Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
1996-02-20
2001-07-10
MacMillan, Keith (Department: 1618)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S334000, C436S527000, C436S172000, C530S388220, C530S389200, C530S391100, C530S391300
Reexamination Certificate
active
06258552
ABSTRACT:
BACKGROUND OF INVENTION
1. Field of Invention
The present invention relates a method for estimation of change in bone mineral density and a method for diagnosis of osteoporosis as well as a kit used for said methods.
2. Related Art
Interleukin-6 (IL-6) is reported to be a multifunctional cytokine, and it has recently become known that one of the functions of IL-6 is stimulation of bone absorption. On the other hand, it is also known that a decrease in the secretion of estradiol in the post-menopausal phase results in an increase of the production of IL-6, and on the basis of these findings, it has been pointed out that there is a possibility that IL-6 is involved in causing osteoporosis.
Interleukin-6 receptor (IL-6R) is a protein which has a molecular weight of about 80 kDa and binds with IL-6 resulting in formation of a ligand-receptor complex. The complex of IL-6 and IL-6R, in turn, binds with a protein called gp130 protein, having a molecular weight of about 130 kDa, so as to be responsible for IL-6-mediated signal transduction (Japanese Unexamined Patent Publication (Kokai) No. 4-29997).
IL-6R is a membrane protein comprising a intramembrane domain, a membrane-penetrating portion and an extracellular domain, and it is known that the extracellular domain having a molecular weight of about 55 kDa is detected in serum and urine (Eur. J. Immunol. Vol. 23, pp. 820-824, 1993).
It is reported that soluble IL-6R (sIL-6R), which is a part of IL-6R and is detected in serum and urine, increases in a patient with myeloma or AIDS, and therefore it is considered that the sIL-6R plays an important role in IL-6R-related diseases (Guilard J. P. et al., Eur. J. Immunol. Vol. 23, pp 820-824, 1993; and Honda M. et al., J. Immunol. Vol. 148, pp. 2175-2180, 1992).
With coming of the so-called high-age society, the number of patients suffering from osteoporosis is increasing, and the foreseeing and treatment thereof are becoming an important matter. One of the most important things relating to osteoporosis is to determined the risk of osteoporosis as easily as possible and to prevent the occurance thereof.
A factor most directly related to the frequency of generation of bone fractures is the amount of bone (bone mineral density), and the bone mineral density is measured by image diagnosis and X-ray absorption methods. Among them, at present, dual X-ray absorptiometry (DXA) is the most popular method, and its reliability is high. However, the apparatus for DXA is so expensive that only a few hospitals have the apparatus, and thus the DXA is difficult to use routinely. Morover, since DXA uses radiation, this method cannot be applied to pregnant women. In addition, although the DXA method can be used to measure bone mineral density at the point time in at which the measurement is carried out, it cannot be used to estimate a future decrease of bone mineral density, in other words, DXA cannot show metabolic turnover of bone.
On the other hand, it is considered that post-menopausal osteoporosis is caused by an unbalance between bone formation and bone resorption resulting in an increase of bone resorption, and measurement of a bone metabolism marker which reflects bone metabolism is brought to attention. Although as a biochemical marker of bone metabolism which can be used to selectively evaluate bone resorption, deoxypyridinoline is brought to attention; and as marker of bone metabolism which can be used to evaluate bone formation osteocalcin is brought to attention, the former is disadvantageous in that since it is measured in a urine sample, the results vary during a day, and are influenced by kidney clearance functions. The obtained data should be corrected using creatinaine concentration. On the other hand, the latter is disadvantageous in that a sample serum includes various degradation products of osteocalcin, and the component measured is not clear.
As can be seen from the above, although the importance of the estimation and diagnosis of the osteoporosis has been recognized, at present, there is no routine method for measurement of a bone metabolism marker.
SUMMARY OF INVENTION
The present inventors, in the above-mentioned state of the art, searched for substances whose concentration changes concomitantly with the loss or increase of bone mineral density which causes the osteoporosis, and as a result found that the concentration of sIL-6R in a blood sample increases with a loss of bone mineral density, and completed the present invention.
Accordingly, the present invention provides a method for estimation of change in bone mineral density, comprising the step of measuring change in a concentration of soluble interleukin-6 receptor (sIL-6R) in a blood sample.
The present invention further provides a method for diagnosis of osteoporosis comprising the step of measuring the concentration of sIL-6R in a blood sample.
The present invention still further provides a kit for estimating change in bone mineral density or diagnosis of osteoporosis, comprising:
(1) an anti-sIL-6R antibody immobilized to a solid carrier, and
(2) an anti-sIL-6R antibody which is bound to a detectable marker or which can bind to a detectable marker.
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Honda et al, The Journal of Immunology, vol. 148, pp. 2175-2180, No. 7, Apr. 1992.*
Manolagas et al, Int. J. Immunopharmac., vol. 17. No. 2, pp. 109-116, 1995.*
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Chen Jui-Tung
Maruo Naoko
Morita Ikuo
Shiraki Masataka
Jacobson Price Holman & Stern PLLC
MacMillan Keith
Ponnalun P.
Tosoh Corporation
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