RU2408605C2 - Полипептид, способный преодолевать гематоэнцефалический барьер, и его конъюгат - Google Patents
Полипептид, способный преодолевать гематоэнцефалический барьер, и его конъюгат Download PDFInfo
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- RU2408605C2 RU2408605C2 RU2007134566/10A RU2007134566A RU2408605C2 RU 2408605 C2 RU2408605 C2 RU 2408605C2 RU 2007134566/10 A RU2007134566/10 A RU 2007134566/10A RU 2007134566 A RU2007134566 A RU 2007134566A RU 2408605 C2 RU2408605 C2 RU 2408605C2
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2703416C2 (ru) * | 2014-03-28 | 2019-10-16 | Эпосенс Лтд. | Соединения для транс-мембранной доставки молекул |
| US11230710B2 (en) | 2017-01-09 | 2022-01-25 | Aposense Ltd | Compounds and methods for trans-membrane delivery of molecules |
| US11318206B2 (en) | 2014-03-28 | 2022-05-03 | Aposense Ltd | Compounds and methods for trans-membrane delivery of molecules |
| US12337036B2 (en) | 2018-01-01 | 2025-06-24 | Aposense Ltd | Compounds and methods for trans-membrane delivery of molecules |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4903036B2 (ja) | 2003-01-06 | 2012-03-21 | アンジオケム・インコーポレーテッド | 血液脳関門を通過する担体としてのアプロチニンおよび類似体 |
| US7485706B2 (en) * | 2003-07-30 | 2009-02-03 | The Board Of Trustees Of The Leland Stanford Junior University | Neurodegenerative protein aggregation inhibition methods and compounds |
| EP1841455A1 (en) * | 2005-01-24 | 2007-10-10 | Amgen Inc. | Humanized anti-amyloid antibody |
| BRPI0520032A2 (pt) | 2005-02-18 | 2009-04-14 | Angiochem Inc | moléculas para transportar um composto através da barreira hematoencefálica |
| US20090016959A1 (en) * | 2005-02-18 | 2009-01-15 | Richard Beliveau | Delivery of antibodies to the central nervous system |
| WO2007009229A1 (en) * | 2005-07-15 | 2007-01-25 | Angiochem Inc. | Use of aprotinin polypeptides as carriers in pharmaceutical conjugates |
| EP2074142A4 (en) * | 2006-10-19 | 2010-10-27 | Angiochem Inc | COMPOUNDS FOR STIMULATING THE FUNCTION OF P-GLYCOPROTEIN AND APPLICATIONS THEREOF |
| DK2164866T3 (da) * | 2007-05-29 | 2014-07-28 | Angiochem Inc | Aprotininlignende polypeptider til fremføring af midler, der er konjugeret dertil, til væv |
| US9365634B2 (en) | 2007-05-29 | 2016-06-14 | Angiochem Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
| AU2008255556B2 (en) * | 2007-05-29 | 2014-08-07 | Angiochem, Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
| MX2010006925A (es) * | 2007-12-20 | 2011-05-02 | Angiochem Inc | Conjugados de polipeptido-acido nucleico y sus usos. |
| CA2709354C (en) | 2007-12-21 | 2014-06-17 | Amgen Inc. | Anti-amyloid antibodies and uses thereof |
| EP2281004A4 (en) * | 2008-04-14 | 2012-02-15 | Proscan Rx Pharma Inc | PROSTATE-SPECIFIC MEMBRANANT ANTIBODIES AND ANTIGEN-BINDING FRAGMENTS |
| WO2009127072A1 (en) * | 2008-04-18 | 2009-10-22 | Angiochem Inc. | Pharmaceutical compositions of paclitaxel, paclitaxel analogs or paclitaxel conjugates and related methods of preparation and use |
| WO2010043047A1 (en) * | 2008-10-15 | 2010-04-22 | Angiochem Inc. | Conjugates of glp-1 agonists and uses thereof |
| CA2740317A1 (en) * | 2008-10-15 | 2010-04-22 | Angiochem Inc. | Etoposide and doxorubicin conjugates for drug delivery |
| RU2011125367A (ru) * | 2008-12-05 | 2013-01-10 | Ангиочем Инк. | Конъюгаты лептина и аналогов лептина и их применение |
| US9914754B2 (en) | 2008-12-05 | 2018-03-13 | Angiochem Inc. | Conjugates of neurotensin or neurotensin analogs and uses thereof |
| CN103665170A (zh) * | 2008-12-05 | 2014-03-26 | 安吉奥开米公司 | 肽治疗剂轭合物及其应用 |
| AU2009327267A1 (en) | 2008-12-17 | 2011-07-14 | Angiochem, Inc. | Membrane type-1 matrix metalloprotein inhibitors and uses thereof |
| ES2729261T3 (es) * | 2009-04-20 | 2019-10-31 | Angiochem Inc | Tratamiento del cáncer de ovario utilizando un agente anticancerígeno conjugado con un análogo de Angiopep-2 |
| US20100284921A1 (en) * | 2009-05-08 | 2010-11-11 | Temple University - Of The Commonwealth System Of Higher Education | Targeted nanoparticles for intracellular cancer therapy |
| CA2764777A1 (en) * | 2009-06-11 | 2010-12-16 | Angiochem Inc. | Fusion proteins for delivery of gdnf and bdnf to the central nervous system |
| WO2011000095A1 (en) | 2009-07-02 | 2011-01-06 | Angiochem Inc. | Multimeric peptide conjugates and uses thereof |
| US20120277158A1 (en) * | 2009-10-06 | 2012-11-01 | Angiochem Inc. | Compositions and methods for the transport of therapeutic agents |
| NO2719708T3 (enExample) | 2009-11-13 | 2018-03-24 | ||
| MX2013000250A (es) | 2010-07-02 | 2013-10-28 | Angiochem Inc | Polipeptidos cortos y que contienen d-aminoacido para conjugados terapeuticos y usos de los mismos. |
| US20130280281A1 (en) * | 2010-07-02 | 2013-10-24 | Jean-Paul Castaigne | Short and d-amino acid-containing polypeptides for therapeutic conjugates and uses thereof |
| JP2013540694A (ja) | 2010-08-06 | 2013-11-07 | ウー３・フアルマ・ゲー・エム・ベー・ハー | Ｈｅｒ３結合剤の前立腺治療における使用 |
| CN102614524A (zh) * | 2011-02-01 | 2012-08-01 | 复旦大学 | 低密度脂蛋白受体相关蛋白配体多肽修饰的脑肿瘤靶向基因递释复合物 |
| WO2013056096A1 (en) * | 2011-10-13 | 2013-04-18 | Angiochem Inc. | Polypeptide-opioid conjugates and uses thereof |
| JP2015526434A (ja) | 2012-08-14 | 2015-09-10 | アンジオケム インコーポレーテッド | ペプチド−デンドリマーコンジュゲート及びその使用 |
| JP6108265B2 (ja) * | 2012-11-19 | 2017-04-05 | 国立大学法人 千葉大学 | 脳送達用キャリアおよびその用途 |
| AU2014312190A1 (en) | 2013-08-28 | 2016-02-18 | Bioasis Technologies Inc. | CNS-targeted conjugates of antibodies |
| WO2015124540A1 (en) * | 2014-02-19 | 2015-08-27 | F. Hoffmann-La Roche Ag | Blood brain barrier shuttle |
| US9993563B2 (en) * | 2014-03-28 | 2018-06-12 | Aposense Ltd. | Compounds and methods for trans-membrane delivery of molecules |
| US11241520B2 (en) | 2014-08-07 | 2022-02-08 | Cook Medical Technologies Llc | Compositions and devices incorporating water-insoluble therapeutic agents and methods of the use thereof |
| US9655998B2 (en) | 2014-08-07 | 2017-05-23 | Cook Medical Technologies Llc | Encapsulated drug compositions and methods of use thereof |
| US9180226B1 (en) | 2014-08-07 | 2015-11-10 | Cook Medical Technologies Llc | Compositions and devices incorporating water-insoluble therapeutic agents and methods of the use thereof |
| US10711270B2 (en) | 2014-10-03 | 2020-07-14 | University Of Massachusetts | High efficiency library-identified AAV vectors |
| US10370432B2 (en) | 2014-10-03 | 2019-08-06 | University Of Massachusetts | Heterologous targeting peptide grafted AAVS |
| EP3222291B1 (en) * | 2014-10-24 | 2020-08-19 | University of Science and Technology of China | Angiopeptin conjugates for amyloid protein targeting |
| EP3215184B1 (en) * | 2014-11-06 | 2021-03-03 | OSE Immunotherapeutics | Therapeutic multi-peptides t specific immune therapy for treatment of brain metastasis |
| EP3256170B1 (en) | 2015-02-13 | 2020-09-23 | University of Massachusetts | Compositions and methods for transient delivery of nucleases |
| JP6612063B2 (ja) * | 2015-06-11 | 2019-11-27 | 国立大学法人滋賀医科大学 | 悪性神経膠腫分子標的ペプチド |
| EP3307326B9 (en) | 2015-06-15 | 2021-02-24 | Angiochem Inc. | Methods for the treatment of leptomeningeal carcinomatosis |
| PL417159A1 (pl) | 2016-05-11 | 2017-11-20 | Instytut Biologii Doświadczalnej Im. Marcelego Nenckiego | Koniugaty białka prionowego z dendrymerami do zastosowania w leczeniu choroby Alzheimera |
| CN110267674A (zh) * | 2016-07-08 | 2019-09-20 | 奥美药业有限公司 | 包含瘦素的融合蛋白及其生产和使用方法 |
| US10702589B2 (en) | 2016-10-04 | 2020-07-07 | Ann And Robert H. Lurie Children's Hospital Of Chicago | Compositions and methods of treating neurological disorder and stress-induced conditions |
| US10688191B2 (en) | 2018-01-19 | 2020-06-23 | Hr Biomed, Llc | Delivery of a chemotherapy agent across the blood-brain barrier |
| CN109666973B (zh) * | 2018-11-21 | 2022-11-04 | 北京大学 | 一种穿过血脑屏障的肽库及其筛选方法 |
| WO2021188802A1 (en) * | 2020-03-18 | 2021-09-23 | Brown Kathlynn C | Molecular transport system to the central nervous system |
| CA3128035A1 (en) | 2020-08-13 | 2022-02-13 | Bioasis Technologies, Inc. | Combination therapies for delivery across the blood brain barrier |
| WO2022156531A1 (zh) * | 2021-01-19 | 2022-07-28 | 中国人民解放军军事科学院军事医学研究院 | 一种能够透过生物屏障的动力蛋白结合肽及其应用 |
| CN112851789B (zh) * | 2021-02-04 | 2022-10-18 | 大理大学 | 一种脑靶向hiv进入抑制剂多肽及其应用 |
| WO2022178425A1 (en) * | 2021-02-22 | 2022-08-25 | Yale University | Targeted bifunctional degraders |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0393431A1 (de) * | 1989-04-18 | 1990-10-24 | Bayer Ag | Gentechnologisch hergestellte Homologe des Alzheimer-Protease-Inhibitors, Wirtstämme sowie Expressionsvektoren für ihre Herstellung für ihre Verwendung als Arzneimittel |
| WO2004060403A2 (en) * | 2003-01-06 | 2004-07-22 | Angiochem Inc. | Aprotinin and anglos as carriers across the blood-brain barrier |
Family Cites Families (86)
| 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 |
| JPS63503086A (ja) | 1986-03-13 | 1988-11-10 | バイオテクノロジ− オ−ストラリア プロプライエタリ− リミテッド | インヒビンの分析法 |
| GB2188322A (en) * | 1986-03-26 | 1987-09-30 | Bayer Ag | Aprotinin and analogues thereof produced by a recombinant host |
| US4902505A (en) | 1986-07-30 | 1990-02-20 | Alkermes | Chimeric peptides for neuropeptide delivery through the blood-brain barrier |
| US4801575A (en) | 1986-07-30 | 1989-01-31 | The Regents Of The University Of California | Chimeric peptides for neuropeptide delivery through the blood-brain barrier |
| US4904768A (en) * | 1987-08-04 | 1990-02-27 | Bristol-Myers Company | Epipodophyllotoxin glucoside 4'-phosphate derivatives |
| GB2208511A (en) | 1987-08-07 | 1989-04-05 | Bayer Ag | Variants of bovine pancreatic trypsin inhibitor produced by recombinant dna technology |
| US4942184A (en) | 1988-03-07 | 1990-07-17 | The United States Of America As Represented By The Department Of Health And Human Services | Water soluble, antineoplastic derivatives of taxol |
| US5632990A (en) * | 1988-04-22 | 1997-05-27 | Cancer Research Campaign Tech. Ltd. | Treatment for tumors comprising conjugated antibody A5B7 and a prodrug |
| US5258499A (en) * | 1988-05-16 | 1993-11-02 | Vestar, Inc. | Liposome targeting using receptor specific ligands |
| US5028697A (en) * | 1988-08-08 | 1991-07-02 | Eli Lilly And Company | Cytotoxic antibody conjugates of hydrazide derivatized methotrexate analogs via simple organic linkers |
| US5169933A (en) * | 1988-08-15 | 1992-12-08 | Neorx Corporation | Covalently-linked complexes and methods for enhanced cytotoxicity and imaging |
| US5948634A (en) | 1988-12-21 | 1999-09-07 | The General Hospital Coporation | Neural thread protein gene expression and detection of alzheimer's disease |
| US6020145A (en) * | 1989-06-30 | 2000-02-01 | Bristol-Myers Squibb Company | Methods for determining the presence of carcinoma using the antigen binding region of monoclonal antibody BR96 |
| US6475781B1 (en) | 1990-05-17 | 2002-11-05 | Dana-Farber Cancer Institute, Inc. | Trans-dominant suppressor genes for oligomeric proteins |
| US5714167A (en) * | 1992-06-15 | 1998-02-03 | Emisphere Technologies, Inc. | Active agent transport systems |
| US6495513B1 (en) * | 1991-03-11 | 2002-12-17 | Curis, Inc. | Morphogen-enhanced survival and repair of neural cells |
| US5955444A (en) | 1991-08-09 | 1999-09-21 | Massachusetts Institute Of Technology | Method of inhibiting abnormal tau hyper phosphorylation in a cell |
| US5627270A (en) | 1991-12-13 | 1997-05-06 | Trustees Of Princeton University | Glycosylated steroid derivatives for transport across biological membranes and process for making and using same |
| CA2145517A1 (en) | 1992-09-25 | 1994-04-14 | Ignace Lasters | Bovine pancreatic trypsin inhibitor derived inhibitors of factor viia - tissue factor complex |
| WO1994019692A1 (en) * | 1993-02-18 | 1994-09-01 | The General Hospital Corporation | Alzheimer's disease therapeutics |
| WO1996031531A2 (en) | 1995-04-04 | 1996-10-10 | Advanced Bioconcept, Inc. | Fluorescent peptides |
| AU5854096A (en) * | 1995-05-08 | 1996-11-29 | Scios Inc. | Kunitz type protease inhibitors |
| ZA963619B (en) | 1995-05-08 | 1996-11-22 | Scios Inc | Protease inhibitor peptides |
| WO1996039183A1 (en) | 1995-05-31 | 1996-12-12 | Fred Hutchinson Cancer Research Center | Compositions and methods for targeted delivery of effector molecules |
| US5780265A (en) * | 1995-06-05 | 1998-07-14 | Genentech, Inc. | Kunitz type plasma kallikrein inhibitors |
| AU6267896A (en) | 1995-06-07 | 1996-12-30 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth oftumors |
| DK0891426T3 (da) * | 1996-03-11 | 2006-10-02 | Bayer Corp | Humant bikunin |
| JP2000509394A (ja) | 1996-05-01 | 2000-07-25 | アンティバイラルズ インコーポレイテッド | 細胞膜を横切って物質を輸送するためのポリペプチド結合体 |
| DE19629982A1 (de) * | 1996-07-25 | 1998-01-29 | Bayer Ag | Aprotinin-Varianten mit verbesserten Eigenschaften |
| EP0932390A1 (en) * | 1996-10-11 | 1999-08-04 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method |
| US6056973A (en) * | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
| AU6682598A (en) | 1997-03-04 | 1998-09-22 | Bio-Technology General Corporation | Isolation of tissue specific peptide ligands and their use for targeting pharmaceuticals to organs |
| US6126965A (en) * | 1997-03-21 | 2000-10-03 | Georgetown University School Of Medicine | Liposomes containing oligonucleotides |
| AU734827B2 (en) * | 1997-05-21 | 2001-06-21 | Board Of Trustees Of The Leland Stanford Junior University | Composition and method for enhancing transport across biological membranes |
| US6093692A (en) * | 1997-09-25 | 2000-07-25 | The University Of Southern California | Method and compositions for lipidization of hydrophilic molecules |
| US6475481B2 (en) | 1997-11-18 | 2002-11-05 | Canji Inc | Purging of stem cell products |
| WO1999026657A1 (en) | 1997-11-25 | 1999-06-03 | Musc Foundation For Research Development | Inhibitors of nitric oxide synthase |
| US5981564A (en) * | 1998-07-01 | 1999-11-09 | Universite Laval | Water-soluble derivatives of paclitaxel, method for producing same and uses thereof |
| GB9814527D0 (en) | 1998-07-03 | 1998-09-02 | Cyclacel Ltd | Delivery system |
| US6703381B1 (en) * | 1998-08-14 | 2004-03-09 | Nobex Corporation | Methods for delivery therapeutic compounds across the blood-brain barrier |
| US5922754A (en) * | 1998-10-02 | 1999-07-13 | Abbott Laboratories | Pharmaceutical compositions containing paclitaxel |
| MXPA01008699A (es) * | 1999-02-24 | 2002-06-21 | Uab Research Foundation | Derivados de taxano para terapia de cancer dirigida. . |
| GB9911683D0 (en) | 1999-05-19 | 1999-07-21 | Chiron Spa | Antigenic peptides |
| US6180607B1 (en) * | 1999-08-05 | 2001-01-30 | Christopher Davies | Protein having proteinase inhibitor activity |
| US6713454B1 (en) * | 1999-09-13 | 2004-03-30 | Nobex Corporation | Prodrugs of etoposide and etoposide analogs |
| US6136846A (en) | 1999-10-25 | 2000-10-24 | Supergen, Inc. | Formulation for paclitaxel |
| DE19953696A1 (de) | 1999-11-09 | 2001-05-10 | Alexander Cherkasky | Selektive proteolytische Synzyme (SPS) |
| CA2355334A1 (en) | 2000-10-16 | 2002-04-16 | Procyon Biopharma Inc. | Pharmaceutical preparations and methods for inhibiting tumors |
| US6825166B2 (en) * | 2001-03-23 | 2004-11-30 | Tapestry Pharmaceuticals, Inc. | Molecular conjugates for use in treatment of cancer |
| JP4202250B2 (ja) * | 2001-07-25 | 2008-12-24 | バイオマリン ファーマシューティカル インコーポレイテッド | 血液脳関門輸送を調節するための組成物および方法 |
| CN1195845C (zh) * | 2001-10-08 | 2005-04-06 | 中国医学科学院阜外心血管病医院 | 人源抑肽酶基因、该基因编码的蛋白质及其应用 |
| US7192921B2 (en) * | 2001-11-08 | 2007-03-20 | The Burnham Institute | Peptides that home to tumor lymphatic vasculature and methods of using same |
| US20050215478A1 (en) * | 2002-02-07 | 2005-09-29 | Ben-Sasson Shmuel A | Amino acid sequences capable of facilitating penetration across a biological barrier |
| EP1472351B1 (en) * | 2002-02-07 | 2007-06-20 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Amino acid sequences capable of facilitating penetration across a biological barrier |
| JP2005537244A (ja) | 2002-06-28 | 2005-12-08 | ナステック・ファーマシューティカル・カンパニー・インコーポレーテッド | 療法化合物の粘膜搬送を増進させるための、上皮接合部接着分子の生理機能を調節する組成物および方法 |
| US7829694B2 (en) * | 2002-11-26 | 2010-11-09 | Medtronic, Inc. | Treatment of neurodegenerative disease through intracranial delivery of siRNA |
| WO2004108071A2 (en) | 2003-06-05 | 2004-12-16 | Salk Institute For Biological Studies | Targeting polypeptides to the central nervous system |
| US20050026823A1 (en) * | 2003-06-20 | 2005-02-03 | Biomarin Pharmaceutical Inc. | Use of the chaperone receptor-associated protein (RAP) for the delivery of therapeutic compounds to the brain and other tissues |
| CA2525236C (en) | 2003-06-20 | 2015-03-24 | Biomarin Pharmaceutical Inc. | Delivery of therapeutic compounds to the brain and other tissues |
| AU2004263458B2 (en) * | 2003-08-08 | 2010-06-24 | Actgen, Inc. | Polypeptides having brain-localizing activity and uses thereof |
| US20050058702A1 (en) * | 2003-09-17 | 2005-03-17 | Ben-Sasson Shmuel A. | Compositions capable of facilitating penetration across a biological barrier |
| US20050208095A1 (en) | 2003-11-20 | 2005-09-22 | Angiotech International Ag | Polymer compositions and methods for their use |
| US7208174B2 (en) * | 2003-12-18 | 2007-04-24 | Hoffmann-La Roche Inc. | Liposome compositions |
| EP1799826B1 (en) * | 2004-09-29 | 2009-08-12 | Children's Memorial Hospital | siRNA-MEDIATED GENE SILENCING OF ALPHA SYNUCLEIN |
| BRPI0520032A2 (pt) * | 2005-02-18 | 2009-04-14 | Angiochem Inc | moléculas para transportar um composto através da barreira hematoencefálica |
| US20090016959A1 (en) * | 2005-02-18 | 2009-01-15 | Richard Beliveau | Delivery of antibodies to the central nervous system |
| WO2006124737A2 (en) * | 2005-05-12 | 2006-11-23 | Tapestry Pharmaceuticals, Inc. | Molecular constructs suitable for targeted conjugates |
| WO2007009229A1 (en) | 2005-07-15 | 2007-01-25 | Angiochem Inc. | Use of aprotinin polypeptides as carriers in pharmaceutical conjugates |
| GB0517092D0 (en) | 2005-08-19 | 2005-09-28 | Novartis Ag | New compositions containing taxane derivatives |
| JP2009507852A (ja) | 2005-09-08 | 2009-02-26 | エムディーアールエヌエー，インコーポレイテッド | リボ核酸の細胞への送達用医薬組成物 |
| CA2627585A1 (en) * | 2005-11-01 | 2007-05-10 | Alnylam Pharmaceuticals, Inc. | Rnai inhibition of influenza virus replication |
| AR054215A1 (es) | 2006-01-20 | 2007-06-13 | Eriochem Sa | Una formulacion farmaceutica de un taxano, una composicion solida de un taxano liofilizado a partir de una solucion de acido acetico, un procedimiento para la preparacion de dicha composicion solida de un taxano, una composicion solubilizante de un taxano liofilizado, y un conjunto de elementos (kit |
| ES2371495T3 (es) | 2006-07-24 | 2012-01-03 | Biorexis Pharmaceutical Corporation | Proteínas de fusión de exendina. |
| EP2074142A4 (en) | 2006-10-19 | 2010-10-27 | Angiochem Inc | COMPOUNDS FOR STIMULATING THE FUNCTION OF P-GLYCOPROTEIN AND APPLICATIONS THEREOF |
| AU2008255556B2 (en) | 2007-05-29 | 2014-08-07 | Angiochem, Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
| US8802631B2 (en) | 2007-09-17 | 2014-08-12 | Ludwig Institute For Cancer Research Ltd. | Peptides and methods for the treatment of gliomas and other cancers |
| WO2009070597A2 (en) | 2007-11-26 | 2009-06-04 | Armagen Technologies, Inc. | Fusion proteins for delivery of gdnf to the cns |
| MX2010006925A (es) | 2007-12-20 | 2011-05-02 | Angiochem Inc | Conjugados de polipeptido-acido nucleico y sus usos. |
| WO2009127072A1 (en) | 2008-04-18 | 2009-10-22 | Angiochem Inc. | Pharmaceutical compositions of paclitaxel, paclitaxel analogs or paclitaxel conjugates and related methods of preparation and use |
| WO2010043047A1 (en) | 2008-10-15 | 2010-04-22 | Angiochem Inc. | Conjugates of glp-1 agonists and uses thereof |
| CA2740317A1 (en) | 2008-10-15 | 2010-04-22 | Angiochem Inc. | Etoposide and doxorubicin conjugates for drug delivery |
| RU2011125367A (ru) | 2008-12-05 | 2013-01-10 | Ангиочем Инк. | Конъюгаты лептина и аналогов лептина и их применение |
| US9914754B2 (en) * | 2008-12-05 | 2018-03-13 | Angiochem Inc. | Conjugates of neurotensin or neurotensin analogs and uses thereof |
| CN103665170A (zh) | 2008-12-05 | 2014-03-26 | 安吉奥开米公司 | 肽治疗剂轭合物及其应用 |
| AU2009327267A1 (en) | 2008-12-17 | 2011-07-14 | Angiochem, Inc. | Membrane type-1 matrix metalloprotein inhibitors and uses thereof |
-
2005
- 2005-07-21 BR BRPI0520032-6A patent/BRPI0520032A2/pt not_active Application Discontinuation
- 2005-07-21 MX MX2007010113A patent/MX2007010113A/es active IP Right Grant
- 2005-07-21 US US11/884,629 patent/US7902156B2/en not_active Expired - Fee Related
- 2005-07-21 AT AT05770546T patent/ATE551422T1/de active
- 2005-07-21 EP EP05770546.9A patent/EP1859041B2/en not_active Expired - Lifetime
- 2005-07-21 WO PCT/CA2005/001158 patent/WO2006086870A1/en not_active Ceased
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- 2005-07-21 AU AU2005327497A patent/AU2005327497B2/en not_active Ceased
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- 2005-07-21 RU RU2007134566/10A patent/RU2408605C2/ru active
- 2005-07-21 PT PT05770546T patent/PT1859041E/pt unknown
- 2005-07-21 EP EP11000946.1A patent/EP2360258B1/en not_active Expired - Lifetime
- 2005-07-21 ES ES05770546.9T patent/ES2383901T5/es not_active Expired - Lifetime
- 2005-07-21 SI SI200531926T patent/SI2360258T1/sl unknown
- 2005-07-21 US US11/185,947 patent/US7557182B2/en not_active Expired - Lifetime
- 2005-07-21 DK DK05770546.9T patent/DK1859041T4/en active
- 2005-07-21 PL PL05770546T patent/PL1859041T5/pl unknown
- 2005-07-21 CN CN201410334833.1A patent/CN104311653B/zh not_active Expired - Fee Related
-
2007
- 2007-08-17 ZA ZA200706917A patent/ZA200706917B/xx unknown
-
2010
- 2010-09-13 RU RU2010137915A patent/RU2611193C2/ru active
-
2011
- 2011-01-13 JP JP2011004842A patent/JP5462193B2/ja not_active Expired - Fee Related
- 2011-03-07 US US13/042,017 patent/US8828949B2/en not_active Expired - Lifetime
-
2012
- 2012-06-26 CY CY20121100562T patent/CY1113299T1/el unknown
-
2013
- 2013-11-28 JP JP2013245690A patent/JP2014088386A/ja active Pending
-
2014
- 2014-08-12 US US14/457,861 patent/US20150174266A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0393431A1 (de) * | 1989-04-18 | 1990-10-24 | Bayer Ag | Gentechnologisch hergestellte Homologe des Alzheimer-Protease-Inhibitors, Wirtstämme sowie Expressionsvektoren für ihre Herstellung für ihre Verwendung als Arzneimittel |
| WO2004060403A2 (en) * | 2003-01-06 | 2004-07-22 | Angiochem Inc. | Aprotinin and anglos as carriers across the blood-brain barrier |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2703416C2 (ru) * | 2014-03-28 | 2019-10-16 | Эпосенс Лтд. | Соединения для транс-мембранной доставки молекул |
| US11318206B2 (en) | 2014-03-28 | 2022-05-03 | Aposense Ltd | Compounds and methods for trans-membrane delivery of molecules |
| US11230710B2 (en) | 2017-01-09 | 2022-01-25 | Aposense Ltd | Compounds and methods for trans-membrane delivery of molecules |
| US12337036B2 (en) | 2018-01-01 | 2025-06-24 | Aposense Ltd | Compounds and methods for trans-membrane delivery of molecules |
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