DK2292249T3 - Ikke-cytotoksiske proteinkonjugater - Google Patents

Ikke-cytotoksiske proteinkonjugater Download PDF

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DK2292249T3
DK2292249T3 DK10184114.6T DK10184114T DK2292249T3 DK 2292249 T3 DK2292249 T3 DK 2292249T3 DK 10184114 T DK10184114 T DK 10184114T DK 2292249 T3 DK2292249 T3 DK 2292249T3
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Keith Foster
John Chaddock
Charles Penn
Roger K Aoki
Joseph Francis
Lance Steward
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Sec Dep For Health
Allergan Inc
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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
    • C07K14/435—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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
    • 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
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
    • A61K38/4893—Botulinum neurotoxin (3.4.24.69)
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6489—Metalloendopeptidases (3.4.24)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/24—Metalloendopeptidases (3.4.24)
    • C12Y304/24069—Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Biotechnology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biophysics (AREA)
  • Toxicology (AREA)
  • Microbiology (AREA)
  • Pain & Pain Management (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Endocrinology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)

Claims (15)

1
1. Ikke-cytotoksisk proteinkonjugat til inhibering eller reduktion af exocytisk fusion i en nociceptiv sensorisk afferent celle, omfattende: (i) targeting-enhed (TM), hvor TM'en er en agonist af en receptor, der forekommer på den nociceptive sensoriske afferente celle, og hvor receptoren undergår endocytose for at blive inkorporeret i et endosom i den nociceptive sensoriske afferente celle; (ii) en ikke-cytotoksisk protease eller et fragment deraf, hvor proteasen eller proteasefragmentet er i stand til at spalte et protein af den exocytiske fusionsindretning af den nociceptive sensoriske afferente celle; og (iii) et translokationsdomæne, hvor translokationsdomænet translokerer proteasen eller proteasefragmentet inde fra endosomet, igennem den endosomale membran og ind i den nociceptive sensoriske afferente celles cytosol, hvor TM'en og translokationsdomænet er adskilt af en spacer med en amino-syresekvens på 20-29 aminosyrerester.
2. Ikke-cytotoksisk proteinkonjugat ifølge krav 1, hvor TM'en og translokationsdomænet er adskilt af en spacer med en aminosyresekvens på 20-27 aminosyrerester.
3. Ikke-cytotoksisk proteinkonjugat ifølge krav 1 eller krav 2, hvor TM'en er udvalgt fra gruppen bestående af: en peptidagonist af ORLrreceptoren; en endomorfin-1; en endomorfin-2; en enkefalin; en β-endorfin; en opioid; en lofentanil; en etorfin; en nociceptin; en dynorfin; og fragmenter deraf.
4. Ikke-cytoksisk proteinkonjugat ifølge krav 3, hvor enkefalin-TM'en er en met-enkefalin, eller en leu-enkefalin.
5. Ikke-cytotoksisk proteinkonjugat ifølge et af kravene 1-4, hvor receptoren er en ORLrreceptor. 2
6. Ikke-cytotoksisk proteinkonjugat ifølge krav 3, hvor nociceptin-TM'en har mindst 70 % eller mindst 80 % homologi med SEQ ID NO. 2, 4, 6, 8, 10, 12, 14 eller et fragment deraf.
7. Ikke-cytotoksisk proteinkonjugat ifølge et hvilket som helst foregående krav, hvor den ikke-cytotoksiske protease er et bakterielt protein eller et fragment deraf, som er i stand til at spalte et protein af den exocytiske fusionsindretning i den nociceptive sensoriske afferente celle; fortrinsvis hvor den ikke-cytotoksiske protease er en clostridiel neurotoksin-protease, eller en IgA-protease.
8. Ikke-cytotoksisk proteinkonjugat ifølge et hvilket som helst foregående krav, hvor translokationsdomænet er et clostridielt neurotoksin-translokationsdomæne; fortrinsvis hvor translokationsdomænet er et botulinum HN-domæne.
9. Ikke-cytotoksisk proteinkonjugat ifølge krav 8, hvor botulinum HN-domænet er kodet af nukleinsyresekvensen ifølge SEQ ID Nos 28, 30 eller 32.
10. Ikke-cytotoksisk proteinkonjugat ifølge et hvilket som helst foregående krav, hvor den nociceptive sensoriske afferente celle er en primær nociceptiv sensorisk afferent celle.
11. Ikke-cytotoksisk proteinkonjugat ifølge krav 1, hvor konjugatet omfatter en aminosyresekvens udvalgt fra gruppen bestående af SEQ ID NOs.44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 73, 76, 79, 81,83, 85, 88, 91,94, 97 og 100.
12. Ikke-cytotoksisk proteinkonjugat ifølge et af kravene 1-11, hvor TM'en, translokationsdomænet og proteasen eller fragmentet deraf er kovalent bundet til hinanden.
13. Farmaceutisk sammensætning omfattende et ikke-cytotoksisk proteinkonjugat ifølge et af kravene 1 til 12 og en farmaceutisk acceptabel bærer. 3
14. Anvendelse af et ikke-cytotoksisk proteinkonjugat ifølge et af kravene 1-12 eller en sammensætning ifølge krav 13, til fremstilling af et lægemiddel til behandling af smerte.
15. Ikke-cytotoksisk proteinkonjugat ifølge et af kravene 1-12 eller en sammensætning ifølge krav 13, til anvendelse til behandling eller undertrykkelse af smerte.
DK10184114.6T 2004-12-01 2005-12-01 Ikke-cytotoksiske proteinkonjugater DK2292249T3 (da)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB0426394A GB0426394D0 (en) 2004-12-01 2004-12-01 Fusion proteins
GB0504966A GB0504966D0 (en) 2004-12-01 2005-03-10 Re-targeted toxin conjugates
GB0504964A GB0504964D0 (en) 2004-12-01 2005-03-10 Fusion proteins
EP05810711.1A EP1877073B1 (en) 2004-12-01 2005-12-01 Non-cytotoxic protein conjugates

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DK2292249T3 true DK2292249T3 (da) 2015-07-06

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DK05810103T DK1830872T3 (da) 2004-12-01 2005-12-01 Fusionsproteiner
DK10157432T DK2204182T3 (da) 2004-12-01 2005-12-01 Ikke-cytotoksiske proteinkonjugater
DK10166556.0T DK2366399T3 (da) 2004-12-01 2005-12-01 Ikke-cytotoksiske proteinkonjugater
DK10184150.0T DK2335718T3 (da) 2004-12-01 2005-12-01 Ikke-cytotoksiske proteinkonjugater
DK10184114.6T DK2292249T3 (da) 2004-12-01 2005-12-01 Ikke-cytotoksiske proteinkonjugater
DK05810711T DK1877073T3 (da) 2004-12-01 2005-12-01 Ikke-cytotoksiske proteinkonjugater

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DK05810103T DK1830872T3 (da) 2004-12-01 2005-12-01 Fusionsproteiner
DK10157432T DK2204182T3 (da) 2004-12-01 2005-12-01 Ikke-cytotoksiske proteinkonjugater
DK10166556.0T DK2366399T3 (da) 2004-12-01 2005-12-01 Ikke-cytotoksiske proteinkonjugater
DK10184150.0T DK2335718T3 (da) 2004-12-01 2005-12-01 Ikke-cytotoksiske proteinkonjugater

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US (5) US8187834B2 (da)
EP (4) EP2292249B1 (da)
JP (7) JP5174463B2 (da)
AT (1) ATE488245T1 (da)
CY (2) CY1111324T1 (da)
DE (1) DE602005024857D1 (da)
DK (6) DK1830872T3 (da)
ES (6) ES2356179T3 (da)
GB (3) GB0426394D0 (da)
HU (2) HUE025964T2 (da)
PL (3) PL2335718T3 (da)
PT (5) PT2366399E (da)
SI (2) SI1877073T1 (da)

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