WO2000026362A2 - Proteines de la famille de la stomatine et leur utilisation comme proteines cibles pour le traitement de la douleur - Google Patents
Proteines de la famille de la stomatine et leur utilisation comme proteines cibles pour le traitement de la douleur Download PDFInfo
- Publication number
- WO2000026362A2 WO2000026362A2 PCT/DE1999/003434 DE9903434W WO0026362A2 WO 2000026362 A2 WO2000026362 A2 WO 2000026362A2 DE 9903434 W DE9903434 W DE 9903434W WO 0026362 A2 WO0026362 A2 WO 0026362A2
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- WO
- WIPO (PCT)
- Prior art keywords
- stomatin
- proteins
- use according
- development
- family
- Prior art date
Links
- 102000048514 Stomatin Human genes 0.000 title claims abstract description 34
- 108700037714 Stomatin Proteins 0.000 title claims abstract description 34
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 26
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 23
- 208000002193 Pain Diseases 0.000 title claims abstract description 13
- 230000036407 pain Effects 0.000 title claims abstract description 12
- 238000002560 therapeutic procedure Methods 0.000 title claims abstract description 8
- 239000002299 complementary DNA Substances 0.000 claims abstract description 8
- 229940035674 anesthetics Drugs 0.000 claims abstract description 6
- 239000003193 general anesthetic agent Substances 0.000 claims abstract description 6
- 238000009007 Diagnostic Kit Methods 0.000 claims abstract description 5
- 150000001413 amino acids Chemical class 0.000 claims abstract description 5
- 229940035676 analgesics Drugs 0.000 claims abstract description 4
- 239000000730 antalgic agent Substances 0.000 claims abstract description 4
- 239000003814 drug Substances 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims abstract description 3
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 3
- 239000012634 fragment Substances 0.000 claims description 5
- 102000054765 polymorphisms of proteins Human genes 0.000 claims description 4
- 238000010276 construction Methods 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 230000004043 responsiveness Effects 0.000 claims 1
- 239000013598 vector Substances 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 abstract description 2
- 125000003729 nucleotide group Chemical group 0.000 abstract description 2
- 230000006870 function Effects 0.000 description 7
- 210000002569 neuron Anatomy 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 5
- 230000036982 action potential Effects 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 210000001044 sensory neuron Anatomy 0.000 description 5
- 210000000170 cell membrane Anatomy 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 101100456536 Caenorhabditis elegans mec-2 gene Proteins 0.000 description 3
- 102000004310 Ion Channels Human genes 0.000 description 3
- 210000003050 axon Anatomy 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 2
- 208000004454 Hyperalgesia Diseases 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 206010053552 allodynia Diseases 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000008058 pain sensation Effects 0.000 description 2
- 230000008447 perception Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 241000244203 Caenorhabditis elegans Species 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 229910001111 Fine metal Inorganic materials 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 101000820460 Homo sapiens Stomatin Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 230000023077 detection of light stimulus Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 102000058183 human STOM Human genes 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- 229940124707 pain therapeutics Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000005316 response function Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000015541 sensory perception of touch Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
Classifications
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- Proteins of the stomatin family and their use as target proteins for pain therapy are also known.
- the invention relates to proteins of the stomatin family and their use as target proteins for pain therapy.
- Red blood cells contain a lot of proteins, both inside the cell and in the cell envelope (cell membrane); one of the main membrane proteins is stomatin. It is absent in patients suffering from overhydrated stomatocytosis. It has long been known that in these patients the red blood cells have an increased permeability of their cell membranes to sodium and potassium. Because of this, it has been postulated that stomatin regulates an - unidentified - ion channel in the cell membrane. Research on stomatin therefore focuses on the function in erythrocytes. The human stomatin cDNA was cloned independently in 1991/92 by three groups (Stewart et al. (1992) Blood 79: 1593-1601).
- mec-2 is involved in the conversion of a mechanical stimulus into a receptor potential (mechanotransduction). This enables the worm to perceive a touch stimulus (Huang et al, (1995) Nature 378: 292-295).
- mec-2 connects an ion channel to the cytoskeleton, thus opening the ion channel through a mechanical stimulus.
- Mec-2 has a high sequence homology to stomatin (66% in the central 260 amino acids).
- the object of the invention is to identify and isolate further members of the stomatin family and to develop medical applications for this protein family. This object is achieved according to the claims.
- the invention relates to stomatin and new proteins of the stomatin family, in particular N-stomatin, comprising 287 amino acids and its fragments, mutants and polymorphisms, its coding cDNA with a length of 1847 nucleotides and their fragments, mutants and polymorphisms and the use as target proteins for pain therapy . Furthermore, it relates to the use for the development of pain therapeutics, analgesics / anesthetics, for the construction of genes, for the development of pharmaceutically relevant substances and for diagnostic kits.
- the invention is based on our own knowledge that stomatin has an important function in mechanotransduction in mammals. Stomatin occurs in the nerve cells that are responsible for the perception of touch and pain stimuli. These cells are called sensory neurons. It was found that the sensitivity to mechanical stimuli in mice that lack stomatin (knockout mice) is severely impaired.
- an in vitro skin-nerve preparation was used, which makes it possible to irritate the skin with defined stimuli and to measure the response of the nerves in the form of action potentials.
- a neuron responds to a weak stimulus with few action potentials, stronger stimuli trigger higher frequencies of action potentials. This transmits the strength of the stimulus to the brain.
- AM receptors A-Mechnanonociceptors
- Stomatin RO mice the AM receptors (A-Mechnanonociceptors), which are responsible for the perception of pain caused by strong mechanical stimulation of the skin, are clearly disturbed in their function in the Stomatin RO mice. They are unable to respond to stronger touch stimuli with higher frequencies of action potentials. Pain perception is disturbed in mice that lack stomatin.
- stomatin is an important target for pain therapy: if the function of stomatin is disturbed, the pain sensation is reduced.
- An essential part of the invention is that a protein analogous to stomatin has been found and isolated.
- the complete coding sequence was cloned using RACE (Rapid Amplification of cDNA Ends).
- This cDNA has a length of 1847 base pairs (sequence II).
- the largest open reading frame contains 864 base pairs and codes for a protein of 287 amino acids in length (sequence I).
- Stomatin and the analog protein called N-stomatin are 67% identical. In situ hybridizations were used to perform expression analysis.
- N-stomatin Since the RNA for N-stomatin is formed by all (with a few exceptions) neurons of the nervous system, N-stomatin stands for neuronal stomatin. It was also found that N-stomatin is most strongly expressed in the nervous system but to a lesser extent in various other parts of the body. Because of its high homology to stomatin, N-stomatin also has a function in mechanotransduction and pain sensation and can therefore also be used as a target protein for pain therapy according to the invention.
- N-stomatin Since stomatin is particularly involved in the warning of strong mechanical stimuli, it is likely that N-stomatin has a function in the perception of weak touch stimuli. With almost all forms of chronic pain or other diseases, even a light touch is felt to be painful. This symptom of touch-induced pain is called allodynia. Since N-stomatin is likely to be involved in the perception of light touches, this protein according to the invention is the target protein for therapeutic agents for the treatment of allodynia.
- both stomatin and N-stomatin are important for the effect of volatile anesthetics on the body.
- the mode of action of volatile anesthetics at the molecular level has so far hardly been investigated. It is only known that they act on the neurons of the central nervous system. Such a function can be assumed especially for N-stomatin, since it is expressed by all neurons of the central nervous system (Stomatin, however, only by a few).
- mice were anesthetized with CO 2 and killed by decapitation.
- the skin of the right hind leg was extracted together with the saphenous nerve, an afferent nerve that innervates this area of the skin.
- the skin was in one Organ chamber with hairy side down. This chamber was permanently filled with 32 ° C warm SIF buffer (synthetic interstitial fluid; 2mM CaCl 2 , 5.5mM glucose, 10mM Hepes, 3.5mM KC1, 0.7mM MgS0 4 , 123mM NaCl, 1.5mM NaH 2 P0 4 , 9.5mM Na Gluconate, 7.5mM sucrose).
- SIF buffer synthetic interstitial fluid
- the nerve was guided into a lead chamber, which is connected to the organ chamber, and split into finer bundles of axons using fine forceps. For extracellular derivation, these were placed in succession on a silver electrode. If you stimulate the receptive field of one of the neurons whose axon is currently touching the lead electrode, you can determine the properties of a single sensory neuron. First, the receptive field was stimulated electrically and the delay until an action potential was triggered was measured. The line speed was calculated from this time delay and the distance between the receptive field and the lead electrode. The receptive field was then stimulated with von Frey hair in order to determine the activation threshold. Finally, the stimulus response function was measured. For this purpose, the receptive field of the neuron was stimulated with permanent stimuli of various strengths by placing the rounded end of a fine metal rod on the receptive field for 10 seconds with the help of a micrometer screw.
- the specific primers tcacgcagggaaacacaat and tcagctggaggcgatgag were used for them.
- the first PCR was carried out with the Oligo dT Anchor Primer and the specific primer agctgagacggcgctgtagattc.
- the PCR anchor primer and the specific primer gtagacgactccatccacttg were used for the second ('nested') PCR.
- the 550 bp fragment resulting from this second PCR was cloned and sequenced and assembled with the EST clone. Based on this sequence, a second RACE experiment was carried out.
- the specific primer CTC GGG TGA ATC CAT CTC ATT was used in the first PCR.
- the sequence for the second specific primer was: CAG ACG TTT GTC AAA TCT CGA.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
L'invention concerne la stomatine et de nouvelles protéines de la famille de la stomatine, notamment la N-stomatine contenant 287 acides aminés, son ADNc codant ayant une longueur de 1847 nucléotides. L'invention concerne également leur utilisation comme protéines cibles pour le traitement des douleurs et leur utilisation pour la production d'agents thérapeutiques pour le traitement de la douleur, analgésiques/anesthésiques, pour la constitution de gènes, pour le développement de substances d'importance pharmaceutique et dans kits de diagnostic.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19850015.7 | 1998-10-30 | ||
| DE1998150015 DE19850015A1 (de) | 1998-10-30 | 1998-10-30 | Proteine der Stomatinfamilie und ihre Verwendung als Zielproteine für die Schm erztherapie |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2000026362A2 true WO2000026362A2 (fr) | 2000-05-11 |
| WO2000026362A3 WO2000026362A3 (fr) | 2000-06-22 |
Family
ID=7886124
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/DE1999/003434 WO2000026362A2 (fr) | 1998-10-30 | 1999-10-28 | Proteines de la famille de la stomatine et leur utilisation comme proteines cibles pour le traitement de la douleur |
Country Status (2)
| Country | Link |
|---|---|
| DE (1) | DE19850015A1 (fr) |
| WO (1) | WO2000026362A2 (fr) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004028555A1 (fr) * | 2002-09-29 | 2004-04-08 | Yeda Research And Development Co. Ltd | Proteines se fixant a la resistine, leur preparation, et leurs utilisations |
| WO2004040299A2 (fr) * | 2002-10-30 | 2004-05-13 | Max-Delbrück-Centrum Für Molekulare Medizin (Mdc) Berlin-Buch | Technique d'identification de composes inhibiteurs de la transduction mecanique dans les neurones |
| US7820876B2 (en) | 2000-09-04 | 2010-10-26 | Institut Pasteur | Mouse mutant for expression of the alpha6 subunit of the nicotinic acetylcholine receptor |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998030690A1 (fr) * | 1997-01-09 | 1998-07-16 | Incyte Pharmaceuticals, Inc. | Nouvelle proteine membranaire humaine |
| WO1999025825A2 (fr) * | 1997-11-13 | 1999-05-27 | Genset | ADNc ETENDUS POUR PROTEINES SECRETEES |
-
1998
- 1998-10-30 DE DE1998150015 patent/DE19850015A1/de not_active Withdrawn
-
1999
- 1999-10-28 WO PCT/DE1999/003434 patent/WO2000026362A2/fr active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998030690A1 (fr) * | 1997-01-09 | 1998-07-16 | Incyte Pharmaceuticals, Inc. | Nouvelle proteine membranaire humaine |
| WO1999025825A2 (fr) * | 1997-11-13 | 1999-05-27 | Genset | ADNc ETENDUS POUR PROTEINES SECRETEES |
Non-Patent Citations (6)
| Title |
|---|
| BARNES T M ET AL: "THE CAENORHABDITIS ELEGANS BEHAVIORAL GENE UNC-24 ENCODES A NOVEL BIPARTITE PROTEIN SIMILAR TO BOTH ERYTHROCYTE BAND 7.2 (STOMATIN) AND NONSPECIFIC LIPID TRANSFER PROTEIN" JOURNAL OF NEUROCHEMISTRY,US,NEW YORK, NY, Bd. 67, 1. Januar 1996 (1996-01-01), Seiten 46-55, XP002063568 ISSN: 0022-3042 * |
| MANNSFELDT, A.G. ET AL.: "Stomatin, a MEC-2 Like Protein, Is Expressed by Mammalian Sensory Neurons" MOL. CELL. NEUROSCI., Bd. 13, Nr. 6, Juni 1999 (1999-06), Seiten 391-404, XP000889811 * |
| RAJARAM, S. ET AL.: "unc-1: A stomatin homologue controls sensitivity to volatile anesthetics in Caenorhabditis elegans." PROC, NATL. ACAD. SCI., Bd. 95, Juli 1998 (1998-07), Seiten 8761-8766, XP002132341 * |
| SCHLEGEL W ET AL: "Cloning and analysis of a cDNA encoding the BALB/c murine erythrocyte band 7 integral membrane protein" GENE: AN INTERNATIONAL JOURNAL ON GENES AND GENOMES,GB,ELSEVIER SCIENCE PUBLISHERS, BARKING, Bd. 178, Nr. 1, 31. Oktober 1996 (1996-10-31), Seiten 115-118, XP004043348 ISSN: 0378-1119 * |
| SEIDEL G ET AL: "Molecular cloning of hSLP-1, a novel human brain-specific member of the band 7/MEC-2 family similar to Caenorhabditis elegans UNC-24" GENE,NL,ELSEVIER BIOMEDICAL PRESS. AMSTERDAM, Bd. 225, Nr. 1-2, 28. Dezember 1998 (1998-12-28), Seiten 23-29, XP004153617 ISSN: 0378-1119 * |
| STEWART G W ET AL: "ISOLATION OF CDNA CODING FOR AN UBIQUITOUS MEMBRANE PROTEIN DEFICIENT IN HIGH NA+, LOW K STOMATOCYTIC ERYTHROCYTES" BLOOD,US,PHILADELPHIA, PA, Bd. 79, 1. Januar 1992 (1992-01-01), Seiten 1593-1601, XP002063567 ISSN: 0006-4971 in der Anmeldung erw{hnt * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7820876B2 (en) | 2000-09-04 | 2010-10-26 | Institut Pasteur | Mouse mutant for expression of the alpha6 subunit of the nicotinic acetylcholine receptor |
| WO2004028555A1 (fr) * | 2002-09-29 | 2004-04-08 | Yeda Research And Development Co. Ltd | Proteines se fixant a la resistine, leur preparation, et leurs utilisations |
| WO2004040299A2 (fr) * | 2002-10-30 | 2004-05-13 | Max-Delbrück-Centrum Für Molekulare Medizin (Mdc) Berlin-Buch | Technique d'identification de composes inhibiteurs de la transduction mecanique dans les neurones |
| WO2004040299A3 (fr) * | 2002-10-30 | 2004-07-15 | Max Delbrueck Centrum | Technique d'identification de composes inhibiteurs de la transduction mecanique dans les neurones |
Also Published As
| Publication number | Publication date |
|---|---|
| DE19850015A1 (de) | 2000-05-04 |
| WO2000026362A3 (fr) | 2000-06-22 |
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| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 122 | Ep: pct application non-entry in european phase |