CN114539417A - 一种有效去除双特异性抗体同源二聚体的层析纯化工艺 - Google Patents
一种有效去除双特异性抗体同源二聚体的层析纯化工艺 Download PDFInfo
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- CN114539417A CN114539417A CN202011347267.XA CN202011347267A CN114539417A CN 114539417 A CN114539417 A CN 114539417A CN 202011347267 A CN202011347267 A CN 202011347267A CN 114539417 A CN114539417 A CN 114539417A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
Abstract
Description
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CN202011347267.XA CN114539417A (zh) | 2020-11-26 | 2020-11-26 | 一种有效去除双特异性抗体同源二聚体的层析纯化工艺 |
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CN202011347267.XA CN114539417A (zh) | 2020-11-26 | 2020-11-26 | 一种有效去除双特异性抗体同源二聚体的层析纯化工艺 |
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20140336361A1 (en) * | 2011-10-11 | 2014-11-13 | Genentech, Inc. | Assembly of bispecific antibodies |
CN104592393A (zh) * | 2015-01-21 | 2015-05-06 | 武汉友芝友生物制药有限公司 | 一种双特异性抗体cd19×cd3的构建及应用 |
WO2018190677A2 (en) * | 2017-04-14 | 2018-10-18 | Cj Healthcare Corporation | Method for purifying analogous antibody using cation-exchange chromatography |
CN109678951A (zh) * | 2018-12-27 | 2019-04-26 | 上海药明生物技术有限公司 | 在亲和层析纯化中减少抗体多聚的方法 |
CN110066314A (zh) * | 2019-04-01 | 2019-07-30 | 上海药明生物技术有限公司 | 一种高效提高多聚体分离分辨率的亲和纯化工艺 |
WO2020061478A2 (en) * | 2018-09-21 | 2020-03-26 | Teneobio, Inc. | Methods for purifying heterodimeric, multispecific antibodies |
-
2020
- 2020-11-26 CN CN202011347267.XA patent/CN114539417A/zh active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20140336361A1 (en) * | 2011-10-11 | 2014-11-13 | Genentech, Inc. | Assembly of bispecific antibodies |
CN104592393A (zh) * | 2015-01-21 | 2015-05-06 | 武汉友芝友生物制药有限公司 | 一种双特异性抗体cd19×cd3的构建及应用 |
WO2018190677A2 (en) * | 2017-04-14 | 2018-10-18 | Cj Healthcare Corporation | Method for purifying analogous antibody using cation-exchange chromatography |
WO2020061478A2 (en) * | 2018-09-21 | 2020-03-26 | Teneobio, Inc. | Methods for purifying heterodimeric, multispecific antibodies |
CN109678951A (zh) * | 2018-12-27 | 2019-04-26 | 上海药明生物技术有限公司 | 在亲和层析纯化中减少抗体多聚的方法 |
CN110066314A (zh) * | 2019-04-01 | 2019-07-30 | 上海药明生物技术有限公司 | 一种高效提高多聚体分离分辨率的亲和纯化工艺 |
Non-Patent Citations (2)
Title |
---|
YI FENG LEE等: "Modeling of bispecific antibody elution in mixed-mode cation-exchange chromatography", 《J SEP SCI.》, vol. 40, no. 18, pages 3632, XP055411884, DOI: 10.1002/jssc.201700313 * |
ZENJIRO SAMPEI等: "Identification and Multidimensional Optimization of an Asymmetric Bispecific IgG Antibody Mimicking the Function of Factor VIII Cofactor Activity", 《PLOS ONE》, vol. 8, no. 2, pages 57479 * |
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