AU2007293169A1 - Compositions and methods for the treatment of ophthalmic disease - Google Patents
Compositions and methods for the treatment of ophthalmic disease Download PDFInfo
- Publication number
- AU2007293169A1 AU2007293169A1 AU2007293169A AU2007293169A AU2007293169A1 AU 2007293169 A1 AU2007293169 A1 AU 2007293169A1 AU 2007293169 A AU2007293169 A AU 2007293169A AU 2007293169 A AU2007293169 A AU 2007293169A AU 2007293169 A1 AU2007293169 A1 AU 2007293169A1
- Authority
- AU
- Australia
- Prior art keywords
- azepanyl
- amino
- piperidinyl
- ethyl
- pyrimidinyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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| KR20060129246A (ko) | 2003-12-05 | 2006-12-15 | 컴파운드 쎄라퓨틱스, 인크. | 타입 2 혈관 내피 성장 인자 수용체의 억제제 |
| JP5272408B2 (ja) * | 2005-02-25 | 2013-08-28 | 小野薬品工業株式会社 | 含窒素複素環化合物およびその医薬用途 |
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| US11078262B2 (en) * | 2007-04-30 | 2021-08-03 | Allergan, Inc. | High viscosity macromolecular compositions for treating ocular conditions |
| KR101589442B1 (ko) * | 2007-08-06 | 2016-02-01 | 녹손 파르마 아게 | 에스디에프-1 결합형 핵산 및 이의 용도 |
| CN102007145A (zh) | 2008-02-14 | 2011-04-06 | 百时美施贵宝公司 | 基于结合egfr的工程化蛋白质的靶向治疗剂 |
| EP2799448A1 (en) | 2008-05-22 | 2014-11-05 | Bristol-Myers Squibb Company | Multivalent fibronectin based scaffold domain proteins |
| US11029313B2 (en) | 2008-09-26 | 2021-06-08 | The General Hospital Corporation | Method of treating cervical neoplasia in patients infected with human papilloma virus |
| WO2010037042A2 (en) | 2008-09-26 | 2010-04-01 | The General Hospital Corporation | Methods for detecting and treating cancer |
| TWI496582B (zh) | 2008-11-24 | 2015-08-21 | 必治妥美雅史谷比公司 | 雙重專一性之egfr/igfir結合分子 |
| US20100204325A1 (en) * | 2009-02-11 | 2010-08-12 | Allergan, Inc. | Valproic acid drug delivery systems and intraocular therapeutic uses thereof |
| EA025415B1 (ru) | 2010-01-11 | 2016-12-30 | Инотек Фармасьютикалз Корпорейшн | Комбинация, набор и способ снижения внутриглазного давления |
| EP2569325A4 (en) | 2010-03-26 | 2013-10-09 | Inotek Pharmaceuticals Corp | METHOD FOR REDUCING INNER EYE PRESSURE IN HUMANS USING N6-CYCLOPENTYLADENOSINE (CPA), CPA DERIVATIVES OR PRODRUGS THEREOF |
| EP2576615B1 (en) | 2010-05-26 | 2016-03-30 | Bristol-Myers Squibb Company | Fibronectin based scaffold proteins having improved stability |
| MX350258B (es) | 2011-07-06 | 2017-08-31 | Novartis Ag | Emulsiones cationicas de aceite en agua. |
| US9655845B2 (en) * | 2011-07-06 | 2017-05-23 | Glaxosmithkline Biologicals, S.A. | Oil-in-water emulsions that contain nucleic acids |
| US9278991B2 (en) | 2012-01-26 | 2016-03-08 | Inotek Pharmaceuticals Corporation | Anhydrous polymorphs of [(2R,3S,4R,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)} methyl nitrate and processes of preparation thereof |
| CA2903114A1 (en) | 2013-03-15 | 2014-09-25 | Inotek Pharmaceuticals Corporation | Ophthalmic formulations |
| WO2015015401A2 (en) | 2013-08-02 | 2015-02-05 | Pfizer Inc. | Anti-cxcr4 antibodies and antibody-drug conjugates |
| WO2015031722A1 (en) | 2013-08-30 | 2015-03-05 | Ramot At Tel-Aviv University Ltd. | Method for treating amyotrophic lateral sclerosis by inhibition of cxcr4/cxcl12 signaling |
| JP6887377B2 (ja) * | 2015-05-29 | 2021-06-16 | 生化学工業株式会社 | グリコサミノグリカン誘導体とケモカイン受容体活性調節材とを含む組成物 |
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| CN109053697A (zh) * | 2018-09-27 | 2018-12-21 | 张淑华 | 一种用于抗癌的嘧啶类化合物及其制备方法 |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4521210A (en) | 1982-12-27 | 1985-06-04 | Wong Vernon G | Eye implant for relieving glaucoma, and device and method for use therewith |
| US4997652A (en) | 1987-12-22 | 1991-03-05 | Visionex | Biodegradable ocular implants |
| US4853224A (en) | 1987-12-22 | 1989-08-01 | Visionex | Biodegradable ocular implants |
| US5164188A (en) | 1989-11-22 | 1992-11-17 | Visionex, Inc. | Biodegradable ocular implants |
| CA2088258C (en) | 1990-07-27 | 2004-09-14 | Phillip Dan Cook | Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression |
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| US5874082A (en) * | 1992-07-09 | 1999-02-23 | Chiron Corporation | Humanized anti-CD40 monoclonal antibodies and fragments capable of blocking B cell proliferation |
| JP3015464B2 (ja) | 1992-07-23 | 2000-03-06 | アイシス・ファーマシューティカルス・インコーポレーテッド | 新規2’−0−アルキルヌクレオシドおよびホスホロアミダイトの製造法およびその使用 |
| WO1994019023A1 (en) | 1993-02-19 | 1994-09-01 | Isis Pharmaceuticals, Inc. | Cyclobutyl antisense oligonucleotides, methods of making and use thereof |
| WO1995003009A1 (en) | 1993-07-22 | 1995-02-02 | Oculex Pharmaceuticals, Inc. | Method of treatment of macular degeneration |
| US5443505A (en) | 1993-11-15 | 1995-08-22 | Oculex Pharmaceuticals, Inc. | Biocompatible ocular implants |
| US5869079A (en) | 1995-06-02 | 1999-02-09 | Oculex Pharmaceuticals, Inc. | Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents |
| US6369116B1 (en) | 1995-06-02 | 2002-04-09 | Oculex Pharmaceuticals, Inc. | Composition and method for treating glaucoma |
| US6506770B1 (en) | 1996-06-06 | 2003-01-14 | Anormed, Inc. | Antiviral compounds |
| US5994515A (en) | 1996-06-25 | 1999-11-30 | Trustees Of The University Of Pennsylvania | Antibodies directed against cellular coreceptors for human immunodeficiency virus and methods of using the same |
| ES2232005T3 (es) | 1997-08-11 | 2005-05-16 | Allergan, Inc. | Dispositivo de implante biodegradable esteril que contiene retinoide con biocompatibilidad mejorada y metodo de preparacion. |
| DE69921609T2 (de) * | 1998-01-15 | 2005-10-27 | King's College London | Ribozymale nukleinsäure die ccr5 oder cxcr4 schneiden |
| CA2245224A1 (en) | 1998-08-14 | 2000-02-14 | Jiang-Hong Giong | Chemokine receptor antagonists and chemotherapeutics |
| CA2305787A1 (en) | 2000-05-09 | 2001-11-09 | The University Of British Columbia | Cxcr4 antagonist treatment of hematopoietic cells |
| WO1999047158A2 (en) | 1998-03-13 | 1999-09-23 | The University Of British Columbia | Therapeutic chemokine receptor antagonists |
| EP1072273B1 (en) * | 1998-03-24 | 2006-07-26 | Chugai Seiyaku Kabushiki Kaisha | Vascularization inhibitors |
| AU4325499A (en) | 1998-06-01 | 1999-12-20 | University Of Maryland Biotechnology Institute | Receptor ligand antagonist complexes and their use in treating or preventing receptor mediated diseases |
| US20050202005A1 (en) | 1998-07-31 | 2005-09-15 | The Trustees Of Columbia University In The City Of New York | Uses of inhibitors for the activation of CXCR4 receptor by SDF-1 in treating rheumatoid arthritis |
| WO2000006086A2 (en) | 1998-07-31 | 2000-02-10 | The Trustees Of Columbia University In The City Of New York | Use of inhibitors of the activation of cxcr4 receptor by sdf-1 in treating rheumatoid arthritis |
| US20050220787A1 (en) | 2002-11-07 | 2005-10-06 | Lobo Peter I | Naturally occuring IgM antibodies that bind to lymphocytes |
| US20030099645A1 (en) | 2000-10-10 | 2003-05-29 | Lobo Peter Isaac | Naturally occuring IgM antibodies that bind to membrane receptors on lymphocytes |
| US6610834B1 (en) | 1998-11-18 | 2003-08-26 | Peter I. Lobo | Human IgM antibodies to chemokine receptors |
| AU1408300A (en) * | 1998-11-24 | 2000-06-13 | Hisamitsu Pharmaceutical Co. Inc. | Hiv infection inhibitors |
| CA2369292C (en) | 1999-04-09 | 2010-09-21 | Kyowa Hakko Kogyo Co. Ltd. | Method of modulating the activity of functional immune molecules |
| US6331313B1 (en) | 1999-10-22 | 2001-12-18 | Oculex Pharmaceticals, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
| US6949243B1 (en) | 1999-11-24 | 2005-09-27 | Schering Corporation | Methods of inhibiting metastasis |
| WO2001044229A1 (en) | 1999-12-17 | 2001-06-21 | Anormed Inc. | Chemokine receptor binding heterocyclic compounds |
| US20030220482A1 (en) | 2000-02-03 | 2003-11-27 | Ziwei Huang | Novel peptide antagonist of CXCR4 derived from the N-terminus of the viral chemokine vMIP-II |
| JP2003522186A (ja) | 2000-02-04 | 2003-07-22 | アメリカ合衆国 | 病原体に対する宿主免疫応答を誘導するか、またはhiv感染を抑制するfprクラス受容体に対するリガンド |
| US6726918B1 (en) | 2000-07-05 | 2004-04-27 | Oculex Pharmaceuticals, Inc. | Methods for treating inflammation-mediated conditions of the eye |
| WO2002022599A2 (en) | 2000-09-15 | 2002-03-21 | Anormed Inc. | Chemokine receptor binding heterocyclic compounds |
| US20030165988A1 (en) | 2002-02-08 | 2003-09-04 | Shaobing Hua | High throughput generation of human monoclonal antibody against peptide fragments derived from membrane proteins |
| US6699493B2 (en) | 2000-11-29 | 2004-03-02 | Oculex Pharmaceuticals, Inc. | Method for reducing or preventing transplant rejection in the eye and intraocular implants for use therefor |
| US20060019917A1 (en) | 2001-05-18 | 2006-01-26 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of stromal cell-derived factor-1 (SDF-1) gene expression using short interfering nucleic acid (siNA) |
| US20050124569A1 (en) | 2001-05-18 | 2005-06-09 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of CXCR4 gene expression using short interfering nucleic acid (siNA) |
| JPWO2002094261A1 (ja) | 2001-05-24 | 2004-09-02 | 呉羽化学工業株式会社 | 含窒素化合物からなるcxcr4拮抗作用を有する薬剤 |
| JPWO2003029218A1 (ja) | 2001-09-28 | 2005-01-13 | 呉羽化学工業株式会社 | 新規含窒素化合物及びその用途 |
| US7354932B2 (en) | 2001-12-21 | 2008-04-08 | Anormed, Inc. | Chemokine receptor binding heterocyclic compounds with enhanced efficacy |
| IL161784A0 (en) | 2001-12-21 | 2005-11-20 | Anormed Inc | Chemokine receptor binding heterocyclic compounds with enhanced efficacy |
| AU2002356400A1 (en) | 2001-12-31 | 2003-07-30 | Consejo Superior De Investigaciones Cientificas | Functional inactivation of cxcr4-mediated responses in growth hormone transgenic mice through socs3 upregulation |
| AU2003228667A1 (en) * | 2002-04-22 | 2003-12-19 | Sirna Therapeutics Inc. | Nucleic acid mediated disruption of hiv fusogenic peptide interactions |
| US20040018528A1 (en) | 2002-05-17 | 2004-01-29 | Sugen, Inc. | Novel biomarkers of tyrosine kinase inhibitor exposure and activity in mammals |
| US7148342B2 (en) * | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| US20050002939A1 (en) | 2002-12-23 | 2005-01-06 | Albert Zlotnik | Tumor killing/tumor regression using CXCR4 antagonists |
| EP1608318A4 (en) * | 2003-03-27 | 2009-07-29 | Univ Emory | CXCR4 ANTAGONISTS AND METHOD OF USE |
| EP1613613B1 (en) | 2003-04-11 | 2021-06-02 | Genzyme Corporation | Cxcr4 chemokine receptor binding compounds |
| WO2005002522A2 (en) | 2003-06-30 | 2005-01-13 | Caritas St. Elizabeth's Medical Center Of Boston, Inc. | Compositions and methods for treating tissue ischemia |
| US20050266009A1 (en) | 2003-06-30 | 2005-12-01 | Savient Pharmaceuticals, Inc. | Antibodies and uses thereof |
| US20050019927A1 (en) | 2003-07-13 | 2005-01-27 | Markus Hildinger | DECREASING GENE EXPRESSION IN A MAMMALIAN SUBJECT IN VIVO VIA AAV-MEDIATED RNAi EXPRESSION CASSETTE TRANSFER |
| WO2005080410A1 (en) | 2004-02-20 | 2005-09-01 | Genesis Research And Development Corporation Limited | Targeted delivery of rna interference molecules for the treatment of ige-mediated disorders |
| US7674829B2 (en) | 2004-03-26 | 2010-03-09 | Novaremed Limited | Compounds for the treatment of AIDS and other viral diseases |
| EP1796675A4 (en) * | 2004-10-01 | 2009-03-04 | Merck & Co Inc | COMPOSITIONS AND METHODS FOR THE TREATMENT OF EYE DISEASES |
| BRPI0518582A2 (pt) | 2004-11-24 | 2008-11-25 | Therakine Corp | implante para liberaÇço de medicamento intra-ocular |
| CA2593578C (en) * | 2005-01-07 | 2013-11-05 | Emory University | Cxcr4 antagonists for the treatment of medical disorders |
| EP1838321A4 (en) * | 2005-01-07 | 2009-03-18 | Univ Emory | CXCR4 ANTAGONISTS FOR THE TREATMENT OF HIV INFECTION |
| JP5272408B2 (ja) | 2005-02-25 | 2013-08-28 | 小野薬品工業株式会社 | 含窒素複素環化合物およびその医薬用途 |
| US20060257359A1 (en) * | 2005-02-28 | 2006-11-16 | Cedric Francois | Modifying macrophage phenotype for treatment of disease |
| US7427605B2 (en) * | 2005-03-31 | 2008-09-23 | Calando Pharmaceuticals, Inc. | Inhibitors of ribonucleotide reductase subunit 2 and uses thereof |
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2007
- 2007-02-02 BR BRPI0707446-8A patent/BRPI0707446A2/pt not_active Application Discontinuation
- 2007-02-02 EP EP11177758A patent/EP2407171A3/en not_active Ceased
- 2007-02-02 AU AU2007293169A patent/AU2007293169A1/en not_active Abandoned
- 2007-02-02 EP EP11177757A patent/EP2397148A3/en not_active Withdrawn
- 2007-02-02 EP EP07848839A patent/EP1993584B1/en active Active
- 2007-02-02 JP JP2008552923A patent/JP2009531283A/ja active Pending
- 2007-02-02 ES ES07848839T patent/ES2385924T3/es active Active
- 2007-02-02 WO PCT/IB2007/003262 patent/WO2008029276A2/en not_active Ceased
- 2007-02-02 US US11/670,883 patent/US7964191B2/en active Active
- 2007-02-02 CA CA002640080A patent/CA2640080A1/en not_active Abandoned
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2011
- 2011-06-10 US US13/158,084 patent/US20120003275A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008029276A2 (en) | 2008-03-13 |
| JP2009531283A (ja) | 2009-09-03 |
| EP2397148A3 (en) | 2012-04-25 |
| US20120003275A1 (en) | 2012-01-05 |
| US7964191B2 (en) | 2011-06-21 |
| ES2385924T3 (es) | 2012-08-03 |
| EP1993584B1 (en) | 2012-05-30 |
| EP2407171A3 (en) | 2012-04-11 |
| CA2640080A1 (en) | 2008-03-13 |
| WO2008029276A8 (en) | 2009-08-06 |
| WO2008029276A3 (en) | 2008-12-04 |
| EP2397148A2 (en) | 2011-12-21 |
| EP2407171A2 (en) | 2012-01-18 |
| EP1993584A2 (en) | 2008-11-26 |
| BRPI0707446A2 (pt) | 2011-05-03 |
| US20070203089A1 (en) | 2007-08-30 |
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