HRP20191215T1 - Formulacije etanercepta stabilizirane ionima magnezija - Google Patents

Formulacije etanercepta stabilizirane ionima magnezija Download PDF

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Publication number
HRP20191215T1
HRP20191215T1 HRP20191215TT HRP20191215T HRP20191215T1 HR P20191215 T1 HRP20191215 T1 HR P20191215T1 HR P20191215T T HRP20191215T T HR P20191215TT HR P20191215 T HRP20191215 T HR P20191215T HR P20191215 T1 HRP20191215 T1 HR P20191215T1
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Croatia
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composition
less
weight
etanercept
peak
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HRP20191215TT
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Mark Manning
Brian Murphy
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Coherus Biosciences, Inc.
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Publication of HRP20191215T1 publication Critical patent/HRP20191215T1/hr

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Claims (12)

1. Vodena farmaceutska kompozicija koja ne sadrži arginin, koja sadrži etanercept i stabilizator za inhibiciju nestabilnosti, agregacije, pogrešnog uvijanja i/ili fragmentacije etanercepta, naznačena time što stabilizator sadrži 2 do 10 mM magnezija.
2. Kompozicija prema patentnom zahtjevu 1, koja dalje sadrži jednu ili više dodatnih komponenti odabranih od: pufera; modifikatora toničnosti i ekscipijensa.
3. Stabilizirana kompozicija etanercepta prema patentnom zahtjevu 2, gdje kompozicija dovodi do stabilnosti pri dugotrajnom skladištenju, naznačena: SEC analizom u T2 sa: sadržajem monomera većim od 90%; sadržajem agregata od manje od 3 tež%; i sadržajem fragmenta 3 manjim od 5 tež%.
4. Stabilizirana kompozicija etanercepta prema patentnom zahtjevu 2 gdje je stabilizator magnezij klorid i formulacija sadrži 2 mM do 10 mM magnezij klorida; po mogućnosti do najviše 6 tež.% saharoze; 25 do 150 mM NaCl; 1 do 30 mM natrij fosfata; pri čemu kompozicija ima pH od 6.0 do 6.6.
5. Kompozicija stabilizirana magnezij kloridom prema patentnom zahtjevu 4, koja dovodi do stabilnosti pri dugotrajnom skladištenju, naznačena: SEC analizom u T2 sa više od 90 tež.% sadržaja monomera; manje od 3 tež.% sadržaja jednog ili više agregata; i manje od 5 tež% fragmenta 3; i HIC analizom u M3 ili T2 ili T4 pri čemu je količina kompozicije predstavljena pikom 1 HIC kromatograma manja od 3 tež.%; količina kompozicije predstavljena pikom 2 HIC kromatograma veća od 80 tež.%; i količina kompozicije predstavljena pikom 3 HIC kromatograma manja od 20 tež.%.
6. Kompozicija stabilizirana magnezij kloridom prema patentnom zahtjevu 5 koja dovodi do stabilnosti pri dugotrajnom skladištenju, naznačena: HIC analizom u M3 ili T2 ili T4 gdje je količina kompozicije predstavljena pikom 2 HIC kromatograma veća od, ili jednaka 95 tež.%; i gdje je, ukoliko je pik 3 prisutan na HIC kromatogramu, količina kompozicije predstavljena pikom 3 manja od, ili jednaka 3 tež.%.
7. Kompozicija stabilizirana magnezij kloridom prema patentnom zahtjevu 5 koja ima, u prosjeku, ne više od 10 000 čestica ispod granice vidljivosti po mL, koje imaju veličinu veću od 5 µm.
8. Kompozicija stabilizirana magnezij kloridom prema patentnom zahtjevu 5, koja sadrži: 50 mg/ml etanercepta; 10 mM magnezij klorida; 10-30 mM natrij fosfata; manje od 150 mM natrij klorida; i manje od 3 tež.% saharoze; i ima pH od 6.3 do 6.5; ili 50 mg/ml etanercepta; 5 mM magnezij klorida; manje od 30 mM natrij fosfata; manje od 100 mM natrij klorida; i manje od 4 tež.% saharoze; i ima pH od 6.3 do 6.5; ili 50 mg/ml etanercepta; 4 mM magnezij klorida; manje od 30 mM natrij fosfata; 100 mM natrij klorida; i 2.5 tež.% saharoze; i ima pH od 6.3 do 6.5; ili 50 mg/ml etanercepta; 10 mM magnezij klorida; manje od 30 mM natrij fosfata; manje od 100 mM natrij klorida; i manje od 5 tež.% saharoze; i ima pH od 6.3 do 6.5.
9. Stabilizirana vodena kompozicija etanercepta koja ne sadrži arginin, koja sadrži 2 do 10 mM magnezija, pri čemu kompozicija u T2 dovodi do stabilnosti pri dugotrajnom skladištenju, koja ispunjava sljedeće kriterije: (A) HIC kromatogram kod koga je (i) pik 3 odsutan, i (ii) pik 2 predstavlja više od 95 tež% kompozicije; (B) SEC kromatogram kod koga (i) nijedan pik ne odgovara agregatu (agregatima); i (ii) sadržaj monomera predstavlja najmanje 95 tež% kompozicije.
10. Kompozicija prema bilo kojem od patentnih zahtjeva 1 do 9 za upotrebu u liječenju.
11. Kompozicija prema bilo kojem od patentnih zahtjeva 1 do 9 za upotrebu u liječenju reumatoidnog artritisa, psorijaznog artritisa, ankilozirajućeg spondilitisa, Vegenerove bolesti (granulomatoze), Kronove bolesti, inflamatorne bolesti crijeva, kronične opstruktivne bolesti pluća (COPD), hepatitisa C, endometrioze, astme, kaheksije, psorijaze ili atopijskog dermatitisa.
12. Uporaba 2 do 10 mM magnezija za stabilizaciju vodene farmaceutske kompozicije koja sadrži etanercept, kako bi bila omogućena stabilnost pri dugotrajnom skladištenju navedene kompozicije, pri čemu je kompozicija bez arginina.
HRP20191215TT 2011-10-18 2019-07-04 Formulacije etanercepta stabilizirane ionima magnezija HRP20191215T1 (hr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201161548518P 2011-10-18 2011-10-18
US201261669480P 2012-07-09 2012-07-09
EP12842352.2A EP2768525B1 (en) 2011-10-18 2012-10-18 Etanercept formulations stabilized with magnesium ions
PCT/US2012/060739 WO2013059406A1 (en) 2011-10-18 2012-10-18 Etanercept formulations stabilized with metal ions

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US (21) US9302002B2 (hr)
EP (6) EP2768535A4 (hr)
JP (6) JP6220789B2 (hr)
KR (7) KR102163150B1 (hr)
CN (6) CN103998060B (hr)
AR (6) AR088382A1 (hr)
AU (6) AU2012326170B2 (hr)
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