JP2016512848A5 - - Google Patents
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- JP2016512848A5 JP2016512848A5 JP2016503420A JP2016503420A JP2016512848A5 JP 2016512848 A5 JP2016512848 A5 JP 2016512848A5 JP 2016503420 A JP2016503420 A JP 2016503420A JP 2016503420 A JP2016503420 A JP 2016503420A JP 2016512848 A5 JP2016512848 A5 JP 2016512848A5
- Authority
- JP
- Japan
- Prior art keywords
- recombinant polypeptide
- antibody
- eluate
- impurities
- support
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229920001184 polypeptide Polymers 0.000 claims 44
- 102000004196 processed proteins & peptides Human genes 0.000 claims 44
- 108090000765 processed proteins & peptides Proteins 0.000 claims 44
- 239000012535 impurity Substances 0.000 claims 31
- 238000000034 method Methods 0.000 claims 27
- 108090001090 Lectins Proteins 0.000 claims 17
- 102000004856 Lectins Human genes 0.000 claims 17
- 239000002523 lectin Substances 0.000 claims 17
- 210000004027 cell Anatomy 0.000 claims 15
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 11
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims 11
- 238000000855 fermentation Methods 0.000 claims 11
- 230000004151 fermentation Effects 0.000 claims 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 11
- 241000235648 Pichia Species 0.000 claims 10
- -1 ML-I-III Proteins 0.000 claims 9
- 102000004169 proteins and genes Human genes 0.000 claims 8
- 108090000623 proteins and genes Proteins 0.000 claims 8
- 229920002684 Sepharose Polymers 0.000 claims 7
- 238000001514 detection method Methods 0.000 claims 7
- 238000012544 monitoring process Methods 0.000 claims 7
- 101001007348 Arachis hypogaea Galactose-binding lectin Proteins 0.000 claims 6
- 238000002965 ELISA Methods 0.000 claims 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 6
- 241000235058 Komagataella pastoris Species 0.000 claims 5
- 230000002538 fungal effect Effects 0.000 claims 5
- 238000004191 hydrophobic interaction chromatography Methods 0.000 claims 5
- 239000003446 ligand Substances 0.000 claims 5
- 239000002609 medium Substances 0.000 claims 5
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 claims 4
- 108010037897 DC-specific ICAM-3 grabbing nonintegrin Proteins 0.000 claims 4
- 241000233866 Fungi Species 0.000 claims 4
- 241000223218 Fusarium Species 0.000 claims 4
- 241000283973 Oryctolagus cuniculus Species 0.000 claims 4
- 241000228143 Penicillium Species 0.000 claims 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 4
- 238000001042 affinity chromatography Methods 0.000 claims 4
- 230000036252 glycation Effects 0.000 claims 4
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims 4
- 238000012434 mixed-mode chromatography Methods 0.000 claims 4
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims 4
- 230000004850 protein–protein interaction Effects 0.000 claims 4
- 239000001488 sodium phosphate Substances 0.000 claims 4
- 229910000162 sodium phosphate Inorganic materials 0.000 claims 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims 4
- 101100022253 Aedes aegypti MAL1 gene Proteins 0.000 claims 3
- 241000228212 Aspergillus Species 0.000 claims 3
- 102100028668 C-type lectin domain family 4 member C Human genes 0.000 claims 3
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- 102100040839 C-type lectin domain family 6 member A Human genes 0.000 claims 3
- 101710125370 C-type lectin domain family 6 member A Proteins 0.000 claims 3
- 102100040840 C-type lectin domain family 7 member A Human genes 0.000 claims 3
- 241000222120 Candida <Saccharomycetales> Species 0.000 claims 3
- 101100005933 Drosophila melanogaster vvl gene Proteins 0.000 claims 3
- 101000766907 Homo sapiens C-type lectin domain family 4 member C Proteins 0.000 claims 3
- 101000749311 Homo sapiens C-type lectin domain family 4 member M Proteins 0.000 claims 3
- 102100033486 Lymphocyte antigen 75 Human genes 0.000 claims 3
- 101710157884 Lymphocyte antigen 75 Proteins 0.000 claims 3
- 102100025354 Macrophage mannose receptor 1 Human genes 0.000 claims 3
- 101710124692 Macrophage mannose receptor 1 Proteins 0.000 claims 3
- 241000235527 Rhizopus Species 0.000 claims 3
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- 101150099477 ail gene Proteins 0.000 claims 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 3
- 239000000919 ceramic Substances 0.000 claims 3
- 238000004587 chromatography analysis Methods 0.000 claims 3
- 108010025838 dectin 1 Proteins 0.000 claims 3
- 238000002296 dynamic light scattering Methods 0.000 claims 3
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- 230000013595 glycosylation Effects 0.000 claims 3
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- 108010084553 jacalin Proteins 0.000 claims 3
- 230000010287 polarization Effects 0.000 claims 3
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- 238000001542 size-exclusion chromatography Methods 0.000 claims 3
- 238000001370 static light scattering Methods 0.000 claims 3
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 claims 3
- 102400000344 Angiotensin-1 Human genes 0.000 claims 2
- 101800000734 Angiotensin-1 Proteins 0.000 claims 2
- 102400000345 Angiotensin-2 Human genes 0.000 claims 2
- 101800000733 Angiotensin-2 Proteins 0.000 claims 2
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- 241001508785 Arxiozyma Species 0.000 claims 2
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 claims 2
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- 241000178289 Botryozyma Species 0.000 claims 2
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 claims 2
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 claims 2
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- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 claims 2
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- 241000283707 Capra Species 0.000 claims 2
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- 102100021866 Hepatocyte growth factor Human genes 0.000 claims 2
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 claims 2
- 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 claims 2
- 101000858064 Homo sapiens C-X-C motif chemokine 13 Proteins 0.000 claims 2
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 claims 2
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 claims 2
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 claims 2
- 101000654356 Homo sapiens Sodium channel protein type 10 subunit alpha Proteins 0.000 claims 2
- 101000654386 Homo sapiens Sodium channel protein type 9 subunit alpha Proteins 0.000 claims 2
- 101000868152 Homo sapiens Son of sevenless homolog 1 Proteins 0.000 claims 2
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 claims 2
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 claims 2
- 102100037850 Interferon gamma Human genes 0.000 claims 2
- 102000006992 Interferon-alpha Human genes 0.000 claims 2
- 108010047761 Interferon-alpha Proteins 0.000 claims 2
- 108010074328 Interferon-gamma Proteins 0.000 claims 2
- 102000003814 Interleukin-10 Human genes 0.000 claims 2
- 108090000174 Interleukin-10 Proteins 0.000 claims 2
- 102000013462 Interleukin-12 Human genes 0.000 claims 2
- 108010065805 Interleukin-12 Proteins 0.000 claims 2
- 102000013691 Interleukin-17 Human genes 0.000 claims 2
- 108050003558 Interleukin-17 Proteins 0.000 claims 2
- 102000003810 Interleukin-18 Human genes 0.000 claims 2
- 108090000171 Interleukin-18 Proteins 0.000 claims 2
- 108010002350 Interleukin-2 Proteins 0.000 claims 2
- 102000000588 Interleukin-2 Human genes 0.000 claims 2
- 102000004388 Interleukin-4 Human genes 0.000 claims 2
- 108090000978 Interleukin-4 Proteins 0.000 claims 2
- 102000004889 Interleukin-6 Human genes 0.000 claims 2
- 108090001005 Interleukin-6 Proteins 0.000 claims 2
- 241000235649 Kluyveromyces Species 0.000 claims 2
- 241001302784 Kodamaea Species 0.000 claims 2
- 241000221479 Leucosporidium Species 0.000 claims 2
- 241000699666 Mus <mouse, genus> Species 0.000 claims 2
- 102000015336 Nerve Growth Factor Human genes 0.000 claims 2
- 108010025020 Nerve Growth Factor Proteins 0.000 claims 2
- 241000221960 Neurospora Species 0.000 claims 2
- 230000004989 O-glycosylation Effects 0.000 claims 2
- 241001236817 Paecilomyces <Clavicipitaceae> Species 0.000 claims 2
- 241001494479 Pecora Species 0.000 claims 2
- 102100033237 Pro-epidermal growth factor Human genes 0.000 claims 2
- 102100022661 Pro-neuregulin-1, membrane-bound isoform Human genes 0.000 claims 2
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 claims 2
- 241000700159 Rattus Species 0.000 claims 2
- 102100031374 Sodium channel protein type 10 subunit alpha Human genes 0.000 claims 2
- 102100031367 Sodium channel protein type 9 subunit alpha Human genes 0.000 claims 2
- 241000235006 Torulaspora Species 0.000 claims 2
- 102000040945 Transcription factor Human genes 0.000 claims 2
- 108091023040 Transcription factor Proteins 0.000 claims 2
- 102100040247 Tumor necrosis factor Human genes 0.000 claims 2
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 claims 2
- 101710181056 Tumor necrosis factor ligand superfamily member 13B Proteins 0.000 claims 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims 2
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- 238000005273 aeration Methods 0.000 claims 2
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- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 claims 2
- 229950006323 angiotensin ii Drugs 0.000 claims 2
- 238000012258 culturing Methods 0.000 claims 2
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- 238000010828 elution Methods 0.000 claims 2
- 229910052587 fluorapatite Inorganic materials 0.000 claims 2
- 239000003102 growth factor Substances 0.000 claims 2
- 229920000140 heteropolymer Polymers 0.000 claims 2
- 108010044853 histidine-rich proteins Proteins 0.000 claims 2
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- 239000005556 hormone Substances 0.000 claims 2
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- 244000005700 microbiome Species 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 238000000569 multi-angle light scattering Methods 0.000 claims 2
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 238000011176 pooling Methods 0.000 claims 2
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- 239000011780 sodium chloride Substances 0.000 claims 2
- 210000005253 yeast cell Anatomy 0.000 claims 2
- GUPXYSSGJWIURR-UHFFFAOYSA-N 3-octoxypropane-1,2-diol Chemical compound CCCCCCCCOCC(O)CO GUPXYSSGJWIURR-UHFFFAOYSA-N 0.000 claims 1
- 239000004475 Arginine Substances 0.000 claims 1
- 241000235172 Bullera Species 0.000 claims 1
- 239000012619 Butyl Sepharose® Substances 0.000 claims 1
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- 102000003816 Interleukin-13 Human genes 0.000 claims 1
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims 1
- 241000228389 Sporidiobolus Species 0.000 claims 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 1
- 238000000149 argon plasma sintering Methods 0.000 claims 1
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- 150000004676 glycans Chemical class 0.000 claims 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000011148 porous material Substances 0.000 claims 1
- 230000006916 protein interaction Effects 0.000 claims 1
- 229910052938 sodium sulfate Inorganic materials 0.000 claims 1
- 235000011152 sodium sulphate Nutrition 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361792935P | 2013-03-15 | 2013-03-15 | |
| US61/792,935 | 2013-03-15 | ||
| PCT/US2014/030558 WO2014145744A1 (en) | 2013-03-15 | 2014-03-17 | Antibody purification and purity monitoring |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016512848A JP2016512848A (ja) | 2016-05-09 |
| JP2016512848A5 true JP2016512848A5 (enExample) | 2017-04-20 |
| JP6472786B2 JP6472786B2 (ja) | 2019-02-20 |
Family
ID=51538079
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016503420A Active JP6472786B2 (ja) | 2013-03-15 | 2014-03-17 | 抗体の精製及び純度のモニタリング |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US9518082B2 (enExample) |
| EP (2) | EP2970865B1 (enExample) |
| JP (1) | JP6472786B2 (enExample) |
| AR (1) | AR095615A1 (enExample) |
| CA (1) | CA2905531C (enExample) |
| ES (1) | ES2834113T3 (enExample) |
| TW (2) | TW201940691A (enExample) |
| WO (1) | WO2014145744A1 (enExample) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9062106B2 (en) | 2011-04-27 | 2015-06-23 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
| US9067990B2 (en) | 2013-03-14 | 2015-06-30 | Abbvie, Inc. | Protein purification using displacement chromatography |
| WO2013158279A1 (en) | 2012-04-20 | 2013-10-24 | Abbvie Inc. | Protein purification methods to reduce acidic species |
| WO2013158273A1 (en) | 2012-04-20 | 2013-10-24 | Abbvie Inc. | Methods to modulate c-terminal lysine variant distribution |
| US9255154B2 (en) | 2012-05-08 | 2016-02-09 | Alderbio Holdings, Llc | Anti-PCSK9 antibodies and use thereof |
| US9512214B2 (en) | 2012-09-02 | 2016-12-06 | Abbvie, Inc. | Methods to control protein heterogeneity |
| SG11201507230PA (en) | 2013-03-12 | 2015-10-29 | Abbvie Inc | Human antibodies that bind human tnf-alpha and methods of preparing the same |
| US10023608B1 (en) | 2013-03-13 | 2018-07-17 | Amgen Inc. | Protein purification methods to remove impurities |
| US9017687B1 (en) | 2013-10-18 | 2015-04-28 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
| WO2014151878A2 (en) | 2013-03-14 | 2014-09-25 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosacharides |
| ES2834113T3 (es) * | 2013-03-15 | 2021-06-16 | H Lundbeck As | Purificación de anticuerpos y monitorización de la pureza |
| EP3052640A2 (en) | 2013-10-04 | 2016-08-10 | AbbVie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
| US9181337B2 (en) | 2013-10-18 | 2015-11-10 | Abbvie, Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
| US9085618B2 (en) | 2013-10-18 | 2015-07-21 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
| WO2015073884A2 (en) | 2013-11-15 | 2015-05-21 | Abbvie, Inc. | Glycoengineered binding protein compositions |
| EP3169710A1 (en) * | 2014-07-14 | 2017-05-24 | Amgen Inc. | Crystalline antibody formulations |
| TW201628649A (zh) | 2014-10-09 | 2016-08-16 | 再生元醫藥公司 | 減少醫藥調配物中微可見顆粒之方法 |
| JP2017537891A (ja) * | 2014-10-31 | 2017-12-21 | ジェネンテック， インコーポレイテッド | 抗ｉｌ−１７ａ及びｉｌ−１７ｆ交差反応性抗体変異体、ならびにそれらを含む組成物、それらを作製する方法、及び使用する方法 |
| MA42613A (fr) | 2015-08-13 | 2018-06-20 | Amgen Inc | Filtration en profondeur chargée de protéines de liaison à un antigène |
| WO2017040992A1 (en) | 2015-09-04 | 2017-03-09 | Mo Bio Laboratories, Inc. | Methods for co-isolation of nucelic acids and proteins |
| GB2565664A (en) * | 2016-03-07 | 2019-02-20 | Hitachi Chemical Advanced Therapeutics Solutions Llc | A closed system for labelling and selecting live cells |
| CA3020839A1 (en) | 2016-04-15 | 2017-10-19 | Alder Biopharmaceuticals, Inc. | Anti-pacap antibodies and uses thereof |
| KR20230041834A (ko) | 2016-08-16 | 2023-03-24 | 리제너론 파아마슈티컬스, 인크. | 혼합물로부터 개별 항체들을 정량하는 방법 |
| CN106371765B (zh) * | 2016-08-29 | 2020-09-18 | 成都科鸿达科技有限公司 | 一种高效大规模系统的ltl模型检测去内存抖动的方法 |
| CN106293544B (zh) * | 2016-08-29 | 2020-06-30 | 成都科鸿达科技有限公司 | 一种高效大规模系统的ltl模型检测方法 |
| CN119492842A (zh) | 2016-10-25 | 2025-02-21 | 里珍纳龙药品有限公司 | 用于色谱数据分析的方法和系统 |
| JP6829357B2 (ja) * | 2017-03-17 | 2021-02-10 | 住友ベークライト株式会社 | 抗体の糖鎖検出法 |
| CN107033236B (zh) * | 2017-05-05 | 2021-03-23 | 浙江大学 | 一种从酵母发酵液中分离人血白蛋白的混合模式层析方法 |
| CN107254502A (zh) * | 2017-07-26 | 2017-10-17 | 兰州名德农牧科技有限公司 | 一种动物蛋白酶制备羊胎盘肽的方法 |
| MA49962A (fr) * | 2017-08-22 | 2020-07-01 | Biogen Ma Inc | Procédés de purification d'anticorps présentant des agrégats réduits à poids moléculaire élevé |
| CN118416215A (zh) | 2017-09-19 | 2024-08-02 | 里珍纳龙药品有限公司 | 减少粒子形成的方法以及由其形成的组合物 |
| KR102825164B1 (ko) * | 2018-03-27 | 2025-06-26 | 브리스톨-마이어스 스큅 컴퍼니 | 자외선 신호를 사용한 단백질 농도의 실시간 모니터링 |
| HUE058711T2 (hu) | 2018-04-20 | 2022-09-28 | Janssen Biotech Inc | Kromatográfiás oszlopos minõség-ellenõrzés anti-IL12/IL23 ellenanyag-készítmények elõállítására szolgáló gyártási eljárásokban |
| CN118599962A (zh) | 2018-04-24 | 2024-09-06 | 凯杰科技有限公司 | 从复杂样品中分离核酸并去除抑制剂 |
| GB201806752D0 (en) * | 2018-04-25 | 2018-06-06 | Ge Healthcare Bioprocess R&D Ab | Method in bioprocess system |
| TWI853823B (zh) | 2018-07-02 | 2024-09-01 | 美商里珍納龍藥品有限公司 | 自混合物製備多肽之系統及方法 |
| SG11202108031VA (en) | 2019-01-30 | 2021-08-30 | Regeneron Pharma | Method of characterization of visible and/or sub-visible particles in biologics |
| EP3934620A1 (en) | 2019-03-05 | 2022-01-12 | Regeneron Pharmaceuticals, Inc. | Human serum albumin in formulations |
| CA3151967A1 (en) | 2019-09-23 | 2021-04-01 | Marina Hincapie | Product quality attribute measurement |
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- 2014-03-17 WO PCT/US2014/030558 patent/WO2014145744A1/en not_active Ceased
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