RU2007127848A - Аффинные лиганды, связывающие антитела - Google Patents

Аффинные лиганды, связывающие антитела Download PDF

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RU2007127848A
RU2007127848A RU2007127848/13A RU2007127848A RU2007127848A RU 2007127848 A RU2007127848 A RU 2007127848A RU 2007127848/13 A RU2007127848/13 A RU 2007127848/13A RU 2007127848 A RU2007127848 A RU 2007127848A RU 2007127848 A RU2007127848 A RU 2007127848A
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arg
gly
dap
dbhba
phe
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RU2007127848/13A
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Иб ЙОХАННСЕН (DK)
Иб ЙОХАННСЕН
Моника Рамос ГАЛЬЕГО (DK)
Моника Рамос ГАЛЬЕГО
Ройс МАЙКЛ (DK)
Ройс МАЙКЛ
Франц НОТЕЛЬФЕР (DE)
Франц НОТЕЛЬФЕР
Дороти АМБРОЗИУС (DE)
Дороти АМБРОЗИУС
Александер ЯКОБИ (DE)
Александер ЯКОБИ
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Ново Нордиск А/С (DK)
Ново Нордиск А/С
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    • B01J20/3217—Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond
    • B01J20/3219—Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond involving a particular spacer or linking group, e.g. for attaching an active group
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    • B01J20/3244—Non-macromolecular compounds
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    • B01J20/3248—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such
    • B01J20/3251—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such comprising at least two different types of heteroatoms selected from nitrogen, oxygen or sulphur
    • C—CHEMISTRY; METALLURGY
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum
    • C07K16/065—Purification, fragmentation
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    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
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    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
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    • C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
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    • C07K5/08—Tripeptides
    • C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
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    • C07K5/10—Tetrapeptides
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    • C—CHEMISTRY; METALLURGY
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Claims (10)

1. Материал твердого носителя, имеющий ковалентно иммобилизованный на нем аффинный лиганд, где указанный лиганд содержит одну или несколько гидрофобных функциональных групп и одну или несколько катионных функциональных групп,
где, по меньшей мере, одна гидрофобная функциональная группа отделена, по меньшей мере, от одной катионной функциональной группы расстоянием между связями от 5 до 20 Å,
где указанный лиганд состоит из менее чем 5 остатков и имеет молекулярную массу от 120 до 1000 Да.
2. Материал твердого носителя по п.1, в котором указанная аффинная смола имеет емкость связывания, большую, чем 5 мг моноклонального антитела на 1 мл аффинной смолы.
3. Материал твердого носителя по любому из предыдущих пунктов, где аффинный лиганд содержит или состоит из ковалентно связанных остатков X1-X2-X3, где X1, X2 и/или X3 необязательно присоединен к линкерному остатку.
4. Материал твердого носителя по п.3, в котором остаток X1 выбирают из группы, состоящей из Arg, Phe, PPC, DBHBA, SAA, DAP, DAB, (DBHBA)2-DAP, (MDCA)2-DAP, DPBBA, DBBA, PCAA, DPPAA, Trp, TMPPA и DBHPA.
5. Материал твердого носителя по п.3, в котором остаток X2 выбирают из группы, состоящей из Arg, Asn, Leu, Lys, Phe, Pro, PPC, DAP, DAB, His, Trp, Tyr и Ser.
6. Материал твердого носителя по п.3, в котором остаток X3 выбирают из группы, состоящей из Arg, Asn, Pro, PPC, Asp, Orn и (1H2NA)Dap.
7. Материал твердого носителя по п. 1, в котором лиганд содержит или состоит из 3 ковалентно связанных остатков X1-X2-X3,
где указанные ковалентно связанные остатки дополнительно ковалентно связаны с линкером L фрагмента L-PM, где L представляет собой линкер и PM представляет собой материал твердого носителя, предпочтительно полимерную матрицу, необязательно, в поперечно-сшитой форме и/или в форме шариков,
где X1 представляет собой природную или неприродную аминокислоту в D- и/или L-конфигурации или остаток карбоновой кислоты, содержащий необязательно замещенную ароматическую группу,
где X2 представляет собой природную или неприродную аминокислоту в D- и/или L-конфигурации либо остаток карбоновой кислоты, содержащий необязательно замещенную ароматическую группу, при условии, что X2 не представляет собой остаток треонина, и
где X3 представляет собой природную или неприродную аминокислоту в D- и/или L-конфигурации либо остаток карбоновой кислоты, содержащий необязательно замещенную ароматическую группу,
где, по меньшей мере, один из X1, X2 и X3 содержит катионную функциональную группу и где, по меньшей мере, один из X1, X2 и X3 содержит гидрофобную функциональную группу,
где X1 выбирают из L-Arg, D-Lys, D-Phe, D-Pro, INA, PPC, DBHBA, 3HBA, 4HBA и SAA;
где X2 выбирают из L-Arg, L-Asn, D-Leu, D-Lys, D-Phe, D-Pro, L-Pro, AIB, AHX, INA, NLE и PPC и
где X3 выбирают из L-Arg, L-Asn, D-Lys, D-Phe, D-Pro, L-Pro и PPC.
8. Материал твердого носителя по п. 1, в котором лиганд выбран из группы, состоящей из
H2N-(D)Phe-(L)Arg-(L)Arg-Gly-OH (SEQ ID NO: 1),
H2N-(L)Arg-(D)Phe-(L)Arg-Gly-OH (SEQ ID NO: 2),
HN-PPC-(D)Pro-(L)Arg-Gly-OH (SEQ ID NO: 3),
DBBA-(L)His-(L)Arg-Gly-OH,
DBBA-His-Arg-Gly-OH,
DBBA-His-Arg-Arg-Gly-OH (SEQ ID NO: 5),
DPPBA-(L)Phe-(L)Arg-Gly-OH,
PCAA-(L)Phe-(L)Arg-Gly-OH,
DPPBA-(L)Lys-(L)Arg-Gly-OH,
SAA-(L)Arg-(L)Pro-Gly-OH,
SAA-(L)Pro-(L)Arg-Gly-OH,
DBHBA-(L)Arg-(L)Asn-Gly-OH,
DBHBA-(L)Asn-(L)Arg-Gly-OH,
DPPBA-(L)Trp-(L)Arg-Gly-OH,
(MDCA)2-DAP-(L)Arg-(L)Orn-Gly-OH (SEQ ID NO: 6),
(MDCA)2-DAP-(L)Arg-(L)Asp-Gly-OH (SEQ ID NO: 7),
DPPAA-(L)Phe-(L)Arg-Gly-OH,
DPPAA-PPC-(L)Arg-Gly-OH,
DBHBA-(D)Phe-(D)Arg-Gly-OH,
DPPAA-(D)tyr-(D)Arg-Gly-OH,
(DPPA)2-DAP-(L)Arg-(L)Orn-Gly-OH (SEQ ID NO: 10),
(DBHBA)2-DAP-(L)Arg-(L)Arg-Gly-OH (SEQ ID NO: 11),
DBHBA-DAP-Arg-Gly-OH,
DBHBA-DAP-Arg-Arg-Gly-OH (SEQ ID NO: 11),
(DBHBA)2-DAP-Arg-Gly-OH,
(DBHBA)3-DAP-Arg-Arg-Gly-OH (SEQ ID NO: 11),
TMPPA-(L)Trp-(L)Arg-Gly-OH, и
DBHPA-(L)Arg-(L)Orn-Gly-OH.
9. Материал твердого носителя по п. 8, в котором лиганд выбирают из группы, состоящей из DBBA-(L)His-(L)Arg-Gly-OH и (DBHBA)2-DAP-(L)Arg-(L)Arg-Gly-OH (SEQ ID NO: 11).
10. Способ выделения антител или их производных, включающий стадии (i) предоставления материала твердого носителя, имеющего ковалентно иммобилизованный на нем аффинный лиганд, как определено в любом из пп.1-9, (ii) предоставления образца, содержащего антитело, имеющее сродство к указанному лиганду, (iii) приведения в контакт указанного лиганда с указанным образцом, содержащим указанное антитело, (iv) селективного связывания указанного антитела, когда указанное антитело содержится в указанном образце, и (v) селективного выделения указанного антитела, когда указанное антитело содержится в указанном образце.
RU2007127848/10A 2004-12-23 2005-12-23 Аффинные лиганды, связывающие антитела RU2440582C2 (ru)

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TWI440469B (zh) 2008-09-26 2014-06-11 Chugai Pharmaceutical Co Ltd Improved antibody molecules
SG178173A1 (en) * 2009-07-28 2012-03-29 Instraction Gmbh Specific sorbent for binding proteins and peptides, and separation method using the same
WO2011041327A1 (en) * 2009-10-01 2011-04-07 The Board Of Trustees Of The Leland Stanford Junior University Light controlled protein dimerization in cells
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