DK2526119T3 - Manipuleret opsonin til patogen detektering og behandling - Google Patents

Manipuleret opsonin til patogen detektering og behandling Download PDF

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DK2526119T3
DK2526119T3 DK11735056.1T DK11735056T DK2526119T3 DK 2526119 T3 DK2526119 T3 DK 2526119T3 DK 11735056 T DK11735056 T DK 11735056T DK 2526119 T3 DK2526119 T3 DK 2526119T3
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mbl
opsonin
binding
fluid
protein
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DK11735056.1T
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Michael Super
Jeffrey Charles Way
Donald E Ingber
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Harvard College
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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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4726—Lectins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56961—Plant cells or fungi
    • 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
    • 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
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/66—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a swap of domains, e.g. CH3-CH2, VH-CL or VL-CH1
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/37—Assays involving biological materials from specific organisms or of a specific nature from fungi
    • G01N2333/39—Assays involving biological materials from specific organisms or of a specific nature from fungi from yeasts
    • G01N2333/40—Assays involving biological materials from specific organisms or of a specific nature from fungi from yeasts from Candida
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/72—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables
    • G01N27/74—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables of fluids
    • G01N27/745—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables of fluids for detecting magnetic beads used in biochemical assays
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56911—Bacteria
    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
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Claims (14)

1. Rekombinant opsoninfusionsprotein, omfattende: et kulhydratgenkendelsesdomæne af en mannose-bindende lectin (MBL), hvor kulhydratgenkendelsesdomænet gør det muligt at bindes til mannose på overfladen af en mikrobe, som er fusioneret med et Fc-afsnit af en immunoglobulin, hvor det rekombinante opsoninfusionsprotein ekskluderer et funktionelt domæne af opsoninen, som binder til en man-nan-bindende lectin-associeret serinprotease (MASP).
2. Rekombinant opsoninfusionsprotein ifølge krav 1, hvor MBL er human MBL.
3. Rekombinant opsoninfusionsprotein ifølge krav 1 eller krav 2, som yderligere omfatter mindst én cysteinrest, som muliggør kemisk tværbinding til et fast substrat.
4. Rekombinant opsoninfusionsprotein ifølge et hvilket som helst af de foregående krav, hvor: (i) Fc-afsnittet af immunoglobulinen omfatter et hængsel eller en CH2- CH3-grænseflade af et IgG-Fc-domæne; (ii) fusionsproteinet yderligere omfatter et glycin+serin-segment eller et pro-lin+alanin+serin-segment, der er anbragt mellem kulhydratgenkendelsesdomænet og Fc-afsnittet af et immunoglobulin; eller (iii) Fc-afsnittet af immunoglobulinen omfatter en aminosyresekvens af SEQ ID NO: 1, eventuelt hvor aminosyrerest 82 er modificeret fra asparagin (N) til asparaginsyre (D).
5. Rekombinant opsoninfusionsprotein ifølge et hvilket som helst af de foregående krav, som er fastgjort til et fast substrat.
6. Rekombinant opsoninfusionsprotein ifølge krav 5, hvor det faste substrat er en magnetisk mikroperle, en paramagnetisk mikroperle, en mikroporøs membran, en hul-fiber eller en hvilken som helst anden fluidfiltreringsmembran eller gennemstrømningsindretning.
7. Rekombinant opsoninfusionsprotein ifølge krav 5, hvor det faste substrat er en levende celle eller ekstracellulær matrix af et biologiskvæv eller organ, eventuelt hvor den levende celle er en phagocyt.
8. Rekombinant opsoninfusionsprotein ifølge et hvilket som helst af de foregående krav, hvor kulhydratgenkendelsesdomænet omfatter: (i) aminosyrerester 81 (prolin) til 228 (isoleucin) af MBL (anført som rester 1-148 af SEQ ID N0:2); (ii) aminosyrerester 81 (prolin) til 228 (isoleucin) af MBL (anført som rester 1-148 af SEQ ID N0:2), fusioneret med Fc-afsnittet af human IgG (Fcy) som angivet i SEQ ID NO: 3; eller (iii) en N-terminus begyndende ved glycin 111 af human MBL.
9. Rekombinant opsoninfusionsprotein ifølge et hvilket som helst af de foregående krav, hvor N-terminus i det væsentlige består af en aminosyresekvens af alanin-lysin-threonin (AKT).
10. Fremgangsmåde til indsamling af en opsonin-bindende mikroorganisme fra en fluid, omfattende at bringe fluiden i kontakt med et rekombinant opsoninfusionsprotein, som er konjugeret til en fast overflade; hvor det rekombi-nante opsoninfusionsprotein omfatter et kulhydratgenkendelsesdomæne af en mannose-bindende lectin (MBL), hvor kulhydratgenkendelsesdomænet gør det muligt at bindes til mannose, som er til stede på overfladen af en mikrobe, som er fusioneret med et Fc-afsnit af et immunoglobulin, hvor fusionsproteinet ekskluderer et funktionelt domæne af opsoninen, som binder til en mannan-bindende lectin-associeret serinprotease (MASP).
11. Fremgangsmåde ifølge krav 10: (i) yderligere omfattende trinnet med identificering af mikroorganismen; (ii) hvor fluiden er en biologisk fluid, eventuelt hvor fluiden er udvalgt fra gruppen bestående af blod, cerebrospinalvæske, ledfluid, urin, sæd, spyt, tårer og fluider indsamlet med nål, biopsi eller aspirationsprocedurer; (iii) hvor fluiden stammer fra en vand- eller fødevareprøve; og/eller (iv) yderligere omfattende adskillelsen af fluiden fra en mikroorganisme-bundet rekombinant opsonin, eventuelt hvor adskillelsen opnås ved at anvende magnetisk kraft til fluiden, efter at den opsonin-bindende mikroorganisme er forbundet med et konjugat af rekombinant opsonin og fast overflade, når den faste overflade er en magnetisk partikel.
12. Fremgangsmåde ifølge krav 11 (ii), hvor den biologisk fluid er blod.
13. Anvendelse af det rekombinante opsoninfusionsprotein ifølge et hvilket som helst krav 1 til 9 til: (i) identificering af et patogen; eller (ii) identificering af vand- eller fødevarekontaminering.
14. Rekombinant opsoninfusionsprotein ifølge et hvilket som helst af kravene 1 til 9 til anvendelse i en fremgangsmåde til behandling af en infektionssygdom eller sepsis, eventuelt hvor behandlingen yderligere kombineres med yderligere behandling eller terapi.
DK11735056.1T 2010-01-19 2011-01-19 Manipuleret opsonin til patogen detektering og behandling DK2526119T3 (da)

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US29622210P 2010-01-19 2010-01-19
PCT/US2011/021603 WO2011090954A2 (en) 2010-01-19 2011-01-19 Engineered opsonin for pathogen detection and treatment

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EP (1) EP2526119B1 (da)
JP (5) JP5959440B2 (da)
CN (1) CN102947341B (da)
AU (1) AU2011207626B2 (da)
CA (1) CA2787376A1 (da)
DK (1) DK2526119T3 (da)
ES (1) ES2678143T3 (da)
IN (1) IN2012DN06589A (da)
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