Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...
Patent
1997-05-09
2000-01-25
Mertz, Prema
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Blood proteins or globulins, e.g., proteoglycans, platelet...
5303879, 5303881, 53038815, 5303891, 435325, 435326, 435328, 435331, 435334, C07K 1628, C12N 518
Patent
active
060180323
DESCRIPTION:
BRIEF SUMMARY
CROSS REFERENCE TO RELATED APPLICATION
This application is a 371 of WO97/10354.
FIELD OF THE INVENTION
The present invention relates to monoclonal antibodies and humanized antibodies which bind specifically to a human interleukin-5 receptor .alpha. chain and which are therefore useful for diagnosis or treatment of diseases such as chronic bronchial asthma. The invention also relates to hybridomas and transformants which produce the antibodies, a method for detecting an interleukin-5 receptor .alpha. chain immunologically by means of the monoclonal antibodies and humanized antibodies, as well as a method for diagnosing and treating diseases such as chronic bronchial asthma by means of the monoclonal antibodies and humanized antibodies.
BACKGROUND OF THE INVENTION
Interleukin-5 (hereinafter referred to a "IL-5") is a kind of lymphokine which is secreted by T cells, mast cells and other cells. Murine IL-5 is known to act as a differentiation and growth factor for B cells and eosinophils. Human IL-5 is known to act mainly as a differentiation and growth factor for eosinophils (Advances in Immunology, 57, 145 (1994); Blood, 79, 3101 (1992)). IL-5 exhibits its action through a specific receptor (IL-5 receptor) which is expressed on the surface of a cell such as eosinophil. It has been shown that human and murine IL-5 receptors (hereinafter referred to as "IL-5Rs") are both composed of two different kinds of proteins, an .alpha. chain (hereinafter referred to as "IL-5R.alpha.") and a .beta. chain (hereinafter referred to as "IL-5R.beta."). In addition, it is known that the binding of IL-5 to IL-5R is via IL-5R.alpha. and that IL-5R.beta. alone can not bind to IL-5 (EMBO J., 9, 4367 (1990); ibid., 10, 2833 (1991); J. Exp. Med., 177, 1523 (1993); ibid., 175, 341 (1992); Cell, 66, 1175 (1991), Proc. Natl. Acad. Sci., 89, 7041 (1992)). Furthermore, IL-5R.beta. is known to be a component of receptors for interleukin-3 (hereinafter referred to as "IL-3"), granulocyte macrophage colony-stimulating factor and others (hereinafter referred to as "GM-CSF") (Proc. Natl. Acad. Sci., 87, 9655 (1990); Cell, 66, 1165 (1991)).
Eosinophils are known to increase in allergic diseases represented by chronic bronchial asthma. Significant infiltration of eosinophils is observed in airways of a patient with chronic bronchial asthma. Eosinophil contains a cytotoxic granular proteins whose deposit is observed in airway tissues of a patient with chronic bronchial asthma or at lesion sites of a patient with atopic dermatitis. These facts suggest that eosinophil plays an important role in the pathogenesis of allergic disorders such as chronic bronchial asthma, atopic dermatitis and the like (Adv. Immunol., 39, 177 (1986); Immunol. Today, 13, 501 (1992)). Hence, studying the kinetics of eosinophils is useful for clinical diagnosis. On the other hand, human IL-5 acts specifically on eosinophils, so IL-5R is believed to be expressed specifically in eosinophils and can therefore be used as a marker specific to human eosinophils. Furthermore, IL-5.beta. is a receptor for cytokines such as IL-3, GM-CSF and others, so IL-5R.alpha. is believed to be a marker specific to eosinophils. Hence, eosinophils can be detected specifically by immunocyte staining using an anti-human IL-5R.alpha. chain antibody (hereinafter referred to as "anti-hIL-5R.alpha. antibody"). However, no anti-hIL-5R.alpha. antibody is presently known that is capable of specific detection of eosinophils.
Significant eosinophilia was observed in IL-5 transgenic mice (J. Exp. Med., 172, 1425 (1990); ibid. 173, 429 (1991); Int. Immunol., 2, 965 (1990)). Eosinophil infiltration in tissues was suppressed by the administration of an anti-IL-5 antibody in animal models of asthma (Am. Rev. Resir. 147, 548 (1993); ibid., 148, 1623 (1993)). These phenomena indicate that IL-5 actually plays an important role in eosinophilia and the infiltration of eosinophils in vivo. It is also reported that IL-5 is expressed in airway mucosal tissues of a human patient with chronic bronchial asthma and
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Anazawa Hideharu
Furuya Akiko
Hanai Nobuo
Iida Akihiro
Koike Masamichi
Kyowa Hakko Kogyo Co. Ltd.
Mertz Prema
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