HRP20180443T1 - Povezujuće domene usmjerene protiv gpcr-a: g proteinski kompleksi i njihove derivirane uporabe - Google Patents

Povezujuće domene usmjerene protiv gpcr-a: g proteinski kompleksi i njihove derivirane uporabe Download PDF

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HRP20180443T1
HRP20180443T1 HRP20180443TT HRP20180443T HRP20180443T1 HR P20180443 T1 HRP20180443 T1 HR P20180443T1 HR P20180443T T HRP20180443T T HR P20180443TT HR P20180443 T HRP20180443 T HR P20180443T HR P20180443 T1 HRP20180443 T1 HR P20180443T1
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nanoparticle
protein
complex
gpcr
nanoparticle according
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HRP20180443TT
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Jan Steyaert
Els Pardon
Toon Laeremans
Brian Kobilka
Soren Rasmussen
Sébastien GRANIER
Roger K. Sunahara
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Vib Vzw
Vrije Universiteit Brussel
The Board Of Trustees Of The Leland Stanford Junior University
The Regents Of The University Of Michigan
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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    • C07ORGANIC CHEMISTRY
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    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4722G-proteins
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70571Receptors; Cell surface antigens; Cell surface determinants for neuromediators, e.g. serotonin receptor, dopamine receptor
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/74Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/22Immunoglobulins specific features characterized by taxonomic origin from camelids, e.g. camel, llama or dromedary
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/569Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2799/00Uses of viruses
    • C12N2799/02Uses of viruses as vector
    • C12N2799/021Uses of viruses as vector for the expression of a heterologous nucleic acid
    • C12N2799/026Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a baculovirus
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/72Assays involving receptors, cell surface antigens or cell surface determinants for hormones
    • G01N2333/726G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00Screening for compounds of potential therapeutic value
    • G01N2500/02Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)

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  • Health & Medical Sciences (AREA)
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  • Preparation Of Compounds By Using Micro-Organisms (AREA)
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  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
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Claims (20)

1. Nanočestica (VHH), naznačena time, da sadržava aminokiselinsku sekvencu koja se sastoji od 4 okvirna područja (FR1 do FR4) i 3 komplementarna područja za određivanje (CDR1 do CDR3) prema sljedećoj formuli (1): FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4 (1), pri čemu navedena nanočestica ima aminokiselinsku sekvencu SEQ ID NO: 1 ili aminokiselinsku sekvencu koja ima najmanje 80% identičnu aminokiselinu s aminokiselinskom sekvencom SEQ ID NO: 1, pri čemu je navedena nanočestica usmjerena protiv i / ili specifično se veže na kompleks koji sadržava GPCR i G protein, i pri čemu se navedena nanočestica specifično veže na G protein, a ne na GPCR u kompleksu.
2. Nanočestica u skladu s patentnim zahtjevom 1, naznačena time, da ima veći afinitet vezanja prema kompleksu u usporedbi s vezanjem na heterotrimerni G protein.
3. Nanočestica u skladu s patentnim zahtjevom 1, naznačena time, da kompleks nadalje sadržava ligand receptora.
4. Nanočestica u skladu s patentnim zahtjevom 3, naznačena time, da je navedeni ligand receptor agonist.
5. Nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačena time, da je G protein prisutan u obliku bez nukleotida.
6. Nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačena time, da specifično veže konformacijski epitop na sučelju između alfa i beta podjedinice spomenutog G proteina.
7. Nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 6, naznačena time, da a) sprječava ili inhibira disocijaciju kompleksa u prisutnosti nukleotida, ili b) sprječava ili inhibira vezanje nukleotida na G protein, ili c) može premjestiti nukleotide iz G proteina.
8. Nanočestica u skladu s bilo kojim od patentnih zahtjeva 5 do 7, naznačena time, da su spomenuti nukleotidi gvaninski nukleotidi, kao stoje GDP ili GTP, ili njihovi analozi, kao što je GTPγS.
9. Nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 8, naznačena time, da je GPCR u aktivnoj konformaciji.
10. Nanočestica u skladu s bilo kojim od patentnih zahtjeva od 1 do 9, naznačena time, da je G protein odabran iz skupine koju čine Gs, Gi, Go, Gt, Ggust, Gz, Golf, Gq, G12, G13.
11. Nanočestica u skladu s bilo kojim od patentnih zahtjeva od 1 do 10, naznačena time, da se navedena nanočestica sastoji od polipeptida.
12. Kompleks, naznačen time, da sadržava nanočesticu u skladu s bilo kojim od patentnih zahtjeva 1 do 11.
13. Sekvenca nukleinske kiseline, naznačena time, da kodira aminokiselinsku sekvencu nanočestice u skladu s bilo kojim od patentnih zahtjeva 1 do 11.
14. Rekombinantni vektor, naznačen time, da sadržava sekvencu nukleinske kiseline u skladu s patentnim zahtjevom 13.
15. Stanica, naznačena time, da sadržava vektor u skladu s patentnim zahtjevom 14 ili sekvencu nukleinske kiseline u skladu s patentnim zahtjevom 13.
16. Upotreba nanočestice u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačena time, da stabilizira in vitro kompleks koji sadržava GPCR i G protein i po izboru ligand receptora u aktivnoj konformaciji.
17. Upotreba nanočestice u skladu s patentnim zahtjevom 16, naznačena time, da se time sprječava disocijacija kompleksa u prisutnosti nukleotida, naročito gvaninskih nukleotida ili njihovih analoga, kao što je GTPγS.
18. Upotreba nanočestica kako je definirano u bilo kojem od patentnih zahtjeva 1 do 11, naznačena time, da se time kristalizira i / ili otapa strukturu kompleksa koji sadržava GPCR i G protein i opcijski ligand receptora.
19. Upotreba nanočestica kako je definirano u bilo kojem od patentnih zahtjeva 1 do 11 ili stanice kako je definirano u patentnom zahtjevu 15, ili membranskog pripravka stanice kako je definirano u patentnom zahtjevu 15, naznačena time, da joj je svrha izlučivanje spojeva koji moduliraju signalnu aktivnost GPCR-a.
20. Postupak in vitro hvatanja i / ili pročišćavanja kompleksa koji sadržava GPCR i G protein, naznačen time, da postupak sadržava korake: a. priprema nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 11, b. omogućavanje vezanja nanočestice na kompleks koji sadržava GPCR i G protein i opcionalno receptor ligand i c. izborno, izoliranje kompleksa dobivenog u koraku b).
HRP20180443TT 2011-06-21 2018-03-15 Povezujuće domene usmjerene protiv gpcr-a: g proteinski kompleksi i njihove derivirane uporabe HRP20180443T1 (hr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201161571159P 2011-06-21 2011-06-21
EP11181357 2011-09-15
EP12730478.0A EP2723764B1 (en) 2011-06-21 2012-06-21 Binding domains directed against gpcr: g protein complexes and uses derived thereof
PCT/EP2012/062036 WO2012175643A2 (en) 2011-06-21 2012-06-21 Binding domains directed against gpcr:g protein complexes and uses derived thereof

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US (3) US9695227B2 (hr)
EP (3) EP2723764B1 (hr)
JP (2) JP6164535B2 (hr)
CN (2) CN104053667B (hr)
AU (1) AU2012273987B2 (hr)
CA (1) CA2839834A1 (hr)
DK (1) DK2723764T3 (hr)
ES (1) ES2662372T3 (hr)
HR (1) HRP20180443T1 (hr)
HU (1) HUE036982T2 (hr)
NO (1) NO2723764T3 (hr)
PL (1) PL2723764T3 (hr)
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EP2352764B1 (en) * 2008-10-14 2018-03-28 Ablynx N.V. AMINO ACID SEQUENCES TARGETING HUMAN CD4 and CXCR4, CCR5, TLR4, ALPHAV INTEGRIN, BETA3-INTEGRIN,BETA1-INTEGRIN, HUMAN ALPHA2-INTEGRIN, CD81, SR-BI, CLAUDIN-1, CLAUDIN-6 AND/OR CLAUDIN-9, RESPECTIVELY, AND NEUTRALIZING VIRAL ENTRY
US20110294983A1 (en) 2008-12-08 2011-12-01 Complix Nv Single-chain antiparallel coiled coil proteins
GB201014715D0 (en) * 2010-09-06 2010-10-20 Vib Vzw Nanobodies stabilizing functional conformational states of GPCRS
DK2723764T3 (en) 2011-06-21 2018-03-12 Vib Vzw Binding domains targeting GPCR: G protein complexes and uses derived therefrom

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CA2839834A1 (en) 2012-12-27
EP4282882A3 (en) 2024-03-06
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US20140275487A1 (en) 2014-09-18
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