ITRM20090558A1 - PROCEDURE FOR THE PRODUCTION OF IMMUNOGLOBULINES EXTRACTED FROM HUMAN PLASMA FOR THERAPEUTIC USE NEUTRALIZING THE VIRUS OF EPSTEIN BARR AND DRUG CONTAINING DETTE IMMUNOGLOBULINE - Google Patents
PROCEDURE FOR THE PRODUCTION OF IMMUNOGLOBULINES EXTRACTED FROM HUMAN PLASMA FOR THERAPEUTIC USE NEUTRALIZING THE VIRUS OF EPSTEIN BARR AND DRUG CONTAINING DETTE IMMUNOGLOBULINE Download PDFInfo
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- ITRM20090558A1 ITRM20090558A1 IT000558A ITRM20090558A ITRM20090558A1 IT RM20090558 A1 ITRM20090558 A1 IT RM20090558A1 IT 000558 A IT000558 A IT 000558A IT RM20090558 A ITRM20090558 A IT RM20090558A IT RM20090558 A1 ITRM20090558 A1 IT RM20090558A1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum
- C07K16/065—Purification, fragmentation
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/081—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from DNA viruses
- C07K16/085—Herpetoviridae, e.g. pseudorabies virus, Epstein-Barr virus
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- 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
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- Animal Behavior & Ethology (AREA)
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
DESCRIZIONE DESCRIPTION
dell'invenzione industriale dal titolo: of the industrial invention entitled:
PROCEDIMENTO PER LA PRODUZIONE DI IMMUNOGLOBULINE ESTRATTE DA PLASMA UMANO, AD USO TERAPEUTICO, NEUTRALIZZANTI IL VIRUS DI EPSTEIN-BARR, E FARMACO CONTENENTE DETTE IMMUNOGLOBULINE PROCEDURE FOR THE PRODUCTION OF IMMUNOGLOBULINS EXTRACTED FROM HUMAN PLASMA, FOR THERAPEUTIC USE, NEUTRALIZING THE EPSTEIN-BARR VIRUS, AND DRUG CONTAINING THESE IMMUNOGLOBULINS
TESTO DELLA DESCRIZIONE TEXT OF THE DESCRIPTION
L'invenzione concerne il settore delle immunoglobuline e dei farmaci da essi derivanti. The invention relates to the field of immunoglobulins and drugs deriving from them.
Più in dettaglio riguarda un procedimento per la produzione di immunoglobuline neutralizzanti il virus di EPSTEIN-BARR, estratte da plasma umano. More in detail, it concerns a process for the production of immunoglobulins neutralizing the EPSTEIN-BARR virus, extracted from human plasma.
E’ noto come, sin dagli anni ’60, il virus di EPSTEIN-BARR sia considerato l’agente patogeno associato a molte e diverse patologie, dalla mononucleosi infettiva a gravi patologie neoplastiche come il linfoma di Burkitt, il linfoma di Hodgkin, altre rare malattie ematologiche come la X-linked lymphoproliferative disorder, carcinomi come quello naso-faringeo, della mammella, l’epatocarcinoma, tumori mesenchimali ed altro. It is known that, since the 1960s, the EPSTEIN-BARR virus has been considered the pathogen associated with many and different pathologies, from infectious mononucleosis to serious neoplastic pathologies such as Burkitt's lymphoma, Hodgkin's lymphoma, others rare haematological diseases such as X-linked lymphoproliferative disorder, carcinomas such as nasopharyngeal, breast, hepatocarcinoma, mesenchymal tumors and more.
E’ altresì noto come, in tempi più recenti, la presenza del virus di EPSTEIN-BARR nell’ organismo umano sia stata messa in relazione all’insorgenza di patologie autoimmuni quali l’artrite reumatoide, il lupus eritematoso, la sindrome di Sjogren, la miastenia gravis, la sclerosi multipla ed altre. It is also known how, in more recent times, the presence of the EPSTEIN-BARR virus in the human organism has been linked to the onset of autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, Sjogren's syndrome, myasthenia gravis, multiple sclerosis and others.
Risulta quindi logico ritenere che, essendo il virus di EPSTEIN-BARR. associato all’insorgenza .di patologie neoplastiche ed autoimmmrr che si manifestano quando un soggetto geneticamente predisposto sviluppa l’infezione, adeguati farmaci antivirali, atti a combatterne la presenza nell’organismo, potrebbero consentire il trattamento delle patologie ad esso correlate. It is therefore logical to assume that, being the EPSTEIN-BARR. associated with the onset of neoplastic and autoimmmrr pathologies that occur when a genetically predisposed subject develops the infection, adequate antiviral drugs, designed to fight their presence in the body, could allow the treatment of the pathologies related to it.
Diversamente da altri virus patogeni, per il virus di EPSTEIN-BARR non esistono antivirali specifici in grado di prevenirne la diffusione o contrastarne efficacemente la sintomatologia a contagio avvenuto, ed inoltre, fra tutti gli Herpesvirus, l’EPSTEIN BARR è quello più resistente alla terapia con composti analoghi della guanosina. Unlike other pathogenic viruses, for the EPSTEIN-BARR virus there are no specific antivirals able to prevent its spread or effectively counteract its symptoms after contagion, and moreover, of all the Herpesviruses, EPSTEIN BARR is the most resistant to therapy. with analogous compounds of guanosine.
E’ scopo della presente invenzione il superamento di tali mancanze. Lo scopo è raggiunto per mezzo di un procedimento per la produzione di immunoglobuline estratte da plasma umano, ad uso terapeutico, neutralizzanti il virus di EPSTEIN-BARR, comprendente le fasi di: The purpose of the present invention is to overcome these shortcomings. The purpose is achieved by means of a process for the production of immunoglobulins extracted from human plasma, for therapeutic use, neutralizing the EPSTEIN-BARR virus, comprising the steps of:
- eseguire primi esami diagnostici, atti all’identificazione di unità di sangue positive all’infezione da virus di EPSTEIN-BARR; - perform initial diagnostic tests, aimed at identifying blood units positive for EPSTEIN-BARR virus infection;
- eseguire successivi esami diagnostici, sulle unità di sangue positive al virus, atti al rilevamento degli anticorpi neutralizzanti il medesimo; - perform subsequent diagnostic tests, on the blood units positive to the virus, aimed at detecting antibodies neutralizing the same;
- realizzare un processo di selezione delle unità ematiche contenenti titoli elevati dei suddetti anticorpi neutralizzanti; - carry out a selection process of the blood units containing high titers of the aforementioned neutralizing antibodies;
- realizzare un processo di estrazione, da dette unità ematiche, di immunoglobuline iperimmuni, ad alta concentrazione di anticorpi neutralizzanti il virus di EPSTEIN-BARR. - carry out a process of extraction, from said blood units, of hyperimmune immunoglobulins, with a high concentration of antibodies neutralizing the EPSTEIN-BARR virus.
Secondo un ulteriore aspetto dell’ invenzione, il procedimentoproduttivo prevede l’ulteriore fase di: According to a further aspect of the invention, the production process involves the further phase of:
- realizzare un processo di estrazione, dalle suddette immunoglobuline iperimmuni, di immunoglobuline specifiche, contenenti pressoché esclusivamente anticorpi neutralizzanti il virus. - carry out a process of extraction, from the aforementioned hyperimmune immunoglobulins, of specific immunoglobulins, containing almost exclusively antibodies neutralizing the virus.
Il trovato presenta i seguenti vantaggi: The invention has the following advantages:
- permette di rendere disponibili immunoglobuline specifiche per il trattamento delle patologie correlate al virus di EPSTEIN-BARR; - permette la realizzazione di farmaci adatti alla prevenzione dell’infezione da virus di EPSTEIN-BARR nei soggetti a rischio di contagio; - makes it possible to make specific immunoglobulins available for the treatment of pathologies related to the EPSTEIN-BARR virus; - allows the creation of drugs suitable for the prevention of EPSTEIN-BARR virus infection in subjects at risk of contagion;
- permette la realizzazione di farmaci adatti al trattamento della mononucleosi infettiva e delle sue complicanze come l’epatite da virus di EPSTEIN-BARR. - allows the creation of drugs suitable for the treatment of infectious mononucleosis and its complications such as EPSTEIN-BARR virus hepatitis.
- permette la realizzazione di farmaci adatti al trattamento delle patologie associate al virus di EPSTEIN-BARR (artrite reumatoide, lupus eritematoso sistemico, sindrome di Sjogren, miastenia gravis, sclerosi multipla); - allows the development of drugs suitable for the treatment of pathologies associated with the EPSTEIN-BARR virus (rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, myasthenia gravis, multiple sclerosis);
- permette la realizzazione di farmaci adatti al trattamento delle neoplasie associate al virus di EPSTEIN-BARR, sia nei soggetti immunocompetenti (linfoma di Burkitt, linfoma di Hodgkin, carcinoma naso-faringeo, carcinomi linfoepiteliali delle ghiandole salivari, del timo, dei polmoni e dello stomaco, carcinoma della mammella, carcinoma epatocellulare, sarcoma a cellule dendritiche follicolari) sia in pazienti con immunodeficienze congenite ed acquisite (linfomi B associati ad AIDS, malattia linfoproliferativa . post trapianto, granulomatosi linfomatoide, linfoma B associato a terapia con methotrexate, linfomi B associati a immunodeficienza severa combinata, a sindrome di Wiskott Aldrich, a disordine linfoproliferativo X-linked, leiomiosarcoma). - allows the development of drugs suitable for the treatment of neoplasms associated with the EPSTEIN-BARR virus, both in immunocompetent subjects (Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma, lymphoepithelial carcinomas of the salivary glands, thymus, lungs and stomach, breast cancer, hepatocellular carcinoma, follicular dendritic cell sarcoma) and in patients with congenital and acquired immunodeficiencies (AIDS-associated B lymphomas, post-transplant lymphoproliferative disease, lymphomatoid granulomatosis, B lymphoma associated with methotrexate therapy, associated B lymphomas at combined severe immunodeficiency, at Wiskott Aldrich's syndrome, at X-linked lymphoproliferative disorder, leiomyosarcoma).
Conformemente all’invenzione, la metodica produttiva oggetto del presente brevetto prevede l’esecuzione di esami diagnostici atti ad identificare con certezza unità di sangue positive all’infezione da virus di EPSTEIN-BARR, attraverso il rilevamento nelle medesime degli anticorpi specifici di tale virus. In accordance with the invention, the production method covered by this patent provides for the execution of diagnostic tests to identify with certainty units of blood positive for EPSTEIN-BARR virus infection, by detecting specific antibodies of this virus in the same.
Successivamente, attraverso esami basati sul micro-test quantitativo di Rocchi-Hewetson, sulla tecnica ELISA, o su test rapidi a citometria di flusso, eseguiti sulle unità di sangue positive al virus, vengono identificate le unità ematiche dotate della maggiore capacità di neutralizzazione del Subsequently, through tests based on the Rocchi-Hewetson quantitative micro-test, on the ELISA technique, or on rapid flow cytometry tests, performed on the virus-positive blood units, the blood units with the greatest capacity to neutralize the virus are identified.
suddetto virus. aforementioned virus.
Detta capacità di neutralizzazione è dovuta alla presenza, nelle unità ematiche, di anticorpi specifici contro gli antigeni del virus localizzati This neutralization capacity is due to the presence, in the blood units, of specific antibodies against localized virus antigens
sull’envelope virale e sulla superficie dei linfociti B infettati durante la fase litica dello stesso, ovvero le glicoproteine classificate, in base al loro peso molecolare, come gp350, gp340, gp270, gp85, e gp42, l’antigene BMRF-2 e altri antigeni rilevanti per la capacità neutralizzante delle rispettive immunoglobuline. on the viral envelope and on the surface of the B lymphocytes infected during the lytic phase of the same, or the glycoproteins classified, based on their molecular weight, as gp350, gp340, gp270, gp85, and gp42, the BMRF-2 antigen and others antigens relevant to the neutralizing capacity of the respective immunoglobulins.
Vengono quindi selezionate le unità ematiche contraddistinte dalla presenza di titoli elevati dei suddetti anticorpi neutralizzanti e da tali uhità ematiche vengono estratte, attraverso il frazionamento con etanolo a freddo previsto dalla metodica Cohn-Oncley, immunoglobuline iperimmuniy-ad alta concentrazione di anticorpi neutralizzanti il virus di EPSTEIN-BARR. The blood units characterized by the presence of high titers of the aforementioned neutralizing antibodies are then selected and from these blood units are extracted, through the fractionation with cold ethanol provided by the Cohn-Oncley method, hyperimmune immunoglobulins - with a high concentration of antibodies neutralizing the virus. EPSTEIN-BARR.
Alternativamente potranno essere utilizzati metodi di frazionamento come la crioprecipitazione, oppure tecniche cromatografiche come la gel precipitazione, la cromatografia a scambio ionico e la cromatografia di affinità. Alternatively, fractionation methods such as cryoprecipitation can be used, or chromatographic techniques such as gel precipitation, ion exchange chromatography and affinity chromatography.
Per quanto riguarda gli aspetti di sicurezza, saranno utilizzate le raccomandazioni espresse dall’Organizzazione Mondiale della Sanità in tema di frazionamento del plasma umano. With regard to safety aspects, the recommendations expressed by the World Health Organization on the fractionation of human plasma will be used.
Da tali immunoglobuline iperimmuni potranno poi essere eventualmente ricavate, sfruttando le proteine virali gp350, gp340, gp270, gp85, gp42, BMRF-2 (o altri antigeni rilevanti per la capacità neutralizzante delle immunoglobuline) come leganti delle suddette in colonne cromatografiche, immunoglobuline specifiche, contenenti pressoché esclusivamente anticorpi neutralizzanti il virus. From these hyperimmune immunoglobulins they can then possibly be obtained, exploiting the viral proteins gp350, gp340, gp270, gp85, gp42, BMRF-2 (or other antigens relevant for the neutralizing capacity of the immunoglobulins) as binders of the aforementioned in chromatographic columns, specific immunoglobulins, containing almost exclusively antibodies neutralizing the virus.
Le immunoglobuline estrattive iperimmuni, e le immunoglobuline estrattive specifiche, prodotte attraverso il suesposto procedimento, dotate di livelli di efficacia proporzionali ài quantitativi di anticorpi neutralizzanti in esse contenuti, potranno essere somministrate ai pazienti come di consueto per via endovenosa, per via intramuscolare, per via sottocutanea oppure per via locale nel trattamento delle infezioni da virus di EPSTEIN-BARR e delle patologie ad esso correlate. The hyperimmune extractive immunoglobulins, and the specific extractive immunoglobulins, produced through the above procedure, with efficacy levels proportional to the quantities of neutralizing antibodies contained in them, can be administered to patients as usual intravenously, intramuscularly, via subcutaneously or locally in the treatment of EPSTEIN-BARR virus infections and related pathologies.
Naturalmente, fermo restando il principio del trovato, le forme di realizzazione dello stesso potranno essere ampiamente variate rispetto a quanto descritto, senza per questo uscire dalfambitò della presente invenzione. Naturally, the principle of the invention remaining the same, the embodiments of the same may be varied widely with respect to what has been described, without thereby departing from the scope of the present invention.
Claims (1)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT000558A ITRM20090558A1 (en) | 2009-11-03 | 2009-11-03 | PROCEDURE FOR THE PRODUCTION OF IMMUNOGLOBULINES EXTRACTED FROM HUMAN PLASMA FOR THERAPEUTIC USE NEUTRALIZING THE VIRUS OF EPSTEIN BARR AND DRUG CONTAINING DETTE IMMUNOGLOBULINE |
| PCT/IT2010/000434 WO2011055398A1 (en) | 2009-11-03 | 2010-10-27 | A process for the production of immunoglobulines extracted from human plasma for therapeutic use, for the neutralization of the epstein-barr virus, and the medicine containing said immunoglobulins" |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT000558A ITRM20090558A1 (en) | 2009-11-03 | 2009-11-03 | PROCEDURE FOR THE PRODUCTION OF IMMUNOGLOBULINES EXTRACTED FROM HUMAN PLASMA FOR THERAPEUTIC USE NEUTRALIZING THE VIRUS OF EPSTEIN BARR AND DRUG CONTAINING DETTE IMMUNOGLOBULINE |
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| Publication Number | Publication Date |
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| ITRM20090558A1 true ITRM20090558A1 (en) | 2011-05-04 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0764658A1 (en) * | 1995-09-22 | 1997-03-26 | Rotkreuzstiftung Zentrallaboratorium Blutspendedienst Srk | Process for obtaining immunoglobulins from fractions originating from the fractionation of human blood plasma |
| WO2007017859A1 (en) * | 2005-08-11 | 2007-02-15 | Omrix Biopharmaceuticals Ltd. | Intravenous immunoglobulin composition |
| WO2007078202A1 (en) * | 2006-01-03 | 2007-07-12 | Tto Nord As | Preparation useful for, and method for treatment of neonatal alloimmune thrombocytopenia (nait) |
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| WO2011055398A1 (en) | 2011-05-12 |
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