Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Patent
1994-04-14
1998-03-31
Mosher, Mary E.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
530300, 530327, 530328, 530329, 424569, A61K 3900, A61K 39385, C07K 412
Patent
active
057335494
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to peptides selected from apolipoprotein (a) that is a constituent of lipoprotein (a) being a risk factor involved in arteriosclerosis and having clinical significance, immunogens for producing antibodies which recognize lipoprotein (a) or apolipoprotein (a) or peptides comprising constituent parts thereof, antibodies recognizing lipoprotein (a) or apolipoprotein (a) or peptides comprising constituent parts thereof, and methods for the determination of lipoprotein (a) or apolipoprotein (a) using these antibodies.
BACKGROUND ART
369-382(1963)!. As a result of subsequent various investigations, it has been found that lipoprotein (a) is a substance consisting of low-density lipoprotein (LDL) which usually plays a major role in transporting (a)! which is a protein peculiar to lipoprotein (a), the protein moiety of LDL (i.e., apolipoprotein B-100) and apolipoprotein (a) being linked to each other by a disulfide bond (see FIG. 36).
Apolipoprotein (a) comprises at most 37 portions having high homology with a structure, called Kringle 4, of plasminogen, a portion having high homology with the Kringle 5 structure of plasminogen, and a serine protease structure portion with a region having high homology with plasminogen. Of these 37 Kringle portions, 28 have a completely repeating structure.
Moreover, it has been reported that various isotypes (phenotypes) of 458-465(1987); H. G. Kraft et al., Arteriosclerosis, 8, 212-216(1988); G. Utermann et al., Hum. Genet., 78, 41-46(1988)!. This is considered to be due to differences in the number of repetition of the Kringle Biol. Chem., 266, 5480-5485(1991)!. As a result of fractionation by a combination of SDS electrophoresis and an immunological blot technique, F, J. Clin. Invest., 80, 458-465(1987)!.
Clinically, it has been found that the level of lipoprotein (a) is high in many patients with ischemic heart diseases such as angina pectoris and 1-29(1972); K. Berg et al., Clin. Genet., 16, 347-352(1979); G. M. Kostner et al., Atherosclerosis, 38, 51-61(1981)!. Moreover, it has been reported that lipoprotein (a) shows no correlation with known risk factors involved in ischemic heart diseases, such as cholesterol, LDL-cholesterol and HDL-cholesterol, and is a new independent risk factor involved in Biophys. Acta, 236, 431-439(1971); H. Schriewer et al., J. Clin. Chem. Clin. Biochem., 22, 591-596(1984)!.
In 1987, Eaton et al. determined the amino acid sequence of apolipoprotein Acad. Sci. U.S.A., 84, 3224-3228(1987)!. Then, McLean et al. determined it 330, 132-137(1987)!.
Thus, it has been found that the greater part of the molecular structure of apolipoprotein (a) is composed of portions having high homology with the plasminogen molecule acting on the fibrinolytic system.
This suggests that lipoprotein (a) and apolipoprotein (a) will provide an important key when arteriosclerosis, lipoprotein and the blood clotting and fibrinolytic system are considered from an identical point of view.
Moreover, it has been reported that lipoprotein (a) is not only a risk factor involved in arteriosclerosis, but also shows an increasing tendency in patients with diabetic nephropathy or reconstriction after PTCA (percutaneous transluminal coronary angioplasty), and that lipoprotein (a) behaves like acute phase reactive proteins such as CRP. Thus, the determination of lipoprotein (a) and apolipoprotein present in biological samples such as blood has come to be of important significance from a clinical point of view and, therefore, there is a demand for a method which enables accurate determination of lipoprotein (a) and apolipoprotein (a).
The determination of lipoprotein (a) is being made according to immunological assay techniques such as single immunodiffusion, rocket immunoelectrophoresis, turbidimetric immunoassay, latex turbidimetric Clin. Chim. Acta, 177, 31-40(1988)!. If an antibody prepared by administering lipoprotein (a) as an immunogen to an animal is used directly in these immunological assay techniques, it is impossible to obtained accura
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Inoue Keiichi
Kitajime Megumi
Sakurabayashi Ikunosuke
Yamada Shingo
Yoshimura Hajime
Mosher Mary E.
Scheiner Laurie
Shino-Test Corporation
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