EP0203088A1 - Anticorps monoclonaux et leur utilisation - Google Patents

Anticorps monoclonaux et leur utilisation

Info

Publication number
EP0203088A1
EP0203088A1 EP19850905083 EP85905083A EP0203088A1 EP 0203088 A1 EP0203088 A1 EP 0203088A1 EP 19850905083 EP19850905083 EP 19850905083 EP 85905083 A EP85905083 A EP 85905083A EP 0203088 A1 EP0203088 A1 EP 0203088A1
Authority
EP
European Patent Office
Prior art keywords
antigen
antibody
antigens
monoclonal antibody
specific
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP19850905083
Other languages
German (de)
English (en)
Inventor
Bruce William Wright
Peter John Church Cottage Church Road COX
Alice Margaret Noyes
Danny Widdows
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
TECHNOLOGY LICENCE Co Ltd
Original Assignee
TECHNOLOGY LICENCE Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by TECHNOLOGY LICENCE Co Ltd filed Critical TECHNOLOGY LICENCE Co Ltd
Publication of EP0203088A1 publication Critical patent/EP0203088A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
    • C07K16/1271—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Micrococcaceae (F), e.g. Staphylococcus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • monoclonal antibodies specific for the antigens or species of Staphylo- cocci are desired which when used will rapidly diagnose the presence of such organisms in speci ⁇ mens.
  • Staphylo- cocci species have been made among the Staphylo- cocci species. Some of the representative members include Staphylococcus aureus, Staphylococcus
  • toxin a variety of toxic substances are produced by Staphylococcus, including hemoly- sins, leucocidin, coagulase, fibrinolysin, exfoli- ative toxins (which attack the skin), entero- toxins, pyogenic toxins (a, b, and c), alpha, gamma, and delta toxins.
  • toxin a variety of toxic substances are produced by Staphylococcus, including hemoly- sins, leucocidin, coagulase, fibrinolysin, exfoli- ative toxins (which attack the skin), entero- toxins, pyogenic toxins (a, b, and c), alpha, gamma, and delta toxins.
  • toxin a variety of toxic substances are produced by Staphylococcus, including hemoly- sins, leucocidin, coagulase, fibrinolysin, exfoli- ative toxins (which attack the skin), entero- toxins,
  • UTSSHEET production is a property of the pathogenic Staphy- lococci, usually of the aureus variety.
  • Staphylococci are not only found frequently in all parts of the body in secondary and mixed infections, but they are also primarily responsi ⁇ ble for a variety of specific pathologic condi ⁇ tions and for injury to particular organs. Staphylococcus is the most cominon cause of abces- ses or boils of the skin. They may produce devastating infections and may rapidly destroy the heart valves, leading to death. They can produce overwhelming pneumonia and they are the most common cause of infections of the bone (osteomyelitis) in children and in adults.
  • a rapid diagnostic agent to detect Staphylo ⁇ cocci infection in certain infections would be of great value, particularly in severely septic patients and in progressive infections of the skin, such as cellulitis.
  • Present diagnos ⁇ tic methods include inspection of tissue and gram staining, which may be time consuming and imprecise; or culture methods, which may be slow, in this often rapidly destructive and highly fatal infection.
  • the need for an immediate diagnosis for these infections is considerable and, when applied either as a diagnostic for blood infections, for respiratory infections, and even on unusual occasions for urinary tract infections, would be of considerable utility.
  • isotopic and nonisotopic immunoassays have been utilized in conjunction with monoclonal antibodies to test for the pres ⁇ ence of an antigenic substance.
  • agglutination, immuno-fluorescent, chemilum- inescent or fluorescent immunoassay, immuno- electron microscopy, radiometric assay systems, radio immunoassays, and enzyme-linked immunoassays are the most common techniques used with the monoclonal antibodies. Other techniques include bioluminescent, fluorescence polarization, and photon-counting immunoassays.
  • EIA enzyme-linked immunoassay procedure
  • the enzyme-linked monoclonal antibody can then be used in the known enzyme-linked immunosor- bent assay procedure to determine the presence of an antigenic substance.
  • the serotype of the infecting organism can be determined, and appropriate treatment can then be initiated to rapidly and efficiently eliminate the disease.
  • the present invention provides novel mono ⁇ clonal antibodies for use in accurately and rapidly diagnosing samples for the presence of Staphylococci antigens and/or organisms.
  • the present invention com ⁇ prises monoclonal antibodies specific for an antigen or species of Staphylococcus; in partic ⁇ ular, the antigens or species of Staphylococcus aureus (such as the common antigen), Staphylococ ⁇ cus epidermidis, Staphylococcus aerogenes, Staphy ⁇ lococcus lactis, and the antigens to the Staphylo- cocci toxins such as exfoliative toxins, beta hemolysins, alpha toxins, delta toxins, entero- toxins a to f (inclusive), leucocidin, gamma toxins, pyogenic toxins (a, b, and/or c), as well as a monoclonal antibody broadly cross- reactive with an antigen for each species of the genus Staphylococc
  • the invention also comprises labeled mono ⁇ clonal antibodies for use in diagnosing the presence of the Staphylococci antigens, each comprising a monoclonal antibody against one of the above-mentioned antigens to Staphylococci or to a particular species or toxin thereof and linked thereto an appropriate label.
  • the label can be chosen from the group consisting of a radioactive isotope, enzyme, fluorescent compound, chemiluminescent compound, biolumines- cent compound, ferromagnetic atom, or particle, or any other label.
  • the invention further comprises the process for diagnosing the presence of Staphylococci antigens, organisms, or toxins in a specimen comprising contacting said specimen with the labeled monoclonal antibody in an appropriate immunoassay procedure.
  • the invention is also directed to a therapeutic composition
  • a therapeutic composition comprising a mono ⁇ clonal antibody for an antigen or toxin of Staphy ⁇ lococcus and a carrier or diluent, as well as kits containing at least one labeled monoclonal antibody to an antigen or toxin of Staphylococcus.
  • the monoclonal antibodies of the present invention are prepared by fusing spleen cells, from a mammal which has been immunized against the particular Staphylococcus antigen, with an appropriate myeloma cell line, preferably NSO (uncloned), P3NS1-Ag4/1, or Sp2/0 Agl4.
  • an appropriate myeloma cell line preferably NSO (uncloned), P3NS1-Ag4/1, or Sp2/0 Agl4.
  • the resultant product is then cultured in a standard HAT (hypoxanthine, aminopterin, and thy idine) medium. Screening tests for the specific monoclonal antibodies are employed utilizing immunoassay techniques which will be described below.
  • the immunized spleen cells may be derived from any mammal, such as primates, humans, rodents (i.e., mice, rats, and rabbits), bovine, ovine, canine, or the like, but the present invention will be described in connection with mice.
  • the mouse is first immunized by injection of the particular Staphylococcus antigen chosen gener ⁇ ally for a period of approximately eleven weeks. When the mouse shows sufficient antibody produc ⁇ tion against the antigen, as determined by conven ⁇ tional assay, it is given a booster injection of the appropriate Staphylococcus antigen, and then killed so that the immunized spleen may be removed. The fusion can then be carried out utilizing immunized spleen cells and an appropriate myeloma cell line.
  • the fused cells yielding an antibody which give a positive response to the presence of the particular Staphylococcus antigen are removed and cloned utilizing any of the standard methods.
  • the monoclonal antibodies from the clones are then tested against standard antigens to determine their specificity for the particular Staphylococ ⁇ cus antigen.
  • the monoclonal antibody selected, which is specific for the particular Staphylococ ⁇ cus antigen, species, or toxin is then bound to an appropriate label. Amounts of antibody sufficient for labeling and subsequent commercial production are produced by the known techniques, such as by batch or continuous tissue culture or culture in vivo in mammals, such as mice.
  • the monoclonal antibodies may be labeled with a multitude of different labels, such as enzymes, fluorescent compounds, luminescent compounds, radioactive compounds, ferromagnetic labels, and the like.
  • labels such as enzymes, fluorescent compounds, luminescent compounds, radioactive compounds, ferromagnetic labels, and the like.
  • the present invention will be described with reference to the- use of an enzyme labeled monoclonal antibody.
  • Some of the enzymes utilized as labels are alkaline phosphatase, glucose oxidase, galactosidase, peroxidase, or urease, and the like.
  • Such linkage with enzymes can be accomplished by any one of the conventional and known methods, such as the Staphylococcal Protein A method, the glutaraldehyde method, the benzoquinone method, or the periodate method.
  • EIA enzyme- linked immunosorbent assay
  • Fluorescent-immunoassay is based on the labeling of antigen or antibody with fluorescent probes. A nonlabeled antigen and a specific antibody are combined with identical luorescently labeled antigen. Both labeled and unlabeled antigen compete for antibody binding sites. The amount of labeled antigen bound to the antibody is dependent upon, and therefore a measurement of, the concentration of nonlabeled antigen. Examples of this particular type of fluorescent- immunoassay would include heterogenous systems such as Enzyme-Linked Fluorescent Immunoassay, or homogeneous systems such as the Substrate Labeled Fluorescent Immunoassay. The most suit ⁇ able fluorescent probe, and the one most widely used is fluorescein. While fluorescein can be subject to considerable interference from scattering, sensitivity can be increased by the use of a fluorometer optimized for the probe utilized in the particular assay and in which the effect of scattering can be minimized.
  • Fluorescence polarization In fluorescence polarization, a labeled sample is excited with polarized light and the degree of polarization of the emitted light is measured. As the antigen binds to the antibody its rotation slows down and the degree of polari ⁇ zation increases. Fluorescence polarization is simple, quick, and precise. However, at the present time its sensitivity is limited to the micromole per liter range and upper nano- mole per liter range with respect to antigens in biological samples.
  • Luminescence is the emission of light by an atom or molecule as an electron is transferred to the ground state from a higher energy state.
  • the free energy of a chemical reaction provides the energy required to produce an inter ⁇ mediate reaction or product in an electronically excited state. Subsequent decay back to the ground state is accompanied by emission of light.
  • Bioluminescence is the name given to a special form of chemiluminescence found in biological systems, in which a catalytic protein or enzyme, such as luciferase, increases the efficiency of the luminescent reaction. The best known chemiluminescent substance is luminol.
  • a further aspect of the present invention is a therapeutic composition
  • a therapeutic composition comprising one or more of the monoclonal antibodies to the particular Staphylococcus antigen, species, or toxin, as well as a pharmacologically accept ⁇ able carrier or diluent.
  • Such compositions can be used to treat humans and/or animals afflic ⁇ ted with some form of Staphylococci infections and they are used in amounts effective to cure; an amount which will vary widely dependent upon the individual being treated and the severity of the infection.
  • One or more of the monoclonal antibodies can be assembled into a diagnostic kit for use in diagnosing for the presence of antigens, toxins, or species of Staphylococci in various specimens. It is also possible to use the broadly cross-reactive monoclonal antibody which can identify the genus Staphylococcus alone or as part of a kit containing antibodies that can identify other bacterial genera or species of Staphylococcus and/or other toxins.
  • kits In the past there have been difficulties in developing rapid kits because of undesirable cross-reactions of specimens with antiserum.
  • the use of monoclonal antibodies can eliminate these problems and provide highly specific and rapid tests for diagnosis.
  • a rapid and precise kit could replace or augment existing tests and permit early direct therapy using precise antibiotics. Avoiding multiple antibiotics or more expensive or hazardous antibiotics would represent substantial patient and hospital sav ⁇ ings.
  • a kit can be used on an out-patient basis. At present the lack of a rapid test giving "same day" answers may delay the initiation of treatment until the patient has developed more severe symptoms or may require the initiation of more costly therapy in a sick patient. A test that would return results within an hour or two would be a substantial convenience to patients.
  • kit could be included as a component in a comprehensive line of compatible immunoassay reagents sold to reference laboratories to detect the species and serotypes of Staphylococci.
  • kits comprising at least one labeled monoclonal antibody against a particular Staphylococcus antigen, toxin, or species, as well as any appropriate stains, counterstains, or reagents.
  • Specific antigens to be detected in this kit include the antigens of Staphylococcus aureus, S ⁇ epidermidis, S_. aerogenes, S_.
  • lactis lactis
  • antigens to the Staphylococci toxins such as exfoliative toxins, beta hemolysins, alpha toxins, delta toxins, enterotoxins a to f (inclus ⁇ ive), leucocidin, gamma toxins, and pyogenic toxins (a, b, and/or c).
  • Monoclonal diagnostics which detect the presence of Staphylococci antigens can also be used in periodic testing of water sources, food supplies and food processing operations.
  • the present invention describes the use of the labeled monoclonal antibodies to determine the presence of a standard antigen
  • the invention can have many applications in diagnosing the presence of antigens by determining whether specimens such as urine, blood, stool, water or milk contain the particular Staphylococcus antigen. More particularly, the invention could be utilised as a public health and safety diagnostic aid, whereby specimens such as water or food could be tested for possible contamination.
  • DMEM Dulbecco's Modified Eagles Medium
  • FCS Foetal Calf Serum
  • PBS phosphate-buffered saline
  • CFA Complete Freunds Adjuvant
  • % T refers to vaccine concentration measured in a 1 cm light path
  • Monoclonal antibodies of the present invention are prepared generally according to the method of Koehler and Milstein, Eur. J. Immunol. _6, (1975) 292.
  • Staphylococcus aureus is obtained from the National Collection of Type Cultures, strain title NCTC 8532. "Dead” organisms were prepared by growing the bacteria in Tryptone Soya Broth in CO reminding; the organisms were washed in saline by repeated centrifugation and were finally resuspended in formol saline. "Live” organisms were prepared in blood agar and suspended in PBS.
  • mice are injected with each preparation of the antigen. They are given an intramuscular injection (0.05 ml 80% T vaccine) of vaccine (in CFA) . The mice are bled approximately six days after the last injection and the serum tested for antibodies by assay. A conventional assay used for this serum titer testing is the enzyme-linked immunosorbent assay system. When the mice show antibody production after this regimen, generally a positive titer of at least 10,000, a mouse is selected as a fusion donor and given a booster injection (0.02 ml 80% T vaccine) intravenously, three days prior to splenectomy.
  • C Cell Fusion Spleen cells from the immune mice are harvested three days after boosting, by conventional techniques.
  • the donor mouse selected is killed and surface-sterilised by immersion in 70% ethyl alcohol.
  • the spleen is then removed and immersed in approximately 2.5 ml DMEM to which has been added 3% FCS.
  • the spleen is then gently homogenised in a LUX homogenising tube until all cells have been released from the membrane, and the cells are washed in 5 ml 3% FCS-DMEM.
  • the cellular debris is then allowed to settle and the spleen cell suspension placed in a 10 ml centrifuge tube.
  • the debris is then rewashed in 5 ml 3% FCS-DMEM. 50 ml -suspension are then made in 3% FCS-DMEM.
  • the myeloma cell line used is NS0 (uncloned) , obtained from the MRC Laboratory of Molecular Biology in Cambridge, England.
  • the myeloma cells are in the log growth phase, and rapidly dividing.
  • Each cell line is washed using, as tissue culture medium, DMEM containing 3% FCS.
  • the spleen cells are then spun down at the same time that a relevant volume of myeloma cells are spun down (room temperature for 7 minutes at 600 g) , and each resultant pellet is then separately resuspended in 10 ml 3% FCS-DMEM.
  • a relevant volume of myeloma cells are spun down (room temperature for 7 minutes at 600 g)
  • each resultant pellet is then separately resuspended in 10 ml 3% FCS-DMEM.
  • 0.1 ml of the suspension is diluted to 1 ml and a haemacytometer with phase microscope is used.
  • 0.1 ml of the suspension is diluted to 1 ml with Methyl Violet-citric acid solution, and a haemacytometer and light microscope are used to count the stained nuclei of the cells.
  • the resultant cell pellet is placed in a 37°C water-bath.
  • each well contains 1.0 ml of the standard HAT medium (hypoxanthine, aminopterin and thymidine and a feeder layer of Balb/c
  • the wells are kept undisturbed, and cultured at 37°C in 9% C0 ⁇ air at approximately 100% humidity.
  • the wells are analysed for growth, utilising the conventional inverted microscope procedure, after about 5 to 10 days.
  • screening tests for the specific monoclonal antibody are made utilising the conventional enzyme immunoassay screening method described below.
  • the monoclonal antibodies from the clones are screened by the standard techniques for binding to the antigen, prepared as in the immunisation, and for specificity in a test battery of the class bearing different antigens. Specifically, a grid of microtiter plates containing a representative selective of organisms is prepared, boiled, and utilised as a template to define the specificity of the parent group.
  • the EIA immunoassay noted above may be used.
  • the cells are then centrifuged at 1200 g for approximately 10 minutes, the cells discarded, and the antibody-rich ascites fluid collected.
  • the fluid is titrated, as noted above, to establish presence and level* of antibody, and purified.
  • Purification is accomplished using the protein A - Sepharose method. More particularly, about 10 ml of the ascites fluid are filtered through glass wool and centrifuged at 30,000 g for 10 minutes. The ascites is then diluted with twice its own volume of cold phosphate buffer (0.1 M sodium phosphate, pH 8.2). The diluted ascites is loaded on to a 2 ml column of protein A - Sepharose which has previously been equilibrated with phosphate buffer. The column is washed with 40 ml phosphate buffer, and the monoclonal antibody is eluted with citrate buffer (0.1 M sodium citrate, pH 3.5) into sufficient IM tris buffer, pH 9.0, to raise the pH immediately to about 7.5. The eluate is dialysed in 2 x 1000 ml PBS at +4°C.
  • citrate buffer 0.1 M sodium citrate, pH 3.5
  • the fluid may then be titrated, as noted above, to establish presence and level of antibody, and purified by a combination of batch ion-exchange chromatography, ammonium sulphate precipitation and column ion-exchange (a possible alternative would be protein A - Sepharose) chromatography.
  • the suspension is stirred for a further 30 minutes.
  • the precipitate is then harvested by centrifugation at 10,000 g for 10 minutes.
  • the precipitate is dissolved in a minimum volume of either cold phosphate/EDTA buffer (20mM sodium phosphate, lOmM EDTA, pH 7.5, + 0.02% sodium azide) for DEAE-cellulose chromatography, or phosphate buffer (0.1M sodium phosphate, pH 8.2 + 0.02% sodium azide) for protein A-Sepharose chromatography.
  • the dissolved precipitate is dialysed versus 2 x 1000 ml of the dissolution buffer at +4°C, and the appropriate chromatography step carried out as previously described.
  • the monoclonal antibody specific against the antigen, prepared as above, is linked to an enzyme, viz. highly-purified alkaline phosphatase.
  • the one-step glutaraldehyde method or benzoquinone conjugation is used.
  • the conjugate is eluted with 3.5 ml PBS and then dialysed against 2 x 2000 ml of TRIS buffer (50 mM TRIS, 1 mM magnesium chloride, pH 8.0, plus 0.02% sodium azide) at +4°C.
  • TRIS buffer 50 mM TRIS, 1 mM magnesium chloride, pH 8.0, plus 0.02% sodium azide
  • To the dialysed conjugate is added l/10th its own volume of 10% BSA in TRIS buffer.
  • the conjugate is then sterile-filtered through a 0.22 ⁇ m membrane filter into a sterile amber vial and stored at +4°C.
  • EXAMPLE 2 The procedure of Example 1 was followed, in most respects.
  • the antigen was Staphylococcus epidermidis NCTC 11047. Animals were immunised intramuscularly in CFA and, after 4 weeks, intravenously.
  • Example 3 The procedure of Example 1 was followed, but using, as the antigen, Staphylococcus toxic shock syndrome toxin obtained as purified antigen from Dublin. Immunisation comprised im (in CFA) and, four months later, iv (in saline) injections.
  • EXAMPLE 4 The procedure of Example 1 was followed, but using, as the antigen, Staphylococcus toxic shock syndrome toxin obtained as purified antigen from Dublin. Immunisation comprised im (in CFA) and, four months later, iv (in saline) injections.
  • Example 1 The general procedure of Example 1 may be followed to produce a monoclonal antibody broadly cross-reactive with an antigen of all species of the genus Staphylococcus.
  • Tests using the present invention are superior to existing tests, based on the following advantages: (i) greater accuracy; (ii) same day results, within an hour or two; (iii) reduction in amount of skilled labour required to administer laboratory procedures, resulting in reduced labour costs; (iv) reduction in laboratory time and space used in connection with tests, resulting in reduced overhead expenses; and (v) improved therapy based upon early, precise diagnosis.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Anticorps monoclonaux pour le genre Staphylococcus, anticorps marqués, compositions et kits les contenant, et leur utilisation pour le diagnostic et le traitement d'antigènes.
EP19850905083 1984-10-19 1985-10-16 Anticorps monoclonaux et leur utilisation Withdrawn EP0203088A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB848426463A GB8426463D0 (en) 1984-10-19 1984-10-19 Monoclonal antibodies
GB8426463 1984-10-19

Publications (1)

Publication Number Publication Date
EP0203088A1 true EP0203088A1 (fr) 1986-12-03

Family

ID=10568432

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19850905083 Withdrawn EP0203088A1 (fr) 1984-10-19 1985-10-16 Anticorps monoclonaux et leur utilisation

Country Status (3)

Country Link
EP (1) EP0203088A1 (fr)
GB (1) GB8426463D0 (fr)
WO (1) WO1986002358A1 (fr)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8621910D0 (en) * 1986-09-11 1986-10-15 Technology Licence Co Ltd Monoclonal antibodies
US5055455A (en) 1988-09-28 1991-10-08 Brigham And Women's Hospital Capsular polysaccharide adhesin antigen, preparation, purification and use
WO1993007487A1 (fr) * 1991-10-09 1993-04-15 Iatron Laboratories, Inc. Procede de detection de staphylococcus aureus resistant au mesitylene, nouveau peptide, et adn le codant
AUPN115095A0 (en) * 1995-02-15 1995-03-09 Butt, Henry Lawrence Analysis of and compositions and methods for the treatment of disease
AUPN350795A0 (en) * 1995-06-13 1995-07-06 Australian National University, The Nucleic acid molecule and its uses in determining pathogenicity of Staphylococcus
US7252828B2 (en) 1998-07-15 2007-08-07 The Brigham And Women's Hospital, Inc. Polysaccharide vaccine for staphylococcal infections
NZ539153A (en) 2002-11-12 2006-11-30 Brigham & Womens Hospital Polysaccharide vaccine for staphylococcal infections
AU2003290867A1 (en) 2002-11-12 2004-06-03 The Brigham And Women's Hospital, Inc. Methods and products for treating staphylococcal infections
EP2439213B1 (fr) 2004-04-21 2018-12-12 The Brigham and Women's Hospital, Inc. Anticorps à liaison de glucosamine poly-N-acétyle (PNAG/DPNAG) et procédés d'utilisation
US7488807B2 (en) 2006-11-22 2009-02-10 3M Innovative Properties Company Antibody with protein A selectivity
ES2660594T3 (es) 2008-07-21 2018-03-23 The Brigham And Women's Hospital, Inc. Métodos y composiciones relacionados con oligosacáridos sintéticos de beta-1,6 glucosamina
TW202311284A (zh) 2017-01-03 2023-03-16 美商再生元醫藥公司 抗金黃色葡萄球菌溶血素ａ毒素之人類抗體
CN115991766A (zh) * 2023-03-13 2023-04-21 广州美健生物技术有限公司 一种细菌抗原检测试剂盒及其应用

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US4461829A (en) * 1981-09-14 1984-07-24 Miles Laboratories, Inc. Homogeneous specific binding assay element and lyophilization production method
CA1262238A (fr) * 1982-09-30 1989-10-10 Richard Insel Anticorps monoclonaux humains contre les toxines bacteriennes

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Also Published As

Publication number Publication date
GB8426463D0 (en) 1984-11-28
WO1986002358A1 (fr) 1986-04-24

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