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HRP20191652T1 - Fuzijski polipeptidi na bazi serpina i postupci za njihovu uporabu - Google Patents

Fuzijski polipeptidi na bazi serpina i postupci za njihovu uporabu Download PDF

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Publication number
HRP20191652T1
HRP20191652T1 HRP20191652T HRP20191652T1 HR P20191652 T1 HRP20191652 T1 HR P20191652T1 HR P20191652 T HRP20191652 T HR P20191652T HR P20191652 T1 HRP20191652 T1 HR P20191652T1
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Croatia
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polypeptide
amino acid
acid sequence
fusion protein
seq
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Inventor
Brendan P Eckelman
John C Timmer
Peter L Nguy
Grant B Guenther
Quinn Deveraux
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Inhibrx Lp
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Publication of HRP20191652T1 publication Critical patent/HRP20191652T1/hr

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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A—HUMAN NECESSITIES
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    • C—CHEMISTRY; METALLURGY
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    • 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
    • C07K1/16—Extraction; Separation; Purification by chromatography
    • C07K1/22—Affinity chromatography or related techniques based upon selective absorption processes
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    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/525—Tumour necrosis factor [TNF]
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    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • C07K14/7151—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for tumor necrosis factor [TNF], for lymphotoxin [LT]
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    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
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    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
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    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8121—Serpins
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    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8121—Serpins
    • C07K14/8125—Alpha-1-antitrypsin
    • C—CHEMISTRY; METALLURGY
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
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Claims (12)

1. Izolirani fuzijski protein koji sadrži najmanje jedan humani polipeptid alfa-1 antitripsin (AAT) koji sadrži aminokiselinsku sekvencu odabranu iz grupe koja se sastoji od SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO: 32 i SEQ ID NO: 33, u kojoj je polipeptid AAT funkcionalno povezan s imunoglobulinskim Fc polipeptidom, naznačen time, što izolirani fuzijski protein pokazuje aktivnost inhibicije serin proteaze i namijenjen je uporabi u postupku za liječenje bolesti ili poremećaja kod subjekta odabranog od nedostatka AAT, emfizema, kronične opstruktivne bolesti pluća (COPD), akutnog respiratornog distres sindroma (ARDS), alergijske astme, cistične fibroze, karcinoma pluća, ishemijsko-reperfuzijske ozljede, ishemijsko/reperfuzijske ozljede nakon transplantacije srca, infarkta miokarda, reumatoidnog artritisa, septičkog artritisa, psorijaznog artritisa, ankiloznog spondilitisa, Chronove bolesti, psorijaze, dijabetesa tipa I i/ili tipa II, upale pluća, sepse, bolesti presatka-protiv-primatelja (GVHD), zarastanja rane, sistemskog eritemskog lupusa i multiple skleroze.
2. Izolirani fuzijski protein za uporabu prema patentnom zahtjevu 1, naznačen time, što je bolest ili poremećaj nedostatak AAT.
3. Izolirani fuzijski protein za uporabu prema patentnom zahtjevu 1, naznačen time, što je bolest ili poremećaj cistična fibroza, ARDS, emfizem uzrokovan pušenjem ili COPD.
4. Izolirani fuzijski protein za uporabu prema bilo kojem od patentnih zahtjeva 1 do 3, naznačen time, što je subjekt čovjek.
5. Izolirani fuzijski protein za uporabu prema patentnom zahtjevu 1, naznačen time, što imunoglobulinski Fc polipeptid sadrži aminokiselinsku sekvencu koja je najmanje 98% identična aminokiselinskoj sekvenci SEQ ID NO: 6.
6. Izolirani fuzijski protein za uporabu prema patentnom zahtjevu 1, naznačen time, što su polipeptid AAT i imunoglobulinski Fc polipeptid funkcionalno povezani putem zglobne regije, regije za povezivanje, ili obje, zglobne regije i regije za povezivanje, gdje opcionalno zglobna regija, regija za povezivanje ili obje, zglobna regija i regija za povezivanje, sadrže peptidnu sekvencu.
7. Izolirani fuzijski protein za uporabu prema patentnom zahtjevu 1, naznačen time, što humani polipeptid AAT sadrži aminokiselinsku sekvencu SEQ ID NO: 1, pri čemu je polipeptid funkcionalno povezan s imunoglobulinskim Fc polipeptidom koji sadrži aminokiselinsku sekvencu koja je najmanje 98% identična aminokiselinskoj sekvenci SEQ ID NO: 6.
8. Izolirani fuzijski protein za uporabu prema patentnom zahtjevu 1, naznačen time, što humani polipeptid AAT sadrži aminokiselinsku sekvencu SEQ ID NO:2, pri čemu je polipeptid povezan s imunoglobulinskim Fc polipeptidom koji sadrži aminokiselinsku sekvencu koja je najmanje 98% identična aminokiselinskoj sekvenci SEQ ID NO: 6.
9. Izolirani fuzijski protein za uporabu prema patentnom zahtjevu 1, naznačen time, što humani polipeptid AAT sadrži aminokiselinsku sekvencu SEQ ID NO: 32, pri čemu je polipeptid povezan s imunoglobulinskim Fc polipeptidom koji sadrži aminokiselinsku sekvencu koja je najmanje 98% identična aminokiselinskoj sekvenci SEQ ID NO: 6.
10. Izolirani fuzijski protein za uporabu prema patentnom zahtjevu 1, naznačen time, što humani polipeptid AAT sadrži aminokiselinsku sekvencu SEQ ID NO: 33, pri čemu je polipeptid povezan s imunoglobulinskim Fc polipeptidom koji sadrži aminokiselinsku sekvencu koja je najmanje 98% identična aminokiselinskoj sekvenci SEQ ID NO: 6.
11. Izolirani fuzijski protein za uporabu prema patentnom zahtjevu 1, naznačen time, što fuzijski protein dodatno sadrži polipeptidnu sekvencu koja sadrži WAP domenu, pri čemu opcionalno: a. polipeptidna sekvenca koja sadrži WAP domenu sadrži sekvencu polipeptida SLPI koja sadrži aminokiselinsku sekvencu odabranu iz grupe koja se sastoji od SEQ ID NO: 10, 9 i 8; ili b. polipeptidna sekvenca koja sadrži WAP domenu sadrži sekvencu polipeptida elafina koja sadrži aminokiselinsku sekvencu odabranu iz grupe koja se sastoji od SEQ ID NO: 13, 12 i 11.
12. Izolirani fuzijski protein za uporabu prema bilo kojem od patentnih zahtjeva 1 do 11, gdje: a. imunoglobulinski Fc polipeptid je modificiran tako da poboljšava vezivanje FcRn; b. imunoglobulinski Fc polipeptid sadrži najmanje jednu od sljedećih mutacija: Met252Tyr, Ser254Thr, Thr256Glu, Met428Leu ili Asn434Ser.
HRP20191652 2011-06-28 2019-09-13 Fuzijski polipeptidi na bazi serpina i postupci za njihovu uporabu HRP20191652T1 (hr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201161502055P 2011-06-28 2011-06-28
US201161570394P 2011-12-14 2011-12-14
US201161577204P 2011-12-19 2011-12-19
US201261638168P 2012-04-25 2012-04-25
EP12804863.4A EP2726092B1 (en) 2011-06-28 2012-06-28 Serpin fusion polypeptides and methods of use thereof
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