HRP20191446T1 - Postupci i sredstva za proizvodnju heterodimernih ig-sličnih molekula - Google Patents

Postupci i sredstva za proizvodnju heterodimernih ig-sličnih molekula Download PDF

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HRP20191446T1
HRP20191446T1 HRP20191446T HRP20191446T1 HR P20191446 T1 HRP20191446 T1 HR P20191446T1 HR P20191446 T HRP20191446 T HR P20191446T HR P20191446 T1 HRP20191446 T1 HR P20191446T1
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amino acid
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Kruif Cornelis Adriaan De
Linda Johanna Aleida Hendriks
Ton Logtenberg
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Merus Nv
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Claims (17)

1. Postupak za proizvodnju najmanje dva različita antitijela od jedne stanice domaćina, naznačen time što svaki od navedena dva antitijela sadrži dvije CH3 domene koje su sposobne formirati sučelje, pri čemu navedeni postupak sadrži dobivanje u navedenoj stanici a. prve molekule nukleinske kiseline koja kodira prvi polipeptidni lanac koji sadrži CH3 domenu humanog IgG koji sadrži lizin (K) ostatak na aminokiselinskom položaju 366 u skladu s EU sustavu numeracije, b. druge molekule nukleinske kiseline koja kodira drugi polipeptidni lanac koji sadrži CH3 domenu humanog IgG, koji sadrži ostatak asparaginske kiseline (D) na aminokiselinskom položaju 351 u skladu s EU sustavu numeracije, c. treće molekule nukleinske kiseline koja kodira treći polipeptidni lanac koji sadrži CH3 domenu i d. četvrte molekule nukleinske kiseline koja kodira četvrti polipeptidni lanac koji sadrži CH3 domenu, pri čemu navedeni postupak dalje sadrži korak kultivacije navedene stanice domaćina i omogućavanja ekspresije navedena najmanje četiri molekule nukleinske kiseline i sakupljanja navedena najmanje dva različita antitijela iz kulture.
2. Postupak u skladu s patentnim zahtjevom 1, koji dalje sadrži osiguravanje navedene stanice domaćina s molekulom nukleinske kiseline koja kodira zajednički laki lanac.
3. Postupak u skladu s patentnim zahtjevom 1 ili 2, naznačen time što navedeni prvi polipeptidni lanac koji sadrži CH3 domenu dalje sadrži ostatak lizina (K) na aminokiselinskom položaju 351 u skladu s EU sustavom numeracije.
4. Postupak u skladu s patentnim zahtjevom 1 ili 2 ili 3, naznačen time što navedeni drugi polipeptidni lanac koji sadrži CH3 domenu dalje sadrži ostatak glutaminske kiseline (E) ili ostatak asparaginske kiseline (D) na aminokiselinskom položaju 349 u skladu s EU sustavom numeracije, i/ili ostatak glutaminske kiseline (E) na aminokiselinskom položaju 368 u skladu s EU sustavom numeracije.
5. Postupak u skladu s patentnim zahtjevom 4, naznačen time što navedeni drugi polipeptidni lanac koji sadrži CH3 domenu dalje sadrži ostatak glutaminske kiseline (E) na aminokiselinskom položaju 368 u skladu s EU sustavom numeracije.
6. Postupak u skladu s bilo kojim od patentnih zahtjeva 1-5, naznačen time što navedeni treći polipeptidni lanac koji sadrži CH3 domenu sadrži lizinski (K) ostatak na aminokiselinskom položaju 356 u skladu s EU sustavu numeracije i lizinski (K) ostatak na aminokiselinskom položaju 399 u skladu s EU sustavu numeracije, i navedeni četvrti polipeptidni lanac koji sadrži CH3 domenu sadrži ostatak asparaginske kiseline (D) na aminokiselinskom položaju 392 u skladu s EU sustavu numeracije i ostatak asparaginske kiseline (D) na aminokiselinskom položaju 409 u skladu s EU sustavu numeracije.
7. Postupak u skladu s bilo kojim od patentnih zahtjeva 1-6, naznačen time što svaki od polipeptidnih lanaca koji sadrže CH3 domenu dalje sadrži varijabilnu regiju koja prepoznaje ciljni epitop.
8. Postupak u skladu s patentnim zahtjevom 7, naznačen time što svaki od 4 varijabilne regije od 4 polipeptida lanca koji sadrže CH3 domenu prepoznaje različite ciljne epitope.
9. Postupak u skladu patentnim zahtjevom 7, naznačen time što varijabilne regije prvog i drugog polipeptidnog lanca koji sadrže CH3 domenu prepoznaju različite ciljne epitope, pri čemu varijabilne regije trećeg i četvrtog polipeptidnog lanca koji sadrže CH3 domenu prepoznaju iste ciljne epitope.
10. Postupak u skladu patentnim zahtjevom 9, naznačen time što je ciljni epitop kojeg prepoznaju varijabilne regije trećeg i četvrtog polipeptidnog lanca koji sadrži CH3 domenu istu kao ciljni epitop kojeg prepoznaje varijabilna regija prvog ili drugog polipeptidnog lanca koji sadrži CH3 domenu.
11. Postupak u skladu s patentnim zahtjevom 9, naznačen time što je ciljni epitop kojeg prepoznaju varijabilne regije trećeg i četvrtog polipeptidnog lanca koji sadrži CH3 domenu različitu od ciljnog epitopa kojeg prepoznaje varijabilnu regiju prvog ili drugog polipeptidnog lanca koji sadrži CH3 domenu.
12. Postupak u skladu s patentnim zahtjevom 7, naznačen time što varijabilne regije prvog i drugog polipeptidnog lanca koji sadrže CH3 domenu prepoznaju isti ciljni epitop, dok varijabilne regije trećeg i četvrtog polipeptidnog lanca koje sadrže CH3 domenu prepoznaju drugi ciljni epitop koji se razlikuje od ciljnog epitopa kojeg prepoznaju navedene prve i druge varijabilne regije.
13. Smjesa najmanje dva različita antitijela koja se može dobiti pomoću postupaka u skladu s bilo kojim od patentnih zahtjeva 1-12.
14. Rekombinantna stanica domaćin koja sadrži sekvence nukleinskih kiselina koje kodiraju najmanje dva različita antitijela, naznačena time što svako od navedena dva antitijela sadrži dvije CH3 domene koje su sposobne da formiraju sučelje, pri čemu navedene sekvence nukleinskih kiselina kodiraju najmanje prvi, drugi, treći i četvrti polipeptidni lanac koji sadrži CH3 domenu, pri čemu navedeni prvi polipeptidni lanac koji sadrži CH3 domenu sadrži CH3 domenu humanog IgG koji sadrži lizin (K) ostatak na aminokiselinskom položaju 366 u skladu s EU sustavom numeracije i pri čemu navedeni drugi polipeptidni lanac koji sadrži CH3 domenu sadrži CH3 domenu humanog IgG koji sadrži ostatak asparaginske kiseline (D) na aminokiselinskom položaju 351 u skladu s EU sustavom numeracije.
15. Farmaceutski spoj koji sadrži najmanje dva različita antitijela u skladu s patentnim zahtjevom 13 i farmaceutski prihvatljiv nosač.
16. Postupak za pripremu stanice domaćina za proizvodnju najmanje dva različita antitijela, pri čemu postupak sadrži korak uvođenja u navedenu stanicu domaćina sekvenci nukleinske kiseline koje kodiraju najmanje prvi, drugi, treći i četvrti polipeptidni lanac koji sadrži CH3 domenu, pri čemu navedeni prvi polipeptidni lanac koji sadrži CH3 domenu sadrži CH3 domenu humanog IgG koji sadrži lizinski (K) ostatak na aminokiselinskom položaju 366 u skladu s EU sustavom numeracije i pri čemu navedeni drugi polipeptidni lanac koji sadrži CH3 domenu sadrži CH3 domenu humanog IgG koji sadrži ostatak asparaginske kiseline (D) na aminokiselinskom položaju 351 u skladu s EU sustavom numeracije, pri čemu navedene sekvence nukleinske kiseline su uvedene uzastopno ili istovremeno.
17. Rekombinantne stanice domaćini u skladu s patentnim zahtjevom 14, ili rekombinantne stanice domaćini dobivene pomoću postupka u skladu s patentnim zahtjevom 16, koje proizvode najmanje dva različita antitijela.
HRP20191446 2012-04-20 2019-08-09 Postupci i sredstva za proizvodnju heterodimernih ig-sličnih molekula HRP20191446T1 (hr)

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Application Number Priority Date Filing Date Title
US201261635935P 2012-04-20 2012-04-20
PCT/NL2013/050293 WO2013157953A1 (en) 2012-04-20 2013-04-19 Methods and means for the production of ig-like molecules
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ZA201407834B (en) 2015-12-23
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US11926859B2 (en) 2024-03-12
KR20200015756A (ko) 2020-02-12
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AU2018201326A1 (en) 2018-03-15
RS59263B1 (sr) 2019-10-31
EA202090591A2 (ru) 2020-08-31
ZA201407835B (en) 2015-12-23
US9248181B2 (en) 2016-02-02
CN104520320A (zh) 2015-04-15
EP2838918B1 (en) 2019-06-05
HUE045944T2 (hu) 2020-02-28
AU2018201325A1 (en) 2018-03-15
JP6639464B2 (ja) 2020-02-05
SG11201406770WA (en) 2014-11-27
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MX360110B (es) 2018-10-23

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