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NZ727871B2 - Composition for treating diabetes mellitus comprising insulin and a glp-1/glucagon dual agonist - Google Patents
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NZ727871B2 - Composition for treating diabetes mellitus comprising insulin and a glp-1/glucagon dual agonist - Google Patents

Composition for treating diabetes mellitus comprising insulin and a glp-1/glucagon dual agonist Download PDF

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Publication number
NZ727871B2
NZ727871B2 NZ727871A NZ72787115A NZ727871B2 NZ 727871 B2 NZ727871 B2 NZ 727871B2 NZ 727871 A NZ727871 A NZ 727871A NZ 72787115 A NZ72787115 A NZ 72787115A NZ 727871 B2 NZ727871 B2 NZ 727871B2
Authority
NZ
New Zealand
Prior art keywords
amino acid
glp
insulin
region
conjugate
Prior art date
Application number
NZ727871A
Other versions
NZ727871A (en
Inventor
In Young Choi
Sang Youn Hwang
Sung Youb Jung
Seung Su Kim
Se Chang Kwon
Original Assignee
Hanmi Pharm Co Ltd
Filing date
Publication date
Application filed by Hanmi Pharm Co Ltd filed Critical Hanmi Pharm Co Ltd
Priority to NZ764889A priority Critical patent/NZ764889B2/en
Priority claimed from PCT/KR2015/005455 external-priority patent/WO2015183054A1/en
Publication of NZ727871A publication Critical patent/NZ727871A/en
Publication of NZ727871B2 publication Critical patent/NZ727871B2/en

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    • 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
    • A61K38/26—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
    • 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
    • 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
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • 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
    • A61P3/08—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
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • 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
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/53—Hinge
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • 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 a composition for preventing or treating diabetes mellitus comprising insulin and a GLP-1/glucagon dual agonist, and a method for preventing or treating diabetes mellitus. More specifically, the present composition can inhibit the weight gain and reduce the danger of hypoglycemia due to the administration of insulin, lower the administration dose and greatly improve the compliance of drugs through a combined administration of a long-acting insulin conjugate and a long-acting GLP-1/glucagon dual agonist conjugate. In addition, the long-acting insulin conjugate and the long-acting GLP-1/glucagon dual agonist conjugate according to the present invention can improve the in vivo sustainability and stability because an insulin and a GLP-1/glucagon dual agonist are linked to the immunoglobulin Fc region via a non-peptidyl linker.

Claims (1)

1.Claims ?Claim 1? A pharmaceutical composition for treating diabetes mellitus comprising a long-acting insulin conjugate and a long-acting GLP-1/glucagon dual agonist conjugate; wherein the long-acting insulin conjugate is a conjugate in which insulin is linked to an immunoglobulin Fc region via a non-peptidyl polymer; wherein the long-acting GLP-1/glucagon dual agonist conjugate is a conjugate in which GLP-1/glucagon dual agonist is linked to an immunoglobulin Fc region via a nonpeptidyl polymer; wherein the insulin is an insulin analog in which B chain (SEQ ID NO 38) or A chain (SEQ ID NO 37) of the insulin is modified by substituting an amino acid selected from the group consisting of amino acid at position 8 with alanine, amino acid at position 23 with alanine, amino acid at position 24 with alanine, and amino acid at position 25 with alanine of the chain B; amino acid at position 1 with alanine, amino acid at position 2 with alanine, amino acid at position 14 with glutamic acid or asparagine, and amino acid at position 19 with alanine of the chain A; and wherein the GLP-1/glucagon dual agonist comprises an amino acid sequence selected from the group consisting of amino acid sequences represented by SEQ ID NOs: 39 to 72, and simultaneously activates GLP-1 receptor and glucagon receptors. ?Claim 2? The composition according to claim 1, wherein the long-acting glucagon-like peptide1 (GLP-1)/glucagon dual agonist has the amino acid sequence of SEQ ID NO.40 and the amino acid at position 16 and 20 form a ring. ?Claim 3? The composition according to claim 1 or claim 2, wherein the non-peptidyl polymer is selected from the group consisting of polyethylene glycol, 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, and a combination thereof. ?Claim 4? The composition according to any one of claims 1 to 3, wherein the immunoglobulin Fc region is aglycosylated. ?Claim 5? The composition according to claim 4, wherein the immunoglobulin Fc region comprises one to four region(s) selected from the group consisting of CH1, CH2, CH3 and CH4 domains. ?Claim 6? The composition according to claim 5, wherein the immunoglobulin Fc region further comprises a hinge region. 32 ?Claim 7? The composition according to claim 6, wherein the immunoglobulin Fc region is an Fc region derived from IgG, IgA, IgD, IgE, or IgM. ?Claim 8? The composition according to claim 7, wherein each domain of the immunoglobulin Fc region is a hybrid of domains having a different origin selected from the group consisting of IgG, IgA, IgD, IgE, and IgM. ?Claim 9? The composition according to claim 8, wherein the immunoglobulin Fc region is a dimer or a multimer consisting of single-chain immunoglobulins consisting of domains having the same origin. ?Claim 10? The composition according to any one of claims 1 to 9, wherein the composition further comprises a pharmaceutically acceptable carrier. ?Claim 11? The composition according to claim 1, wherein the long-acting insulin is a conjugate in which an insulin analog comprising substitution of the 14th amino acid in the insulin Achain with a glutamic acid and an immunoglobulin Fc region are linked by a non-peptidyl polymer linker, and the long-acting GLP-1/glucagon dual agonist is a conjugate in which a GLP-1/glucagon dual agonist represented by SEQ ID NO: 40 and an immunoglobulin Fc region are linked by a non-peptidyl polymer linker. ?Claim 12? The composition according to claim 11, wherein the 16th and 20th amino acid of the long-acting glucagon-like peptide-1 (GLP-1)/glucagon dual agonist represented by SEQ ID NO: 40 form a ring. ?Claim 13? The composition according to any one of claims 1 to 12, wherein the non-peptidyl polymer linker is PEG. ?Claim 14? Use of a composition of any one of claims 1 to 13 in the manufacture of a medicament for preventing or treating diabetes mellitus. ?Claim 15? The use according to claim 14, wherein the long-acting insulin conjugate and the longacting GLP-1/glucagon dual agonist conjugate is for simultaneous, sequential, or reverse administration.
NZ727871A 2015-06-01 Composition for treating diabetes mellitus comprising insulin and a glp-1/glucagon dual agonist NZ727871B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
NZ764889A NZ764889B2 (en) 2015-06-01 Composition for treating diabetes mellitus comprising insulin and a GLP-1/glucagon dual agonist

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR20140066554 2014-05-30
PCT/KR2015/005455 WO2015183054A1 (en) 2014-05-30 2015-06-01 Composition for treating diabetes mellitus comprising insulin and a glp-1/glucagon dual agonist

Publications (2)

Publication Number Publication Date
NZ727871A NZ727871A (en) 2024-02-23
NZ727871B2 true NZ727871B2 (en) 2024-05-24

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