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NZ739250B2 - Glucagon derivative and a composition comprising a long acting conjugate of the same - Google Patents
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NZ739250B2 - Glucagon derivative and a composition comprising a long acting conjugate of the same - Google Patents

Glucagon derivative and a composition comprising a long acting conjugate of the same Download PDF

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Publication number
NZ739250B2
NZ739250B2 NZ739250A NZ73925016A NZ739250B2 NZ 739250 B2 NZ739250 B2 NZ 739250B2 NZ 739250 A NZ739250 A NZ 739250A NZ 73925016 A NZ73925016 A NZ 73925016A NZ 739250 B2 NZ739250 B2 NZ 739250B2
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NZ
New Zealand
Prior art keywords
peptide
group
derivative
region
domain
Prior art date
Application number
NZ739250A
Other versions
NZ739250A (en
Inventor
In Young Choi
Sung Youb Jung
Jung Kuk Kim
Young Jin Park
Original Assignee
Hanmi Pharm Co Ltd
Filing date
Publication date
Application filed by Hanmi Pharm Co Ltd filed Critical Hanmi Pharm Co Ltd
Priority claimed from PCT/KR2016/006984 external-priority patent/WO2017003191A1/en
Publication of NZ739250A publication Critical patent/NZ739250A/en
Publication of NZ739250B2 publication Critical patent/NZ739250B2/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/2264—Obesity-gene products, e.g. leptin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/2278—Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/26—Glucagons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/28—Insulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • 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
    • 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
    • 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
    • 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
    • C07K14/605—Glucagons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The present invention relates to the glucagon derivatives or long-acting conjugates of the glucagon derivatives, and the combination of i) the glucagon derivatives or conjugates thereof and ii) agents having therapeutic activity for metabolic syndromes, and uses thereof in treating metabolic syndromes.

Claims (39)

Claims
1. Use of a pharmaceutical composition in the preparation of a medicament for treating or preventing metabolic syndromes, wherein the composition comprises i) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 20 to 24, 27, 29, 33, 37, 38 and 44 and ii) at least one compound or material having a therapeutic activity for metabolic syndrome, wherein the nd or material having a eutic activity for metabolic syndrome is selected from the group ting of an insulinotropic peptide, a peroxisome erator-activated receptor alpha ) agonist, a peroxisome proliferator-activated receptor delta (PPARd) agonist, a Farnesoid X receptor (FXR) agonist, an acetyl-CoA carboxylase inhibitor, a peptide YY, xenin, glicentin, obestatin, secretin, nesfatin, insulin, and a glucose-dependent insulinotropic peptide (GIP).
2. The use of claim 1, wherein the e has an isoelectric point (pI) value different to that of native on (6.8).
3. The use of claim 1, wherein, in the peptide, the amino acids at position 16 and 20 form a ring.
4. The use of claim 1, wherein the peptide is a glucagon derivative capable of activating a glucagon receptor.
5. The use of claim 1, wherein the peptide ses an amino acid sequence selected from the group consisting of SEQ ID NOS: 20, 22, 33, 37, and 38.
6. The use of claim 1, wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 37, 38 and 44.
7. The use of claim 1, wherein the insulinotropic peptide is selected from the group consisting of GLP-1, exendin-3, n-4, an agonist thereof, a derivative thereof, a fragment thereof, a variant thereof, and a combination thereof.
8. The use of claim 7, wherein the insulinotropic peptide is an insulinotropic e derivative, in which the N-terminal ine residue is substituted with one selected from the group consisting of desamino-histidyl, N-dimethyl-histidyl, ß-hydroxy imidazopropionyl, 4- imidazoacetyl, and ß-carboxy imidazopropionyl.
9. The use of claim 7, wherein the insulinotropic peptide is selected from the group consisting of a native n-4; an exendin-4 derivative in which the inal amine group of exendin-4 is deleted; an exendin-4 derivative in which the N-terminal amine group of exendin-4 is substituted with a hydroxyl group; an n-4 derivative in which the N- terminal amine group of exendin-4 is modified with a yl group; an exendin-4 derivative in which the a-carbon of the 1st amino acid of exendin-4, histidine, is deleted; an exendin-4 derivative in which the 12th amino acid of exendin-4, lysine, is tuted with serine, and an exendin-4 derivative in which the 12th amino acid of exendin-4, lysine, is substituted with arginine.
10. The use of claim 1, wherein: the peptide is in the form of a long-acting conjugate, to which a biocompatible material capable of increasing in vivo half-life of the peptide is linked; and the insulinotropic peptide is in the form of a long-acting conjugate, to which a biocompatible material capable of increasing in vivo half-life of the insulinotropic peptide is linked.
11. The use of claim 10, wherein the biocompatible material is selected from the group consisting of polyethylene , fatty acid, cholesterol, albumin and a fragment thereof, an albumin-binding material, a r of repeating units of a particular amino acid sequence, an antibody, an antibody fragment, an FcRn-binding material, in vivo tive tissue or a derivative thereof, a nucleotide, fibronectin, transferrin, a saccharide, and a polymer.
12. The use of claim 10, n the peptide and the insulinotropic peptide are respectively linked to a biocompatible material by a linker selected from the group consisting of polyethylene , polypropylene glycol, an ethylene glycol-propylene glycol copolymer, polyoxyethylated polyol, polyvinyl alcohol, a polysaccharide, dextran, polyvinyl ethyl ether, a biodegradable polymer including polylactic acid (PLA) or polylactic-glycolic acid , lipid polymer, chitin, hyaluronic acid, fatty acid, a polymer, a low molecular weight compound, a nucleotide, and a combination thereof.
13. The use of claim 10, wherein the patible material is an FcRn-binding material, and the peptide and the insulinotropic e are respectively linked to a biocompatible material by a peptide linker or a non-peptide linker selected from the group consisting of polyethylene glycol, polypropylene glycol, an ethylene -propylene glycol copolymer, polyoxyethylated polyol, polyvinyl alcohol, a polysaccharide, dextran, polyvinyl ethyl ether, a biodegradable polymer ing polylactic acid (PLA) or ctic-glycolic acid (PLGA), lipid polymer, , hyaluronic acid, and a combination thereof.
14. The use of claim 13, wherein the FcRn-binding material is a ptide comprising an immunoglobulin Fc region.
15. The use of claim 14, wherein the immunoglobulin Fc region is sylated.
16. The use of claim 14, wherein the immunoglobulin Fc region is selected from the group consisting of: (a) a CH1 , a CH2 domain, a CH3 domain, and a CH4 domain; (b) a CH1 domain and a CH2 domain; (c) a CH1 domain and a CH3 ; (d) a CH2 domain and a CH3 domain; (e) a combination n one or at least two domains among a CH1 domain, a CH2 domain, a CH3 domain, and a CH4 domain, and an immunoglobulin hinge region or a part of the hinge region; and (f) a dimer between each domain of the heavy chain constant region and the light chain constant region.
17. The use of claim 14, n the polypeptide comprising the immunoglobulin Fc region is in the form of a dimer.
18. The use of claim 14, wherein the immunoglobulin Fc region is a native Fc derivative in which the region capable of forming a disulfide bond is deleted, a native Fc derivative in which a part of the amino acid(s) in the N-terminus is removed, a native Fc derivative in which a methionine is added to the N-terminus, a native Fc derivative in which a ment-binding site is deleted, or a native Fc derivative in which an antibody dependent cell mediated cytotoxicity (ADCC) site is deleted.
19. The use of claim 14, wherein the immunoglobulin Fc region is derived from an immunoglobulin ed from the group consisting of IgG, IgA, IgD, IgE, and IgM.
20. The use of claim 19, wherein the immunoglobulin Fc region is an IgG4 Fc region.
21. The use of claim 14, wherein the globulin Fc region is an aglycosylated Fc region derived from human IgG4.
22. The use of claim 13, wherein the non-peptide linker is linked to the cysteine residue of the peptide.
23. The use of claim 13, wherein both ends of the ptide linker are respectively linked to an amine group or a thiol group of the peptide, or an insulinotropic e, and a biocompatible material.
24. The use of any one of claims 1 to 23, wherein the metabolic syndrome is selected from the group consisting of impaired glucose tolerance, hypercholesterolemia, dyslipidemia, obesity, diabetes, hypertension, nonalcoholic steatohepatitis (NASH), sclerosis caused by dyslipidemia, sclerosis, arteriosclerosis, coronary heart disease, and stroke.
25. An isolated peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 37, 38 and 44.
26. The peptide of claim 25, wherein, in the peptide, the amino acids at positions 16 and 20 form a ring.
27. The peptide of claim 25, wherein the C-terminus of the peptide is amidated.
28. The peptide of claim 25, wherein the peptide is a glucagon derivative capable of activating a glucagon receptor.
29. The peptide of claim 25, wherein the peptide comprises an amino acid sequence of SEQ ID NO: 37, or 38.
30. An isolated polynucleotide encoding the isolated peptide of any one of claims 25 to
31. A vector comprising the isolated polynucleotide of claim 30.
32. An isolated conjugate, wherein the isolated peptide of claim 25 and a biocompatible material capable of increasing in vivo half-life are linked.
33. The isolated conjugate of claim 32, wherein the biocompatible material is selected from the group consisting of polyethylene glycol, fatty acid, cholesterol, n and a fragment thereof, an albumin-binding material, a polymer of repeating units of a particular amino acid sequence, an antibody, an antibody nt, an FcRn-binding material, in vivo connective tissue or a derivative thereof, a tide, fibronectin, transferrin, a ride, and a polymer.
34. The isolated conjugate of claim 32, wherein the peptide is linked to a biocompatible material by a linker selected from the group consisting of polyethylene glycol, polypropylene glycol, an ethylene glycol-propylene glycol copolymer, polyoxyethylated , polyvinyl alcohol, a polysaccharide, dextran, polyvinyl ethyl ether, a biodegradable polymer including polylactic acid (PLA) or polylactic-glycolic acid (PLGA), lipid polymer, chitin, hyaluronic acid, fatty acid, a polymer, a low lar weight compound, a nucleotide, and a combination thereof.
35. The isolated conjugate of claim 32, wherein the biocompatible material is an FcRn-binding material, and the isolated peptide is linked to a biocompatible material by a peptide linker or a nonpeptide linker selected from the group consisting of polyethylene glycol, polypropylene , an ethylene glycol-propylene glycol copolymer, yethylated polyol, polyvinyl alcohol, a polysaccharide, dextran, polyvinyl ethyl ether, a biodegradable polymer including polylactic acid (PLA) or polylactic-glycolic acid (PLGA), lipid polymer, , onic acid, and a combination f.
36. The isolated conjugate of claim 35, wherein the FcRn-binding material is a ptide comprising an immunoglobulin Fc region.
37. A composition sing the isolated peptide of claim 25 or the isolated conjugate of claim 32.
38. The composition of claim 37, which is a ceutical composition for treating or preventing hypoglycemia or metabolic syndrome.
39. The composition according to claim 37, further comprising at least one compound or material having a therapeutic activity for metabolic syndrome. None set by CAR MigrationNone set by CAR Unmarked set by CAR None set by CAR MigrationNone set by CAR Unmarked set by CAR None set by CAR MigrationNone set by CAR Unmarked set by CAR [
NZ739250A 2016-06-29 Glucagon derivative and a composition comprising a long acting conjugate of the same NZ739250B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR20150093265 2015-06-30
PCT/KR2016/006984 WO2017003191A1 (en) 2015-06-30 2016-06-29 Glucagon derivative and a composition comprising a long acting conjugate of the same

Publications (2)

Publication Number Publication Date
NZ739250A NZ739250A (en) 2024-02-23
NZ739250B2 true NZ739250B2 (en) 2024-05-24

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