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WO2009066131A1 - Procédés de préparation de vaccins, de nécessaires de laboratoire et de composants thérapeutiques - Google Patents

Procédés de préparation de vaccins, de nécessaires de laboratoire et de composants thérapeutiques Download PDF

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Publication number
WO2009066131A1
WO2009066131A1 PCT/IB2007/054691 IB2007054691W WO2009066131A1 WO 2009066131 A1 WO2009066131 A1 WO 2009066131A1 IB 2007054691 W IB2007054691 W IB 2007054691W WO 2009066131 A1 WO2009066131 A1 WO 2009066131A1
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WIPO (PCT)
Prior art keywords
rbcs
kits
vaccines
patients
group
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Application number
PCT/IB2007/054691
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English (en)
Inventor
Mahmoud Rafea
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Mahmoud Rafea
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Application filed by Mahmoud Rafea filed Critical Mahmoud Rafea
Priority to PCT/IB2007/054691 priority Critical patent/WO2009066131A1/fr
Publication of WO2009066131A1 publication Critical patent/WO2009066131A1/fr

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/0005Vertebrate antigens
    • A61K39/0008Antigens related to auto-immune diseases; Preparations to induce self-tolerance
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/0005Vertebrate antigens
    • A61K39/0011Cancer antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/02Bacterial antigens
    • A61K39/04Mycobacterium, e.g. Mycobacterium tuberculosis
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/564Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56911Bacteria
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G01N33/57488Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds identifable in body fluids
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/80Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood groups or blood types or red blood cells
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/24Immunology or allergic disorders
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/24Immunology or allergic disorders
    • G01N2800/245Transplantation related diseases, e.g. graft versus host disease

Definitions

  • RBCs' absorbed antigens will reach the central organ of the immune system (e.g., thymus and bone marrow) and induce central tolerance.
  • the degree of induced tolerance is dependant on the size of the RBCs antigens store. In effect, the larger the size of the store, the higher is the probability these antigens meet their corresponding premature lymphocytes in thymus and bone marrow with consequent induction of their apoptosis.
  • Antigens are tolerated as far as there are enough stores of those antigens in RBCs. In this way, the degree of immune response to a particular antigen may vary.
  • the immune system distinguishes between what is self and what is non- self (foreign body): tolerates self antigens and responds to non-self antigens.
  • the phenomenon of tolerating antigens is called immune tolerance or simply tolerance. It can be defined as "a specific unresponsive state induced by prior exposure to an antigen which is due to either a programmed failure of the immune system or active suppression.” Tolerance is a basic function of the immune system that is important to maintain body integrity and health.
  • tolerance to self antigens is a process that continues throughout life but begins during fetal development.
  • There are a number of mechanisms that describe how tolerance occurs which can be classified into: central, peripheral, and anergy.
  • central tolerance immature self -reactive T lymphocytes recognize antigens in the thymus and undergo negative selection (deletion).
  • peripheral tolerance mature self- reactive T lymphocytes that escape central tolerance and recognize self antigens in peripheral tissues can be inactivated (anergy), killed (deletion) or regulated (suppressed).
  • anergy mature self-reactive lymphocytes do not respond to antigens in non-inflamed environment. Those mechanisms are explained through the following theories: clonal deletion, clonal anergy, clonal ignorance, receptor editing, and suppressor cells.
  • RBCs are specialized for transport. Besides, RBCs have pinocytic activity which is well documented. Their cell membrane antigens can function as receptors, e.g., Duffy antigen has been proved to act as a receptor for Plasmodium vivax malaria to invade RBCs. Consequently, RBCs easily absorb soluble antigens through pinocytosis while particulate antigen need receptor sites on RBCs in order to be absorbed. [26] It is important that the discovered function of RBCs fill a gap in understanding of tolerance. Notice that there is a general agreement about this gap. Part of this gap can be expressed in the following questions:
  • Blood samples were taken on heparin.
  • the lymphocytes were separated using the Ficoll hypaque technique.
  • the RBCs were then separated to prepare the hemolysate.
  • the hemolysate is prepared by washing RBCs in phosphate buffer saline several times, and then frozen until RBCs are ruptured.
  • the fourth is used to detect male spouse HLA antigens in female spouse hemolysate
  • the first and second trays are used for typing of HLA Class I for the couple.
  • mice • A number of white mice were slaughtered to collect their blood on sodium citrate and their organs (liver, kidney and spleen) were preserved on 10 % formalin.
  • RBCs were injected subcutaneously into a number of rabbits for four times on weekly intervals.
  • mice were infected by Escherichia coli 0157 through subcutaneous injection. • Mice were slaughtered after 5 days to collect their blood on sodium citrate.
  • Rabbits were vaccinated by those RBCs. Rabbits were injected subcu- taneously with one ml on weekly basis for three weeks.
  • EBI European Bioinformatics Institute
  • NH American National Institute of Health
  • HPO Human Proteome Organization
  • DM Data Mining in locally built database: DM can be targeted towards the identification of RBCs' proteins related to a particular disease or towards the identification of RBCs' proteins that are missing in a particular disease. Notice that in disorders that are caused by microorganisms, DM may not be essential.
  • the invention of new generation of microorganisms' vaccines depends on identifying antigen(s) in RBCs of patients or animals, which belong(s) to a particular microorganism. Antibodies against those antigens will be used in the diagnosis of their corresponding diseases' conditions. Those antibodies can be prepared to be used as passive vaccines, too. In this regard, new technologies, such as Affibody, can be efficiently used to replace natural antibodies.
  • Example 1 Preparing a vaccine and diagnostic kits for Tuberculosis
  • Mycobacterium tuberculosis is the causative microorganism of tuberculosis disease.
  • Collecting blood samples from patients suffering from tuberculosis will enable the identifications of protein(s) related to M. tuberculosis in the samples' RBCs. This is done through the following steps:
  • step 2 Use protein(s) identified in step 2 to query public databases.
  • the dose and the number of injections that can make an individual immune are to be determined. Also, the interpretation of the titer of the antigen(s) that indicates active TB, immunity, or exposure is to be determined.
  • the monoclonal antibodies against this active vaccine can be packaged as kits suitable for different laboratory equipment (e.g., ELISA, Flowcytometry, etc.).
  • Example 2 Preparing vaccines and diagnostic kits for a malignant tumor
  • Every type of malignancy has its specific tissue antigens.
  • a group of tumors may share (a) specific tissue antigen(s). Consequently, collecting blood samples from patients suffering from the same type of tumor will enable the identification of malignancy antigen(s) of that tumor. The use of data mining will be very helpful. It will enable the identification of malignant tissue antigens that are shared between a group of tumors. If the proteome of the malignant tumor is known, then steps similar to "Example I" can be applied. Consequently, the steps done are:
  • the monoclonal antibodies against this active vaccine can be packaged as diagnostic kits suitable for different laboratory equipment (e.g., ELISA, Flowcytometry, etc.).
  • diagnostic kits suitable for different laboratory equipment e.g., ELISA, Flowcytometry, etc.
  • Example 3 Preparing diagnostic kits and treatment components for autoimmune disorders and chronic rejection syndrome
  • step 2 Use proteins identified in step 2 to query public databases so that tissues or organs of these proteins may be determined.
  • FIG. 1 depicts the methods of preparing different products for humans. These methods can be described in the following steps:
  • the main resource is the RBCs samples of patients and normal individuals.
  • the sample proteome is stored in the local database.
  • the proteins that are found in a particular disease are used to query external databases storing human proteomes, microorganism proteomes, and other proteomes.
  • the disease related proteins are used in methods of antibodies preparation and vaccine preparation.
  • the proteins that are found in normal individuals and identified are used in methods of antibody preparation and component preparation.
  • Diagnostic kits are produced using prepared antibodies, if proteins exist in RBCs of patients. If proteins do not exist in patients and exist in normal individual, diagnostic kits are prepared from prepared components to detect circulating antibodies.
  • Fig. 2 depicts the methods of preparing different products for animals.
  • animals we mean the dictionary definition: "A multicellular organism of the kingdom Animalia, differing from plants in certain typical characteristics such as capacity for locomotion, nonphotosynthetic metabolism, pronounced response to stimuli, restricted growth, and fixed bodily structure.”
  • the sample proteome is stored in the local database.
  • the proteins that are found in a particular disease are used to query external databases storing microorganism proteomes.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Microbiology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Mycology (AREA)
  • Cell Biology (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Pulmonology (AREA)
  • Communicable Diseases (AREA)
  • Virology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Rehabilitation Therapy (AREA)
  • Hospice & Palliative Care (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne des procédés de production d'un certain nombre de produits. Ces produits comprennent des vaccins, des nécessaires de laboratoire clinique et des composants thérapeutiques. Les produits vaccinaux comprennent des vaccins contre les bactéries, les virus et les parasites chez l'être humain et l'animal, ainsi que des vaccins prévenant la formation de tumeurs malignes chez des patients présentant une évolution maligne ou encore des vaccins constituant un traitement d'appoint chez des patients souffrant déjà d'une tumeur. Les nécessaires de laboratoire clinique comprennent des nécessaires de diagnostic permettant un diagnostic efficace de maladies provoquées par des micro-organismes chez l'homme et l'animal ; des nécessaires de diagnostic de tumeurs malignes ; des nécessaires de typage tissulaire pour les greffes d'organes ; et des nécessaires de suivi du rejet et de l'hypersensibilité en cas de greffe. Les composants thérapeutiques contribueront au traitement de troubles complexes, notamment, par exemple, les troubles d'hypersensibilité, le rejet de greffe chronique et les affections auto-immunes. En effet, les produits pouvant être obtenus sur la base de la présente découverte sont innombrables. Les procédés de l'invention sont fondés sur notre découverte d'une nouvelle fonction des globules rouges : leur capacité à transporter de façon sélective des auto-antigènes et antigènes étrangers.
PCT/IB2007/054691 2007-11-19 2007-11-19 Procédés de préparation de vaccins, de nécessaires de laboratoire et de composants thérapeutiques WO2009066131A1 (fr)

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PCT/IB2007/054691 WO2009066131A1 (fr) 2007-11-19 2007-11-19 Procédés de préparation de vaccins, de nécessaires de laboratoire et de composants thérapeutiques

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012059112A1 (fr) * 2010-11-01 2012-05-10 Mahmoud Abdel Wahed Rafea Développement de produits médicaux fondés sur une fonction nouvellement découverte des érythrocytes

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US6632599B1 (en) * 1997-12-19 2003-10-14 Dade Behring Marburg Gmbh Detection and determination of solid phase-associated factors
WO2006031544A2 (fr) * 2004-09-09 2006-03-23 New England Medical Center Hospitals, Inc. Methodes de detection d'agents pathogenes dans des erythrocytes

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US6632599B1 (en) * 1997-12-19 2003-10-14 Dade Behring Marburg Gmbh Detection and determination of solid phase-associated factors
WO2000014547A1 (fr) * 1998-09-04 2000-03-16 Powderject Research Limited Immunodiagnostics au moyen de procedes d'administration de particules
WO2006031544A2 (fr) * 2004-09-09 2006-03-23 New England Medical Center Hospitals, Inc. Methodes de detection d'agents pathogenes dans des erythrocytes

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012059112A1 (fr) * 2010-11-01 2012-05-10 Mahmoud Abdel Wahed Rafea Développement de produits médicaux fondés sur une fonction nouvellement découverte des érythrocytes

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