RU2018139610A - Эффективность конъюгатов антитела против trop-2 с лекарственным средством sn-38 для терапии рецидивирующих/рефрактерных к ингибиторам контрольной точки опухолей - Google Patents

Эффективность конъюгатов антитела против trop-2 с лекарственным средством sn-38 для терапии рецидивирующих/рефрактерных к ингибиторам контрольной точки опухолей Download PDF

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RU2018139610A
RU2018139610A RU2018139610A RU2018139610A RU2018139610A RU 2018139610 A RU2018139610 A RU 2018139610A RU 2018139610 A RU2018139610 A RU 2018139610A RU 2018139610 A RU2018139610 A RU 2018139610A RU 2018139610 A RU2018139610 A RU 2018139610A
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seq
cancer
antibody
group
trop
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RU2018139610A
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RU2725292C2 (ru
RU2018139610A3 (ru
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Серенгулам В. ГОВИНДАН
Девид М. ГОЛДЕНБЕРГ
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Иммьюномедикс, Инк.
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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Claims (29)

1. Способ лечения Trop-2-положительного рака, включающий введение пациенту-человеку с Trop-2-положительным раком ADC, содержащего SN-38, конъюгированный с линкерным фрагментом, присоединенным к антителу против Trop-2 или его антигенсвязывающему фрагменту, характеризующийся тем, что у указанного пациента произошел рецидив после лечения ингибитором контрольной точки или наблюдается рефрактерность к лечению ингибитором контрольной точки.
2. Способ по п. 1, характеризующийся тем, что указанный ингибитор контрольной точки представляет собой ингибитор PD-1, PD-L1 или CTLA-4.
3. Способ по п. 1, характеризующийся тем, что указанный ингибитор контрольной точки выбран из группы, состоящей из MPDL3280A, пембролизумаба, ниволумаба, ипилимумаба, пидилизумаба, MDX-1105, дурвалумаба, BMS-936559 и тремелимумаба.
4. Способ по п. 1, характеризующийся тем, что указанный ингибитор контрольной точки представляет собой MPDL3280A.
5. Способ по п. 1, характеризующийся тем, что указанное антитело против Trop-2 представляет собой антитело hRS7, содержащее последовательности CDR легкой цепи CDR1 (KASQDVSIAVA, SEQ ID NO: 1); CDR2 (SASYRYT, SEQ ID NO: 2); и CDR3 (QQHYITPLT, SEQ ID NO: 3), и последовательности CDR тяжелой цепи CDR1 (NYGMN, SEQ ID NO: 4); CDR2 (WINTYTGEPTYTDDFKG, SEQ ID NO: 5) и CDR3 (GGFGSSYWYFDV, SEQ ID NO: 6).
6. Способ по п. 1, характеризующийся тем, что указанное антитело против Trop-2 конкурирует за связывание Trop-2 с антителом, содержащим последовательности CDR легкой цепи CDR1 (KASQDVSIAVA, SEQ ID NO: 1); CDR2 (SASYRYT, SEQ ID NO: 2); и CDR3 (QQHYITPLT, SEQ ID NO: 3), и последовательности CDR тяжелой цепи CDR1 (NYGMN, SEQ ID NO: 4); CDR2 (WINTYTGEPTYTDDFKG, SEQ ID NO: 5) и CDR3 (GGFGSSYWYFDV, SEQ ID NO: 6).
7. Способ по п. 1, характеризующийся тем, что указанный линкер представляет собой CL2A, a ADC имеет структуру MAb-CL2A-SN-38
Figure 00000001
8. Способ по п. 7, характеризующийся тем, что указанное антитело против Trop-2 представляет собой антитело hRS7, содержащее последовательности CDR легкой цепи CDR1 (KASQDVSIAVA, SEQ ID NO: 1); CDR2 (SASYRYT, SEQ ID NO: 2); и CDR3 (QQHYITPLT, SEQ ID NO: 3), и последовательности CDR тяжелой цепи CDR1 (NYGMN, SEQ ID NO: 4); CDR2 (WINTYTGEPTYTDDFKG, SEQ ID NO: 5) и CDR3 (GGFGSSYWYFDV, SEQ ID NO: 6).
9. Способ по п. 1, характеризующийся тем, что указанный рак выбран из группы, состоящей из рака ободочной и прямой кишки, легкого, желудка, мочевого пузыря, почки, поджелудочной железы, молочной железы, яичника, матки, пищевода и предстательной железы.
10. Способ по п. 1, характеризующийся тем, что указанный рак представляет собой рак молочной железы с тройным негативным фенотипом.
11. Способ по п. 1, характеризующийся тем, что указанный рак выбран из группы, состоящей из рака молочной железы с тройным негативным фенотипом, HER+, ER+, прогестерон-положительного рака молочной железы, метастатического немелкоклеточного рака легкого, метастатического мелкоклеточного рака легкого, метастатического рака эндометрия, метастатического уротелиального рака и метастатического рака поджелудочной железы.
12. Способ по п. 1, характеризующийся тем, что указанный ADC вводят в дозировке от 3 мг/кг до 18 мг/кг.
13. Способ по п. 12, характеризующийся тем, что указанная дозировка выбрана из группы, состоящей из 3 мг/кг, 4 мг/кг, 6 мг/кг, 7 мг/кг, 8 мг/кг, 9 мг/кг, 10 мг/кг, 11 мг/кг, 12 мг/кг, 16 мг/кг и 18 мг/кг.
14. Способ по п. 1, характеризующийся тем, что указанный ADC вводят в дозировке от 8 мг/кг до 12 мг/кг.
15. Способ по п. 1, характеризующийся тем, что указанный ADC вводят в дозировке от 8 мг/кг до 10 мг/кг.
16. Способ по п. 1, характеризующийся тем, что указанный ADC вводят в дозировке 10 мг/кг.
17. Способ по п. 1, характеризующийся тем, что лечение приводит к снижению размера опухоли, составляющему по меньшей мере 15%, по меньшей мере 20%, по меньшей мере 30% или по меньшей мере 40%.
18. Способ по п. 1, характеризующийся тем, что указанный ADC содержит 4 или более молекул SN-38, конъюгированных с указанным антителом или его антигенсвязывающим фрагментом.
19. Способ по п. 1, характеризующийся тем, что указанный ADC содержит от 6 до 8 молекул SN-38, конъюгированных с указанным антителом или его антигенсвязывающим фрагментом.
20. Способ по п. 1, характеризующийся тем, что указанный рак является метастатическим.
21. Способ по п. 20, дополнительно включающий уменьшение размеров или элиминацию метастазов.
22. Способ по п. 7, характеризующийся тем, что в положении 10-гидроксила SN-38 в MAb-CL2A-SN-38 находится 10-О-сложный эфир или 10-О-карбонатное производное, куда входит фрагмент «COR», где «СО» представляет собой карбонил, а группа «R» выбрана из (i) N,N-двузамещенной аминоалкильной группы «N(CH3)2-(CH2)n-», где n представляет собой 1-10, а концевая аминогруппа необязательно находится в форме четвертичной соли; (ii) алкильного остатка «СН3-(СН2)n-», где n представляет собой 0-10; (iii) алкокси-фрагмента «СН3-(СН2)n-O-», где n представляет собой 0-10; (iv) «N(CH3)2-(CH2)n-O-», где n представляет собой 2-10; или (v) «R1O-(CH2-CH2-O)n-CH2-CH2-О-», где R1 представляет собой этил или метил, и n представляет собой целое число, принимающее значения 0-10.
23. Способ по п. 1, дополнительно включающий применение у указанного пациента по меньшей мере одного другого вида противораковой терапии, выбранного из группы, состоящей из хирургического вмешательства, внешнего облучения, радиоиммунотерапии, иммунотерапии, химиотерапии, антисмысловой терапии, терапии с применением РНК-интерференции, лечения терапевтическим агентом и генной терапии.
24. Способ по п. 23, характеризующийся тем, что указанный терапевтический агент представляет собой лекарственное средство, токсин, иммуномодулятор, второе антитело, антигенсвязывающий фрагмент второго антитела, проапоптотический агент, токсин, РНКазу, гормон, радионуклид, антиангиогенный агент, миРНК, РНК-интерференцию, химиотерапевтический агент, цитокин, хемокин, пролекарство или фермент.
25. Способ по п. 24, характеризующийся тем, что указанное лекарственное средство выбрано из группы, состоящей из 5-фторурацила, афатиниба, аплидина, азарибина, анастрозола, антрациклинов, акситиниба, AVL-101, AVL-291, бендамустина, блеомицина, бортезомиба, бозутиниба, бриостатина-1, бусульфана, калихеамицина, камптотецина, карбоплатина, 10-гидроксикамптотецина, кармустина, целебрекса, хлорамбуцила, цисплатины, ингибиторов Сох-2, иринотекана (СРТ-11), SN-38, карбоплатина, кладрибина, камптотеканов, кризотиниба, циклофосфамида, цитарабина, дакарбазина, дазатиниба, динациклиба, доцетаксела, дактиномицина, даунорубицина, доксорубицина, 2-пирролинодоксорубицина (2P-DOX), циано-морфолинодоксорубицина, глюкуронида доксорубицина, глюкуронида эпирубицина, эрлотиниба, эстрамустина, эпидофиллотоксина, эрлотиниба, энтиностата, связывающих рецепторы эстрогена агентов, этопозида (VP16), глюкуронида этопозида, фосфата этопозида, эксеместана, финголимода, флоксуридина (FUdR), 3',5'-O-диолеоил-FUdR (FUdR-dO), флударабина, флутамида, ингибиторов фарнезил-протеинтрансферазы, флавопиридола, фостаматиниба, ганетеспиба, GDC-0834, GS-1101, гефинитиба, гемцитабина, гидроксимочевины, ибрутиниба, идарубицина, иделалисиба, ифосфамида, иматиниба, L-аспарагиназы, лапатиниба, леналидомида, лейковорина, LFM-A13, ломустина, мехлорэтамина, мелфалана, меркаптопурина, 6-меркаптопурина, метотрексата, митоксантрона, митрамицина, митомицина, митотана, навельбина, нератиниба, нилотиниба, нитрозомочевины, олапариба, пликамицина, прокарбазина, паклитаксела, PCI-32765, пентостатина, PSI-341, ралоксифена, семустина, сорафениба, стрептозоцина, SU11248, сунитиниба, тамоксифена, темозоломида (водная форма дакарбазина (DTIC)), трансплатины, талидомида, тиогуанина, тиотепы, тенипозида, топотекана, урамустина, ваталаниба, винорелбина, винбластина, винкристина, алкалоидов барвинка и ZD1839.
26. Способ по п. 24, характеризующийся тем, что указанный иммуномодулятор выбран из группы, состоящей из цитокинов, лимфокинов, монокинов, факторов роста стволовых клеток, лимфотоксинов, гематопоэтических факторов, колониестимулирующих факторов (КСФ), интерферонов (ИФН), паратиреоидного гормона, тироксина, инсулина, проинсулина, релаксина, прорелаксина, фолликулостимулирующего гормона (ФСГ), тиреотропного гормона (ТТГ), лютеинизирующего гормона (ЛГ), фактора роста печени, простагландина, фактора роста фибробластов, пролактина, плацентарного лактогена, белка ОВ, трансформирующего фактора роста (ТФР), ТФР-α, ТФР-β, инсулиноподобного фактора роста (ИФР), эритропоэтина, тромбопоэтина, фактора некроза опухоли (ФНО), ФНО-α, ФНО-β, мюллеровой ингибирующей субстанции, гонадотропин-ассоциированного пептида мышей, ингибина, активина, фактора роста эндотелия сосудов, интегрина, интерлейкина (ИЛ), гранулоцитарного колониестимулирующего фактора (Г-КСФ), гранулоцитарно-макрофагального колониестимулирующего фактора (ГМ-КСФ), интерферона-α, интерферона-β, интерферона-γ, фактора S1, ИЛ-1, ИЛ-1-cc, ИЛ-2, ИЛ-3, ИЛ-4, ИЛ-5, ИЛ-6, ИЛ-7, ИЛ-8, ИЛ-9, ИЛ-10, ИЛ-11, ИЛ-12, ИЛ-13, ИЛ-14, ИЛ-15, ИЛ-16, ИЛ-17, ИЛ-18 ИЛ-21, ИЛ-23, ИЛ-25, лейкоз-ингибирующего фактора (ЛИФ), Kit-лиганда, FLT-3, ангиостатина, тромбоспондина и эндостатина.
27. Способ по п. 24, характеризующийся тем, что указанный радионуклид выбран из группы, состоящей из 11C, 13N, 15O, 32Р, 33Р, 47Sc, 51Cr, 57Со, 58Со, 59Fe, 62Cu, 67Cu, 67Ga, 67Ga, 75Br, 75Se, 75Se, 76Br, 77As, 77Br, 80mBr, 89Sr, 90Y, 95Ru, 97Ru, 99Mo, 99mTc, 103mRh, 103Ru, 105Rh, 105Ru, 107Hg, 109Pd, 109Pt, 111Ag, 111In, 113mIn, 119Sb, 121mTe, 122mTe, 125I, 125mTe, 126I, 131I, 133I, 142Pr, 143Pr, 149Pm, 152Dy, 153Sm, 161Ho, 161Tb, 165Tm, 166Dy, 166Ho, 167Tm, 168Tm, 169Er, 169Yb, 177Lu, I86Re, 188Re, 189mOs, 189Re, 192Ir, I94Ir, 197Pt, 198Au, 199Au, 199Au, 201Tl, 203Hg, 211At, 211Bi, 211Pb, 212Bi, 212Pb, 213Bi, 215Po, 217At, 219Rn, 221Fr, 223Ra, 225Ac, 227Th и 255Fm.
28. Способ по п. 24, характеризующийся тем, что указанный токсин выбран из группы, состоящей из рицина, абрина, рибонуклеазы (РНКазы), ДНКазы I, стафилококкового энтеротоксина А, противовирусного белка лаконоса, гелонина, дифтерийного токсина, экзотоксина Pseudomonas и эндотоксина Pseudomonas.
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Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TR201910848T4 (tr) * 2009-02-13 2019-08-21 Immunomedics Inc İntraselüler olarak ayrilabi̇len bi̇r bağa sahi̇p i̇mmunokonjugatlar
US10413539B2 (en) * 2012-12-13 2019-09-17 Immunomedics, Inc. Therapy for metastatic urothelial cancer with the antibody-drug conjugate, sacituzumab govitecan (IMMU-132)
US20210393617A1 (en) * 2012-12-13 2021-12-23 Immunomedics, Inc. Therapy for metastatic urothelial cancer with the antibody-drug conjugate, sacituzumab govitecan (immu-132)
US10744129B2 (en) * 2012-12-13 2020-08-18 Immunomedics, Inc. Therapy of small-cell lung cancer (SCLC) with a topoisomerase-I inhibiting antibody-drug conjugate (ADC) targeting Trop-2
US9492566B2 (en) * 2012-12-13 2016-11-15 Immunomedics, Inc. Antibody-drug conjugates and uses thereof
WO2016057398A1 (en) * 2014-10-07 2016-04-14 Immunomedics, Inc. Neoadjuvant use of antibody-drug conjugates
US10195175B2 (en) * 2015-06-25 2019-02-05 Immunomedics, Inc. Synergistic effect of anti-Trop-2 antibody-drug conjugate in combination therapy for triple-negative breast cancer when used with microtubule inhibitors or PARP inhibitors
EP3448260A4 (en) * 2016-04-27 2019-10-09 Immunomedics, Inc. EFFICACY OF ANTI-TROP-2 SN-38 ANTIBODY CONJUGATES FOR THE THERAPY OF REZIDIVATED / REFRACTORY TUMORS AGAINST CHECKPOINT INHIBITORS
CA3087628A1 (en) * 2018-01-12 2019-07-18 Prolynx Llc Synergistic cancer treatment
CN111542324B (zh) * 2018-02-11 2023-09-12 四川科伦博泰生物医药股份有限公司 细胞毒性剂及其偶联物、其制备方法及用途
CN114573699A (zh) * 2018-07-09 2022-06-03 启德医药科技（苏州）有限公司 滋养层细胞表面抗原2(trop2)特异性抗体
US11219689B2 (en) 2018-10-16 2022-01-11 Tae Life Sciences, Llc Boron enriched linker (“BEL”) compositions for boron neutron capture therapy and methods thereof
CN111001012A (zh) * 2018-10-19 2020-04-14 四川百利药业有限责任公司 一种亲水碳酸酯型抗体偶联药物
WO2020092344A1 (en) * 2018-10-31 2020-05-07 Health Research, Inc. Combination treatment with anti-cd123 antibody drug conjugate and parp inhibitor
EP3990008A1 (en) * 2019-06-27 2022-05-04 eTheRNA Immunotherapies NV Combination therapy
RU2705257C2 (ru) * 2019-07-12 2019-11-06 Федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр радиологии" Министерства здравоохранения Российской Федерации (ФГБУ "НМИЦ радиологии" Минздрава России) Способ оценки эффективности неоадъювантной химиолучевой терапии больных раком прямой кишки
CN110639025B (zh) * 2019-10-15 2021-11-09 无锡市人民医院 一种聚酰胺-酰亚胺载药纳米粒子及其应用
CA3163098A1 (en) * 2019-12-05 2021-06-10 Imaginab, Inc. Methods of imaging using multiple imaging agents
US20230101266A1 (en) * 2019-12-31 2023-03-30 Genequantum Healthcare (Suzhou) Co., Ltd. Anti-trop2 antibodies, antibody-drug conjugates, and application of the same
CN115052632A (zh) * 2020-01-15 2022-09-13 北京海步医药科技有限公司 靶向多肽-药物缀合物及其用途
KR20230015888A (ko) * 2020-03-20 2023-01-31 이뮤노메딕스, 인코오포레이티드 사시투주맙 고비테칸 요법에 대한 바이오마커
US11673930B2 (en) * 2020-05-12 2023-06-13 Regeneran Pharmaceuticals, Inc. IL10 agonists and methods of use thereof
IT202000031838A1 (it) * 2020-12-22 2022-06-22 Saverio Alberti Piattaforma per ottenere anticorpi monoclonali diretti contro antigeni processati tumore-specifici
WO2023060283A2 (en) * 2021-10-08 2023-04-13 Board Of Regents, The University Of Texas System Anti-trop2 antibody combination therapies and methods of use thereof
WO2023232745A1 (en) * 2022-05-30 2023-12-07 Mediterranea Theranostic S.R.L. Anti-idiotype antibodies and uses thereof
CN116621927B (zh) * 2023-01-09 2024-03-26 联宁（苏州）生物制药有限公司 带有伊喜替康和C-lock定点偶联基团的抗体偶联中间体、偶联方法及抗体偶联药物

Family Cites Families (125)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1541435A (en) 1975-02-04 1979-02-28 Searle & Co Immunological materials
US4036945A (en) 1976-05-03 1977-07-19 The Massachusetts General Hospital Composition and method for determining the size and location of myocardial infarcts
US4200690A (en) 1976-12-16 1980-04-29 Millipore Corporation Immunoassay with membrane immobilized antibody
US4331647A (en) 1980-03-03 1982-05-25 Goldenberg Milton David Tumor localization and therapy with labeled antibody fragments specific to tumor-associated markers
US5204095A (en) 1980-04-09 1993-04-20 National Research Development Corporation Monoclonal antibodies against hepatitis B virus
US4359457A (en) 1980-09-30 1982-11-16 Neville Jr David M Anti Thy 1.2 monoclonal antibody-ricin hybrid utilized as a tumor suppressant
US4925922A (en) 1983-02-22 1990-05-15 Xoma Corporation Potentiation of cytotoxic conjugates
US4916213A (en) 1983-02-22 1990-04-10 Xoma Corporation Ribosomal inhibiting protein-immunoglobulin conjugates with specificity for tumor cell surface antigens, and mixtures thereof
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US5672347A (en) 1984-07-05 1997-09-30 Genentech, Inc. Tumor necrosis factor antagonists and their use
US4824659A (en) 1985-06-07 1989-04-25 Immunomedics, Inc. Antibody conjugates
US5525338A (en) 1992-08-21 1996-06-11 Immunomedics, Inc. Detection and therapy of lesions with biotin/avidin conjugates
US5776093A (en) 1985-07-05 1998-07-07 Immunomedics, Inc. Method for imaging and treating organs and tissues
US4918163A (en) 1985-09-27 1990-04-17 Pfizer Inc. Monoclonal antibodies specific for lipid-A determinants of gram negative bacteria
US5618920A (en) 1985-11-01 1997-04-08 Xoma Corporation Modular assembly of antibody genes, antibodies prepared thereby and use
US5057313A (en) 1986-02-25 1991-10-15 The Center For Molecular Medicine And Immunology Diagnostic and therapeutic antibody conjugates
US4699784A (en) 1986-02-25 1987-10-13 Center For Molecular Medicine & Immunology Tumoricidal methotrexate-antibody conjugate
US4997913A (en) 1986-06-30 1991-03-05 Oncogen pH-sensitive immunoconjugates and methods for their use in tumor therapy
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
US4704692A (en) 1986-09-02 1987-11-03 Ladner Robert C Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides
US5567610A (en) 1986-09-04 1996-10-22 Bioinvent International Ab Method of producing human monoclonal antibodies and kit therefor
CA1320905C (en) 1986-11-06 1993-08-03 Joseph M. Cummins Treatment of immuno-resistant disease
US4932412A (en) 1986-12-18 1990-06-12 Immunomedics, Inc. Intraoperative and endoscopic tumor detection and therapy
WO1988007553A1 (en) 1987-03-26 1988-10-06 Teijin Limited Process for preparing antibody complex
US4981979A (en) 1987-09-10 1991-01-01 Neorx Corporation Immunoconjugates joined by thioether bonds having reduced toxicity and improved selectivity
IL89220A (en) 1988-02-11 1994-02-27 Bristol Myers Squibb Co Immunoconjugates of anthracycline, their production and pharmaceutical preparations containing them
US5112954A (en) 1988-02-26 1992-05-12 Neorx Corporation Method of enhancing the effect of cytotoxic agents
US4861579A (en) 1988-03-17 1989-08-29 American Cyanamid Company Suppression of B-lymphocytes in mammals by administration of anti-B-lymphocyte antibodies
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
GB8903021D0 (en) 1989-02-10 1989-03-30 Celltech Ltd Chemical compounds
US5134075A (en) 1989-02-17 1992-07-28 Oncogen Limited Partnership Monoclonal antibody to novel antigen associated with human tumors
US5171665A (en) 1989-04-17 1992-12-15 Oncogen Monoclonal antibody to novel antigen associated with human tumors
JPH02283294A (ja) 1989-04-24 1990-11-20 Sumitomo Chem Co Ltd ヒトモノクローナル抗体
EP0438803B1 (en) 1990-01-26 1997-03-12 Immunomedics, Inc. Vaccines against cancer and infectious diseases
AU7566991A (en) 1990-03-14 1991-10-10 Biomembrane Institute, The Monoclonal antibody and immunoconjugates for the treatment and detection of b cell disorders
US5229275A (en) 1990-04-26 1993-07-20 Akzo N.V. In-vitro method for producing antigen-specific human monoclonal antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
GB9020075D0 (en) 1990-09-14 1990-10-24 Filler Aaron G Contrast agents for magnetic resonance imaging of axonal transport
US5679640A (en) 1991-02-12 1997-10-21 Cytel Corporation Immunosuppressant peptides
JP3105629B2 (ja) 1991-04-23 2000-11-06 サングスタット メディカル コーポレイション 特異的結合ペアのメンバーの細胞活性調節接合体
MX9204374A (es) 1991-07-25 1993-03-01 Idec Pharma Corp Anticuerpo recombinante y metodo para su produccion.
CA2116774C (en) 1991-09-19 2003-11-11 Paul J. Carter Expression in e. coli antibody fragments having at least a cysteine present as a free thiol. use for the production of bifunctional f(ab') 2 antibodies
US5622929A (en) 1992-01-23 1997-04-22 Bristol-Myers Squibb Company Thioether conjugates
US5965132A (en) 1992-03-05 1999-10-12 Board Of Regents, The University Of Texas System Methods and compositions for targeting the vasculature of solid tumors
US6096289A (en) 1992-05-06 2000-08-01 Immunomedics, Inc. Intraoperative, intravascular, and endoscopic tumor and lesion detection, biopsy and therapy
ATE194916T1 (de) 1992-05-06 2000-08-15 Immunomedics Inc Intraoperative, intravaskulare und endoskopische bestimmung und behandlung von verletzungen und tumoren
US5686072A (en) 1992-06-17 1997-11-11 Board Of Regents, The University Of Texas Epitope-specific monoclonal antibodies and immunotoxins and uses thereof
ES2091684T3 (es) 1992-11-13 1996-11-01 Idec Pharma Corp Aplicacion terapeutica de anticuerpos quimericos y radiomarcados contra el antigeno de diferenciacion restringida de los linfocitos b humanos para el tratamiento del linfoma de las celulas b.
MX9401351A (es) 1993-02-22 1994-08-31 Alza Corp Composiciones para suministro oral para agentes activos.
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
WO1994026297A1 (en) 1993-05-17 1994-11-24 Immunomedics, Inc. Improved detection and therapy of lesions with biotin/avidin-metal chelating protein conjugates
US5484892A (en) 1993-05-21 1996-01-16 Dana-Farber Cancer Institute, Inc. Monoclonal antibodies that block ligand binding to the CD22 receptor in mature B cells
US5565215A (en) 1993-07-23 1996-10-15 Massachusettes Institute Of Technology Biodegradable injectable particles for imaging
US5417972A (en) 1993-08-02 1995-05-23 The Board Of Trustees Of The Leland Stanford Junior University Method of killing B-cells in a complement independent and an ADCC independent manner using antibodies which specifically bind CDIM
WO1995009917A1 (en) 1993-10-07 1995-04-13 The Regents Of The University Of California Genetically engineered bispecific tetravalent antibodies
US5824701A (en) 1993-10-20 1998-10-20 Enzon, Inc. Taxane-based prodrugs
US5443953A (en) 1993-12-08 1995-08-22 Immunomedics, Inc. Preparation and use of immunoconjugates
US5639725A (en) 1994-04-26 1997-06-17 Children's Hospital Medical Center Corp. Angiostatin protein
US5686578A (en) 1994-08-05 1997-11-11 Immunomedics, Inc. Polyspecific immunoconjugates and antibody composites for targeting the multidrug resistant phenotype
AU3272695A (en) 1994-08-12 1996-03-07 Immunomedics Inc. Immunoconjugates and humanized antibodies specific for b-cell lymphoma and leukemia cells
US8771694B2 (en) 1994-08-12 2014-07-08 Immunomedics, Inc. Immunoconjugates and humanized antibodies specific for B-cell lymphoma and leukemia cells
US5874540A (en) 1994-10-05 1999-02-23 Immunomedics, Inc. CDR-grafted type III anti-CEA humanized mouse monoclonal antibodies
US5798554A (en) 1995-02-24 1998-08-25 Consorzio Per La Ricerca Sulla Microelettronica Nel Mezzogiorno MOS-technology power device integrated structure and manufacturing process thereof
AUPO591797A0 (en) 1997-03-27 1997-04-24 Commonwealth Scientific And Industrial Research Organisation High avidity polyvalent and polyspecific reagents
US6441025B2 (en) 1996-03-12 2002-08-27 Pg-Txl Company, L.P. Water soluble paclitaxel derivatives
US6254868B1 (en) 1996-03-20 2001-07-03 Immunomedics, Inc. Glycosylated humanized B-cell specific antibodies
CA2253904A1 (en) 1996-05-03 1997-11-13 Immunomedics, Inc. Targeted combination immunotherapy of cancer
JP2000516594A (ja) 1996-07-26 2000-12-12 スミスクライン・ビーチャム・コーポレイション 免疫細胞介在全身性疾患の改良された治療法
DE19640207A1 (de) 1996-09-30 1998-04-02 Bayer Ag Glycokonjugate von modifizierten Camptothecin-Derivaten (A- oder B-Ring-Verknüpfung)
US6056973A (en) 1996-10-11 2000-05-02 Sequus Pharmaceuticals, Inc. Therapeutic liposome composition and method of preparation
US6653104B2 (en) 1996-10-17 2003-11-25 Immunomedics, Inc. Immunotoxins, comprising an internalizing antibody, directed against malignant and normal cells
US7122636B1 (en) 1997-02-21 2006-10-17 Genentech, Inc. Antibody fragment-polymer conjugates and uses of same
US6183744B1 (en) 1997-03-24 2001-02-06 Immunomedics, Inc. Immunotherapy of B-cell malignancies using anti-CD22 antibodies
US6306393B1 (en) 1997-03-24 2001-10-23 Immunomedics, Inc. Immunotherapy of B-cell malignancies using anti-CD22 antibodies
AU745823B2 (en) 1997-05-02 2002-04-11 Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The Immunotoxins, comprising an onc protein, directed against malignant cells
US6368596B1 (en) 1997-07-08 2002-04-09 Board Of Regents, The University Of Texas System Compositions and methods for homoconjugates of antibodies which induce growth arrest or apoptosis of tumor cells
US6165440A (en) 1997-07-09 2000-12-26 Board Of Regents, The University Of Texas System Radiation and nanoparticles for enhancement of drug delivery in solid tumors
US6051228A (en) 1998-02-19 2000-04-18 Bristol-Myers Squibb Co. Antibodies against human CD40
DE69909459T2 (de) 1998-04-21 2004-05-27 Micromet Ag Cd19xcd3 spezifische polypeptide und deren verwendung
PT1135498E (pt) 1998-11-18 2008-04-30 Genentech Inc Variantes de anticorpos com maior afinidade de ligação em comparação com os anticorpos parentais
US6201104B1 (en) 1998-12-04 2001-03-13 Entremed, Inc. Angiogenesis—inhibiting protein binding peptides and proteins and methods of use
US6379698B1 (en) 1999-04-06 2002-04-30 Isis Pharmaceuticals, Inc. Fusogenic lipids and vesicles
JP2002544174A (ja) 1999-05-07 2002-12-24 ジェネンテック・インコーポレーテッド Ｂ細胞表面マーカーに結合するアンタゴニストを用いた自己免疫疾患の治療
US7312318B2 (en) 2002-03-01 2007-12-25 Immunomedics, Inc. Internalizing anti-CD74 antibodies and methods of use
US8119101B2 (en) 1999-05-10 2012-02-21 The Ohio State University Anti-CD74 immunoconjugates and methods of use
DE19926154A1 (de) 1999-06-09 2000-12-14 Ktb Tumorforschungs Gmbh Verfahren zur Herstellung einer injizierbaren Arzneimittelzubereitung
JP4286483B2 (ja) 1999-06-09 2009-07-01 イムノメディクス， インコーポレイテッド Ｂ細胞をターゲットとする抗体を使用する自己免疫疾患に対する免疫療法
EP2289549A3 (en) 1999-10-01 2011-06-15 Immunogen, Inc. Immunoconjugates for treating cancer
US6530944B2 (en) 2000-02-08 2003-03-11 Rice University Optically-active nanoparticles for use in therapeutic and diagnostic methods
US20030133972A1 (en) 2000-10-11 2003-07-17 Targesome, Inc. Targeted multivalent macromolecules
GB0028361D0 (en) 2000-11-21 2001-01-03 Glaxo Group Ltd Method of separating extra chromosomal dna from other cellular components
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
SE0104462D0 (sv) 2001-12-29 2001-12-29 Carlbiotech Ltd As Peptide purifcation (Peptidrening)
RU2004127458A (ru) 2002-02-14 2005-10-27 Иммуномедикс, Инк. (Us) Анти-cd20 антитела, их гибридные белки и способы их использования
US8877901B2 (en) 2002-12-13 2014-11-04 Immunomedics, Inc. Camptothecin-binding moiety conjugates
US7591994B2 (en) 2002-12-13 2009-09-22 Immunomedics, Inc. Camptothecin-binding moiety conjugates
ATE417067T1 (de) * 2002-03-01 2008-12-15 Immunomedics Inc Rs7 antikörper
US9770517B2 (en) * 2002-03-01 2017-09-26 Immunomedics, Inc. Anti-Trop-2 antibody-drug conjugates and uses thereof
FR2840532B1 (fr) 2002-06-11 2005-05-06 Ethypharm Sa Nanocapsules lipidiques furtives, procede de preparation et utilisation comme vecteur de principes(s) actif(s)
AU2003282752A1 (en) 2002-10-08 2004-05-04 Immunomedics, Inc. Antibody therapy
CA2508831C (en) 2002-12-13 2012-05-01 Immunomedics, Inc. Immunoconjugates with an intracellularly-cleavable linkage
US8420086B2 (en) 2002-12-13 2013-04-16 Immunomedics, Inc. Camptothecin conjugates of anti-CD22 antibodies for treatment of B cell diseases
US8551480B2 (en) 2004-02-13 2013-10-08 Immunomedics, Inc. Compositions and methods of use of immunotoxins comprising ranpirnase (Rap) show potent cytotoxic activity
US7560100B2 (en) 2004-09-09 2009-07-14 Yeda Research And Development Co., Ltd. Mixtures of polypeptides, compositions containing and processes for preparing same, for treating neurodegenerative diseases
WO2006047419A2 (en) 2004-10-25 2006-05-04 Intezyne Technologies, Incorporated Heterobifunctional poly(ethylene glycol) and uses thereof
JP5214252B2 (ja) 2005-03-03 2013-06-19 イミューノメディクス、インコーポレイテッド ヒト化ｌ２４３抗体
US8349332B2 (en) 2005-04-06 2013-01-08 Ibc Pharmaceuticals, Inc. Multiple signaling pathways induced by hexavalent, monospecific and bispecific antibodies for enhanced toxicity to B-cell lymphomas and other diseases
CN101478968A (zh) 2006-04-19 2009-07-08 比奥纽默里克药物公司 具有新的“触发”内酯稳定的e环的喜树碱类似物及其制备和使用方法
TR201910848T4 (tr) 2009-02-13 2019-08-21 Immunomedics Inc İntraselüler olarak ayrilabi̇len bi̇r bağa sahi̇p i̇mmunokonjugatlar
CA2774015A1 (en) 2009-09-15 2011-03-24 Cerulean Pharma Inc. A cdp-camptothecin conjugate, particle or composition and uses thereof
WO2011100131A2 (en) 2010-01-28 2011-08-18 Alnylam Pharmacuticals, Inc. Monomers and oligonucleotides comprising cycloaddition adduct(s)
US9772329B2 (en) 2011-01-11 2017-09-26 The Governing Council Of The University Of Toronto Protein detection method
CN107115526A (zh) 2011-05-02 2017-09-01 免疫医疗公司 用于小体积施用的同种异型选择的抗体的超滤浓缩
US9382329B2 (en) * 2012-08-14 2016-07-05 Ibc Pharmaceuticals, Inc. Disease therapy by inducing immune response to Trop-2 expressing cells
US9682143B2 (en) 2012-08-14 2017-06-20 Ibc Pharmaceuticals, Inc. Combination therapy for inducing immune response to disease
US9492566B2 (en) * 2012-12-13 2016-11-15 Immunomedics, Inc. Antibody-drug conjugates and uses thereof
KR20230078823A (ko) 2012-12-13 2023-06-02 이뮤노메딕스, 인코오포레이티드 개선된 효능 및 감소된 독성을 위한 항체 및 sn-38의 면역컨쥬게이트의 투약
US10413539B2 (en) 2012-12-13 2019-09-17 Immunomedics, Inc. Therapy for metastatic urothelial cancer with the antibody-drug conjugate, sacituzumab govitecan (IMMU-132)
US9107960B2 (en) * 2012-12-13 2015-08-18 Immunimedics, Inc. Antibody-SN-38 immunoconjugates with a CL2A linker
CN105209068A (zh) * 2013-02-07 2015-12-30 免疫医疗公司 用于靶向癌症治疗的缀合至抗体的高效2-吡咯啉多柔比星的前药形式(p2pdox)
JP6361039B2 (ja) * 2013-04-03 2018-07-25 アイビーシー ファーマスーティカルズ，インコーポレイテッド 疾患に対する免疫反応を誘導するための併用療法
EP3049443A4 (en) * 2013-09-27 2017-04-05 Immunomedics, Inc. Anti-trop-2 antibody-drug conjugates and uses thereof
US20160009805A1 (en) 2014-07-11 2016-01-14 Genentech, Inc. Anti-pd-l1 antibodies and diagnostic uses thereof
US10195175B2 (en) 2015-06-25 2019-02-05 Immunomedics, Inc. Synergistic effect of anti-Trop-2 antibody-drug conjugate in combination therapy for triple-negative breast cancer when used with microtubule inhibitors or PARP inhibitors
EP3448260A4 (en) * 2016-04-27 2019-10-09 Immunomedics, Inc. EFFICACY OF ANTI-TROP-2 SN-38 ANTIBODY CONJUGATES FOR THE THERAPY OF REZIDIVATED / REFRACTORY TUMORS AGAINST CHECKPOINT INHIBITORS

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