NZ750267B2 - Glucagon derivative, conjugate thereof, composition comprising same and therapeutic use thereof - Google Patents

Glucagon derivative, conjugate thereof, composition comprising same and therapeutic use thereof

Info

Publication number
NZ750267B2
NZ750267B2 NZ750267A NZ75026717A NZ750267B2 NZ 750267 B2 NZ750267 B2 NZ 750267B2 NZ 750267 A NZ750267 A NZ 750267A NZ 75026717 A NZ75026717 A NZ 75026717A NZ 750267 B2 NZ750267 B2 NZ 750267B2
Authority
NZ
New Zealand
Prior art keywords
domain
peptide
region
immunoglobulin
group
Prior art date
Application number
NZ750267A
Other versions
NZ750267A (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/KR2017/006922 external-priority patent/WO2018004283A2/en
Publication of NZ750267A publication Critical patent/NZ750267A/en
Publication of NZ750267B2 publication Critical patent/NZ750267B2/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
    • 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
    • A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
    • A61K38/1774—Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
    • 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
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • 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
    • 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
    • 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
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin

Abstract

The present invention relates to a glucagon derivative, a conjugate thereof, a composition comprising the same and a use thereof and, more particularly, to a therapeutic use for the metabolic syndrome, hypoglycemia and concomitant hyperinsulinemia.

Claims (25)

CLAIMS ]
1.[Claim 1] Use of the isolated peptide comprising the amino acid sequence of General Formula 2 in the manufacture of a medicament for treating congenital hyperinsulinism: General Formula 2 Y-Aib-QGTF-X7-SD-X10-S-X12-Y-L-X15-X16-X17-R-A-X20-X21-F-V-X24-W- L-M-N-T-X30 (General Formula 2, SEQ ID NO: 46) wherein, in General Formula 2, X7 is threonine (T), valine (V), or cysteine (C); X10 is tyrosine (Y) or cysteine (C); X12 is lysine (K) or cysteine (C); X15 is aspartic acid (D) or cysteine (C); X16 is glutamic acid (E) or serine (S); X17 is lysine (K) or arginine (R); X20 is glutamine (Q) or lysine (K); X21 is aspartic acid (D) or glutamic acid (E); X24 is valine (V) or glutamine (Q); and X30 is cysteine (C) or is absent, with the proviso that the amino acid sequence of of the isolated peptide does not comprise SEQ ID NO: 1 or SEQ ID NO:12.
2.[Claim 2] The use of claim 1, wherein the peptide has an isoelectric point (pI) value different from that of native glucagon (6.8).
3.[Claim 3] The use of claim 1, wherein, in General Formula 2, X16 is glutamic acid, X20 is lysine, and the side chains of X16 and X20 form a lactam ring.
4.[Claim 4] The use of claim 1, wherein the C-terminus of the peptide is amidated.
5.[Claim 5] The use of claim 1, wherein the C-terminus of the peptide is unmodified.
6.[Claim 6] The use of claim 1, wherein the peptide is a native glucagon derivative capable of activating a glucagon receptor. MARKED-UP COPY
7.[Claim 7] The use of claim 1, wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 13, 15, and 36 to 44.
8.[Claim 8] The use of claim 1, wherein the peptide comprises the amino acid sequence of SEQ ID NO: 37.
9.[Claim 9] The use according to any one of claims 1 to 8, wherein the peptide is in the form of a long-acting conjugate, in which a biocompatible material moiety is linked to the peptide moiety.
10.[Claim 10] The use of claim 9, wherein the biocompatible material moiety is selected from the group consisting of a polymer, fatty acid, cholesterol, albumin and a fragment thereof, an albumin-binding material, a polymer of repeating units of a particular amino acid sequence, an antibody, an antibody fragment, an FcRn-binding material, a nucleotide, fibronectin, transferrin, a saccharide, heparin, and elastin.
11.[Claim 11] The use of claim 10, wherein the polymer is selected from the group consisting of a polyethylene glycol, a polypropylene glycol, an ethylene glycol-propylene glycol copolymer, polyoxyethylated polyol, polyvinyl alcohol, a polysaccharide, dextran, polyvinyl ethyl ether, a biodegradable polymer, a lipid polymer, chitin, hyaluronic acid, an oligonucleotide, and a combination thereof.
12.[Claim 12] The use of claim 10, wherein the FcRn-binding material is a polypeptide comprising an immunoglobulin Fc region.
13.[Claim 13] The use of claim 9, wherein the peptide moiety and the biocompatible material moiety are linked with each other through a linker.
14.[Claim 14] The use of claim 13, wherein the linker is selected from the group consisting of a peptide, fatty acid, a saccharide, a polymer, a low molecular weight compound, a nucleotide, and a combination thereof.
15.[Claim 15] The use of claim 14, wherein the polymer is selected from the group consisting of a polyethylene glycol, a polypropylene glycol, an ethylene glycol-propylene glycol MARKED-UP COPY copolymer, polyoxyethylated polyol, polyvinyl alcohol, a polysaccharide, dextran, polyvinyl ethyl ether, a biodegradable polymer, a lipid polymer, chitin, hyaluronic acid, an oligonucleotide, and a combination thereof.
16.[Claim 16] The use of claim 13, wherein the linker is a polyethylene glycol.
17.[Claim 17] The use of claim 12, wherein the immunoglobulin Fc region is aglycosylated.
18.[Claim 18] The use of claim 12, wherein the immunoglobulin Fc region is selected from the group consisting of: (a) a CH1 domain, 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 domain; (d) a CH2 domain and a CH3 domain; (e) a combination between 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.
19.[Claim 19] The use of claim 12, wherein the polypeptide comprising an immunoglobulin Fc region is in the form of a dimer.
20.[Claim 20] The use of claim 12, 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 residue is added to the N-terminus, a native Fc derivative in which a complement-binding site is deleted, or a native Fc derivative in which an antibody dependent cell mediated cytotoxicity (ADCC) site is deleted.
21.[Claim 21] The use of claim 12, wherein the immunoglobulin Fc region is derived from an immunoglobulin selected from the group consisting of IgG, IgA, IgD, IgE, and IgM.
22.[Claim 22] The use of claim 21, wherein the immunoglobulin Fc region is an IgG4 Fc region. MARKED-UP COPY
23.[Claim 23] The use of claim 12, wherein the immunoglobulin Fc region is an aglycosylated Fc region derived from human IgG4.
24.[Claim 24] The use of claim 13, wherein the linker is linked to a cysteine residue of a peptide comprising the amino acid sequence of General Formula 2.
25.[Claim 25] The use of claim 13, wherein the linker is respectively linked to the peptide moiety and the biocompatible material moiety through covalent bonds, which are respectively formed by reacting one end of the linker with an amine group or thiol group of the biocompatible material moiety and reacting the other end of the linker with an amine group or thiol group of the peptide moiety including the amino acid sequence of General Formula 2.
NZ750267A 2017-06-29 Glucagon derivative, conjugate thereof, composition comprising same and therapeutic use thereof NZ750267B2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20160081995 2016-06-29
KR20160182982 2016-12-29
KR20170069217 2017-06-02
PCT/KR2017/006922 WO2018004283A2 (en) 2016-06-29 2017-06-29 Glucagon derivative, conjugate thereof, composition comprising same and therapeutic use thereof

Publications (2)

Publication Number Publication Date
NZ750267A NZ750267A (en) 2023-12-22
NZ750267B2 true NZ750267B2 (en) 2024-03-26

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