Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
2001-06-22
2004-12-07
Nguyen, Bao-Thuy L. (Department: 1641)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S007100, C435S007940, C435S007920, C436S518000, C436S547000, C436S548000, C530S380000, C530S388100, C530S388150, C530S389300
Reexamination Certificate
active
06828114
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a monoclonal antibody against a specific human apolipoprotein A-I (hereinafter referred to as “apoA-I”); a method of immunologically assaying a specific apoA-I by use of the antibody; and an immunological assay reagent containing the antibody.
BACKGROUND ART
ApoA-I is a predominant apoprotein that constitutes HDL and plays an important role in reserve cholesterol transportation from peripheral cells to the liver (Philips M. C. et al.,
Biochem. Biophys
. Acta, 906: p. 223 (1987)). Therefore, apoA-I assay is performed in the diagnosis of arteriosclerosis.
In recent years, researchers have elucidated that an HDL containing apoA-I but containing no apolipoprotein A-II (hereinafter referred to as “apoA-II”) (Ishizuka et al., “
Igaku to Yakugaku
,” Vol. 39, No. 5, p. 1041, 1988) exhibits a stronger effect of pulling cholesterol from cells as compared with an HDL containing both apoA-I and apoA-II, and that an apoA-I not binding to a lipid and an apoA-I which is in the form of small particles and occurs in pre&bgr;1-HDL containing a small amount of lipid (T. Miida et al.,
Biochemistry
, 29: p. 10469 (1990)) play an important role in reverse cholesterol transport system from cells. Accordingly, assaying these specific apoA-I's is of increased importance. Among HDLs containing apoA-I but containing no apoA-II, pre&bgr;1-HDL pulls cholesterol from peripheral cells through interaction specific to the cell surface (Fielding, C. et al.,
Lipid Res
., 36: p. 211-228 (1995)), and its action is more effective than that of HDL. Thus, pre&bgr;1-HDL is particularly attracting researcher' attention.
However, since no antibody that selectively reacts with a specific apoA-I has been found, the target apoA-I must be isolated from other apoA-I's through a method such as electrophoresis or immune precipitation. Thus, a specific apoA-I cannot be assayed in a simple manner.
DISCLOSURE OF THE INVENTION
In view of the foregoing, the present inventors have carried out extensive studies and have successfully obtained a monoclonal antibody which specifically reacts with a certain species of apoA-I. The inventors have found that, by use of the monoclonal antibody, apoA-I's such as the aforementioned apoA-I not binding to a lipid and apoA-I composing pre&bgr;1-HDL can be assayed accurately in a simple manner, thereby enabling more accurate diagnosis of lipid metabolism disorder to be performed. The present invention has been accomplished on the basis of this finding.
Accordingly, the present invention provides a monoclonal antibody reacting specifically with (1) an apoA-I occurring in HDL which contains no apoA-II and has a molecular weight of 150,000 or less and (2) an apoA-I not binding to a lipid.
The present invention also provides a hybridoma for producing the monoclonal antibody.
The present invention also provides a method of immunologically assaying apoA-I, characterized by reacting the monoclonal antibody with a specimen.
Furthermore, the present invention provides a reagent for assaying an apoA-I containing the monoclonal antibody.
REFERENCES:
S. Marcovina, et al., Journal of Lipid Research, vol. 31, pp. 375-384, XP-001057022, “Immunochemical Characterization of Six Monoclonal Antibodies to Human Apolipoprotein A-I : Epitope Mapping and Expression”, Mar. 1990.
O. Miyazaki, et al., Journal of Lipid Research, vol. 41, pp. 2083-2088, XP-001057017, “A New Sandwich Enzyme Immunoassay for Measurement of Plasma PRE-&bgr; 1-HDL Levels”, Dec. 2000.
C. J. Fielding, et al., Journal of Lipid Research, vol. 36, No. 2, pp. 211-228, “Molecular Physiology of Reverse Cholesterol Transport”, 1995.
P. E. Fielding, et al., Ciochemistry, vol. 33, No. 22, pp. 6981-6985, “Unique Epitope of Apolipoprotein A-I Expressed in PRE-&bgr;-1 High-Density Lipoprotein and its Role in the Catalyzed Efflux of Cellular Cholesterol”, 1994.
O. Gursky, et al., Proc. Natl. Acad. Sci. USA, vol. 93, No. 7, pp. 2991-2995, “Thermal Unfolding of Human High-Density Apolipoprotein A-1: Implication for a Lipid-Free Molten Globular State”, Apr. 1996.
D. L. Sparks, et al., Biochemistry, vol. 38, No. 6, pp. 1727-1735, “Effect of Apolipoprotein A-I Lipidation on the Formation and Function of PRE-&bgr; and &agr;-Migrating LpA-I Particles”, Feb. 1999.
T. Miida, et al., Biochemistry, vol. 29, No. 46, pp. 10469-10474, “Mechanism of Transfer of LDL-Derived Free Cholesterol to HDL Subfractions in Human Plasma”, 1990.
E.D. Bekaert, et al., Clinical Chemistry, vol. 34, No. 6, pp. 1030-1035, “Competitive Enzyme Inhibition Immunoassay of Apolipoprotein A-I: Use of Monoclonal Antibodies”, 1988.
Fukamachi Isamu
Miyazaki Osamu
Daiichi Pure Chemicals Co. Ltd.
Nguyen Bao-Thuy L.
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