AR014946A1 - UNA PROTEINA O FRAGMENTO DE PROTEINA, PROCEDIMIENTO DE PREPARACIoN, COMPOSICION TERAPEUTICA, COMPOSICION FARMACEUTICA Y VACUNA - Google Patents
UNA PROTEINA O FRAGMENTO DE PROTEINA, PROCEDIMIENTO DE PREPARACIoN, COMPOSICION TERAPEUTICA, COMPOSICION FARMACEUTICA Y VACUNAInfo
- Publication number
- AR014946A1 AR014946A1 ARP980106645A ARP980106645A AR014946A1 AR 014946 A1 AR014946 A1 AR 014946A1 AR P980106645 A ARP980106645 A AR P980106645A AR P980106645 A ARP980106645 A AR P980106645A AR 014946 A1 AR014946 A1 AR 014946A1
- Authority
- AR
- Argentina
- Prior art keywords
- protein
- fragment
- hiv
- effects
- carboxymethylated
- Prior art date
Links
- 239000012634 fragment Substances 0.000 title abstract 8
- 108090000623 proteins and genes Proteins 0.000 title abstract 7
- 102000004169 proteins and genes Human genes 0.000 title abstract 7
- 238000000034 method Methods 0.000 title abstract 3
- 230000001225 therapeutic effect Effects 0.000 title abstract 2
- 239000000203 mixture Substances 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 229960005486 vaccine Drugs 0.000 title 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 abstract 3
- 230000001506 immunosuppresive effect Effects 0.000 abstract 3
- 102000006992 Interferon-alpha Human genes 0.000 abstract 2
- 108010047761 Interferon-alpha Proteins 0.000 abstract 2
- 108010052104 Viral Regulatory and Accessory Proteins Proteins 0.000 abstract 2
- 239000003814 drug Substances 0.000 abstract 2
- 102000034356 gene-regulatory proteins Human genes 0.000 abstract 2
- 108091006104 gene-regulatory proteins Proteins 0.000 abstract 2
- 230000002163 immunogen Effects 0.000 abstract 2
- 229950000038 interferon alfa Drugs 0.000 abstract 2
- 208000031886 HIV Infections Diseases 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 abstract 1
- 230000024932 T cell mediated immunity Effects 0.000 abstract 1
- 102000040945 Transcription factor Human genes 0.000 abstract 1
- 108091023040 Transcription factor Proteins 0.000 abstract 1
- 238000007385 chemical modification Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 230000002074 deregulated effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 230000005847 immunogenicity Effects 0.000 abstract 1
- 230000006698 induction Effects 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 230000001590 oxidative effect Effects 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/212—IFN-alpha
-
- 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
- A61K39/12—Viral antigens
-
- 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
- A61K39/12—Viral antigens
- A61K39/21—Retroviridae, e.g. equine infectious anemia virus
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- 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
- A61K2039/525—Virus
- A61K2039/5252—Virus inactivated (killed)
-
- 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16311—Human Immunodeficiency Virus, HIV concerning HIV regulatory proteins
- C12N2740/16322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16311—Human Immunodeficiency Virus, HIV concerning HIV regulatory proteins
- C12N2740/16334—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/82—Proteins from microorganisms
- Y10S530/826—Viruses
Abstract
Tiene la finalidad de aportar nuevos toxoides y un nuevo método simple y eficiente para producir estos toxoides, principalmente a partir de las proteínasreguladoras de HIV-1, que contribuyen al efecto inmunosupresor de HIV-1, o del IFN-a, cuyaproduc cion está desregulada durante la infeccion por HIV-1. Entrelas proteínas reguladoras que mencionaremos se incluyen Tat, Nef, Vpr, Vif. Esta presentacion se refiere a una proteína reguladora viral o a un fragmento deuna proteína reguladoraviral o al interferon alfa o a un fragmento del interferon alfa, que sea carboximetilado. Esta presentacion tiene como objeto unprocedimiento de preparacion de una proteína o un fragmento tal como se define anteriormente, caracterizado por lacarboximetilacion de dicha proteína o dedicho fragmento. Esta modificacion química da lugar a nuevas proteínas o fragmentos que son biologicamente inactivos pero preservan su inmunogenicidad. Loscompuestos objeto de la presente invencion tienenpropiedades farmacologi cas muy interesantes. Son biologicamente inactivos con respecto a las funciones quegeneralmente ejercen tales como efectos inmunosupresores, los efectos del transactivador del promotor de HIV-1, o los efectos oxidantes deTat, o los efectosinmunosupr esores para el IFNalfa. Son inmunogénicos en raton pero también en humanos. Mayoritariamente, permiten la induccion de una respuesta inmunitariacelular. Por este motivo se refiere esta invencion también a una proteína ofragmento carboximetilado para su uso en el tratamiento terapéutico de humanos oanimales, o sea, como un medicamento. La invencion tiene finalmente como objeto el uso de una proteína o un fragmento carboximetilado antes mencionado para laobtencionde un medicamento con la finalid ad de ser empleado al menos como inmunogeno.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9716589A FR2773156B1 (fr) | 1997-12-26 | 1997-12-26 | Nouveaux immunogenes anti-retroviraux (toxoides), nouveaux procedes de preparation et application a la prevention et au traitement du sida |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR014946A1 true AR014946A1 (es) | 2001-04-11 |
Family
ID=9515202
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP980106645A AR014946A1 (es) | 1997-12-26 | 1998-12-23 | UNA PROTEINA O FRAGMENTO DE PROTEINA, PROCEDIMIENTO DE PREPARACIoN, COMPOSICION TERAPEUTICA, COMPOSICION FARMACEUTICA Y VACUNA |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US6420141B1 (es) |
| EP (3) | EP1042363B1 (es) |
| JP (2) | JP2001527029A (es) |
| AR (1) | AR014946A1 (es) |
| AT (2) | ATE330970T1 (es) |
| AU (2) | AU1568499A (es) |
| BR (1) | BR9814473A (es) |
| CA (1) | CA2316811A1 (es) |
| CY (1) | CY1106152T1 (es) |
| DE (2) | DE69835031T2 (es) |
| DK (1) | DK1042363T3 (es) |
| ES (1) | ES2267199T3 (es) |
| FR (1) | FR2773156B1 (es) |
| MX (1) | MXPA00006263A (es) |
| PT (1) | PT1042363E (es) |
| WO (2) | WO1999033872A1 (es) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2773156B1 (fr) | 1997-12-26 | 2000-03-31 | Biovacs Inc | Nouveaux immunogenes anti-retroviraux (toxoides), nouveaux procedes de preparation et application a la prevention et au traitement du sida |
| FR2781158B1 (fr) | 1998-07-15 | 2002-12-13 | Vacs Internat | Nouvelles proteines modifiees immunogenes non immunosuppressives, leur procede de preparation et leurs applications |
| CA2358385C (en) | 1998-12-31 | 2013-08-06 | Chiron Corporation | Polynucleotides encoding antigenic hiv type c polypeptides, polypeptides and uses thereof |
| FR2792639B1 (fr) | 1999-04-26 | 2003-06-06 | Neovacs | Nouveaux immunogenes anti-vih (toxoides), nouveaux procedes de preparation et application a la prevention et au traitement du sida |
| US20050226890A1 (en) * | 1999-08-12 | 2005-10-13 | Cohen David I | Tat-based vaccine compositions and methods of making and using same |
| CN1326873C (zh) * | 2000-01-31 | 2007-07-18 | 史密丝克莱恩比彻姆生物有限公司 | 用于hiv预防或治疗性免疫的疫苗 |
| WO2005090392A1 (en) * | 2004-03-16 | 2005-09-29 | Inist Inc. | Tat-based tolerogen compositions and methods of making and using same |
| NO314587B1 (no) * | 2000-09-04 | 2003-04-14 | Bionor Immuno As | HIV regulatoriske- og hjelpepeptider, antigener, vaksinepreparater, immunoassay testsett og en metode for påvisning av antistoffer fremkaltav HIV |
| EP2412242A3 (en) | 2001-07-05 | 2012-06-13 | Novartis Vaccines and Diagnostics, Inc. | Polynucleotides encoding antigenic HIV Type C polypeptides, polypeptides and uses thereof |
| FR2828404B1 (fr) * | 2001-08-10 | 2005-07-15 | Neovacs | Superimmunogene composite a usage vaccinal bifonctionnel pour le traitement des maladies associees a un desordre tissulaire stromal |
| WO2003054006A2 (en) * | 2001-12-11 | 2003-07-03 | Aventis Pasteur | Mutated hiv tat |
| WO2003097675A1 (en) * | 2002-05-16 | 2003-11-27 | Bavarian Nordic A/S | Fusion protein of hiv regulatory/accessory proteins |
| US20040115830A1 (en) * | 2002-09-25 | 2004-06-17 | Igor Touzov | Components for nano-scale Reactor |
| FR2862306B1 (fr) | 2003-11-17 | 2008-05-30 | Aventis Pasteur | Composition vaccinale |
| US7927580B2 (en) * | 2004-03-16 | 2011-04-19 | Nanirx, Inc. | Tat-based immunomodulatory compositions and methods of their discovery and use |
| AR054822A1 (es) | 2005-07-07 | 2007-07-18 | Sanofi Pasteur | Emulsion inmuno adyuvante |
| US8168165B2 (en) * | 2008-12-23 | 2012-05-01 | Abbott Laboratories | Alkylated interleukin-18 compositions |
| CN102405057B (zh) | 2009-03-23 | 2016-05-25 | 那尼尔科斯治疗公司 | 用免疫刺激性Hiv Tat衍生物多肽治疗癌症 |
| EP3187585A1 (en) | 2010-03-25 | 2017-07-05 | Oregon Health&Science University | Cmv glycoproteins and recombinant vectors |
| PL2691530T3 (pl) | 2011-06-10 | 2019-02-28 | Oregon Health & Science University | Glikoproteiny i rekombinowane wektory CMV |
| US20130189754A1 (en) | 2011-09-12 | 2013-07-25 | International Aids Vaccine Initiative | Immunoselection of recombinant vesicular stomatitis virus expressing hiv-1 proteins by broadly neutralizing antibodies |
| US9402894B2 (en) | 2011-10-27 | 2016-08-02 | International Aids Vaccine Initiative | Viral particles derived from an enveloped virus |
| ES2631608T3 (es) | 2012-06-27 | 2017-09-01 | International Aids Vaccine Initiative | Variante de la glicoproteína Env del VIH-1 |
| US20150065381A1 (en) | 2013-09-05 | 2015-03-05 | International Aids Vaccine Initiative | Methods of identifying novel hiv-1 immunogens |
| WO2015051245A1 (en) | 2013-10-04 | 2015-04-09 | Pin Pharma, Inc. | Immunostimulatory hiv tat derivative polypeptides for use in cancer treatment |
| EP2873423B1 (en) | 2013-10-07 | 2017-05-31 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
| KR20170042605A (ko) * | 2014-08-18 | 2017-04-19 | 사노피 파스퇴르 인코포레이티드 | 알킬화된 인플루엔자 백신 |
| EP3069730A3 (en) | 2015-03-20 | 2017-03-15 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
| EP3072901A1 (en) | 2015-03-23 | 2016-09-28 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
| FR3057438B1 (fr) | 2016-10-14 | 2020-10-02 | Univ Limoges | Procede d'elicitation d'une plante au moyen d'extraits de champignons macroscopiques comestibles |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4258029A (en) | 1979-04-23 | 1981-03-24 | Connaught Laboratories Limited | Synthetic adjuvants for stimulation of antigenic responses |
| US4235877A (en) | 1979-06-27 | 1980-11-25 | Merck & Co., Inc. | Liposome particle containing viral or bacterial antigenic subunit |
| DE3650175T3 (de) * | 1985-04-29 | 2007-09-06 | Bio-Rad Laboratories, Inc., Hercules | Synthetische antigene zum nachweis von aids. |
| US5057540A (en) | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
| WO1991018454A1 (en) * | 1990-05-18 | 1991-11-28 | Centre National De La Recherche Scientifique | Compositions capable of blocking cytotoxicity of viral regulatory proteins and neurotoxic symptoms associated with retroviral infection |
| WO1994015634A1 (en) * | 1992-12-30 | 1994-07-21 | Matthias Rath | Tat and rev oligopeptides in hiv treatment |
| WO1995031999A1 (en) | 1994-05-23 | 1995-11-30 | Immunogiology Research Institute, Inc. | Compositions of transactivating proteins of human immunodeficiency virus |
| WO1996027389A1 (fr) * | 1995-03-08 | 1996-09-12 | Neovacs | Immunogenes denues de toxicite derivant d'une proteine de regulation retrovirale, anticorps, procede de preparation et compositions pharmaceutiques les renfermant |
| US6200575B1 (en) * | 1996-03-07 | 2001-03-13 | Neovacs | Non-toxic immunogens derived from a retroviral regulatory protein antibodies preparation process and pharmaceutical compositions comprising them |
| FR2773156B1 (fr) | 1997-12-26 | 2000-03-31 | Biovacs Inc | Nouveaux immunogenes anti-retroviraux (toxoides), nouveaux procedes de preparation et application a la prevention et au traitement du sida |
-
1997
- 1997-12-26 FR FR9716589A patent/FR2773156B1/fr not_active Expired - Fee Related
-
1998
- 1998-12-14 US US09/582,519 patent/US6420141B1/en not_active Expired - Lifetime
- 1998-12-14 EP EP98959984A patent/EP1042363B1/fr not_active Expired - Lifetime
- 1998-12-14 ES ES98959984T patent/ES2267199T3/es not_active Expired - Lifetime
- 1998-12-14 AU AU15684/99A patent/AU1568499A/en not_active Abandoned
- 1998-12-14 AT AT98959984T patent/ATE330970T1/de active
- 1998-12-14 DE DE69835031T patent/DE69835031T2/de not_active Expired - Lifetime
- 1998-12-14 DK DK98959984T patent/DK1042363T3/da active
- 1998-12-14 PT PT98959984T patent/PT1042363E/pt unknown
- 1998-12-14 WO PCT/FR1998/002727 patent/WO1999033872A1/fr active IP Right Grant
- 1998-12-22 AT AT98964219T patent/ATE412006T1/de not_active IP Right Cessation
- 1998-12-22 EP EP98964219A patent/EP1041888B1/en not_active Expired - Lifetime
- 1998-12-22 MX MXPA00006263A patent/MXPA00006263A/es not_active IP Right Cessation
- 1998-12-22 BR BR9814473-1A patent/BR9814473A/pt not_active Application Discontinuation
- 1998-12-22 DE DE69840152T patent/DE69840152D1/de not_active Expired - Fee Related
- 1998-12-22 JP JP2000526120A patent/JP2001527029A/ja active Pending
- 1998-12-22 AU AU19397/99A patent/AU1939799A/en not_active Abandoned
- 1998-12-22 CA CA002316811A patent/CA2316811A1/en not_active Abandoned
- 1998-12-22 EP EP07123075A patent/EP1975173A1/en not_active Withdrawn
- 1998-12-22 WO PCT/US1998/027263 patent/WO1999033346A1/en active Application Filing
- 1998-12-23 AR ARP980106645A patent/AR014946A1/es active IP Right Grant
-
2000
- 2000-05-17 US US09/572,451 patent/US7022326B1/en not_active Expired - Fee Related
-
2006
- 2006-06-09 JP JP2006161682A patent/JP2006257102A/ja active Pending
- 2006-08-31 CY CY20061101235T patent/CY1106152T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1042363B1 (fr) | 2006-06-21 |
| AU1568499A (en) | 1999-07-19 |
| US7022326B1 (en) | 2006-04-04 |
| BR9814473A (pt) | 2001-10-23 |
| EP1042363A1 (fr) | 2000-10-11 |
| AU1939799A (en) | 1999-07-19 |
| CY1106152T1 (el) | 2011-06-08 |
| MXPA00006263A (es) | 2003-07-14 |
| PT1042363E (pt) | 2006-11-30 |
| EP1041888A4 (en) | 2000-10-18 |
| WO1999033346A1 (en) | 1999-07-08 |
| EP1041888A1 (en) | 2000-10-11 |
| DK1042363T3 (da) | 2006-10-30 |
| ATE412006T1 (de) | 2008-11-15 |
| CA2316811A1 (en) | 1999-07-08 |
| FR2773156B1 (fr) | 2000-03-31 |
| JP2001527029A (ja) | 2001-12-25 |
| FR2773156A1 (fr) | 1999-07-02 |
| DE69840152D1 (de) | 2008-12-04 |
| WO1999033872A1 (fr) | 1999-07-08 |
| ATE330970T1 (de) | 2006-07-15 |
| JP2006257102A (ja) | 2006-09-28 |
| EP1975173A1 (en) | 2008-10-01 |
| DE69835031T2 (de) | 2007-01-18 |
| ES2267199T3 (es) | 2007-03-01 |
| DE69835031D1 (de) | 2006-08-03 |
| EP1041888B1 (en) | 2008-10-22 |
| US6420141B1 (en) | 2002-07-16 |
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