RU2562862C2 - Конъюгаты меченных радиоактивным цирконием сконструированных антител с цистеиновыми заменами - Google Patents
Конъюгаты меченных радиоактивным цирконием сконструированных антител с цистеиновыми заменами Download PDFInfo
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- RU2562862C2 RU2562862C2 RU2012123007/10A RU2012123007A RU2562862C2 RU 2562862 C2 RU2562862 C2 RU 2562862C2 RU 2012123007/10 A RU2012123007/10 A RU 2012123007/10A RU 2012123007 A RU2012123007 A RU 2012123007A RU 2562862 C2 RU2562862 C2 RU 2562862C2
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| PCT/US2010/055465 WO2011056983A1 (en) | 2009-11-05 | 2010-11-04 | Zirconium-radiolabeled, cysteine engineered antibody conjugates |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11779649B2 (en) | 2018-12-21 | 2023-10-10 | Novartis Ag | Antibodies to PMEL17 and conjugates thereof |
| US20230390426A1 (en) * | 2020-10-22 | 2023-12-07 | Nihon Medi-Physics Co., Ltd. | Method for producing radioactive zirconium complex |
| RU2831785C2 (ru) * | 2018-12-21 | 2024-12-13 | Новартис Аг | Антитела к рмel17 и конъюгаты на их основе |
Families Citing this family (168)
| 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 |
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| US20100008978A1 (en) * | 2008-05-09 | 2010-01-14 | The Regents Of The University Of California | Nanoparticles effective for internalization into cells |
| WO2010014222A1 (en) * | 2008-07-30 | 2010-02-04 | Dana-Farber Cancer Institute, Inc. | Compositions for detecting cell death and methods of use thereof |
| ES2712732T3 (es) | 2009-02-17 | 2019-05-14 | Cornell Res Foundation Inc | Métodos y kits para el diagnóstico de cáncer y la predicción de valor terapéutico |
| WO2010099273A1 (en) * | 2009-02-27 | 2010-09-02 | Genentech, Inc. | Methods and compositions for protein labelling |
| AU2010325969B2 (en) | 2009-12-02 | 2016-10-20 | Imaginab, Inc. | J591 minibodies and cys-diabodies for targeting human prostate specific membrane antigen |
| WO2011106297A2 (en) | 2010-02-23 | 2011-09-01 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
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| AU2011265054B2 (en) | 2010-06-08 | 2016-09-15 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
| TW201302793A (zh) | 2010-09-03 | 2013-01-16 | Glaxo Group Ltd | 新穎之抗原結合蛋白 |
| EP3296321B1 (en) | 2010-12-20 | 2020-07-15 | F. Hoffmann-La Roche AG | Anti-mesothelin antibodies and immunoconjugates |
| AR089028A1 (es) | 2011-11-29 | 2014-07-23 | Genentech Inc | Composiciones y metodos para el analisis de cancer de prostata |
| AR090549A1 (es) | 2012-03-30 | 2014-11-19 | Genentech Inc | Anticuerpos anti-lgr5 e inmunoconjugados |
| SG11201407106XA (en) | 2012-05-01 | 2014-11-27 | Genentech Inc | Anti-pmel17 antibodies and immunoconjugates |
| TWI614265B (zh) | 2012-05-21 | 2018-02-11 | 建南德克公司 | 抗-Ly6E抗體及免疫結合物及其使用方法 |
| KR102006997B1 (ko) * | 2012-07-03 | 2019-08-02 | 한국생명공학연구원 | IgG Fc 위치선택적 결합 펩티드 및 이를 포함하는 하이브리드 분자 |
| MX353951B (es) | 2012-07-04 | 2018-02-07 | Hoffmann La Roche | Anticuerpos de anti-teofilina y metodos de uso. |
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| MX354303B (es) | 2012-07-04 | 2018-02-23 | Hoffmann La Roche | Anticuerpos de anti-biotina y metodos de uso. |
| WO2014011327A1 (en) * | 2012-07-12 | 2014-01-16 | Dana-Farber Cancer Institute, Inc. | Radiolabeled probes for the non-invasive detection and imaging of cell death |
| RU2015106946A (ru) | 2012-08-02 | 2016-09-27 | Дженентек, Инк. | Антитела к рецептору эндотелина типа в (etbr) и их иммуноконъюгаты |
| CN104717979A (zh) | 2012-08-02 | 2015-06-17 | 基因泰克公司 | 抗etbr抗体和免疫偶联物 |
| US10344099B2 (en) * | 2012-11-05 | 2019-07-09 | Zenyaku Kogyo Kabushikikaisha | Antibody and antibody composition production method |
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| WO2014100095A1 (en) | 2012-12-19 | 2014-06-26 | Genentech, Inc. | Methods and compositions for radiohalogen protein labeling |
| WO2014124316A2 (en) | 2013-02-08 | 2014-08-14 | Irm Llc | Specific sites for modifying antibodies to make immunoconjugates |
| WO2014164988A1 (en) * | 2013-03-13 | 2014-10-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Tetrahydroxamate chelators of zirconium89 and niobium90 for use in diagnostic applications |
| KR20150127199A (ko) | 2013-03-14 | 2015-11-16 | 제넨테크, 인크. | 항-b7-h4 항체 및 면역접합체 |
| US9562099B2 (en) | 2013-03-14 | 2017-02-07 | Genentech, Inc. | Anti-B7-H4 antibodies and immunoconjugates |
| WO2014144960A2 (en) * | 2013-03-15 | 2014-09-18 | Abbvie Biotherapeutics Inc. | Fc variants |
| US20170035917A1 (en) * | 2013-06-10 | 2017-02-09 | Millennium Pharmaceuticals, Inc. | Methods of treatment of cancer |
| HK1218124A1 (zh) | 2013-09-17 | 2017-02-03 | 豪夫迈.罗氏有限公司 | 使用抗lgr5抗体的方法 |
| KR20160068963A (ko) | 2013-10-21 | 2016-06-15 | 제넨테크, 인크. | 항-Ly6E 항체 및 사용 방법 |
| TW201533060A (zh) | 2013-12-13 | 2015-09-01 | Genentech Inc | 抗cd33抗體及免疫結合物 |
| WO2015095227A2 (en) | 2013-12-16 | 2015-06-25 | Genentech, Inc. | Peptidomimetic compounds and antibody-drug conjugates thereof |
| HK1222577A1 (zh) | 2013-12-16 | 2017-07-07 | Genentech Inc. | 擬肽化合物及其抗體藥物偶聯物 |
| EP3736292B1 (en) | 2013-12-17 | 2024-05-08 | Genentech, Inc. | Anti-cd3 antibodies and methods of use |
| MX373017B (es) | 2014-01-03 | 2020-04-28 | Hoffmann La Roche | Conjugados de toxina polipeptidica-anticuerpo unidos covalentemente. |
| RU2694981C2 (ru) | 2014-01-03 | 2019-07-18 | Ф. Хоффманн-Ля Рош Аг | Ковалентно связанные конъюгаты хеликар-антитело против хеликара и их применения |
| PL3089996T3 (pl) | 2014-01-03 | 2021-12-13 | F. Hoffmann-La Roche Ag | Dwuswoiste przeciwciała przeciw haptenowi/przeciw receptorowi występującemu w barierze krew-mózg, ich kompleksy i ich zastosowanie jako przenośniki wahadłowe występujące w barierze krew-mózg |
| SG11201605903SA (en) | 2014-01-24 | 2016-08-30 | Genentech Inc | Methods of using anti-steap1 antibodies and immunoconjugates |
| EA201691827A1 (ru) * | 2014-03-12 | 2017-01-30 | Новартис Аг | Конкретные участки для модификации антител с целью получения иммуноконъюгатов |
| WO2015179658A2 (en) | 2014-05-22 | 2015-11-26 | Genentech, Inc. | Anti-gpc3 antibodies and immunoconjugates |
| MX2016016233A (es) | 2014-06-11 | 2017-03-31 | Genentech Inc | Anticuerpos anti-lgr5 y sus usos. |
| ES3034398T3 (en) | 2014-08-28 | 2025-08-18 | Bioatla Inc | Conditionally active chimeric antigen receptors for modified t-cells |
| JP6943760B2 (ja) | 2014-09-12 | 2021-10-06 | ジェネンテック, インコーポレイテッド | 抗b7−h4抗体及び免疫複合体 |
| EA201790569A1 (ru) | 2014-09-12 | 2017-08-31 | Дженентек, Инк. | Антитела и иммуноконъюгаты против cll-1 |
| BR112017003236A2 (pt) | 2014-09-12 | 2017-11-28 | Genentech Inc | anticorpos elaborados com cisteína, conjugados de droga e anticorpos, método de preparação de conjugado de droga e anticorpo e composição farmacêutica |
| SG11201701623UA (en) | 2014-09-12 | 2017-03-30 | Genentech Inc | Anti-her2 antibodies and immunoconjugates |
| SI3262071T1 (sl) | 2014-09-23 | 2020-07-31 | F. Hoffmann-La Roche Ag | Način uporabe imunokonjugatov proti CD79b |
| ES2980073T3 (es) * | 2014-10-16 | 2024-09-27 | Univ Melbourne | Composición novedosa de diagnóstico por imágenes y usos de la misma |
| DK3215616T3 (da) * | 2014-11-05 | 2020-03-02 | Illumina Cambridge Ltd | Reducering af DNA-skade under prøvepræparering og sekventering ved anvendelse af siderophor-chelatorer |
| SG11201704625UA (en) | 2014-12-17 | 2017-07-28 | Hoffmann La Roche | Novel methods for enzyme mediated polypeptide conjugation using sortase |
| CN104645364A (zh) * | 2015-01-27 | 2015-05-27 | 南京江原安迪科正电子研究发展有限公司 | 89Zr标记地诺单抗的标记产物及其制备方法、应用 |
| CN114456272A (zh) | 2015-04-03 | 2022-05-10 | 优瑞科生物技术公司 | 靶向afp肽/mhc复合体的构建体及其用途 |
| EP3778640A1 (en) | 2015-05-01 | 2021-02-17 | Genentech, Inc. | Masked anti-cd3 antibodies and methods of use |
| CN108064246A (zh) * | 2015-06-15 | 2018-05-22 | 基因泰克公司 | 抗体和免疫结合物 |
| EP3310811B1 (en) | 2015-06-16 | 2021-06-16 | Genentech, Inc. | Anti-cd3 antibodies and methods of use |
| CN115960230A (zh) | 2015-08-07 | 2023-04-14 | 伊麦吉纳博公司 | 靶向分子的抗原结合构建体 |
| WO2017050889A1 (en) | 2015-09-25 | 2017-03-30 | F. Hoffmann-La Roche Ag | Recombinant immunoglobulin heavy chains comprising a sortase conjugation loop and conjugates thereof |
| CN108026560A (zh) | 2015-09-25 | 2018-05-11 | 豪夫迈·罗氏有限公司 | 在低共熔溶剂中使用分选酶的转酰胺反应 |
| JP6895953B2 (ja) | 2015-09-25 | 2021-06-30 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | ソルターゼaを利用してチオエステルを作製するための方法 |
| JP6998862B2 (ja) | 2015-09-25 | 2022-02-04 | エフ.ホフマン-ラ ロシュ アーゲー | 可溶性ソルターゼa |
| MA43345A (fr) | 2015-10-02 | 2018-08-08 | Hoffmann La Roche | Conjugués anticorps-médicaments de pyrrolobenzodiazépine et méthodes d'utilisation |
| US10758634B2 (en) | 2016-03-18 | 2020-09-01 | Wake Forest University | Compounds, compositions and associated methods using zirconium-89 in immuno-positron emission tomography |
| EP3436578B1 (en) | 2016-03-30 | 2022-01-19 | F. Hoffmann-La Roche AG | Improved sortase |
| EP3441088B1 (en) | 2016-04-06 | 2022-10-05 | Alteogen, Inc. | Antibody-drug conjugate comprising modified antibody |
| AU2017248830B2 (en) | 2016-04-15 | 2023-03-09 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
| CA3019199A1 (en) | 2016-04-15 | 2017-10-19 | Alpine Immune Sciences, Inc. | Icos ligand variant immunomodulatory proteins and uses thereof |
| WO2017180842A1 (en) | 2016-04-15 | 2017-10-19 | Bioatla, Llc | Anti-axl antibodies, antibody fragments and their immunoconjugates and uses thereof |
| CN109311987A (zh) | 2016-05-13 | 2019-02-05 | 生物蛋白有限公司 | 抗ror2抗体、抗体片段和它们的免疫缀合物以及其用途 |
| WO2017223405A1 (en) | 2016-06-24 | 2017-12-28 | Genentech, Inc. | Anti-polyubiquitin multispecific antibodies |
| US11834490B2 (en) | 2016-07-28 | 2023-12-05 | Alpine Immune Sciences, Inc. | CD112 variant immunomodulatory proteins and uses thereof |
| EP3491013A1 (en) | 2016-07-28 | 2019-06-05 | Alpine Immune Sciences, Inc. | Cd155 variant immunomodulatory proteins and uses thereof |
| US11471488B2 (en) | 2016-07-28 | 2022-10-18 | Alpine Immune Sciences, Inc. | CD155 variant immunomodulatory proteins and uses thereof |
| JP7062640B2 (ja) | 2016-07-29 | 2022-05-06 | ジュノー セラピューティクス インコーポレイテッド | 抗cd19抗体に対する抗イディオタイプ抗体 |
| TWI782930B (zh) | 2016-11-16 | 2022-11-11 | 美商再生元醫藥公司 | 抗met抗體,結合met之雙特異性抗原結合分子及其使用方法 |
| EP3543337B1 (en) | 2016-11-18 | 2022-04-20 | Astellas Pharma Inc. | Novel anti-human muc1 antibody fab fragment |
| KR102532256B1 (ko) | 2016-11-21 | 2023-05-12 | 쿠레아브 게엠베하 | 항-gp73 항체 및 면역접합체 |
| MA46952A (fr) | 2016-12-01 | 2019-10-09 | Regeneron Pharma | Anticorps anti-pd-l1 radiomarqués pour imagerie immuno-pet |
| KR20190104528A (ko) | 2016-12-03 | 2019-09-10 | 주노 쎄러퓨티크스 인코퍼레이티드 | Car-t 세포들 투여를 결정하는 방법 |
| WO2018132597A1 (en) | 2017-01-12 | 2018-07-19 | Eureka Therapeutics, Inc. | Constructs targeting histone h3 peptide/mhc complexes and uses thereof |
| WO2018147960A1 (en) | 2017-02-08 | 2018-08-16 | Imaginab, Inc. | Extension sequences for diabodies |
| MY200034A (en) | 2017-02-10 | 2023-12-05 | Regeneron Pharma | Radiolabeled anti-lag3 antibodies for immuno-pet imaging |
| CA3053812A1 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Pd-l2 variant immunomodulatory proteins and uses thereof |
| IL319966A (en) | 2017-03-16 | 2025-05-01 | Alpine Immune Sciences Inc | CD80 Variant Immune Modulator Proteins and Uses Thereof |
| IL320149A (en) | 2017-03-16 | 2025-06-01 | Alpine Immune Sciences Inc | Pd-l1 variant immunomodulatory proteins and uses thereof |
| JP7161490B2 (ja) | 2017-04-12 | 2022-10-26 | エフ.ホフマン-ラ ロシュ アーゲー | アルデヒドを含有する標的分子を標識する方法 |
| MX420947B (es) | 2017-04-26 | 2025-02-10 | Eureka Therapeutics Inc | Constructos que reconocen específicamente glipicano 3 y usos de estos. |
| MX2019014288A (es) | 2017-06-02 | 2020-08-03 | Juno Therapeutics Inc | Articulos de manufactura y metodos relacionados a toxicidad asociada con terapia celular. |
| TWI795415B (zh) | 2017-07-07 | 2023-03-11 | 日商安斯泰來製藥股份有限公司 | 新穎的抗人類CEACAM5抗體Fab片段 |
| CN118307679A (zh) | 2017-07-13 | 2024-07-09 | 豪夫迈·罗氏有限公司 | Pivka的新结合剂和测定 |
| BR112020001360A2 (pt) | 2017-07-24 | 2020-08-11 | Regeneron Pharmaceuticals, Inc. | anticorpo monoclonal isolado ou fragmento de ligação a antígeno deste que se liga a cd8, composição farmacêutica, molécula de ácido nucleico, vetor de expressão, célula hospedeira, conjugado de anticorpo, métodos para gerar imagens de um tecido que expressa cd8, para tratar um sujeito tendo um tumor sólido, para prever uma resposta positiva a uma terapia antitumoral, para monitorar uma resposta de um tumor em um sujeito a uma terapia antitumoral, para prever ou monitorar a eficácia da terapia antitumoral e para monitorar a presença de células t em um tumor ao longo do tempo, e, composto. |
| US11672877B2 (en) * | 2017-08-23 | 2023-06-13 | Wayne State University | In vivo immunoimaging of interferon-gamma |
| KR102813968B1 (ko) | 2017-10-10 | 2025-05-29 | 알파인 이뮨 사이언시즈, 인코포레이티드 | Ctla-4 변이체 면역조절 단백질 및 이의 용도 |
| TW202500579A (zh) | 2017-10-18 | 2025-01-01 | 美商艾爾潘免疫科學有限公司 | 變異型icos 配位體免疫調節蛋白及相關組合物及方法 |
| WO2019077113A1 (en) | 2017-10-20 | 2019-04-25 | F. Hoffmann-La Roche Ag | COPY PROTECTION FOR ANTIBODIES |
| US12031975B2 (en) | 2017-11-01 | 2024-07-09 | Juno Therapeutics, Inc. | Methods of assessing or monitoring a response to a cell therapy |
| US11564946B2 (en) | 2017-11-01 | 2023-01-31 | Juno Therapeutics, Inc. | Methods associated with tumor burden for assessing response to a cell therapy |
| KR20200116081A (ko) | 2017-12-01 | 2020-10-08 | 주노 쎄러퓨티크스 인코퍼레이티드 | 유전자 조작된 세포의 투약 및 조절 방법 |
| US12297253B2 (en) | 2018-01-03 | 2025-05-13 | Alpine Immune Sciences, Inc. | Multi-domain immunomodulatory proteins and methods of use thereof |
| WO2019147912A1 (en) * | 2018-01-26 | 2019-08-01 | Wake Forest University | Kit technology for the production and long-term storage of zr-89-pet radiopharmaceuticals |
| US20200405890A1 (en) * | 2018-02-21 | 2020-12-31 | Cytomx Therapeutics, Inc. | Positron emission tomography imaging of activatable binding polypeptides and related compositions thereof |
| CN111801351A (zh) | 2018-03-14 | 2020-10-20 | 豪夫迈·罗氏有限公司 | 抗体亲和力成熟的方法 |
| CN111971300B (zh) | 2018-03-14 | 2024-10-29 | 豪夫迈·罗氏有限公司 | 新颖的抗-肌钙蛋白t抗体 |
| CN111936522B (zh) | 2018-04-18 | 2024-07-02 | 豪夫迈·罗氏有限公司 | 新型抗胸苷激酶抗体 |
| WO2019221269A1 (ja) | 2018-05-17 | 2019-11-21 | アステラス製薬株式会社 | 抗ヒトMUC1抗体Fabフラグメント、ペプチドリンカー及び/又は配位子を含む複合体 |
| WO2019241758A1 (en) | 2018-06-15 | 2019-12-19 | Alpine Immune Sciences, Inc. | Pd-1 variant immunomodulatory proteins and uses thereof |
| US11993661B2 (en) | 2018-06-18 | 2024-05-28 | Eureka Therapeutics, Inc. | Constructs targeting prostate-specific membrane antigen (PSMA) and uses thereof |
| EP3844503B1 (en) | 2018-08-31 | 2024-05-29 | F. Hoffmann-La Roche AG | Thymidine kinase (tk-1) in prognostic indices for dlbcl |
| CN112839683B (zh) | 2018-10-10 | 2023-11-14 | 安斯泰来制药株式会社 | 含有标记部-抗人抗体Fab片段复合物的药物组合物 |
| CN120623346A (zh) | 2018-10-11 | 2025-09-12 | 因荷布瑞克斯生物科学公司 | Pd-1单结构域抗体及其治疗组合物 |
| CN113166263A (zh) | 2018-10-11 | 2021-07-23 | 印希比股份有限公司 | Dll3单域抗体及其治疗性组合物 |
| US20210340273A1 (en) | 2018-10-11 | 2021-11-04 | Inhlbrx, inc. | 5t4 single domain antibodies and therapeutic compositions thereof |
| US20230124851A1 (en) | 2018-10-11 | 2023-04-20 | Inhibrx, lnc. | B7h3 single domain antibodies and therapeutic compositions thereof |
| WO2020113141A2 (en) | 2018-11-30 | 2020-06-04 | Alpine Immune Sciences, Inc. | Cd86 variant immunomodulatory proteins and uses thereof |
| JP7695882B2 (ja) | 2018-11-30 | 2025-06-19 | ジュノー セラピューティクス インコーポレイテッド | 養子細胞療法を用いた処置のための方法 |
| KR20210100668A (ko) | 2018-12-06 | 2021-08-17 | 제넨테크, 인크. | 항-CD79b 면역접합체, 알킬화제 및 항-CD20 항체를 포함하는 미만성 큰 B-세포 림프종의 조합 요법 |
| WO2020163589A1 (en) | 2019-02-08 | 2020-08-13 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| EP3948274A1 (en) | 2019-03-29 | 2022-02-09 | Rakuten Medical, Inc. | Methods for photoimmunotherapy and related biomarkers |
| KR20220007136A (ko) | 2019-05-14 | 2022-01-18 | 제넨테크, 인크. | 소포 림프종을 치료하기 위한 항-CD79b 면역접합체의 사용 방법 |
| WO2020236679A1 (en) * | 2019-05-17 | 2020-11-26 | Cytomx Therapeutics, Inc. | Methods and compositions for determining the biodistribution of activatable anti-cd166 antibody conjugates |
| CA3142322A1 (en) * | 2019-05-31 | 2020-12-03 | D&D Pharmatech Inc. | Physiologically active substance bound to biotin moiety, and composition for oral administration including the same |
| JP7784899B2 (ja) * | 2019-06-17 | 2025-12-12 | タグワークス ファーマシューティカルス ビー.ブイ. | 高速で且つ効率的なクリック放出の為の化合物 |
| US20200399372A1 (en) | 2019-06-21 | 2020-12-24 | Regeneron Pharmaceuticals, Inc. | Use of bispecific antigen-binding molecules that bind psma and cd3 in combination with 4-1bb co-stimulation |
| CN113993547B (zh) | 2019-06-21 | 2024-04-26 | 瑞泽恩制药公司 | 结合muc16和cd3的双特异性抗原结合分子与4-1bb共刺激组合的用途 |
| KR20220063185A (ko) | 2019-09-16 | 2022-05-17 | 리제너론 파마슈티칼스 인코포레이티드 | 면역-pet 영상화를 위한 방사성 표지된 met 결합 단백질 |
| KR20220086618A (ko) | 2019-10-18 | 2022-06-23 | 제넨테크, 인크. | 미만성 거대 B-세포 림프종을 치료하기 위한 항-CD79b 면역접합체의 사용 방법 |
| EP4069742A1 (en) | 2019-12-06 | 2022-10-12 | Juno Therapeutics, Inc. | Anti-idiotypic antibodies to gprc5d-targeted binding domains and related compositions and methods |
| WO2021113776A1 (en) | 2019-12-06 | 2021-06-10 | Juno Therapeutics, Inc. | Anti-idiotypic antibodies to bcma-targeted binding domains and related compositions and methods |
| IL294879A (en) | 2020-01-29 | 2022-09-01 | Inhibrx Inc | Monodomain antibodies of cd28 and their multivalent and multispecific constructs |
| CN115916822A (zh) | 2020-04-24 | 2023-04-04 | 基因泰克公司 | 使用抗CD79b免疫缀合物的方法 |
| KR20230095918A (ko) | 2020-08-05 | 2023-06-29 | 주노 쎄러퓨티크스 인코퍼레이티드 | Ror1-표적 결합 도메인에 대한 항이디오타입 항체 및 관련 조성물 및 방법 |
| EP4196612A1 (en) | 2020-08-12 | 2023-06-21 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| JP7641374B2 (ja) | 2020-10-30 | 2025-03-06 | エフ. ホフマン-ラ ロシュ アーゲー | 胆管癌のマーカーとしてのtimp1 |
| EP4271482A2 (en) | 2020-12-31 | 2023-11-08 | Alamar Biosciences, Inc. | Binder molecules with high affinity and/ or specificity and methods of making and use thereof |
| CN117396232A (zh) | 2021-05-12 | 2024-01-12 | 基因泰克公司 | 使用抗cd79b免疫缀合物治疗弥漫性大b细胞淋巴瘤的方法 |
| US20240336697A1 (en) | 2021-08-07 | 2024-10-10 | Genentech, Inc. | Methods of using anti-cd79b immunoconjugates to treat diffuse large b-cell lymphoma |
| EP4396223A1 (en) | 2021-08-30 | 2024-07-10 | Genentech, Inc. | Anti-polyubiquitin multispecific antibodies |
| WO2023111168A1 (en) | 2021-12-17 | 2023-06-22 | F. Hoffmann-La Roche Ag | A novel antibody for detection of amyloid beta 42 (aβ42) |
| WO2023172883A1 (en) | 2022-03-07 | 2023-09-14 | Alpine Immune Sciences, Inc. | Immunomodulatory proteins of variant cd80 polypeptides, cell therapies thereof and related methods and uses |
| CN119562970A (zh) | 2022-03-18 | 2025-03-04 | 进化免疫治疗公司 | 双特异性抗体融合分子及其使用方法 |
| KR20250133750A (ko) | 2023-01-09 | 2025-09-08 | 오디세이 테라퓨틱스, 인코포레이티드 | 항-tnfr2 항원-결합 단백질 및 그의 용도 |
| US20240299601A1 (en) | 2023-02-17 | 2024-09-12 | Regeneron Pharmaceuticals, Inc. | Radiolabeled anti-lag3 antibodies for immuno-pet imaging |
| AU2024234615A1 (en) | 2023-03-14 | 2025-08-21 | Odyssey Therapeutics, Inc. | Anti-cd25 antigen-binding proteins and uses thereof |
| WO2024196776A2 (en) * | 2023-03-17 | 2024-09-26 | Dana-Farber Cancer Institute, Inc. | Developing an anti-human cd45 imaging probe for noninvasive detection of human immune cells |
| AR132699A1 (es) | 2023-05-17 | 2025-07-23 | Odyssey Therapeutics Inc | Anticuerpos de dominio único modificados |
| TW202504641A (zh) | 2023-06-08 | 2025-02-01 | 美商建南德克公司 | 用於淋巴瘤之診斷及治療方法的巨噬細胞特徵 |
| AU2024308381A1 (en) | 2023-06-29 | 2025-11-20 | Odyssey Therapeutics, Inc. | Anti-trailr2 antigen-binding proteins and uses thereof |
| WO2025038492A1 (en) | 2023-08-11 | 2025-02-20 | Abalytics Oncology, Inc. | Anti-ctla-4 antibodies and related binding molecules and methods and uses thereof |
| CN117198390B (zh) * | 2023-09-08 | 2024-03-12 | 中国科学院广州生物医药与健康研究院 | 通过设计和改造二硫键交联位点的slc膜蛋白复合物的制备方法 |
| TW202530265A (zh) | 2023-10-13 | 2025-08-01 | 美商奧迪希治療公司 | 抗cdh17抗原結合蛋白及其用途 |
| WO2025111402A1 (en) | 2023-11-21 | 2025-05-30 | Board Of Regents Of The University Of Nebraska | Anti-amyloid beta antibodies and related compositions and methods thereof |
| WO2025137344A1 (en) | 2023-12-20 | 2025-06-26 | Bristol-Myers Squibb Company | Antibodies targeting il-18 receptor beta (il-18rβ) and related methods |
| WO2025199352A2 (en) | 2024-03-20 | 2025-09-25 | Juno Therapeutics, Inc. | Antibodies specific for solute carrier family 34 member 2 (slc34a2) |
| WO2025217240A1 (en) | 2024-04-10 | 2025-10-16 | Odyssey Therapeutics, Inc. | Anti-tnfr2 antigen-binding proteins and uses thereof |
| WO2025240670A2 (en) | 2024-05-15 | 2025-11-20 | Abalytics Oncology, Inc. | Anti-pd-1 antibodies and related binding molecules and methods and uses thereof |
| WO2025255558A2 (en) | 2024-06-07 | 2025-12-11 | Odyssey Therapeutics, Inc. | Anti-thymic stromal lymphopoietin (tslp) antigen-binding proteins and uses thereof |
| WO2025255435A2 (en) | 2024-06-07 | 2025-12-11 | Odyssey Therapeutics, Inc. | Antigen-binding proteins against serum albumin and uses thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006034488A2 (en) * | 2004-09-23 | 2006-03-30 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
Family Cites Families (290)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US4275149A (en) | 1978-11-24 | 1981-06-23 | Syva Company | Macromolecular environment control in specific receptor assays |
| US4318980A (en) | 1978-04-10 | 1982-03-09 | Miles Laboratories, Inc. | Heterogenous specific binding assay employing a cycling reactant as label |
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US4415732A (en) | 1981-03-27 | 1983-11-15 | University Patents, Inc. | Phosphoramidite compounds and processes |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| JPS6098584A (ja) | 1983-11-02 | 1985-06-01 | Canon Inc | カメラ―体形vtr |
| US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
| US5342606A (en) | 1984-10-18 | 1994-08-30 | Board Of Regents, The University Of Texas System | Polyazamacrocyclic compounds for complexation of metal ions |
| US5316757A (en) | 1984-10-18 | 1994-05-31 | Board Of Regents, The University Of Texas System | Synthesis of polyazamacrocycles with more than one type of side-chain chelating groups |
| US4737456A (en) | 1985-05-09 | 1988-04-12 | Syntex (U.S.A.) Inc. | Reducing interference in ligand-receptor binding assays |
| US5091178A (en) | 1986-02-21 | 1992-02-25 | Oncogen | Tumor therapy with biologically active anti-tumor antibodies |
| IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
| GB8720833D0 (en) * | 1987-09-04 | 1987-10-14 | Celltech Ltd | Recombinant dna product |
| WO1989006692A1 (en) | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Method of treating tumor cells by inhibiting growth factor receptor function |
| US5262530A (en) | 1988-12-21 | 1993-11-16 | Applied Biosystems, Inc. | Automated system for polynucleotide synthesis and purification |
| US5047524A (en) | 1988-12-21 | 1991-09-10 | Applied Biosystems, Inc. | Automated system for polynucleotide synthesis and purification |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| WO1991002536A1 (en) | 1989-08-23 | 1991-03-07 | Scripps Clinic And Research Foundation | Compositions and methods for detection and treatment of epstein-barr virus infection and immune disorders |
| US5183884A (en) | 1989-12-01 | 1993-02-02 | United States Of America | Dna segment encoding a gene for a receptor related to the epidermal growth factor receptor |
| US5256643A (en) | 1990-05-29 | 1993-10-26 | The Government Of The United States | Human cripto protein |
| AU9016591A (en) | 1990-10-25 | 1992-05-26 | Tanox Biosystems, Inc. | Glycoproteins associated with membrane-bound immunoglobulins as antibody targets on B cells |
| US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
| CA2407304A1 (en) | 1991-03-29 | 1992-10-15 | Genentech, Inc. | Human pf4a receptors and their use |
| US5543503A (en) | 1991-03-29 | 1996-08-06 | Genentech Inc. | Antibodies to human IL-8 type A receptor |
| US5440021A (en) | 1991-03-29 | 1995-08-08 | Chuntharapai; Anan | Antibodies to human IL-8 type B receptor |
| DE122004000008I1 (de) | 1991-06-14 | 2005-06-09 | Genentech Inc | Humanisierter Heregulin Antikörper. |
| JP3050424B2 (ja) | 1991-07-12 | 2000-06-12 | 塩野義製薬株式会社 | ヒトエンドセリンリセプター |
| US5264557A (en) | 1991-08-23 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Polypeptide of a human cripto-related gene, CR-3 |
| FI941572A7 (fi) | 1991-10-07 | 1994-05-27 | Oncologix Inc | Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenete lmä |
| US6153408A (en) | 1991-11-15 | 2000-11-28 | Institut Pasteur And Institut National De La Sante Et De La Recherche Medicale | Altered major histocompatibility complex (MHC) determinant and methods of using the determinant |
| US6011146A (en) | 1991-11-15 | 2000-01-04 | Institut Pasteur | Altered major histocompatibility complex (MHC) determinant and methods of using the determinant |
| EP1136556B1 (en) | 1991-11-25 | 2005-06-08 | Enzon, Inc. | Method of producing multivalent antigen-binding proteins |
| US5428139A (en) | 1991-12-10 | 1995-06-27 | The Dow Chemical Company | Bicyclopolyazamacrocyclophosphonic acid complexes for use as radiopharmaceuticals |
| US5739294A (en) | 1991-12-10 | 1998-04-14 | The Dow Chemical Company | Bicyclopol yazamacrocyclophosphonic acid complexes for use as contrast agents |
| US5480990A (en) | 1991-12-10 | 1996-01-02 | The Dow Chemical Company | Bicyclopolyazamacrocyclocarboxylic acid complexes for use as contrast agents |
| JPH08500962A (ja) | 1992-02-06 | 1996-02-06 | クリエイティブ バイオモレキュルズ,インコーポレイテッド | 癌マーカー用生物合成結合蛋白質 |
| WO1993021319A1 (en) | 1992-04-08 | 1993-10-28 | Cetus Oncology Corporation | HUMANIZED C-erbB-2 SPECIFIC ANTIBODIES |
| IL107366A (en) | 1992-10-23 | 2003-03-12 | Chugai Pharmaceutical Co Ltd | Genes coding for megakaryocyte potentiator |
| EP1005870B1 (en) | 1992-11-13 | 2009-01-21 | Biogen Idec Inc. | Therapeutic application of chimeric antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma |
| CA2103323A1 (en) | 1992-11-24 | 1994-05-25 | Gregory D. Plowman | Her4 human receptor tyrosine kinase |
| US5644033A (en) | 1992-12-22 | 1997-07-01 | Health Research, Inc. | Monoclonal antibodies that define a unique antigen of human B cell antigen receptor complex and methods of using same for diagnosis and treatment |
| US5801005A (en) | 1993-03-17 | 1998-09-01 | University Of Washington | Immune reactivity to HER-2/neu protein for diagnosis of malignancies in which the HER-2/neu oncogene is associated |
| US5869445A (en) | 1993-03-17 | 1999-02-09 | University Of Washington | Methods for eliciting or enhancing reactivity to HER-2/neu protein |
| US5385893A (en) | 1993-05-06 | 1995-01-31 | The Dow Chemical Company | Tricyclopolyazamacrocyclophosphonic acids, complexes and derivatives thereof, for use as contrast agents |
| US5462725A (en) | 1993-05-06 | 1995-10-31 | The Dow Chemical Company | 2-pyridylmethylenepolyazamacrocyclophosphonic acids, complexes and derivatives thereof, for use as contrast agents |
| US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
| US5773223A (en) | 1993-09-02 | 1998-06-30 | Chiron Corporation | Endothelin B1, (ETB1) receptor polypeptide and its encoding nucleic acid methods, and uses thereof |
| CZ292061B6 (cs) | 1994-03-17 | 2003-07-16 | Merck Patent Gmbh | Jednořetězcové fragmenty protilátek a protilátky proti receptoru epidermálního růstového faktoru, způsob jejich přípravy a farmaceutický prostředek, který je obsahuje |
| US5750370A (en) | 1995-06-06 | 1998-05-12 | Human Genome Sciences, Inc. | Nucleic acid encoding human endothlein-bombesin receptor and method of producing the receptor |
| US5707829A (en) | 1995-08-11 | 1998-01-13 | Genetics Institute, Inc. | DNA sequences and secreted proteins encoded thereby |
| MX9800684A (es) | 1995-07-27 | 1998-04-30 | Genentech Inc | Formulacion de proteinas liofilizadas isotonicas estables. |
| US20020193567A1 (en) | 1995-08-11 | 2002-12-19 | Genetics Institute, Inc. | Secreted proteins and polynucleotides encoding them |
| AU7240096A (en) * | 1995-09-18 | 1997-04-09 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Neutralizing monoclonal antibodies to respiratory syncytial virus |
| US5834456A (en) | 1996-02-23 | 1998-11-10 | The Dow Chemical Company | Polyazamacrocyclofluoromonoalkylphosphonic acids, and their complexes, for use as contrast agents |
| JP3646191B2 (ja) | 1996-03-19 | 2005-05-11 | 大塚製薬株式会社 | ヒト遺伝子 |
| EP1728802A3 (en) | 1996-03-27 | 2006-12-13 | Genentech, Inc. | ErbB3 antibodies |
| WO1997044452A1 (en) | 1996-05-17 | 1997-11-27 | Schering Corporation | Human b-cell antigens, related reagents |
| US5945511A (en) | 1997-02-20 | 1999-08-31 | Zymogenetics, Inc. | Class II cytokine receptor |
| US20030185830A1 (en) | 1997-02-25 | 2003-10-02 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of prostate cancer |
| US7033827B2 (en) | 1997-02-25 | 2006-04-25 | Corixa Corporation | Prostate-specific polynucleotide compositions |
| US6261791B1 (en) | 1997-03-10 | 2001-07-17 | The Regents Of The University Of California | Method for diagnosing cancer using specific PSCA antibodies |
| US6541212B2 (en) | 1997-03-10 | 2003-04-01 | The Regents Of The University Of California | Methods for detecting prostate stem cell antigen protein |
| EP0981541B1 (en) | 1997-03-10 | 2004-06-02 | The Regents Of The University Of California | Psca: prostate stem cell antigen |
| US6555339B1 (en) | 1997-04-14 | 2003-04-29 | Arena Pharmaceuticals, Inc. | Non-endogenous, constitutively activated human protein-coupled receptors |
| US6319688B1 (en) | 1997-04-28 | 2001-11-20 | Smithkline Beecham Corporation | Polynucleotide encoding human sodium dependent phosphate transporter (IPT-1) |
| WO1998051824A1 (en) | 1997-05-15 | 1998-11-19 | Abbott Laboratories | Reagents and methods useful for detecting disease of the urinary tract |
| US6890749B2 (en) | 1997-05-15 | 2005-05-10 | Abbott Laboratories | Reagents and methods useful for detecting diseases of the prostate |
| US6753165B1 (en) * | 1999-01-14 | 2004-06-22 | Bolder Biotechnology, Inc. | Methods for making proteins containing free cysteine residues |
| US6248564B1 (en) * | 1997-08-29 | 2001-06-19 | Harvard University | Mutant MHC class I molecules |
| WO1999019488A1 (en) | 1997-10-15 | 1999-04-22 | Children's Medical Center Corporation | Novel human egf receptors and use thereof |
| US20030060612A1 (en) | 1997-10-28 | 2003-03-27 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
| US20020034749A1 (en) | 1997-11-18 | 2002-03-21 | Billing-Medel Patricia A. | Reagents and methods useful for detecting diseases of the breast |
| US6110695A (en) | 1997-12-02 | 2000-08-29 | The Regents Of The University Of California | Modulating the interaction of the chemokine, B Lymphocyte Hemoattractant, and its Receptor, BLR1 |
| WO2004031238A2 (en) | 2002-10-03 | 2004-04-15 | Mcgill Univeristy | Antibodies and cyclic peptides which bind cea (carcinoembryonic antigen) and their use as cancer therapeutics |
| JP4603157B2 (ja) | 1998-03-13 | 2010-12-22 | ザ バーナム インスティチュート | 種々の選択された器官または組織にホーミングする分子 |
| US6528624B1 (en) | 1998-04-02 | 2003-03-04 | Genentech, Inc. | Polypeptide variants |
| US6534482B1 (en) | 1998-05-13 | 2003-03-18 | Epimmune, Inc. | Expression vectors for stimulating an immune response and methods of using the same |
| US20030064397A1 (en) | 1998-05-22 | 2003-04-03 | Incyte Genomics, Inc. | Transmembrane protein differentially expressed in prostate and lung tumors |
| US20020187472A1 (en) | 2001-03-09 | 2002-12-12 | Preeti Lal | Steap-related protein |
| WO2000012130A1 (en) | 1998-08-27 | 2000-03-09 | Smithkline Beecham Corporation | Rp105 agonists and antagonists |
| 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 |
| AU5963699A (en) | 1998-10-02 | 2000-04-26 | Mcmaster University | Spliced form of (erb)b-2/neu oncogene |
| WO2001057188A2 (en) | 2000-02-03 | 2001-08-09 | Hyseq, Inc. | Novel nucleic acids and polypeptides |
| US6858710B2 (en) | 1998-12-17 | 2005-02-22 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of ovarian cancer |
| US6468546B1 (en) | 1998-12-17 | 2002-10-22 | Corixa Corporation | Compositions and methods for therapy and diagnosis of ovarian cancer |
| US20030091580A1 (en) | 2001-06-18 | 2003-05-15 | Mitcham Jennifer L. | Compositions and methods for the therapy and diagnosis of ovarian cancer |
| US6962980B2 (en) | 1999-09-24 | 2005-11-08 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of ovarian cancer |
| US20020119158A1 (en) | 1998-12-17 | 2002-08-29 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of ovarian cancer |
| WO2000040614A2 (en) | 1998-12-30 | 2000-07-13 | Beth Israel Deaconess Medical Center, Inc. | Characterization of the soc/crac calcium channel protein family |
| CA2361009C (en) | 1999-01-29 | 2012-10-23 | Corixa Corporation | Her-2/neu fusion proteins |
| GB9905124D0 (en) | 1999-03-05 | 1999-04-28 | Smithkline Beecham Biolog | Novel compounds |
| US7232889B2 (en) | 1999-03-08 | 2007-06-19 | Genentech, Inc. | PRO300 antibodies |
| AU3395900A (en) | 1999-03-12 | 2000-10-04 | Human Genome Sciences, Inc. | Human lung cancer associated gene sequences and polypeptides |
| US7304126B2 (en) | 1999-05-11 | 2007-12-04 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| US7049410B2 (en) | 1999-05-14 | 2006-05-23 | Majumdar Adhip P N | Antibodies to a novel EGF-receptor related protein (ERRP) |
| US6399743B1 (en) | 1999-05-14 | 2002-06-04 | Dept. Of Veterans Affairs | Isolation and characterization of a rat epidermal growth factor related protein |
| AU4952600A (en) | 1999-06-03 | 2000-12-28 | Takeda Chemical Industries Ltd. | Screening method with the use of cd100 |
| HU230586B1 (hu) | 1999-06-25 | 2017-02-28 | Genentech, Inc. | Anti-ErbB antitest/maytansinoid konjugátumok alkalmazása rákos betegségek kezelésére szolgáló gyógyszer előállítására |
| MXPA01013458A (es) | 1999-06-25 | 2002-07-30 | Genentech Inc | Anticuerpos humanizados anti-erbb2 y tratamiento con anticuerpos anti-erbb2. |
| US7589172B2 (en) | 1999-07-20 | 2009-09-15 | Genentech, Inc. | PRO256 polypeptides |
| US7297770B2 (en) | 1999-08-10 | 2007-11-20 | Genentech, Inc. | PRO6496 polypeptides |
| US7294696B2 (en) | 1999-08-17 | 2007-11-13 | Genentech Inc. | PRO7168 polypeptides |
| AU7573000A (en) | 1999-09-01 | 2001-03-26 | Genentech Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| US20030232056A1 (en) | 1999-09-10 | 2003-12-18 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of ovarian cancer |
| US20030206918A1 (en) | 1999-09-10 | 2003-11-06 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of ovarian cancer |
| US20030129192A1 (en) | 1999-09-10 | 2003-07-10 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of ovarian cancer |
| AU778199B2 (en) | 1999-10-29 | 2004-11-25 | Genentech Inc. | Anti-prostate stem cell antigen (PSCA) antibody compositions and methods of use |
| US6372907B1 (en) | 1999-11-03 | 2002-04-16 | Apptera Corporation | Water-soluble rhodamine dye peptide conjugates |
| ES2586850T3 (es) | 1999-11-29 | 2016-10-19 | The Trustees Of Columbia University In The City Of New York | Aislamiento de cinco genes novedosos que codifican nuevos melanomas de tipo receptor de Fc implicados en la patogénesis del linfoma/melanoma |
| CA2392510A1 (en) | 1999-11-30 | 2001-06-07 | Corixa Corporation | Compositions and methods for therapy and diagnosis of breast cancer |
| JP2003530083A (ja) | 1999-12-10 | 2003-10-14 | エピミューン インコーポレイテッド | ペプチドおよび核酸組成物を使用する、HER2/neuに対する細胞性免疫応答の誘導 |
| WO2001046261A1 (en) | 1999-12-23 | 2001-06-28 | Zymogenetics, Inc. | Method for treating inflammation |
| DE60045139D1 (de) | 1999-12-23 | 2010-12-02 | Zymogenetics Inc | Löslicher Interleukin-20-Rezeptor |
| NZ502058A (en) | 1999-12-23 | 2003-11-28 | Ovita Ltd | Isolated mutated nucleic acid molecule for regulation of ovulation rate |
| US6610286B2 (en) | 1999-12-23 | 2003-08-26 | Zymogenetics, Inc. | Method for treating inflammation using soluble receptors to interleukin-20 |
| US20040001827A1 (en) | 2002-06-28 | 2004-01-01 | Dennis Mark S. | Serum albumin binding peptides for tumor targeting |
| WO2001045746A2 (en) | 1999-12-24 | 2001-06-28 | Genentech, Inc. | Methods and compositions for prolonging elimination half-times of bioactive compounds |
| US7294695B2 (en) | 2000-01-20 | 2007-11-13 | Genentech, Inc. | PRO10268 polypeptides |
| WO2001053463A2 (en) | 2000-01-21 | 2001-07-26 | Corixa Corporation | COMPOUNDS AND METHODS FOR PREVENTION AND TREATMENT OF HER-2/neu ASSOCIATED MALIGNANCIES |
| US20030224379A1 (en) | 2000-01-21 | 2003-12-04 | Tang Y. Tom | Novel nucleic acids and polypeptides |
| AU2001238596A1 (en) | 2000-02-22 | 2001-09-03 | Millennium Pharmaceuticals, Inc. | 18607, a novel human calcium channel |
| US20030219806A1 (en) | 2000-02-22 | 2003-11-27 | Millennium Pharmaceuticals, Inc. | Novel 18607, 15603, 69318, 12303, 48000, 52920, 5433, 38554, 57301, 58324, 55063, 52991, 59914, 59921 and 33751 molecules and uses therefor |
| US20040005561A1 (en) | 2000-03-01 | 2004-01-08 | Corixa Corporation | Compositions and methods for the detection, diagnosis and therapy of hematological malignancies |
| US20040002068A1 (en) | 2000-03-01 | 2004-01-01 | Corixa Corporation | Compositions and methods for the detection, diagnosis and therapy of hematological malignancies |
| WO2001066689A2 (en) | 2000-03-07 | 2001-09-13 | Hyseq, Inc. | Novel nucleic acids and polypeptides |
| US7097840B2 (en) * | 2000-03-16 | 2006-08-29 | Genentech, Inc. | Methods of treatment using anti-ErbB antibody-maytansinoid conjugates |
| AU4941101A (en) | 2000-03-24 | 2001-10-08 | Fahri Saatcioglu | Novel prostate-specific or testis-specific nucleic acid molecules, polypeptides,and diagnostic and therapeutic methods |
| AU2001250412A1 (en) | 2000-03-31 | 2001-10-08 | Ipf Pharmaceuticals Gmbh | Diagnostic and medicament for analysing the cell surface proteome of tumour and inflammatory cells and for treating tumorous and inflammatory diseases, preferably using specific chemokine receptor analysis and the chemokine receptor-ligand interaction |
| AU2001253140A1 (en) | 2000-04-03 | 2001-10-15 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Tumor markers in ovarian cancer |
| JP2003532057A (ja) | 2000-04-07 | 2003-10-28 | アリーナ・フアーマシユーチカルズ・インコーポレーテツド | 非内因性の、構成的に活性化される既知gタンパク質−共役受容体 |
| US20030119115A1 (en) | 2000-05-17 | 2003-06-26 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| AU2001263105A1 (en) | 2000-05-18 | 2001-11-26 | Lexicon Genetics Incorporated | Human semaphorin homologs and polynucleotides encoding the same |
| AU2001274888A1 (en) | 2000-05-19 | 2001-12-03 | Human Genome Sciences, Inc. | Nucleic acids, proteins, and antibodies |
| WO2001094641A2 (en) | 2000-06-09 | 2001-12-13 | Idec Pharmaceuticals Corporation | Gene targets and ligands that bind thereto for treatment and diagnosis of ovarian carcinomas |
| WO2001098351A2 (en) | 2000-06-16 | 2001-12-27 | Incyte Genomics, Inc. | G-protein coupled receptors |
| JP2004502414A (ja) | 2000-06-30 | 2004-01-29 | ヒューマン ジノーム サイエンシーズ, インコーポレイテッド | B7様ポリヌクレオチド、ポリペプチドおよび抗体 |
| JP2004528003A (ja) | 2000-06-30 | 2004-09-16 | インサイト・ゲノミックス・インコーポレイテッド | 細胞外マトリクスおよび細胞接着分子 |
| MXPA02012749A (es) | 2000-06-30 | 2003-10-06 | Amgen Inc | Moleculas semejantes a b7 y sus usos. |
| AU2002214531A1 (en) | 2000-07-03 | 2002-01-30 | Curagen Corporation | Proteins and nucleic acids encoding same |
| US20040044179A1 (en) | 2000-07-25 | 2004-03-04 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| AU2001283507A1 (en) | 2000-07-27 | 2002-02-13 | Mayo Foundation For Medical Education And Research | B7-h3 and b7-h4, novel immunoregulatory molecules |
| AU2001287639A1 (en) | 2000-07-28 | 2002-02-13 | Ulrich Wissenbach | Trp8, trp9 and trp10, markers for cancer |
| US7229623B1 (en) | 2000-08-03 | 2007-06-12 | Corixa Corporation | Her-2/neu fusion proteins |
| PL365789A1 (pl) | 2000-08-14 | 2005-01-10 | Corixa Corporation | Kompozycje oraz sposoby leczenia i diagnozowania nowotworów związanych z Her-2/neu |
| WO2002013847A2 (en) | 2000-08-14 | 2002-02-21 | Corixa Corporation | Methods for diagnosis and therapy of hematological and virus-associated malignancies |
| KR20030029847A (ko) | 2000-08-24 | 2003-04-16 | 제넨테크, 인크. | 종양의 진단 및 치료를 위한 조성물 및 방법 |
| GB0020953D0 (en) | 2000-08-24 | 2000-10-11 | Smithkline Beecham Biolog | Vaccine |
| US20020119148A1 (en) | 2000-09-01 | 2002-08-29 | Gerritsen Mary E. | ErbB4 antagonists |
| CA2421949A1 (en) | 2000-09-11 | 2002-03-21 | Hyseq, Inc. | Novel nucleic acids and polypeptides |
| US6613567B1 (en) | 2000-09-15 | 2003-09-02 | Isis Pharmaceuticals, Inc. | Antisense inhibition of Her-2 expression |
| WO2002022153A2 (en) | 2000-09-15 | 2002-03-21 | Zymogenetics, Inc. | Use of a polypeptide comprising the extracellular domains of il-20rb for the treatment of inflammation |
| US7491797B2 (en) | 2000-09-15 | 2009-02-17 | Genentech, Inc. | PRO6308 polypeptide |
| UA83458C2 (uk) | 2000-09-18 | 2008-07-25 | Байоджен Айдек Ма Інк. | Виділений поліпептид baff-r (рецептор фактора активації в-клітин сімейства tnf) |
| NZ525380A (en) | 2000-09-18 | 2008-06-30 | Biogen Idec Inc | Non-fucosylated forms of Cripto and their use as tumor blocking agents |
| JP2005506033A (ja) | 2000-10-13 | 2005-03-03 | イーオーエス バイオテクノロジー インコーポレイテッド | 前立腺癌の診断法、前立腺癌モジュレータースクリーニングの組成物及び方法 |
| DE60138927D1 (de) | 2000-11-07 | 2009-07-16 | Zymogenetics Inc | Menschlicher rezeptor für tumor necrosis factor |
| US20020150573A1 (en) | 2000-11-10 | 2002-10-17 | The Rockefeller University | Anti-Igalpha-Igbeta antibody for lymphoma therapy |
| WO2002061087A2 (en) | 2000-12-19 | 2002-08-08 | Lifespan Biosciences, Inc. | Antigenic peptides, such as for g protein-coupled receptors (gpcrs), antibodies thereto, and systems for identifying such antigenic peptides |
| 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 |
| US20030119133A1 (en) | 2001-01-16 | 2003-06-26 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| US20030119125A1 (en) | 2001-01-16 | 2003-06-26 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
| JP2005503760A (ja) | 2001-01-24 | 2005-02-10 | プロテイン デザイン ラブス, インコーポレイテッド | 乳癌の診断方法、組成物および乳癌のモジュレーターのスクリーニング方法 |
| WO2002060317A2 (en) | 2001-01-30 | 2002-08-08 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of pancreatic cancer |
| US20040170994A1 (en) | 2001-02-12 | 2004-09-02 | Callen David Frederick | DNA sequences for human tumour suppressor genes |
| US20030087250A1 (en) | 2001-03-14 | 2003-05-08 | Millennium Pharmaceuticals, Inc. | Nucleic acid molecules and proteins for the identification, assessment, prevention, and therapy of ovarian cancer |
| WO2002078524A2 (en) | 2001-03-28 | 2002-10-10 | Zycos Inc. | Translational profiling |
| WO2003008537A2 (en) | 2001-04-06 | 2003-01-30 | Mannkind Corporation | Epitope sequences |
| US6820011B2 (en) | 2001-04-11 | 2004-11-16 | The Regents Of The University Of Colorado | Three-dimensional structure of complement receptor type 2 and uses thereof |
| EP1414477B1 (en) | 2001-04-17 | 2015-06-10 | The Board Of Trustees Of The University Of Arkansas | Repeat sequences of the ca125 gene and their use for diagnostic interventions |
| 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 |
| JP4307845B2 (ja) | 2001-04-26 | 2009-08-05 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | Criptoをブロックする抗体およびその使用 |
| US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
| JP2005504513A (ja) | 2001-05-09 | 2005-02-17 | コリクサ コーポレイション | 前立腺癌の治療及び診断のための組成物及び方法 |
| WO2002092836A2 (en) | 2001-05-11 | 2002-11-21 | Sloan-Kettering Institute For Cancer Research | Nucleic acid sequence encoding ovarian antigen, ca125, and uses thereof |
| DE60234202D1 (de) | 2001-05-24 | 2009-12-10 | Zymogenetics Inc | Taci-immunoglobulin-fusionsproteine |
| JP2005518185A (ja) | 2001-06-04 | 2005-06-23 | キュラジェン コーポレイション | 新規タンパク質およびそれをコード化する核酸 |
| 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 |
| ATE483976T1 (de) | 2001-06-05 | 2010-10-15 | Exelixis Inc | Gfats als modifikatoren des p53-wegs und verwendungsverfahren |
| JP2004528046A (ja) | 2001-06-05 | 2004-09-16 | 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DGKsおよび使用方法 |
| US7235358B2 (en) | 2001-06-08 | 2007-06-26 | Expression Diagnostics, Inc. | Methods and compositions for diagnosing and monitoring transplant rejection |
| US7125663B2 (en) | 2001-06-13 | 2006-10-24 | Millenium Pharmaceuticals, Inc. | Genes, compositions, kits and methods for identification, assessment, prevention, and therapy of cervical cancer |
| US7189507B2 (en) | 2001-06-18 | 2007-03-13 | Pdl Biopharma, Inc. | Methods of diagnosis of ovarian cancer, compositions and methods of screening for modulators of ovarian cancer |
| WO2002102235A2 (en) | 2001-06-18 | 2002-12-27 | Eos Biotechnology Inc. | Methods of diagnosis of ovarian cancer, compositions and methods of screening for modulators of ovarian cancer |
| US7705120B2 (en) | 2001-06-21 | 2010-04-27 | Millennium Pharmaceuticals, Inc. | Compositions, kits, and methods for identification, assessment, prevention, and therapy of breast cancer |
| WO2003002717A2 (en) | 2001-06-28 | 2003-01-09 | Schering Corporation | Biological activity of ak155 |
| US20030120040A1 (en) | 2001-06-29 | 2003-06-26 | Genentech, Inc. | Secreted and Transmembrane polypeptides and nucleic acids encoding the same |
| WO2003004529A2 (en) | 2001-07-02 | 2003-01-16 | Licentia Ltd. | Ephrin-tie receptor materials and methods |
| 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 |
| WO2003003984A2 (en) | 2001-07-05 | 2003-01-16 | Curagen Corporation | Novel proteins and nucleic acids encoding same |
| WO2003055439A2 (en) | 2001-07-18 | 2003-07-10 | The Regents Of The University Of California | Her2/neu target antigen and use of same to stimulate an immune response |
| US20030108963A1 (en) | 2001-07-25 | 2003-06-12 | Millennium Pharmaceuticals, Inc. | Novel genes, compositions, kit, and methods for identification, assessment, prevention and therapy of prostate cancer |
| PL377119A1 (pl) | 2001-08-03 | 2006-01-23 | Genentech, Inc. | Peptydy TACIs i BR3 i ich zastosowanie |
| WO2003016475A2 (en) | 2001-08-14 | 2003-02-27 | The General Hospital Corporation | Nucleic acid and amino acid sequences involved in pain |
| US20030092013A1 (en) | 2001-08-16 | 2003-05-15 | Vitivity, Inc. | Diagnosis and treatment of vascular disease |
| AU2002313559A1 (en) | 2001-08-23 | 2003-03-10 | Oxford Biomedica (Uk) Limited | Genes |
| US6902930B2 (en) | 2001-08-29 | 2005-06-07 | Vanderbilt University | Human Mob-5 (IL-24) receptors and uses thereof |
| US20040235068A1 (en) * | 2001-09-05 | 2004-11-25 | Levinson Arthur D. | Methods for the identification of polypeptide antigens associated with disorders involving aberrant cell proliferation and compositions useful for the treatment of such disorders |
| US20030124579A1 (en) | 2001-09-05 | 2003-07-03 | Eos Biotechnology, Inc. | Methods of diagnosis of ovarian cancer, compositions and methods of screening for modulators of ovarian cancer |
| EP2287186B1 (en) | 2001-09-06 | 2014-12-31 | Agensys, Inc. | Nucleic acid and corresponding protein entitled STEAP-1 useful in treatment and detection of cancer |
| JP2005518782A (ja) | 2001-09-17 | 2005-06-30 | プロテイン デザイン ラブス, インコーポレイテッド | ガンの診断方法、ガンのモジュレータのスクリーニング組成物及び方法 |
| EP2153843B1 (en) | 2001-09-18 | 2012-08-15 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
| US20050004017A1 (en) | 2001-09-18 | 2005-01-06 | Yuval Reiss | Methods and compositions for treating hcap associated diseases |
| CA2460621A1 (en) | 2001-09-19 | 2003-03-27 | Nuvelo, Inc. | Novel nucleic acids and polypeptides |
| US7091186B2 (en) | 2001-09-24 | 2006-08-15 | Seattle Genetics, Inc. | p-Amidobenzylethers in drug delivery agents |
| WO2003026577A2 (en) | 2001-09-24 | 2003-04-03 | Seattle Genetics, Inc. | P-amidobenzylethers in drug delivery agents |
| WO2003026493A2 (en) | 2001-09-28 | 2003-04-03 | Bing Yang | Diagnosis and treatment of diseases caused by mutations in cd72 |
| US20050130117A1 (en) | 2001-10-03 | 2005-06-16 | Davis Cong L. | Modulators of lymphocyte activation and migration |
| AU2002362454A1 (en) | 2001-10-03 | 2003-04-14 | Origene Technologies, Inc. | Regulated breast cancer genes |
| US20050123925A1 (en) | 2002-11-15 | 2005-06-09 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
| AU2002351505B2 (en) | 2001-10-19 | 2008-04-03 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of inflammatory bowel disorders |
| US7825089B2 (en) | 2001-10-24 | 2010-11-02 | National Jewish Health | Three-dimensional structures of TALL-1 and its cognate receptors and modified proteins and methods related thereto |
| RU2336902C2 (ru) | 2001-10-31 | 2008-10-27 | Алькон, Инк. | Морфогенные белки кости (вмр), рецепторы вмр и связывающие вмр белки и их применение для диагностики и лечения глаукомы |
| 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 |
| US20030232350A1 (en) | 2001-11-13 | 2003-12-18 | Eos Biotechnology, Inc. | Methods of diagnosis of cancer, compositions and methods of screening for modulators of cancer |
| US20050123536A1 (en) | 2001-11-20 | 2005-06-09 | Che-Leung Law | Treatment of immunological disorders using anti-dc30 antibodies |
| EP1448226A1 (en) | 2001-11-29 | 2004-08-25 | Genset S.A. | Agonists and antagonists of prolixin for the treatment of metabolic disorders |
| AU2002349784A1 (en) | 2001-12-03 | 2003-06-17 | Asahi Kasei Pharma Corporation | Nf-kappab activating genes |
| CA2469941A1 (en) | 2001-12-10 | 2003-07-03 | Nuvelo, Inc. | Novel nucleic acids and polypeptides |
| 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 |
| US7452675B2 (en) | 2002-01-25 | 2008-11-18 | The Queen's Medical Center | Methods of screening for TRPM4b modulators |
| CA2476776A1 (en) | 2002-02-21 | 2003-09-04 | Duke University | Reagents and treatment methods for autoimmune diseases |
| WO2003072035A2 (en) | 2002-02-22 | 2003-09-04 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
| US20030219795A1 (en) | 2002-03-01 | 2003-11-27 | Marcia Belvin | SCDs as modifiers of the p53 pathway and methods of use |
| WO2003101400A2 (en) | 2002-06-04 | 2003-12-11 | Avalon Pharmaceuticals, Inc. | Cancer-linked gene as target for chemotherapy |
| EP2258712A3 (en) | 2002-03-15 | 2011-05-04 | Multicell Immunotherapeutics, Inc. | Compositions and Methods to Initiate or Enhance Antibody and Major-histocompatibility Class I or Class II-restricted T Cell Responses by Using Immunomodulatory, Non-coding RNA Motifs |
| WO2004000997A2 (en) | 2002-03-19 | 2003-12-31 | Curagen Corporation | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
| JP2005534286A (ja) | 2002-03-21 | 2005-11-17 | サネシス ファーマシューティカルズ, インコーポレイテッド | キナーゼインヒビターの同定 |
| EP1494693B1 (en) | 2002-03-22 | 2010-12-08 | Biogen Idec MA Inc. | Cripto-specific antibodies |
| US7193069B2 (en) | 2002-03-22 | 2007-03-20 | Research Association For Biotechnology | Full-length cDNA |
| AU2003245239A1 (en) | 2002-03-25 | 2003-11-03 | Uab Research Foundation | FC receptor homolog, reagents, and uses thereof |
| AU2003222103A1 (en) | 2002-03-28 | 2003-10-13 | Idec Pharmaceuticals Corporation | Novel gene targets and ligands that bind thereto for treatment and diagnosis of colon carcinomas |
| US20030194704A1 (en) | 2002-04-03 | 2003-10-16 | Penn Sharron Gaynor | Human genome-derived single exon nucleic acid probes useful for gene expression analysis two |
| CA2481503A1 (en) | 2002-04-05 | 2003-10-23 | Agensys, Inc. | Nucleic acid and corresponding protein entitled 98p4b6 useful in treatment and detection of cancer |
| AU2003223520A1 (en) | 2002-04-12 | 2003-10-27 | Mitokor | Targets for therapeutic intervention identified in the mitochondrial proteome |
| KR20040101502A (ko) | 2002-04-16 | 2004-12-02 | 제넨테크, 인크. | 종양의 진단 및 치료 방법 및 이를 위한 조성물 |
| WO2003089904A2 (en) | 2002-04-17 | 2003-10-30 | Baylor College Of Medicine | Aib1 as a prognostic marker and predictor of resistance to encocrine therapy |
| AU2003228869A1 (en) | 2002-05-03 | 2003-11-17 | Incyte Corporation | Transporters and ion channels |
| CA2485983A1 (en) | 2002-05-15 | 2003-11-27 | Avalon Pharmaceuticals | Cancer-linked gene as target for chemotherapy |
| US20030224454A1 (en) | 2002-05-30 | 2003-12-04 | Ryseck Rolf Peter | Human solute carrier family 7, member 11 (hSLC7A11) |
| AU2003240495A1 (en) | 2002-06-04 | 2003-12-19 | Incyte Corporation | Diagnostics markers for lung cancer |
| JP4594085B2 (ja) | 2002-06-06 | 2010-12-08 | オンコセラピー・サイエンス株式会社 | ヒト結腸癌に関連する遺伝子およびポリペプチド |
| WO2003104270A2 (en) | 2002-06-06 | 2003-12-18 | Ingenium Pharmaceuticals Ag | Dudulin 2 genes, expression products, non-human animal model: uses in human hematological disease |
| EP1576111A4 (en) | 2002-06-07 | 2006-10-18 | Avalon Pharmaceuticals | CANCER-ASSOCIATED GENE AS A TARGET FOR CHEMOTHERAPY |
| WO2003105758A2 (en) | 2002-06-12 | 2003-12-24 | Avalon Pharmaceuticals, Inc. | Cancer-linked gene as target for chemotherapy |
| WO2003106659A2 (en) | 2002-06-18 | 2003-12-24 | Archemix Corp. | Aptamer-toxin molecules and methods for using same |
| US20040249130A1 (en) | 2002-06-18 | 2004-12-09 | Martin Stanton | Aptamer-toxin molecules and methods for using same |
| EP1539218A4 (en) | 2002-06-20 | 2007-08-22 | Univ California | COMPOSITIONS AND METHODS FOR MODULATING LYMPHOCYTE ACTIVITY |
| EP1947470A3 (en) | 2002-06-20 | 2011-09-28 | Snaptrack Inc. | Reducing cross-interference in a combined GPS receiver and communication system |
| JP2005530856A (ja) | 2002-06-21 | 2005-10-13 | ジョンズ ホプキンス ユニバーシティー スクール オブ メディシン | 膜関連腫瘍内皮マーカー |
| AU2003281515A1 (en) | 2002-07-19 | 2004-02-09 | Cellzome Ag | Protein complexes of cellular networks underlying the development of cancer and other diseases |
| MXPA05000940A (es) | 2002-07-25 | 2005-05-16 | Genentech Inc | Anticuerpos taci y su uso. |
| EP1575514A2 (en) | 2002-07-31 | 2005-09-21 | Seattle Genetics, Inc. | Anti-cd20 antibody-drug conjugates for the treatment of cancer and immune disorders |
| JP2004121218A (ja) | 2002-08-06 | 2004-04-22 | Jenokkusu Soyaku Kenkyusho:Kk | 気管支喘息または慢性閉塞性肺疾患の検査方法 |
| AU2003251471A1 (en) | 2002-08-06 | 2004-02-25 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with human cxc chemokine receptor 5(cxcr5) |
| MXPA05001933A (es) | 2002-08-19 | 2005-04-28 | Genentech Inc | Composiciones y metodos para el diagnostico y tratamiento de tumores. |
| US7504211B2 (en) | 2002-08-27 | 2009-03-17 | Bristol-Myers Squibb Company | Methods of using EPHA2 for predicting activity of compounds that interact with and/or modulate protein tyrosine kinases and/or protein tyrosine kinase pathways in breast cells |
| WO2004020595A2 (en) | 2002-08-29 | 2004-03-11 | Five Prime Therapeutics, Inc. | Novel human polypeptides encoded by polynucleotides |
| AU2002951346A0 (en) | 2002-09-05 | 2002-09-26 | Garvan Institute Of Medical Research | Diagnosis of ovarian cancer |
| JP2005537800A (ja) | 2002-09-06 | 2005-12-15 | マンカインド コーポレイション | エピトープ配列 |
| JP2006513702A (ja) | 2002-09-09 | 2006-04-27 | ヌラ インコーポレーティッド | Gタンパク質共役受容体およびその使用 |
| JP2004113151A (ja) | 2002-09-27 | 2004-04-15 | Sankyo Co Ltd | 癌遺伝子及びその用途 |
| WO2004032842A2 (en) | 2002-10-04 | 2004-04-22 | Van Andel Research Institute | Molecular sub-classification of kidney tumors and the discovery of new diagnostic markers |
| US7608429B2 (en) * | 2002-10-31 | 2009-10-27 | Genentech, Inc. | Methods and compositions for increasing antibody production |
| CA2503748A1 (en) | 2002-11-08 | 2004-05-27 | Genentech, Inc. | Compositions and methods for the treatment of natural killer cell related diseases |
| AU2003295511A1 (en) | 2002-11-13 | 2004-06-03 | Genentech, Inc. | Methods and compositions for diagnosing dysplasia |
| AU2003298650B2 (en) | 2002-11-15 | 2010-03-11 | Musc Foundation For Research Development | Complement receptor 2 targeted complement modulators |
| MXPA05005237A (es) | 2002-11-15 | 2005-08-16 | Univ Arkansas | Gen ca125 y su uso para diagnostico e intervenciones terapeuticas. |
| WO2004046342A2 (en) | 2002-11-20 | 2004-06-03 | Biogen Idec Inc. | Novel gene targets and ligands that bind thereto for treatment and diagnosis of carcinomas |
| EP2410332A1 (en) | 2002-11-21 | 2012-01-25 | The University Of Utah | Method for identifying purinergic modulators of the olfactory system |
| AU2003298786A1 (en) | 2002-11-26 | 2004-06-18 | Protein Design Labs, Inc. | Methods of detecting soft tissue sarcoma, compositions and methods of screening for soft tissue sarcoma modulators |
| US20070154886A1 (en) | 2002-12-06 | 2007-07-05 | Macina Roberto A | Composition, splice variants and methods relating to ovarian specific genes and proteins |
| US20040157278A1 (en) | 2002-12-13 | 2004-08-12 | Bayer Corporation | Detection methods using TIMP 1 |
| US7276372B2 (en) | 2002-12-20 | 2007-10-02 | Pdl Biopharma, Inc. | Antibodies against GPR64 and uses thereof |
| WO2004058309A1 (en) | 2002-12-23 | 2004-07-15 | Human Genome Sciences, Inc. | Neutrokine-alpha conjugate, neutrokine-alpha complex, and uses thereof |
| JP2007520995A (ja) | 2003-01-08 | 2007-08-02 | ブリストル−マイヤーズ スクイブ カンパニー | 上皮増殖因子受容体モデュレーターに対する感受性を決定するためのバイオマーカーおよび方法 |
| US20050227301A1 (en) | 2003-01-10 | 2005-10-13 | Polgen | Cell cycle progression proteins |
| WO2004063355A2 (en) | 2003-01-10 | 2004-07-29 | Protein Design Labs, Inc. | Novel methods of diagnosis of metastatic cancer, compositions and methods of screening for modulators of matastatic cancer |
| WO2004065577A2 (en) | 2003-01-14 | 2004-08-05 | Bristol-Myers Squibb Company | Polynucleotides and polypeptides associated with the nf-kb pathway |
| WO2004065576A2 (en) | 2003-01-15 | 2004-08-05 | Millennium Pharmaceuticals, Inc. | Methods and compositions for the treatment of urological disorder using differential expressed polypeptides |
| US7575893B2 (en) * | 2003-01-23 | 2009-08-18 | Genentech, Inc. | Methods for producing humanized antibodies and improving yield of antibodies or antigen binding fragments in cell culture |
| AU2004213432A1 (en) | 2003-02-14 | 2004-09-02 | Sagres Discovery, Inc. | Novel therapeutic targets in cancer |
| US20030224411A1 (en) | 2003-03-13 | 2003-12-04 | Stanton Lawrence W. | Genes that are up- or down-regulated during differentiation of human embryonic stem cells |
| RS54163B1 (sr) * | 2006-05-30 | 2015-12-31 | Genentech Inc. | Anti-cd22 antitela, njihovi imunokonjugati i njihova upotreba |
| CN101652389A (zh) * | 2007-02-09 | 2010-02-17 | 健泰科生物技术公司 | 抗robo4抗体及其用途 |
| AU2008251608B2 (en) * | 2007-05-08 | 2014-03-27 | Genentech, Inc. | Cysteine engineered anti-MUC16 antibodies and antibody drug conjugates |
| AR067543A1 (es) * | 2007-07-16 | 2009-10-14 | Genentech Inc | Anticuerpos anti-cd79b e inmunoconjugados humanizados y metodos de uso |
| CN106432496B (zh) * | 2007-07-16 | 2020-02-07 | 健泰科生物技术公司 | 抗cd79b抗体和免疫偶联物及使用方法 |
| NZ584514A (en) * | 2007-10-19 | 2012-07-27 | Genentech Inc | Cysteine engineered anti-tenb2 antibodies and antibody drug conjugates |
-
2009
- 2009-11-05 US US12/612,912 patent/US20100111856A1/en not_active Abandoned
-
2010
- 2010-11-04 RU RU2012123007/10A patent/RU2562862C2/ru active
- 2010-11-04 EP EP10776064.7A patent/EP2496270B1/en active Active
- 2010-11-04 KR KR1020177034613A patent/KR20170136652A/ko not_active Ceased
- 2010-11-04 MX MX2012005211A patent/MX340674B/es active IP Right Grant
- 2010-11-04 BR BR112012007774A patent/BR112012007774A2/pt not_active IP Right Cessation
- 2010-11-04 CN CN201080050134.4A patent/CN102596260B/zh active Active
- 2010-11-04 KR KR1020127011607A patent/KR20120102625A/ko not_active Ceased
- 2010-11-04 WO PCT/US2010/055465 patent/WO2011056983A1/en not_active Ceased
- 2010-11-04 JP JP2012537224A patent/JP5850843B2/ja active Active
- 2010-11-04 CA CA2780216A patent/CA2780216A1/en not_active Abandoned
-
2014
- 2014-06-10 US US14/300,630 patent/US20150017094A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006034488A2 (en) * | 2004-09-23 | 2006-03-30 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
Non-Patent Citations (1)
| Title |
|---|
| DIJKERS E.C.F. et al, Development and Characterization of Clinical-Grade 89Zr-Trastuzumab for HER2/neu ImmunoPET Imaging, The Journal of Nuclear Medicine, 2009, v. 50, n. 6, p. 974-981. GOVINDAN S.V. et al, Deferoxamine as a chelator for 67Ga in the preparation of antibody conjugates, 2005, v. 32, p. 513-519. РОЙТ А. и др., Иммунология, Москва, "Мир", 2000, стр. 110-111 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11779649B2 (en) | 2018-12-21 | 2023-10-10 | Novartis Ag | Antibodies to PMEL17 and conjugates thereof |
| RU2831785C2 (ru) * | 2018-12-21 | 2024-12-13 | Новартис Аг | Антитела к рмel17 и конъюгаты на их основе |
| US20230390426A1 (en) * | 2020-10-22 | 2023-12-07 | Nihon Medi-Physics Co., Ltd. | Method for producing radioactive zirconium complex |
Also Published As
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|---|---|
| CN102596260A (zh) | 2012-07-18 |
| US20150017094A1 (en) | 2015-01-15 |
| JP5850843B2 (ja) | 2016-02-03 |
| MX2012005211A (es) | 2012-06-13 |
| KR20120102625A (ko) | 2012-09-18 |
| KR20170136652A (ko) | 2017-12-11 |
| JP2013510093A (ja) | 2013-03-21 |
| WO2011056983A1 (en) | 2011-05-12 |
| EP2496270A1 (en) | 2012-09-12 |
| US20100111856A1 (en) | 2010-05-06 |
| CN102596260B (zh) | 2017-04-05 |
| MX340674B (es) | 2016-07-20 |
| CA2780216A1 (en) | 2011-05-12 |
| BR112012007774A2 (pt) | 2016-11-22 |
| RU2012123007A (ru) | 2013-12-10 |
| EP2496270B1 (en) | 2018-01-31 |
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