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WO2017065626A1 - Fabrication et utilisation d'œuf hyper-immun personnalisé dans le traitement du psoriasis - Google Patents

Fabrication et utilisation d'œuf hyper-immun personnalisé dans le traitement du psoriasis Download PDF

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Publication number
WO2017065626A1
WO2017065626A1 PCT/RO2016/000002 RO2016000002W WO2017065626A1 WO 2017065626 A1 WO2017065626 A1 WO 2017065626A1 RO 2016000002 W RO2016000002 W RO 2016000002W WO 2017065626 A1 WO2017065626 A1 WO 2017065626A1
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WIPO (PCT)
Prior art keywords
igy
patient
chickens
specific
psoriasis
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Ceased
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PCT/RO2016/000002
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English (en)
Inventor
Chiurciu CONSTANTIN
Chiurciu VIORICA
Lucica SIMA
Iuliana MIHAI
Victor Patrascu Ionel
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Romvac Co SA
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Romvac Co SA
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Priority to EP16716713.9A priority Critical patent/EP3362092A1/fr
Publication of WO2017065626A1 publication Critical patent/WO2017065626A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/02—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from eggs
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • 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

Definitions

  • This invention describes the production of Ovopach hyperimmune egg and proteins extracted from it for the personalized treatment of psoriasis patients.
  • Psoriasis is an autoimmune chronic, sometimes hereditary disease, affecting about 3% of people around the world, usually between the ages of 11 and 45 years. Psoriasis is considered an incurable disease. Treatments known so far have been used to control disease symptoms. The experts purport that the causes of psoriasis are unknown, but the disease is a result of excessive growth and multiplication of keratocytes, the cells in the deep layers of skin. Psoriasis is considered an autoimmune disease. In this case, T lymphocytes accidentally recognize the normal epidermal cells as being foreign antigens.
  • T lymphocytes activate the B lymphocytes transferring to them the negative image as negative information to the T lymphocyte negative and which, at the patterning of IgG antibodies, becomes positive image identical with the information on the IgY-idiotypic orally administered in people and prepared from chickens.
  • This invention refers to the preparation of the personalized hyperimmune egg Ovopach against the antigens prepared from pathogenic agents, modified opportunistic flora, cells different from normal from structural and antigenic point of view present in the pathological material sampled from the patient; the following step is that further lab assays should identify pathogenic germs and their antibiotic resistance.
  • the pathological product sampled from the skin wounds of patients can be considered a total immunological cell-microbial stimulus (1).
  • the immunogen is then prepared and administered in chicken.
  • immunoglobulins extracted from the yolk (IgY) of chickens immunized with specific antigens mixed with adjuvant QS21 these IgY must be specific, with direct effect against the pathogenic germs in the organism of the patient.
  • the Ovopach hyperimmune egg contains anti-anti-personalized pathogenic complex (AIAACPI) idiopathic antibodies which recognize the epitopes defined by the peptides in the personalized pathogenic product (15).
  • AIAACPI anti-anti-personalized pathogenic complex
  • the inactivated antigenic product mixed with adjuvant QS21 is used for the fast immunization of laying chickens. For this purpose, 24-50 weeks old chickens at high laying season are used. The inoculums is assessed depending on the total protein determined by spectrophotometer or Patrascu radial ID method (unreleased data). The isolation of pathogenic germs found in this pathologic product is carried out at the same time with immunization. Depending on the species of pathogenic germs, resistance or sensitivity to antibiotics, they can be used during treatment with personalized IgY.
  • the immune response of immunized chickens is daily monitored by highlighting IgY in egg yolk.
  • the specific qualitative and quantitative . immune response against the administered antigen shall be monitored.
  • the immune response of each and every chicken is different from the quantitative point of view.
  • Eggs are collected from chickens producing amounts of IgY higher than 1,500 OD by ELISA.
  • a mixture is performed from yolks of chickens with more than 1,500 OD in the egg by ELISA, from which IgY is immediately extracted by Patrascu method.
  • the extracted IgY is twenty times concentrated by tangential filtration.
  • the IgY concentration is determined by ELISA and diluted to the amount expressed in mg/dose depending on treatment.
  • the personalized IgY is sterilized by filtration through 0,45 ⁇ and 0,22 ⁇ Millipore filters.
  • Much more eggs can be collected in the following days, which can be used as such, freeze- dried as whole egg or immunoglobulin and/or purified proteins.
  • the anti idiotypic antibodies were first and independently described by Henry Kunkel and Jacques Oudin (1963). They both noticed that an animal immunized with an antigen generates an antibody response (Abl). If these Abl antibodies are isolated and inoculated in other naive animals, these animals produce anti Abl antibodies. These Ab2 antibodies are called anti- idiotypic antibodies because they recognize an epitope on Abl which is unique for Abl . Oudin noticed that the antigenic specificity of Abl tends to correlate with the idiotypic expression of Abl. In other words, various antibodies were defined as Abl -specific antibodies or a group of Abl antibodies linked to a specific antigen.
  • Ab2a and Ab2 ⁇ Two types of Ab2, namely Ab2a and Ab2 ⁇ , if Ab2 was capable of binding to Abl in the presence of the antigen.
  • the anti idiotypic antibody Ab2p does not bind to Abl in the excessive presence of the antigen, maybe because Ab2 binds with the binding sites of Abl .
  • the anti-idiotypic Ab2a antigens binds with an idiotype distinct from the Abl antigen site.
  • the immunological data transfer is carried out from chicken to human, via IgY (Abl) by the naive T lymphocytes, from T lymphocyte clones to B lymphocytes which take over the negative - negative data and reproduce a positive IgG similar to the original IgY-idiotypic (Patrascu I.V.).
  • the artificial passive immunity is generally produced from the blood which contains large amounts of specific antibodies.
  • Another modern form of artificial passive immunity was obtained by using immunoglobulins (Ig) extracted from the egg yolk (Y) which contains large amounts of specific antibodies.
  • chickens are actively immunized with antigenic stimuli prepared for this purpose.
  • the chicken immune response is found in blood and yolk of eggs which are collected after the antibody level can be detected in blood.
  • the artificial passive immunity provides immediate protection with antibodies against the microorganisms the antibodies have been generated against. These antibodies produced by the actively immunized chicken cannot be produced by the patient because he is not capable of
  • the person receiving IgY will have a temporary passive immunity for as long as the antibodies last in the organism. This type of immunity acts immediately when the patient needs protection, with antibodies provided by other person or, in this case, by the chicken. As per the information from the CDC Atlanta, Georgia USA, which has studied the immunity of a group/ population, there are people who can receive blood products, such as immunoglobulins which provide immediate protection against a specific disease. This is the utmost benefit of passive immunity because the protection is instant, while the active immunity from vaccines requires time, several weeks maybe, to reach an appropriate protection level (14).
  • IgY for the prevention and treatment of pathogenic germ infections in humans and animals involved the oral administration of certain drug formulas containing active antibodies. Research to this extent carried out from 1893 until 2015 intended the preventive or curative administration in people and animals of some IgY obtained in the poultry immunized with bacterial or fungal strains, yeasts or reference (distinct) viruses or with bacterial strains isolated directly from patients (12).
  • An egg (Ovopach) was developed under these conditions using a new manufacture and control protocol of specific IgY produced by the chicken and the antigenic stimulus administered together with the adjuvant QS21.
  • the multiple antigenic stimulus is represented by pathogenic agents, modified opportunistic flora, cells different from normal from structural and antigenic point of view (1) sampled from the patients.
  • Topley WWC Wilson GS. The spread of bacterial infection: the problem of herd immunity. J Hyg 1923; 21 :243-9
  • the objective of this invention is to obtain Ovopach hyperimmune egg as product and method of preparation, active immunological Ovopach specific against bacterial antigens, yeasts, fungi, cell structures present in the pathological material sampled from the psoriasis skin wounds of the patient.
  • the immune response of Ovopach-producing chickens was defined by highlighting and quantification of the immune effectors found in the aqueous extract from the yolks of immunized chickens.
  • the pathological material used for the rapid immunization of chickens in order to obtain an appropriate specific immune response (1,500 OD or higher by ELISA) is used in vitro and for the isolation, identification and description of various microorganisms existing in this product.
  • This activity, including the antibiogram, contributes to the description of psoriasis wound infections in the patient.
  • Various products can be prepared from the Ovopach eggs and they can be used in case of emergency for psoriasis treatment in the patient whom the pathogenic material has been collected from.
  • IgY solution to 200 mg/80 ml
  • IgY solution to 25 mg/ml in 2 ml vials
  • whole egg whole freeze-dried egg
  • IgY ointment to 20 mg/ml
  • IgY spray to 20 mg/ml which can be locally or generally administered.
  • This invention refers to the preparation and description of the hyperimmune egg called Ovopach intended for psoriasis treatment, the extraction stages of which are described in the Invention Patent (14).
  • Ovopach hyperimmune egg has a simultaneous specific reaction against one or more antigens used for chicken immunization.
  • the anti-psoriasis Ovopach hyperimmune egg is obtained from the chickens immunized with the antigen obtained from the pathological material samples from the patient, mixed with adjuvant Q by a single intramuscular administration in four distinct sites in the breast of over 24 weeks old laying chickens.
  • the eggs can be used as such or a whole freeze-dried or atomized egg can be prepared from these eggs and IgY can be extracted after detection in the egg yolk of a specific antibody level of 1500 OD or higher by ELISA.
  • the eggs with appropriate response are used for this purpose.
  • One of the objectives of this invention is the registration of anti-psoriasis Ovopach as biological product, of its method of preparation and of the method of treatment of psoriasis.
  • chickens are immunized at the age of 24-30 weeks, in the high laying season, with a pathological product sampled from the patient.
  • This product contains specific pathogenic germs which represent a mixture of proteins present after 24-48 hours at 37 °C in the culture medium inactivated in formalin, thermally or by gamma rays, mixed with adjuvant QS21 and administered intramuscularly.
  • the amount of protein mixed with adjuvant QS21 cannot be higher than 200 mg per ml diluted in PBS per dose.
  • Each chicken is immunized with 2 ml inoculums, in 4 distinct sites of the pectoral muscles. If 14 days after inoculation there is no specific immune response against the immunization antigen at minimum 1,500 OD by ELISA, the immunization must be carried on according to the program described in the Invention patent application no. A/00810 from 29.10.2014 (14). In emergency cases, an antibody concentration can be performed by tangential filtration.
  • Combined powder feed must be administered ad libitum throughout the treatment period.
  • the immune response is assessed directly by monitoring the eggs collected from the immunized chickens.
  • the yolk harvested from each egg is treated with PEG 6000 for IgY extraction.
  • IgY is tested separately identifying the chickens with an immune response above 1,500 OD by ELISA.
  • the eggs with immune response below 1,500 OD by ELISA can be used for obtaining IgY by concentrating it.
  • the Ovopach hyperimmune eggs are collected and used for various purposes.
  • This biological product and its derivatives are personalized products and the antigens used for the immunization of laying chickens are prepared from the pathological material sampled from a single patient.
  • Ovopach hyperimmune egg and yolk immunoglobulins contain specific antibodies against the pathogenic germs present in the pathological material sampled from the patient, which implicitly contains one of the main triggers of the disease.
  • the method of preparation of Ovopach and its byproducts involves a self-methodology for the first time in the world.
  • the personalized antigen is prepared from the pathological material sampled from the psoriasis wounds of the patient.
  • This product contains pathogenic agents, modified opportunistic flora, cells different from normal from structural and antigenic point of view.
  • the pathogenic material is harvested from each patient and the finished product is personalized and represents the hyperimmune egg or the byproducts.
  • the pathological product found in the transport medium is cultivated on liquid culture media for 24 or 48 hours.
  • the cell material is prepared separately by centrifugation at 5000 rpm at +4 °C.
  • the mixture of these products is inactivated in formalin or thermally or under gamma rays, washed three times in phosphate buffer (PBS) and centrifuged at 4000 rpm for 15 minutes.
  • the sediment is resuspended in PBS at predetermined concentration. 1. Immunization of conventional or SPF laying chickens
  • the antigen is administered by intramuscular inoculation of 0.5 ml in four distinct sites on the chest muscles of conventional or SPF laying chickens.
  • the antigen is inoculated three times every 14 days.
  • the presence of specific antibodies in blood and eggs is tested after the second administration, by ELISA and ID.
  • Eggs are harvested 14 days after the third antigen inoculation, when the antibody titer is assessed on regular basis from the eggs of chickens immunized with the target antigen (12).
  • the immunization of laying chickens with a target antigen is a well known technique.
  • This invention can undertake any method of chicken immunization which consists of the administration of the target antigen by any route: subcutaneous, intracutaneous, intramuscular, intravenous.
  • Adjuvant QS21 was used for this invention.
  • Other types of adjuvants can also be used such as complete or incomplete Freund adjuvant or a mixture of them.
  • antigen QS21 mixed with the target antigen enhances the immune response, induces no local reactions and has been demonstrated to be efficient for the production and maintenance of a high titer for a long period of time.
  • the presence of specific immunoglobulin against the prepared and administered antigen is separately monitored starting from the tenth day after antigen administration.
  • the eggs can be collected and used for treatment purposes either as raw, mixed in warm milk or other juices.
  • the specific immunoglobulin can be extracted from the Ovopach hyperimmune egg using the previously patented methodology of preparation and control (12).
  • the personalized antigen is prepared from the pathological material sampled from the patient. This material can be sampled from the skin surface (scalls).
  • the pathological product transported in vials to the lab is transferred in nutritive broth and incubated for 24-48 hours at 37 °C.
  • the finished product together with the cell debris are inactivated in formalin or thermally or under gamma rays and purified by washing.
  • the sediment is used as antigenic material mixed with adjuvant QS21. Microorganism inactivation control is performed after preparation of the antigenic mass.
  • Chickens at high laying season and raised in separated cages are immunized by receiving 2 ml antigen four distinct sites in the pectoral muscles. If the immune response monitored during 10-14 days after the first administration of the antigen is appropriate (2,000-3,000 OD by ELISA), the eggs of these chickens can be used either as administered as such or by extracting immunoglobulins from the yolk.
  • the immunization program can be carried on and the eggs collected from immunized chickens will be used for IgY extraction, purification of egg white and yolk proteins and preparation of a purified protein complex.
  • this personalized biological product is filled as follows:
  • Immunoglobulin (IgY) extracted from Ovopach egg yolk (200 mg/80 ml liquid, 50 mg/ml, spray, Vaseline, granules, capsules)
  • Purified protein mixture extracted from Ovopach, from the yolk (IgY) and egg white (ovo transferrin, ovomucin, lysozyme).
  • IgY prepared from the hyperimmune egg Ovopach proved to be capable of specifically reacting with epitopes on the bacteria and fungi in the pathological product sampled from the patient and used for chicken immunization, resembling to that of immunoglobulin (IgY) extracted from the yolk of the same eggs.
  • the ID assay is based on the migration of antigen (IgY) and antibodies (anti IgY rabbit serum) to the agar gel where they specifically mix and form a precipitate revealed as a precipitation line.
  • IgG was placed in the central well and in wells no. 1 and 4.
  • Romvac substandard IgY anti S. aureus was placed in wells 2 and 6.
  • IgY Ovopach was placed in wells 3 and 5. It is obvious that the precipitation lines generated by the substandard and IgY Ovopach agglutinate, demonstrating that the products belong to the same protein and antigenic group.
  • Anti-IgY IgG is mixed with the agar gel in proportion of 2 ml whole/g of agar. 3 or 6 mm wells are performed in gel. IgY Ovopach is distributed in these wells and it can be from various batches or at various concentrations. The reaction plate is incubated at +22 °C for 20- 24 hours, then it is read under indirect light. The presence of a precipitation plate proves the
  • ELISA is "in house” prepared for each and every assay. The minimum detected amount of Ovopach is 10 nanograms in the tested material. Due to the specificity and reproducibility of immunoenzymatic reaction, ELISA is used in the manufacturing process of Ovopach, on production stages and during qualitative and quantitative control. a) Perform the ELISA to be used in the quantitative control of Ovopach by comparing with an international IgY standard (USA) or with an IgY substandard prepared at Romvac. b) Cover the wells with 150 ⁇ anti-avian rabbit serum IgG at 3,75 ⁇ /ml concentration in carbonate-bicarbonate buffer;
  • ELISA detects minimum 10 ng/ml and it is performed in comparison with standard IgY.
  • the specific anti psoriasis activity of IgY is determined by a quantitative method against the antigen represented by the inactivated and freeze-dried pathological material.
  • MD Serum patient from Constanta supplemented with hyperimmune eggs + local skin treatment with personalized IgY solution
  • - 3 mL serum received from Romar Clinic Constanta 250 mL serum/tube, stored at -20 °C.
  • the reaction has been performed accurately and the plate had no impact on the enzymatic reaction.
  • the sample extracted from the SPF chicken egg had a negative reaction (wells CI, Dl and Dl).
  • the positive IgY control and the IgY of the patient reacted specifically at intensity of 3,340 OD450.
  • the immune response intensity in this experiment depends on the concentration of the antigen covering the reaction plate at 10 ⁇ g per well.
  • Figure 4 Evolution of wounds on the legs after administering personalized IgY; (A) Photo taken on 17.06.2015 after about 3 months of treatment and (B) Photo taken on 21.08.2015 after about 5 months of treatment;
  • the patient eats a raw egg in milk in the morning and performs throat wash for 2 minutes in the evening with IgY-polyvalent and then swallows the contents. After 3 days of treatment, the patient is free of itching and smarting. After 19 days of treatment the wounds start to subside, the silver-white scalls fall and the overall status of the patient is good. Photos are shown below from the beginning of treatment and after 19 days of treatment.
  • FIG. 7 Evolution of wounds on the upper left arm after administering personalized IgY; (A) Photo taken at the beginning of treatment and (B) Photo taken after 19 days of treatment
  • FIG. 8 Evolution of wounds on the upper right arm after administering personalized IgY; (A) Photo taken at the beginning of treatment and (B) Photo taken after 19 days of treatment
  • Figure 9 Evolution of wounds on the skin after administering personalized IgY; (A) Photo taken at the beginning of treatment and (B) Photo taken after 30 days of treatment
  • Figure 11 Evolution of wounds on the leg after administering personalized IgY for 30 days;

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  • Proteomics, Peptides & Aminoacids (AREA)
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Abstract

Cette invention concerne la découverte d'une méthode de traitement du psoriasis au moyen d'une thérapie par immunoglobuline de poule personnalisée. Les poules sont immunisées avec un immunogène préparé à partir d'échantillons de plaie cutanée prélevés sur chaque patient. Cette invention concerne un immunogène particulier, prélevé à partir du patient, mélangé avec un adjuvant et qui, lorsqu'il est administré à des poules, produit une réponse immunitaire spécifique dans un délai approprié de sorte que les œufs Ovopach obtenus à partir de ces poules doivent être utilisé dans des conditions stringentes dans le traitement du psoriasis du patient. L'immunogène est polyspécifique et contient des antigènes microbiens et cellulaires présents dans les plaies de psoriasis du patient. La réponse immunitaire spécifique des poules immunisées est suivie sur une base quotidienne par extraction d'immunoglobulines (Ig) à partir du jaune d'œuf (Y) et évaluation qualitative et quantitative par ELISA, essai d'immunodiffusion radiale et d'immunodiffusion d'Ouchterlony. La réponse immunitaire des poules, exprimée par les anticorps extraits de jaune d'œuf, est une réponse multiple, complexe contre tous les stimuli antigéniques présents dans le produit pathogène prélevé à partir du patient.
PCT/RO2016/000002 2015-10-16 2016-01-08 Fabrication et utilisation d'œuf hyper-immun personnalisé dans le traitement du psoriasis Ceased WO2017065626A1 (fr)

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EP16716713.9A EP3362092A1 (fr) 2015-10-16 2016-01-08 Fabrication et utilisation d' uf hyper-immun personnalisé dans le traitement du psoriasis

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ROA201500735A RO130965A8 (ro) 2015-10-16 2015-10-16 Producerea şi utilizarea oului hiperimun personalizat () în tratamentul psoriazisului
ROA/2015/00735 2015-10-16

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019039948A1 (fr) * 2017-06-06 2019-02-28 Fântână, Raul Sorin Composition, procédé de préparation et évaluation d'un immunogène complexe appelé i-spga pour la production de protéines immunologiquement actives (iap)
US11319382B1 (en) 2021-06-28 2022-05-03 King Abdulaziz University Methods for producing and using IgY antibodies targeting the middle east respiratory syndrome coronavirus spike protein to treat or prevent MERS-CoV infection

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WO1998058671A1 (fr) * 1997-06-23 1998-12-30 Yes Biotech Laboratories Ltd. Traitement topique du psoriasis mettant en oeuvre des anticorps aptes a neutraliser il-8
WO1999036077A1 (fr) * 1998-01-19 1999-07-22 Dcv, Inc. Composition et methode de traitement et de prevention de l'arthrite et/ou de maladies auto-immunes
WO2000029444A1 (fr) * 1998-11-16 2000-05-25 Genway Biotech, Inc. Generation d'anticorps par vaccination polynucleotidique dans le cas d'une espece aviaire
WO2008025099A1 (fr) * 2006-08-31 2008-03-06 A.C.N. 135 493 391 Pty Ltd As Trustee For Conca Unit Trust Traitement et/ou prévention des affections médicales non infectieuses en utilisant des compositions contenant des anticorps
WO2009027470A1 (fr) * 2007-08-30 2009-03-05 ÅGERUP, Bengt Administration locale d'immunoglobulines de jaune d'œuf de poulet (igy) pour prevenir et traiter les infections fongiques
EP2500034A1 (fr) * 2009-11-13 2012-09-19 Kabushiki Kaisha Saiwai Medix Agent thérapeutique pour le psoriasis ou la dermatite atopique
RO129645A0 (ro) * 2014-02-25 2014-07-30 Romvac Company S.A. Procedeu de obţinere şi utilizare a imunoglobulinelor de găină ()
RO130213A0 (ro) * 2014-10-29 2015-05-29 Romvac Company S.A. Producerea şi folosirea oului hiperimun - pc2

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WO1998058671A1 (fr) * 1997-06-23 1998-12-30 Yes Biotech Laboratories Ltd. Traitement topique du psoriasis mettant en oeuvre des anticorps aptes a neutraliser il-8
WO1999036077A1 (fr) * 1998-01-19 1999-07-22 Dcv, Inc. Composition et methode de traitement et de prevention de l'arthrite et/ou de maladies auto-immunes
WO2000029444A1 (fr) * 1998-11-16 2000-05-25 Genway Biotech, Inc. Generation d'anticorps par vaccination polynucleotidique dans le cas d'une espece aviaire
WO2008025099A1 (fr) * 2006-08-31 2008-03-06 A.C.N. 135 493 391 Pty Ltd As Trustee For Conca Unit Trust Traitement et/ou prévention des affections médicales non infectieuses en utilisant des compositions contenant des anticorps
WO2009027470A1 (fr) * 2007-08-30 2009-03-05 ÅGERUP, Bengt Administration locale d'immunoglobulines de jaune d'œuf de poulet (igy) pour prevenir et traiter les infections fongiques
EP2500034A1 (fr) * 2009-11-13 2012-09-19 Kabushiki Kaisha Saiwai Medix Agent thérapeutique pour le psoriasis ou la dermatite atopique
RO129645A0 (ro) * 2014-02-25 2014-07-30 Romvac Company S.A. Procedeu de obţinere şi utilizare a imunoglobulinelor de găină ()
RO130213A0 (ro) * 2014-10-29 2015-05-29 Romvac Company S.A. Producerea şi folosirea oului hiperimun - pc2

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019039948A1 (fr) * 2017-06-06 2019-02-28 Fântână, Raul Sorin Composition, procédé de préparation et évaluation d'un immunogène complexe appelé i-spga pour la production de protéines immunologiquement actives (iap)
CN111263639A (zh) * 2017-06-06 2020-06-09 R·S·凡塔纳 用于免疫活性蛋白(iap)生产的名为i-spga的复合免疫原的组分、制备方法和评估
US11458196B2 (en) 2017-06-06 2022-10-04 Raul Sorin Fântâna Composition, preparation method and evaluation of a complex immunogen named I-SPGA for production of immunological active proteins (IAP)
US11319382B1 (en) 2021-06-28 2022-05-03 King Abdulaziz University Methods for producing and using IgY antibodies targeting the middle east respiratory syndrome coronavirus spike protein to treat or prevent MERS-CoV infection

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MA42973A (fr) 2018-08-22
EP3362092A1 (fr) 2018-08-22
RO130965A8 (ro) 2017-06-30
RO130965A0 (ro) 2016-03-30

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