Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Monoclonal antibody or fragment thereof
Reexamination Certificate
2001-03-27
2004-02-17
Gambel, Phillip (Department: 1644)
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Monoclonal antibody or fragment thereof
C424S130100, C424S141100, C424S143100, C424S152100, C424S172100, C530S387100, C530S388100, C530S388200, C530S388220
Reexamination Certificate
active
06692741
ABSTRACT:
BACKGROUND OF THE INVENTION
Integrins are heterodimeric cell adhesion receptors composed of two subunits, &agr; and &bgr;. The integrin &agr;v&bgr;6 is a fibronectin and tenascin receptor expressed predominantly by epithelial cells. In healthy adult primate tissues, &bgr;6 mRNA and protein are rarely detected, although &bgr;6 is expressed during fetal development, wound healing, and in some epithelial tumors. When the &bgr;6 subunit is expressed in a colon carcinoma cell line, from which it is normally absent, expression of the subunit confers an enhanced ability to proliferate. An 11 amino acid COOH-terminal region, unique to the &bgr;6 subunit, is required for the proliferation-enhancing activity of the &agr;v&bgr;6 integrin (Agrez et al.
J. Cell. Biol.
127:547-556 (1994). &bgr;6 expression is induced in type II aveolar epithelial cells during injury caused by injection of live bacteria, and &bgr;6 expression is observed at focal sites of subclinical inflammation, as well as in a variety of clinical specimens from patients with chronic or acute inflammation of the lungs or kidneys (Breuss et al.
J. Cell Sci.
108:2241-2251 (1995).
Huang et al. (
J. Cell Biol.
133:921-928 (1996)) disclosed mice homozygous for a null mutation in the gene encoding the &bgr;6 subunit had juvenile baldness associated with infiltration of macrophages into the skin, and accumulated activated lymphocytes around conducting airways in the lungs.
Pulmonary fibrosis is a common disorder thought to be due to the destructive effects of products released from leukocytes (see, for example, Marshall et al.,
Int. J Biochem. Cell Bio.,
29:107-120 (1997)). Bleomycin-induced lung injury and pulmonary fibrosis are associated with and may depend upon the recruitment and activation of lymphocytes (Schrier, D. J. et al.,
Am. J. Pathol,
116:270-278 (1984)). Among proposed therapies for parenchymal lung injury and pulmonary fibrosis is the use of “anticytokine” therapeutic approaches (Coker et al.
Thorax
52 (2):294-296 (1997)).
However, current therapies for acute lung injury and pulmonary fibrosis are largely inadequate (see, for example, King et al., “Idiopathyic Pulmonary Fibrosis and other Interstitial Lung Diseases of Unknown Etiology,” in
Textbook of Respiratory Medicine,
Murray and Nadel, eds., W. B. Saunders, Philadelphia, Pa., pp. 1827-1839 (1994)). Thus, a need exists for therapies for acute lung injury and pulmonary fibrosis. This need and others are addressed by the instant invention.
SUMMARY OF THE INVENTION
One aspect of the invention is a method of treating acute lung injury in a patient comprising administering to the patient a therapeutic dose of an antagonist of &agr;v&bgr;6. The invention also provides methods of inhibiting lung metastasis comprising administering to the patient a therapeutic dose of an antagonist of &agr;v&bgr;6. A further aspect of the invention is a method of treating fibrosis in a patient comprising administering to the patient a therapeutic dose of an antagonist of &agr;v&bgr;6.
A further aspect of the invention is a monoclonal antibody produced by the hybridoma ATCC HD 12382.
A further aspect of the invention is the hybridoma ATCC HB 12382.
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patent: 5654270 (1997-08-01), Ruoslahti et al.
patent: 5770565 (1998-06-01), Cheng
patent: 5985278 (1999-11-01), Mitjans
patent: 6316601 (2001-11-01), Huang
patent: WO 90/06767 (1990-06-01), None
Breuss, J.M. et al. Expression of the beta6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling. Journal of Cell Science, 108:2241-2251 (1995).
Lehmann, M. et al. A monoclonal antibody inhibits adhesion to fibronectin and vitronectin of a colon carcinoma cell line and recognizes the integrins alpha-v-beta3, alpha-v-beta5 and alpha-v-beta6. Cancer Research 54:2102-2107 (1994).
Wang, A. et al. Differential regulation of airway epithelial integrins by growth factors. American Journal of Respiratory Cell and Molecular Biology, 15:664-672 (1996).
Vaderslice, et al., “A Cyclic Hexapeptide is a Potent Antagonist of &agr;4Integrins”;The Journal of Immunology158:1710-1718.
JPA va Pelt, et al., “The Regulation of CD11b Integrin Levels on Human Blood Leukocytes and Leukotriene B4-Stimulated Skin by a Specific Leukotriene B4 Receptor Antagonist (LY293111)”;Biochemical Pharmacologyvol. 53, pp. 1005-1012 (1997).
McIntyre, et al., “Regulation of Human T Lymphocyte Coactivation with an &agr;4Integrin Antagonist Peptide”;The Journal of Immunology158:4180-4186 (1997).
Engleman, et al., “A Peptidomimetic Antagonist of the &agr;v&bgr;3Integrin Inhibits Bone Resorption In Vitro and Prevents Osteoporosis In Vivo”;J. Clin. Invest., vol. 99, No. 9 (May 1997).
Kapil, et al., “Biological Matrix-Dependent Pharmacokinetic and Pharmacodynamic Parameters of a Novel Platelet Glycoprotein IIB/IIIA Receptor Antagonist, XU063, In Beagle Dogs”;Thrombosis Research, vol. 86, No. 3, pp. 221-232 (1997).
Craig, et al., “Concept and Progress in the Development of RGD-Containing Peptide Pharmaceuticals”;Biopolymers(Peptide Science), vol. 37, 157-175 (1995).
Huang Xiaozhu
Sheppard Dean
Gambel Phillip
The Regents of the University of California
Townsend and Townsend / and Crew LLP
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