HRP20201399T1 - Novi modulatori i postupci njihove uporabe - Google Patents

Novi modulatori i postupci njihove uporabe Download PDF

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HRP20201399T1
HRP20201399T1 HRP20201399TT HRP20201399T HRP20201399T1 HR P20201399 T1 HRP20201399 T1 HR P20201399T1 HR P20201399T T HRP20201399T T HR P20201399TT HR P20201399 T HRP20201399 T HR P20201399T HR P20201399 T1 HRP20201399 T1 HR P20201399T1
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Croatia
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seq
residues
variable region
antibody
chain variable
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HRP20201399TT
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Orit Foord
Scott J. Dylla
Robert A. Stull
Alex Bankovich
Alexandra Leida Liana LAZETIC
Jeffrey Bernstein
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Abbvie Stemcentrx Llc
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Priority claimed from PCT/US2011/050451 external-priority patent/WO2012031280A2/en
Application filed by Abbvie Stemcentrx Llc filed Critical Abbvie Stemcentrx Llc
Publication of HRP20201399T1 publication Critical patent/HRP20201399T1/hr

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Claims (19)

1. Kimerno, CDR-kalemljeno, humanizirano ili rekombinantno ljudsko protutijelo, ili njegov fragment koji veže antigen, naznačeno time, da se specifično veže na ljudski PTK7 i pritom obuhvaća varijabilne regije lakog i teškog lanca, pri čemu: (a) varijabilna regija lakog lanca obuhvaća tri CDR-a koji su predstavljeni kao ostaci 24-34 od SEQ ID NO:62 za VL CDR1, ostaci 50-56 od SEQ ID NO:62 za VL CDR2 i ostaci 89-97 od SEQ ID NO:62 za VL CDR3, i varijabilna regija teškog lanca obuhvaća tri CDR-a koji su predstavljeni kao ostaci 31-35 od SEQ ID NO:63 za VH CDR1, ostaci 50-65 od SEQ ID NO:63 za VH CDR2 i ostaci 95-102 od SEQ ID NO:63 za VH CDR3, pri čemu je CDR-numeriranje u skladu s Kabat shemom; (b) varijabilna regija lakog lanca obuhvaća tri CDR-a koji su predstavljeni kao ostaci 23-34 od SEQ ID NO:62 za VL CDR1, ostaci 50-56 od SEQ ID NO:62 za VL CDR2 i ostaci 89-97 od SEQ ID NO:62 za VL CDR3, i varijabilna regija teškog lanca obuhvaća tri CDR-a koji su predstavljeni kao ostaci 26-32 od SEQ ID NO:63 za VH CDR1, ostaci 50-58 od SEQ ID NO:63 za VH CDR2 i ostaci 95-102 od SEQ ID NO:63 za VH CDR3, pri čemu je CDR-numeriranje u skladu s Chothia shemom; ili (c) varijabilna regija lakog lanca obuhvaća tri CDR-a koji su predstavljeni kao ostaci 30-36 od SEQ ID NO:62 za VL CDR1, ostaci 46-55 od SEQ ID NO:62 za VL CDR2 i ostaci 89-96 od SEQ ID NO:62 za VL CDR3, i varijabilna regija teškog lanca obuhvaća tri CDR-a koji su predstavljeni kao ostaci 30-35 od SEQ ID NO:63 za VH CDR1, ostaci 47-58 od SEQ ID NO:63 za VH CDR2 i ostaci 93-101 od SEQ ID NO:63 za VH CDR3, pri čemu je CDR-numeriranje u skladu s MacCallum shemom.
2. Kimerno, CDR-kalemljeno, humanizirano ili rekombinantno ljudsko protutijelo, ili njegov fragment koji veže antigen, naznačeno time, da se specifično veže na ljudski PTK7 i pritom obuhvaća varijabilne regije lakog i teškog lanca, pri čemu: (a) varijabilna regija lakog lanca obuhvaća tri CDR-a koji su predstavljeni kao ostaci 24-34 od SEQ ID NO:64 za VL CDR1, ostaci 50-56 od SEQ ID NO:64 za VL CDR2 i ostaci 89-97 od SEQ ID NO:64 za VL CDR3, i varijabilna regija teškog lanca obuhvaća tri CDR-a koji su predstavljeni kao ostaci 31-35 od SEQ ID NO:65 za VH CDR1, ostaci 50-65 od SEQ ID NO:65 za VH CDR2 i ostaci 95-102 od SEQ ID NO:65 za VH CDR3, pri čemu je CDR-numeriranje u skladu s Kabat shemom; (b) varijabilna regija lakog lanca obuhvaća tri CDR-a koji su predstavljeni kao ostaci 23-34 od SEQ ID NO:64 za VL CDR1, ostaci 50-56 od SEQ ID NO:64 za VL CDR2 i ostaci 89-97 od SEQ ID NO:64 za VL CDR3, i varijabilna regija teškog lanca obuhvaća tri CDR-a koji su predstavljeni kao ostaci 26-32 od SEQ ID NO:65 za VH CDR1, ostaci 50-58 od SEQ ID NO:65 za VH CDR2 i ostaci 95-102 od SEQ ID NO:65 za VH CDR3, pri čemu je CDR-numeriranje u skladu s Chothia shemom; ili (c) varijabilna regija lakog lanca obuhvaća tri CDR-a koji su predstavljeni kao ostaci 30-36 od SEQ ID NO:64 za VL CDR1, ostaci 46-55 od SEQ ID NO:64 za VL CDR2 i ostaci 89-96 od SEQ ID NO:64 za VL CDR3, i varijabilna regija teškog lanca obuhvaća tri CDR-a koji su predstavljeni kao ostaci 30-35 od SEQ ID NO:65 za VH CDR1, ostaci 47-58 od SEQ ID NO:65 za VH CDR2 i ostaci 93-101 od SEQ ID NO:65 za VH CDR3, pri čemu je CDR-numeriranje u skladu s MacCallum shemom.
3. Protutijelo ili njegov fragment koji veže antigen, prema patentnom zahtjevu 1 ili 2, naznačeno time, da obuhvaća: (a) varijabilnu regiju lakog lanca koja posjeduje aminokiselinsku sekvencu koja je najmanje 60% identična kao SEQ ID NO:62 i varijabilnu regiju teškog lanca koja posjeduje aminokiselinsku sekvencu koja je najmanje 60% identična kao SEQ ID NO:63; ili (b) varijabilnu regiju lakog lanca koja posjeduje aminokiselinsku sekvencu koja je najmanje 60% identična kao SEQ ID NO:64 i varijabilnu regiju teškog lanca koja posjeduje aminokiselinsku sekvencu koja je najmanje 60% identična kao SEQ ID NO:65.
4. Protutijelo ili njegov fragment koji veže antigen, prema patentnom zahtjevu 1, naznačeno time, da obuhvaća varijabilnu regiju lakog lanca koja je predstavljena kao SEQ ID NO:62 i varijabilnu regiju teškog lanca koja je predstavljena kao SEQ ID NO:63.
5. Protutijelo ili njegov fragment koji veže antigen, prema patentnom zahtjevu 2, naznačeno time, da obuhvaća varijabilnu regiju lakog lanca koja je predstavljena kao SEQ ID NO:64 i varijabilnu regiju teškog lanca koja je predstavljena kao SEQ ID NO:65.
6. Protutijelo ili njegov fragment koji veže antigen, prema bilo kojem od patentnih zahtjeva 1 do 5, naznačeno time, da je to neutralizirajuće, iscrpljujuće protutijelo, i/ili je internalizirajuće protutijelo.
7. Protutijelo ili njegov fragment koji veže antigen, prema bilo kojem od patentnih zahtjeva 1 do 6, naznačeno time, da se specifično veže na PTK7 izooblik koji je odabran iz skupine koju čine: izooblik a, izooblik b, izooblik c i izooblik d.
8. Konjugat protutijela, naznačen time, da obuhvaća protutijelo ili njegov fragment koji veže antigen, prema bilo kojem od patentnih zahtjeva 1 do 7, gdje je to protutijelo konjugirano, povezano, ili na neki drugi način udruženo sa citotoksičnim sredstvom.
9. Farmaceutski pripravak, naznačen time, da obuhvaća protutijelo ili njegov fragment koji veže antigen, prema bilo kojem od patentnih zahtjeva 1 do 7, ili konjugat protutijela u skladu s patentnim zahtjevom 8.
10. Nukleinska kiselina, naznačena time, da kodira varijabilnu regiju teškog lanca i/ili varijabilnu regiju lakog lanca protutijela ili njegovog fragmenta koji veže antigen, prema bilo kojem od patentnih zahtjeva 1 do 7.
11. Vektor ili stanica domaćina, naznačeni time, da sadrže nukleinsku kiselinu u skladu s patentnim zahtjevom 10.
12. Stanica, naznačena time, da obuhvaća protutijelo koje se specifično veže na ljudski PTK7, pri čemu stanica obuhvaća jednu ili više nukleinskih kiselina koje kodiraju sljedeće: (a) varijabilnu regiju lakog lanca koja je predstavljena kao SEQ ID NO:62 i varijabilnu regiju teškog lanca koja je predstavljena kao SEQ ID NO:63; ili (b) varijabilnu regiju lakog lanca koja je predstavljena kao SEQ ID NO:64 i varijabilnu regiju teškog lanca koja je predstavljena kao SEQ ID NO:65.
13. Protutijelo ili njegov fragment koji veže antigen, prema bilo kojem od patentnih zahtjeva 1 do 7, ili konjugat protutijela prema patentnom zahtjevu 8, naznačeni time, da se upotrebljavaju kao farmaceutski proizvod.
14. Protutijelo ili njegov fragment koji veže antigen, prema bilo kojem od patentnih zahtjeva 1 do 7, naznačeno time, da se upotrebljava u detektiranju, dijagnosticiranju ili nadgledanju poremećaja koji je povezan s PTK7 kod pojedinca, pri čemu je poremećaj koji je povezan s PTK7 proliferativni poremećaj, gdje je to opcionalno neoplastični poremećaj koji obuhvaća čvrsti tumor, kao što je rak dojke, rak jajnika, kolorektalni rak, rak gušterače, rak pluća ili rak kože.
15. Protutijelo ili njegov fragment koji veže antigen, prema bilo kojem od patentnih zahtjeva 1 do 7, ili konjugat protutijela prema patentnom zahtjevu 8, naznačeni time, da se upotrebljavaju u liječenju poremećaja koji je povezan s PTK7 kod pojedinca, pri čemu je poremećaj koji je povezan s PTK7 proliferativni poremećaj, dok je to opcionalno neoplastični poremećaj koji obuhvaća čvrsti tumor, kao što je rak dojke, rak jajnika, kolorektalni rak, rak gušterače, rak pluća ili rak kože.
16. Protutijelo ili njegov fragment koji veže antigen, prema bilo kojem od patentnih zahtjeva 1 do 7, ili konjugat protutijela prema patentnom zahtjevu 8, naznačeni time, da se upotrebljavaju u smanjivanju frekvencije stanica koje iniciraju tumor kod pojedinca.
17. Protutijelo ili njegov fragment koji veže antigen, prema bilo kojem od patentnih zahtjeva 1 do 7, naznačeno time, da se upotrebljava u postupku in vivo za detektiranje, dijagnosticiranje ili nadgledanje poremećaja koji je povezan s PTK7 kod pojedinca, pri čemu je poremećaj koji je povezan s PTK7 proliferativni poremećaj, gdje je to opcionalno neoplastični poremećaj koji obuhvaća čvrsti tumor, kao što je rak dojke, rak jajnika, kolorektalni rak, rak gušterače, rak pluća ili rak kože.
18. Postupak in vivo za detektiranje, dijagnosticiranje ili nadgledanje poremećaja koji je povezan s PTK7, naznačen time, da se provodi uporabom protutijela ili njegovog fragmenta koji veže antigen, prema bilo kojem od patentnih zahtjeva 1 do 7, pri čemu je poremećaj koji je povezan s PTK7 proliferativni poremećaj, gdje je to opcionalno neoplastični poremećaj koji obuhvaća čvrsti tumor, kao što je rak dojke, rak jajnika, kolorektalni rak, rak gušterače, rak pluća ili rak kože.
19. Protutijelo ili njegov fragment koji veže antigen, za uporabu u skladu s bilo kojim od patentnih zahtjeva 14 do 15 ili 17, ili konjugat protutijela za uporabu u skladu s patentnim zahtjevom 15, ili postupak prema patentnom zahtjevu 18, naznačeni time, da poremećaj koji je povezan s PTK7 je rak.
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