Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Monoclonal antibody or fragment thereof
Patent
1998-04-27
2000-05-30
Saunders, David
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Monoclonal antibody or fragment thereof
4241331, 4241521, 5303873, 53038823, A61K 39395, C07K 1618
Patent
active
060688416
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to therapeutic agents for hepatitis, and in particular to therapeutic agents for hepatitis, comprising an antibody against a human Fas ligand (hereinafter may be abbreviated as "FasL"), or an active fragment thereof as an active ingredient. The therapeutic agents for hepatitis according to the present invention are particularly effective for the treatment of hepatitis caused by the death of hepatocytes due to apoptosis among many kinds of hepatitis.
PRIOR ART
Multicellular organisms skillfully control the proliferation and death of cells to maintain their homeostasis. Many cells are removed by cell death in the course of ontogeny. In an adult, organ constituting cells always maintain their functions while well keeping a balance between their proliferation and death. Such cell death is preliminarily programmed death called "programmed cell death". On the other hand, cell death caused by physical or chemical factors is called "accidental cell death" and is distinguished from the programmed cell death.
These two deaths are different from each other in process. In the programmed cell death, cells are considered to die via the process of apoptosis defined by morphological features such as reduction in cell volume, disappearance and pycnosis of nuclear reticular structure, disappearance of microvilli and formation of vesicles on a cell surface, and formation of apoptotic bodies subsequent thereto. In many cases, the apoptosis is accompanied by a fragmentation reaction of a chromosomal DNA. On the other hand, in the accidental cell death, cells are considered to die via a process of necrosis in which cells and nuclei are imbibed and destroyed.
However, cell death by anticancer agents and radiation, cell death by viral infection or the death of target cells by cytotoxic lymphocytes has been known to go through the process of apoptosis though it is by no means considered to be programmed cell death. At present, this fact had led to the thought that the apoptosis is not always identical with the programmed cell death, and so both have come to be distinguished from each other.
At present, many have been known as factors or substances which induce apoptosis. Fas (Fas antigen) is known as a cell-surface protein that mediates apoptosis. The Fas is isolated as a cell-surface protein that mediates a signal of death to cells, and is a type I transmembrane protein belonging to the TNF/NGF receptor family and having a molecular weight of 45 kDa. Most of members of the TNF/NGF receptor family are considered receptors for their specific ligands. The Fas is also considered a receptor or a ligand mediating a signal of apoptosis. Cells in which Fas has been expressed are led to death by switching on apoptosis due to binding of the Fas to its ligand, Fas ligand.
The Fas ligand is a physiological ligand of Fas and is a cell-surface protein of 40 kDa. The Fas ligand is known from its structure to belong to the TNF family. The Fas ligand has activity to induce apoptosis to cells in which Fas has been expressed.
A system of Fas and Fas ligand (namely, Fas system) is a field in which investigations as to the apoptosis have been most evolved to date, and many investigation reports have been made. For example, the fact that Fas plays the role of a switch in apoptosis may go back to a paper by Yonehara, et al. on the production of anti-Fas antibody (J. Exp. Med., Vol. 169, pp. 1747-1756, 1989). After that, the structure of Fas has been clarified by cloning of the Fas gene (Cell, Vol. 66, pp. 233-243, 1991). Further, it has been reported that the expression of Fas is recognized in T cells infected with HIV which is a causative virus of AIDS (Proc. Natl. Acad. Sci., U.S.A., Vol. 87, pp. 9620-9624, 1990), and that when an anti-Fas antibody (Jo-2 antibody) is administered to mice, the mice undergo a phenomenon similar to fulminant hepatitis to die (Nature, Vol. 364, pp. 806-809, 1993). Besides these, various investigation reports have been made. These reports are collected in detail in "Apopto
REFERENCES:
patent: 5830469 (1998-11-01), Lunch et al.
Takahashi, T. et al. Human Fas ligand: Gene structure, chromosomal location and species specificity. International Immunology vol. 6, pp. 1567-1574, Oct. 25, 1994.
"Purification and Characterization of the Fas-ligand that Induces Apoptosis", Suda et al., J. Exp. Med., vol. 179, No. 3, pp. 873-879, Mar. 1994.
"The Fas Death Factor", Nagata et al., Science, vol. 267, No. 5203, pp. 1449-1456, Mar. 10, 1995.
"Hepatitis and Apoptosis", Eiji Mita et al., Experimental Medicine, vol. 13, No. 16, Oct. 20, 1995, pp. 200-204, abstract only.
"The Polypeptide Encoded by the cDNA for Human Cell Surface Antigen Fas Can Mediate Apoptosis", Itoh et al., Cell, vol. 66, Jul. 26, 1991, pp. 233-243.
"Anti-Fas monoclonal antibody is cytocidal to human immunodeficiency virus-infected cells without augmenting viral replication", Kobayashi et al., Proc. Natl. Acad. Sci., vol. 87, Dec. 1990, pp. 9620-9624.
"Lethal effect of the anti-Fas antibody in mice", Nature, vol. 364, Aug. 26, 1993, pp. 806-809.
S. Yonehara et al., "A Cell-Killing Monoclonal Antibody (Anti-Fas) to a Cell Surface Antigen Co-Downregulated with the Receptor of Tumor Necrosis Factor", J. Exp. Med., vol. 169, May 1989, pp. 1747-1756.
"Apoptosis-Mechanism of Cell Death", Experimental Medicine, vol. 11, No. 17, 1993, pp. 61-66, Abstract only.
Gayle C. Bosma et al., "A severe combined immunodeficiency mutation in the mouse", Nature, vol. 301, Feb. 10, 1983, pp. 527-530.
Sheri M Krams et al., "Generation of Biliary Lesions after Transfer of Human Lymphocytes into Severe Combined Immunodeficient (SCID) Mice", J. Exp. Med., vol. 170, Dec. 1989, pp. 1919-1930.
Michael A. Duchosal et al., "Transfer of Human Systemic Lupus Erythematosus in Severe Combined Immunodeficient (SCID) Mice", J. Exp. Med., Sep. 1990, pp. 985-988.
L. Macht et al., "Severe combined immunodeficient (SCID) mice: a model for investigating human thyroid autoantibody synthesis", Clin. exp. Immunol., vol. 84, 1991, pp. 34-42.
L. Presta et al., "Helix Signals in Protein", Science, vol. 240, Jun. 1988, pp. 1632-1639.
A.E. Ringwood, "Terrestrial origin of the Moon", Nature, vol. 322, Jul. 1986, pp. 323-327.
Peter T. Jones et al., "Replacing the complementarily-determining regions in a human antibody with those from a mouse", Nature, vol. 321, May 1986, pp. 522-525.
S. Roberts et al., "Generation of an antibody with enchanced affinity and specificity for its antigen by protein engineering", Nature, pp. 741-734, 1987.
Kayagaki Nobuhiko
Nakata Motomi
Okumura Ko
Seino Ken-ichiro
Yagita Hideo
Saunders David
Sumitomo Electric Industries Ltd.
LandOfFree
Antibodies to Fas-L for treatment of hepatitis does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Antibodies to Fas-L for treatment of hepatitis, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antibodies to Fas-L for treatment of hepatitis will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1908147