino acid
  • X36 is Y or no amino acid.
  • a mimylin peptide according to the present invention is a peptide comprising SEQ ID NO : 1C;
  • XI is selected from the group consisting of E or A or no amino acid
  • X2 is selected from the group consisting of L, A or P,
  • X3 is selected from the group consisting of S or P
  • X4 is selected from the group consisting of E, P, K, Q or G
  • X5 is selected from the group consisting of L, V, or I,
  • X6 is S, T or H
  • X8 is selected from the group consisting of L or A,
  • X9 is selected from the group consisting of A, V, I, S or T,
  • X10 is selected from the group consisting of L, A, I, H or V,
  • X12 is selected from the group consisting of R, H or K,
  • X14 is selected from the group consisting of S, T or E,
  • X15 is selected from the group consisting of A, Q, E, e or T
  • X16 is selected from the group consisting of R, E, K or Q
  • X17 is selected from the group consisting of L or I,
  • X18 is selected from the group consisting of H or A,
  • X19 is selected from the group consisting of E, R or K,
  • X20 is selected from the group consisting of L, I or V,
  • X21 is selected from the group consisting of A, Q, S, E or T,
  • X23 is selected from the group consisting of T, Y or L,
  • X25 is selected from the group consisting of R, P, H or K,
  • X27 is selected from the group consisting of E, Q, G or K,
  • X28 is selected from the group consisting of T or P,
  • X30 is selected from the group consisting of P, S or T,
  • X31 is selected from the group consisting of E, Q, G, A, P or K,
  • X32 is selected from the group consisting of T, S, H, P or A and
  • X33 is P, Y, H, F, L, S, G or A.
  • a mimylin peptide according to this invention can be a peptide SEQ ID NO : 1A, IB or 1C, wherein an additional amino acid is added to the N-terminal.
  • a mimylin peptide according to this invention can be a peptide SEQ ID NO : 1A, IB or 1C, wherein an additional amino acid is added to the N-terminal, wherein said additional amino acid is E.
  • a mimylin peptide according to this invention can be described according to any one of the SEQ ID NO : 1A, IB or 1C, wherein said mimylin peptide is derivatised with a side chain in the alpha amino group of the N-terminal amino acid, wherein said side chain comprises a protracting moiety as defined in the present invention and optionally comprises a linker.
  • the mimylin peptide has a substituent on one amino acid residue, which amino acid residue is either the amino acid residue in the N-terminal residue or the amino acid residue is a Lysine, wherein said lysine can be at any of the positions 1-33 according to the numbering of SEQ ID NO : 1.
  • the mimylin peptide has a substituent on the N-terminal amino acid residue bound via the a(alpha)-amino group of the N-terminal amino acid residue.
  • the N-terminal amino acid residue is Lysine and the mimylin peptide has a substituent on the N-terminal amino acid residue bound via the £(epsilon)-amino group of the lysine amino residue.
  • the mimylin peptide is extended by addition of a Lysine residue at the N-terminal and the mimylin peptide has a substituent on the N-terminal amino acid residue bound via the ⁇ -amino group of the lysine amino residue.
  • the mimylin peptide is extended by addition of a Glutamic acid residue at the N-terminal and the mimylin peptide has a substituent on the N-terminal amino acid residue bound via the a-amino group of the lysine amino residue.
  • the mimylin peptide is extended by addition of an amino acid residue at the N-terminal and the mimylin peptide has a substituent on the N-terminal amino acid residue bound via the a-amino group of the N-terminal amino acid residue.
  • an amylin derivative is produced by derivatising a mimylin peptide with a side chain attached in the N-terminal of said mimylin peptide. In some embodiments an amylin derivative is produced by derivatising a mimylin peptide with a side chain attached at a K (Lys) within the sequence of said mimylin peptide. In some embodiments such attachment at a K (Lys) can be in position 4, 12, 16, 23, 18, 27 or 34.
  • SEQ ID NO : 1A, IB or 1C are analogues of SEQ ID NO : 1.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is up to 11 amino acids different from SEQ ID NO : 1.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein the sequence is up to 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1, preferably 1, 2 or 3, more preferably 4, 3 or 5 amino acids different from SEQ ID NO : 1.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is up to 5 amino acids different from SEQ ID NO : 1. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is up to 4 amino acids different from SEQ ID NO : 1. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is up to 3 amino acids different from SEQ ID NO : 1.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is up to 2 amino acids different from SEQ ID NO: 1. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is 1 amino acid different from SEQ ID NO : 1. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is at least 22 amino acids identical with SEQ ID NO : 1.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is at least 23 amino acids identical with SEQ ID NO: 1. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein the sequence is at least 24 amino acids identical with SEQ ID NO: 1. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is at least 25 amino acids identical with SEQ ID NO : 1.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is at least 26 amino acids identical with SEQ ID NO : 1.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is at least 27 amino acids identical with SEQ ID NO: 1. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein the sequence is at least 28 amino acids identical with SEQ ID NO : 1.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is at least 29 amino acids identical with SEQ ID NO: l.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein the sequence is at least 30 amino acids identical with SEQ ID NO: 1.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is at least 31 amino acids identical with SEQ ID NO : 1.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein the sequence is at least 32 amino acids identical with SEQ ID NO : 1.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C and a c-terminal amide group.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein XI is E.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein XI is E and the mimylin peptide is derivatised with a side chain attached to the mimylin peptide at the N-terminal.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein XI is E and the mimylin peptide is derivatised with a side chain attached to the mimylin peptide at the N-terminal, wherein said side chain comprises a protracting moiety and a linker.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein XI is E and the mimylin peptide is derivatised with a side chain attached to the mimylin peptide at the N-terminal, wherein said side chain comprises a protracting moiety and no linker.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein XI is A. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein XI is A and the mimylin peptide is derivatised with a side chain attached to the mimylin peptide at the N-terminal.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein XI is A and the mimylin peptide is derivatised with a side chain attached to the mimylin peptide at the N-terminal, wherein said side chain comprises a protracting moiety and a linker.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein XI is any amino acid except E.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein XI is any amino acid except E and the mimylin peptide is derivatised with a side chain attached to the mimylin peptide at the N-terminal.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein XI is any amino acid except E and the mimylin peptide is derivatised with a side chain attached to the mimylin peptide at the N-terminal, wherein said side chain comprises a protracting moiety and a linker.
  • the side chain and/or the protracting moiety are lipophilic, and/or negatively charged at physiological pH (pH about 7.4).
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X2 is L. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X2 is A. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X2 is P. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X3 is S. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X3 is P.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X4 is L. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X4 is A.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X5 is L. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X5 is I. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X5 is V.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X7 is T.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X8 is L. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X8 is A.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X9 is A. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X9 is V. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X9 is I. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X9 is S.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X9 is T. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X9 is L.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X10 is L. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X10 is A. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X10 is V. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X10 is I.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X12 is R. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X12 is H . In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X12 is K.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X15 is A. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X15 is Q. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X15 is E.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X15 is e, wherein e is the d-isoform of Glutamic acid. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X15 is T.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X19 is E. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X19 is R. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X19 is K.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X20 is L. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X20 is I. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X20 is V.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X21 is A. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X21 is Q. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X21 is S. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X21 is S.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X21 is E. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X21 is T.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X23 is Y. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X23 is L.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X27 is E. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X27 is Q. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X27 is G. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X27 is K.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X30 is P. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X20 is S. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X30 is T.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X31 is E. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X31 is Q. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X31 is G. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X31 is A.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X31 is P. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X31 is K. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X32 is T. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X32 is S.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X32 is H . In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X32 is P. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X32 is A.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X33 is Y. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X33 is S. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X16 is H . In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, wherein X33 is F.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X16 is L. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X33 is S. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X33 is G. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X33 is A.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A or IB, wherein X34 is R. In some embodiments a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A or IB, wherein X34 is deleted.
  • the mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein one or all of X5, X10, X13, X17, X20 and X23 are L. In some embodiments the mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein at least four of X5, X10, X13, X17, X20 and X23 are L.
  • the mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein at least three of X5, X10, X13, X17, X20 and X23 are L.
  • the mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein X12 and/or X25 is R. In some embodiments the mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO : 1A, IB or 1C, wherein one or all of X5, X10, X13, X17, X20 and X23 are L and wherein X12 and/or X25 is R.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, which does not comprise any N .
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, which does not comprise any Q.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, which does not comprise any C.
  • a mimylin peptide according to the present invention comprises a sequence according to SEQ ID NO: 1A, IB or 1C, which does not comprise any disulfide bridges.
  • a mimylin derivative according to this invention is represented by the compounds listed in Table 1.
  • the compound names as used herein are listed in Table 1.
  • Table 2 indicates the amino acid modifications relative to SEQ ID NO : 1, also designated mimylin.
  • Table 2 indicates the modifications relative to mimylin in the mimylin peptides, i.e. the mimylin peptides, which are derivatised with a side chain to form the mimylin derivatives listed in Table 1.
  • Table 2 represents the mimylin analogues which have been derivatised, resulting in the corresponding mimylin derivative represented in Table 1.
  • EX. #8 in Table 1 or 3 respectively is a derivative of a mimylin analogue which has been modified with the amino acids as indicated in Table 2 or 4 as Ex. #8bb
  • a mimylin derivative comprising a mimylin peptide with up to 11 amino acid modifications relative to SEQ ID NO: 1 (mimylin) according to this invention is represented by the compounds listed in Table 3.
  • Table 2 and 4 respectively, represent the mimylin analogues which have been derivatised, resulting in the corresponding mimylin derivative represented in Table 1 or 3 respectively.
  • the compound in EX. #8 in Table 1 or 3 respectively is a derivative of a mimylin analogue which has been modified with the amino acids as indicated in Table 2 or 4 as Ex. #8bb.
  • a mimylin peptide with up to 11 amino acid modifications relative to SEQ ID NO : 1 (mimylin) according to this invention is represented by the compounds listed in Table 4.
  • the compound in Ex. #8 in Table 1 or 3 respectively is a derivative of a mimylin analogue which has been modified with the amino acids as indicated in Table 2 or 4 as Ex. #8bb.
  • mimylin derivatives of this invention can be presented by thei structure formula as presented in Table 5.
  • the invention relates to a method for weight management making use of a mimylin peptide or derivative a pharmaceutical formulation, co- formulation or co-treatment of any one of the non-limiting numbered aspects of this invention.
  • the invention relates to a method for reduction of appetite making use of a mimylin peptide or derivative a pharmaceutical formulation, co- formulation or co-treatment of any one of the non-limiting numbered aspects of this invention.
  • the invention relates to a method for reduction of food intake making use of a mimylin peptide or derivative a pharmaceutical formulation, co- formulation or co-treatment of any one of the non-limiting numbered aspects of this invention.
  • the invention relates to a method for treatment or prevention of obesity making use of a mimylin peptide or derivative a pharmaceutical formulation, co-formulation or co-treatment of any one of the non-limiting numbered aspects of this invention.
  • the invention relates to use of a mimylin peptide or derivative or a pharmaceutical formulation, co-formulation or co-treatment according to the non-limiting numbered aspects of this invention for treatment or prevention of obesity.
  • the subject suffering from obesity is human, such as an adult human or a paediatric human (including infants, children, and adolescents).
  • a human subject suffering from obesity may have a BMI of >30; this subject may also be referred to as obese.
  • the human subject suffering from obesity may have a BMI of >35 or a BMI in the range of >30 to ⁇ 40.
  • the obesity is severe obesity or morbid obesity, wherein the human subject may have a BMI of >40.
  • the invention relates to a method for treatment or prevention of overweight making use of a mimylin peptide or derivative a pharmaceutical formulation, co-formulation or co-treatment of any one of the non-limiting numbered aspects of this invention, optionally in the presence of at least one weight-related comorbidity.
  • the invention relates to use of the a mimylin peptide or derivative or a pharmaceutical formulations, co-formulation or co-treatment according to the non-limiting numbered aspects of this invention for treatment or prevention of overweight, optionally in the presence of at least one weight-related comorbidity.
  • the subject suffering from overweight is human, such as an adult human or a paediatric human (including infants, children, and adolescents).
  • a human subject suffering from overweight may have a BMI of >25, such as a BMI of >27.
  • a human subject suffering from overweight has a BMI in the range of 25 to ⁇ 30 or in the range of 27 to ⁇ 30.
  • the weight-related comorbidity is selected from the group consisting of hypertension, diabetes (such as type 2 diabetes), dyslipidaemia, high cholesterol, and obstructive sleep apnoea.
  • the invention relates to a method for reduction of body weight making use of a mimylin peptide or derivative a pharmaceutical formulation, co- formulation or co-treatment of any one of the non-limiting numbered aspects of this invention.
  • the invention relates to use of a mimylin peptide or derivative or a pharmaceutival formulations according to the non-limiting numbered aspects of this invention for reduction of body weight.
  • a human to be subjected to reduction of body weight according to the present invention may have a BMI of >25, such as a BMI of >27 or a BMI of >30.
  • the human to be subjected to reduction of body weight according to the present invention may have a BMI of >35 or a BMI of >40.
  • the term "reduction of body weight" may include treatment or prevention of obesity and/or overweight.
  • a mimylin peptide comprising a sequence with at least 54% sequence identity to SEQ ID NO : 1;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has at least about 72% sequence identity to SEQ ID NO : l;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has at least about 75% sequence identity to SEQ ID NO : l;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has at least about 78% sequence identity to SEQ ID NO : l;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has at least about 81% sequence identity to SEQ ID NO : l;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has at least about 84% sequence identity to SEQ ID NO : l;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has at least about 87% sequence identity to SEQ ID NO : l;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has at least about 90% sequence identity to SEQ ID NO : l;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has at least about 93% sequence identity to SEQ ID NO : l;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has at least about 96% sequence identity to SEQ ID NO : l;
  • mimylin peptide according to any one of the preceding aspects, having ⁇ about 70% sequence identity with salmon calcitonin;
  • mimylin peptide according to any one of the preceding aspects, having having ⁇ about 70% sequence identity with eel calcitonin;
  • mimylin peptide according to any one of the preceding aspects, having ⁇ about 66% sequence identity with salmon calcitonin;
  • mimylin peptide according to any one of the preceding aspects, having having ⁇ about 66% sequence identity with eel calcitonin;
  • the mimylin peptide according to any one of the preceding aspects having having ⁇ about 60% sequence identity with eel calcitonin; 22. The mimylin peptide according to any one of the preceding aspects, having having ⁇ about 60% sequence identity with any calcitonin variant;
  • mimylin peptide according to any one of the preceding aspects wherein 1 amino acid has been modified by means of substitution or deletion of one amino acid relative to SEQ ID NO : 1 ;
  • a mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises an amide group in its c-terminal;
  • a mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises a c-terminal acid;
  • a mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide does not comprise a c-terminal acid;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide does not comprise any disulfide bridge;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide does not comprise a disulfide bridge between the amino acids in positions 2 and 8, wherein the amino acid numbering corresponds to SEQ ID NO : 1
  • said mimylin peptide does not comprise cystein residues in one or both positions 2 and 8, wherein the amino acid numbering corresponds to SEQ ID NO : 1 ;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises up to one cystein residue;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide does not comprise any cysteins;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises L in one, more or all of the positions selected from 5, 10, 13, 17, 20 and 23, wherein the amino acid numbering corresponds to SEQ ID NO : 1;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises L in positions 5, 10 and 13, wherein the amino acid numbering corresponds to SEQ ID NO : 1;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises L in positions 5, 10, 13 and 17, wherein the amino acid numbering corresponds to SEQ ID NO : 1;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises L in positions 5, 10, 13, 17 and 20, wherein the amino acid numbering corresponds to SEQ ID NO: 1;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises L in positions 10, 13, 17 and 20, wherein the amino acid numbering corresponds to SEQ ID NO : 1; 48.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises L in positions 5, 10, 13, 17, 20 and 23, wherein the amino acid numbering corresponds to SEQ ID NO: 1;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises R in one or more of the positions 12 or 25, wherein the amino acid numbering corresponds to SEQ ID NO : 1;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises R in both positions 12 and 25, wherein the amino acid numbering corresponds to SEQ ID NO : 1;
  • mimylin peptide according to any one of the preceding aspects 35-41 further comprising R in one or both of the positions 12 or 25, wherein the amino acid numbering corresponds to SEQ ID NO : 1;
  • the mimylin peptide according to any one of the aspects 35-41 further comprising R in both positions 12 and 25, wherein the amino acid numbering corresponds to SEQ ID NO : 1;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises a P, Y, H, F, L, S, G or A in position 33, wherein the amino acid numbering corresponds to SEQ ID NO: 1;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises a P, Y, H, F, L, S or A in position 33, wherein the amino acid numbering corresponds to SEQ ID NO: 1 ;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises a P, Y, H or F in position 33, wherein the amino acid numbering corresponds to SEQ ID NO: 1 ;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises a P, Y or F in position 33, wherein the amino acid numbering corresponds to SEQ ID NO: 1 ;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises a P or Y in position 33, wherein the amino acid numbering corresponds to SEQ ID NO : 1;
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises a P or in position 33, wherein the amino acid numbering corresponds to SEQ ID NO : 1; 60.
  • mimylin peptide according to any one of the preceding aspects 1-65, wherein said mimylin peptide comprises at least one of the following amino acids or modifications relative to SEQ ID NO : 1 :
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises at least one of the following amino acids or modifications relative to SEQ ID NO : 1 :
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises at least one of the following amino acids or modifications relative to SEQ ID NO : 1 :
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises any one of the following amino acids or modifications relative to SEQ ID NO : 1 :
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises any one of the following amino acids or modifications relative to SEQ ID NO : 1 :
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises any one of the following amino acids or modifications relative to SEQ ID NO : 1 : a. E or no amino acid in position -1,
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, most preferably 1 2, 3, 4 or 5 of the following amino acids or modifications relative to SEQ ID NO: 1 :
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, most preferably 1, 2, 3, 4 or 5 of the following amino acids or modifications relative to SEQ ID NO: 1 :
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, most preferably 1, 2, 3, 4 or 5 of the following amino acids or modifications relative to SEQ ID NO: 1 :
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, most preferably 1 2, 3, 4 or 5 of the following amino acids or modifications relative to SEQ
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, most preferably 1 2, 3, 4 or 5 of the following amino acids or modifications relative to SEQ
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, most preferably 1 2, 3, 4 or 5 of the following amino acids or modifications relative to SEQ
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, most preferably 1 2, 3, 4 or 5 of the following amino acids or modifications relative to SEQ ID NO: 1 :
  • mimylin peptide according to any one of the preceding aspects 1-67, wherein said mimylin peptide comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, most preferably 1, 2, 3, 4 or 5 of the following amino acids or modifications relative to SEQ ID NO: 1 :
  • mimylin peptide according to any one of the preceding aspects 65, wherein said mimylin peptide comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, most preferably 1, 2, 3, 4 or 5 of the following amino acids or modifications relative to SEQ ID NO: 1 : a. E or no amino acid in position -1,
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises T in position 7, G in position 11, L in position 13, T in position 22, P in position 24, T in position 26 and G in position 29 , wherein the amino acid numbering corresponds to SEQ ID NO: 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises T in position 7, G in position 11, L in position 13, T in position 22, P in position 24, T in position 26 and G in position 29 , wherein position 33 remains P or is modifired to Y, F, H, S, G or A, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • the mimylin peptide according to any one of the preceding aspects wherein said mimylin peptide comprises T in position 7, G in position 11, L in position 13, T in position 22, P in position 24, T in position 26 and G in position 29 , wherein position 33 remains P, Y or F, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • said mimylin peptide according to any one of the preceding wherein said mimylin peptide comprises T in position 7, G in position 11, L in position 13, T in position 22, P in position 24, T in position 26 and G in position 29, wherein the amino acid numbering corresponds to SEQ ID NO: 1.
  • mimylin peptide according to any one of the any one of the preceding, wherein said mimylin peptide comprises T in position 7, G in position 11, L in position 13, T in position 22, P in position 24, T in position 26 and G in position 29 , wherein position 33 remains P, Y, F, H, S, G or A, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the any one of the preceding, wherein said mimylin peptide comprises T in position 7, G in position 11, L in position 13, T in position 22, P in position 24, T in position 26 and G in position 29 , wherein position 33 remains P, Y or F, wherein the amino acid numbering corresponds to SEQ ID NO: 1.
  • amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in up to 11, up to 10, up to 9, up to 8, up to 7, up to 6, preferably up to 5, up to 4, up to 3, up to 2 or 1 of the positions selected from the group consisting of: 1, 2, 3, 4, 5, 6, 8, 9, 10, 12, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 27, 28, 30, 31, 32 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1, 2, 4, 8, 9, 15, 21, 23, 25, 30, 31, 32, 33 of SEQ ID NO: 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1 , 2, 4, 8, 9, 15, 21, 23, 25, 30, 31, 32, 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1, wherein said one or more modifications are selected from the list consisting of:
  • position 9 can be modified to V or T,
  • position 23 can be modified to Y
  • position 31 can be modified to G or Q,
  • position 33 can be modified to Y, H, F, L, S, G or A, preferably Y.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1, 4, 9, 15, 21, 23, 25, 27, 30, 31, 32, 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified up to 10 of the positions 1, 4, 9, 15, 21, 23, 25, 27, 30, 31, 32, 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the 1, 4, 9, 15, 21, 23, 25, 27, 30, 31, 32, 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1, wherein said one or more modifications are selected from the list consisting of:
  • position 4 can be modified to G or Q,
  • position 9 can be modified to V or T,
  • position 23 can be modified to Y
  • position 25 can be modified to H or P,
  • position 31 can be modified to G, Q or A,
  • position 33 can be modified to Y.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1, 4, 15, 21, 23, 30, 32, 32 or 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO: 1
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified up to 9 of the positions 1, 4, 15, 21, 23, 30, 32, 32 and 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in 9 of the positions 1, 4, 15, 21, 23, 30, 32, 32 and 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the 1, 4, 15, 21, 23, 30, 32, 32 or 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO:
  • position 15 can be modified to Q
  • position 23 can be modified to Y
  • position 31 can be modified to G, Q or K,
  • position 33 can be modified to Y.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1, 4, 6, 9, 14, 15, 21, 23, 30, 31, 32 or 33 of SEQ ID NO: 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified up to 8 of the positions 1, 4, 6, 9, 14, 15, 21, 23,
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in 8 of the positions 1, 4, 6, 9, 14, 15, 21, 23, 30,
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1, 4, 6, 9, 14, 15,
  • position 14 can be modified to T or S,
  • position 21 can be modified to Q, T or E,
  • position 23 can be modified to Y
  • position 30 can be modified to S or T,
  • position 33 can be modified to Y. 107.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified up to 7 of the positions 1, 4, 5, 6, 9, 10, 12, 20, 21, 23, 25, 30, 31, 32 and 33 of SEQ ID NO: 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in 7 of the positions 1, 4, 5, 6, 9, 10, 12, 20, 21, 23, 25, 30, 31, 32 and 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1, 4, 5, 6, 9, 10, 12, 20, 21, 23, 25, 30, 31, 21 or 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1, wherein said one or more modifications are selected from the list consisting of:
  • position 9 can be modified to V, T or S,
  • position 23 can be modified to Y
  • position 33 can be modified to Y.
  • the mimylin peptide according to aspect 107 does not comprise K.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1, 5, 6, 9, 10, 21, 23, 30, 31, 32 or 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified up to 6 of the positions 1, 5, 6, 9, 10, 21, 23, 30, 31, 32 and 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in 6 of the positions 1, 5, 6, 9, 10, 21, 23, 30, 31, 32 and 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the 1, 5, 6, 9, 10, 21, 23, 30, 31, 32 or 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO: 1, wherein said one or more modifications are selected from the list consisting of:
  • position 9 can be modified to V, T or S,
  • position 23 can be modified to Y
  • position 30 can be modified to S or T,
  • position 33 can be modified to Y.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions -1, 1, 4, 5, 6, 9, 12, 16, 21, 23, 25, 30, 31, 32, 33 or 34 of SEQ ID NO: 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified up to 5 of the positions -1, 1, 4, 5, 6, 9, 12, 16, 21, 23, 25, 30, 31, 32, 33 and 34 of SEQ ID NO: 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in 5 of the positions -1, 1, 4, 5, 6, 9, 12, 16, 21, 23, 25, 30, 31, 32, 33 and 34 of SEQ ID NO: 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • position -1 can be modified to E or is absent
  • position 1 can be modified to A or deleted
  • position 23 can be modified to Y
  • position 33 can be modified to Y and
  • position 34 can be modified to K.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1, 4, 5, 9, 12, 15, 16, 19, 20, 23, 25, 27, 30, 31, 32 or 33 of SEQ ID NO: 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified up to 4 of the positions 1, 4, 5, 9, 12, 15, 16, 19, 20, 23, 25, 27, 30, 31, 32 and 33 of SEQ ID NO: 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in 4 of the positions 1, 4, 5, 9, 12, 15, 16, 19, 20, 23, 25, 27, 30, 31, 32 and 33 of SEQ ID NO: 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1, 4, 5, 9, 10 12, 15, 16, 19, 20, 23, 25, 27, 30, 31, 32 or 33 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1, wherein said one or more modifications are selected from the list consisting of:
  • position 1 can be modified to A or deleted
  • position 4 can be modified to K or Q
  • position 9 can be modified to V or I,
  • position 15 can be modified to E or e
  • position 23 can be modified to Y
  • position 32 can be modified to T or P, and
  • position 33 can be modified Y, H, F, L, S, A or G, preferably Y.
  • the mimylin peptide according to any one of the preceding aspects wherein said mimylin peptide has been modified up to 3 of the positions 1, 3, 4, 5, 9, 10, 12, 20, 23, 25, 30 and 31, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • the mimylin peptide according to any one of the preceding aspects wherein said mimylin peptide has been modified in 3 of the positions 1, 3, 4, 5, 9, 10, 12, 20, 23, 25, 30 and 31, wherein the amino acid numbering corresponds to SEQ ID NO: 1.
  • the mimylin peptide according to any one of the preceding aspects wherein said mimylin peptide has been modified in one or more of the positions 1, 3, 4, 5, 9, 10,
  • position 4 can be modified to P
  • position 5 can be modified to I
  • position 9 can be modified to V or I,
  • position 23 can be modified to Y
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1, 2,3, 4, 5, 9, 10, 18, 25, 28, 30 or 31 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified up to 2 of the positions 1, 2,3, 4, 5, 9, 10, 18 25,
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in 2 of the positions 1, 2,3, 4, 5, 9, 10, 18 25, 28, 30 and 31 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1, 2,3, 4, 5, 9, 10, 18, 25, 28, 30 and 31 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1, wherein said one or more modifications are selected from the list consisting of:
  • position 5 can be modified to I or V
  • position 9 can be modified to V or I,
  • position 28 can be modified with P
  • position 30 can be modified to S
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one of the positions 1, 5, 6, 8, 9, 17, 20, 23 or 32 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO :
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide has been modified in one or more of the positions 1, 5, 6, 8, 9, 17, 20, 23 and 32 of SEQ ID NO : 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1, wherein said one or more modifications are selected from the list consisting of:
  • position 9 can be modified to L, V or I,
  • position 23 can be modified to Y
  • position 32 can be modified to H.
  • mimylin peptide according to any one of the preceding aspects, wherein said mimylin peptide comprises an E in position 1, wherein the amino acid numbering corresponds to SEQ ID NO : 1.
  • the mimylin peptide according to any one of the preceding aspects comprising the sequence EASELSTAALGRLSAELHELATLPRTETGPESP (SEQ ID NO : 1).
  • the mimylin peptide according to any one of the preceding aspects comprising the sequence EASELSTAALGRLSAELHELATLPRTETGSGSP (SEQ ID NO : 19).
  • the mimylin peptide according to any one of the preceding aspects comprising the sequence selected from the group consisting of the compounds listed in Table 2.
  • the mimylin peptide according to any one of the preceding aspects comprising the sequence selected from the group consisting of the compounds listed in Table 4.
  • the mimylin peptide according to any one of the preceding aspects having the sequence EASELSTAALGRLSAELHELATLPRTETGPESP (SEQ ID NO: 1).
  • the mimylin peptide according to any one of the preceding aspects having the sequence EASELSTAALGRLSAELHELATLPRTETGSGSP (SEQ ID NO: 19).
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. # lbb to EX. #7bb.
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. #8bb to EX. #20bb.
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. #21bb to EX. #33bb
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. #34bb to EX. #51bb
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. #52bb to EX. #55bb and EX. #68bb to EX. #72bb.
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. #56bb to EX. #67bb and EX. #72bb to EX. #78bb and EX. # 107bb.
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. #79bb to EX. #90bb.
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. #91bb to EX. #97bb.
  • the mimylin peptide according to any one of the preceding aspects comprising a sequence selected from the group consisting of EX. #98bb to EX. # 102bb. 157. The mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. # 103bb to EX. # 106bb.
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. #8bb to EX. #20bb.
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. # 107bb to EX. # 114bb.
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. # 115bb to EX. # 124bb.
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. # 125bb to EX. # 127bb.
  • the mimylin peptide according to any one of the preceding aspects, comprising a sequence selected from the group consisting of EX. # 128bb to EX. # 133bb.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: 5I]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: 9I]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: 17I]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: 18A]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: 8L]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: 5H]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [23Y]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [5V, 9V]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [51, 9I]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [9V, 10I]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [9L, 10A]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [2P, 9V]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [3P, 9V]mimylin.
  • mimylin peptide according to any one of the preceding aspects, comprising sequence: [4P, 9V]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [9V, 25P]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [9V, 28P]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [23Y, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31P]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [3P, 4P, 9V]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [9V, 12K, 25K]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects, comprising sequence: [desl, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects, comprising sequence: [desl, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 4K, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 16K, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 23Y, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [ 1A, 23Y, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects, comprising sequence: [desl, 23Y, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G, 33Y]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G, 33H]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G, 33F]mimylin.
  • the mimylin peptide according to any one of the preceding aspects, comprising sequence: [desl, 30S, 31G, 33L]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G, 33S]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G, 33G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G, 33A]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 15E, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 15e, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 19K, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 27K, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 30S, 31G, 32P]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 9V, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 4Q, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 4G, 23Y, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 23Y, 30S, 31G, 33Y]mimylin.
  • the mimylin peptide according to any one of the preceding aspects, comprising sequence: [desl, 23Y, 30S, 31G, 32A]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 21S, 23Y, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [-1E, 1A, 23Y, 30S, 31G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 12H, 25H, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 6T, 9V, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 5V, 9V, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 23Y, 30S, 31G, 33Y]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 23Y, 30S, 31G, 34G]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 9T, 21S, 23Y, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 12H, 25H, 30T, 31G, 32T]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 6T, 9V, 30S, 31G, 32T]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 6T, 9V, 30T, 31G, 32T]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 5V, 9V, 10V, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 21S, 23Y, 30S, 31G, 33Y]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 4G, 9V, 23Y, 30S, 31G, 32T]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 9T, 21S, 23Y, 30S, 31G, 33Y]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 9S, 21S, 23Y, 30S, 31G, 33Y]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 12K, 23Y, 25K, 30S, 31G, 33Y]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 5V, 9V, 10V, 20V, 30S, 31G]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: 4G, 15Q, 21Q, 23Y, 30S, 31G, 32T, 33Y]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 4G, 9V, 23Y, 30S, 31G, 32T, 33Y]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 6T, 9V, 14T, 21E, 30T, 31G, 32T]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 6T, 9V, 14E, 21T, 30T, 31G, 32T]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: desl, 4G, 15Q, 21Q, 23Y, 30S, 31K, 32T, 33Y]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 4G, 15Q, 21Q, 23Y, 30S, 31G, 32T, 33Y]mimylin.
  • the mimylin peptide according to any one of the preceding aspects, comprising sequence: [desl, 4G, 15T, 21E, 23Y, 30S, 31G, 32T, 33Y]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 4G, 15E, 21Q, 23Y, 30S, 31G, 32T, 33Y]mimylin.
  • mimylin peptide according to any one of the preceding aspects, comprising sequence: [desl, 9V, 15Q, 21Q, 23Y, 30S, 31G, 32T, 33Y]mimylin.
  • mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 4G, 15Q, 21Q, 23Y, 25H, 30S, 31G, 32T, 33Y]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 4G, 9V, 15Q, 21Q, 23Y, 30S, 31G, 32T, 33Y]mimylin.
  • the mimylin peptide according to any one of the preceding aspects, comprising sequence: [desl, 4G, 9V, 15Q, 21Q, 23Y, 30S, 31Q, 32T, 33Y]mimylin.
  • the mimylin peptide according to any one of the preceding aspects 1-162, comprising sequence: [desl, 4G, 9V, 15Q, 21Q, 23Y, 30S, 31A, 32T, 33Y]mimylin.

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ES15766071T ES2887370T3 (es) 2014-09-04 2015-09-02 Nuevo agonista del receptor de amilina y calcitonina
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US15/151,093 US9593149B2 (en) 2014-09-04 2016-05-10 Amylin and calcitonin receptor agonist
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US10071140B2 (en) 2016-09-09 2018-09-11 Zealand Pharma A/S Amylin analogues
US10766939B2 (en) 2015-03-18 2020-09-08 Zealand Pharma A/S Amylin analogues
WO2022133187A1 (en) 2020-12-18 2022-06-23 Eli Lilly And Company Dual amylin and calcitonin receptor agonists and uses thereof
WO2022248419A2 (en) 2021-05-22 2022-12-01 Adocia Compositions comprising short-acting hormones for treating or preventing obesity and pumps comprising said composition
EP4129324A1 (en) 2021-08-02 2023-02-08 Adocia Compositions comprising at least an amylin receptor agonist and a glp-1 receptor agonist
EP4144362A1 (en) 2021-09-06 2023-03-08 Adocia Compositions comprising short-acting hormones for treating or preventing obesity and pumps comprising said composition
WO2024050289A1 (en) 2022-08-29 2024-03-07 Eli Lilly And Company Compositions for oral delivery
US12018059B2 (en) 2018-10-11 2024-06-25 I2O Therapeutics, Inc. Human amylin analog polypeptides and methods of use
US12054528B2 (en) 2020-12-18 2024-08-06 Novo Nordisk A/S Co-agonists of the GLP-1 and amylin receptors
US12116388B2 (en) 2022-12-22 2024-10-15 Novo Nordisk A/S Amylin receptor agonists
US12233112B2 (en) 2021-11-10 2025-02-25 I20 Therapeutics, Inc. Compositions comprising pharmaceutically acceptable salts of amylin analogs and uses thereof
WO2025114501A1 (en) 2023-11-30 2025-06-05 Novo Nordisk A/S Tri-agonists of the glp-1, gip, and amylin receptors
WO2025240893A1 (en) 2024-05-17 2025-11-20 Eli Lilly And Company 4-phenyl-1h-pyrazolo[3,4-b]pyridine-5-carboxamide derivatives as amylin and/or calcitonin receptor agonists for the treatment of type 2 diabetes, obesity or overweight

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CN116621944A (zh) * 2022-02-10 2023-08-22 成都奥达生物科技有限公司 一种长效肝炎病毒进入抑制剂

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US10766939B2 (en) 2015-03-18 2020-09-08 Zealand Pharma A/S Amylin analogues
US10071140B2 (en) 2016-09-09 2018-09-11 Zealand Pharma A/S Amylin analogues
US11382956B2 (en) 2016-09-09 2022-07-12 Zealand Pharma A/S Amylin analogues
US12083164B2 (en) 2016-09-09 2024-09-10 Zealand Pharma A/S Amylin analogues
WO2018083335A1 (en) 2016-11-07 2018-05-11 Novo Nordisk A/S Dchbs-active esters of peg compounds and their use
US12018059B2 (en) 2018-10-11 2024-06-25 I2O Therapeutics, Inc. Human amylin analog polypeptides and methods of use
WO2022133187A1 (en) 2020-12-18 2022-06-23 Eli Lilly And Company Dual amylin and calcitonin receptor agonists and uses thereof
US11541123B2 (en) 2020-12-18 2023-01-03 Eli Lilly And Company Dual amylin and calcitonin receptor agonists and uses thereof
US12054528B2 (en) 2020-12-18 2024-08-06 Novo Nordisk A/S Co-agonists of the GLP-1 and amylin receptors
WO2022248419A2 (en) 2021-05-22 2022-12-01 Adocia Compositions comprising short-acting hormones for treating or preventing obesity and pumps comprising said composition
EP4129324A1 (en) 2021-08-02 2023-02-08 Adocia Compositions comprising at least an amylin receptor agonist and a glp-1 receptor agonist
EP4144362A1 (en) 2021-09-06 2023-03-08 Adocia Compositions comprising short-acting hormones for treating or preventing obesity and pumps comprising said composition
US12233112B2 (en) 2021-11-10 2025-02-25 I20 Therapeutics, Inc. Compositions comprising pharmaceutically acceptable salts of amylin analogs and uses thereof
US12233110B2 (en) 2021-11-10 2025-02-25 I20 Therapeutics, Inc. Compositions comprising pharmaceutically acceptable salts of glucagon-like peptide-1 analogs and uses thereof
US12233111B2 (en) 2021-11-10 2025-02-25 I2O Therapeutics, Inc. Compositions comprising pharmaceutically acceptable salts of glucagon-like peptide-1 analogs and uses thereof
US12337029B2 (en) 2021-11-10 2025-06-24 I2O Therapeutics, Inc. Compositions comprising pharmaceutically acceptable salts of amylin analogs and uses thereof
US12350320B2 (en) * 2021-11-10 2025-07-08 I2O Therapeutics, Inc. Compositions comprising pharmaceutically acceptable salts of glucagon-like peptide-1 analogs and pharmaceutically acceptable salts of amylin analogs, and uses thereof
WO2024050289A1 (en) 2022-08-29 2024-03-07 Eli Lilly And Company Compositions for oral delivery
US12116388B2 (en) 2022-12-22 2024-10-15 Novo Nordisk A/S Amylin receptor agonists
WO2025114501A1 (en) 2023-11-30 2025-06-05 Novo Nordisk A/S Tri-agonists of the glp-1, gip, and amylin receptors
WO2025240893A1 (en) 2024-05-17 2025-11-20 Eli Lilly And Company 4-phenyl-1h-pyrazolo[3,4-b]pyridine-5-carboxamide derivatives as amylin and/or calcitonin receptor agonists for the treatment of type 2 diabetes, obesity or overweight

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CN106687474A (zh) 2017-05-17
US10174082B2 (en) 2019-01-08
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US9593149B2 (en) 2017-03-14
JP2022130522A (ja) 2022-09-06
US20170145059A1 (en) 2017-05-25
JP7095027B2 (ja) 2022-07-04
TW201625671A (zh) 2016-07-16
AR101742A1 (es) 2017-01-11
JP2017530108A (ja) 2017-10-12
EP3189071A1 (en) 2017-07-12
JP6728141B2 (ja) 2020-07-22
JP2020169197A (ja) 2020-10-15
US20160272683A1 (en) 2016-09-22
ES2887370T3 (es) 2021-12-22

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