BRPI0513024A - processo para a preparação e uso de uma vacina bivalente contra vìcio de morfina-heroìna - Google Patents
processo para a preparação e uso de uma vacina bivalente contra vìcio de morfina-heroìnaInfo
- Publication number
- BRPI0513024A BRPI0513024A BRPI0513024-7A BRPI0513024A BRPI0513024A BR PI0513024 A BRPI0513024 A BR PI0513024A BR PI0513024 A BRPI0513024 A BR PI0513024A BR PI0513024 A BRPI0513024 A BR PI0513024A
- Authority
- BR
- Brazil
- Prior art keywords
- morphine
- heroin addiction
- heroin
- bivalent
- formulations
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1267—Gram-positive bacteria
- C07K16/1282—Clostridium (G)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
-
- 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
- A61K39/0013—Therapeutic immunisation against small organic molecules, e.g. cocaine, nicotine
-
- 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
- A61K39/02—Bacterial antigens
- A61K39/08—Clostridium, e.g. Clostridium tetani
-
- 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
- A61K39/385—Haptens or antigens, bound to carriers
-
- 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
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/646—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
-
- 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
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- 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
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
-
- 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
- A61K2039/575—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 humoral response
-
- 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
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6037—Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
-
- 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
- A61K2039/70—Multivalent vaccine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- 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
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/141111—Diverse hetero atoms in same or different rings [e.g., alkaloids, opiates, etc.]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Neurology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Toxicology (AREA)
- Neurosurgery (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Abstract
PROCESSO PARA A PREPARAçãO E USO DE UMA VACINA BIVALENTE CONTRA VìCIO DE MORFINA-HEROìNA. A presente invenção refere-se a um projeto estrutural, métodos preparativos e composição química de duas formulações estruturais de vacinas bivalentes contra vício de morfina-heroína (morfina-6-hemissuccinil-EDC-TFCS-toxóide do tétano e 3-O-carboximetilmorfina-EDC-TFCS-toxóide do tétano). Essas vacinas são adequadas para uso humano onde elas são capazes de disparar a síntese de anticorpos policlonais contra opiato morfina e seu análogo estrutural, heroína, através da administração in vivo repetida dessas formulações, em protocolos de vacinação ativa, em estudos pré-clínicas em roedores. O paradigma de vacinação ativa através do qual esses imunógenos disparam uma resposta imune humoral consolidada com uma memória imunológica de longo prazo, caracterizada pela presença de altos títulos de anticorpos específicos contra essas duas drogas de abuso, é também descrito. Ainda, a presente invenção revela a eficácia dessas formulações conjugadas para disparar uma imunoproteção sustentada contra vício de morfina e heroína usando um paradigma de auto-administração intravenosa dessas suas substâncias opiato no roedor. Finalmente, é realizada também uma discussão sobre o uso futuro potencial desses imunoconjugados em protocolos de vacinação ativa para tratamento de vício de ambas morfina e heroína nos humanos.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| MXPA04006617A MXPA04006617A (es) | 2004-07-07 | 2004-07-07 | Proceso para la preparacion y uso de una vacuna bivalente contra la adiccion a la morfina-heroina. |
| PCT/MX2005/000049 WO2006004390A2 (es) | 2004-07-07 | 2005-07-05 | Proceso para la preparación y uso de una vacuna bivalente contra la adicción a la morfina-heroína |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0513024A true BRPI0513024A (pt) | 2008-04-22 |
Family
ID=35431510
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0513024-7A BRPI0513024A (pt) | 2004-07-07 | 2005-07-05 | processo para a preparação e uso de uma vacina bivalente contra vìcio de morfina-heroìna |
Country Status (15)
| Country | Link |
|---|---|
| US (4) | US8008457B2 (pt) |
| EP (1) | EP1767221B1 (pt) |
| AR (1) | AR049962A1 (pt) |
| BR (1) | BRPI0513024A (pt) |
| CA (1) | CA2573042C (pt) |
| CU (1) | CU23917B1 (pt) |
| CY (1) | CY1114673T1 (pt) |
| DK (1) | DK1767221T3 (pt) |
| ES (1) | ES2435769T3 (pt) |
| MX (1) | MXPA04006617A (pt) |
| PE (1) | PE20060377A1 (pt) |
| PL (1) | PL1767221T3 (pt) |
| PT (1) | PT1767221E (pt) |
| SI (1) | SI1767221T1 (pt) |
| WO (1) | WO2006004390A2 (pt) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA04006617A (es) | 2004-07-07 | 2006-01-12 | Inst Nac De Psiquiatria Ramon | Proceso para la preparacion y uso de una vacuna bivalente contra la adiccion a la morfina-heroina. |
| US8170546B2 (en) | 2006-03-22 | 2012-05-01 | Broadcom Corporation | Client device characterization of other client device transmissions and reporting of signal qualities to access point(s) |
| EP1982729A1 (en) * | 2007-04-20 | 2008-10-22 | Cytos Biotechnology AG | Vaccination Regimen for B-Cell Vaccines |
| EP2482838A4 (en) * | 2009-09-30 | 2013-04-10 | Toxcure Inc | USE OF BOTULINUM NEUROTOXIN FOR THE TREATMENT OF SUBSTANCE DEPENDENCE |
| CN102002049B (zh) * | 2010-10-12 | 2013-01-02 | 北京大学 | 一种抗原及其制备方法与应用 |
| CN102539764A (zh) * | 2010-12-27 | 2012-07-04 | 北京库尔科技有限公司 | 盐酸哌替啶检测试剂盒及其制备方法 |
| EP2717057A1 (en) * | 2012-10-04 | 2014-04-09 | Cisbio Bioassays | Morphine-6-glucuronide derivatives, immunogens and immunoassay |
| RU2526807C2 (ru) * | 2012-11-28 | 2014-08-27 | Общество с ограниченной ответственностью "ДИАМЕДИКА" ООО "ДИАМЕДИКА" | Синтетический иммуноген для защиты от токсического действия наркотических и психоактивных веществ |
| US9127008B2 (en) | 2013-03-15 | 2015-09-08 | Johnson Matthey Public Limited Company | Morphine sulfate methanolic solvate, processes for making same and related compositions and methods for treating pain |
| US10262505B1 (en) * | 2013-12-03 | 2019-04-16 | Ca, Inc. | Anti-skimming solution |
| US11305010B2 (en) | 2016-01-21 | 2022-04-19 | The Scripps Research Institute | Synthetic opioid vaccine |
| WO2019094528A1 (en) | 2017-11-09 | 2019-05-16 | The Scripps Research Institute | An improved heroin vaccine |
| WO2020012245A1 (en) | 2018-07-13 | 2020-01-16 | Alkermes Pharma Ireland Limited | Thienothiophene-naltrexone prodrugs for long-acting injectable compositions |
| US10799496B2 (en) | 2018-07-13 | 2020-10-13 | Alkermes Pharma Ireland Limited | Naphthylenyl compounds for long-acting injectable compositions and related methods |
| US10975099B2 (en) | 2018-11-05 | 2021-04-13 | Alkermes Pharma Ireland Limited | Thiophene compounds for long-acting injectable compositions and related methods |
| RU2703494C1 (ru) * | 2018-11-12 | 2019-10-18 | Федеральное государственное унитарное предприятие "Государственный научно-исследовательский институт особо чистых биопрепаратов" Федерального медико-биологического агентства | Моноклональное антитело 6g1 к производным морфина |
| WO2024238822A1 (en) * | 2023-05-17 | 2024-11-21 | Regents Of The University Of Minnesota | Heroin vaccine compositions and methods thereof |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH678394A5 (pt) * | 1990-08-22 | 1991-09-13 | Cerny Erich H | |
| US6210677B1 (en) * | 1993-01-29 | 2001-04-03 | Robert C. Bohannon | Method to reduce the physiologic effects of drugs on mammals |
| ATE362380T1 (de) | 1995-03-31 | 2007-06-15 | Xenova Res Ltd | Hapten-träger-konjugate zur anwendung in der drogen-missbrauchs-therapie |
| US20020032316A1 (en) * | 1995-03-31 | 2002-03-14 | Cantab Pharmaceuticals Research Limited | Hapten-carrier conjugates for use in drug-abuse therapy and methods for preparation of same |
| US5876727A (en) * | 1995-03-31 | 1999-03-02 | Immulogic Pharmaceutical Corporation | Hapten-carrier conjugates for use in drug-abuse therapy and methods for preparation of same |
| CN1069544C (zh) | 1998-04-24 | 2001-08-15 | 昆明市生物技术工程研究中心 | 人用阿片类毒品戒毒疫苗 |
| AU2004215125B2 (en) * | 2003-02-26 | 2011-01-06 | Institute For Research In Biomedicine | Monoclonal antibody production by EBV transformation of B cells |
| MXPA04006617A (es) | 2004-07-07 | 2006-01-12 | Inst Nac De Psiquiatria Ramon | Proceso para la preparacion y uso de una vacuna bivalente contra la adiccion a la morfina-heroina. |
-
2004
- 2004-07-07 MX MXPA04006617A patent/MXPA04006617A/es active IP Right Grant
-
2005
- 2005-07-05 SI SI200531802T patent/SI1767221T1/sl unknown
- 2005-07-05 ES ES05761917T patent/ES2435769T3/es not_active Expired - Lifetime
- 2005-07-05 DK DK05761917.3T patent/DK1767221T3/da active
- 2005-07-05 PE PE2005000780A patent/PE20060377A1/es active IP Right Grant
- 2005-07-05 BR BRPI0513024-7A patent/BRPI0513024A/pt not_active Application Discontinuation
- 2005-07-05 PL PL05761917T patent/PL1767221T3/pl unknown
- 2005-07-05 WO PCT/MX2005/000049 patent/WO2006004390A2/es not_active Ceased
- 2005-07-05 EP EP05761917.3A patent/EP1767221B1/en not_active Expired - Lifetime
- 2005-07-05 PT PT57619173T patent/PT1767221E/pt unknown
- 2005-07-05 AR ARP050102788A patent/AR049962A1/es not_active Application Discontinuation
- 2005-07-05 US US11/632,085 patent/US8008457B2/en not_active Expired - Fee Related
- 2005-07-05 CA CA2573042A patent/CA2573042C/en not_active Expired - Lifetime
-
2007
- 2007-01-05 CU CU2007000002A patent/CU23917B1/es active IP Right Grant
-
2011
- 2011-07-14 US US13/182,634 patent/US8357375B2/en not_active Expired - Fee Related
-
2012
- 2012-12-10 US US13/709,507 patent/US8916170B2/en not_active Expired - Lifetime
-
2013
- 2013-11-20 CY CY20131101023T patent/CY1114673T1/el unknown
-
2014
- 2014-11-06 US US14/535,007 patent/US20150064212A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20130236478A1 (en) | 2013-09-12 |
| ES2435769T3 (es) | 2013-12-23 |
| WO2006004390A3 (es) | 2006-09-21 |
| PE20060377A1 (es) | 2006-05-05 |
| WO2006004390A2 (es) | 2006-01-12 |
| CA2573042A1 (en) | 2006-01-12 |
| AR049962A1 (es) | 2006-09-20 |
| CU23917B1 (es) | 2013-07-31 |
| EP1767221B1 (en) | 2013-08-21 |
| US20150064212A1 (en) | 2015-03-05 |
| CY1114673T1 (el) | 2016-10-05 |
| US8357375B2 (en) | 2013-01-22 |
| US20110318381A1 (en) | 2011-12-29 |
| CA2573042C (en) | 2013-01-15 |
| US8008457B2 (en) | 2011-08-30 |
| MXPA04006617A (es) | 2006-01-12 |
| PT1767221E (pt) | 2013-11-27 |
| PL1767221T3 (pl) | 2014-02-28 |
| SI1767221T1 (sl) | 2014-01-31 |
| DK1767221T3 (da) | 2013-11-25 |
| CU20070002A7 (es) | 2009-09-08 |
| US20080241183A1 (en) | 2008-10-02 |
| EP1767221A2 (en) | 2007-03-28 |
| US8916170B2 (en) | 2014-12-23 |
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