JP5153057B2 - カリチェアミシン誘導体−キャリアコンジュゲート - Google Patents
カリチェアミシン誘導体−キャリアコンジュゲート Download PDFInfo
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- JP5153057B2 JP5153057B2 JP2004500808A JP2004500808A JP5153057B2 JP 5153057 B2 JP5153057 B2 JP 5153057B2 JP 2004500808 A JP2004500808 A JP 2004500808A JP 2004500808 A JP2004500808 A JP 2004500808A JP 5153057 B2 JP5153057 B2 JP 5153057B2
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- prednisone
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Families Citing this family (135)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6905669B2 (en) | 2001-04-24 | 2005-06-14 | Supergen, Inc. | Compositions and methods for reestablishing gene transcription through inhibition of DNA methylation and histone deacetylase |
US20110045005A1 (en) * | 2001-10-19 | 2011-02-24 | Craig Crowley | Compositions and methods for the treatment of tumor of hematopoietic origin |
PL224001B1 (pl) | 2002-05-02 | 2016-11-30 | Wyeth Corp | Sposób wytwarzania stabilnej liofilizowanej kompozycji obejmującej monomeryczne koniugaty pochodna kalicheamycyny/przeciwciało anty-CD22, kompozycja otrzymana tym sposobem oraz jej zastosowanie |
GB0210121D0 (en) * | 2002-05-02 | 2002-06-12 | Celltech R&D Ltd | Biological products |
TW200539855A (en) * | 2004-03-15 | 2005-12-16 | Wyeth Corp | Calicheamicin conjugates |
JP5470597B2 (ja) * | 2004-05-26 | 2014-04-16 | 国立大学法人 香川大学 | 希少糖d−アロースを利用した細胞・組織・臓器保存液及び該液を用いる保存方法 |
TW200621282A (en) * | 2004-08-13 | 2006-07-01 | Wyeth Corp | Stabilizing formulations |
US7300773B2 (en) | 2004-08-27 | 2007-11-27 | Wyeth Research Ireland Limited | Production of TNFR-Ig |
US7294484B2 (en) | 2004-08-27 | 2007-11-13 | Wyeth Research Ireland Limited | Production of polypeptides |
US7335491B2 (en) | 2004-08-27 | 2008-02-26 | Wyeth Research Ireland Limited | Production of anti-abeta |
AU2004224925C1 (en) * | 2004-08-30 | 2011-07-21 | Biotest Ag | Immunoconjugates targeting syndecan-1 expressing cells and use thereof |
EP1786469A2 (en) * | 2004-09-10 | 2007-05-23 | Wyeth a Corporation of the State of Delaware | Humanized anti-5t4 antibodies and anti-5t4 antibody / calicheamicin conjugates |
EP1661584A1 (en) * | 2004-11-26 | 2006-05-31 | Heinz Dr. Faulstich | Use of conjugates of amatoxins and phallotoxins with macromolecules for cancer and inflammation therapy |
US20110166319A1 (en) * | 2005-02-11 | 2011-07-07 | Immunogen, Inc. | Process for preparing purified drug conjugates |
US7250416B2 (en) | 2005-03-11 | 2007-07-31 | Supergen, Inc. | Azacytosine analogs and derivatives |
US20070003559A1 (en) * | 2005-07-01 | 2007-01-04 | Wyeth | Methods of determining pharmacokinetics of targeted therapies |
AU2006279891B2 (en) | 2005-08-16 | 2010-03-11 | Synta Pharmaceuticals Corp. | Bis(thio-hydrazide amide) formulation |
NZ609752A (en) | 2005-08-24 | 2014-08-29 | Immunogen Inc | Process for preparing maytansinoid antibody conjugates |
US7700567B2 (en) | 2005-09-29 | 2010-04-20 | Supergen, Inc. | Oligonucleotide analogues incorporating 5-aza-cytosine therein |
CA2631714C (en) | 2005-12-02 | 2014-09-16 | Novartis Ag | Nanoparticles for use in immunogenic compositions |
US20070160577A1 (en) * | 2005-12-06 | 2007-07-12 | Wyeth | Interleukin-11 compositions and methods of use |
NZ596295A (en) | 2006-03-10 | 2013-01-25 | Wyeth Corp | Anti-5T4 antibodies and uses thereof |
ATE521366T1 (de) * | 2006-05-27 | 2011-09-15 | Faulstich Heinz Dr | Anwendung von amatoxin-konjugaten und phallotoxin-konjugaten mit makromolekülen zur krebstherapie und therapie von entzündungen |
DK2495307T5 (en) | 2006-07-13 | 2018-07-16 | Wyeth Llc | Preparation of coagulation factor IX with improved glycosylation pattern |
WO2008024303A2 (en) | 2006-08-21 | 2008-02-28 | Synta Pharmaceuticals Corp. | Compounds for treating proliferative disorders |
CN101522219A (zh) * | 2006-10-12 | 2009-09-02 | 惠氏公司 | 改变抗体溶液中离子强度以减少乳光/聚集物 |
MX2009004519A (es) | 2006-11-03 | 2009-05-12 | Wyeth Corp | Sustancias que inhiben la glucolisis en un cultivo de celulas. |
ES2678060T3 (es) | 2006-12-01 | 2018-08-08 | E. R. Squibb & Sons, L.L.C. | Anticuerpos, en particular, anticuerpos humanos, que se unen a CD22 y usos de los mismos |
AU2007336897A1 (en) * | 2006-12-22 | 2008-07-03 | The Regents Of The University Of California | Macromolecular conjugates of cystic fibrosis transmembrane conductance regulator protein inhibitors and uses thereof |
EP2121750A2 (en) * | 2007-01-16 | 2009-11-25 | Wyeth | Inflammation treatment, detection and monitoring via trem-1 |
DK2115126T3 (en) | 2007-03-02 | 2015-05-04 | Wyeth Llc | Use of copper and glutamate in cell culture for the preparation of polypeptides |
CA2687852A1 (en) | 2007-05-22 | 2008-12-04 | Wyeth | Improved processes for making hydrazides |
PE20090309A1 (es) * | 2007-06-04 | 2009-04-18 | Wyeth Corp | Conjugado portador-caliqueamicina y un metodo de deteccion de caliqueamicina |
SI2211904T1 (sl) * | 2007-10-19 | 2016-12-30 | Seattle Genetics, Inc. | CD19 vezavna sredstva in njihove uporabe |
KR20100102172A (ko) * | 2007-12-21 | 2010-09-20 | 제넨테크, 인크. | 리툭시마브-난치성 류마티스성 관절염 환자의 요법 |
PL2238168T3 (pl) * | 2007-12-26 | 2014-11-28 | Biotest Ag | Środki które mają za cel CD138 i ich zastosowania |
BRPI0821449A2 (pt) * | 2007-12-26 | 2015-06-16 | Biotest Ag | Imunoconjugado, métodos para tratar mieloma múltiplo em um indíviduo, para dispensar medicamento mediado por imunoconjugado, para inibir, atrasar e/ou evitar o desenvolvimento de um tumor e/ou dispensar células tumorais malignas em um paciente em necessidade do mesmo, para tratar um indíviduo tendo uma condição e opara diminuir uma quantidade de células em contato direto ou indireto com as imunoconjugado, método para tratar mieloma múltiplo em um indivíduo, para dispensar medicamento mediado por imunoconjugado, para inibir, atrasar e/ou evitar o desenvolvimento de células tumorais em uma cultura celular, para inibir, atrasar e/ou evitar o desenvolvimento de um tumor e/ou dispensar células tumorais malignas em um paciente em necessidade do mesmo, para tratar um indivíduo tendo uma condição e para diminuir uma quantidade de células em contato direto ou indireto com as células tumorais, composição farmacêutica, e, kit. |
MX2010007101A (es) * | 2007-12-26 | 2011-07-01 | Biotest Ag | Metodos y agentes para mejorar el reconocimiento de celulas de tumor que expresan cd138. |
JP2011507933A (ja) * | 2007-12-26 | 2011-03-10 | バイオテスト・アクチエンゲゼルシヤフト | 免疫複合体の細胞傷害性副作用の低減及び有効性の改善方法 |
US20090186026A1 (en) * | 2008-01-18 | 2009-07-23 | Wyeth | Ephrin and eph receptor agonists for modulation of bone formation and resorption |
US8591889B2 (en) * | 2008-04-04 | 2013-11-26 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Human monoclonal antibodies specific for CD22 |
FR2930443B1 (fr) * | 2008-04-29 | 2010-06-25 | Oreal | Produit extemporane de soin a base d'un lyophilisat de microorganisme et de tensioactif(s) de hlb superieur ou egal a 12 |
KR101764081B1 (ko) | 2008-04-30 | 2017-08-01 | 이뮤노젠 아이엔씨 | 가교제 및 그 용도 |
PT2437790T (pt) | 2009-06-03 | 2019-06-04 | Immunogen Inc | Métodos de conjugação |
WO2011098518A2 (en) * | 2010-02-11 | 2011-08-18 | Ablynx Nv | Delivery of immunoglobulin variable domains and constructs thereof |
EP2600901B1 (en) | 2010-08-06 | 2019-03-27 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
US20130150554A1 (en) | 2010-08-20 | 2013-06-13 | Wyeth Llc | Cell culture of growth factor-free adapted cells |
DE19177059T1 (de) | 2010-10-01 | 2021-10-07 | Modernatx, Inc. | N1-methyl-pseudouracile enthältendes ribonucleinsäuren sowie ihre verwendungen |
WO2012065161A2 (en) | 2010-11-12 | 2012-05-18 | Scott & White Healthcare | Antibodies to tumor endothelial marker 8 |
US8512679B2 (en) * | 2011-03-04 | 2013-08-20 | Elwha Llc | Glassy compositions |
RS58367B1 (sr) | 2011-03-29 | 2019-03-29 | Immunogen Inc | Priprema konjugata antitela i majtanzinoida jednostepenim postupkom |
WO2012135805A2 (en) | 2011-03-31 | 2012-10-04 | modeRNA Therapeutics | Delivery and formulation of engineered nucleic acids |
MY163296A (en) | 2011-08-30 | 2017-09-15 | Astex Pharmaceuticals Inc | Drug formulations |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
LT3682905T (lt) | 2011-10-03 | 2022-02-25 | Modernatx, Inc. | Modifikuoti nukleozidai, nukleotidai ir nukleorūgštys bei jų naudojimas |
US20140322758A1 (en) | 2011-10-21 | 2014-10-30 | Pfizer Inc. | Addition of iron to improve cell culture |
US10117932B2 (en) | 2011-12-08 | 2018-11-06 | Biotest Ag | Uses of immunoconjugates targeting CD138 |
PL2791160T3 (pl) | 2011-12-16 | 2022-06-20 | Modernatx, Inc. | Kompozycje zmodyfikowanego mrna |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
DE18200782T1 (de) | 2012-04-02 | 2021-10-21 | Modernatx, Inc. | Modifizierte polynukleotide zur herstellung von proteinen im zusammenhang mit erkrankungen beim menschen |
US9878056B2 (en) | 2012-04-02 | 2018-01-30 | Modernatx, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
KR20150036346A (ko) | 2012-07-03 | 2015-04-07 | 워싱턴 유니버시티 | Tau에 대한 항체 |
US8883979B2 (en) | 2012-08-31 | 2014-11-11 | Bayer Healthcare Llc | Anti-prolactin receptor antibody formulations |
IN2015DN03202A (US20030051240A1-20030313-M00001.png) | 2012-10-04 | 2015-10-02 | Immunogen Inc | |
EP2922818B1 (en) | 2012-11-24 | 2018-09-05 | Hangzhou Dac Biotech Co., Ltd | Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules |
RS63237B1 (sr) | 2012-11-26 | 2022-06-30 | Modernatx Inc | Terminalno modifikovana rnk |
US9943610B2 (en) | 2012-12-21 | 2018-04-17 | Bioalliance C.V. | Hydrophilic self-immolative linkers and conjugates thereof |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
PL2992015T3 (pl) * | 2013-05-02 | 2019-01-31 | F.Hoffmann-La Roche Ag | Leczenie skojarzone niefukozylowanym przeciwciałem anty-CD20 z koniugatem przeciwciało anty-CD22-lek |
US10023626B2 (en) | 2013-09-30 | 2018-07-17 | Modernatx, Inc. | Polynucleotides encoding immune modulating polypeptides |
EA201690675A1 (ru) | 2013-10-03 | 2016-08-31 | Модерна Терапьютикс, Инк. | Полинуклеотиды, кодирующие рецептор липопротеинов низкой плотности |
CN108047287B (zh) * | 2013-11-04 | 2021-04-27 | 辉瑞大药厂 | 用于合成加利车霉素衍生物的中间体和方法 |
EP3065780A1 (en) | 2013-11-04 | 2016-09-14 | Pfizer Inc. | Anti-efna4 antibody-drug conjugates |
WO2015127685A1 (en) | 2014-02-28 | 2015-09-03 | Hangzhou Dac Biotech Co., Ltd | Charged linkers and their uses for conjugation |
WO2015140708A1 (en) | 2014-03-19 | 2015-09-24 | Pfizer Inc. | Method of cell culture |
US11998594B2 (en) | 2014-04-02 | 2024-06-04 | Case Western Reserve University | Anti-cancer plant virus particles linked to HER2 antigens |
JP2017528418A (ja) | 2014-06-20 | 2017-09-28 | バイオアライアンス コマンディテール フェンノートシャップ | 抗葉酸受容体アルファ(fra)抗体−薬物コンジュゲート及びその使用方法 |
TW202136296A (zh) | 2014-06-27 | 2021-10-01 | 美商C2N醫療診斷有限責任公司 | 人類化抗-tau抗體 |
GB201412658D0 (en) | 2014-07-16 | 2014-08-27 | Ucb Biopharma Sprl | Molecules |
US9925281B2 (en) | 2014-08-05 | 2018-03-27 | Case Western Reserve University | Coated plant virus imaging agents |
EP3957644B1 (en) | 2014-11-07 | 2024-08-07 | Case Western Reserve University | Cancer immunotherapy using virus particles |
US10548989B2 (en) | 2015-04-07 | 2020-02-04 | Memorial Sloan Kettering Cancer Center | Nanoparticle immunoconjugates |
BR112017022682A2 (pt) * | 2015-04-21 | 2018-07-10 | Abbvie Stemcentrx Llc | construções de caliqueamicina e métodos de uso |
GB201506870D0 (en) | 2015-04-22 | 2015-06-03 | Ucb Biopharma Sprl | Method |
IL274151B (en) | 2015-05-21 | 2022-07-01 | Harpoon Therapeutics Inc | Trispecific binding proteins and methods of use |
EP3313527B1 (en) | 2015-06-29 | 2021-02-24 | Case Western Reserve University | Anticancer drug-containing plant virus particles |
CA2991167A1 (en) | 2015-07-02 | 2017-01-05 | Otsuka Pharmaceutical Co., Ltd. | Lyophilized pharmaceutical compositions |
AU2015242213A1 (en) | 2015-07-12 | 2018-03-08 | Hangzhou Dac Biotech Co., Ltd | Bridge linkers for conjugation of cell-binding molecules |
US9839687B2 (en) | 2015-07-15 | 2017-12-12 | Suzhou M-Conj Biotech Co., Ltd. | Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule |
EP3322485B1 (en) * | 2015-07-16 | 2020-07-01 | Case Western Reserve University | Plant virus particles for delivery of antimitotic agents |
GB201601075D0 (en) | 2016-01-20 | 2016-03-02 | Ucb Biopharma Sprl | Antibodies molecules |
GB201601077D0 (en) | 2016-01-20 | 2016-03-02 | Ucb Biopharma Sprl | Antibody molecule |
GB201601073D0 (en) | 2016-01-20 | 2016-03-02 | Ucb Biopharma Sprl | Antibodies |
CA3214798A1 (en) | 2015-09-23 | 2017-03-30 | Pfizer Inc. | Cells and method of cell culture |
KR20180073693A (ko) | 2015-11-09 | 2018-07-02 | 브리스톨-마이어스 스큅 컴퍼니 | Cho 세포에서 생산되는 폴리펩티드의 품질 속성을 조작하는 방법 |
NZ743815A (en) | 2016-01-08 | 2023-06-30 | Altrubio Inc | Tetravalent anti-psgl-1 antibodies and uses thereof |
US20170281758A1 (en) * | 2016-03-29 | 2017-10-05 | Sorrento Therapeutics, Inc. | Calicheamicin antibody drug conjugates linking an amidoacetyl group to a sugar moiety on calicheamicin |
BR112018070063A2 (pt) | 2016-04-05 | 2019-02-12 | Pfizer Inc. | processo de cultivo de células |
US11623958B2 (en) | 2016-05-20 | 2023-04-11 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
GB201610512D0 (en) | 2016-06-16 | 2016-08-03 | Autolus Ltd | Chimeric antigen receptor |
EP3487527A4 (en) | 2016-07-21 | 2020-03-11 | Case Western Reserve University | PARTICLES OF VEGETABLE OR VIRAL-LIKE PARTICLES |
WO2018085658A1 (en) | 2016-11-03 | 2018-05-11 | Case Western Reserve University | Melt processed viral nanoparticle constructs |
KR20220150408A (ko) | 2016-11-14 | 2022-11-10 | 항저우 디에이씨 바이오테크 씨오, 엘티디 | 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용 |
US11590183B2 (en) | 2017-03-10 | 2023-02-28 | Case Western Reserve University | Cancer immunotherapy using virus particles |
US20200056190A1 (en) | 2017-03-16 | 2020-02-20 | Pfizer Inc. | Tyrosine prototrophy |
WO2018209298A1 (en) | 2017-05-12 | 2018-11-15 | Harpoon Therapeutics, Inc. | Mesothelin binding proteins |
WO2018213587A1 (en) | 2017-05-17 | 2018-11-22 | Case Western Reserve University | Anticancer trail-targeted plant virus particles |
CN111182908A (zh) | 2017-08-03 | 2020-05-19 | 大塚制药株式会社 | 药物化合物及其纯化方法 |
JP2020533983A (ja) | 2017-09-15 | 2020-11-26 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 目的のポリペプチドのラージスケールの製造間のオンラインバイオマス静電容量モニタリング |
CR20200195A (es) | 2017-10-13 | 2020-08-14 | Harpoon Therapeutics Inc | Proteínas de unión a antigenos de maduraciòn de celulas b |
US11739301B2 (en) | 2017-10-27 | 2023-08-29 | Case Western Reserve University | Tymovirus virus and virus-like particles as nanocarriers for imaging and therapeutic agents |
US20210010055A1 (en) | 2018-03-16 | 2021-01-14 | Bristol-Myers Squibb Company | Metabolic enzyme activity and disulfide bond reduction during protein production |
CN110507824A (zh) * | 2018-05-21 | 2019-11-29 | 荣昌生物制药(烟台)有限公司 | 一种抗间皮素抗体及其抗体药物缀合物 |
MX2020012788A (es) * | 2018-05-30 | 2021-02-15 | Abbvie Stemcentrx Llc | Conjugados de farmaco y anticuerpo anti-sez6 y metodos de uso. |
AU2019346466A1 (en) | 2018-09-25 | 2021-05-20 | Harpoon Therapeutics, Inc. | DLL3 binding proteins and methods of use |
SG11202104900SA (en) | 2018-11-20 | 2021-06-29 | Univ Cornell | Macrocyclic complexes of radionuclides and their use in radiotherapy of cancer |
CA3121884A1 (en) | 2018-12-06 | 2020-06-11 | Pfizer Inc. | Cells with reduced inhibitor production and methods of use thereof |
KR20220012839A (ko) | 2019-03-19 | 2022-02-04 | 펀다시오 프리바다 인스티튜트 드인베스티가시오 온콜로지카 데 발 헤브론 | Omomyc와 pd-1 또는 ctla-4에 결합하는 항체를 이용한 암 치료용 조합 요법 |
US11390853B2 (en) | 2019-04-26 | 2022-07-19 | Case Western Reserve University | Freeze dried viral nanoparticle constructs |
WO2021024020A1 (en) | 2019-08-06 | 2021-02-11 | Astellas Pharma Inc. | Combination therapy involving antibodies against claudin 18.2 and immune checkpoint inhibitors for treatment of cancer |
US11896676B2 (en) | 2019-08-07 | 2024-02-13 | Case Western Reserve University | Targeting cancer cells and tissue using filamentous plant virus particles |
US20230071019A1 (en) * | 2019-12-04 | 2023-03-09 | The Research Foundation For The State University Of New York | Compositions and methods for reducing off-target toxicity of antibody drug conjugates |
AU2021306613A1 (en) | 2020-07-07 | 2023-02-02 | BioNTech SE | Therapeutic RNA for HPV-positive cancer |
TW202245808A (zh) | 2020-12-21 | 2022-12-01 | 德商拜恩迪克公司 | 用於治療癌症之治療性rna |
WO2022135666A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Treatment schedule for cytokine proteins |
WO2022135667A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Therapeutic rna for treating cancer |
CN112724263B (zh) * | 2021-04-02 | 2021-08-03 | 上海偌妥生物科技有限公司 | 改造抗cd20单克隆抗体以提高其药物疗效的方法及其应用 |
JP2024525758A (ja) | 2021-07-13 | 2024-07-12 | ビオンテック・ソシエタス・エウロパエア | がんのための併用療法におけるcd40およびcd137に対する多重特異性結合剤 |
TW202333802A (zh) | 2021-10-11 | 2023-09-01 | 德商拜恩迪克公司 | 用於肺癌之治療性rna(二) |
WO2023148598A1 (en) | 2022-02-02 | 2023-08-10 | Pfizer Inc. | Cysteine prototrophy |
WO2024058201A1 (ja) * | 2022-09-16 | 2024-03-21 | 国立研究開発法人量子科学技術研究開発機構 | 放射性医薬組成物の中間体の製造方法、放射性医薬組成物の中間体の精製用キット |
WO2024089013A1 (en) | 2022-10-25 | 2024-05-02 | Peptomyc, S.L. | Combination therapy for the treatment of cancer |
WO2024126457A1 (en) | 2022-12-14 | 2024-06-20 | Astellas Pharma Europe Bv | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and immune checkpoint inhibitors |
WO2024218706A1 (en) | 2023-04-21 | 2024-10-24 | Pfizer Inc. | Improved cells and cell cultures |
Family Cites Families (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4671958A (en) | 1982-03-09 | 1987-06-09 | Cytogen Corporation | Antibody conjugates for the delivery of compounds to target sites |
US4970198A (en) | 1985-10-17 | 1990-11-13 | American Cyanamid Company | Antitumor antibiotics (LL-E33288 complex) |
US5225539A (en) * | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US4771128A (en) * | 1986-10-10 | 1988-09-13 | Cetus Corporation | Method of purifying toxin conjugates using hydrophobic interaction chromatography |
US5079233A (en) | 1987-01-30 | 1992-01-07 | American Cyanamid Company | N-acyl derivatives of the LL-E33288 antitumor antibiotics, composition and methods for using the same |
US5037651A (en) | 1987-01-30 | 1991-08-06 | American Cyanamid Company | Dihydro derivatives of LL-E33288 antibiotics |
US5053394A (en) | 1988-09-21 | 1991-10-01 | American Cyanamid Company | Targeted forms of methyltrithio antitumor agents |
US5530101A (en) * | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5134075A (en) * | 1989-02-17 | 1992-07-28 | Oncogen Limited Partnership | Monoclonal antibody to novel antigen associated with human tumors |
GB8928874D0 (en) * | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
DK0489149T3 (da) * | 1990-06-27 | 2001-12-27 | Univ Princeton | Prober til påvisning af mutant P53 |
US5558864A (en) * | 1991-03-06 | 1996-09-24 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Humanized and chimeric anti-epidermal growth factor receptor monoclonal antibodies |
US5714350A (en) * | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
US5686072A (en) * | 1992-06-17 | 1997-11-11 | Board Of Regents, The University Of Texas | Epitope-specific monoclonal antibodies and immunotoxins and uses thereof |
US5484892A (en) * | 1993-05-21 | 1996-01-16 | Dana-Farber Cancer Institute, Inc. | Monoclonal antibodies that block ligand binding to the CD22 receptor in mature B cells |
US6180377B1 (en) * | 1993-06-16 | 2001-01-30 | Celltech Therapeutics Limited | Humanized antibodies |
US5436265A (en) * | 1993-11-12 | 1995-07-25 | Merck Frosst Canada, Inc. | 1-aroyl-3-indolyl alkanoic acids and derivatives thereof useful as anti-inflammatory agents |
US6310185B1 (en) | 1994-03-08 | 2001-10-30 | Memorial Sloan Kettering Cancer Center | Recombinant human anti-Lewis Y antibodies |
US5773001A (en) | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
DE69521002T3 (de) | 1994-08-12 | 2010-02-25 | The University Of Utah Research Foundation, Salt Lake City | Mutationen des mit 17q verbundenen Ovarial- und Brustkrebs Empfindlichkeitsgens |
DE69534530T2 (de) * | 1994-08-12 | 2006-07-06 | Immunomedics, Inc. | Für b-zell-lymphom und leukämiezellen spezifische immunkonjugate und humane antikörper |
US5714586A (en) * | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
US5712374A (en) * | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
US7147851B1 (en) * | 1996-08-15 | 2006-12-12 | Millennium Pharmaceuticals, Inc. | Humanized immunoglobulin reactive with α4β7 integrin |
US20020141990A1 (en) * | 1996-11-01 | 2002-10-03 | Smithkline Beecham Corporation | Anti-RSV human monoclonal antibodies |
US5980898A (en) | 1996-11-14 | 1999-11-09 | The United States Of America As Represented By The U.S. Army Medical Research & Material Command | Adjuvant for transcutaneous immunization |
EP0970227B1 (en) * | 1997-03-20 | 2008-01-09 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES | Recombinant antibodies and immunoconjugates targeted to cd-22 bearing cells and tumors |
US6183744B1 (en) | 1997-03-24 | 2001-02-06 | Immunomedics, Inc. | Immunotherapy of B-cell malignancies using anti-CD22 antibodies |
US6306393B1 (en) | 1997-03-24 | 2001-10-23 | Immunomedics, Inc. | Immunotherapy of B-cell malignancies using anti-CD22 antibodies |
AU740284B2 (en) * | 1997-06-13 | 2001-11-01 | Genentech Inc. | Stabilized antibody formulation |
AT408613B (de) | 1998-06-17 | 2002-01-25 | Immuno Ag | Pharmazeutisches faktor vii-präparat |
US6183477B1 (en) * | 1998-09-04 | 2001-02-06 | Smith & Nephew, Inc. | Attachment tool for drill guide |
KR100345463B1 (ko) * | 1998-11-19 | 2003-01-08 | 주)녹십자 | B형간염바이러스의표면항원프리-s1에대한인간화항체및이의제조방법 |
JP2000226336A (ja) * | 1998-11-30 | 2000-08-15 | Sankyo Co Ltd | 免疫グロブリン製剤 |
CA2351346C (en) | 1998-12-10 | 2015-09-01 | Phylos, Inc. | Protein scaffolds for antibody mimics and other binding proteins |
AU782160B2 (en) | 1999-06-09 | 2005-07-07 | Immunomedics Inc. | Immunotherapy of autoimmune disorders using antibodies which target B-cells |
EP1210361B1 (en) * | 1999-08-17 | 2004-04-14 | Novo Nordisk Health Care AG | Stabilisation of freeze-dried cake |
SI1232392T1 (en) * | 1999-10-12 | 2003-10-31 | Connex Gesellschaft Zur Optimierung Von Forschung Und | Improved method for the detection of acid resistant bacteria of the genus helicobacter in stool |
US20010046496A1 (en) * | 2000-04-14 | 2001-11-29 | Brettman Lee R. | Method of administering an antibody |
GB0013810D0 (en) * | 2000-06-06 | 2000-07-26 | Celltech Chiroscience Ltd | Biological products |
PL224001B1 (pl) * | 2002-05-02 | 2016-11-30 | Wyeth Corp | Sposób wytwarzania stabilnej liofilizowanej kompozycji obejmującej monomeryczne koniugaty pochodna kalicheamycyny/przeciwciało anty-CD22, kompozycja otrzymana tym sposobem oraz jej zastosowanie |
GB0210121D0 (en) * | 2002-05-02 | 2002-06-12 | Celltech R&D Ltd | Biological products |
-
2003
- 2003-05-02 PL PL410218A patent/PL224001B1/pl unknown
- 2003-05-02 PT PT111579819T patent/PT2371392E/pt unknown
- 2003-05-02 SG SG200607459-5A patent/SG165158A1/en unknown
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