WO2003030965A2 - Noeud lymphatique artificiel - Google Patents
Noeud lymphatique artificiel Download PDFInfo
- Publication number
- WO2003030965A2 WO2003030965A2 PCT/DE2002/003465 DE0203465W WO03030965A2 WO 2003030965 A2 WO2003030965 A2 WO 2003030965A2 DE 0203465 W DE0203465 W DE 0203465W WO 03030965 A2 WO03030965 A2 WO 03030965A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antigen
- lymph node
- module
- artificial lymph
- cell
- Prior art date
Links
- 210000001165 lymph node Anatomy 0.000 title claims abstract description 17
- 210000004027 cell Anatomy 0.000 claims abstract description 20
- 239000000427 antigen Substances 0.000 claims abstract description 16
- 102000036639 antigens Human genes 0.000 claims abstract description 12
- 108091007433 antigens Proteins 0.000 claims abstract description 12
- 210000004443 dendritic cell Anatomy 0.000 claims description 19
- 210000002865 immune cell Anatomy 0.000 claims description 7
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 230000003213 activating effect Effects 0.000 claims description 3
- 210000001124 body fluid Anatomy 0.000 claims 1
- 239000010839 body fluid Substances 0.000 claims 1
- 230000009918 complex formation Effects 0.000 claims 1
- 230000003612 virological effect Effects 0.000 abstract description 5
- 206010028980 Neoplasm Diseases 0.000 abstract description 3
- 244000052769 pathogen Species 0.000 abstract description 3
- 230000024932 T cell mediated immunity Effects 0.000 abstract description 2
- 208000035143 Bacterial infection Diseases 0.000 abstract 1
- 208000036142 Viral infection Diseases 0.000 abstract 1
- 208000022362 bacterial infectious disease Diseases 0.000 abstract 1
- 230000002950 deficient Effects 0.000 abstract 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 239000012636 effector Substances 0.000 description 8
- 230000028993 immune response Effects 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 241000941423 Grom virus Species 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000013638 trimer Substances 0.000 description 2
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 201000009053 Neurodermatitis Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 231100000749 chronicity Toxicity 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000004049 embossing Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0639—Dendritic cells, e.g. Langherhans cells in the epidermis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5154—Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/20—Pathogenic agents
- A61M2202/203—Bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/20—Pathogenic agents
- A61M2202/206—Viruses
Definitions
- the present invention relates to an artificial lymph node and a method for activating immune cells.
- the aim of the present invention is to provide a module which is suitable for activating immune cells.
- a method using the module is to be made available.
- the object underlying the present invention is achieved by the artificial lymph node according to claim 1.
- This artificial lymph node consists of a module with an inlet and outlet opening, a complex of antigen-presenting cell, MHC and antigen being immobilized in the module on a support.
- the module according to the invention can be used in patients or clinical situations with a poor cellular immune response, for example against viral or bacterial pathogens or tumor antigens.
- the module according to the invention can, for example, in the
- the module with autologous dendritic cells plus MHC-antigen complex (for example tetramers) with specific immune-relevant peptides is used for transient introduction into the patient's blood stream via a Shaldon catheter.
- MHC-antigen complex for example tetramers
- circulating peptide-specific T cells bind to the tetramers in the module and thus come into contact with the DC.
- the effector cells with insufficient specific function are stimulated and leave the module as highly active cells.
- CD4 and CD8 memory cells that have previously been in contact with the natural peptide also bind to the tetramers and / or to the DC. These already imprinted cells are also strongly activated.
- T cells bind to the DC and are tested against the presented peptide.
- the co-stimulatory factors in the module e.g. DC adhesion molecules, cytokines etc.
- activate these cells return to the bloodstream in order to eliminate the pathogen there or after extravasation in the diseased tissue using specific effector mechanisms.
- the induction of a humoral immune response can follow (T cell mediated B cell activation).
- the advantages of the invention over the conventional methods are that the invention allows the de novo induction or enhancement of a highly specific immune response against the pathogen.
- peptide-presenting DC By combining the peptide-presenting DC with the MHC / peptide constructs, already imprinted immune cells can be specifically strengthened in their immune response.
- the in low frequency in the blood cells contained need not consuming isolated and expanded ex vivo, since the cell will automatically pass via 'the blood stream into the filter. Only those cells that have already been in contact with the peptide bind to the MHC-antigen complexes (tetramers, bimers or trimers loaded with peptide) and are sufficiently activated with the help of the co-stimulation by the neighboring DC. After their activation, the effector cells go directly into the bloodstream and into the affected tissues.
- activation in the present invention includes both increasing the activity of already activated immune cells as well as the 'embossing yet unembossed immune cells.
- lymph node according to the invention is the high achievable density of the DC in the module.
- An additional advantage is that, in contrast to the ex vivo stimulation of the effector cells, no large amount of effector cells has to be enriched for the return in the patient. Defects that prevent DC from settling in the patient's natural lymph nodes can be avoided with the aid of the lymph node according to the invention.
- the artificial lymph node according to the invention can also be used to induce tolerance in patients with pathologically increased immune reactions to natural antigens (allergies) or the body's own structures (autoimmune diseases). Examples include:
- the artificial lymph node according to the invention preferably consists of a housing with a diameter of 10 cm, for example.
- the diameter of the inflow and outflow connections is adapted to the hose connections of the catheter connections.
- a carrier for example a three-dimensionally folded polyester membrane with a modified surface, for the application of MHC antigen
- DC dentritic cells
- the pretreatment of the DC includes the immunological maturation of the DC in various ways. In this way, a peptide-specific immune response, but also the tolerance to individual peptides can be induced as desired.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Genetics & Genomics (AREA)
- Public Health (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Microbiology (AREA)
- Wood Science & Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- General Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Anesthesiology (AREA)
- Cardiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2002349265A AU2002349265A1 (en) | 2001-09-27 | 2002-09-16 | Artificial lymph node |
DE10294532T DE10294532D2 (de) | 2001-09-27 | 2002-09-16 | Künstlicher Lymphknoten |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10147639 | 2001-09-27 | ||
DE10147639.6 | 2001-09-27 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2003030965A2 true WO2003030965A2 (fr) | 2003-04-17 |
WO2003030965A3 WO2003030965A3 (fr) | 2004-04-01 |
Family
ID=7700471
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/DE2002/003465 WO2003030965A2 (fr) | 2001-09-27 | 2002-09-16 | Noeud lymphatique artificiel |
Country Status (3)
Country | Link |
---|---|
AU (1) | AU2002349265A1 (fr) |
DE (1) | DE10294532D2 (fr) |
WO (1) | WO2003030965A2 (fr) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1571204A1 (fr) | 2004-03-04 | 2005-09-07 | LeukoCare GmbH | Matrice de stimulation de leucocytes |
WO2007069755A1 (fr) * | 2005-12-12 | 2007-06-21 | Riken | Procédé pour la production avec un bon rendement d'un hybridome spécifique à un antigène en utilisant un ganglion lymphatique artificiel |
CN101001954B (zh) * | 2004-05-27 | 2013-01-30 | 西尔斯公司 | 用于改变植物特征的核苷酸序列及其编码的多肽 |
EP2969149A4 (fr) * | 2013-03-14 | 2016-12-21 | Brian J Leberthon | Procédé et dispositif pour traiter le cancer |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993020185A1 (fr) * | 1992-04-01 | 1993-10-14 | Steinman Ralph M | Procede permettant de faire proliferer in vitro des precurseurs de cellules dendritiques et utilisation de celles-ci pour produire des immunogenes |
WO1997003186A2 (fr) * | 1995-07-12 | 1997-01-30 | Activated Cell Therapy, Inc. | Procede de proliferation in vitro de cellules dendritiques, contenant les cellules piegees dans une matrice tridimensionnelle et utilisation en immunisation |
WO2000027999A2 (fr) * | 1998-11-12 | 2000-05-18 | Cell Science Therapeutics, Inc. | Production de cellules lymphoides specifiques d'un tissu a partir de cellules souches hematopoietiques se trouvant dans des dispositifs tridimensionnels |
-
2002
- 2002-09-16 AU AU2002349265A patent/AU2002349265A1/en not_active Abandoned
- 2002-09-16 DE DE10294532T patent/DE10294532D2/de not_active Expired - Fee Related
- 2002-09-16 WO PCT/DE2002/003465 patent/WO2003030965A2/fr not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993020185A1 (fr) * | 1992-04-01 | 1993-10-14 | Steinman Ralph M | Procede permettant de faire proliferer in vitro des precurseurs de cellules dendritiques et utilisation de celles-ci pour produire des immunogenes |
WO1997003186A2 (fr) * | 1995-07-12 | 1997-01-30 | Activated Cell Therapy, Inc. | Procede de proliferation in vitro de cellules dendritiques, contenant les cellules piegees dans une matrice tridimensionnelle et utilisation en immunisation |
WO2000027999A2 (fr) * | 1998-11-12 | 2000-05-18 | Cell Science Therapeutics, Inc. | Production de cellules lymphoides specifiques d'un tissu a partir de cellules souches hematopoietiques se trouvant dans des dispositifs tridimensionnels |
Non-Patent Citations (1)
Title |
---|
BANCHEREAU J & STEINMAN R M: "Dendritic cells and the control of immunity" NATURE, MACMILLAN JOURNALS LTD. LONDON, GB, Bd. 392, Nr. 6673, 19. M{rz 1998 (1998-03-19), Seiten 245-252, XP002134557 ISSN: 0028-0836 * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1571204A1 (fr) | 2004-03-04 | 2005-09-07 | LeukoCare GmbH | Matrice de stimulation de leucocytes |
WO2005085420A2 (fr) * | 2004-03-04 | 2005-09-15 | Leukocare Gmbh | Matrice de stimulation des leucocytes |
WO2005085420A3 (fr) * | 2004-03-04 | 2005-11-17 | Leukocare Gmbh | Matrice de stimulation des leucocytes |
CN101001954B (zh) * | 2004-05-27 | 2013-01-30 | 西尔斯公司 | 用于改变植物特征的核苷酸序列及其编码的多肽 |
WO2007069755A1 (fr) * | 2005-12-12 | 2007-06-21 | Riken | Procédé pour la production avec un bon rendement d'un hybridome spécifique à un antigène en utilisant un ganglion lymphatique artificiel |
EP2969149A4 (fr) * | 2013-03-14 | 2016-12-21 | Brian J Leberthon | Procédé et dispositif pour traiter le cancer |
Also Published As
Publication number | Publication date |
---|---|
DE10294532D2 (de) | 2004-08-26 |
AU2002349265A1 (en) | 2003-04-22 |
WO2003030965A3 (fr) | 2004-04-01 |
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