RU2016130501A - Способы конъюгации - Google Patents
Способы конъюгации Download PDFInfo
- Publication number
- RU2016130501A RU2016130501A RU2016130501A RU2016130501A RU2016130501A RU 2016130501 A RU2016130501 A RU 2016130501A RU 2016130501 A RU2016130501 A RU 2016130501A RU 2016130501 A RU2016130501 A RU 2016130501A RU 2016130501 A RU2016130501 A RU 2016130501A
- Authority
- RU
- Russia
- Prior art keywords
- carbon atoms
- alkyl containing
- antibody
- maytansinoid
- branched
- Prior art date
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- 238000000034 method Methods 0.000 title claims 27
- 230000021615 conjugation Effects 0.000 title 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 12
- 239000003153 chemical reaction reagent Substances 0.000 claims 6
- 239000012636 effector Substances 0.000 claims 6
- 239000000203 mixture Substances 0.000 claims 6
- -1 TGF-a Proteins 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 5
- 230000001588 bifunctional effect Effects 0.000 claims 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
- 125000001424 substituent group Chemical group 0.000 claims 5
- 239000011230 binding agent Substances 0.000 claims 4
- 229940127089 cytotoxic agent Drugs 0.000 claims 4
- 239000002254 cytotoxic agent Substances 0.000 claims 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims 4
- 239000003795 chemical substances by application Substances 0.000 claims 3
- 231100000599 cytotoxic agent Toxicity 0.000 claims 3
- 238000010791 quenching Methods 0.000 claims 3
- 230000000171 quenching effect Effects 0.000 claims 3
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- 102000050554 Eph Family Receptors Human genes 0.000 claims 2
- 108091008815 Eph receptors Proteins 0.000 claims 2
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims 2
- 102000000588 Interleukin-2 Human genes 0.000 claims 2
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- 102000000646 Interleukin-3 Human genes 0.000 claims 2
- 108010002386 Interleukin-3 Proteins 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
- 125000000304 alkynyl group Chemical group 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 150000001450 anions Chemical class 0.000 claims 2
- 239000000427 antigen Substances 0.000 claims 2
- 102000036639 antigens Human genes 0.000 claims 2
- 108091007433 antigens Proteins 0.000 claims 2
- 150000001768 cations Chemical class 0.000 claims 2
- 125000000524 functional group Chemical group 0.000 claims 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims 2
- 229940076264 interleukin-3 Drugs 0.000 claims 2
- 229940028885 interleukin-4 Drugs 0.000 claims 2
- QPPUSXURIGJCFQ-UHFFFAOYSA-N 2-[(2-iodoacetyl)amino]propanoic acid Chemical compound OC(=O)C(C)NC(=O)CI QPPUSXURIGJCFQ-UHFFFAOYSA-N 0.000 claims 1
- IUTPJBLLJJNPAJ-UHFFFAOYSA-N 3-(2,5-dioxopyrrol-1-yl)propanoic acid Chemical compound OC(=O)CCN1C(=O)C=CC1=O IUTPJBLLJJNPAJ-UHFFFAOYSA-N 0.000 claims 1
- NCPQROHLJFARLL-UHFFFAOYSA-N 4-(2,5-dioxopyrrol-1-yl)butanoic acid Chemical compound OC(=O)CCCN1C(=O)C=CC1=O NCPQROHLJFARLL-UHFFFAOYSA-N 0.000 claims 1
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims 1
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- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims 1
- 101150013553 CD40 gene Proteins 0.000 claims 1
- 102100032912 CD44 antigen Human genes 0.000 claims 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 claims 1
- 102100037241 Endoglin Human genes 0.000 claims 1
- 102000051096 EphA2 Receptor Human genes 0.000 claims 1
- 108010055196 EphA2 Receptor Proteins 0.000 claims 1
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 claims 1
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 claims 1
- 101150021185 FGF gene Proteins 0.000 claims 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims 1
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- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims 1
- 102100023915 Insulin Human genes 0.000 claims 1
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- 102000014150 Interferons Human genes 0.000 claims 1
- 108010050904 Interferons Proteins 0.000 claims 1
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- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 claims 1
- 101710127797 Macrophage colony-stimulating factor 1 Proteins 0.000 claims 1
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- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims 1
- GHAZCVNUKKZTLG-UHFFFAOYSA-N N-ethyl-succinimide Natural products CCN1C(=O)CCC1=O GHAZCVNUKKZTLG-UHFFFAOYSA-N 0.000 claims 1
- HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 claims 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 claims 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 claims 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 claims 1
- 102100035721 Syndecan-1 Human genes 0.000 claims 1
- 229940123237 Taxane Drugs 0.000 claims 1
- 102000004338 Transferrin Human genes 0.000 claims 1
- 108090000901 Transferrin Proteins 0.000 claims 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims 1
- 238000005377 adsorption chromatography Methods 0.000 claims 1
- 229950002903 bivatuzumab Drugs 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 230000001268 conjugating effect Effects 0.000 claims 1
- 238000009295 crossflow filtration Methods 0.000 claims 1
- 238000000502 dialysis Methods 0.000 claims 1
- 108010087914 epidermal growth factor receptor VIII Proteins 0.000 claims 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 238000002523 gelfiltration Methods 0.000 claims 1
- 150000007857 hydrazones Chemical class 0.000 claims 1
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- 102000006495 integrins Human genes 0.000 claims 1
- 108010044426 integrins Proteins 0.000 claims 1
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- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 claims 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 239000002245 particle Substances 0.000 claims 1
- 229960002087 pertuzumab Drugs 0.000 claims 1
- 238000001556 precipitation Methods 0.000 claims 1
- 229960004641 rituximab Drugs 0.000 claims 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims 1
- 150000007970 thio esters Chemical class 0.000 claims 1
- 150000003568 thioethers Chemical class 0.000 claims 1
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 1
- 239000012581 transferrin Substances 0.000 claims 1
- 229960000575 trastuzumab Drugs 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K16/46—Hybrid immunoglobulins
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Claims (43)
1. Способ получения очищенного конъюгата в растворе, где конъюгат содержит эффекторную или репортерную молекулу, соединенную со связывающимся с клетками агентом, включающий этапы:
(а) контактирование эффекторной или репортерной молекулы с бифункциональным линкерным реагентом для ковалентного присоединения линкера к эффекторной или репортерной молекуле и приготовления таким образом неочищенной первой смеси, содержащей эффекторные или репортерные молекулы, связанные с линкером,
(б) конъюгацию связывающегося с клетками агента с эффекторной или репортерной молекулой, связанной с линкером, путем реакции неочищенной первой смеси со связывающимся с клетками агентом для приготовления второй смеси, и
(в) воздействие на вторую смесь путем тангенциальной поточной фильтрации, диализа, гелевой фильтрации, адсорбционной хроматографии, селективного осаждения или их комбинации для получения очищенного конъюгата.
2. Способ по п. 1, отличающийся тем, что этап (б) выполняют в растворе с рН от около 4 до около 9.
3. Способ по п. 1, отличающийся тем, что вторая смесь на этапе (б) по большей части свободна от нежелаемых поперечно-сшитых гидролизованных частиц, образовавшихся в результате внутримолекулярных или межмолекулярных реакций.
4. Способ по п. 1, отличающийся тем, что эффекторная молекула является цитотоксичным агентом.
5. Способ по п. 4, отличающийся тем, что цитотоксичный агент является майтансиноидом, таксаном, СС1065 или их аналогом.
6. Способ по п. 4, отличающийся тем, что цитотоксичный агент является майтансиноидом.
7. Способ по п. 6, отличающийся тем, что майтансиноид включает в себя тиоловую группу.
8. Способ по п. 6, отличающийся тем, что майтансиноид является DM1.
9. Способ по п. 6, отличающийся тем, что майтансиноид является DM4.
10. Способ по п. 1, отличающийся тем, что связывающийся с клетками агент является интерферонами, интерлейкином 2, (IL-2), интерлейкином 3 (IL-3), интерлейкином 4 (IL-4), интерлейкином 6 (IL-6), инсулином, EGF, TGF-a, FGF, G-CSF, VEGF, MCSF, GM-CSF, трансферрином или антителами.
11. Способ по п. 10, отличающийся тем, что связывающийся с клетками агент является антителом.
12. Способ по п. 11, отличающийся тем, что антитело является моноклональным антителом.
13. Способ по п. 11, отличающийся тем, что антитело является человеческим или гуманизированным моноклональным антителом.
14. Способ по п. 10, отличающийся тем, что антитело является MY9, анти-В4, С242, или антителом, которое связывается с антигеном, выбранным из группы ЕрСАМ, CD2, CD3, CD4, CD5, CD6, CD11, CD19, CD20, CD22, CD26, CD30, CD33, CD37, CD38, CD40, CD44, CD56, CD79, CD105, CD138, EphA рецепторами, EphB рецепторами, EGFR, EGFRvIII, HER2, HER3, мезотелином, крипто, альфаvбета3, альфаvбета5; альфаvбета6 интегрином.
15. Способ по п. 13, отличающийся тем, что человеческое или гуманизированное антитело является huMy9-6, huB4, huC242, huN901, DS6, CNTO 95, B-B4, трастузумабом, пертузумабом, биватузумабом, зибротузумабом, ритуксимабом, или человеческим или гуманизированным антителом, которое связывается с антигеном, выбранным из группы, состоящей из рецептора EphA2, CD38 и IGF-IR.
16. Способ по п. 1, отличающийся тем, что линкер является расщепляемым или нерасщепляемым линкером.
17. Способ по п. 1, отличающийся тем, что репортерная молекула является радиоизотопом.
18. Способ по п. 2, отличающийся тем, что рН раствора на стадии (b) составляет от примерно 5 до примерно 8.7.
19. Способ по п. 2, отличающийся тем, что рН раствора на стадии (b)) составляет от примерно 6.5 до примерно 8.5.
20. Способ по п. 6, где используется избыточное количество майтансиноида относительно бифункционального линкерного реагента.
21. Способ по п. 6, где способ дополнительно включает этап гашения избыточного майтансиноида в неочищенной первой смеси с помощью реагента для гашения между этапами (а) и (b).
22. Способ по п. 21, где реагент для гашения выбран из группы, состоящей из 4-малеимидомасляной кислоты, 3-малеимидопропионовой кислоты, N-этилмалеимида, йодацетамида и йодацетамидопропионовой кислоты.
23. Способ по п. 1, где бифункциональный линкерный реагент представлен следующей формулой:
где:
Y' представляет собой реакционноспособную функциональную группу, которая может реагировать со связывающимся с клетками агентом;
Q представляет собой функциональную группу, которая может реагировать с цитотоксическим лекарством через дисульфидную, тиоэфирную, сложную тиоэфирную, пептидную, гидразоновую, эфирную, сложную эфирную, карбаматную или амидную связь;
R1, R2, R3, R4, R5, R6, R7, R8, R9, и R10 являются одинаковыми или различными и представляют собой Н, линейный алкил, содержащий 1-6 атомов углерода, разветвленный или циклический алкил, содержащий от 3 до 6 атомов углерода, линейный, разветвленный или циклический алкенил или алкинил, содержащий от 2 до 6 атомов углерода, заряженный заместитель, выбранный из анионов, выбранных из SO3 -, X-SO3 -, ОРО3 2-, X-ОРО3 2-, РО3 2-, Х-РО3 2-, СО2-, и катионов, выбранных из азотсодержащих гетероциклов, N+R11R12R13 и X-N+R11R12R13, или фенила, где:
R11, R12 и R13 являются одинаковыми или различными и представляют собой Н, линейный алкил, содержащий 1-6 атомов углерода, разветвленный или циклический алкил, содержащий от 3 до 6 атомов углерода и X представляет собой фенил или линейный алкил, содержащий 1-6 атомов углерода, или разветвленный или циклический алкил, содержащий 3-6 атомов углерода;
l, m и n представляют собой 0 или целое число от 1 до 4;
А является фенилом или замешенным фенилом, где заместитель является линейным алкилом, содержащим 1-6 атомов углерода, разветвленным или циклическим алкилом, содержащим от 3 до 6 атомов углерода, или заряженным заместителем, выбранным из анионов, выбранных из SO3 - X-SO3 -, ОРО3 2-, Х-ОРО3 2-, РО3 2-, Х-РО3 2-, СO2-, и катионов, выбранных из азотсодержащих гетероциклов, N+R11R12R13 и X-N+R11R12R13, или фенила, где X имеет то же определение, что и выше, и g имеет значение 0 или 1; и
Z является необязательным полиэтиленокси звеном формулы (ОСH2СH2)p, где р является 0 или целым числом от 2 до примерно 1000, или F1-E1-P-E2-F2 звеном, в котором E1 и Е2 являются одинаковыми или различаются и представлены С=O, О, или NR14, где R14 является Н, линейным алкилом, содержащим 1-6 атомов углерода, разветвленным или циклическим алкилом, содержащим от 3 до 6 атомов углерода, линейным, разветвленным или циклическим алкенилом или алкинилом, содержащим от 2 до 6 атомов углерода; Р является пептидным звеном от 2 до 20 аминокислот в длину, где Е1 илиr Е2 могут быть связаны с пептидом через азот на конце, углерод на конце, или через боковую цепь одной из аминокислот пептида; и F1 и F2 являются одинаковыми или различными и представляют собой необязательное полиэтиленокси звено формулы (ОСH2СH2)р, где р является 0 или целым числом от 2 до примерно 1000, при условии, что когда Z не является F1-E1-P-E2-F2, по меньшей мере один из R1, R2, R3, R4, R5, R6, R7, R8, R9, и R10 является заряженным заместителем или когда g равно 1, по меньшей мере один из A, R1, R2, R3, R4, R5, R6, R7, R8, R9, и R10 является заряженным заместителем.
24. Способ по п. 23, где бифункциональный линкерный реагент представлен одной из следующих формул:
25. Способ по п. 23, где бифункциональный линкерный реагент представлен следующей формулой:
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7276497B2 (en) * | 2003-05-20 | 2007-10-02 | Immunogen Inc. | Cytotoxic agents comprising new maytansinoids |
US20110166319A1 (en) * | 2005-02-11 | 2011-07-07 | Immunogen, Inc. | Process for preparing purified drug conjugates |
EP2399609B1 (en) | 2005-08-24 | 2015-03-18 | ImmunoGen, Inc. | Process for preparing maytansinoid antibody conjugates |
UY32560A (es) | 2009-04-29 | 2010-11-30 | Bayer Schering Pharma Ag | Inmunoconjugados de antimesotelina y usos de los mismos |
HUE043645T2 (hu) | 2009-06-03 | 2019-08-28 | Immunogen Inc | Konjugációs módszerek |
CA2818583A1 (en) * | 2010-11-19 | 2012-05-24 | Venus Remedies Limited | Novel conjugates for targeted drug delivery |
PT2691155T (pt) | 2011-03-29 | 2019-02-19 | Immunogen Inc | Preparação de conjugados de anticorpo de maitansinoide por processo de uma etapa |
US9289512B2 (en) | 2011-06-21 | 2016-03-22 | Immunogen, Inc. | Maytansinoid derivatives with peptide linker and conjugates thereof |
SG11201400275YA (en) * | 2011-08-31 | 2014-08-28 | Nikolai Vladimirovich Bovin | Facile laboratory method for localising biomolecules to the surface of cells and viruses |
BR112014014464A2 (pt) * | 2011-12-13 | 2017-06-13 | Immunogen Inc | uso de n-hidroxisuccinimida para melhorar a estabilidade do conjugado |
PT3486248T (pt) | 2012-09-26 | 2021-07-12 | Immunogen Inc | Métodos melhorados para a acilação de maitansinol |
CA2886993A1 (en) | 2012-10-04 | 2014-04-10 | Immunogen, Inc. | Use of a pvdf membrane to purify cell-binding agent cytotoxic agent conjugates |
US20150306242A1 (en) * | 2012-10-04 | 2015-10-29 | Immunogen, Inc. | Process for preparing stable antibody maytansinoid conjugates |
WO2014055893A1 (en) * | 2012-10-04 | 2014-04-10 | Immunogen, Inc. | Use of an ion exchange membrane to remove impurities from cell-binding agent cytotoxic agent conjugates |
WO2014082080A2 (en) * | 2012-11-26 | 2014-05-30 | Callidus Biopharma, Inc. | Methods for coupling targeting peptides onto recombinant lysosomal enzymes for improved treatments of lysosomal storage diseases |
WO2014089177A2 (en) | 2012-12-04 | 2014-06-12 | Massachusetts Institute Of Technology | Compounds, conjugates and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines |
US9901647B2 (en) | 2013-02-28 | 2018-02-27 | Immunogen, Inc. | Conjugates comprising cell-binding agents and cytotoxic agents |
JP6494533B2 (ja) | 2013-02-28 | 2019-04-03 | イミュノジェン・インコーポレーテッド | 細胞結合剤及び細胞毒性剤としてのマイタンシノイドを含む複合体 |
US9498532B2 (en) | 2013-03-13 | 2016-11-22 | Novartis Ag | Antibody drug conjugates |
AP2015008656A0 (en) | 2013-03-15 | 2015-08-31 | Novartis Ag | Antibody drug conjugates |
EP2994164B1 (en) | 2013-05-08 | 2020-08-05 | Zymeworks Inc. | Bispecific her2 and her3 antigen binding constructs |
WO2014194030A2 (en) | 2013-05-31 | 2014-12-04 | Immunogen, Inc. | Conjugates comprising cell-binding agents and cytotoxic agents |
CN108969753B (zh) | 2013-06-14 | 2022-05-10 | 康思葆(北京)生物技术有限公司 | 蛋白-细胞偶联物、其制备方法和用途 |
US10208125B2 (en) | 2013-07-15 | 2019-02-19 | University of Pittsburgh—of the Commonwealth System of Higher Education | Anti-mucin 1 binding agents and uses thereof |
AU2014348552A1 (en) | 2013-11-13 | 2016-06-02 | Zymeworks Inc. | Monovalent antigen binding constructs targeting EGFR and/or HER2 and uses thereof |
WO2015077891A1 (en) | 2013-11-27 | 2015-06-04 | Zymeworks Inc. | Bispecific antigen-binding constructs targeting her2 |
TWI541022B (zh) | 2013-12-18 | 2016-07-11 | 應克隆公司 | 針對纖維母細胞生長因子受體-3(fgfr3)之化合物及治療方法 |
RU2685728C2 (ru) * | 2014-01-29 | 2019-04-23 | Шанхай Хэнжуй Фармасьютикал Ко., Лтд. | Конъюгат лиганд - цитотоксическое лекарственное средство, способ его получения и его применения |
EP3682904A1 (en) | 2014-06-30 | 2020-07-22 | Glykos Finland Oy | Saccharide derivative of a toxic payload and antibody conjugates thereof |
EP3180360A1 (en) | 2014-08-12 | 2017-06-21 | Novartis AG | Anti-cdh6 antibody drug conjugates |
GB201416960D0 (en) * | 2014-09-25 | 2014-11-12 | Antikor Biopharma Ltd | Biological materials and uses thereof |
GB201419184D0 (en) * | 2014-10-28 | 2014-12-10 | Adc Biotechnology Ltd | Method of synthesising biomolecule-effector/reporter-conjugates using affinity resins |
MA40934A (fr) * | 2014-11-19 | 2017-09-27 | Immunogen Inc | Procédé de préparation de conjugués agent de liaison cellulaire-agent cytotoxique |
AU2015354360B2 (en) | 2014-11-27 | 2021-09-09 | Zymeworks Bc Inc. | Methods of using bispecific antigen-binding constructs targeting HER2 |
BR112017011773A2 (pt) | 2014-12-04 | 2018-02-20 | Celgene Corporation | composto isolado, conjugados isolados, composiçôes farmacêuticas, e métodos de tratamento de um distúrbio em um mamífero |
TW201711702A (zh) | 2015-06-04 | 2017-04-01 | 應克隆公司 | 使用針對纖維母細胞生長因子受體3(fgfr3)之化合物的療法 |
US10449258B2 (en) * | 2015-06-09 | 2019-10-22 | Xdcexplorer (Shanghai) Co., Ltd. | Antibody drug conjugate, intermediate, preparation method, pharmaceutical composition and uses thereof |
EP3310813A1 (en) | 2015-06-17 | 2018-04-25 | Novartis AG | Antibody drug conjugates |
EP3359576A4 (en) | 2015-10-08 | 2019-08-28 | Zymeworks Inc. | ANTIGENBINDING POLYPEPTIDE CONSTRUCTS WITH KAPPA AND LAMBDA LIGHT CHAINS AND USES THEREOF |
CN106606784B (zh) * | 2015-10-19 | 2020-01-21 | 泰州迈博太科药业有限公司 | 一种靶向表达egfr肿瘤细胞的前抗体偶联药物及其应用 |
US10918627B2 (en) | 2016-05-11 | 2021-02-16 | Massachusetts Institute Of Technology | Convergent and enantioselective total synthesis of Communesin analogs |
KR102617264B1 (ko) | 2016-10-19 | 2023-12-29 | 인벤라 인코포레이티드 | 항체 구조물 |
RU2644280C1 (ru) * | 2016-12-12 | 2018-02-08 | Федеральное государственное бюджетное учреждение науки Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук (ИХБФМ СО РАН) | Способ получения противоопухолевого коньюгата на основе человеческого сывороточного альбумина, содержащего терапевтические и контрастирующий агенты |
WO2018115485A1 (en) | 2016-12-22 | 2018-06-28 | Pierfrancesco Tassone | A monoclonal antibody targeting a unique sialoglycosilated cancer-associated epitope of cd43 |
TWI783957B (zh) | 2016-12-23 | 2022-11-21 | 美商伊繆諾金公司 | 靶向adam9之免疫共軛物及其使用方法 |
JOP20190187A1 (ar) | 2017-02-03 | 2019-08-01 | Novartis Ag | مترافقات عقار جسم مضاد لـ ccr7 |
WO2018185618A1 (en) | 2017-04-03 | 2018-10-11 | Novartis Ag | Anti-cdh6 antibody drug conjugates and anti-gitr antibody combinations and methods of treatment |
WO2018209239A1 (en) | 2017-05-11 | 2018-11-15 | Massachusetts Institute Of Technology | Potent agelastatin derivatives as modulators for cancer invasion and metastasis |
KR102611853B1 (ko) | 2017-06-30 | 2023-12-08 | 자임워크스 비씨 인코포레이티드 | 안정화된 키메라 fabs |
US10640508B2 (en) | 2017-10-13 | 2020-05-05 | Massachusetts Institute Of Technology | Diazene directed modular synthesis of compounds with quaternary carbon centers |
US11274121B2 (en) | 2018-01-12 | 2022-03-15 | Immunogen, Inc. | Methods for antibody drug conjugation, purification, and formulation |
EP3552631A1 (en) | 2018-04-10 | 2019-10-16 | Inatherys | Antibody-drug conjugates and their uses for the treatment of cancer |
WO2019234136A1 (en) | 2018-06-05 | 2019-12-12 | King's College London | Btnl3/8 targeting constructs for delivery of payloads to the gastrointestinal system |
AU2019311557A1 (en) | 2018-07-25 | 2021-02-04 | Daiichi Sankyo Company, Limited | Effective method for manufacturing antibody-drug conjugate |
EP3941508A1 (en) * | 2019-03-18 | 2022-01-26 | The Trustees of Columbia University in the City of New York | Non-hydrolyzable, non-cleavable, stable linkers for precision therapeutics and uses thereof |
US20220162225A1 (en) * | 2019-03-29 | 2022-05-26 | Purdue Research Foundation | Ph-dependent composition matters useful for study and diagnosis of alzheimer's disease |
WO2020247054A1 (en) | 2019-06-05 | 2020-12-10 | Massachusetts Institute Of Technology | Compounds, conjugates, and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines and uses thereof |
KR20220051332A (ko) | 2019-07-10 | 2022-04-26 | 싸이브렉사 3, 인크. | 치료제로서의 미세소관 표적화제의 펩티드 접합체 |
TW202116778A (zh) | 2019-07-10 | 2021-05-01 | 美商斯布雷克薩二號公司 | 作為治療劑之細胞毒素之肽結合物 |
KR20220045047A (ko) * | 2019-08-19 | 2022-04-12 | 션양 파마슈티컬 유니버시티 | 항체 변이체 및 이의 적용 |
CN113121670B (zh) * | 2020-01-15 | 2022-11-22 | 天津键凯科技有限公司 | 二取代peg化白细胞介素2及其制备方法、应用 |
US20230181756A1 (en) | 2020-04-30 | 2023-06-15 | Novartis Ag | Ccr7 antibody drug conjugates for treating cancer |
US11878986B2 (en) | 2020-06-22 | 2024-01-23 | National Health Research Institutes | Poly heterocyclic conjugates and their pharmaceutical uses |
CA3215049A1 (en) | 2021-04-10 | 2022-10-13 | Baiteng ZHAO | Folr1 binding agents, conjugates thereof and methods of using the same |
WO2022226317A1 (en) | 2021-04-23 | 2022-10-27 | Profoundbio Us Co. | Anti-cd70 antibodies, conjugates thereof and methods of using the same |
WO2023092099A1 (en) | 2021-11-19 | 2023-05-25 | Ardeagen Corporation | Gpc3 binding agents, conjugates thereof and methods of using the same |
Family Cites Families (190)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4166105A (en) | 1973-07-30 | 1979-08-28 | Block Engineering, Inc. | Dye tagged reagent |
SE430062B (sv) | 1977-03-04 | 1983-10-17 | Pharmacia Fine Chemicals Ab | Kopplings- eller tioleringsreagens |
US4152411A (en) | 1977-07-27 | 1979-05-01 | Akzona Incorporated | High specific activity labeled substances |
US4137230A (en) | 1977-11-14 | 1979-01-30 | Takeda Chemical Industries, Ltd. | Method for the production of maytansinoids |
US4307016A (en) | 1978-03-24 | 1981-12-22 | Takeda Chemical Industries, Ltd. | Demethyl maytansinoids |
US4256746A (en) | 1978-11-14 | 1981-03-17 | Takeda Chemical Industries | Dechloromaytansinoids, their pharmaceutical compositions and method of use |
JPS55102583A (en) | 1979-01-31 | 1980-08-05 | Takeda Chem Ind Ltd | 20-acyloxy-20-demethylmaytansinoid compound |
JPS55162791A (en) | 1979-06-05 | 1980-12-18 | Takeda Chem Ind Ltd | Antibiotic c-15003pnd and its preparation |
JPS5645483A (en) | 1979-09-19 | 1981-04-25 | Takeda Chem Ind Ltd | C-15003phm and its preparation |
JPS5645485A (en) | 1979-09-21 | 1981-04-25 | Takeda Chem Ind Ltd | Production of c-15003pnd |
EP0028683A1 (en) | 1979-09-21 | 1981-05-20 | Takeda Chemical Industries, Ltd. | Antibiotic C-15003 PHO and production thereof |
WO1982001188A1 (en) | 1980-10-08 | 1982-04-15 | Takeda Chemical Industries Ltd | 4,5-deoxymaytansinoide compounds and process for preparing same |
US4450254A (en) | 1980-11-03 | 1984-05-22 | Standard Oil Company | Impact improvement of high nitrile resins |
US4315929A (en) | 1981-01-27 | 1982-02-16 | The United States Of America As Represented By The Secretary Of Agriculture | Method of controlling the European corn borer with trewiasine |
US4313946A (en) | 1981-01-27 | 1982-02-02 | The United States Of America As Represented By The Secretary Of Agriculture | Chemotherapeutically active maytansinoids from Trewia nudiflora |
US4563304A (en) | 1981-02-27 | 1986-01-07 | Pharmacia Fine Chemicals Ab | Pyridine compounds modifying proteins, polypeptides or polysaccharides |
JPS57192389A (en) | 1981-05-20 | 1982-11-26 | Takeda Chem Ind Ltd | Novel maytansinoid |
US4664911A (en) | 1983-06-21 | 1987-05-12 | Board Of Regents, University Of Texas System | Immunotoxin conjugates employing toxin B chain moieties |
DE3587294T2 (de) | 1985-01-22 | 1993-09-30 | Saint Gobain Vitrage | Verfahren zur Herstellung einer dünnen Metalloxidbeschichtung auf einem Substrat, insbesondere Glas und deren Verwendung als Verglasung. |
US5223242A (en) | 1985-11-05 | 1993-06-29 | The General Hospital Corporation | Negatively charged specific affinity reagents |
GB8600582D0 (en) | 1986-01-10 | 1986-02-19 | Ca Minister Nat Defence | Purifying biological materials |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
US4956303A (en) | 1986-04-28 | 1990-09-11 | Antibody Technology Limited | Secondary antibodies against complexes of small molecules and binding partners therefor, their preparation, and their use in diagnostic methods |
US4859449A (en) * | 1987-09-14 | 1989-08-22 | Center For Molecular Medicine And Immunology | Modified antibodies for enhanced hepatocyte clearance |
US5241078A (en) | 1988-06-14 | 1993-08-31 | Cetus Oncology | Coupling agents and sterically hindered disulfide linked conjugates prepared therefrom |
JP2818827B2 (ja) | 1988-06-24 | 1998-10-30 | サンヨーファイン株式会社 | 鉄補給飲料 |
US5024834A (en) | 1988-07-12 | 1991-06-18 | Cetus Corporation | Thioether linked immunotoxin conjugates |
CA2006408A1 (en) | 1988-12-27 | 1990-06-27 | Susumu Iwasa | Bispecific monoclonal antibody, its production and use |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5714149A (en) * | 1989-02-10 | 1998-02-03 | Celltech Therapeutics Limited | Crosslinked antibodies and processes for their preparation |
CA2026147C (en) | 1989-10-25 | 2006-02-07 | Ravi J. Chari | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US6316003B1 (en) | 1989-12-21 | 2001-11-13 | Whitehead Institute For Biomedical Research | Tat-derived transport polypeptides |
FR2656555B1 (fr) | 1989-12-29 | 1994-10-28 | Serimer | Systeme mecanique de guidage automatique d'une ou plusieurs torches d'une unite de soudage a l'arc. |
US5137877B1 (en) | 1990-05-14 | 1996-01-30 | Bristol Myers Squibb Co | Bifunctional linking compounds conjugates and methods for their production |
GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
CA2048078A1 (en) | 1990-11-15 | 1992-05-16 | Wolfgang A. Wrasidlo | Chemical modification of antibodies for creation of immunoconjugates |
US5252714A (en) | 1990-11-28 | 1993-10-12 | The University Of Alabama In Huntsville | Preparation and use of polyethylene glycol propionaldehyde |
SE9102074D0 (sv) | 1991-07-03 | 1991-07-03 | Kabi Pharmacia Ab | Tomour antigen specific antibody |
SE470006B (sv) | 1991-09-26 | 1993-10-25 | Corline Systems Ab | Nytt konjugat, dess framställning och användning samt substrat preparerat med konjugatet |
US5885793A (en) | 1991-12-02 | 1999-03-23 | Medical Research Council | Production of anti-self antibodies from antibody segment repertoires and displayed on phage |
EP0563475B1 (en) | 1992-03-25 | 2000-05-31 | Immunogen Inc | Cell binding agent conjugates of derivatives of CC-1065 |
US5501952A (en) | 1992-07-17 | 1996-03-26 | Aprogenex, Inc. | Analogues of reporter groups as background reducers in hybridization assays |
US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
US5635483A (en) | 1992-12-03 | 1997-06-03 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Tumor inhibiting tetrapeptide bearing modified phenethyl amides |
US5556623A (en) | 1993-03-30 | 1996-09-17 | Eli Lilly And Company | Antibody-drug conjugates |
US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
GB9320575D0 (en) | 1993-10-06 | 1993-11-24 | Amp Gmbh | Coaxial connector having improved locking mechanism |
IL111748A0 (en) | 1993-12-03 | 1995-01-24 | Zeneca Ltd | Proteins |
US5919758A (en) | 1994-03-22 | 1999-07-06 | Beth Israel Deaconess Medical Center | Modified polypeptides with altered biological activity |
US5580853A (en) | 1994-03-22 | 1996-12-03 | New England Deaconess Hospital | Modified polypeptides with increased biological activity |
US5747446A (en) | 1994-03-22 | 1998-05-05 | Beth Israel Deaconess Medical Center | Modified polypeptides with increased biological activity |
US5612474A (en) | 1994-06-30 | 1997-03-18 | Eli Lilly And Company | Acid labile immunoconjugate intermediates |
US6355780B1 (en) | 1995-02-22 | 2002-03-12 | Yeda Research And Development Co. Ltd. | Antibodies to the death domain motifs of regulatory proteins |
WO1996039183A1 (en) | 1995-05-31 | 1996-12-12 | Fred Hutchinson Cancer Research Center | Compositions and methods for targeted delivery of effector molecules |
US6265150B1 (en) | 1995-06-07 | 2001-07-24 | Becton Dickinson & Company | Phage antibodies |
US5714352A (en) | 1996-03-20 | 1998-02-03 | Xenotech Incorporated | Directed switch-mediated DNA recombination |
WO1998026747A2 (en) * | 1996-12-17 | 1998-06-25 | Terman David S | Superantigen based methods and compositions for treatment of diseases |
US6462070B1 (en) | 1997-03-06 | 2002-10-08 | The General Hospital Corporation | Photosensitizer conjugates for pathogen targeting |
US6371975B2 (en) | 1998-11-06 | 2002-04-16 | Neomend, Inc. | Compositions, systems, and methods for creating in situ, chemically cross-linked, mechanical barriers |
ES2231991T3 (es) | 1997-06-11 | 2005-05-16 | Borean Pharma A/S | Modulo de trimerizacion. |
US6171586B1 (en) | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
US5958677A (en) | 1997-07-28 | 1999-09-28 | The New York Blood Center, Inc. | Method for purifying viral nucleic acids |
EP1005569A2 (en) | 1997-08-01 | 2000-06-07 | MorphoSys AG | Novel method and phage for the identification of nucleic acid sequences encoding members of a multimeric (poly)peptide complex |
US5965714A (en) | 1997-10-02 | 1999-10-12 | Connaught Laboratories, Inc. | Method for the covalent attachment of polysaccharides to protein molecules |
ATE296105T1 (de) | 1997-10-03 | 2005-06-15 | Galenica Pharmaceuticals Inc | Iminbildende polysaccharide, deren herstellung und verwendung als zusatzmittel und immunstimulierende mittel |
US6121236A (en) | 1998-03-24 | 2000-09-19 | The Children's Medical Center Corporation | Multivalent ligands which modulate angiogenesis |
JP2002513028A (ja) | 1998-04-28 | 2002-05-08 | ガレニカ ファーマシューティカルズ, インコーポレイテッド | ポリサッカリド抗原結合体 |
US5981564A (en) | 1998-07-01 | 1999-11-09 | Universite Laval | Water-soluble derivatives of paclitaxel, method for producing same and uses thereof |
ES2188202T3 (es) | 1998-07-13 | 2003-06-16 | Univ Texas | Metodos de tratamiento para el cancer usando conjugados terapeuticos que se enlazan con aminofosfolipidos. |
CA2341471C (en) | 1998-08-27 | 2009-04-07 | Spirogen Limited | Pyrrolbenzodiazepines |
AUPQ014799A0 (en) | 1999-05-04 | 1999-05-27 | Access Pharmaceuticals Australia Pty Limited | Amplification of folate-mediated targeting to tumor cells using polymers |
EP1229934B1 (en) | 1999-10-01 | 2014-03-05 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
DE60032633T2 (de) | 1999-11-24 | 2007-10-04 | Immunogen Inc., Cambridge | Zytotoxische mittel, die taxane enthalten und ihre therapeutische anwendung |
DK1242438T3 (da) | 1999-12-29 | 2007-02-12 | Immunogen Inc | Cytotoksiske midler omfattende modificerede doxorubiciner og daunorubiciner og deres terapeutiske anvendelse |
CA2398136A1 (en) | 2000-02-08 | 2001-08-16 | The Penn State Research Foundation | Immunotherapy using interleukin 13 receptor subunit alpha 2 |
US7097840B2 (en) | 2000-03-16 | 2006-08-29 | Genentech, Inc. | Methods of treatment using anti-ErbB antibody-maytansinoid conjugates |
US6632979B2 (en) * | 2000-03-16 | 2003-10-14 | Genentech, Inc. | Rodent HER2 tumor model |
US6333410B1 (en) | 2000-08-18 | 2001-12-25 | Immunogen, Inc. | Process for the preparation and purification of thiol-containing maytansinoids |
US6596503B1 (en) | 2000-08-18 | 2003-07-22 | East Carolina University | Monoclonal antibody DS6, tumor-associated antigen CA6, and methods of use thereof |
US20060062786A1 (en) * | 2000-11-08 | 2006-03-23 | Human Genome Sciences, Inc. | Antibodies that immunospecifically bind to TRAIL receptors |
US7767802B2 (en) | 2001-01-09 | 2010-08-03 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of anti-apoptotic genes |
EA007388B1 (ru) | 2001-01-29 | 2006-10-27 | Идек Фармасьютикалз Корпорейшн | Модифицированные антитела и способы применения |
JP2005507857A (ja) | 2001-02-07 | 2005-03-24 | ベズ イズレイル ディーコネス メディカル センター | 改変psmaリガンド及びそれに関する利用 |
US20020197261A1 (en) * | 2001-04-26 | 2002-12-26 | Chun Li | Therapeutic agent/ligand conjugate compositions, their methods of synthesis and use |
EP1392361A4 (en) | 2001-05-11 | 2009-08-05 | Univ Texas | THERAPY BASED ON ANTI-CD26 MONOCLONAL ANTIBODIES AGAINST DISORDERS ASSOCIATED WITH CELLS EXPRESSING CD26 |
EP1258255A1 (en) | 2001-05-18 | 2002-11-20 | Boehringer Ingelheim International GmbH | Conjugates of an antibody to CD44 and a maytansinoid |
US6441163B1 (en) * | 2001-05-31 | 2002-08-27 | Immunogen, Inc. | Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents |
EP1392360B1 (en) | 2001-06-01 | 2011-11-30 | Cornell Research Foundation, Inc. | Modified antibodies to prostate-specific membrane antigen and uses thereof |
TW593239B (en) | 2001-06-04 | 2004-06-21 | Kevin Dale Allen | One-step production of 1,3-propanediol from ethylene oxide and syngas with a catalyst with a phospholanoalkane ligand |
DE60230670D1 (de) | 2001-12-11 | 2009-02-12 | Merck & Co Inc | Staphylococcus aureus exopolysaccharid und verfahren |
US6716821B2 (en) | 2001-12-21 | 2004-04-06 | Immunogen Inc. | Cytotoxic agents bearing a reactive polyethylene glycol moiety, cytotoxic conjugates comprising polyethylene glycol linking groups, and methods of making and using the same |
WO2003057163A2 (en) | 2002-01-03 | 2003-07-17 | Smithkline Beecham Corporation | Methods for preparing immunoconjugates |
DE10202419A1 (de) | 2002-01-22 | 2003-08-07 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines durch eine Chromosomen-Aberration entstandenen Zielgens |
US7591994B2 (en) | 2002-12-13 | 2009-09-22 | Immunomedics, Inc. | Camptothecin-binding moiety conjugates |
US8877901B2 (en) | 2002-12-13 | 2014-11-04 | Immunomedics, Inc. | Camptothecin-binding moiety conjugates |
US6660856B2 (en) | 2002-03-08 | 2003-12-09 | Kaohsiung Medical University | Synthesis of pyrrolo[2,1-c][1,4]benzodiazepine analogues |
US6534660B1 (en) | 2002-04-05 | 2003-03-18 | Immunogen, Inc. | CC-1065 analog synthesis |
US6756397B2 (en) | 2002-04-05 | 2004-06-29 | Immunogen, Inc. | Prodrugs of CC-1065 analogs |
US7323553B2 (en) | 2002-04-26 | 2008-01-29 | Genentech, Inc. | Non-affinity purification of proteins |
DK2371392T3 (en) * | 2002-05-02 | 2015-08-31 | Wyeth Holdings Llc | Calicheamicin derivative / carrier conjugates |
US20090068178A1 (en) | 2002-05-08 | 2009-03-12 | Genentech, Inc. | Compositions and Methods for the Treatment of Tumor of Hematopoietic Origin |
US6596757B1 (en) | 2002-05-14 | 2003-07-22 | Immunogen Inc. | Cytotoxic agents comprising polyethylene glycol-containing taxanes and their therapeutic use |
AU2003251592A1 (en) | 2002-06-21 | 2004-01-06 | Biogen Idec Inc. | Buffered formulations for concentrating antibodies and methods of use thereof |
PT2357006E (pt) | 2002-07-31 | 2016-01-22 | Seattle Genetics Inc | Conjugados de fármacos e sua utilização para tratamento do cancro, de uma doença autoimune ou de uma doença infeciosa |
US7390898B2 (en) | 2002-08-02 | 2008-06-24 | Immunogen Inc. | Cytotoxic agents containing novel potent taxanes and their therapeutic use |
ATE499116T1 (de) | 2002-08-16 | 2011-03-15 | Immunogen Inc | Vernetzer mit hoher reaktivität und löslichkeit und ihre verwendung bei der herstellung von konjugaten für die gezielte abgabe von kleinmolekularen arzneimitteln |
US7538092B2 (en) | 2002-10-08 | 2009-05-26 | Fresenius Kabi Deutschland Gmbh | Pharmaceutically active oligosaccharide conjugates |
HUE033651T2 (en) | 2002-10-30 | 2017-12-28 | Nuevolution As | A method for producing two-function complexes |
MXPA05004712A (es) | 2002-11-07 | 2005-11-23 | Immunogen Inc | Anticuerpos anti-cd33 y metodo para tratamiento de leucemia mieloide aguda utilizando los mismos. |
ATE421967T1 (de) | 2003-03-31 | 2009-02-15 | Council Scient Ind Res | Nichtvernetzende pyrroloä2,1-cüä1, 4übenzodiazepine als potentielle antitumor- agentien und ihre herstellung |
WO2004094595A2 (en) | 2003-04-17 | 2004-11-04 | Alnylam Pharmaceuticals Inc. | MODIFIED iRNA AGENTS |
US8088387B2 (en) * | 2003-10-10 | 2012-01-03 | Immunogen Inc. | Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates |
CA2737127C (en) | 2003-05-14 | 2016-07-26 | Immunogen, Inc. | Maytansinoid-antibody conjugate compositions |
US7276497B2 (en) * | 2003-05-20 | 2007-10-02 | Immunogen Inc. | Cytotoxic agents comprising new maytansinoids |
ES2559670T3 (es) | 2003-05-20 | 2016-02-15 | Immunogen, Inc. | Agentes citotóxicos mejorados que comprenden nuevos maitansinoides |
US7595306B2 (en) | 2003-06-09 | 2009-09-29 | Alnylam Pharmaceuticals Inc | Method of treating neurodegenerative disease |
ES2905724T3 (es) | 2003-06-13 | 2022-04-11 | Alnylam Europe Ag | Acido ribonucleico bicatenario con elevada eficacia en un organismo |
KR20140033239A (ko) | 2003-06-27 | 2014-03-17 | 암젠 프레몬트 인코포레이티드 | 상피 성장 인자 수용체의 결실 돌연변이체 지향 항체 및 그 용도 |
WO2005002597A1 (en) | 2003-07-02 | 2005-01-13 | Polycord, Inc. | Method for delivering polymerized therapeutic agent compositions and compositions thereof |
CA2542886A1 (en) | 2003-11-05 | 2005-05-19 | Neelima M. Bhat | Enhanced b cell cytotoxicity of cdim binding antibody |
EA018427B1 (ru) | 2003-12-16 | 2013-07-30 | Нектар Терапьютикс | Химически модифицированный налоксон |
US20050175619A1 (en) | 2004-02-05 | 2005-08-11 | Robert Duffy | Methods of producing antibody conjugates |
US20110064754A1 (en) | 2005-03-03 | 2011-03-17 | Center For Molecular Medicine And Immunology | Immunoconjugates Comprising Poxvirus-Derived Peptides and Antibodies Against Antigen-Presenting Cells for Subunit-Based Poxvirus Vaccines |
EP1610818A4 (en) | 2004-03-03 | 2007-09-19 | Millennium Pharm Inc | MODIFIED ANTIBODIES AGAINST A PROSTATE-SPECIFIC MEMBRANE-ANTIGEN AND USE THEREOF |
US7189710B2 (en) | 2004-03-30 | 2007-03-13 | Council Of Scientific And Industrial Research | C2-fluoro pyrrolo [2,1−c][1,4]benzodiazepine dimers |
US6951853B1 (en) | 2004-03-30 | 2005-10-04 | Council Of Scientific And Industrial Research | Process for preparing pyrrolo[2, 1-c] [1,4] benzodiazepine hybrids |
WO2005115477A2 (en) | 2004-04-13 | 2005-12-08 | Quintessence Biosciences, Inc. | Non-natural ribonuclease conjugates as cytotoxic agents |
EP1768998A2 (en) | 2004-04-27 | 2007-04-04 | Alnylam Pharmaceuticals Inc. | Single-stranded and double-stranded oligonucleotides comprising a 2-arylpropyl moiety |
EP3034510A1 (en) | 2004-04-30 | 2016-06-22 | Alnylam Pharmaceuticals Inc. | Oligonucleotides comprising a c5-modified pyrimidine |
US20060073528A1 (en) | 2004-05-14 | 2006-04-06 | Jean-Michel Lecerf | Measurement methods |
MXPA06013413A (es) | 2004-05-19 | 2007-01-23 | Medarex Inc | Enlazadores quimicos y conjugados de los mismos. |
RU2402548C2 (ru) * | 2004-05-19 | 2010-10-27 | Медарекс, Инк. | Химические линкеры и их конъюгаты |
BRPI0510883B8 (pt) | 2004-06-01 | 2021-05-25 | Genentech Inc | composto conjugado de droga e anticorpo, composição farmacêutica, método de fabricação de composto conjugado de droga e anticorpo e usos de uma formulação, de um conjugado de droga e anticorpo e um agente quimioterapêutico e de uma combinação |
AU2005327517B2 (en) | 2004-06-30 | 2011-05-26 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a non-phosphate backbone linkage |
AU2005328382C1 (en) | 2004-07-21 | 2013-01-24 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a modified or non-natural nucleobase |
JP4193771B2 (ja) | 2004-07-27 | 2008-12-10 | セイコーエプソン株式会社 | 階調電圧発生回路及び駆動回路 |
EP1913011B1 (en) | 2004-08-04 | 2016-11-02 | Alnylam Pharmaceuticals Inc. | Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase |
AU2004224925C1 (en) | 2004-08-30 | 2011-07-21 | Biotest Ag | Immunoconjugates targeting syndecan-1 expressing cells and use thereof |
PL1791565T3 (pl) | 2004-09-23 | 2016-10-31 | Modyfikowane cysteiną przeciwciała i koniugaty | |
AR052774A1 (es) * | 2004-10-08 | 2007-04-04 | Wyeth Corp | Inmunoterapia para trastornos autoinmunes |
CA2587589A1 (en) | 2004-11-29 | 2006-06-22 | Seattle Genetics, Inc. | Engineered antibodies and immunoconjugates |
AU2005314392B2 (en) | 2004-12-09 | 2011-04-14 | Centocor, Inc. | Anti-integrin immunoconjugates, methods and uses |
US7408030B2 (en) | 2005-01-13 | 2008-08-05 | North Carolina State University | Purification of immunoglobulins using affinity chromatography and peptide ligands |
AU2006213662B2 (en) | 2005-02-11 | 2010-08-05 | Immunogen, Inc. | Process for preparing stable drug conjugates |
US20110166319A1 (en) | 2005-02-11 | 2011-07-07 | Immunogen, Inc. | Process for preparing purified drug conjugates |
WO2006113623A2 (en) | 2005-04-15 | 2006-10-26 | Immunogen, Inc. | Elimination of heterogeneous or mixed cell population in tumors |
GB2427360A (en) | 2005-06-22 | 2006-12-27 | Complex Biosystems Gmbh | Aliphatic prodrug linker |
ES2424242T3 (es) | 2005-07-15 | 2013-09-30 | Angiochem Inc. | Uso de polipéptidos de aprotinina como portadores en conjugados farmacéuticos |
EA014513B1 (ru) | 2005-08-03 | 2010-12-30 | Иммьюноджен, Инк. | Композиция иммуноконъюгата |
US20070213292A1 (en) | 2005-08-10 | 2007-09-13 | The Rockefeller University | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
EP2399609B1 (en) | 2005-08-24 | 2015-03-18 | ImmunoGen, Inc. | Process for preparing maytansinoid antibody conjugates |
AU2006293426A1 (en) | 2005-09-22 | 2007-03-29 | Hadasit Medical Research Services & Development Limited | Dextran and arabinogalactan conjugates of therapeutically active compounds |
JP5290756B2 (ja) * | 2005-09-26 | 2013-09-18 | メダレックス インコーポレイテッド | 抗体−薬剤コンジュゲート及びその使用 |
US7928113B2 (en) | 2005-11-14 | 2011-04-19 | University Of Southern California | Integrin-binding small molecules |
WO2007062466A1 (en) | 2005-11-29 | 2007-06-07 | The University Of Sydney | Demibodies: dimerisation-activated therapeutic agents |
EP1996612A4 (en) | 2006-03-03 | 2010-10-20 | Univ Kingston | COMPOSITIONS FOR THE TREATMENT OF CANCER |
US7964415B2 (en) | 2006-04-26 | 2011-06-21 | Cardiogenics Inc. | Stable water-soluble polyethylenimine conjugates and methods of use thereof |
SG172656A1 (en) * | 2006-05-30 | 2011-07-28 | Genentech Inc | Antibodies and immunoconjugates and uses therefor |
EP2047252B1 (en) | 2006-06-22 | 2013-01-23 | Walter and Eliza Hall Institute of Medical Research | Structure of the insulin receptor ectodomain |
KR101528939B1 (ko) | 2006-07-18 | 2015-06-15 | 사노피 | 암 치료를 위한 epha2에 대한 길항제 항체 |
US20080213349A1 (en) | 2006-09-11 | 2008-09-04 | Deepak Ramesh Thakker | Liposome Complexes Containing Pharmaceutical Agents and Methods |
JP2010505874A (ja) | 2006-10-03 | 2010-02-25 | ノヴォ ノルディスク アー/エス | ポリペプチドコンジュゲートの精製方法 |
PT2019104E (pt) | 2007-07-19 | 2013-12-03 | Sanofi Sa | Agentes citotóxicos compreendendo novos derivados de tomaimicina e sua utilização terapêutica |
US8084589B2 (en) | 2007-08-31 | 2011-12-27 | University Of Massachusetts | Phosphoramidite nucleoside analogs |
MY157165A (en) | 2008-04-30 | 2016-05-13 | Immunogen Inc | Cross-linkers and their uses |
EP2276506A4 (en) | 2008-04-30 | 2014-05-07 | Immunogen Inc | EFFICIENT CONJUGATES AND HYDROPHILIC BINDER |
GB0811743D0 (en) | 2008-06-26 | 2008-07-30 | Hemosol Biopharma Inc | Composition |
US20110223257A1 (en) | 2008-11-17 | 2011-09-15 | Enzon Pharmaceuticals, Inc. | Releasable fusogenic lipids for nucleic acids delivery systems |
KR102021728B1 (ko) | 2009-02-05 | 2019-09-16 | 이뮤노젠 아이엔씨 | 신규한 벤조디아제핀 유도체 |
HUE043645T2 (hu) * | 2009-06-03 | 2019-08-28 | Immunogen Inc | Konjugációs módszerek |
FR2947269B1 (fr) | 2009-06-29 | 2013-01-18 | Sanofi Aventis | Nouveaux composes anticancereux |
UY32914A (es) | 2009-10-02 | 2011-04-29 | Sanofi Aventis | Anticuerpos que se usan específicamente al receptor epha2 |
SG10201501342UA (en) | 2010-02-24 | 2015-04-29 | Immunogen Inc | Folate receptor 1 antibodies and immunoconjugates and uses thereof |
KR20110103182A (ko) | 2010-03-12 | 2011-09-20 | 삼성전자주식회사 | 입체 영상 표시 장치 |
US20120149732A1 (en) | 2010-12-14 | 2012-06-14 | Alexander Chucholowski | Multifunctional linkers and methods for the use thereof |
WO2012112708A1 (en) | 2011-02-15 | 2012-08-23 | Immunogen, Inc. | Cytotoxic benzodiazepine derivatives and methods of preparation |
WO2012135522A2 (en) | 2011-03-29 | 2012-10-04 | Immunogen, Inc. | Process for manufacturing conjugates of improved homogeneity |
PT2691155T (pt) | 2011-03-29 | 2019-02-19 | Immunogen Inc | Preparação de conjugados de anticorpo de maitansinoide por processo de uma etapa |
CN103619357A (zh) | 2011-03-29 | 2014-03-05 | 伊缪诺金公司 | 用于制造具有改善的同质性的缀合物的方法 |
EP2694106B1 (en) | 2011-04-01 | 2017-12-13 | ImmunoGen, Inc. | Methods for increasing efficacy of folr1 cancer therapy |
US20130071482A1 (en) | 2011-09-20 | 2013-03-21 | The University Of Kentucky Research Foundation | Block copolymer cross-linked nanoassemblies as modular delivery vehicles |
BR112014014464A2 (pt) | 2011-12-13 | 2017-06-13 | Immunogen Inc | uso de n-hidroxisuccinimida para melhorar a estabilidade do conjugado |
CA2886993A1 (en) | 2012-10-04 | 2014-04-10 | Immunogen, Inc. | Use of a pvdf membrane to purify cell-binding agent cytotoxic agent conjugates |
US20150306242A1 (en) | 2012-10-04 | 2015-10-29 | Immunogen, Inc. | Process for preparing stable antibody maytansinoid conjugates |
WO2014055893A1 (en) | 2012-10-04 | 2014-04-10 | Immunogen, Inc. | Use of an ion exchange membrane to remove impurities from cell-binding agent cytotoxic agent conjugates |
US10253099B2 (en) | 2012-12-05 | 2019-04-09 | Ruprecht-Karls-Universität Heidelberg | Conjugates of proteins and multivalent cell-penetrating peptides and their uses |
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