RU2012133970A - Стабилизированные составы, содержащие антитела к рецептору интерлейкина 6 (il-6r) - Google Patents
Стабилизированные составы, содержащие антитела к рецептору интерлейкина 6 (il-6r) Download PDFInfo
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Abstract
1. Фармацевтический состав, содержащий: (i) антитело человека, специфически связывающееся с рецептором интерлейкина 6 человека (hIL-6R); (ii) гистидин; и (iii) углевод.2. Фармацевтический состав по п.1, где углевод представляет собой сахар, выбранный из группы, состоящей из сахарозы, глюкозы, маннита, лактозы и трегалозы.3. Фармацевтический состав по п.1, где углевод представляет собой сахарозу.4. Фармацевтический состав по любому из пп.1-3, где указанное антитело человека, специфически связывающееся с hIL-6R, содержит вариабельную область тяжелой цепи (HCVR) и вариабельную область легкой цепи (LCVR), где HCVR содержат определяющие комплементарность области тяжелой и легкой цепи (HCDR1-HCDR2-HCDR3/LCDR1-LCDR2-LCDR3) с аминокислотными последовательностями: (i) SEQ ID NO:4-6-8/SEQ ID NO:12-14-16; (ii) SEQ ID NO:20-22-24/SEQ ID NO:28-30-32; (iii) SEQ ID NO:36-38-40/SEQ ID NO:44-46-48; или (iv) SEQ ID NO:52-54-56/SEQ ID NO:60-62-64.5. Фармацевтический состав по п.4, где указанное антитело человека, специфически связывающееся с hIL-6R, содержит пары аминокислотных последовательностей вариабельных областей тяжелой цепи и легкой цепи (HCVR/LCVR), выбранные из группы, состоящей из: (i) SEQ ID NO:2/10; (ii) SEQ ID NO:18/26; (iii) SEQ ID NO:34/42; и (iv) SEQ ID NO:50/58.6. Фармацевтический состав по п.1, где указанное антитело человека, специфически связывающееся с рецептором интерлейкина 6 человека (hIL-6R), содержится в концентрации приблизительно от 5 до 200 мг/мл.7. Фармацевтический состав по п.1, где гистидин содержится в концентрации приблизительно от 5 до 50 мМ.8. Фармацевтический состав по п.1, где углевод содержится в концентрации приблизительно от 1 до 20%.9. Фармацевтический состав по п.1, дополнительно содержащий неионное поверхностно-активное вещество.10. Фармацевтический состав по п.9, г
Claims (33)
1. Фармацевтический состав, содержащий: (i) антитело человека, специфически связывающееся с рецептором интерлейкина 6 человека (hIL-6R); (ii) гистидин; и (iii) углевод.
2. Фармацевтический состав по п.1, где углевод представляет собой сахар, выбранный из группы, состоящей из сахарозы, глюкозы, маннита, лактозы и трегалозы.
3. Фармацевтический состав по п.1, где углевод представляет собой сахарозу.
4. Фармацевтический состав по любому из пп.1-3, где указанное антитело человека, специфически связывающееся с hIL-6R, содержит вариабельную область тяжелой цепи (HCVR) и вариабельную область легкой цепи (LCVR), где HCVR содержат определяющие комплементарность области тяжелой и легкой цепи (HCDR1-HCDR2-HCDR3/LCDR1-LCDR2-LCDR3) с аминокислотными последовательностями: (i) SEQ ID NO:4-6-8/SEQ ID NO:12-14-16; (ii) SEQ ID NO:20-22-24/SEQ ID NO:28-30-32; (iii) SEQ ID NO:36-38-40/SEQ ID NO:44-46-48; или (iv) SEQ ID NO:52-54-56/SEQ ID NO:60-62-64.
5. Фармацевтический состав по п.4, где указанное антитело человека, специфически связывающееся с hIL-6R, содержит пары аминокислотных последовательностей вариабельных областей тяжелой цепи и легкой цепи (HCVR/LCVR), выбранные из группы, состоящей из: (i) SEQ ID NO:2/10; (ii) SEQ ID NO:18/26; (iii) SEQ ID NO:34/42; и (iv) SEQ ID NO:50/58.
6. Фармацевтический состав по п.1, где указанное антитело человека, специфически связывающееся с рецептором интерлейкина 6 человека (hIL-6R), содержится в концентрации приблизительно от 5 до 200 мг/мл.
7. Фармацевтический состав по п.1, где гистидин содержится в концентрации приблизительно от 5 до 50 мМ.
8. Фармацевтический состав по п.1, где углевод содержится в концентрации приблизительно от 1 до 20%.
9. Фармацевтический состав по п.1, дополнительно содержащий неионное поверхностно-активное вещество.
10. Фармацевтический состав по п.9, где указанное неионное поверхностно-активное вещество выбрано из группы, состоящей из полисорбата 20, полисорбата 80 и полиоксиэтиленсорбитанмоноолеата.
11. Фармацевтический состав по п.9, где указанное неионное поверхностно-активное вещество представляет собой полисорбат 20.
12. Фармацевтический состав по п.9, где указанное неионное поверхностно-активное вещество содержится в концентрации приблизительно от 0,01 до 1%.
13. Фармацевтический состав по п.9, содержащий: (i) приблизительно от 25 до 200 мг/мл указанного антитела человека, специфически связывающегося с hIL-6R; (ii) приблизительно от 10 до 25 мМ гистидина; (iii) приблизительно от 5 до 10% сахарозы; и (iv) приблизительно от 0,1 до 0,2% полисорбата 20.
14. Фармацевтический состав по п.9, содержащий: (i) приблизительно 100 мг/мл антитела человека, специфически связывающегося с hIL-6R; (ii) приблизительно 10 мМ гистидина; (iii) приблизительно 10% сахарозы; и (iv) приблизительно 0,2% полисорбата 20.
15. Фармацевтический состав по п.9, дополнительно содержащий аргинин.
16. Фармацевтический состав по п.15, где аргинин содержится в концентрации приблизительно от 5 до 100 мМ.
17. Фармацевтический состав по п.15, где аргинин содержится в концентрации приблизительно от 25 до 50 мМ.
18. Фармацевтический состав по п.15, содержащий: (i) приблизительно 150 мг/мл указанного антитела человека, специфически связывающегося с hIL-6R; (ii) приблизительно 25 мМ гистидина; (iii) приблизительно 5% сахарозы; (iv) приблизительно 0,2% полисорбата 20; и (v) приблизительно 25 мМ аргинина.
19. Фармацевтический состав по п.15, содержащий: (i) приблизительно 175 мг/мл указанного антитела человека, специфически связывающегося с hIL-6R; (ii) приблизительно 25 мМ гистидина; (iii) приблизительно 5% сахарозы; (iv) приблизительно 0,2% полисорбата 20; и (v) приблизительно 50 мМ аргинина.
20. Фармацевтический состав по п.19, где указанное антитело человека, специфически связывающееся с рецептором интерлейкина 6 человека (hIL-6R), содержит пару аминокислотных последовательностей вариабельных областей тяжелой цепи и легкой цепи (HCVR/ LCVR) SEQ ID NO:18/26.
21. Фармацевтический состав по п.19 или 20, где получают по меньшей мере 90% нативной формы указанного антитела после девяти месяцев хранения при 5°C, как определяют посредством эксклюзионной высокоэффективной жидкостной хроматографии (ЭВЭЖХ).
22. Фармацевтический состав п.19 или 20, где получают по меньшей мере 95% нативной формы указанного антитела после девяти месяцев хранения при 5°C, как определяют посредством эксклюзионной высокоэффективной жидкостной хроматографии (ЭВЭЖХ).
23. Фармацевтический состав п.19 или 20, где получают по меньшей мере 96% нативной формы указанного антитела после девяти месяцев хранения при 5°C, как определяют посредством эксклюзионной высокоэффективной жидкостной хроматографии (ЭВЭЖХ).
24. Фармацевтический состав по п.19, где состав демонстрирует вязкость менее чем приблизительно 15 сПуаз.
25. Фармацевтический состав по п.19, где состав демонстрирует вязкость менее чем приблизительно 12 сПуаз.
26. Фармацевтический состав по п.19, где состав демонстрирует вязкость менее чем приблизительно 9 сПуаз.
27. Фармацевтический состав по п.16, содержащийся в стеклянном флаконе.
28. Фармацевтический состав по п.16, содержащийся в шприце.
29. Фармацевтический состав по п.16, содержащийся в микроинфузоре.
30. Фармацевтический состав по п.28, где указанный шприц содержит покрытый фторуглеродом плунжер.
31. Фармацевтический состав по п.28, где указанный шприц представляет собой шприц с низким содержанием вольфрама.
32. Фармацевтический состав содержащий: (i) приблизительно от 5 до 200 мг/мл антитела человека, специфически связывающегося с рецептором интерлейкина 6 человека (hIL-6R); (ii) приблизительно от 5 до 50 мМ гистидина; (iii) приблизительно от 1 до 20% сахарозы; и (iv) приблизительно от 0,01 до 1% полисорбата 20.
33. Фармацевтический состав, содержащий: (i) приблизительно 175 мг/мл антитела человека, специфически связывающегося с рецептором интерлейкина 6 человека (hIL-6R), где указанное антитело содержит пару аминокислотных последовательностей вариабельных областей тяжелой цепи и легкой цепи (HCVR/LCVR) SEQ ID NO:18/26; (ii) приблизительно 25 мМ гистидина; (iii) приблизительно 5% сахарозы; (iv) приблизительно 0,2% полисорбата 20; и (v) приблизительно 50 мМ аргинина.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29322710P | 2010-01-08 | 2010-01-08 | |
| US61/293,227 | 2010-01-08 | ||
| US12/986,223 | 2011-01-07 | ||
| PCT/US2011/020457 WO2011085158A2 (en) | 2010-01-08 | 2011-01-07 | Stabilized formulations containing anti-interleukin-6 receptor (il-6r) antibodies |
| US12/986,223 US9173880B2 (en) | 2010-01-08 | 2011-01-07 | Stabilized formulations containing anti-interleukin-6 receptor (IL-6R) antibodies |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2012133970A true RU2012133970A (ru) | 2014-02-20 |
| RU2554779C2 RU2554779C2 (ru) | 2015-06-27 |
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