HRP20131135T1 - Rekombinantni proteini elastaze i postupci proizvodnje i uporabe istih - Google Patents

Rekombinantni proteini elastaze i postupci proizvodnje i uporabe istih Download PDF

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Publication number
HRP20131135T1
HRP20131135T1 HRP20131135AT HRP20131135T HRP20131135T1 HR P20131135 T1 HRP20131135 T1 HR P20131135T1 HR P20131135A T HRP20131135A T HR P20131135AT HR P20131135 T HRP20131135 T HR P20131135T HR P20131135 T1 HRP20131135 T1 HR P20131135T1
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protein
elastase
mature
type
pancreatic
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HRP20131135AT
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English (en)
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F. Nicholas Franano
Kimberly Bland
Marco D. Wong
Bee C. Ding
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Proteon Therapeutics, Inc.
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Publication of HRP20131135T1 publication Critical patent/HRP20131135T1/hr

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    • 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
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6448—Elastases, e.g. pancreatic elastase (3.4.21.36); leukocyte elastase (3.4.31.37)
    • 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)
    • A61K38/482—Serine endopeptidases (3.4.21)
    • A61K38/486—Elastase (3.4.21.36 or 3.4.21.37)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14—Extraction; Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
    • C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
    • C12N15/815—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts for yeasts other than Saccharomyces
    • 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)
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00—Preparation of peptides or proteins
    • C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
    • 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)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21036—Pancreatic elastase (3.4.21.36)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site
    • 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)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21037—Leukocyte elastase (3.4.21.37), i.e. neutrophil-elastase
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Claims (16)

1. Autoaktivacijski protein elastaze pankreasa tipa I koji sadrži (i) aktivacijsku sekvencu elastaze koja sadrži sekvencu prepoznavanja elastaze koja je operativno povezana sa (ii) sekvencom amino kiselina zrele elastaze tipa I pankreasa.
2. Protein prema patentnom zahtjevu 1, gdje ostatak druge amino kiseline N-terminalan vezi koja se cijepa kako bi se dobio zreo protein elastaze tipa I pankreasa je prolin, ili gdje navedena sekvenca prepoznavanja sadrži sekvencu odabranu iz grupe koja se sastoji od SEQ IN brojeva: 11, 13, 15, 20 i 93, ili gdje navedena aktivacijska sekvenca sadrži sekvencu odabranu iz grupe koja se sastoji od SEQ ID brojeva: 80, 72 i 73, ili gdje navedeni protein sadrži mjesto cijepanja koje sadrži sekvencu odabranu iz grupe koja se sastoji od SEQ ID brojeva: 42, 48, 49, 53 i 55, gdje, po izboru, navedena sekvenca zrele elastaze sadrži sekvencu koja ima najmanje 85% identičnosti sekvence sa sekvencom amino kiseline sa položaja 6 do kraja SEQ ID broj: 84 ili SEQ ID broj: 1, ili gdje navedeni protein sadrži sekvencu odabranu iz grupe koja se sastoji od SEQ IN brojeva: 64, 65, 67 i 69; i/ili gdje navedeni protein sadrži signalnu sekvencu.
3. Molekula nukleinske kiseline koja kodira protein prema bilo kojem od patentnih zahtjeva 1 ili 2.
4. Vektor koji sadrži molekulu nukleinske kiseline prema patentnom zahtjevu 3.
5. Stanica domaćina koja je genetički napravljena da izrazi molekule nukleinske kiseline prema patentnom zahtjevu 3, ili stanica domaćina koja sadrži vektor prema patentnom zahtjevu 4 gdje je, po izboru, barem jedna kopija navedenog vektora integrirana unutar genoma stanice domaćina.
6. Postupak proizvodnje proteina elastaze tipa I pankreasa koji sadrži uzgoj stanice domaćina prema patentnom zahtjevu 5, pod uvjetima u kojima se proizvodi protein proelastaze, koji nadalje po izboru može sadržavati podvrgavanje proteina aktivacijskim uvjetima u kakvim se proizvodi zreli protein elastaze tipa I pankreasa.
7. Postupak prema patentnom zahtjevu 6, gdje tripsin nije upotrjebljen ni u jednom dijelu procesa proizvodnje.
8. Postupak prema patentnim zahtjevima 6 ili 7, gdje je ćelija domaćina uzgojena u prisustvu spoja citrata, sukcinata ili acetata kako bi se zaobišla auto-aktivacija auto-aktivirane proelastaze, ili gdje je jedan spoj citrata, sukcinata ili acetata prisutan u navedenoj kulturi u koncentraciji od 5-50 mM, 7.5-100 mM, 10-150 mM, 50-200 mM, 100-150 mM, 75-125 mM ili 90-110 mM; gdje je spoj citrata, sukcinata ili acetata po izboru natrij citrat, natrij sukcinat ili natrij acetat i/ili gdje navedeni uvjeti prema patentnom zahtjevu 6 uključuju period rasta ili indukcije pri pH 2 do 6 te navedeni postupak nadalje sadrži povišavanje pH otopine koja sadrži protein sa pH 6 do 12.
9. Postupak za proizvodnju zrelog proteina elastaze tipa I pankreasa, koji sadrži: (a) uzgoj ćelije domaćina konstruirane da izrazi nukleinsku kiselinu kako je definirana u patentnom zahtjevu 3 pod uvjetima u kojima je proizveden protein proelastaze; i (b) izlaganje navedenog proteina proelastaze aktivacijskim uvjetima u kakvim se proizvodi zreo protein elastaze gdje navedenu aktivaciju iz koraka (b) izvršava elastaza.
10. Postupak prema patentnom zahtjevu 9, gdje je navedeni zreli protein elastaze tipa I pankreasa izoliran.
11. Postupak proizvodnje farmaceutskog pripravka koji sadrži zreli protein elastaze tipa I pankreasa, i sadrži: (a) izlaganje autoaktiviranog proteina proelastaze tipa I pankreasa autoaktivacijskim uvjetima da bi se proizveo zreli protein elastaze tipa I pankreasa; gdje je navedena autoaktivacija izvršena elastazom, i (b) formuliranje zrelog proteina elastaze tipa I pankreasa, tako da se proizvede farmaceutski pripravak koji sadrži navedeni zreli protein elastaze tipa I pankreasa.
12. Postupak prema patentnom zahtjevu 11, koji nadalje sadrži korake (i) proizvodnje lipofilizirane zrele elastaze tipa I pankreasa; i (ii) rekonstituiranje lipofilizirane zrele elastaze tipa I pankreasa u vodi ili farmaceutski prihvatljivom nosaču, čime se proizvodi farmaceutski pripravak koji sadrži zrelu elastazu tipa I ljudskog pankreasa.
13. Postupak prema bilo kojem od patentnih zahtjeva 6-12, gdje je aktivacija navedenog proteina proelastaze započeta dodatkom kataličke količine elastaze.
14. Farmaceutski pripravak koji (a) se može dobiti postupkom prema bilo kojem od patentnih zahtjeva 11, 12 ili 13 u zavisnosti od patentnih zahtjeva 11 ili 12 i/ili (b) sadrži (i) terapeutski efektivnu količinu zrele elastaze tipa I ljudskog pankreasa i (ii) farmaceutski prihvatljivi nosač, pri čemu u svakom pripravku (a) i/ili (b) (c) zrela elastaza tipa I ljudskog pankreasa je naznačena specifičnom aktivnošću od 1 do 40 U/mg proteina i/ili (d) aktivnost tripsina u navedenom pripravku odgovara manje od 4 ng po 1 mg proteina zrele elastaze.
15. Farmaceutski pripravak prema patentnom zahtjevu 14, gdje je pripravak oslobođen bilo kojeg proteina koji se sastoji od SEQ ID broj; 70 i 71, i/ili koji je oslobođen tripsina.
16. Farmaceutski pripravak prema bilo kojem od patentnih zahtjeva 14 ili 15, koji je otopina za parenteralnu primjenu i sadrži fosfat, fosfatni pufer ili fosfatnu puferiranu slanu otopinu.
HRP20131135AT 2007-12-04 2013-11-27 Rekombinantni proteini elastaze i postupci proizvodnje i uporabe istih HRP20131135T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US99231907P 2007-12-04 2007-12-04
US12/327,809 US8501449B2 (en) 2007-12-04 2008-12-03 Recombinant elastase proteins and methods of manufacturing and use thereof
PCT/US2008/085559 WO2009079220A2 (en) 2007-12-04 2008-12-04 Recombinant elastase proteins and methods of manufacturing and use thereof

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HRP20170755TT HRP20170755T1 (hr) 2007-12-04 2017-05-19 Rekombinantni proteini elastaze i postupci proizvodnje i uporabe istih

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US (14) US8501449B2 (hr)
EP (3) EP3176262A1 (hr)
JP (3) JP5829808B2 (hr)
KR (3) KR101732190B1 (hr)
CN (4) CN109893647A (hr)
AR (1) AR069584A1 (hr)
AU (1) AU2008338743B2 (hr)
BR (1) BRPI0819977A2 (hr)
CA (1) CA2707051C (hr)
CY (2) CY1114724T1 (hr)
DK (2) DK2666854T3 (hr)
ES (2) ES2627066T3 (hr)
HK (1) HK1148772A1 (hr)
HR (2) HRP20131135T1 (hr)
HU (1) HUE032739T2 (hr)
IL (2) IL206157A (hr)
LT (1) LT2666854T (hr)
MX (2) MX2010006211A (hr)
NZ (2) NZ601592A (hr)
PL (2) PL2666854T3 (hr)
PT (2) PT2229440E (hr)
RS (2) RS55982B1 (hr)
RU (1) RU2611200C2 (hr)
SI (2) SI2229440T1 (hr)
TW (2) TWI619726B (hr)
WO (1) WO2009079220A2 (hr)

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