JP2011528360A5 - - Google Patents
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- JP2011528360A5 JP2011528360A5 JP2011518840A JP2011518840A JP2011528360A5 JP 2011528360 A5 JP2011528360 A5 JP 2011528360A5 JP 2011518840 A JP2011518840 A JP 2011518840A JP 2011518840 A JP2011518840 A JP 2011518840A JP 2011528360 A5 JP2011528360 A5 JP 2011528360A5
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- methoxy
- drug conjugate
- anthracycline derivative
- conjugate compound
- 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.)
- Granted
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- 229940045799 anthracyclines and related substance Drugs 0.000 claims description 50
- -1 3-pyridylmethyl - Chemical class 0.000 claims description 47
- 150000001875 compounds Chemical class 0.000 claims description 42
- 229940049595 antibody-drug conjugate Drugs 0.000 claims description 28
- 239000003814 drug Substances 0.000 claims description 27
- 239000000611 antibody drug conjugate Substances 0.000 claims description 26
- 229940079593 drug Drugs 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 22
- 239000000562 conjugate Substances 0.000 claims description 21
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 16
- 150000001413 amino acids Chemical group 0.000 claims description 15
- 125000005647 linker group Chemical group 0.000 claims description 15
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 238000010276 construction Methods 0.000 claims description 13
- 125000006850 spacer group Chemical group 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 10
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 230000008878 coupling Effects 0.000 claims description 9
- 238000010168 coupling process Methods 0.000 claims description 9
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- 125000000217 alkyl group Chemical group 0.000 claims description 8
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
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- 125000003118 aryl group Chemical group 0.000 claims description 5
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
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- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
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- 101000846911 Homo sapiens Fc receptor-like protein 2 Proteins 0.000 claims 2
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- 101001136592 Homo sapiens Prostate stem cell antigen Proteins 0.000 claims 2
- 102000052922 Large Neutral Amino Acid-Transporter 1 Human genes 0.000 claims 2
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- 102100038437 Sodium-dependent phosphate transport protein 2B Human genes 0.000 claims 2
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Families Citing this family (112)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6136311A (en) | 1996-05-06 | 2000-10-24 | Cornell Research Foundation, Inc. | Treatment and diagnosis of cancer |
| WO2007109321A2 (en) | 2006-03-20 | 2007-09-27 | The Regents Of The University Of California | Engineered anti-prostate stem cell antigen (psca) antibodies for cancer targeting |
| CA2698343C (en) | 2007-09-04 | 2018-06-12 | The Regents Of The University Of California | High affinity anti-prostate stem cell antigen (psca) antibodies for cancer targeting and detection |
| EP2740490A1 (en) * | 2007-10-03 | 2014-06-11 | Cornell University | Treatment of proliferative disorders using antibodies to PSMA |
| WO2009099741A1 (en) * | 2008-02-01 | 2009-08-13 | Genentech, Inc. | Nemorubicin metabolite and analog reagents, antibody-drug conjugates and methods |
| MX2011000509A (es) * | 2008-07-15 | 2011-04-05 | Genentech Inc | Conjugados derivados de antraciclina, proceso para su preparacion y su uso como compuestos antitumorales. |
| US20100069616A1 (en) * | 2008-08-06 | 2010-03-18 | The Regents Of The University Of California | Engineered antibody-nanoparticle conjugates |
| EP2398504B1 (en) * | 2009-02-17 | 2018-11-28 | Cornell Research Foundation, Inc. | Methods and kits for diagnosis of cancer and prediction of therapeutic value |
| US8772459B2 (en) | 2009-12-02 | 2014-07-08 | Imaginab, Inc. | J591 minibodies and Cys-diabodies for targeting human prostate specific membrane antigen (PSMA) and methods for their use |
| MX2012009215A (es) | 2010-02-23 | 2012-11-23 | Genentech Inc | Composiciones y metodos para el diagnostico y tratamiento de tumores. |
| CA2788289C (en) * | 2010-03-02 | 2018-08-21 | Seattle Genetics, Inc. | Methods for screening antibodies |
| SG10201501803YA (en) | 2010-03-12 | 2015-05-28 | Immunogen Inc | Cd37-binding molecules and immunoconjugates thereof |
| WO2012019024A2 (en) | 2010-08-04 | 2012-02-09 | Immunogen, Inc. | Her3-binding molecules and immunoconjugates thereof |
| AU2011320314B2 (en) | 2010-10-29 | 2015-08-06 | Immunogen, Inc. | Novel EGFR-binding molecules and immunoconjugates thereof |
| EA201390575A1 (ru) | 2010-10-29 | 2014-01-30 | Иммьюноджен, Инк. | Неантагонистические egfr-связывающие молекулы и их иммуноконъюгаты |
| KR101897307B1 (ko) | 2010-12-02 | 2018-09-10 | 네르비아노 메디칼 사이언시스 에스.알.엘. | 모르폴리닐 안트라사이클린 유도체의 제조 방법 |
| UA115641C2 (uk) | 2010-12-20 | 2017-11-27 | Дженентек, Інк. | Виділене антитіло, яке зв'язує мезотелін, та імунокон'югат, що його містить |
| EP2694105A4 (en) | 2011-04-01 | 2015-04-29 | Immunogen Inc | CD37 BINDING MOLECULES AND IMMUNOCONJUGATES THEREOF |
| EP2592103A1 (en) | 2011-11-08 | 2013-05-15 | Adriacell S.p.A. | Polymer aldehyde derivatives |
| SG11201402343SA (en) | 2011-11-21 | 2014-06-27 | Immunogen Inc | Method of treatment of tumors that are resistant to egfr therapies by egfr antibody cytotoxic agent conjugate |
| BR112014013526A8 (pt) * | 2011-12-05 | 2017-06-13 | Igenica Biotherapeutics Inc | conjugados de anticorpo-fármaco e compostos, composições e métodos relacionados |
| WO2013109994A1 (en) | 2012-01-20 | 2013-07-25 | Sea Lane Biotechnologies, Llc | Surrobody cojugates |
| WO2013132268A1 (en) * | 2012-03-09 | 2013-09-12 | Ucl Business Plc | Chemical modification of antibodies |
| AR090549A1 (es) | 2012-03-30 | 2014-11-19 | Genentech Inc | Anticuerpos anti-lgr5 e inmunoconjugados |
| CN107011358B (zh) | 2012-04-05 | 2020-05-05 | 内尔维阿诺医学科学有限公司 | 新的烷化剂 |
| RU2632199C2 (ru) | 2012-04-05 | 2017-10-03 | НЕРВИАНО МЕДИКАЛ САЙЕНСИЗ С.р.л. | Функционализированные производные тиеноиндола для лечения ракового заболевания |
| AR090903A1 (es) | 2012-05-01 | 2014-12-17 | Genentech Inc | Anticuerpos e inmunoconjugados anti-pmel17 |
| JP6262209B2 (ja) * | 2012-05-07 | 2018-01-17 | 日東電工株式会社 | リンカーを有するポリマー結合体 |
| EP2849797B1 (en) | 2012-05-15 | 2019-12-18 | Concortis Biosystems, Corp | Drug-conjugates, conjugation methods, and uses thereof |
| AR091098A1 (es) | 2012-05-21 | 2015-01-14 | Genentech Inc | ANTICUERPOS E INMUNOCONJUGADOS CONTRA Ly6E Y METODOS DE USO |
| PE20150325A1 (es) * | 2012-07-09 | 2015-03-05 | Genentech Inc | Inmunoconjugados que comprenden anticuerpos anti-cd22 y derivados de nemorrubicina. |
| EP2869847B1 (en) * | 2012-07-09 | 2017-12-06 | Genentech, Inc. | Immunoconjugates comprising anti-cd79b antibodies |
| AR091961A1 (es) * | 2012-08-02 | 2015-03-11 | Genentech Inc | Inmunoconjugados y anticuerpos anti-etbr (receptor de endotelina b) |
| MX2015001407A (es) * | 2012-08-02 | 2015-05-08 | Genentech Inc | Inmunoconjugados y anticuerpos anti-etbr. |
| CN104755482B (zh) | 2012-10-30 | 2017-04-26 | 内尔维阿诺医学科学有限公司 | 官能化的9‑溴‑喜树碱衍生物 |
| KR102447350B1 (ko) * | 2013-02-08 | 2022-09-23 | 노파르티스 아게 | 면역접합체의 제조를 위한 항체의 변형에 사용되는 특정 부위 |
| US9562099B2 (en) | 2013-03-14 | 2017-02-07 | Genentech, Inc. | Anti-B7-H4 antibodies and immunoconjugates |
| AU2014244424A1 (en) | 2013-03-14 | 2015-08-27 | Genentech, Inc. | Anti-B7-H4 antibodies and immunoconjugates |
| EP2777714A1 (en) | 2013-03-15 | 2014-09-17 | NBE-Therapeutics LLC | Method of producing an immunoligand/payload conjugate by means of a sequence-specific transpeptidase enzyme |
| RU2666356C2 (ru) * | 2013-04-29 | 2018-09-07 | НЕРВИАНО МЕДИКАЛ САЙЕНСИЗ С.р.л. | Новые производные морфолинилантрациклина |
| GB201309807D0 (en) | 2013-05-31 | 2013-07-17 | Pharma Mar Sau | Antibody drug conjugates |
| US10781259B2 (en) | 2013-06-06 | 2020-09-22 | Magenta Therapeutics, Inc. | Modified antibodies and related compounds, compositions, and methods of use |
| TWI725931B (zh) * | 2013-06-24 | 2021-05-01 | 美商建南德克公司 | 抗fcrh5抗體 |
| CA2928568A1 (en) | 2013-07-26 | 2015-01-29 | Update Pharma Inc. | Combinatorial methods to improve the therapeutic benefit of bisantrene |
| US9475874B2 (en) | 2013-08-26 | 2016-10-25 | MabVax Therapeutics, Inc. | Nucleic acids encoding human antibodies to sialyl-lewisa |
| JP2016537399A (ja) * | 2013-09-17 | 2016-12-01 | ジェネンテック, インコーポレイテッド | 抗lgr5抗体を使用する方法 |
| US10266547B2 (en) | 2013-09-25 | 2019-04-23 | Nerviano Medical Sciences S.R.L. | Thieno[2,3-e]indole derivatives as new antitumor agents |
| WO2015057876A1 (en) | 2013-10-15 | 2015-04-23 | Sorrento Therapeutics Inc. | Drug-conjugates with a targeting molecule and two different drugs |
| MX2016004853A (es) | 2013-10-21 | 2016-07-19 | Genentech Inc | Metodos de uso de anticuerpos anti-ly6e. |
| AU2014362238A1 (en) | 2013-12-13 | 2016-06-09 | Genentech, Inc. | Anti-CD33 antibodies and immunoconjugates |
| EP3082874A2 (en) | 2013-12-16 | 2016-10-26 | Genentech, Inc. | Peptidomimetic compounds and antibody-drug conjugates thereof |
| KR102357961B1 (ko) | 2013-12-17 | 2022-02-08 | 제넨테크, 인크. | 항-cd3 항체 및 이의 사용 방법 |
| WO2015149001A1 (en) * | 2014-03-27 | 2015-10-01 | The Brigham And Women's Hospital, Inc. | Metabolically-activated drug conjugates to overcome resistance in cancer therapy |
| MX2016015162A (es) | 2014-05-22 | 2017-03-03 | Genentech Inc | Anticuerpos anti - gpc3 e inmunoconjugados. |
| PT3154583T (pt) | 2014-06-04 | 2021-03-24 | Biontech Res And Development Inc | Anticorpos monoclonais humanos para o gangliósido gd2 |
| KR102557615B1 (ko) | 2014-06-06 | 2023-07-20 | 레드우드 바이오사이언스 인코포레이티드 | 항-her2 항체-메이탄신 컨쥬게이트 및 이것의 사용 방법 |
| EP3186284B1 (en) | 2014-08-28 | 2022-04-06 | BioAtla, Inc. | Conditionally active chimeric antigen receptors for modified t-cells |
| AU2015314826A1 (en) | 2014-09-12 | 2017-03-02 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
| CN107001479B (zh) | 2014-09-12 | 2021-09-28 | 基因泰克公司 | 抗her2抗体和免疫缀合物 |
| JP6622293B2 (ja) | 2014-09-12 | 2019-12-18 | ジェネンテック, インコーポレイテッド | アントラサイクリンジスルフィド中間体、抗体−薬物複合体、及び方法 |
| CN113698485A (zh) | 2014-09-12 | 2021-11-26 | 基因泰克公司 | 抗-b7-h4抗体及免疫缀合物 |
| CA2958479A1 (en) | 2014-09-12 | 2016-03-17 | Genentech, Inc. | Anti-cll-1 antibodies and immunoconjugates |
| GB201419108D0 (en) * | 2014-10-27 | 2014-12-10 | Glythera Ltd | Materials and methods relating to linkers for use in antibody drug conjugates |
| JP6785780B2 (ja) * | 2014-11-05 | 2020-11-18 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | 官能基化モルホリニルアントラサイクリン誘導体 |
| KR20170086121A (ko) * | 2014-12-03 | 2017-07-25 | 제넨테크, 인크. | 4급 아민 화합물 및 그의 항체-약물 접합체 |
| CA2971634C (en) * | 2014-12-23 | 2024-06-04 | Nbe-Therapeutics Ag | Binding protein drug conjugates comprising anthracycline derivatives |
| EP3250238B1 (en) | 2015-01-28 | 2022-06-01 | Sorrento Therapeutics, Inc. | Antibody drug conjugates |
| EP3253212A4 (en) * | 2015-02-06 | 2018-09-19 | Sorrento Therapeutics, Inc. | Antibody drug conjugates |
| JP6979877B2 (ja) | 2015-06-08 | 2021-12-15 | デビオファーム インターナショナル, エス. アー. | 抗cd37イムノコンジュゲートおよび抗cd20抗体の組み合わせ |
| US10323094B2 (en) | 2015-06-16 | 2019-06-18 | Genentech, Inc. | Humanized and affinity matured antibodies to FcRH5 and methods of use |
| ES3020458T3 (en) | 2015-08-07 | 2025-05-22 | Imaginab Inc | Antigen binding constructs to target molecules |
| CA2995243A1 (en) | 2015-08-28 | 2017-03-09 | Debiopharm International, S.A. | Antibodies and assays for detection of cd37 |
| CN108136013B (zh) | 2015-10-05 | 2023-04-18 | 弗雷达克斯有限责任公司 | 抗体多肽及其用途 |
| MA43354A (fr) | 2015-10-16 | 2018-08-22 | Genentech Inc | Conjugués médicamenteux à pont disulfure encombré |
| TWI660741B (zh) | 2015-11-03 | 2019-06-01 | 財團法人工業技術研究院 | 抗體藥物複合物及其製造方法 |
| JP7327899B2 (ja) * | 2015-11-25 | 2023-08-16 | レゴケム バイオサイエンシズ, インク. | 分岐リンカーを含む抗体-薬物複合体及びそれらに関連する方法 |
| US11583593B2 (en) | 2016-01-14 | 2023-02-21 | Synthis Therapeutics, Inc. | Antibody-ALK5 inhibitor conjugates and their uses |
| MX390630B (es) * | 2016-01-25 | 2025-03-21 | Regeneron Pharma | Derivados de maitansinoide, conjugados de los mismos y metodos de uso. |
| CA3016474A1 (en) | 2016-03-15 | 2017-09-21 | Mersana Therapeutics, Inc. | Napi2b-targeted antibody-drug conjugates and methods of use thereof |
| EP3433621A1 (en) * | 2016-03-25 | 2019-01-30 | H. Hoffnabb-La Roche Ag | Multiplexed total antibody and antibody-conjugated drug quantification assay |
| WO2017180842A1 (en) | 2016-04-15 | 2017-10-19 | Bioatla, Llc | Anti-axl antibodies, antibody fragments and their immunoconjugates and uses thereof |
| JP7051715B2 (ja) | 2016-05-13 | 2022-04-11 | バイオアトラ、エルエルシー | 抗Ror2抗体、抗体断片、それらの免疫コンジュゲートおよびそれらの使用 |
| PL3458101T3 (pl) | 2016-05-20 | 2021-05-31 | F. Hoffmann-La Roche Ag | Koniugaty PROTAC-przeciwciało i sposoby ich stosowania |
| WO2017205741A1 (en) | 2016-05-27 | 2017-11-30 | Genentech, Inc. | Bioanalytical method for the characterization of site-specific antibody-drug conjugates |
| US10668166B2 (en) | 2016-05-30 | 2020-06-02 | Toxinvent Ou | Antibody-drug-conjugates comprising novel anthracycline-derivatives for cancer treatment |
| WO2018005660A1 (en) * | 2016-06-28 | 2018-01-04 | University Of Kentucky Research Foundation | Prostaglandin e synthase inhibitors and methods for utilizing the same |
| JP2020510608A (ja) | 2016-11-02 | 2020-04-09 | デビオファーム インターナショナル, エス. アー. | 抗cd37イムノコンジュゲート療法を改善するための方法 |
| NZ750948A (en) | 2016-11-21 | 2020-06-26 | Cureab Gmbh | Anti-gp73 antibodies and immunoconjugates |
| CN108210935B (zh) * | 2016-12-09 | 2023-08-18 | 凯惠科技发展(上海)有限公司 | 抗体药物偶联物、制备方法、中间体、药物组合物及应用 |
| US11266745B2 (en) | 2017-02-08 | 2022-03-08 | Imaginab, Inc. | Extension sequences for diabodies |
| JOP20190254A1 (ar) | 2017-04-27 | 2019-10-27 | Pharma Mar Sa | مركبات مضادة للأورام |
| AU2018289581C1 (en) | 2017-06-23 | 2025-01-30 | VelosBio Inc. | ROR1 antibody immunoconjugates |
| CN111492246A (zh) | 2017-09-20 | 2020-08-04 | 梅尔莎纳医疗公司 | 用于预测对napi2b靶向疗法的响应的组合物和方法 |
| CN111630069B (zh) | 2017-10-13 | 2024-05-31 | 勃林格殷格翰国际有限公司 | 针对Thomsen-nouvelle(Tn)抗原的人抗体 |
| JP2021525735A (ja) | 2018-05-30 | 2021-09-27 | デビオファーム インターナショナル, エス. アー. | 抗cd37免疫コンジュゲート投薬レジメン |
| CA3104934A1 (en) * | 2018-07-09 | 2020-01-16 | Synthis Therapeutics, Inc. | Antibody-alk5 inhibitor conjugates and their uses |
| JP2021532116A (ja) * | 2018-07-23 | 2021-11-25 | マジェンタ セラピューティクス インコーポレイテッドMagenta Therapeutics, Inc. | 同種異系の細胞療法における抗−cd5抗体薬物コンジュゲート(adc)の使用 |
| CA3109790A1 (en) | 2018-08-17 | 2020-02-20 | Mersana Therapeutics, Inc. | Napi2b-targeted polymer antibody-drug conjugates and methods of use thereof |
| WO2020245229A1 (en) | 2019-06-03 | 2020-12-10 | Synaffix B.V. | Acetal-based cleavable linkers |
| CN114206392A (zh) * | 2019-06-10 | 2022-03-18 | 苏特罗生物制药公司 | 免疫调节剂抗体药物偶联物及其用途 |
| GB201908886D0 (en) * | 2019-06-20 | 2019-08-07 | Almac Discovery Ltd | Anthracycline derivatives |
| KR20230042032A (ko) | 2020-07-21 | 2023-03-27 | 제넨테크, 인크. | Brm 분해의 항체 접합 화학 유도제 및 이의 방법 |
| WO2022122709A1 (en) | 2020-12-07 | 2022-06-16 | Sotio Biotech A.S. | Antibody-drug conjugates based on humanized cldn18.2 antibodies |
| AU2021405049A1 (en) * | 2020-12-23 | 2023-06-22 | Sotio Biotech A.S. | Tumor-specific claudin 18.2 antibody-drug conjugates |
| JP7731066B2 (ja) * | 2020-12-25 | 2025-08-29 | パナソニックIpマネジメント株式会社 | 作物収量向上剤、及び、作物収量向上方法 |
| CN112924665B (zh) * | 2021-02-19 | 2023-10-03 | 山东莱博生物科技有限公司 | 一种抗体辣根过氧化物酶标记物及其制备与应用 |
| US12036286B2 (en) | 2021-03-18 | 2024-07-16 | Seagen Inc. | Selective drug release from internalized conjugates of biologically active compounds |
| EP4180061A1 (en) | 2021-11-10 | 2023-05-17 | Nerviano Medical Sciences S.r.l. | Anthracycline derivative linker reagents, antibody-drug conjugates and methods |
| AR128331A1 (es) | 2022-01-26 | 2024-04-17 | Genentech Inc | Inductores químicos de degradación conjugados con anticuerpos y métodos de estos |
| AR128330A1 (es) | 2022-01-26 | 2024-04-17 | Genentech Inc | Inductores químicos de degradación conjugados con anticuerpo y métodos de estos |
| TW202525277A (zh) * | 2023-08-10 | 2025-07-01 | 瑞典商阿斯特捷利康公司 | 蒽環黴素衍生物和綴合物及其用途 |
| WO2025168481A1 (en) | 2024-02-05 | 2025-08-14 | Nerviano Medical Sciences S.R.L. | Imino-anthracycline derivatives and methods |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US5162512A (en) | 1982-03-09 | 1992-11-10 | Cytogen Corporation | Amine derivatives of anthracycline antibodies |
| US4826964A (en) | 1982-07-20 | 1989-05-02 | Sri International | Bridged oxygen analogs of daunorubcin and doxorubicin |
| GB2172594B (en) | 1985-03-22 | 1988-06-08 | Erba Farmitalia | New morpholino derivatives of daunorubicin and doxorubicin |
| US5583024A (en) | 1985-12-02 | 1996-12-10 | The Regents Of The University Of California | Recombinant expression of Coleoptera luciferase |
| IL106992A (en) * | 1988-02-11 | 1994-06-24 | Bristol Myers Squibb Co | Acylhydrazone derivatives of anthracycline and methods for their preparation |
| CA2016584C (en) * | 1989-05-17 | 1999-06-29 | Robert S. Greenfield | Anthracycline conjugates having a novel linker and methods for their production |
| US5304687A (en) | 1989-12-19 | 1994-04-19 | Farmitalia Carlo Erba S.R.L. | Morpholinyl derivatives of doxorubicin and process for their preparation |
| GB9017024D0 (en) * | 1990-08-03 | 1990-09-19 | Erba Carlo Spa | New linker for bioactive agents |
| GB9019933D0 (en) | 1990-09-12 | 1990-10-24 | Erba Carlo Spa | 13-dihydro-3'-(2-alkoxy-4-morphlinyl)anthracyclines |
| CA2048089A1 (en) | 1990-09-17 | 1992-03-18 | Wolfgang A. Wrasidlo | Chemical conjugation of morpholino anthracyclines to antibodies |
| US5776458A (en) * | 1990-12-05 | 1998-07-07 | Pharmacia & Upjohn S.P.A. | Anthracycline-conjugates |
| GB9026491D0 (en) * | 1990-12-05 | 1991-01-23 | Erba Carlo Spa | Anthracycline-conjugates |
| EP0590058B1 (en) | 1991-06-14 | 2003-11-26 | Genentech, Inc. | HUMANIZED Heregulin ANTIBODy |
| US5362852A (en) | 1991-09-27 | 1994-11-08 | Pfizer Inc. | Modified peptide derivatives conjugated at 2-hydroxyethylamine moieties |
| WO1993021319A1 (en) | 1992-04-08 | 1993-10-28 | Cetus Oncology Corporation | HUMANIZED C-erbB-2 SPECIFIC ANTIBODIES |
| EP0616812B1 (en) | 1993-03-24 | 1999-11-03 | Berlex Biosciences | Combination with anti-hormonal compounds and binding molecules for the treatment of cancer |
| GB2296495B (en) | 1994-12-23 | 1998-04-15 | Erba Carlo Spa | Anthracycline derivatives |
| JPH08336393A (ja) | 1995-04-13 | 1996-12-24 | Mitsubishi Chem Corp | 光学活性なγ−置換−β−ヒドロキシ酪酸エステルの製造法 |
| MX9800684A (es) | 1995-07-27 | 1998-04-30 | Genentech Inc | Formulacion de proteinas liofilizadas isotonicas estables. |
| US5843903A (en) | 1995-11-27 | 1998-12-01 | The Administrators Of The Tulane Educational Fund | Targeted cytotoxic anthracycline analogs |
| GB2315067B (en) * | 1996-07-11 | 2000-02-16 | Pharmacia Spa | Morpholinyl anthracycline derivatives |
| US6602677B1 (en) | 1997-09-19 | 2003-08-05 | Promega Corporation | Thermostable luciferases and methods of production |
| JP4689781B2 (ja) | 1998-09-03 | 2011-05-25 | 独立行政法人科学技術振興機構 | アミノ酸輸送蛋白及びその遺伝子 |
| NZ502058A (en) | 1999-12-23 | 2003-11-28 | Ovita Ltd | Isolated mutated nucleic acid molecule for regulation of ovulation rate |
| CA2395660A1 (en) | 1999-12-29 | 2001-07-12 | Immunogen, Inc. | Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use |
| EP1474528A4 (en) | 2000-10-13 | 2006-06-14 | Protein Design Labs Inc | METHODS FOR DIAGNOSING PROSTATE CANCER, COMPOSITIONS AND METHODS FOR SCREENING PROSTATE CANCER MODULATORS |
| AU2002243495A1 (en) | 2001-01-12 | 2002-07-24 | University Of Medicine And Dentistry Of New Jersey | Bone morphogenetic protein-2 in the treatment and diagnosis of cancer |
| MXPA03006617A (es) | 2001-01-24 | 2004-12-02 | Protein Design Labs Inc | Metodos de diagnostico de cancer de pecho, composiciones y metodos de rastreo de moduladores de cancer de pecho. |
| US20040170994A1 (en) | 2001-02-12 | 2004-09-02 | Callen David Frederick | DNA sequences for human tumour suppressor genes |
| EP1243276A1 (en) | 2001-03-23 | 2002-09-25 | Franciscus Marinus Hendrikus De Groot | Elongated and multiple spacers containing activatible prodrugs |
| US20040236091A1 (en) | 2001-03-28 | 2004-11-25 | Chicz Roman M. | Translational profiling |
| AU2002309583A1 (en) | 2001-04-18 | 2002-11-05 | Protein Desing Labs, Inc. | Methods of diagnosis of lung cancer, compositions and methods of screening for modulators of lung cancer |
| AU2002314901A1 (en) | 2001-06-04 | 2002-12-16 | Eos Biotechnology, Inc. | Methods of diagnosis and treatment of androgen-dependent prostate cancer, prostate cancer undergoing androgen-withdrawal, and androgen-independent prostate cancer |
| JP2005505257A (ja) | 2001-06-05 | 2005-02-24 | エクセリクシス・インコーポレイテッド | p53経路のモディファイヤーとしてのIGsおよび使用方法 |
| ATE483976T1 (de) | 2001-06-05 | 2010-10-15 | Exelixis Inc | Gfats als modifikatoren des p53-wegs und verwendungsverfahren |
| JP2005508144A (ja) | 2001-06-18 | 2005-03-31 | イオス バイオテクノロジー,インコーポレイティド | 卵巣癌の診断方法、卵巣癌のモジュレーターをスクリーニングする組成物及び方法 |
| US20050107595A1 (en) | 2001-06-20 | 2005-05-19 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
| US7803915B2 (en) | 2001-06-20 | 2010-09-28 | Genentech, Inc. | Antibody compositions for the diagnosis and treatment of tumor |
| US20040076955A1 (en) | 2001-07-03 | 2004-04-22 | Eos Biotechnology, Inc. | Methods of diagnosis of bladder cancer, compositions and methods of screening for modulators of bladder cancer |
| AU2002324700A1 (en) | 2001-08-14 | 2003-03-03 | Bayer Ag | Nucleic acid and amino acid sequences involved in pain |
| EP1434881A4 (en) | 2001-09-17 | 2005-10-26 | Protein Design Labs Inc | METHOD FOR DIAGNOSIS OF CANCER COMPOSITIONS AND METHOD FOR SCREENING ON CANCER MODULATORS |
| KR101008758B1 (ko) | 2001-09-18 | 2011-01-14 | 제넨테크, 인크. | 종양의 진단 및 치료를 위한 방법 및 이를 위한 조성물 |
| AU2002362454A1 (en) | 2001-10-03 | 2003-04-14 | Origene Technologies, Inc. | Regulated breast cancer genes |
| CN1685055A (zh) | 2001-10-31 | 2005-10-19 | 爱尔康公司 | 骨形态发生蛋白(bmp)、bmp受体和bmp结合蛋白及它们在诊断和治疗青光眼中的用途 |
| WO2003042661A2 (en) | 2001-11-13 | 2003-05-22 | Protein Design Labs, Inc. | Methods of diagnosis of cancer, compositions and methods of screening for modulators of cancer |
| US20030134790A1 (en) | 2002-01-11 | 2003-07-17 | University Of Medicine And Dentistry Of New Jersey | Bone Morphogenetic Protein-2 And Bone Morphogenetic Protein-4 In The Treatment And Diagnosis Of Cancer |
| AU2003232453A1 (en) | 2002-05-30 | 2003-12-19 | David K. Bol | Human solute carrier family 7 member 11 (hslc7a11) |
| EP1570078A4 (en) | 2002-10-04 | 2006-09-13 | Van Andel Res Inst | MOLECULAR CLASSIFICATION OF RENAL TUMORS AND DISCOVERING NEW DIAGNOSTIC MARKERS |
| US20040253606A1 (en) | 2002-11-26 | 2004-12-16 | Protein Design Labs, Inc. | Methods of detecting soft tissue sarcoma, compositions and methods of screening for soft tissue sarcoma modulators |
| US20050227301A1 (en) | 2003-01-10 | 2005-10-13 | Polgen | Cell cycle progression proteins |
| US20040202666A1 (en) | 2003-01-24 | 2004-10-14 | Immunomedics, Inc. | Anti-cancer anthracycline drug-antibody conjugates |
| AU2004222527A1 (en) | 2003-03-18 | 2004-09-30 | Pharmacia Italia Spa | Combined therapy comprising nemorubicin and a cyclooxygenase-2-inhibitor |
| WO2004082579A2 (en) | 2003-03-18 | 2004-09-30 | Pharmacia Italia S.P.A. | Nemorubicin as radiosensitizer in combination with radiation therapy against tumors |
| EP1646401A4 (en) | 2003-06-30 | 2007-07-18 | Bio Technology General Israel | SPECIFIC HUMAN ANTIBODIES |
| NZ583292A (en) | 2003-11-06 | 2012-03-30 | Seattle Genetics Inc | Monomethylvaline compounds capable of conjugation to ligands |
| MXPA06014065A (es) | 2004-06-01 | 2007-01-31 | Genentech Inc | Conjugados de droga-anticuerpo y metodos. |
| ES2579805T3 (es) | 2004-09-23 | 2016-08-16 | Genentech, Inc. | Anticuerpos y conjugados modificados por ingeniería genética con cisteína |
| US20070060534A1 (en) | 2005-06-30 | 2007-03-15 | Threshold Pharmaceuticals, Inc. | Anthracycline analogs |
| PT3248613T (pt) | 2005-07-18 | 2022-03-16 | Seagen Inc | Conjugados de ligante de fármaco e beta-glucuronida |
| CL2008001334A1 (es) | 2007-05-08 | 2008-09-22 | Genentech Inc | Anticuerpo anti-muc16 disenado con cisteina; conjugado que lo comprende; metodo de produccion; formulacion farmaceutica que lo comprende; y su uso para tratar el cancer. |
| WO2009099741A1 (en) * | 2008-02-01 | 2009-08-13 | Genentech, Inc. | Nemorubicin metabolite and analog reagents, antibody-drug conjugates and methods |
| MX2011000509A (es) * | 2008-07-15 | 2011-04-05 | Genentech Inc | Conjugados derivados de antraciclina, proceso para su preparacion y su uso como compuestos antitumorales. |
| KR101897307B1 (ko) * | 2010-12-02 | 2018-09-10 | 네르비아노 메디칼 사이언시스 에스.알.엘. | 모르폴리닐 안트라사이클린 유도체의 제조 방법 |
-
2009
- 2009-07-14 MX MX2011000509A patent/MX2011000509A/es active IP Right Grant
- 2009-07-14 WO PCT/US2009/050537 patent/WO2010009124A2/en not_active Ceased
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- 2009-07-14 SG SG2013053939A patent/SG192517A1/en unknown
- 2009-07-14 KR KR1020117003368A patent/KR101667062B1/ko not_active Expired - Fee Related
- 2009-07-14 AU AU2009270988A patent/AU2009270988A1/en not_active Abandoned
- 2009-07-14 JP JP2011518840A patent/JP6067222B2/ja not_active Expired - Fee Related
- 2009-07-14 EP EP09790394.2A patent/EP2303332B1/en active Active
- 2009-07-14 CN CN2009801359822A patent/CN102159248B/zh not_active Expired - Fee Related
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- 2009-07-14 ES ES09790394.2T patent/ES2532635T3/es active Active
- 2009-07-14 CA CA2727915A patent/CA2727915C/en active Active
- 2009-07-14 TW TW098123764A patent/TWI461428B/zh not_active IP Right Cessation
- 2009-07-14 US US12/502,433 patent/US8900589B2/en active Active
- 2009-07-14 PE PE2011000027A patent/PE20110571A1/es not_active Application Discontinuation
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- 2010-12-15 IL IL210003A patent/IL210003A0/en unknown
- 2010-12-20 ZA ZA2010/09122A patent/ZA201009122B/en unknown
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- 2012-01-27 US US13/360,212 patent/US8389697B2/en not_active Expired - Fee Related
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- 2014-10-30 US US14/528,142 patent/US9695240B2/en not_active Expired - Fee Related
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- 2015-06-03 JP JP2015113517A patent/JP2016006045A/ja active Pending
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