RU2001119156A - The expression system for factor VIII - Google Patents

The expression system for factor VIII

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Publication number
RU2001119156A
RU2001119156A RU2001119156/13A RU2001119156A RU2001119156A RU 2001119156 A RU2001119156 A RU 2001119156A RU 2001119156/13 A RU2001119156/13 A RU 2001119156/13A RU 2001119156 A RU2001119156 A RU 2001119156A RU 2001119156 A RU2001119156 A RU 2001119156A
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RU
Russia
Prior art keywords
cells
stage
factor viii
protein
human
Prior art date
Application number
RU2001119156/13A
Other languages
Russian (ru)
Other versions
RU2249041C2 (en
Inventor
Миунг-Сэм ЧО
Шэм Йуен ЧЭН
Вильям КЕЛСИ
Хелена ЙИ
Original Assignee
Байер Корпорейшн
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Publication date
Priority claimed from US09/209,916 external-priority patent/US6358703B1/en
Application filed by Байер Корпорейшн filed Critical Байер Корпорейшн
Publication of RU2001119156A publication Critical patent/RU2001119156A/en
Application granted granted Critical
Publication of RU2249041C2 publication Critical patent/RU2249041C2/en

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Claims (19)

1. Способ получения клеток, экспрессирующих белок, обладающий прокоагулирующей активностью фактора VIII, включающий следующие последовательные этапы: a) получение клеток исключительно человеческого происхождения, b) взаимодействие клеток стадии а) с вектором в условиях, позволяющих вектору проникнуть в клетки, причем вектор включает селективный маркер и последовательность, кодирующую белок, обладающий прокоагулирующей активностью фактора VIII, оперативно связанную с промотором, c) отбор клеток стадии b) при помощи агента селекции и d) выделение из клеток, полученных на стадии с) отдельных клонов, экспрессирующих большие количества белка, обладающего прокоагулирующей активностью фактора VIII.1. A method of producing cells expressing a protein having procoagulating activity of factor VIII, comprising the following sequential steps: a) obtaining cells of exclusively human origin, b) interaction of the cells of stage a) with the vector under conditions allowing the vector to penetrate the cells, the vector comprising selective marker and sequence encoding a protein having procoagulating activity of factor VIII operably linked to a promoter, c) selection of cells of stage b) using a selection agent and d) isolated and from the cells obtained in step c) of individual clones expressing large amounts of a protein having procoagulating factor VIII activity. 2. Способ по п.1, включающий далее стадию e) адаптации клонов стадии d) к росту в среде, свободной от белков плазмы.2. The method according to claim 1, further comprising stage e) adaptation of the clones of stage d) to growth in a medium free of plasma proteins. 3. Способ по п.1, где клетки стадии а) являются гибридами клеток лимфомы человека и клеток 293 S.3. The method according to claim 1, where the cells of stage a) are hybrids of human lymphoma cells and 293 S. cells. 4. Способ по п.1, где клетки стадии а) являются гибридами клеток 2В8 (АТСС CRL-12569) и клеток 293S.4. The method according to claim 1, where the cells of stage a) are hybrids of 2B8 cells (ATCC CRL-12569) and 293S cells. 5. Способ по п.1, где клетки стадии а) являются клетками НКВ11 (АТСС CRL-12568).5. The method according to claim 1, where the cells of stage a) are NKB11 cells (ATCC CRL-12568). 6. Способ по п.1, где стадии с) и d) выполняются больше, чем один раз.6. The method according to claim 1, where stages c) and d) are performed more than once. 7. Способ по п.1, где последовательность стадии b) кодирует последовательность, представленную на Фиг.1 (SEQ ID NO: 1).7. The method according to claim 1, where the sequence of step b) encodes the sequence shown in Figure 1 (SEQ ID NO: 1). 8. Способ по п.1, где последовательность стадии b) кодирует фактор VIII человека.8. The method according to claim 1, where the sequence of stage b) encodes a human factor VIII. 9. Способ по п.1, где селективный маркер стадии b) - dhfr и агент селекции стадии с) - метотрексат.9. The method according to claim 1, where the selective marker of stage b) is dhfr and the selection agent of stage c) is methotrexate. 10. Способ по п.1, где селективный маркер стадии b) - gs и агент селекции стадии с) - метионин сульфоксиимин.10. The method according to claim 1, where the selective marker of stage b) is gs and the selection agent of stage c) is methionine sulfoxyimine. 11. Способ по п.1, где селективный маркер стадии b) - mdr и агент селекции стадии с) - колхицин.11. The method according to claim 1, where the selective marker of stage b) is mdr and the selection agent of stage c) is colchicine. 12. Способ получения белка, обладающего активностью фактора VIII, включающий выращивание клеток, полученных способом по п.1, в ростовой среде, и дальнейшее выделение из среды белка, обладающего активностью фактора VIII.12. A method of obtaining a protein having a factor VIII activity, comprising growing cells obtained by the method according to claim 1, in a growth medium, and further isolating a protein having a factor VIII activity from the medium. 13. Способ по п.11, где белок является фактором VIII человека.13. The method according to claim 11, where the protein is a human factor VIII. 14. Способ по п.11, где белок имеет аминокислотную последовательность, приведенную на Фиг.1 (SEQ ID NO: 1).14. The method according to claim 11, where the protein has the amino acid sequence shown in Figure 1 (SEQ ID NO: 1). 15. Линия клеток человека, полученная из клеток лимфомы человека и клеток 293S, экспрессирующая на высоком уровне белок, обладающий активностью фактора VIII.15. A human cell line derived from human lymphoma cells and 293S cells expressing at a high level a protein having factor VIII activity. 16. Линия клеток человека по п.14, где линия клеток человека получена из клеток HKB11(ATCCCRL-12568).16. The human cell line of claim 14, wherein the human cell line is derived from HKB11 cells (ATCCCRL-12568). 17. Линия клеток человека, полученная из клеток лимфомы человека и клеток 293S, экспрессирующая на высоком уровне белок, обладающий активностью фактора VIII, при выращивании в среде, свободной от белков плазмы.17. The human cell line obtained from human lymphoma cells and 293S cells, expressing at a high level a protein having the activity of factor VIII, when grown in a medium free of plasma proteins. 18. Клеточная линия по п.16, где клеточная линия получена из клеток НКВ11 (АТСС CRL-12568).18. The cell line according to clause 16, where the cell line is obtained from NKB11 cells (ATCC CRL-12568). 19. Клеточная линия, обозначенная 20В8 (АТСС CRL-12582).19. The cell line designated 20B8 (ATCC CRL-12582).
RU2001119156/13A 1998-12-10 1999-12-08 Method for preparing and isolating protein eliciting activity of factor viii, strain of cells hkb expressing protein eliciting activity of factor viii (variants) RU2249041C2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/209,916 1998-12-10
US09/209,916 US6358703B1 (en) 1998-12-10 1998-12-10 Expression system for factor VIII

Publications (2)

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RU2001119156A true RU2001119156A (en) 2003-07-27
RU2249041C2 RU2249041C2 (en) 2005-03-27

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US (10) US6358703B1 (en)
EP (1) EP1137797B1 (en)
JP (1) JP4240818B2 (en)
KR (1) KR100616028B1 (en)
AT (1) ATE412765T1 (en)
AU (1) AU761801B2 (en)
BG (1) BG65431B1 (en)
BR (1) BRPI9916069B8 (en)
CA (1) CA2354845C (en)
CZ (1) CZ302330B6 (en)
DE (1) DE69939839D1 (en)
DK (1) DK1137797T3 (en)
ES (1) ES2315026T3 (en)
HU (1) HU228489B1 (en)
IL (2) IL143353A0 (en)
NO (1) NO329544B1 (en)
NZ (1) NZ512234A (en)
PL (1) PL200676B1 (en)
PT (1) PT1137797E (en)
RO (1) RO121604B1 (en)
RU (1) RU2249041C2 (en)
SI (1) SI20644B (en)
SK (1) SK286945B6 (en)
TR (1) TR200101592T2 (en)
UA (1) UA77383C2 (en)
WO (1) WO2000034505A1 (en)

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