SI2233156T1 - Uporaba polipeptidov aprotinina kot nosilce v farmacevtskih konjugatih - Google Patents
Uporaba polipeptidov aprotinina kot nosilce v farmacevtskih konjugatihInfo
- Publication number
- SI2233156T1 SI2233156T1 SI200631629T SI200631629T SI2233156T1 SI 2233156 T1 SI2233156 T1 SI 2233156T1 SI 200631629 T SI200631629 T SI 200631629T SI 200631629 T SI200631629 T SI 200631629T SI 2233156 T1 SI2233156 T1 SI 2233156T1
- Authority
- SI
- Slovenia
- Prior art keywords
- carriers
- pharmaceutical conjugates
- aprotinin polypeptides
- aprotinin
- polypeptides
- Prior art date
Links
- 108010039627 Aprotinin Proteins 0.000 title 1
- 229960004405 aprotinin Drugs 0.000 title 1
- 239000000969 carrier Substances 0.000 title 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 title 1
- 229920001184 polypeptide Polymers 0.000 title 1
- 102000004196 processed proteins & peptides Human genes 0.000 title 1
- 108090000765 processed proteins & peptides Proteins 0.000 title 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- 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
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/57—Protease inhibitors from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- 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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- 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)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- 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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US69937505P | 2005-07-15 | 2005-07-15 | |
| US75853206P | 2006-01-13 | 2006-01-13 | |
| EP10006638.0A EP2233156B1 (en) | 2005-07-15 | 2006-07-14 | Use of aprotinin polypeptides as carriers in pharmaceutical conjugates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI2233156T1 true SI2233156T1 (sl) | 2013-09-30 |
Family
ID=37668389
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI200631629T SI2233156T1 (sl) | 2005-07-15 | 2006-07-14 | Uporaba polipeptidov aprotinina kot nosilce v farmacevtskih konjugatih |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US8969310B2 (enExample) |
| EP (4) | EP1907009A4 (enExample) |
| JP (3) | JP5436856B2 (enExample) |
| CN (1) | CN101262890B (enExample) |
| AU (1) | AU2006272405B2 (enExample) |
| BR (1) | BRPI0613005A8 (enExample) |
| CA (1) | CA2614687C (enExample) |
| DK (2) | DK2433653T3 (enExample) |
| ES (2) | ES2744225T3 (enExample) |
| HR (1) | HRP20130720T1 (enExample) |
| PL (1) | PL2233156T3 (enExample) |
| PT (1) | PT2233156E (enExample) |
| RU (2) | RU2422143C2 (enExample) |
| SI (1) | SI2233156T1 (enExample) |
| WO (1) | WO2007009229A1 (enExample) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI1583562T1 (sl) | 2003-01-06 | 2011-10-28 | Angiochem Inc | AngioPep-1, sorodne spojine in njihove uporabe |
| WO2006081171A1 (en) | 2005-01-24 | 2006-08-03 | Amgen Inc. | Humanized anti-amyloid antibody |
| AU2005327497B2 (en) | 2005-02-18 | 2012-04-12 | Angiochem Inc. | Aprotinin polypeptides 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 |
| DK2433653T3 (da) | 2005-07-15 | 2019-08-19 | Angiochem Inc | Anvendelse af aprotininpolypeptider som bærere i farmaceutiske konjugater |
| EP2399609B1 (en) | 2005-08-24 | 2015-03-18 | ImmunoGen, Inc. | Process for preparing maytansinoid antibody conjugates |
| CA2666841A1 (en) | 2006-10-19 | 2008-04-24 | Angiochem, Inc. | Compounds for stimulating p-glycoprotein function and uses 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 |
| PT2164866E (pt) * | 2007-05-29 | 2014-08-04 | Angiochem Inc | Polipéptidos de tipo aprotinina para administrar agentes conjugados com os mesmos aos tecidos |
| MX2010006925A (es) * | 2007-12-20 | 2011-05-02 | Angiochem Inc | Conjugados de polipeptido-acido nucleico y sus usos. |
| EP2261254A3 (en) | 2007-12-21 | 2011-04-13 | Amgen, Inc | Anti-amyloid antibodies and uses thereof |
| 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 |
| CA2740317A1 (en) | 2008-10-15 | 2010-04-22 | Angiochem Inc. | Etoposide and doxorubicin conjugates for drug delivery |
| CA2740316A1 (en) | 2008-10-15 | 2010-04-22 | Angiochem Inc. | Conjugates of glp-1 agonists and uses thereof |
| CA2745524C (en) * | 2008-12-05 | 2020-06-09 | Angiochem Inc. | Conjugates of neurotensin or neurotensin analogs and uses thereof |
| CN102300987A (zh) | 2008-12-17 | 2011-12-28 | 安吉奥开米公司 | 膜型-1基质金属蛋白抑制剂及其用途 |
| 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 |
| 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 |
| IL300840A (en) | 2009-06-03 | 2023-04-01 | Immunogen Inc | coupling methods |
| RU2012103240A (ru) | 2009-07-02 | 2013-08-10 | Ангиокем Инк. | Мультимерные пептидные конъюгаты и их применение |
| EP2588490B1 (en) | 2010-07-02 | 2017-02-22 | Angiochem Inc. | Short and d-amino acid-containing polypeptides for therapeutic conjugates and uses thereof |
| 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 |
| SI2691155T1 (sl) | 2011-03-29 | 2019-03-29 | Immunogen, Inc. | Priprava majtanzinoidnih konjugatov protiteles v postopku z enim korakom |
| EP2885318A4 (en) | 2012-08-14 | 2016-03-30 | Angiochem Inc | PEPTIDE DENDRIMER CONJUGATES AND ITS USES |
| MX359599B (es) * | 2012-10-04 | 2018-09-12 | Immunogen Inc | Uso de una membrana de pvdf para purificar conjugados de agentes de unión celular y agentes citotóxicos. |
| CA2891190C (en) * | 2012-11-12 | 2021-08-31 | Angiochem Inc. | Aprotinin-derived polypeptide-antibody conjugates |
| EP3016670A4 (en) * | 2013-07-03 | 2017-01-18 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Method for treating cognitive dysfunction |
| CN105452293B (zh) | 2013-07-03 | 2021-03-16 | 首尔大学校产学协力团 | 转化为半胱氨酸的鸡抗体和使用其的位点特异性缀合 |
| 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 |
| AU2015294371B2 (en) | 2014-07-21 | 2018-02-01 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Ang-(1-7) derivative oligopeptides and methods for using and producing the same |
| GB201502447D0 (en) | 2015-02-13 | 2015-04-01 | Univ Liverpool | Method and apparatus for sample analysis |
| CA2989400A1 (en) | 2015-06-15 | 2016-12-22 | Angiochem Inc. | Ang1005 for the treatment of leptomeningeal carcinomatosis |
| WO2019148181A1 (en) | 2018-01-29 | 2019-08-01 | Cognos Therapeutics, Inc. | Intratumoral delivery of bortezomib |
| 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. |
| IL81889A0 (en) | 1986-03-13 | 1987-10-20 | Biotech Australia Pty Ltd | Assay of inhibin |
| 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 |
| 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 |
| EP0671944A4 (en) | 1992-09-25 | 1996-07-24 | Corvas Int Inc | TISSUE VIA-THROMBOPLASTIN FACTOR COMPLEX INHIBITORS DERIVED FROM A BOVINE PANCREATIC TRYPSIN INHIBITOR. |
| EP0599303A3 (en) | 1992-11-27 | 1998-07-29 | Takeda Chemical Industries, Ltd. | Peptide conjugate |
| IL107950A (en) | 1992-12-15 | 2001-04-30 | Upjohn Co | 7β, 8β - METHANO-TAXOLS, THEIR PREPARATION AND ANTINEOPLASTIC PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
| 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 |
| KR19990008458A (ko) | 1995-05-08 | 1999-01-25 | 쉬어러 피터 알. | 쿠니츠(kunitz) 타입 프로테아제 억제 물질 |
| 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 |
| CA2222231A1 (en) | 1995-06-07 | 1996-12-19 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth of tumors |
| TR199801794T2 (xx) | 1996-03-11 | 2000-07-21 | Bayer Corporation | �nsan bikunini. |
| 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 |
| EP0966303A2 (en) | 1996-05-01 | 1999-12-29 | Antivirals Inc. | Polypeptide conjugates for transporting substances across cell membranes |
| 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 |
| 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 |
| 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 |
| 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 |
| US6919370B2 (en) | 2000-11-28 | 2005-07-19 | Transform Pharmaceuticals, Inc. | Pharmaceutical formulations comprising paclitaxel, derivatives, and pharmaceutically acceptable salts thereof |
| US7115565B2 (en) * | 2001-01-18 | 2006-10-03 | Pharmacia & Upjohn Company | Chemotherapeutic microemulsion compositions of paclitaxel with improved oral bioavailability |
| AU2002254400B2 (en) | 2001-03-23 | 2007-08-09 | Napro Biotherapeutics, Inc. | Molecular conjugates for use in treatment of cancer |
| IL158418A0 (en) | 2001-04-19 | 2004-05-12 | Scripps Research Inst | In vivo incorporation of unnatural amino acids |
| 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 |
| RS52904A (sr) * | 2001-12-20 | 2006-12-15 | Bristol-Myers Squib Company | Farmaceutske smeše oralno aktivnih derivata taksana koje imaju povećanu bioraspoloživost |
| 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 |
| JP2005517024A (ja) | 2002-02-07 | 2005-06-09 | イッサム リサーチ ディベロプメント カンパニー オブ ザ ヘブリュー ユニバーシティ オブ エルサレム | 生物学的障壁を横切る透過を促進し得るアミノ酸配列 |
| US6881829B2 (en) | 2002-04-26 | 2005-04-19 | Chimeracom, L.L.C. | Chimeric hybrid analgesics |
| 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 |
| US7388079B2 (en) | 2002-11-27 | 2008-06-17 | The Regents Of The University Of California | Delivery of pharmaceutical agents via the human insulin receptor |
| 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 |
| SI1583562T1 (sl) * | 2003-01-06 | 2011-10-28 | Angiochem Inc | AngioPep-1, sorodne spojine in njihove uporabe |
| 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 |
| EP1638605B1 (en) * | 2003-06-20 | 2014-01-08 | Raptor Pharmaceutical, Inc. | Delivery of therapeutic compounds to the brain and other tissues |
| 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 |
| CN100457775C (zh) | 2003-08-08 | 2009-02-04 | 普洛图斯科学株式会社 | 具有脑定位活性的多肽及其用途 |
| EP1663278A4 (en) * | 2003-08-28 | 2009-07-29 | Biorexis Pharmaceutical Corp | 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 |
| US7638299B2 (en) | 2004-07-21 | 2009-12-29 | Ambrx, Inc. | Biosynthetic polypeptides utilizing non-naturally encoded amino acids |
| NZ553224A (en) | 2004-07-26 | 2009-05-31 | Asterion Ltd | Linkers |
| WO2006039253A2 (en) | 2004-09-29 | 2006-04-13 | Children's Memorial Hospital | Sirna-mediated gene silencing of alpha synuclein |
| SI2301531T1 (sl) | 2005-02-18 | 2018-11-30 | Abraxis Bioscience, Llc | Kombinacije in načini dajanja terapevtskih sredstev in kombinacijska terapija |
| US20090016959A1 (en) | 2005-02-18 | 2009-01-15 | Richard Beliveau | Delivery of antibodies to the central nervous system |
| AU2005327497B2 (en) | 2005-02-18 | 2012-04-12 | Angiochem Inc. | Aprotinin polypeptides for transporting a compound across the blood-brain barrier |
| KR20080030564A (ko) | 2005-05-12 | 2008-04-04 | 태피스트리 파마슈티컬스 인코퍼레이티드 | 표적 컨쥬게이트에 적합한 분자 구조물 |
| US8877714B2 (en) | 2005-06-14 | 2014-11-04 | Raptor Pharmaceutical Inc. | Compositions comprising receptor-associated protein (RAP) variants specific for LRP2 and uses thereof |
| DK2433653T3 (da) | 2005-07-15 | 2019-08-19 | Angiochem Inc | Anvendelse af aprotininpolypeptider som bærere i farmaceutiske konjugater |
| CA2615617A1 (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 |
| WO2007035716A2 (en) | 2005-09-16 | 2007-03-29 | Raptor Pharmaceutical Inc. | Compositions comprising receptor-associated protein (rap) variants specific for cr-containing proteins and uses thereof |
| US8142781B2 (en) | 2005-10-07 | 2012-03-27 | Armagen Technologies, Inc. | Fusion proteins for blood-brain barrier delivery |
| US20070197460A1 (en) | 2005-11-01 | 2007-08-23 | 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 |
| DK2046826T3 (da) | 2006-07-24 | 2011-10-24 | Biorexis Pharmaceutical Corp | Exendin-fusionsproteiner |
| WO2008036682A2 (en) | 2006-09-18 | 2008-03-27 | Raptor Pharmaceutical Inc. | Treatment of liver disorders by administration of receptor-associated protein (rap)-conjugates |
| CA2666841A1 (en) | 2006-10-19 | 2008-04-24 | Angiochem, Inc. | Compounds for stimulating p-glycoprotein function and uses thereof |
| US9365634B2 (en) | 2007-05-29 | 2016-06-14 | Angiochem Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
| EP2789628A3 (en) | 2007-05-29 | 2015-03-04 | 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. |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| AU2009215426B2 (en) | 2008-02-21 | 2015-06-11 | Burnham Institute For Medical Research | Methods and compositions related to peptides and proteins with C-terminal elements |
| 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 |
| CA2740316A1 (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 |
| WO2010063123A1 (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 |
| CN102300987A (zh) | 2008-12-17 | 2011-12-28 | 安吉奥开米公司 | 膜型-1基质金属蛋白抑制剂及其用途 |
| 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 |
| CN103819564A (zh) | 2009-06-11 | 2014-05-28 | 安吉奥开米公司 | 用于将gdnf和bdnf递送至中枢神经系统的融合蛋白 |
| RU2012103240A (ru) | 2009-07-02 | 2013-08-10 | Ангиокем Инк. | Мультимерные пептидные конъюгаты и их применение |
| HUE026708T2 (en) | 2009-07-14 | 2016-07-28 | Mayo Foundation | Peptide-mediated, non-covalent delivery of active substances in blood glucose |
| JP2013506697A (ja) | 2009-10-06 | 2013-02-28 | アンジオケム インコーポレーテッド | 治療薬を輸送するための組成物と方法 |
| 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 |
| EP2588490B1 (en) | 2010-07-02 | 2017-02-22 | Angiochem Inc. | Short and d-amino acid-containing polypeptides for therapeutic conjugates and uses thereof |
| WO2012037687A1 (en) | 2010-09-23 | 2012-03-29 | Angiochem Inc. | Therapeutic polypeptides and uses thereof |
| EP2640359A4 (en) | 2010-11-18 | 2015-11-04 | Gen Hospital Corp | NOVEL COMPOSITIONS AND USES OF HYPOTENSE AGENTS IN THE TREATMENT OF CANCER |
| WO2013056096A1 (en) | 2011-10-13 | 2013-04-18 | Angiochem Inc. | Polypeptide-opioid conjugates and uses thereof |
| AU2012344700A1 (en) | 2011-12-01 | 2014-06-19 | Angiochem Inc. | Targeted iduronate-2-sulfatase compounds |
| JP2015505824A (ja) | 2011-12-01 | 2015-02-26 | アンジオケム インコーポレーテッド | 標的化リソソーム酵素化合物 |
| AU2013273894A1 (en) | 2012-06-15 | 2015-02-05 | Angiochem Inc. | Targeted iduronidase compounds |
| EP2885318A4 (en) | 2012-08-14 | 2016-03-30 | Angiochem Inc | PEPTIDE DENDRIMER CONJUGATES AND ITS USES |
| AU2013302273A1 (en) | 2012-08-14 | 2015-02-19 | Angiochem Inc. | Conjugates including an antibody moiety, a polypeptide that traverses the blood-brain barrier, and a cytotoxin |
| CA2891190C (en) | 2012-11-12 | 2021-08-31 | Angiochem Inc. | Aprotinin-derived polypeptide-antibody conjugates |
| GB201220474D0 (en) | 2012-11-14 | 2012-12-26 | Sagetis Biotech Sl | Polypeptides |
| US20150290341A1 (en) | 2012-11-30 | 2015-10-15 | Anglachem Inc. | Targeted iduronate-2-sulfatase compounds |
| 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 |
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