ES2543222T3 - Aptámero para NGF y uso del mismo - Google Patents
Aptámero para NGF y uso del mismo Download PDFInfo
- Publication number
- ES2543222T3 ES2543222T3 ES09816140.9T ES09816140T ES2543222T3 ES 2543222 T3 ES2543222 T3 ES 2543222T3 ES 09816140 T ES09816140 T ES 09816140T ES 2543222 T3 ES2543222 T3 ES 2543222T3
- Authority
- ES
- Spain
- Prior art keywords
- seq
- ngf
- aptamer
- binding
- trka
- 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.)
- Active
Links
- 108091023037 Aptamer Proteins 0.000 abstract description 15
- 108091008604 NGF receptors Proteins 0.000 abstract description 2
- 102000007339 Nerve Growth Factor Receptors Human genes 0.000 abstract description 2
- 239000002773 nucleotide Substances 0.000 abstract 1
- 125000003729 nucleotide group Chemical group 0.000 abstract 1
- 239000002719 pyrimidine nucleotide Substances 0.000 abstract 1
- 150000003230 pyrimidines Chemical class 0.000 abstract 1
- 101150111783 NTRK1 gene Proteins 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 5
- 210000002241 neurite Anatomy 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 2
- 230000014511 neuron projection development Effects 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 201000003352 adrenal gland pheochromocytoma Diseases 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/115—Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
-
- 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
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/22—Affinity chromatography or related techniques based upon selective absorption processes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/16—Aptamers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Un aptámero que se une a NGF e inhibe la unión de NGF a un receptor de NGF, que comprende una secuencia UGAAAAAAACC (SEQ ID NO: 91), UGAAAGAAACC (SEQ ID NO: 92), UGAAAGAAACU (SEQ ID NO: 93), UGAAACAAACC (SEQ ID NO: 94), UGAAAAGAACC (SEQ ID NO: 95), UGAAAAAACCC (SEQ ID NO: 96), UGAAAAAACCU (SEQ ID NO: 97), UGAAAACAACC (SEQ ID NO: 98), UGAAAUAAACC (SEQ ID NO: 99), UGAAAUAAACU (SEQ ID NO: 100), UGAAAAAAUCU (SEQ ID NO: 101), AGAAUGAAACU (SEQ ID NO: 102), CGAACAAAACU (SEQ ID NO: 103), CGAAAGAAACU (SEQ ID NO: 104), UGAAAGGAACC (SEQ ID NO: 105), UGAAAAAAACY (SEQ ID NO: 110), UGAAAGAAACY (SEQ ID NO: 111), CGAACAAAACY (SEQ ID NO: 112), o CGAAAGAAACY (SEQ ID NO: 113); en donde Y es un nucleótido de pirimidina, y al menos un nucleótido está modificado.
Description
E09816140
09-07-2015
SEQ ID NO: 59:
SEQ ID NO: 60:
SEQ ID NO: 61:
SEQ ID NO: 62:
SEQ ID NO: 63:
SEQ ID NO: 64:
SEQ ID NO: 65:
15 SEQ ID NO: 66:
22
E09816140
09-07-2015
la cantidad de unión de NGF y receptor de NGF añadido con un aptámero como un valor de corrección. Aquí, la cantidad de unión es el valor de UR en la parte superior del pico del sensograma de BIAcore (valor de UR inmediatamente después de completarse la inyección de NGF). El valor de corrección se restó de 100 para dar un % de actividad inhibidora, donde no menos de 60% muestra la presencia de actividad inhibidora. Como resultado del 5 experimento, se encontró que todos los aptámeros mostrados por los SEQ ID NO: 1 -9, 12, 37 -55, 57 -87 inhibían la unión de NGF y TrkA (Tabla 1). Como ejemplo, la inhibición de la unión de NGF y TrkA por el aptámero mostrado por el SEQ ID NO: 6 se muestra en la Fig. 12. Se realizó un experimento similar para otro receptor P75 (p75-Fc; R&D Systems). Como resultado, se encontró que todos los aptámeros mostrados por los SEQ ID NO: 1 -9, 12, 37 55, 57 -87 inhibían la unión de NGF y P75 no menos de 60% (Tabla 1). Como ejemplo, la inhibición de la unión de
10 NGF y P75 por el aptámero mostrado por el SEQ ID NO: 6 se muestra en la Fig. 13.
Tabla 1
- imagen33
-
imagen34 Experimento de inhibición por BIACore
- imagen35
- Longitud TrKA P75
- SEQ ID NO: 1
- 79 + +
- SEQ ID NO: 2
- 78 + +
- SEQ ID NO: 3
- 79 + +
- SEQ ID NO: 4
- 79 + +
- SEQ ID NO: 5
- 79 + +
- SEQ ID NO: 6
- 79 + +
- SEQ ID NO: 7
- 79 + +
- SEQ ID NO: 8
- 78 + +
- SEQ ID NO: 9
- 79 + +
- SEQ ID NO: 12
- 79 + +
- SEQ ID NO: 24
- 69 + +
- SEQ ID NO: 25
- 47 + +
- SEQ ID NO: 26
- 46 + +
- SEQ ID NO: 27
- 45 + +
- SEQ ID NO: 28
- 40 + +
- SEQ ID NO: 29
- 61 + +
- SEQ ID NO: 30
- 41 + +
- SEQ ID NO: 31
- 34 + +
- SEQ ID NO: 32
- 38 + +
- SEQ ID NO: 33
- 36 + +
- SEQ ID NO: 34
- 34 + +
- SEQ ID NO: 35
- 38 + +
- SEQ ID NO: 36
- 35 + +
- SEQ ID NO: 37
- 74 + +
- SEQ ID NO: 38
- 74 + +
27
E09816140
09-07-2015
- imagen36
-
imagen37 Experimento de inhibición por BIACore
- imagen38
- Longitud TrKA P75
- SEQ ID NO: 39
- 74 + +
- SEQ ID NO: 40
- 74 + +
- SEQ ID NO: 41
- 74 + +
- SEQ ID NO: 42
- 74 + +
- SEQ ID NO: 43
- 73 + +
- SEQ ID NO: 44
- 73 + +
- SEQ ID NO: 45
- 74 + +
- SEQ ID NO: 46
- 74 + +
- SEQ ID NO: 47
- 74 + +
- SEQ ID NO: 48
- 74 + +
- SEQ ID NO: 49
- 74 + +
- SEQ ID NO: 50
- 74 + +
- SEQ ID NO: 51
- 77 + +
- SEQ ID NO: 52
- 73 + +
- SEQ ID NO: 53
- 74 + +
- SEQ ID NO: 54
- 74 + +
- SEQ ID NO: 55
- 72 + +
- SEQ ID NO: 57
- 75 + +
- SEQ ID NO: 58
- 74 + +
- SEQ ID NO: 59
- 74 + +
- SEQ ID NO: 60
- 74 + +
- SEQ ID NO: 61
- 74 + +
- SEQ ID NO: 62
- 74 + +
- SEQ ID NO: 63
- 74 + +
- SEQ ID NO: 64
- 74 + +
- SEQ ID NO: 65
- 74 + +
- SEQ ID NO: 66
- 74 + +
- SEQ ID NO: 67
- 74 + +
- SEQ ID NO: 68
- 74 + +
- SEQ ID NO: 69
- 83 + +
- SEQ ID NO: 70
- 82 + +
28
E09816140
09-07-2015
- imagen39
-
imagen40 Experimento de inhibición por BIACore
- imagen41
- Longitud TrKA P75
- SEQ ID NO: 71
- 82 + +
- SEQ ID NO: 72
- 82 + +
- SEQ ID NO: 73
- 81 + +
- SEQ ID NO: 74
- 82 + +
- SEQ ID NO: 75
- 78 + +
- SEQ ID NO: 76
- 78 + +
- SEQ ID NO: 77
- 78 + +
- SEQ ID NO: 78
- 78 + +
- SEQ ID NO: 79
- 78 + +
- SEQ ID NO: 80
- 78 + +
- SEQ ID NO: 81
- 78 + +
- SEQ ID NO: 82
- 78 + +
- SEQ ID NO: 83
- 79 + +
- SEQ ID NO: 84
- 78 + +
- SEQ ID NO: 85
- 78 + +
- SEQ ID NO: 86
- 78 + +
- SEQ ID NO: 87
- 71 + +
- SEQ ID NO: 88
- 33 + +
- SEQ ID NO: 89
- 34 + +
- SEQ ID NO: 90
- 32 + +
La Tabla 1 muestra aptámeros que inhiben la unión de TrkA o p75 y NGF. "+" muestra una actividad inhibidora (%) de no menos de 60%, y "-" muestra una de menos de 60%.
En cuanto al aptámero mostrado por el SEQ ID NO: 87, se realizó un experimento inhibidor similar al mencionado
5 anteriormente en unas condiciones de razón molar de NGF-aptámero de 1:1 (0,1 µM). Se utilizó la misma mezcla disolvente preparada de NGF y aptámero para los experimentos de TrkA y P75, y el experimento se realizó sin la influencia de variaciones en la preparación de la muestra. Como resultado, el aptámero mostrado por el SEQ ID NO: 87 inhibió la unión de NGF y TrkA en 93%, pero inhibió la unión de NGF y p75 solamente en 29%.
Ejemplo 7: Evaluación de la actividad fisiológica del aptámero utilizando células PC-12
10 Se evaluó la actividad fisiológica del aptámero por medio de un experimento supresor del crecimiento de neuritas utilizando células PC-12. Las células PC-12, que son una línea celular derivada de feocromocitoma de glándula suprarrenal de rata, son un modelo de célula del sistema nervioso, prolongan la neuritas por estimulación con NGF, y se diferencian como células nerviosas. Se evaluó si el aptámero inhibe o no el crecimiento de las neuritas. Las células PC-12 se sembraron sobre una placa de fondo plano de 96 pocillos recubierta con colágeno, y se añadió una
15 mezcla disolvente de NGF (concentración final 25 ng/mL o 1,9 nM) que se había hecho reaccionar previamente durante1 hr a 37°C y un aptámero (concentración final 500 nM) para iniciar el cultivo celular. Después de eso, se añadió la misma cantidad de aptámero dos veces cada 24 horas y se observó el nivel de crecimiento de las neuritas y se evaluó el día 3 con un microscopio. Para la evaluación, se utilizaron puntuaciones de 0 -3, donde la puntuación 0 representa sin crecimiento de las neuritas, la puntuación 1 representa un ligero crecimiento de las neuritas, la
29
E09816140
09-07-2015
Tabla 3
- imagen44
- 100 nM 10 nM CI50 (nM)
- SEQ ID NO: 5
- 96,5 0,0 21,0
- SEQ ID NO: 6
- 98,6 20,1 17,7
- SEQ ID NO: 12
- 92,8 0,0 43,4
- SEQ ID NO: 30
- 81,9 29,2 57,6
- SEQ ID NO: 30(5)
- 93,7 N.D. <100
- SEQ ID NO: 30(6)
- 98,2 16,2 58,9
- SEQ ID NO: 32
- 64,0 0,0 84,7
- SEQ ID NO: 35
- 57,0 0,0 91,5
- SEQ ID NO: 35(1)
- 54,1 0,0 94,7
- SEQ ID NO: 35(5)
- 70,3 0,0 79,8
- SEQ ID NO: 35(6)
- 80,4 0,0 73,5
- SEQ ID NO: 37
- 98,9 96,0 6,6
- SEQ ID NO: 38
- 98,1 82,2 7,3
- SEQ ID NO: 39
- 99,0 98,8 6,3
- SEQ ID NO: 40
- 99,6 100,0 2,4
- SEQ ID NO: 42
- 96,1 98,3 6,6
- SEQ ID NO: 43
- 97,3 67,4 <10
- SEQ ID NO: 44
- 99,4 0,0 26,1
- SEQ ID NO: 45
- 99,1 12,3 20,2
- SEQ ID NO: 46
- 99,3 0,0 25,4
- SEQ ID NO: 47
- 98,2 35,9 14,6
- SEQ ID NO: 48
- 97,8 0,0 46,4
- SEQ ID NO: 49
- 98,3 97,9 4,6
- SEQ ID NO: 50
- 97,5 0,0 25,4
- SEQ ID NO: 51
- 99,4 45,1 11,9
- SEQ ID NO: 52
- 99,8 95,3 6,7
- SEQ ID NO: 53
- 100,0 53,4 <10
- SEQ ID NO: 54
- 94,4 76,0 7,6
- SEQ ID NO: 55
- 96,2 0,0 49,9
- SEQ ID NO: 56
- 92,8 19,2 18,8
- SEQ ID NO: 57
- 94,1 96,8 6,4
32
Claims (1)
-
imagen1 imagen2
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008244982 | 2008-09-24 | ||
| JP2008244982 | 2008-09-24 | ||
| PCT/JP2009/066457 WO2010035725A1 (ja) | 2008-09-24 | 2009-09-18 | Ｎｇｆに対するアプタマー及びその使用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2543222T3 true ES2543222T3 (es) | 2015-08-17 |
Family
ID=42059724
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09816140.9T Active ES2543222T3 (es) | 2008-09-24 | 2009-09-18 | Aptámero para NGF y uso del mismo |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US10260070B2 (es) |
| EP (1) | EP2354225B1 (es) |
| JP (1) | JP5602020B2 (es) |
| KR (1) | KR101694559B1 (es) |
| CN (1) | CN102171339B (es) |
| AU (1) | AU2009297626B2 (es) |
| BR (1) | BRPI0919268B8 (es) |
| CA (1) | CA2738129C (es) |
| DK (1) | DK2354225T3 (es) |
| ES (1) | ES2543222T3 (es) |
| HU (1) | HUE026595T2 (es) |
| IL (1) | IL211929A0 (es) |
| MX (1) | MX2011003144A (es) |
| RU (1) | RU2011116175A (es) |
| WO (1) | WO2010035725A1 (es) |
| ZA (1) | ZA201102682B (es) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8975026B2 (en) | 2007-01-16 | 2015-03-10 | Somalogic, Inc. | Method for generating aptamers with improved off-rates |
| CA2808233C (en) | 2010-03-03 | 2017-07-11 | Somalogic, Inc. | Aptamers to 4-1bb and their use in treating diseases and disorders |
| CN102844436B (zh) * | 2010-03-24 | 2015-11-25 | 力博美科股份有限公司 | 针对ngf的适配体及其用途 |
| CN104069512A (zh) * | 2010-04-12 | 2014-10-01 | 私募蛋白质体公司 | 针对β-NGF的适体及其在治疗β-NGF介导的疾病和失调中的用途 |
| JP5696830B2 (ja) * | 2010-04-27 | 2015-04-08 | 株式会社アップウェル | Ｐａｒ−２活性化阻害物質 |
| JP2012024026A (ja) * | 2010-07-23 | 2012-02-09 | Tdk Corp | Ｓｍ菌特異的アプタマー、Ｓｍ菌増殖抑制剤及びＳｍ菌の検出方法 |
| KR101964954B1 (ko) | 2010-08-31 | 2019-04-03 | 바이오뉴레 파르마, 에스.엘. | 뉴로트로핀 수용체의 효현제 및 약제로서의 이의 용도 |
| DK2762569T3 (en) * | 2011-09-28 | 2018-08-27 | Ribomic Inc | NGF aptamer and its use. |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0533838T3 (da) | 1990-06-11 | 1998-02-23 | Nexstar Pharmaceuticals Inc | Nukleinsyreligander |
| US5660985A (en) * | 1990-06-11 | 1997-08-26 | Nexstar Pharmaceuticals, Inc. | High affinity nucleic acid ligands containing modified nucleotides |
| WO1994008050A1 (en) | 1992-09-29 | 1994-04-14 | Nexagen, Inc. | Nucleic acid ligands and methods for producing the same |
| CA2169536A1 (en) | 1993-09-08 | 1995-03-16 | Larry Gold | Nucleic acid ligands and improved methods for producing the same |
| US20060057573A1 (en) | 2002-02-15 | 2006-03-16 | Somalogic, Inc | Methods and reagents for detecting target binding by nucleic acid ligands |
| US20030054360A1 (en) | 1999-01-19 | 2003-03-20 | Larry Gold | Method and apparatus for the automated generation of nucleic acid ligands |
| US7638464B2 (en) * | 1999-04-26 | 2009-12-29 | Biocept, Inc. | Three dimensional format biochips |
| EP1265995A2 (en) * | 2000-02-11 | 2002-12-18 | Ribozyme Pharmaceuticals, Inc. | Method and reagent for the modulation and diagnosis of cd20 and nogo gene expression |
| US20030077251A1 (en) * | 2001-05-23 | 2003-04-24 | Nicolas Escriou | Replicons derived from positive strand RNA virus genomes useful for the production of heterologous proteins |
| US20050043256A1 (en) * | 2001-07-30 | 2005-02-24 | Isis Pharmaceuticals, Inc. | Antisense modulation of stearoyl-CoA desaturase expression |
| US20050215506A1 (en) * | 2001-12-20 | 2005-09-29 | Bennett C F | Modulation of tyrosinase expression |
| UA80447C2 (en) | 2002-10-08 | 2007-09-25 | Methods for treating pain by administering nerve growth factor antagonist and opioid analgesic | |
| US7255860B2 (en) | 2002-10-08 | 2007-08-14 | Rinat Neuroscience Corp. | Methods for treating post-surgical pain by administering an anti-nerve growth factor antagonist antibody |
| UA89610C2 (ru) | 2002-10-08 | 2010-02-25 | Ринат Ньюросайенс Корп. | Способы лечения послеоперационной боли путем применения антагониста фактора роста нервов и композиции, которые его содержат |
| US7250496B2 (en) * | 2002-11-14 | 2007-07-31 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory genes and uses thereof |
| US7569364B2 (en) | 2002-12-24 | 2009-08-04 | Pfizer Inc. | Anti-NGF antibodies and methods using same |
| US7655231B2 (en) | 2003-02-19 | 2010-02-02 | Pfizer Inc. | Methods for treating pain by administering a nerve growth factor antagonist and an NSAID |
| US20050136395A1 (en) * | 2003-05-08 | 2005-06-23 | Affymetrix, Inc | Methods for genetic analysis of SARS virus |
| US7888497B2 (en) * | 2003-08-13 | 2011-02-15 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory oligonucleotides and uses thereof |
| SI2206728T1 (en) | 2004-04-07 | 2018-07-31 | Rinat Neuroscience Corp. | Methods for the treatment of bone cancer pain by administration of an antagonist nerve growth factor |
| US7592441B2 (en) * | 2004-10-04 | 2009-09-22 | Rosetta Genomics Ltd | Liver cancer-related nucleic acids |
| US8080649B2 (en) | 2006-11-14 | 2011-12-20 | Ribomic Inc. | Aptamer against midkine and use thereof |
| JP5012135B2 (ja) | 2007-03-28 | 2012-08-29 | コニカミノルタアドバンストレイヤー株式会社 | 超深度画像生成装置 |
| JP5704638B2 (ja) | 2008-07-14 | 2015-04-22 | 国立大学法人 東京大学 | Ｉｌ−１７に対するアプタマー及びその使用 |
-
2009
- 2009-09-18 MX MX2011003144A patent/MX2011003144A/es active IP Right Grant
- 2009-09-18 CA CA2738129A patent/CA2738129C/en not_active Expired - Fee Related
- 2009-09-18 WO PCT/JP2009/066457 patent/WO2010035725A1/ja active Application Filing
- 2009-09-18 AU AU2009297626A patent/AU2009297626B2/en not_active Ceased
- 2009-09-18 BR BRPI0919268A patent/BRPI0919268B8/pt not_active IP Right Cessation
- 2009-09-18 ES ES09816140.9T patent/ES2543222T3/es active Active
- 2009-09-18 EP EP20090816140 patent/EP2354225B1/en not_active Not-in-force
- 2009-09-18 CN CN200980137647.6A patent/CN102171339B/zh not_active Expired - Fee Related
- 2009-09-18 US US13/120,650 patent/US10260070B2/en not_active Expired - Fee Related
- 2009-09-18 DK DK09816140.9T patent/DK2354225T3/en active
- 2009-09-18 JP JP2010530841A patent/JP5602020B2/ja not_active Expired - Fee Related
- 2009-09-18 RU RU2011116175/10A patent/RU2011116175A/ru unknown
- 2009-09-18 KR KR1020117009135A patent/KR101694559B1/ko not_active Expired - Fee Related
- 2009-09-18 HU HUE09816140A patent/HUE026595T2/hu unknown
-
2011
- 2011-03-24 IL IL211929A patent/IL211929A0/en unknown
- 2011-04-11 ZA ZA2011/02682A patent/ZA201102682B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2009297626A2 (en) | 2011-05-19 |
| AU2009297626A1 (en) | 2010-04-01 |
| KR20110059888A (ko) | 2011-06-07 |
| WO2010035725A1 (ja) | 2010-04-01 |
| MX2011003144A (es) | 2011-05-19 |
| US10260070B2 (en) | 2019-04-16 |
| US20110251266A1 (en) | 2011-10-13 |
| DK2354225T3 (en) | 2015-06-29 |
| EP2354225A9 (en) | 2012-06-27 |
| BRPI0919268A2 (pt) | 2017-11-07 |
| IL211929A0 (en) | 2011-06-30 |
| BRPI0919268B8 (pt) | 2021-05-25 |
| ZA201102682B (en) | 2012-06-27 |
| JPWO2010035725A1 (ja) | 2012-02-23 |
| EP2354225A1 (en) | 2011-08-10 |
| BRPI0919268A8 (pt) | 2018-02-06 |
| JP5602020B2 (ja) | 2014-10-08 |
| EP2354225A4 (en) | 2012-03-21 |
| CA2738129C (en) | 2017-11-14 |
| EP2354225B1 (en) | 2015-04-22 |
| CN102171339B (zh) | 2017-06-09 |
| KR101694559B1 (ko) | 2017-01-09 |
| BRPI0919268B1 (pt) | 2021-01-12 |
| AU2009297626B2 (en) | 2016-01-14 |
| RU2011116175A (ru) | 2012-10-27 |
| HUE026595T2 (hu) | 2016-06-28 |
| CA2738129A1 (en) | 2010-04-01 |
| CN102171339A (zh) | 2011-08-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2543222T3 (es) | Aptámero para NGF y uso del mismo | |
| Borroto-Escuela et al. | Fibroblast growth factor receptor 1–5-hydroxytryptamine 1A heteroreceptor complexes and their enhancement of hippocampal plasticity | |
| Wojnacki et al. | Rho GTPases at the crossroad of signaling networks in mammals: impact of Rho-GTPases on microtubule organization and dynamics | |
| Spillane et al. | Nerve growth factor-induced formation of axonal filopodia and collateral branches involves the intra-axonal synthesis of regulators of the actin-nucleating Arp2/3 complex | |
| Nuamnaichati et al. | Sustained β-AR stimulation induces synthesis and secretion of growth factors in cardiac myocytes that affect on cardiac fibroblast activation | |
| Leo et al. | Cisplatin-induced neuropathic pain is mediated by upregulation of N-type voltage-gated calcium channels in dorsal root ganglion neurons | |
| Castano et al. | Actin complexes in the cell nucleus: new stones in an old field | |
| Fromigué et al. | Peptide‐based activation of alpha5 integrin for promoting osteogenesis | |
| BRPI0812504B8 (pt) | composto para profilaxia ou tratamento de doença ou condição associada a receptor de canabinoides em sujeito mamífero | |
| BRPI0410720A (pt) | quinazolinas e pirido[3,4-d]pirimidinas como inibidores do receptor de tirosina cinase | |
| BRPI0514553A (pt) | composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, métodos para inibir o receptor de histamina h3 em um mamìfero, para o tratamento de um distúrbio do sistema nervoso, para o tratamento de obesidade e para o tratamento de um distúrbio ou doença, e, uso de um composto ou um sal do mesmo | |
| Ciska et al. | NMCP/LINC proteins: putative lamin analogs in plants? | |
| Kerkhoff | Actin dynamics at intracellular membranes: the Spir/formin nucleator complex | |
| JP7449648B2 (ja) | リプログラミング前駆体組成物およびその使用方法 | |
| Li et al. | Acid-sensing ion channel 1a is involved in acid-induced osteoclastogenesis by regulating activation of the transcription factor NFATc1 | |
| AR054252A1 (es) | Composicion farmaceutica oral que contiene sales de ditosilato de 4-quinazolinamina | |
| BRPI0707842B8 (pt) | Ácido nucleico capaz de se ligar à mcp-1, seus usos, seu método de detecção, bem como composição farmacêutica, complexo, método para a triagem de um antagonista de quimiocina ou um agonista de quimiocina e kit para a detecção de uma quimiocina | |
| MX342712B (es) | Macromolecula para el suministro de farmacos de proteina, polipeptido o peptido y un metodo de produccion para la misma, y una composicion de liberacion lenta para farmacos de proteina, polipeptido o peptido y un metodo de produccion para la misma. | |
| BRPI0714844B8 (pt) | molécula de ácido nucleico e seus usos, composição farmaceutica e complexo | |
| Govoni et al. | Senescence of the brain: focus on cognitive kinases | |
| Simpson et al. | Early endocytic Rabs: functional prediction to functional characterization. | |
| Zaru et al. | Structural and functional basis for p38-MK2-activated Rsk signaling in toll-like receptor-stimulated dendritic cells | |
| Ramasamy et al. | NogoR1 and PirB signaling stimulates neural stem cell survival and proliferation | |
| Summers et al. | Adhesion to the extracellular matrix is required for interleukin-1 beta actions leading to reactive phenotype in rat astrocytes | |
| PE20091580A1 (es) | Compuesto heterociclico fusionado |