RU2009125616A - Фармакодинамические маркеры, индуцированные интерфероном альфа - Google Patents
Фармакодинамические маркеры, индуцированные интерфероном альфа Download PDFInfo
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Abstract
1. Способ лечения пациента с заболеванием или расстройством, опосредованным интерфероном I типа (ИФН I типа) или интерфероном альфа (ИФНα), включающий: ! введение агента, который связывает и модулирует активность ИФН I типа или ИФНα, пациенту, нуждающемуся в этом, ! в котором пациент обладает профилем экспрессии ФД маркеров, индуцируемых ИФН I типа или ИФНα, ! и в котором агент нейтрализует профиль экспрессии ФД маркеров, индуцируемых ИФН I типа или ИФНα, у пациента. ! 2. Способ по п.1, в котором профиль экспресссии ФД маркеров, индуцируемых ИФН I типа или ИФНα, включает набор генов с повышенной регуляцией экспрессии или действия, выбранных из группы, включающей: ! а. МХ1, LY6E, IFI27, OAS1, IFIT1, IFI6, IFI44L, ISG15, LAMP3, OASL, RSAD2, IFI44; ! б. IFI27, SIGLEC1, RSAD2, IFI6, IFI44L, IFI44, USP18, IFIT2, SAMD9L, BIRC4BP, DNAPTP6, OAS3, LY6E, IFIT1, LIPA, LOC129607, ISG15, PARP14, МХ1, OAS2, OASL, CCL2, HERC5, OAS1; ! в. IFIT1, IFIT3, IRF7, IFI6, IL6ST, IRF2, LY6E, MARCKS, МХ1, МХ2, OAS1, EIF2AK2, ISG15, STAT2, OAS3, IFI44, IFI44L, HERC5, RAB8B, LILRA5, RSAD2, FCHO2; ! г. SERPING1, IFIT2, IFIT3, IFI6, LY6E, МХ1, OAS1, ISG15, IFI27, OAS1, ISG15, IFI27, OAS3, IFI44, LAMP3, DNAPTP6, ETV7, HERC5, OAS2, USP18, XAF1, RTP4, SIGLEC1, EPSTI1; ! д. RTP4, RSAD2, HERC5, SIGLEC1, USP18, LY6E, ETV7, SERPING1, IFIT3, OAS1, HSXIAPAF1, G1P3, МХ1, OAS3, IFI27, DNAPTP6, LAMP3, EPSTI1, IFI44, OAS2, IFIT2, ISG15; ! е. LAMP3, SIGLEC1, DNAPTP6, IFIT2, ETV7, RTP4, SERPING1, HERC5, XAF1, МХ1, EPSTI1, OAS2, OAS1, OAS3, IFIT3, IFI6, USP18, RSAD2, IFI44, LY6E, ISG15, IFI27; ! ж. DNAPTP6, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMPS, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, PSAD2, RTP4, SIGLEC1, USP18; ! з. SAMD9L, IFI6, IFI44, IFIT2, ZC3HAV1, ETV6, DAPP1, IL1RN, CEACAM1, OAS1, IFI27, OAS3, IFI44L, HERC5, IFIT1, EPSTI1, ISG15, SERPING1, OASL, GBP1, MX1; ! и. SAMD9L, IFI6, IFI44, IFIT2, OAS1, IFI27, OAS3, IFI44L, HERC5, IFIT1, EPSTI1, ISG15, SERPING1, OASL, GBP1, MX1; ! к. IFI6, RSAD2, IFI44, IFI44L, IFI27, MX1, IFIT1, ISG15, LAMP3, OAS3, OAS1, EPSTI1, IFIT3, OAS2, SIGLEC1, USP18; ! л. IFI6, RSAD2, IFI44, IFI44L, IFI27; ! м. MX1, IFIT1, IFI6, RSAD2, IFI44, IFI44L, IFI27; ! н. OAS2, OAS1, MX1, IFIT1, IFI6, RSAD2, IFI44, IFI44L, IFI27. ! 3. Способ по п.2, в котором профиль экспрессии ФД маркеров, индуцируемых ИФН I типа ил
Claims (20)
1. Способ лечения пациента с заболеванием или расстройством, опосредованным интерфероном I типа (ИФН I типа) или интерфероном альфа (ИФНα), включающий:
введение агента, который связывает и модулирует активность ИФН I типа или ИФНα, пациенту, нуждающемуся в этом,
в котором пациент обладает профилем экспрессии ФД маркеров, индуцируемых ИФН I типа или ИФНα,
и в котором агент нейтрализует профиль экспрессии ФД маркеров, индуцируемых ИФН I типа или ИФНα, у пациента.
2. Способ по п.1, в котором профиль экспресссии ФД маркеров, индуцируемых ИФН I типа или ИФНα, включает набор генов с повышенной регуляцией экспрессии или действия, выбранных из группы, включающей:
а. МХ1, LY6E, IFI27, OAS1, IFIT1, IFI6, IFI44L, ISG15, LAMP3, OASL, RSAD2, IFI44;
б. IFI27, SIGLEC1, RSAD2, IFI6, IFI44L, IFI44, USP18, IFIT2, SAMD9L, BIRC4BP, DNAPTP6, OAS3, LY6E, IFIT1, LIPA, LOC129607, ISG15, PARP14, МХ1, OAS2, OASL, CCL2, HERC5, OAS1;
в. IFIT1, IFIT3, IRF7, IFI6, IL6ST, IRF2, LY6E, MARCKS, МХ1, МХ2, OAS1, EIF2AK2, ISG15, STAT2, OAS3, IFI44, IFI44L, HERC5, RAB8B, LILRA5, RSAD2, FCHO2;
г. SERPING1, IFIT2, IFIT3, IFI6, LY6E, МХ1, OAS1, ISG15, IFI27, OAS1, ISG15, IFI27, OAS3, IFI44, LAMP3, DNAPTP6, ETV7, HERC5, OAS2, USP18, XAF1, RTP4, SIGLEC1, EPSTI1;
д. RTP4, RSAD2, HERC5, SIGLEC1, USP18, LY6E, ETV7, SERPING1, IFIT3, OAS1, HSXIAPAF1, G1P3, МХ1, OAS3, IFI27, DNAPTP6, LAMP3, EPSTI1, IFI44, OAS2, IFIT2, ISG15;
е. LAMP3, SIGLEC1, DNAPTP6, IFIT2, ETV7, RTP4, SERPING1, HERC5, XAF1, МХ1, EPSTI1, OAS2, OAS1, OAS3, IFIT3, IFI6, USP18, RSAD2, IFI44, LY6E, ISG15, IFI27;
ж. DNAPTP6, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMPS, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, PSAD2, RTP4, SIGLEC1, USP18;
з. SAMD9L, IFI6, IFI44, IFIT2, ZC3HAV1, ETV6, DAPP1, IL1RN, CEACAM1, OAS1, IFI27, OAS3, IFI44L, HERC5, IFIT1, EPSTI1, ISG15, SERPING1, OASL, GBP1, MX1;
и. SAMD9L, IFI6, IFI44, IFIT2, OAS1, IFI27, OAS3, IFI44L, HERC5, IFIT1, EPSTI1, ISG15, SERPING1, OASL, GBP1, MX1;
к. IFI6, RSAD2, IFI44, IFI44L, IFI27, MX1, IFIT1, ISG15, LAMP3, OAS3, OAS1, EPSTI1, IFIT3, OAS2, SIGLEC1, USP18;
л. IFI6, RSAD2, IFI44, IFI44L, IFI27;
м. MX1, IFIT1, IFI6, RSAD2, IFI44, IFI44L, IFI27;
н. OAS2, OAS1, MX1, IFIT1, IFI6, RSAD2, IFI44, IFI44L, IFI27.
3. Способ по п.2, в котором профиль экспрессии ФД маркеров, индуцируемых ИФН I типа или ИФНα, дополнительно включает гены NOG, SLC4A1, PRSS33 и FEZ1 с пониженной регуляцией экспрессии или действия.
4. Способ по п.1, в котором профиль экспрессии ФД маркеров, индуцируемых ИФН I типа или ИФНα, дополнительно включает:
а. повышенные уровни в сыворотке полипептидов ракового антигена 125, ферритина, тканевого фактора или ММР-3; или
б. пониженные уровни в сыворотке полипептидов EGF, тромбопоэтипа или лиганда CD40.
5. Способ по п.1, в котором профиль экспрессии ФД маркеров, индуцируемых ИФН I типа или ИФНα, включает гены NOG, SLC4A1, PRSS33 и FEZ1 с пониженной регуляцией экспрессии или действия.
6. Способ по п.1, в котором профиль экспрессии ФД маркеров, индуцируемых ИФН I типа или ИФНα, включает повышенную регуляцию экспрессии или действия по меньшей мере подтипов 1, 2, 8 и 14 ИФНα.
7. Способ по п.1, в котором агентом является MEDI-545.
8. Способ по п.1, в котором агентом является антитело, специфичное в отношении одного или нескольких подтипов ИФН I типа или ИФНα и отличное от MEDI-545.
9. Способ по п.1, в котором агент является антителом, введенным в дозе примерно 0,03-30 мг/кг, 0,3-3 мг/кг или 0,03-1 мг/кг.
10. Способ по п.1, в котором агент нейтрализует профиль экспрессии ФД маркеров, индуцируемых ИФН I типа- или ИФНα, у пациента по меньшей мере на 10%, по меньшей мере на 20%, по меньшей мере на 30%, по меньшей мере на 40% или по меньшей мере на 50%.
11. Способ по п.1, в котором ИФН I типа или ИФНα-опосредованное заболевание или расстройство является волчанкой, псориазом, васкулитом, саркоидозом, синдромом Шегрена или идиопатическим воспалительным миозитом.
12. Способ нейтрализации профиля экспрессии ФД маркеров, индуцируемых ИФН I типа или ИФНα, у пациента, нуждающегося в этом, включающий:
введение агента, который связывает и модулирует ИФН I типа или ИФНα-индуцируемое действие у пациента;
в котором агент нейтрализует профиль экспрессии ФД маркеров, индуцируемых ИФН I типа или ИФНα, у пациента.
13. Способ выявления пациента в качестве кандидата для применения терапевтического агента, который связывает и модулирует действие ИФНα, включающий:
выявление наличия или отсутствия профиля экспрессии ФД маркеров, индуцируемых ИФНα, в образце, взятом у пациента,
причем выявление наличия профиля экспрессии ФД маркеров, индуцируемых ИФНα, характеризует пациента в качестве кандидата для применения терапевтического агента, который связывает и модулирует действие ИФНα.
14. Способ по п.13, в котором профиль экспрессии ФД маркеров, индуцируемых ИФНα, включает набор генов с повышенной регуляцией экспрессии, выбранных из группы, включающей:
а. МХ1, LY6E, IFI27, OAS1, IFIT1, IFI6, IFI44L, ISG15, LAMP3, OASL, RSAD2, IFI44;
б. IFI27, SIGLEC1, RSAD2, IFI6, IFI44L, IFI44, USP18, IFIT2, SAMD9L, BIRC4BP, DNAPTP6, OAS3, LY6E, IFIT1, LIPA, LOC129607, ISG15, PARP14, МХ1, OAS2, OASL, CCL2, HERC5, OAS1;
в. IFIT1, IFIT3, IRF7, IFI6, IL6ST, IRF2, LY6E, MARCKS, МХ1, МХ2, OAS1, EIF2AK2, ISG15, STAT2, OAS3, IFI44, IFI44L, HERC5, RAB8B, LILRA5, RSAD2, FCHO2;
г. SERPING1, IFIT2, IPIT3, IFI6, LY6E, МХ1, OAS1, ISG15, IFI27, OAS1, ISG15, IFI27, OAS3, IFI44, LAMP3, DNAPTP6, ETV7, HERC5, OAS2, USP18, XAF1, RTP4, SIGLEC1, EPSTI1;
д. RTP4, RSAD2, HERC5, SIGLEC1, USP18, LY6E, ETV7, SERPING1, IFIT3, OAS1, HSXIAPAF1, G1P3, МХ1, OAS3, IFI27, DNAPTP6, LAMP3, EPSTI1, IFI44, OAS2, IFIT2, ISG15;
е. LAMP3, SIGLEC1, DNAPTP6, IFIT2, ETV7, RTP4, SERPING1, HERC5, XAF1, МХ1, EPSTI1, OAS2, OAS1, OAS3, IFIT3, IFI6, USP18, RSAD2, IFI44, LY6E, ISG15, IFI27;
ж. DNAPTP6, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, МХ1, OAS1, OAS2, OAS3, PLSCR1, PSAD2, RTP4, SIGLEC1, USP18;
з. SAMD9L, IFI6, IFI44, IFIT2, ZC3HAV1, ETV6, DAPP1, IL1RN, СЕАСАМ1, OAS1, IFI27, OAS3, IFI44L, HERC5, IFIT1, EPSTI1, ISG15, SERPING1, OASL, GBP1, МХ1;
и. SAMD9L, IFI6, IFI44, IFIT2, OAS1, IFI27, OAS3, IFI44L, HERC5, IFIT1, EPSTI1, ISG15, SERPING1, OASL, GBP1, МХ1;
к. IFI6, RSAD2, IFI44, IFI44L, IFI27, МХ1, IFIT1, ISG15, LAMP3, OAS3, OAS1, EPSTI1, IFIT3, OAS2, SIGLEC1, USP18;
л. IFI6, RSAD2, IFI44, IFI44L, IFI27.
15. Способ по п.14, в котором экспрессия или действие с повышенной регуляцией включают:
а. по меньшей мере двухкратное увеличение экспрессии одного или нескольких генов,
б. по меньшей мере трехкратное увеличение экспрессии одного или нескольких генов,
в. увеличение уровней иРНК одного или нескольких генов,
г. увеличение уровней белков одного или нескольких генов, или
д. увеличение ферментативной активности белка, экспрессированного с одного или нескольких генов.
16. Способ по п.13, в котором профиль экспрессии ФД маркеров, индуцируемых ИФН I типа или ИФНα, включает:
а. пониженную регуляцию экспрессии или действия генов NOG, SLC4A1, PRSS33, FEZ1;
б. повышенные уровни в сыворотке полипептидов ракового антигена 125, ферритина, тканевого фактора и ММР-3, или
в. пониженные уровни в сыворотке полипептидов EGF, тромбопоэтина и лиганда CD40.
17. Способ по п.13, в котором у пациента диагностируют расстройство, выбранное из группы, включающей волчанку, идиопатический воспалительный миозит, синдромом Шегрена, васкулит, саркоидоз и псориаз.
18. Способ по п.13, в котором терапевтическим агентом является антитело MEDI-545.
19. Способ по п.13, в котором терапевтическим агентом является антитело, специфичное в отношении одного или нескольких подтипов ИФН I типа или ИФНα и отличное от MEDI-545.
20. Набор зондов, представляющих полинуклеотиды, которые специфически выявляют экспрессию какого-либо одного из следующих наборов генов:
а. МХ1, LY6E, IFI27, OAS1, IFIT1, IFI6, IFI44L, ISG15, LAMP3, OASL, RSAD2, IFI44; или
б. IFI27, SIGLEC1, RSAD2, IFI6, IFI44L, IFI44. USP18, IFIT2, SAMD9L, BIRC4BP, DNAPTP6, OAS3, LY6E, IFIT1, LIPA, LOC129607, ISG15, PARP14, МХ1, OAS2, OASL, CCL2, HERC5, OAS1; или
в. IFIT1, IFIT3, IRF7, IFI6, IL6ST, IRF2, LY6E, MARCKS, МХ1, МХ2, OAS1, EIF2AK2, ISG15, STAT2, OAS3, IFI44, IFI44L, HERC5, RAB8B, LILRA5, RSAD2, FCHO2; или
г. SERPING1, IFIT2, IFIT3, IFI6, LY6E, МХ1, OAS1, ISG15, IFI27, OAS1, ISG15, IFI27, OAS3, IFI44, LAMP3, DNAPTP6, ETV7, HERC5, OAS2, USP18, XAF1, RTP4, SIGLEC1, EPSTI1; или
д. RTP4, RSAD2, HERC5, SIGLEC1, USP18, LY6E, ETV7, SERPING1, IFIT3, OAS1, HSXIAPAF1, G1P3, МХ1, OAS3, IFI27, DNAPTP6, LAMP3, EPSTI1, IFI44, OAS2, IFIT2, ISG15; или
е. LAMP3, SIGLEC1, DNAPTP6, IFIT2, ETV7, RTP4, SERPING1, HERC5, XAF1, МХ1, EPSTI1, OAS2, OAS1, OAS3, IFIT3, IFI6, USP18, RSAD2, IFI44, LY6E, ISG15, IFI27; или
ж. DNAPTP6, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, МХ1, OAS1, OAS2, OAS3, PLSCR1, PSAD2, RTP4, SIGLEC1, USP18; или
з. SAMD9L, IFI6, IFI44, IFIT2, ZC3HAV1, ETV6, DAPP1, IL1RN, СЕАСАМ1, OAS1, IFI27, OAS3, IFI44L, HERC5, IFIT1, EPSTI1, ISG15, SERPING1, OASL, GBP1, МХ1; или
и. SAMD9L, IFI6, IFI44, IFIT2, OAS1, IFI27, OAS3, IFI44L, HERC5, IFIT1, EPSTI1, ISG15, SERPING1, OASL, GBP1, МХ1; или.
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BRPI0720035A2 (pt) * | 2006-12-06 | 2019-05-07 | Medimmune, Llc | métodos para tratar um paciente tendo uma doença ou distúrbio, para tratar um paciente com doença autoimune, para neutralizar um perfil de expressão do marcador pd indutível por ifn do tipo 1 ou ifnalfa em um paciente, para monitorar ou prognosticar progressão de doença autoimune de um paciente, para monitorar a progressão da doença de um paciente que recebe o tratamento com um agente terapêutico que liga-se a e modula a atividade de ifnalfa, para identificar um paciente como um candidato para um agente terapêutico que liga-se a e modula a atividade de ifnalfa, para diagnosticar um paciente como tendo um distùrbio associado com níveis aumentados de ifnalfa, para identificar um terapêutico candidato para o tratamento de distùrbios mediados por ifnalfa e para detectar atividade de ifn em uma amostra, conjunto de sondas, e, kit |
AU2008232902B2 (en) * | 2007-03-30 | 2013-10-03 | Medlmmune, Llc | Antibody formulation |
KR20120101340A (ko) * | 2009-09-03 | 2012-09-13 | 메디뮨 엘엘씨 | 1형 인터페론 진단 |
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