AU2013302270A1 - Peptide-dendrimer conjugates and uses thereof - Google Patents
Peptide-dendrimer conjugates and uses thereof Download PDFInfo
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- AU2013302270A1 AU2013302270A1 AU2013302270A AU2013302270A AU2013302270A1 AU 2013302270 A1 AU2013302270 A1 AU 2013302270A1 AU 2013302270 A AU2013302270 A AU 2013302270A AU 2013302270 A AU2013302270 A AU 2013302270A AU 2013302270 A1 AU2013302270 A1 AU 2013302270A1
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Landscapes
- Health & Medical Sciences (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261682991P | 2012-08-14 | 2012-08-14 | |
| US61/682,991 | 2012-08-14 | ||
| PCT/CA2013/050621 WO2014026283A1 (en) | 2012-08-14 | 2013-08-14 | Peptide-dendrimer conjugates and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2013302270A1 true AU2013302270A1 (en) | 2015-03-26 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2013302270A Abandoned AU2013302270A1 (en) | 2012-08-14 | 2013-08-14 | Peptide-dendrimer conjugates and uses thereof |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US9687561B2 (https=) |
| EP (1) | EP2885318A4 (https=) |
| JP (1) | JP2015526434A (https=) |
| CN (1) | CN104781276A (https=) |
| AU (1) | AU2013302270A1 (https=) |
| CA (1) | CA2881602A1 (https=) |
| WO (1) | WO2014026283A1 (https=) |
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| ES2744225T3 (es) | 2005-07-15 | 2020-02-24 | Angiochem Inc | Uso de polipéptidos de aprotinina como portadores en conjugados farmacéuticos |
| 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 |
| 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 |
| WO2016090495A1 (en) * | 2014-12-11 | 2016-06-16 | Angiochem Inc. | TARGETED α-L-IDURONIDASE CONJUGATES AND USES THEREOF |
| ES2965764T3 (es) | 2015-02-24 | 2024-04-16 | Hope City | Plataformas de cribado de bibliotecas abordadas espacialmente codificadas químicamente |
| EP3307326B9 (en) | 2015-06-15 | 2021-02-24 | Angiochem Inc. | Methods for the treatment of leptomeningeal carcinomatosis |
| WO2017048789A1 (en) * | 2015-09-14 | 2017-03-23 | The Board Of Regents Of The University Of Texas System | Lipocationic dendrimers and uses thereof |
| CN108289872B (zh) * | 2015-10-29 | 2021-04-02 | 约翰霍普金斯大学 | 树枝状聚合物组合物和其在坏死性小肠结肠炎和其它胃肠道病症治疗中的用途 |
| CN106854231B (zh) * | 2015-12-09 | 2020-08-11 | 中国科学院大连化学物理研究所 | 一种硫巯化多肽的富集方法 |
| US11530243B2 (en) * | 2016-02-18 | 2022-12-20 | Veiove Animal Health Inc. | Non-cleavable substance P conjugates and methods of use thereof |
| 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 |
| PL3458074T3 (pl) * | 2016-05-16 | 2024-11-12 | Board Of Regents Of The University Of Texas System | KOMPOZYCJA DO DOSTARCZANIA tRNA W POSTACI NANOCZĄSTEK I SPOSOBY ICH STOSOWANIA |
| CN106279635B (zh) * | 2016-08-10 | 2019-01-25 | 同济大学 | 类抗菌肽和囊泡及其制备方法和应用 |
| ES2677242B1 (es) * | 2017-01-31 | 2019-03-27 | Univ Alcala Henares | Nanoconjugados formados por moléculas dendríticas y péptidos como agentes antitumorales frente al cáncer |
| IL270169B2 (en) | 2017-04-27 | 2024-08-01 | Univ Johns Hopkins | Dendrimer preparations for use in angiography |
| US11918657B2 (en) | 2017-11-10 | 2024-03-05 | The Johns Hopkins University | Dendrimer delivery system and methods of use thereof |
| US12357580B2 (en) | 2018-06-19 | 2025-07-15 | The Board Of Regents Of The University Of Texas System | Lipid nanoparticle compositions for delivery of mRNA and long nucleic acids |
| WO2020051223A1 (en) | 2018-09-04 | 2020-03-12 | The Board Of Regents Of The University Of Texas System | Compositions and methods for organ specific delivery of nucleic acids |
| EP3846857A4 (en) | 2018-09-04 | 2022-10-12 | The Board Of Regents Of The University Of Texas System | COMPOSITIONS AND METHODS FOR ORGAN-SPECIFIC DELIVERY OF NUCLEIC ACIDS |
| WO2020113036A2 (en) * | 2018-11-28 | 2020-06-04 | Promega Corporation | Reactive peptide labeling |
| CN110170055A (zh) * | 2019-06-04 | 2019-08-27 | 哈尔滨理工大学 | 一种新型双重脑缺血靶向纳米载体材料的制备方法 |
| WO2021046307A1 (en) * | 2019-09-04 | 2021-03-11 | North Carolina State University | Hybridized poly(amidoamine)-amino acid dendrimers |
| JP7759322B2 (ja) | 2019-12-04 | 2025-10-23 | アシュバッタ セラピューティクス, インコーポレイテッド | 眼に薬物送達するためのデンドリマー組成物および方法 |
| WO2021207020A1 (en) * | 2020-04-06 | 2021-10-14 | Tiba Biotech Llc | Carriers for efficient nucleic acid delivery |
| CA3208643A1 (en) | 2021-01-18 | 2022-07-21 | Conserv Bioscience Limited | Coronavirus immunogenic compositions, methods and uses thereof |
| CN119630790A (zh) * | 2022-08-05 | 2025-03-14 | 一丸自然美健有限公司 | 新型lrp1结合肽 |
| CN117363697A (zh) * | 2023-10-10 | 2024-01-09 | 上海烈冰生物医药科技有限公司 | 一种用于核酸捕获的高密度探针磁珠制备方法 |
| WO2025096681A1 (en) | 2023-10-31 | 2025-05-08 | Tiba Biotech Llc | Novel gene delivery agents |
Family Cites Families (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5258499A (en) | 1988-05-16 | 1993-11-02 | Vestar, Inc. | Liposome targeting using receptor specific ligands |
| US5714167A (en) | 1992-06-15 | 1998-02-03 | Emisphere Technologies, Inc. | Active agent transport systems |
| EP0599303A3 (en) | 1992-11-27 | 1998-07-29 | Takeda Chemical Industries, Ltd. | Peptide conjugate |
| KR19990008458A (ko) | 1995-05-08 | 1999-01-25 | 쉬어러 피터 알. | 쿠니츠(kunitz) 타입 프로테아제 억제 물질 |
| WO1996039183A1 (en) | 1995-05-31 | 1996-12-12 | Fred Hutchinson Cancer Research Center | Compositions and methods for targeted delivery of effector molecules |
| JP3469584B2 (ja) | 1996-03-11 | 2003-11-25 | バイエル コーポレイション | ヒト ビクニン |
| AU729643B2 (en) | 1996-05-01 | 2001-02-08 | Antivirals Inc. | Polypeptide conjugates for transporting substances across cell membranes |
| 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 |
| CN1263473A (zh) | 1997-05-21 | 2000-08-16 | 利兰·斯坦福青年大学托管委员会 | 增加跨生物膜转运的组合物和方法 |
| US6372250B1 (en) | 2000-04-25 | 2002-04-16 | The Regents Of The University Of California | Non-invasive gene targeting to the brain |
| AU2002322720B2 (en) | 2001-07-25 | 2008-11-13 | Raptor Pharmaceutical Inc. | Compositions and methods for modulating blood-brain barrier transport |
| AU2002347910A1 (en) | 2001-10-16 | 2003-04-28 | Symbiontics Inc. | Methods and compositions for targeting proteins across the blood brain barrier |
| AU2003209577A1 (en) | 2002-02-07 | 2003-09-02 | 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 |
| WO2004060403A2 (en) | 2003-01-06 | 2004-07-22 | Angiochem Inc. | Aprotinin and anglos as carriers across the blood-brain barrier |
| AU2003286870A1 (en) | 2003-06-05 | 2005-01-04 | 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 |
| KR20060036476A (ko) | 2003-08-08 | 2006-04-28 | 가부시키가이샤 티슈 타겟팅 쟈판 | 뇌 이동 활성을 가지는 폴리펩티드 및 그 이용 |
| US20050058702A1 (en) | 2003-09-17 | 2005-03-17 | Ben-Sasson Shmuel A. | Compositions capable of facilitating penetration across a biological barrier |
| JP2008510829A (ja) * | 2004-08-25 | 2008-04-10 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | デンドリマーに基づく組成物およびそれらの使用法 |
| US20060078535A1 (en) * | 2004-10-13 | 2006-04-13 | The Regents Of The University Of Michigan | Anticancer compounds and methods |
| RU2408605C2 (ru) | 2005-02-18 | 2011-01-10 | Анджиокем Инк. | Полипептид, способный преодолевать гематоэнцефалический барьер, и его конъюгат |
| US20090016959A1 (en) | 2005-02-18 | 2009-01-15 | Richard Beliveau | Delivery of antibodies to the central nervous system |
| ES2744225T3 (es) | 2005-07-15 | 2020-02-24 | Angiochem Inc | Uso de polipéptidos de aprotinina como portadores en conjugados farmacéuticos |
| 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 |
| US8053569B2 (en) | 2005-10-07 | 2011-11-08 | Armagen Technologies, Inc. | Nucleic acids encoding and methods of producing fusion proteins |
| JP2010506860A (ja) | 2006-10-19 | 2010-03-04 | アンジオケム,インコーポレーテッド | P−糖タンパク質機能を刺激するための化合物およびその使用 |
| 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 |
| BRPI0821310A2 (pt) | 2007-12-20 | 2015-06-16 | Angiochem Inc | Conjugados polipeptídeos-ácido nucleico e usos dos mesmos |
| MX355683B (es) | 2008-04-18 | 2018-04-26 | Angiochem Inc | Composiciones farmacéuticas de paclitaxel, análogos de paclitaxel o conjugados de paclitaxel, y métodos relacionados de preparación y uso. |
| CA2740316A1 (en) | 2008-10-15 | 2010-04-22 | Angiochem Inc. | Conjugates of glp-1 agonists and uses thereof |
| WO2010043049A1 (en) | 2008-10-15 | 2010-04-22 | Angiochem Inc. | Etoposide and doxorubicin conjugates for drug delivery |
| CN102348723A (zh) | 2008-12-05 | 2012-02-08 | 安吉奥开米公司 | 肽治疗剂轭合物及其应用 |
| CA2745524C (en) | 2008-12-05 | 2020-06-09 | Angiochem Inc. | Conjugates of neurotensin or neurotensin analogs and uses thereof |
| EP2370472A4 (en) | 2008-12-05 | 2013-04-24 | Angiochem Inc | LEPTIN AND LEPTIN ANALOGUE CONJUGATES AND ITS USES |
| US8853353B2 (en) | 2008-12-17 | 2014-10-07 | Angiochem, Inc. | Membrane type-1 matrix metalloprotein inhibitors and uses thereof |
| US20110318322A1 (en) | 2009-01-12 | 2011-12-29 | Nektar Therapeutics | Conjugates of a Lysosomal Enzyme Moiety and a Water Soluble Polymer |
| MX2011011023A (es) | 2009-04-20 | 2012-01-20 | Angiochem Inc | Tratamiento de cancer de ovarios usando un agente anti-cancer conjugado con un analogo 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 |
| EP3000481A3 (en) | 2009-07-14 | 2016-05-11 | Mayo Foundation for Medical Education and Research | Peptide-mediated non-covalent delivery of active agent agents across the blood brain barrier |
| AU2010305284A1 (en) | 2009-10-06 | 2012-05-03 | Angiochem Inc. | Compositions and methods for the transport of therapeutic agents |
| US8530429B2 (en) | 2009-11-24 | 2013-09-10 | Arch Cancer Therapeutics, Inc. | Brain tumor targeting peptides and methods |
| US9095541B2 (en) | 2009-11-24 | 2015-08-04 | Arch Cancer Therapeutics, Inc. | Brain tumor targeting peptides and methods |
| EP2333074A1 (en) | 2009-12-14 | 2011-06-15 | Robert Steinfeld | Substances and methods for the treatment of lysosmal storage diseases |
| WO2011153642A1 (en) | 2010-06-10 | 2011-12-15 | Angiochem Inc. | Leptin and leptin analog conjugates and fusion proteins and uses thereof |
| JP2013530993A (ja) * | 2010-07-02 | 2013-08-01 | アンジオケム インコーポレーテッド | 治療用コンジュゲートのための短く且つd−アミノ酸を含有するポリペプチドおよびその使用 |
| CN102406949B (zh) | 2010-09-21 | 2013-05-29 | 复旦大学 | 一种靶向示踪的多模式诊断纳米影像药物 |
| WO2012037687A1 (en) * | 2010-09-23 | 2012-03-29 | Angiochem Inc. | Therapeutic polypeptides and uses thereof |
| CN102552928A (zh) | 2010-12-19 | 2012-07-11 | 复旦大学 | 一种治疗脑部肿瘤的双级靶向递药系统及其制备方法 |
| CN102614105A (zh) | 2011-01-28 | 2012-08-01 | 复旦大学 | 一种脑靶向载两性霉素b聚合物胶束给药系统 |
| WO2013056096A1 (en) | 2011-10-13 | 2013-04-18 | Angiochem Inc. | Polypeptide-opioid conjugates and uses thereof |
| CN104145015A (zh) | 2011-12-01 | 2014-11-12 | 安吉奥开米公司 | 靶向的溶酶体酶化合物 |
| BR112014013250A2 (pt) | 2011-12-01 | 2019-09-24 | Angiochem Inc | compostos com enzima alvo e usos dos mesmos |
| AU2013273894A1 (en) | 2012-06-15 | 2015-02-05 | Angiochem Inc. | Targeted iduronidase compounds |
| 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 |
| US20160106856A1 (en) | 2012-08-14 | 2016-04-21 | Angiochem Inc. | Conjugates including an antibody moiety, a polypeptide that traverses the blood-brain barrier, and a cytotoxin |
| JP2015535523A (ja) | 2012-11-12 | 2015-12-14 | アンジオケム インコーポレーテッド | アプロチニン由来ポリペプチド−抗体コンジュゲート |
| 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 |
| WO2014194428A1 (en) | 2013-06-06 | 2014-12-11 | Angiochem Inc. | Targeted heparan sulfatase compounds |
| WO2014194429A1 (en) | 2013-06-06 | 2014-12-11 | Angiochem Inc. | Targeted enzyme compounds and uses thereof |
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| US20160015823A1 (en) | 2016-01-21 |
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| CN104781276A (zh) | 2015-07-15 |
| WO2014026283A1 (en) | 2014-02-20 |
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