CA2778678A1 - Improved neurturin molecules - Google Patents
Improved neurturin molecules Download PDFInfo
- Publication number
- CA2778678A1 CA2778678A1 CA2778678A CA2778678A CA2778678A1 CA 2778678 A1 CA2778678 A1 CA 2778678A1 CA 2778678 A CA2778678 A CA 2778678A CA 2778678 A CA2778678 A CA 2778678A CA 2778678 A1 CA2778678 A1 CA 2778678A1
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- Prior art keywords
- neurturin
- polypeptide
- polynucleotide
- neurturin polypeptide
- disease
- 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.)
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/4756—Neuregulins, i.e. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Endocrinology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Ophthalmology & Optometry (AREA)
- Communicable Diseases (AREA)
- Dermatology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25635209P | 2009-10-30 | 2009-10-30 | |
| US61/256,352 | 2009-10-30 | ||
| PCT/US2010/054419 WO2011053675A2 (en) | 2009-10-30 | 2010-10-28 | Improved neurturin molecules |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2778678A1 true CA2778678A1 (en) | 2011-05-05 |
Family
ID=43922977
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2778678A Abandoned CA2778678A1 (en) | 2009-10-30 | 2010-10-28 | Improved neurturin molecules |
Country Status (9)
| Country | Link |
|---|---|
| EP (2) | EP2493918A4 (https=) |
| JP (1) | JP2013509422A (https=) |
| CN (1) | CN102695723A (https=) |
| AU (1) | AU2010313456A1 (https=) |
| BR (1) | BR112012009801A8 (https=) |
| CA (1) | CA2778678A1 (https=) |
| ES (1) | ES2632431T3 (https=) |
| NZ (1) | NZ599543A (https=) |
| WO (1) | WO2011053675A2 (https=) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112013031652A2 (pt) | 2011-06-09 | 2019-09-24 | Univ Miami | métodos de tratamento para doenças retinais |
| FR3093640B1 (fr) * | 2019-03-15 | 2021-10-01 | Biophytis | Phytoecdysones et leurs dérivés pour leur utilisation dans le traitement de maladies neuromusculaires |
Family Cites Families (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4352883A (en) | 1979-03-28 | 1982-10-05 | Damon Corporation | Encapsulation of biological material |
| US4409331A (en) | 1979-03-28 | 1983-10-11 | Damon Corporation | Preparation of substances with encapsulated cells |
| US4542025A (en) | 1982-07-29 | 1985-09-17 | The Stolle Research And Development Corporation | Injectable, long-acting microparticle formulation for the delivery of anti-inflammatory agents |
| US5231112A (en) | 1984-04-12 | 1993-07-27 | The Liposome Company, Inc. | Compositions containing tris salt of cholesterol hemisuccinate and antifungal |
| US5916588A (en) | 1984-04-12 | 1999-06-29 | The Liposome Company, Inc. | Peptide-containing liposomes, immunogenic liposomes and methods of preparation and use |
| US4684479A (en) | 1985-08-14 | 1987-08-04 | Arrigo Joseph S D | Surfactant mixtures, stable gas-in-liquid emulsions, and methods for the production of such emulsions from said mixtures |
| US4829000A (en) | 1985-08-30 | 1989-05-09 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Reconstituted basement membrane complex with biological activity |
| US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
| US6759057B1 (en) | 1986-06-12 | 2004-07-06 | The Liposome Company, Inc. | Methods and compositions using liposome-encapsulated non-steroidal anti-inflammatory drugs |
| IE60901B1 (en) | 1986-08-21 | 1994-08-24 | Vestar Inc | Improved treatment of systemic fungal infections with phospholipid particles encapsulating polyene antifungal antibiotics |
| US5811128A (en) | 1986-10-24 | 1998-09-22 | Southern Research Institute | Method for oral or rectal delivery of microencapsulated vaccines and compositions therefor |
| US4920016A (en) | 1986-12-24 | 1990-04-24 | Linear Technology, Inc. | Liposomes with enhanced circulation time |
| US6406713B1 (en) | 1987-03-05 | 2002-06-18 | The Liposome Company, Inc. | Methods of preparing low-toxicity drug-lipid complexes |
| US4897268A (en) | 1987-08-03 | 1990-01-30 | Southern Research Institute | Drug delivery system and method of making the same |
| AU598958B2 (en) | 1987-11-12 | 1990-07-05 | Vestar, Inc. | Improved amphotericin b liposome preparation |
| US4904584A (en) | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
| US5034229A (en) | 1988-12-13 | 1991-07-23 | Alza Corporation | Dispenser for increasing feed conversion of hog |
| US5110596A (en) | 1988-12-13 | 1992-05-05 | Alza Corporation | Delivery system comprising means for delivering agent to livestock |
| WO1990013361A1 (en) | 1989-05-04 | 1990-11-15 | Southern Research Institute | Improved encapsulation process and products therefrom |
| US6517859B1 (en) | 1990-05-16 | 2003-02-11 | Southern Research Institute | Microcapsules for administration of neuroactive agents |
| US5215680A (en) | 1990-07-10 | 1993-06-01 | Cavitation-Control Technology, Inc. | Method for the production of medical-grade lipid-coated microbubbles, paramagnetic labeling of such microbubbles and therapeutic uses of microbubbles |
| US5252479A (en) | 1991-11-08 | 1993-10-12 | Research Corporation Technologies, Inc. | Safe vector for gene therapy |
| DE4137649C2 (de) | 1991-11-15 | 1997-11-20 | Gerhard Dingler | Bauelement |
| US5587308A (en) | 1992-06-02 | 1996-12-24 | The United States Of America As Represented By The Department Of Health & Human Services | Modified adeno-associated virus vector capable of expression from a novel promoter |
| US5478745A (en) | 1992-12-04 | 1995-12-26 | University Of Pittsburgh | Recombinant viral vector system |
| US5554730A (en) | 1993-03-09 | 1996-09-10 | Middlesex Sciences, Inc. | Method and kit for making a polysaccharide-protein conjugate |
| ATE163230T1 (de) | 1993-03-09 | 1998-02-15 | Epic Therapeutics Inc | Makromolekulare mikropartikel und verfahren zu ihrer herstellung |
| US5981719A (en) | 1993-03-09 | 1999-11-09 | Epic Therapeutics, Inc. | Macromolecular microparticles and methods of production and use |
| US6090925A (en) | 1993-03-09 | 2000-07-18 | Epic Therapeutics, Inc. | Macromolecular microparticles and methods of production and use |
| US5814618A (en) | 1993-06-14 | 1998-09-29 | Basf Aktiengesellschaft | Methods for regulating gene expression |
| US5464758A (en) | 1993-06-14 | 1995-11-07 | Gossen; Manfred | Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters |
| US5446090A (en) | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
| NL9401150A (nl) | 1994-07-12 | 1996-02-01 | Nederland Ptt | Werkwijze voor het aan een ontvangzijde aanbieden van een van een zendzijde afkomstig eerste aantal videosignalen, alsmede systeem, alsmede zender, alsmede netwerk, en alsmede ontvanger. |
| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| PT788351E (pt) | 1994-11-10 | 2003-06-30 | Univ Kentucky Res Foundation T | Dispositivo implantavel recarregavel de libertacaocontrolada para administrar medicamentos direc tamente numa porcao interna do corpo |
| US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| US5739307A (en) * | 1995-08-28 | 1998-04-14 | Washington University | Polynucleotide encoding neurturin neurotrophic factor |
| US6156331A (en) | 1996-02-02 | 2000-12-05 | Alza Corporation | Sustained delivery of an active agent using an implantable system |
| ES2233768T3 (es) | 1996-02-02 | 2005-06-16 | Alza Corporation | Liberacion prolongada de un agente activo utilizando un sistema implantable. |
| US6395292B2 (en) | 1996-02-02 | 2002-05-28 | Alza Corporation | Sustained delivery of an active agent using an implantable system |
| US5976109A (en) | 1996-04-30 | 1999-11-02 | Medtronic, Inc. | Apparatus for drug infusion implanted within a living body |
| CA2263455C (en) | 1996-08-23 | 2002-10-29 | Sequus Pharmaceuticals, Inc. | Liposomes containing a cisplatin compound |
| 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 |
| SK283760B6 (sk) | 1996-10-15 | 2004-01-08 | The Liposome Company, Inc. | Farmaceutický prostriedok na dopravu bioaktívnych látok |
| US6395302B1 (en) | 1996-11-19 | 2002-05-28 | Octoplus B.V. | Method for the preparation of microspheres which contain colloidal systems |
| EP0842657A1 (en) | 1996-11-19 | 1998-05-20 | OctoPlus B.V. | Microspheres for controlled release and processes to prepare these microspheres |
| AU736707B2 (en) | 1997-06-11 | 2001-08-02 | Anaphore, Inc. | Trimerising module |
| US6043221A (en) * | 1997-07-30 | 2000-03-28 | Amgen Inc. | Method for preventing and treating hearing loss using a neuturin protein product |
| AU1124499A (en) | 1997-10-28 | 1999-05-17 | Maxygen, Inc. | Human papillomavirus vectors |
| ES2182379T3 (es) | 1997-12-22 | 2003-03-01 | Alza Corp | Membrana de regulacion del regimen de liberacion para dispositivos de administracion controlada de farmacos. |
| WO1999033449A1 (en) | 1997-12-30 | 1999-07-08 | Alza Corporation | Beneficial agent delivery system with membrane plug |
| US6458387B1 (en) | 1999-10-18 | 2002-10-01 | Epic Therapeutics, Inc. | Sustained release microspheres |
| US6283949B1 (en) | 1999-12-27 | 2001-09-04 | Advanced Cardiovascular Systems, Inc. | Refillable implantable drug delivery pump |
| AU2001262992A1 (en) | 2000-05-10 | 2002-02-18 | University Of Kentucky Research Foundation | System and method for intranasal administration of opioids |
| DE60140625D1 (de) | 2000-08-15 | 2010-01-07 | Univ Illinois | Verfahren zur herstellung von mikropartikeln |
| FR2814642B1 (fr) | 2000-10-03 | 2005-07-01 | Ass Pour Le Dev De La Rech En | Souris transgenique pour la recombinaison ciblee mediee par la cre-er modifiee |
| US6436386B1 (en) | 2000-11-14 | 2002-08-20 | Shearwater Corporation | Hydroxyapatite-targeting poly (ethylene glycol) and related polymers |
| CN1114690C (zh) | 2001-05-15 | 2003-07-16 | 乔良 | 乳头瘤假病毒及其制备方法 |
| US7812120B2 (en) | 2003-03-21 | 2010-10-12 | Par Pharmaceutical, Inc. | Nasal calcitonin formulations containing chlorobutanol |
| WO2005039643A2 (en) * | 2003-10-20 | 2005-05-06 | Nsgene A/S | In vivo gene therapy of parkinson's disease |
| JP4838724B2 (ja) * | 2003-11-27 | 2011-12-14 | デヴェロゲン アクチエンゲゼルシャフト | ニュールツリンを用いる糖尿病の予防と治療方法 |
| MXPA06012980A (es) | 2004-05-10 | 2007-06-12 | Nastech Pharm Co | Composiciones y metodos para el suministro mucosal mejorado de la hormona paratiroidea. |
| US7790446B2 (en) | 2005-02-11 | 2010-09-07 | Kosagen Cell Factory Oü | Vectors, cell lines and their use in obtaining extended episomal maintenance replication of hybrid plasmids and expression of gene products |
| US8034572B2 (en) * | 2006-08-30 | 2011-10-11 | Mart Saarma | Receptor for GDNF family ligands |
| US20100129354A1 (en) | 2006-10-27 | 2010-05-27 | Ablynx N.V. | Intranasal delivery of polypeptides and proteins |
| KR20150139982A (ko) * | 2007-11-05 | 2015-12-14 | 데벨로겐 악틴게젤샤프트 | 제약학적으로 용도되는 신규한 뉴트린 접합체 |
-
2010
- 2010-10-28 NZ NZ599543A patent/NZ599543A/en not_active IP Right Cessation
- 2010-10-28 ES ES14165977.1T patent/ES2632431T3/es active Active
- 2010-10-28 EP EP10827453.1A patent/EP2493918A4/en not_active Withdrawn
- 2010-10-28 CA CA2778678A patent/CA2778678A1/en not_active Abandoned
- 2010-10-28 WO PCT/US2010/054419 patent/WO2011053675A2/en not_active Ceased
- 2010-10-28 CN CN2010800543012A patent/CN102695723A/zh active Pending
- 2010-10-28 AU AU2010313456A patent/AU2010313456A1/en not_active Abandoned
- 2010-10-28 EP EP14165977.1A patent/EP2774935B8/en active Active
- 2010-10-28 BR BR112012009801A patent/BR112012009801A8/pt not_active IP Right Cessation
- 2010-10-28 JP JP2012537030A patent/JP2013509422A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP2493918A2 (en) | 2012-09-05 |
| BR112012009801A8 (pt) | 2016-08-30 |
| EP2774935A1 (en) | 2014-09-10 |
| AU2010313456A1 (en) | 2012-05-17 |
| JP2013509422A (ja) | 2013-03-14 |
| EP2774935B1 (en) | 2017-04-19 |
| WO2011053675A2 (en) | 2011-05-05 |
| WO2011053675A3 (en) | 2011-08-25 |
| CN102695723A (zh) | 2012-09-26 |
| EP2774935B8 (en) | 2017-06-21 |
| NZ599543A (en) | 2014-02-28 |
| ES2632431T3 (es) | 2017-09-13 |
| EP2493918A4 (en) | 2013-04-10 |
| BR112012009801A2 (pt) | 2016-08-09 |
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