ES2424242T3 - Uso de polipéptidos de aprotinina como portadores en conjugados farmacéuticos - Google Patents
Uso de polipéptidos de aprotinina como portadores en conjugados farmacéuticos Download PDFInfo
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- ES2424242T3 ES2424242T3 ES10006638T ES10006638T ES2424242T3 ES 2424242 T3 ES2424242 T3 ES 2424242T3 ES 10006638 T ES10006638 T ES 10006638T ES 10006638 T ES10006638 T ES 10006638T ES 2424242 T3 ES2424242 T3 ES 2424242T3
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Classifications
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- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Oncology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US69937505P | 2005-07-15 | 2005-07-15 | |
| US699375P | 2005-07-15 | ||
| US75853206P | 2006-01-13 | 2006-01-13 | |
| US758532P | 2006-01-13 |
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| ES2424242T3 true ES2424242T3 (es) | 2013-09-30 |
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| ES10006638T Active ES2424242T3 (es) | 2005-07-15 | 2006-07-14 | Uso de polipéptidos de aprotinina como portadores en conjugados farmacéuticos |
| ES11010125T Active ES2744225T3 (es) | 2005-07-15 | 2006-07-14 | Uso de polipéptidos de aprotinina como portadores en conjugados farmacéuticos |
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| Application Number | Title | Priority Date | Filing Date |
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| ES11010125T Active ES2744225T3 (es) | 2005-07-15 | 2006-07-14 | Uso de polipéptidos de aprotinina como portadores en conjugados farmacéuticos |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US8969310B2 (https=) |
| EP (4) | EP1907009A4 (https=) |
| JP (3) | JP5436856B2 (https=) |
| CN (1) | CN101262890B (https=) |
| AU (1) | AU2006272405B2 (https=) |
| BR (1) | BRPI0613005A8 (https=) |
| CA (1) | CA2614687C (https=) |
| DK (2) | DK2233156T3 (https=) |
| ES (2) | ES2424242T3 (https=) |
| HR (1) | HRP20130720T1 (https=) |
| PL (1) | PL2233156T3 (https=) |
| PT (1) | PT2233156E (https=) |
| RU (2) | RU2422143C2 (https=) |
| SI (1) | SI2233156T1 (https=) |
| WO (1) | WO2007009229A1 (https=) |
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| US7906625B2 (en) | 2005-01-24 | 2011-03-15 | Amgen Inc. | Humanized anti-amyloid antibody |
| US7557182B2 (en) | 2005-02-18 | 2009-07-07 | Angiochem Inc. | Molecules for transporting a compound across the blood-brain barrier |
| US20090016959A1 (en) * | 2005-02-18 | 2009-01-15 | Richard Beliveau | Delivery of antibodies to the central nervous system |
| JP5436856B2 (ja) | 2005-07-15 | 2014-03-05 | アンジオケム インコーポレーティッド | 薬学的複合体における担体としてのアプロチニンポリペプチドの使用 |
| EP3539572A1 (en) | 2005-08-24 | 2019-09-18 | ImmunoGen, Inc. | Process for preparing maytansinoid antibody conjugates |
| EP2074142A4 (en) | 2006-10-19 | 2010-10-27 | Angiochem Inc | COMPOUNDS FOR STIMULATING THE FUNCTION OF P-GLYCOPROTEIN AND APPLICATIONS THEREOF |
| EP2789628A3 (en) | 2007-05-29 | 2015-03-04 | Angiochem Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
| PT2164866E (pt) * | 2007-05-29 | 2014-08-04 | Angiochem Inc | Polipéptidos de tipo aprotinina para administrar agentes conjugados com os mesmos aos tecidos |
| US9365634B2 (en) | 2007-05-29 | 2016-06-14 | Angiochem Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
| EP2235175A4 (en) * | 2007-12-20 | 2012-04-25 | Angiochem Inc | POLYPEPTIDE NUCLEIC ACID CONJUGATES AND USES THEREOF |
| WO2009085200A2 (en) | 2007-12-21 | 2009-07-09 | Amgen Inc. | Anti-amyloid antibodies and uses thereof |
| TR201905480T4 (tr) * | 2008-04-18 | 2019-05-21 | Angiochem Inc | Paklitaksel, paklitaksel analogları veya paklitaksel konjugatlarının farmasötik bileşimleri ve ilgili preparasyon ve kullanım yöntemleri. |
| BRPI0920209A2 (pt) | 2008-10-15 | 2015-12-22 | Angiochem Inc | conjugados de agonistas de glp-1 e usos dos mesmos |
| MX2011004019A (es) | 2008-10-15 | 2011-06-24 | Angiochem Inc | Conjugados de etoposido y doxorubicina para entrega de farmacos. |
| CA2745524C (en) | 2008-12-05 | 2020-06-09 | Angiochem Inc. | Conjugates of neurotensin or neurotensin analogs and uses thereof |
| WO2010069074A1 (en) | 2008-12-17 | 2010-06-24 | Universite Du Quebec A Montreal | Membrane type-1 matrix metalloprotein inhibitors and uses thereof |
| DE102009006228A1 (de) | 2009-01-27 | 2010-07-29 | Epo Experimentelle Pharmakologie & Onkologie Berlin-Buch Gmbh | Liposomale Zusammensetzung zur Behandlung von Hirnmetastasen |
| JP2010229122A (ja) * | 2009-03-06 | 2010-10-14 | Kumamoto Univ | 抗癌剤、医薬、及び癌疾患の検査薬 |
| WO2010121379A1 (en) * | 2009-04-20 | 2010-10-28 | Angiochem Inc | Treatment of ovarian cancer using an anticancer agent conjugated to an angiopep-2 analog |
| BRPI1010620B8 (pt) | 2009-06-03 | 2021-05-25 | Immunogen Inc | métodos de conjugação |
| AU2010268726A1 (en) | 2009-07-02 | 2012-01-19 | Angiochem Inc. | Multimeric peptide conjugates and uses thereof |
| RU2013103763A (ru) | 2010-07-02 | 2014-08-10 | Ангиохем Инк. | Короткие и содержащие d-аминокислоты полипептиды для терапевтических конъюгатов и их применения |
| WO2012037687A1 (en) * | 2010-09-23 | 2012-03-29 | Angiochem Inc. | Therapeutic polypeptides and uses thereof |
| CN102085157B (zh) * | 2011-01-27 | 2012-02-01 | 中国水产科学研究院黄海水产研究所 | 扇贝抗氧化肽纳米脂质体及其制备方法 |
| 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 |
| RS58367B1 (sr) | 2011-03-29 | 2019-03-29 | Immunogen Inc | Priprema konjugata antitela i majtanzinoida jednostepenim postupkom |
| EP2885318A4 (en) | 2012-08-14 | 2016-03-30 | Angiochem Inc | PEPTIDE DENDRIMER CONJUGATES AND ITS USES |
| WO2014055877A1 (en) | 2012-10-04 | 2014-04-10 | Immunogen, Inc. | Use of a pvdf membrane to purify cell-binding agent cytotoxic agent conjugates |
| US20160213760A1 (en) * | 2012-11-12 | 2016-07-28 | Angiochem Inc. | Aprotinin-derived polypeptide-antibody conjugates |
| JP6254692B2 (ja) * | 2013-07-03 | 2017-12-27 | ジ アリゾナ ボード オブ リージェンツ オン ビハーフ オブ ザ ユニヴァーシティー オブ アリゾナ | 認知機能不全を治療するための方法 |
| KR101899306B1 (ko) | 2013-07-03 | 2018-10-04 | 서울대학교산학협력단 | 시스테인으로 변형된 닭의 항체 및 이를 이용한 부위-특이적 접합 |
| US9796759B2 (en) | 2014-07-21 | 2017-10-24 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Ang-(1-7) derivative oligopeptides and methods for using and producing the same |
| US10183055B2 (en) | 2014-07-21 | 2019-01-22 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Ang-(1-7) derivative oligopeptides for the treatment of pain and other indications |
| GB201502447D0 (en) | 2015-02-13 | 2015-04-01 | Univ Liverpool | Method and apparatus for sample analysis |
| DK3307326T3 (da) | 2015-06-15 | 2020-10-19 | Angiochem Inc | Fremgangsmåder til behandling af leptomeningeal karcinomatose |
| JP2021512165A (ja) | 2018-01-29 | 2021-05-13 | コグノス・セラピューティクス・インコーポレイテッド | ボルテゾミブの腫瘍内送達 |
| CN111529716B (zh) * | 2020-06-02 | 2021-05-28 | 南方医科大学 | 一种多肽-紫杉醇偶联物及其应用 |
Family Cites Families (140)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US508697A (en) * | 1893-11-14 | Jar or bottle receiver | ||
| US4671958A (en) | 1982-03-09 | 1987-06-09 | Cytogen Corporation | Antibody conjugates for the delivery of compounds to target sites |
| ES8407536A1 (es) * | 1983-10-07 | 1984-10-01 | Jumberca Sa | Mejoras en los alimentadores de hilo para telares circulares de genero de punto dotados de dispositivos listadores. |
| AU599373B2 (en) | 1986-03-13 | 1990-07-19 | Biotechnology Australia Proprietary Limited | Method of assay of inhibin |
| 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 |
| US4902505A (en) | 1986-07-30 | 1990-02-20 | Alkermes | 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 |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| US5948634A (en) | 1988-12-21 | 1999-09-07 | The General Hospital Coporation | Neural thread protein gene expression and detection of alzheimer's disease |
| DE3912638A1 (de) | 1989-04-18 | 1990-10-31 | Bayer Ag | Gentechnologisch hergestellte homologe des alzheimer protease inhibitors, wirtstaemme sowie expressionsvektoren fuer ihre herstellung und ihre verwendung als arzneimittel |
| 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 |
| GB9213077D0 (en) | 1992-06-19 | 1992-08-05 | Erba Carlo Spa | Polymerbound taxol derivatives |
| WO1994007528A1 (en) | 1992-09-25 | 1994-04-14 | Corvas International, Inc. | Bovine pancreatic trypsin inhibitor derived inhibitors of factor viia-tissue factor complex |
| EP0599303A3 (en) | 1992-11-27 | 1998-07-29 | Takeda Chemical Industries, Ltd. | Peptide conjugate |
| MX9307777A (es) | 1992-12-15 | 1994-07-29 | Upjohn Co | 7-HALO-Y 7ß, 8ß-METANO-TAXOLES, USO ANTINEOPLASTICO Y COMPOSICIONES FARMACEUTICAS QUE LOS CONTIENEN. |
| WO1994019692A1 (en) | 1993-02-18 | 1994-09-01 | The General Hospital Corporation | Alzheimer's disease therapeutics |
| EP0820466A2 (en) | 1995-04-04 | 1998-01-28 | Advanced Bioconcept Inc. | Fluorescent peptides |
| JPH11504938A (ja) | 1995-05-08 | 1999-05-11 | サイオス インク． | クニッツ型プロテアーゼ阻害因子 |
| 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 |
| US5665702A (en) | 1995-06-06 | 1997-09-09 | Biomeasure Incorporated | Ionic molecular conjugates of N-acylated derivatives of poly(2-amino-2-deoxy-D-glucose) and polypeptides |
| AU6267896A (en) | 1995-06-07 | 1996-12-30 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth oftumors |
| IL126115A (en) | 1996-03-11 | 2007-03-08 | Aerovance Inc | Significantly purified protein with suppressive activity for sirin protease and its pharmaceutical preparations |
| WO1997040160A1 (en) | 1996-04-24 | 1997-10-30 | Rijksuniversiteit Te Groningen | A prokaryotic protein having functional and structural homology with the human p-glycoprotein encoded by the mdr-1 gene, nucleic acids encoding and cells expressing said protein |
| AU729643B2 (en) | 1996-05-01 | 2001-02-08 | Antivirals Inc. | Polypeptide conjugates for transporting substances across cell membranes |
| US6056973A (en) | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
| EP0932390A1 (en) | 1996-10-11 | 1999-08-04 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method |
| US5948750A (en) | 1996-10-30 | 1999-09-07 | Merck & Co., Inc. | Conjugates useful in the treatment of prostate cancer |
| JP4116683B2 (ja) | 1997-02-28 | 2008-07-09 | ツェー・エス・エル・ベーリング・ゲー・エム・ベー・ハー | 徐放性局所送達製剤 |
| WO1998039469A1 (en) * | 1997-03-04 | 1998-09-11 | Bio-Technology General Corp. | 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 |
| IL132941A0 (en) | 1997-05-21 | 2001-03-19 | Univ Leland Stanford Junior | Composition and method for enhancing transport across biological membranes |
| US6391305B1 (en) | 1997-09-10 | 2002-05-21 | Merck & Co., Inc. | Conjugates useful in the treatment of prostate cancer |
| 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 |
| AU768027B2 (en) | 1999-02-24 | 2003-11-27 | Uab Research Foundation, The | Taxane derivatives for targeted therapy of cancer |
| 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) |
| CA2307393A1 (en) * | 2000-05-01 | 2001-11-01 | The University Of British Columbia | Ginsenoside chemotherapy |
| CA2355334A1 (en) | 2000-10-16 | 2002-04-16 | Procyon Biopharma Inc. | Pharmaceutical preparations and methods for inhibiting tumors |
| JP2004536026A (ja) | 2000-11-28 | 2004-12-02 | トランスフォーム ファーマシューティカルズ，インコーポレーティッド． | パクリタキセル、その誘導体、および薬剤として許容される塩を含む医薬品製剤 |
| US7115565B2 (en) * | 2001-01-18 | 2006-10-03 | Pharmacia & Upjohn Company | Chemotherapeutic microemulsion compositions of paclitaxel with improved oral bioavailability |
| CA2441484A1 (en) | 2001-03-23 | 2002-10-03 | Napro Biotherapeutics, Inc. | Molecular conjugates for use in treatment of cancer |
| US7083970B2 (en) | 2001-04-19 | 2006-08-01 | The Scripps Research Institute | Methods and compositions for the production of orthogonal tRNA-aminoacyl tRNA synthetase pairs |
| 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 |
| US20040161776A1 (en) | 2001-10-23 | 2004-08-19 | Maddon Paul J. | PSMA formulations and uses thereof |
| US7192921B2 (en) | 2001-11-08 | 2007-03-20 | The Burnham Institute | Peptides that home to tumor lymphatic vasculature and methods of using same |
| CA2470826A1 (en) * | 2001-12-20 | 2003-07-03 | Bristol-Myers Squibb Company | Pharmaceutical compositions of orally active taxane derivatives having enhanced bioavailability |
| RU2196604C1 (ru) * | 2001-12-21 | 2003-01-20 | Северин Евгений Сергеевич | Полипептид, являющийся аналогом рецепторсвязывающего фрагмента эпидермального фактора роста с 21-й по 31-ю аминокислоту, его конъюгат с доксорубицином и фармацевтическая композиция на его основе |
| 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 |
| US6881829B2 (en) | 2002-04-26 | 2005-04-19 | Chimeracom, L.L.C. | Chimeric hybrid analgesics |
| WO2004003145A2 (en) | 2002-06-28 | 2004-01-08 | Nastech Pharmaceutical Company Inc. | Compositions and methods for modulating physiology of epithelial junctional adhesion molecules for enhanced mucosal delivery of therapeutic compounds |
| US7829694B2 (en) | 2002-11-26 | 2010-11-09 | Medtronic, Inc. | Treatment of neurodegenerative disease through intracranial delivery of siRNA |
| US20040102369A1 (en) | 2002-11-27 | 2004-05-27 | The Regents Of The University Of California | Transport of basic fibroblast growth factor across the blood brain barrier |
| US7388079B2 (en) | 2002-11-27 | 2008-06-17 | The Regents Of The University Of California | Delivery of pharmaceutical agents via the human insulin receptor |
| BRPI0406647A (pt) * | 2003-01-06 | 2005-12-06 | Angiochem Inc | Método para transportar um composto através da barreira sanguìnea do cérebro |
| CA2520655A1 (en) * | 2003-04-08 | 2004-11-04 | Biotempt, B.V. | Compositions for mucosal and oral administration comprising hcg fragments |
| KR101424624B1 (ko) | 2003-05-14 | 2014-07-31 | 이뮤노젠 아이엔씨 | 약물 콘쥬게이트 조성물 |
| 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 |
| CA2534899A1 (en) | 2003-08-08 | 2005-02-17 | Tissue Targeting Japan Inc. | Polypeptides having brain-localizing activity and uses thereof |
| US20070275871A1 (en) * | 2003-08-28 | 2007-11-29 | Biorexis Technology, Inc. | Epo Mimetic Peptides and Fusion Proteins |
| 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 |
| JP2008507280A (ja) | 2004-07-21 | 2008-03-13 | アンブレツクス・インコーポレイテツド | 非天然コードアミノ酸を用いた生合成ポリペプチド |
| EP1771467A2 (en) | 2004-07-26 | 2007-04-11 | Asterion Limited | Linkers |
| WO2006039253A2 (en) | 2004-09-29 | 2006-04-13 | Children's Memorial Hospital | Sirna-mediated gene silencing of alpha synuclein |
| SI1853250T1 (sl) | 2005-02-18 | 2012-01-31 | Abraxis Bioscience Llc | Kombinacije in reĹľimi dajanja terapevtskih sredstev in kombinirana terapija |
| US20090016959A1 (en) | 2005-02-18 | 2009-01-15 | Richard Beliveau | Delivery of antibodies to the central nervous system |
| US7557182B2 (en) * | 2005-02-18 | 2009-07-07 | Angiochem Inc. | Molecules for transporting a compound across the blood-brain barrier |
| AU2006247471A1 (en) | 2005-05-12 | 2006-11-23 | Tapestry Pharmaceuticals, Inc. | Molecular constructs suitable for targeted conjugates |
| WO2006138343A2 (en) | 2005-06-14 | 2006-12-28 | Raptor Pharmaceutical Inc. | Compositions comprising receptor - associated protein (rap) variants specific for lrp2 and uses thereof |
| JP5436856B2 (ja) | 2005-07-15 | 2014-03-05 | アンジオケム インコーポレーティッド | 薬学的複合体における担体としてのアプロチニンポリペプチドの使用 |
| AU2006269879A1 (en) | 2005-07-19 | 2007-01-25 | The Board Of Trustees Of The University Of Illinois | Transport agents for crossing the blood-brain barrier and into brain cancer cells, and methods of use thereof |
| GB0517092D0 (en) | 2005-08-19 | 2005-09-28 | Novartis Ag | New compositions containing taxane derivatives |
| WO2007030619A2 (en) | 2005-09-08 | 2007-03-15 | Nastech Pharmaceutical Company Inc. | Pharmaceutical compositions for delivery of ribonucleic acid to a cell |
| US9062126B2 (en) | 2005-09-16 | 2015-06-23 | Raptor Pharmaceuticals Inc. | Compositions comprising receptor-associated protein (RAP) variants specific for CR-containing proteins and uses thereof |
| US8053569B2 (en) | 2005-10-07 | 2011-11-08 | Armagen Technologies, Inc. | Nucleic acids encoding and methods of producing fusion proteins |
| EP2202239A1 (en) | 2005-11-01 | 2010-06-30 | 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 |
| WO2008012629A2 (en) | 2006-07-24 | 2008-01-31 | Biorexis Pharmaceutical Corporation | Exendin fusion proteins |
| MX2009002893A (es) | 2006-09-18 | 2009-07-10 | Raptor Pharmaceutical Inc | Tratamiento de trastornos hepaticos mediante la administracion de conjugados de la proteina asociada al receptor (rap). |
| EP2074142A4 (en) | 2006-10-19 | 2010-10-27 | Angiochem Inc | COMPOUNDS FOR STIMULATING THE FUNCTION OF P-GLYCOPROTEIN AND APPLICATIONS THEREOF |
| EP2789628A3 (en) | 2007-05-29 | 2015-03-04 | Angiochem Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
| US9365634B2 (en) | 2007-05-29 | 2016-06-14 | 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 |
| EP2235175A4 (en) | 2007-12-20 | 2012-04-25 | Angiochem Inc | POLYPEPTIDE NUCLEIC ACID CONJUGATES AND USES THEREOF |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| US11260133B2 (en) | 2008-02-21 | 2022-03-01 | Sanford-Burnham Medical Research Institute | Methods and compositions related to peptides and proteins with C-terminal elements |
| TR201905480T4 (tr) | 2008-04-18 | 2019-05-21 | Angiochem Inc | Paklitaksel, paklitaksel analogları veya paklitaksel konjugatlarının farmasötik bileşimleri ve ilgili preparasyon ve kullanım yöntemleri. |
| MX2011004019A (es) * | 2008-10-15 | 2011-06-24 | Angiochem Inc | Conjugados de etoposido y doxorubicina para entrega de farmacos. |
| BRPI0920209A2 (pt) | 2008-10-15 | 2015-12-22 | Angiochem Inc | conjugados de agonistas de glp-1 e usos dos mesmos |
| CA2745527A1 (en) | 2008-12-05 | 2010-06-10 | Angiochem Inc. | Leptin and leptin analog conjugates and uses thereof |
| BRPI0923283A2 (pt) | 2008-12-05 | 2017-06-06 | Angiochem Inc | conjugados terapêuticos de peptídeo e usos dos mesmos |
| CA2745524C (en) | 2008-12-05 | 2020-06-09 | Angiochem Inc. | Conjugates of neurotensin or neurotensin analogs and uses thereof |
| WO2010069074A1 (en) | 2008-12-17 | 2010-06-24 | Universite Du Quebec A Montreal | Membrane type-1 matrix metalloprotein inhibitors and uses thereof |
| WO2010121379A1 (en) | 2009-04-20 | 2010-10-28 | Angiochem Inc | Treatment of ovarian cancer using an anticancer agent conjugated to an angiopep-2 analog |
| US20100284921A1 (en) | 2009-05-08 | 2010-11-11 | Temple University - Of The Commonwealth System Of Higher Education | Targeted nanoparticles for intracellular cancer therapy |
| WO2010142035A1 (en) | 2009-06-11 | 2010-12-16 | Angiochem Inc. | Fusion proteins for delivery of gdnf and bdnf to the central nervous system |
| AU2010268726A1 (en) | 2009-07-02 | 2012-01-19 | Angiochem Inc. | Multimeric peptide conjugates and uses thereof |
| SI2453923T1 (sl) | 2009-07-14 | 2016-04-29 | Mayo Foundation For Medical Education And Research | S peptidi posredovana ne-kovalentna dostava aktivnih učinkovin preko krvno možganske bariere |
| CN102781965A (zh) | 2009-10-06 | 2012-11-14 | 安吉奥开米公司 | 用于转运治疗剂的组合物和方法 |
| US8530429B2 (en) | 2009-11-24 | 2013-09-10 | Arch Cancer Therapeutics, Inc. | Brain tumor targeting peptides and methods |
| WO2011153642A1 (en) | 2010-06-10 | 2011-12-15 | Angiochem Inc. | Leptin and leptin analog conjugates and fusion proteins and uses thereof |
| RU2013103763A (ru) | 2010-07-02 | 2014-08-10 | Ангиохем Инк. | Короткие и содержащие d-аминокислоты полипептиды для терапевтических конъюгатов и их применения |
| WO2012037687A1 (en) | 2010-09-23 | 2012-03-29 | Angiochem Inc. | Therapeutic polypeptides and uses thereof |
| RU2013127625A (ru) | 2010-11-18 | 2014-12-27 | Зе Дженерал Хоспитал Корпорейшен | Новые композиции и применения антигипертензивных средств для терапии рака |
| WO2013056096A1 (en) | 2011-10-13 | 2013-04-18 | Angiochem Inc. | Polypeptide-opioid conjugates and uses thereof |
| EP2785838A4 (en) | 2011-12-01 | 2015-07-01 | Angiochem Inc | VECTORIZED LYSOSOMAL ENZYME COMPOUNDS |
| WO2013078562A2 (en) | 2011-12-01 | 2013-06-06 | Angiochem Inc. | Targeted enzyme compounds and uses thereof |
| AU2013273894A1 (en) | 2012-06-15 | 2015-02-05 | Angiochem Inc. | Targeted iduronidase compounds |
| EP2885321A4 (en) | 2012-08-14 | 2016-03-30 | Angiochem Inc | CONJUGATES WITH AN ANTIBODY PART, A POLYPEPTIDE THROUGH THE BLOOD BRAIN BARRIER, AND A CYTOTOXIN |
| EP2885318A4 (en) | 2012-08-14 | 2016-03-30 | Angiochem Inc | PEPTIDE DENDRIMER CONJUGATES AND ITS USES |
| US20160213760A1 (en) | 2012-11-12 | 2016-07-28 | Angiochem Inc. | Aprotinin-derived polypeptide-antibody conjugates |
| GB201220474D0 (en) | 2012-11-14 | 2012-12-26 | Sagetis Biotech Sl | Polypeptides |
| JP2015536658A (ja) | 2012-11-30 | 2015-12-24 | アンジオケム インコーポレーテッド | 標的化イズロン酸−２−スルファターゼ化合物 |
| HK1179821A2 (en) | 2013-05-28 | 2013-10-04 | 捷迅视讯器材有限公司 | High voltage discharge protection device and radio frequency transmission apparatus using the same |
| HK1223632A1 (zh) | 2013-06-06 | 2017-08-04 | Angiochem Inc. | 靶向的酶化合物及其用途 |
| WO2014194428A1 (en) | 2013-06-06 | 2014-12-11 | Angiochem Inc. | Targeted heparan sulfatase compounds |
-
2006
- 2006-07-14 JP JP2008520685A patent/JP5436856B2/ja not_active Expired - Fee Related
- 2006-07-14 WO PCT/CA2006/001165 patent/WO2007009229A1/en not_active Ceased
- 2006-07-14 AU AU2006272405A patent/AU2006272405B2/en not_active Ceased
- 2006-07-14 EP EP06761127A patent/EP1907009A4/en not_active Withdrawn
- 2006-07-14 CN CN200680033365.8A patent/CN101262890B/zh not_active Expired - Fee Related
- 2006-07-14 EP EP10006638.0A patent/EP2233156B1/en not_active Not-in-force
- 2006-07-14 ES ES10006638T patent/ES2424242T3/es active Active
- 2006-07-14 DK DK10006638.0T patent/DK2233156T3/da active
- 2006-07-14 SI SI200631629T patent/SI2233156T1/sl unknown
- 2006-07-14 EP EP11010071A patent/EP2471555A3/en not_active Withdrawn
- 2006-07-14 ES ES11010125T patent/ES2744225T3/es active Active
- 2006-07-14 PT PT100066380T patent/PT2233156E/pt unknown
- 2006-07-14 PL PL10006638T patent/PL2233156T3/pl unknown
- 2006-07-14 EP EP11010125.0A patent/EP2433653B1/en active Active
- 2006-07-14 BR BRPI0613005A patent/BRPI0613005A8/pt not_active Application Discontinuation
- 2006-07-14 CA CA2614687A patent/CA2614687C/en not_active Expired - Fee Related
- 2006-07-14 RU RU2008105677/15A patent/RU2422143C2/ru active
- 2006-07-14 DK DK11010125.0T patent/DK2433653T3/da active
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2007
- 2007-05-30 US US11/807,917 patent/US8969310B2/en active Active
-
2011
- 2011-04-19 RU RU2011115418/15A patent/RU2011115418A/ru not_active Application Discontinuation
-
2012
- 2012-10-18 JP JP2012230853A patent/JP2013047249A/ja not_active Withdrawn
-
2013
- 2013-08-01 HR HRP20130720TT patent/HRP20130720T1/hr unknown
-
2015
- 2015-03-02 US US14/635,856 patent/US9713646B2/en not_active Expired - Fee Related
- 2015-06-03 JP JP2015112969A patent/JP2015163641A/ja active Pending
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2017
- 2017-06-30 US US15/639,758 patent/US20180221497A1/en not_active Abandoned
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