WO1992019755A1 - ANTICORPS MONOCLONAL CONTRE LA β2 GLYCOPROTEINE I HUMAINE ET UTILISATION DE CET ANTICORPS - Google Patents

ANTICORPS MONOCLONAL CONTRE LA β2 GLYCOPROTEINE I HUMAINE ET UTILISATION DE CET ANTICORPS

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Publication number
WO1992019755A1
WO1992019755A1 PCT/JP1992/000528 JP9200528W WO9219755A1 WO 1992019755 A1 WO1992019755 A1 WO 1992019755A1 JP 9200528 W JP9200528 W JP 9200528W WO 9219755 A1 WO9219755 A1 WO 9219755A1
Authority
WO
WIPO (PCT)
Prior art keywords
human
antibody
glycoprotein
monoclonal antibody
gpi
Prior art date
Application number
PCT/JP1992/000528
Other languages
English (en)
Japanese (ja)
Inventor
Takao Koike
Eiji Matsuura
Hisato Nagae
Original Assignee
Yamasa Shoyu Kabushiki Kaisha
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 Yamasa Shoyu Kabushiki Kaisha filed Critical Yamasa Shoyu Kabushiki Kaisha
Publication of WO1992019755A1 publication Critical patent/WO1992019755A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans

Definitions

  • the present invention relates to a monoclonal antibody specifically reacting with human; 82-glycoprotein I, and use thereof.
  • the first step in solving this challenge is to use anti-Cardio
  • an object of the present invention is to provide a monoclonal antibody capable of specifically measuring human / 3-glycoprotein I, and another object is to provide a monoclonal antibody capable of specifically measuring human / 3-2 glycoprotein I.
  • An object of the present invention is to provide a method and a kit for specifically measuring human / 3-glycoprotein I using a monoclonal antibody.
  • the present inventors have conducted studies to achieve the above object, and as a result, have been able to efficiently obtain a monoclonal antibody that meets the above object, and to use this monoclonal antibody.
  • the present inventors have found that human / 32-glycoprotein I can be specifically measured, and completed the present invention.
  • the present invention relates to a monoclonal antibody that specifically reacts with human / 5-glycoprotein I (hereinafter, may be referred to as “monoclonal antibody of the present invention”). Is concerned.
  • the present invention also provides a kit for measuring human / 32-glycoprotein I containing the monoclonal antibody of the present invention as one of its constituent reagents (hereinafter referred to as “the present invention”). (Kit of the invention).)
  • the present invention provides a method for measuring human 2-glycoprotein I, which comprises using the monoclonal antibody of the present invention as a measuring reagent (hereinafter referred to as “the measuring method of the present invention”). ).
  • FIG. 1 shows the reactivity of the monoclonal antibody CoF15.
  • FIG. 2 shows the reactivity of the monoclonal antibody CoF16.
  • Figure 3 shows the cross-reactivity of the monoclonal antibody CoF5 against various human apolipoproteins.
  • FIG. 4 shows the cross-reactivity of the monoclonal antibody CoF15 with various human-derived apolipoproteins.
  • Figure 5 shows the cross-reactivity of the monoclonal antibody CoF16 against various human apolipoproteins from humans.
  • FIG. 6 shows the species specificity of the monoclonal antibody CoF15.
  • FIG. 7 shows the species specificity of the monoclonal antibody CoF16. (1) in the figure means no serum added.
  • FIG. 8 shows a standard curve in the competitive ELISA method described later.
  • the monoclonal antibody of the present invention typically has the following characteristics, and the use of such a monoclonal antibody only makes it possible to obtain human / 32-glycoprotein in a sample for the first time. I It has become possible to specifically measure
  • the method for producing the monoclonal antibody of the present invention is not particularly limited, and it can be produced by appropriately applying a known method.
  • the immunogen used is human / 3-glycoprotein I, which is described, for example, by the method of McNeill et al. (Pro Natl. Acad. ScL. USA 87: 4120, 1). 990) Can be prepared from fresh water.
  • the degree of purification of the immunogen is not particularly limited.
  • the amino acid sequence and base sequence of human / 5-glycoprotein I are known, and peptides corresponding to a part or all of this known amino acid sequence can be obtained. It may be prepared chemically by a known method and used as an immunogen. If the synthesized peptide has poor antigenicity, it may be combined with a polymer carrier commonly used for the production of antibodies for hapten antigens such as serum albumin and keyhole lysate. It is preferable to use the body as an immunogen.
  • human / 52-glycoprotein I may be prepared by a DNA recombination technique using a known nucleotide sequence, and this may be used as an immunogen.
  • the animals to which the immunogen is to be administered include: horses, horses, pigs, sheep, goats, rats, mice, guinea pigs, dogs, dogs, bushes, rabbits, rabbits, pigeons, nits
  • the mouse, rat, guinea pig, egret, goat, sheep, etc. are particularly convenient for use.
  • the administration of the immunogen to such animals may be performed in a conventional manner, for example, complete Freund's adjuvant, incomplete Freund's adjuvant, myocardial adjuvant, or water.
  • a suspension of various adjuvants such as aluminum oxide adjuvant and B. pertussis adjuvant and the above-mentioned immunogen may be prepared and administered to the above animals intravenously, intraperitoneally, subcutaneously or intradermally. .
  • Dosage should be 0.1 to 10 mgZ per mouse or rat, or 0.1 to 10 mgZ if a guinea pig is used. About 01 to lmg animals are preferred.
  • booster immunization against human / S2-daricoprotein I is performed in the animal body by boosting about 1 to 5 times as above every 1 to 4 weeks. Induces antibody production.
  • antibody-producing cells such as spleen cells, lymph node cells, and peripheral blood lymphocytes from the animals that have acquired immunity are obtained by a conventional method.
  • myeloma cells to be fused with the antibody-producing cells cell lines derived from various animals such as mice, rats, and humans and commonly available to those skilled in the art are used.
  • a cell line to be used a cell line which has drug resistance, cannot survive in a selection medium in an unfused state, and can survive only in a state fused to an antibody-producing cell is preferable.
  • an 8-azaguanine resistant strain is used, and this cell line is deficient in hypoxanthine-guanine phosphophorase (Hypoxantine guanine p osphoribosyl transferase).
  • Hypoxanthine ' cannot grow on AMINO-Pterin-Thymidine (HAT) medium, and it is a so-called non-secretory cell line that does not secrete immunoglobulin. I like it. '
  • a specific example of a myeloma cell line is P3X63Ag8 (ATCCTIB-9) (Nature, 256, 495- 497 (1975 ", P 3 x 63 Ag 8 U. 1 (P3U 1) (ATCCCRL-1597) (Current Topics in Microbiology and Immunology, 81, 1-7 (1978)), P 3 x63Ag8.653 (ATCCCRL-1580) (J. Immunology.123.1548-1550 (1979)), P2 / NSI-Ag4-1 (ATCCTIB-18) (European J. Immunology, 6, 511-519 (1976)).
  • Cell fusion Eagle's minimum essential medium (ME M), da ⁇ Beck co-modified Eagle's medium (DMEM), RPMI - 1 6 4 0 medium of any animal cell culture medium 1 0 6-1 0 3
  • ME M Eagle's minimum essential medium
  • DMEM da ⁇ Beck co-modified Eagle's medium
  • Can In order to promote cell fusion, polyethylen glycol (PEG) with an average molecular weight of 1,000 to 6,000 and polyvinyl alcohol (PEG) are used to promote cell fusion. And fusion promoters such as Sendai virus can be used.
  • antibody-producing cells and myeloma cells can be fused using a commercially available cell fusion device using electric pulses.
  • a method utilizing selective growth of cells in a selective medium can be used.
  • cell suspension 1 5% ⁇ Shi calf serum (FCS) containing RPMI - 1 6 4 0 medium, etc.
  • FCS Shi calf serum
  • microphones LOP rate on the 1 0 3 to 1 0 6 Add a selection medium (for example, HAT medium) to each well until the wells are about the same volume, and then exchange the selection medium appropriately before culturing.
  • HAT medium for example, unfused myeloma cells died by about day 10 of culture, and were normal. Since antibody-producing cells, which are cells, cannot grow in vitro (in vitro) for a long period of time, the cells that grow on the 10th to 14th day of cultivation are defined as Neubridomas. Obtainable.
  • the search for hybridomas producing monoclonal antibodies recognizing human / S2-glycoprotein I was performed by enzyme-linked immunosorbent assay (EIA, ELISA) and radioimmunoassay. This can be done by using an RIA, for example.
  • EIA enzyme-linked immunosorbent assay
  • ELISA enzyme-linked immunosorbent assay
  • radioimmunoassay radioimmunoassay.
  • RIA for example, 96-well E with human / 32-glycoprotein I adsorbed A culture supernatant containing a monoclonal antibody is added to the microplate for LISA to react with human ⁇ 2-glycoprotein I, and then the enzyme-labeled anti-immunoglobulin antibody is added to the bound specific antibody.
  • an avidin D—enzyme receptor is reacted. Then, in each case, an enzyme substrate is added to each well to develop color. Reacts specifically with human jS2-glycoprotein I by selecting the culture supernatant that develops color only with the wells on which human 32-glycoprotein I is immobilized. You can search for hybridomas that produce antibodies.
  • human 2-glycoprotein I used in the above-mentioned screening those having a high degree of purification are preferred, and specifically, those having a degree of purification of 90% or more are preferably used. As a result, it is possible to efficiently screen a hybridoma that produces a monoclonal antibody that specifically reacts with human ⁇ 2-glycoprotein I.
  • Cloning of the hybridoma can be performed by a limiting dilution method, a soft agar method, a fibringel method, a fluorescence excitation cell sorter method, or the like.
  • a normal cell culture method As a method for producing a monoclonal antibody obtained in this manner, a normal cell culture method, an ascites formation method, or the like may be employed.
  • the hybridomas are RPMI-164 medium containing 10 to 15% FCS, serum-free medium, etc.
  • the antibody can be obtained from the culture supernatant by culturing in an animal cell culture medium in a usual manner.
  • the method of recovery from ascites involves the use of minerals such as pristane (2,6,10,14—tetramethyl pentyldecane) in animals of high predominance and tumor tissue compatibility.
  • minerals such as pristane (2,6,10,14—tetramethyl pentyldecane)
  • the oil is intraperitoneally administered, for example, in the case of a mouse, about 100 s of hybridomas are intraperitoneally administered.
  • Hybridomas form ascites tumors around 10 to 18 days and produce high concentrations of antibodies in serum and ascites.
  • the measurement method of the present invention is characterized by using the above-described monoclonal antibody of the present invention as a reagent, and is not limited by the measurement principle, conditions, and the like.
  • a competitive reaction method and a non-competitive reaction method are known, and either method can be employed in the present invention.
  • Classification according to the detection method includes a non-labeling method that directly detects the results of the antigen-antibody reaction (such as nephrometry) and a labeling method that detects using a marker. Is known However, in the present invention, any method may be used.
  • Heterogeneous methods that require BF separation and homogenous methods that do not require BF separation are known, and any of these methods may be applied to the present invention.
  • the liquid phase method in which the entire reaction is carried out in the liquid phase and the solid phase method in which the reaction of the immune reaction is performed by immobilizing the partner on the solid phase are known. Can also be adopted.
  • a method suitable for the purpose of the measurement method of the present invention may be appropriately selected from these known general methods.
  • the mode of use of the monoclonal antibody of the present invention used in the assay of the present invention may be appropriately derived according to the assay used.
  • Specific examples include a labeled antibody and a solid-phased antibody.
  • the antibody to be used may be the antibody itself, but it is preferable to use an active fragment of the antibody from the viewpoint of preventing nonspecific adsorption.
  • the active fragment of an antibody can be any fragment that retains the characteristics of the antibody (for example, F (ab ') 2Fab', Fab, etc.). It may be. Preparation of these active fragments can be carried out by applying a known method such as a method of subjecting the purified antibody to limited degradation using a protease such as papine, pepsin, or trypsin. (See, for example, "Research Methods for Immunochemical Chemistry (Seismic Chemistry Laboratory Course 5) J, edited by The Biochemical Society of Japan, p. 89 (1989))."
  • Labeling agents that bind to antibodies include radioisotopes (for example, 32 P, 3 H, 14 C, etc.), enzymes (for example, Lactosidase, peroxidase, alkaline phosphatase, glucose-6-phosphate dehydrogenase, power tarase, glucosoxidase, lactate oxidase, alcoholoxidase, monoamido Oxidases), coenzyme / prosthetic groups (eg, FAD, FMN, ATP, piotin, heme), fluorescein derivatives (eg, fluorescein isothiocyanate, fluorescein thiofluva) Mil), rhodamin derivatives (eg, tetramethyl rhodamin B isothiocyanate), umbelliferone, and 1-anilino-1 8 Fluorescent dyes such as naphthalenesulfonate, luminol derivatives (for example, luminol, iso
  • the carrier substance for immobilizing the antibody for example, poly (vinyl chloride), polystyrene, styrene-vinyl divinylbenzene copolymer, styrene-monovinyl maleate copolymer are used.
  • Polymer Nylon, Polyvinyl alcohol, Polyacrylamide, Polyacrylonitrile, Polypropylene, Polymethylenemethacrylate Synthetic organic polymer compounds such as Polysaccharides such as kisstran derivatives (such as Sephadex), agarose gels (such as Sepharose and biogel), cellulose (such as paper discs and filter paper), glass, silica gel, Examples thereof include inorganic polymer compounds such as silicones, which may have a functional group such as an amino group, an aminoalkyl group, a carboxyl group, an acyl group, or a hydroxyl group introduced therein. .
  • the material of the carrier substance is preferably a substance having a low protein-binding ability, and examples of such a material include untreated polystyrene and polyvinyl chloride.
  • the carrier material can be in the form of a plate (microtiter plate, disk, etc.), particulate (beads, etc.), tubular (test tube, etc.), fibrous, film-like, particulate (lambda). Examples thereof include particles such as particles, capsules, and endoplasmic reticulum, and a carrier having an appropriate shape can be selected according to the measurement method.
  • ribosomes multilayer or monolayer lipid membrane
  • the binding method between the monoclonal antibody of the present invention and the carrier substance may be a known method such as a physical adsorption method, an ion binding method, a covalent binding method, and an inclusive method (for example, “immobilized enzyme” (Chibatake) (Ichiro Edition, March 20, 1980, published by Kodansha Co., Ltd.)).
  • a physical adsorption method for example, “immobilized enzyme” (Chibatake) (Ichiro Edition, March 20, 1980, published by Kodansha Co., Ltd.)
  • the physical adsorption method is preferred because it is simple.
  • the above-mentioned binding may be performed directly, or may be performed via another substance between the two substances.
  • Kit of the present invention The kit of the present invention is characterized in that the monoclonal antibody of the present invention is contained as one of the constituent reagents of the kit. It may be different depending on the law.
  • the following reagent composition is used.
  • Anticancer antigen (antibody)
  • Antibody J is the monoclonal antibody of the present invention, and" antigen "is human yS2-glycoprotein I, needless to say. Absent.
  • the "first antibody” and the “second antibody j” recognize different antigenic determinants on human S2-glycoprotein I. This can be easily understood from the measurement principle, and the kit configuration based on the sandwich method is, for example, as follows.
  • the present invention is useful as a tool for elucidating the mechanism of onset of anti-cardiolipin antibody syndrome.
  • Human / S2-GPI (0.2 mg / m 1) prepared by a known method (Pro Natl. Acad. Sci. USA 87: 4120 (1990)) was dissolved in physiological saline and completely dissolved.
  • BALBZc mice female, 6-week-old were intraperitoneally administered 10 g / 00 a1 (ip, mixed with Freund's adjuvant in a 1: 1 ratio to give emalgiones). ) And the first immunization.
  • immunizations i.P.
  • a human / 32-GPI saline solution (1 OzgZlO0 / 1 ) was administered (i.V.) to the tail vein of the mouse.
  • MEM Eagle's minimum essential medium
  • the mouse myeloma P3X63Ag8U1 (P3U1) (ATCCCRL-1579) is washed with MEM, and spleen cells and P3U1 are mixed at a ratio of 10: 1. After centrifugation, add 50% poly to the pellet obtained by centrifugation. Cell fusion was performed by gradually adding 1 ml of a MEM solution containing 1000 g of polyethylene glycol (PEG). Further, add the MEM solution to make up to 1 Oml, and centrifuge the pellet, and add P3U1 to the RFMI-164 medium containing 10% fetal calf serum (FCS). to 3 xl 0 4 were suspended at a cell Z 0.
  • PEG polyethylene glycol
  • HAT medium MEMS medium containing hypoxanthin-thymidine-aminobuterin
  • Hybridomas were screened on day 14 after fusion. That is, 96-Elmic was coated with purified human 52-GPI (purity: 999 or more) (10 g / ml) and blocked with 1% serum albumin (BSA). (B) The culture supernatant (501) was added to the evening plate and reacted at room temperature for 1 hour. After washing three times with PBS200Z1, 5001 of a solution of a biotinylated anti-mouse IgG (manufactured by Vector) was added, and the mixture was further reacted at room temperature for 1 hour.
  • a biotinylated anti-mouse IgG manufactured by Vector
  • the plate was washed three times with PBS, added with a solution of avidin D-peroxidase (manufactured by Vector Inc.) 50 // 1 and reacted at room temperature for 30 minutes.
  • the substrate solution (4-aminoantipyrine (0.25 mgZm1)), phenol (0.25 mg / ml), 0.2% Add 4 25 M hydrogen peroxide), react at room temperature, measure the absorbance at 550 nm, and specifically react with human 2-GPI. Reactive antibodies were detected, and specific antibody-producing hybridomas were selected (Table 1).
  • C0F5, C0F15, C0F16 Three types of established cell lines (C0F5, C0F15, C0F16) were intraperitoneally injected with mouse treated with 0.5 ml of virgin pristine. 3 ⁇ 10 6 were administered to the mice, and ascites was collected about 2 weeks later. After diluting by adding an equal volume of PBS in the collected ascites, addition of sulfuric acid A Nmoniu ⁇ , 5 fractions precipitated at 0% saturation A emissions monitor ⁇ beam sulfate concentration was recovered by centrifugation (precipitated fraction of this Was re-dissolved in PBS and dialyzed against the same buffer for 2 days, followed by protein A-Sepharose scalar to purify IgG from the crude ammonium sulfate fraction described above.
  • the nitrocellulose membrane thus obtained was cut into strips along the electrophoresis line of the sample, and a portion was stained for protein using an amide black.
  • the other membrane was blocked by immersing it in a 3% gelatin solution at 37 ° C for 1 hour, and then appropriately diluted with PBS.
  • Monoclonal anti-human / 52-GPI antibody (Cof5, C O F 15 and C O F 16) were reacted at room temperature for 1 hour. After sufficient washing with PBS, the cells were reacted with a peroxidase-labeled anti-mouse IgG antibody for 1 hour at room temperature.
  • nitrose cellulose membrane was washed in the same manner, and a substrate solution (30 mg of color developer (manufactured by Biorad), 10 ml of methanol, 50 ml of PBS, and 50 ml of PBS) And hydrogen peroxide solution (containing 301)), and when the color of the mixture became suitable, the reaction was stopped by washing with water.
  • a substrate solution (30 mg of color developer (manufactured by Biorad), 10 ml of methanol, 50 ml of PBS, and 50 ml of PBS) And hydrogen peroxide solution (containing 301)
  • the reaction was stopped by washing with water.
  • all three monoclonal antibodies (Cof5, Cofl5, and Cofl6) showed extremely strong reactivity with human 2-GPI with a molecular weight of 5 OkD. It did not react with any other human-derived serum proteins.
  • the basic ELISA procedure for the specificity analysis of monoclonal antibodies is as follows. Purified human / S2-GPI in PBS (5 ⁇ gZml) was added to each of the 96-well micromicroplate evening plates, and left at 4 ° C for 1 2. , 1% BSA-containing PBS 200 // 1 in each well It was left at room temperature for 1 hour before blocking. After washing three times with PBS, various monoclonal antibodies
  • Figures 1 and 2 show the reactivity of the monoclonal antibodies C0F15 and CoF16 with the immobilized human S2-GPI, respectively. That is, as shown in the figure, a plate coated with human / 32-GPI (5 ⁇ g / m 1, PBS as a control) and blocked with 1% BSA as shown in the figure. When the antibody was reacted with ⁇ 20 g Zml, CoFl5 and CofF16 were applied to the human / 52-GPI (10 ⁇ g / ml) immobilized plate. Both antibodies bound in a concentration-dependent manner.
  • Antigen specificity of monoclonal antibodies comparison of the inhibitory activities of apolipoproteins from various humans
  • Figures 3 to 5 show apolipoproteins (apolipoprotein H (ap0H), apolipoprotein A1 (apoAl), and apolipoprotein A derived from various human antibodies. 2 (ap 0 A 2), Apolipoprotein B (apo B), And the results of examining the presence / absence of cross-reactivity to apolipoprotein E (apoE)).
  • the binding of any of the monoclonal antibodies (Cof5, Cof15, Cof16) to immobilized human 52-GPI was 0.4 to 10 gm aml.
  • lipoprotein H ie, 2-GPI
  • apolipoproteins ie, apo A1, apo A2, apo B, and apo E
  • hybridomas other than the above C0F5, C0F6, C0F18, C0F19, C0F20, C0F21, Similar results were obtained when the same experiment was performed with respect to the monoclonal antibody produced by Cof22 and Cof23).
  • each antibody was confirmed by measuring the inhibitory activity using a human / 82-GPI solid phase plate.
  • a purified human / 52-GPI antigen solution dissolved in PBS to a concentration of 10 ⁇ g nom 1 was applied to 96-well microplates (Falcon) at a volume of 1 ⁇ l per 5 ⁇ l. Aliquots of 0 to 1 were added, and the mixture was allowed to stand at 4 ° C to bind the antigen to the plate. Remove the residual antigen solution using an aspirator, dispense 2001 PBS per well, and remove the plate using an aspirator. Was washed. The above washing operation was repeated three times. Invert the washed plate and gently tap it several times on a paper towel to remove the liquid remaining in the gel, and then add 3% gelatin-PBS solution to 200 ⁇ l per 1 ⁇ l. The mixture was dispensed and allowed to stand at 25 ° C for 30 minutes. After standing, the liquid was removed from the gel, and the liquid was thoroughly beaten several times on paper paper to completely remove the remaining liquid.
  • the plate was washed three times according to the above procedure, and the secondary antibody was dispensed at a concentration of 501 per unit.
  • a peroxidase (HR ⁇ ) -labeled goat anti-money IgG antibody was used for the ale to which the antiserum derived from heron was reacted.
  • HRP-labeled goat anti-mouse IgG antibody was appropriately diluted with a 1% BSA-PBS buffer solution and dispensed into the wells reacted with the clonal antibody solution.
  • the inhibitory activity was expressed as the inhibition rate (), where the color development of the control group was 100, the color development of the wells containing each solution was calculated, and the value was subtracted from the force of 100. .
  • the binding of the egret antiserum to human ⁇ 2-GPI was significantly inhibited in both rat serum and chicken serum.
  • the binding of mouse antiserum was also inhibited by rat serum.
  • the monoclonal antibodies of the present invention (C of 6, C0f20, Cof22, and Cof23) can be used in any of rat serum and human serum. Almost no inhibition of binding was observed, and the monoclonal antibody of the present invention did not react with rat ⁇ 2-GPI and cis-2-GPI, and was specific for human / 32-GPI This was reconfirmed.
  • the previously prepared human S 2 -GPI solid phase plate was subjected to washing and blocking treatments in the same procedure as in Example 4, and the standard was treated with HEPES buffer.
  • a purified human ⁇ 2-GPI solution dissolved at a concentration of 0.06 to 64 g / ml, and a HEPES buffer solution as a control group were dispensed at a ratio of 25 1 per well.
  • the measured value obtained as described above is calculated as the inhibition ratio expressed by determining the color development ratio of the control group as 100, and then subtracting that value from 100.
  • the human ⁇ 2 in the range of about 1 to 300 ⁇ g Zml was used. -It is possible to measure GPI.
  • the present invention specifically reacts with human ⁇ 2-glycoprotein I
  • the monoclonal antibody of the present invention is extremely useful as a tool for elucidating the onset mechanism of, for example, anti-cardiolipin antibody syndrome.

Abstract

La présente invention permet d'obtenir un anticorps monoclonal réagissant spécifiquement avec la β2 glycoprotéine I humaine et de détecter spécifiquement la β2 glycoprotéine I humaine dans un spécimen par l'utilisation de l'anticorps.
PCT/JP1992/000528 1991-04-24 1992-04-23 ANTICORPS MONOCLONAL CONTRE LA β2 GLYCOPROTEINE I HUMAINE ET UTILISATION DE CET ANTICORPS WO1992019755A1 (fr)

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JP3/94313 1991-04-24
JP9431391 1991-04-24

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0643077A1 (fr) * 1993-09-14 1995-03-15 Sumitomo Electric Industries, Ltd Anticorps monoclonal contre la molécule B70
WO1995009363A1 (fr) * 1993-09-29 1995-04-06 Yamasa Corporation Procede de titrage de lipoproteine oxydee et applications de ce procede
FR2723204A1 (fr) * 1994-08-01 1996-02-02 Orstom Procede de detection et/ou de dosage de compose(s) infectueux dans un materiau biologique et support utilise pour ledit procede
WO1996004559A1 (fr) * 1994-08-01 1996-02-15 Institut Français De Recherches Scientifiques Pour Le Developpement En Cooperation - Orstom Procede de separation et/ou de detection et/ou de quantification de compose(s) infectieux et support pour la mise en ×uvre du procede
JP2013501920A (ja) * 2009-08-07 2013-01-17 アスチュート メディカル，インコーポレイテッド 腎損傷および腎不全の診断および予後診断のための方法ならびに組成物

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
AMERICAN JOURNAL OF HUMAN GENETICS, Vol. 42, No. 3, (1988), M.I. KAMBOH et al., "Genetic Studies of Human Apolipoproteins. IV. Structural Heterogeneity of Apolipoprotein H (beta2-Glycoprotein I)", p. 452-457. *
JOURNAL OF BIOLOGICAL CHEMISTRY, Vol. 260, No. 24, (1985), J. BORENSZTAJN et al., "Fractionation of Chylomicrons by Heparin-Sepharose Chromatography", p. 13047-13052. *
JOURNAL OF LABORATORY AND CLINICAL MEDICINE, Vol. 111, No. 5, (1988), M.L. HENRY et al., "Inhibition of the Activation of Hageman Factor (Factor XII) by beta2-Glycoprotein I", p. 519-523. *
NATURE, Vol. 256, (1975), G. KOEHLER et al., "Continuous Cultures of Fused Cells Secreting Antibody of Predefined Specificity", p. 495-497. *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0643077A1 (fr) * 1993-09-14 1995-03-15 Sumitomo Electric Industries, Ltd Anticorps monoclonal contre la molécule B70
WO1995009363A1 (fr) * 1993-09-29 1995-04-06 Yamasa Corporation Procede de titrage de lipoproteine oxydee et applications de ce procede
FR2723204A1 (fr) * 1994-08-01 1996-02-02 Orstom Procede de detection et/ou de dosage de compose(s) infectueux dans un materiau biologique et support utilise pour ledit procede
WO1996004559A1 (fr) * 1994-08-01 1996-02-15 Institut Français De Recherches Scientifiques Pour Le Developpement En Cooperation - Orstom Procede de separation et/ou de detection et/ou de quantification de compose(s) infectieux et support pour la mise en ×uvre du procede
US6465191B1 (en) 1994-08-01 2002-10-15 Institut Francais De Recherches Scientifiques Pour Le Developpement En Cooperation-Orstom Process for separating and/or detecting and/or quantifying (an) infectious compound(s) and support for implementing the process
JP2013501920A (ja) * 2009-08-07 2013-01-17 アスチュート メディカル，インコーポレイテッド 腎損傷および腎不全の診断および予後診断のための方法ならびに組成物

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