Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Structurally-modified antibody – immunoglobulin – or fragment...
Patent
1996-06-06
1999-01-19
Eisenschenk, Frank C.
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Structurally-modified antibody, immunoglobulin, or fragment...
4241721, 5303873, 53038822, A61K 39395, C12P 2108, C07K 1600
Patent
active
058611550
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to humanized antibodies and binding proteins thereof, capable of binding to T cells exhibiting particular variable beta chains, and particularly those subpopulations expressing human V.beta. 5.2 and/or 5.3, and V.beta. 8.1. The present invention also relates to the preparation of such antibodies, to pharmaceutical compositions containing them, and therapeutic utilization of the antibodies, specifically in autoimmune diseases.
T cells play a pivotal role in the differentiation and regulation of effector mechanisms within the immune system (Paul et al., (1987) Science 195:1293-1300). The co-recognition of antigen and major histocompatibility molecules by a T cell must be specific and precisely regulated, since improper immune regulation fosters autoimmunity. Several laboratories have studied diseases in which there appears to be improper immune regulation, such as autoimmunity, and some forms of immunodeficiency, and have implicated T cells in the pathogenesis of such diseases.
Several situations exist where there have been reported a clonal or oligoclonal expansion of a particular T cell receptor composition. The most obvious examples are in conditions of malignancy which have resulted in a T cell leukemia or lymphoma. In situations of T cell leukemias or lymphomas, the T cell receptor acts as a unique tumor marker since the T cell receptor is stably rearranged and presented on the surface of the cell. Another situation where a particular T cell receptor composition is implicated is in the recipient of an organ graft whose T lymphocytes have T cell receptors making them aggressive against the MHC molecules of the donor individual, as for instance the donor of a bone marrow graft.
More importantly, several groups have reported selective T cell antigen receptor V region gene usage in certain autoimmune situations. For instance, Grunwald et al. have noted a preferential expression of the V.alpha. 2.3 gene product in CD4+ T cells in the broncheoalveolar lavage when compared to peripheral blood lymphocytes of patients with Sarcoidosis (Grunwald et al., (1992) Eur. J. Immunol. 22:129). In Kawasaki disease, the preferential expansion of V.beta. 2 and V.beta. 8 T cells was noted at the onset of disease (Abe et al., (1992) Proc. Natl. Acad. Sci. USA 89:4066).
Rheumatoid arthritis has also been extensively studied in this regard. Several investigators have noted preferential expansion of subsets of T cells, as for instance: DerSimonian et al., (1993) J. Exp. Med. 177:1623 (preferential expansion of V.alpha. 12.1 bearing T cells in CD8+ peripheral blood T lymphocytes); Stamenkovic et al., (1988) Proc. Natl. Acad. Sci. USA 85:1179 (synovial membrane-infiltrating T cells grown in IL2 were oligoclonal by southern blot analysis); Paliard et al., (1991) Science 253:34 (hypothesized that a Superantigen activated V.beta. 14+ T cells, including autoreactive T cells which expand clonally and migrate to the synovial fluid of rheumatoid arthritis patients); Howell et al., (1991) Proc. Natl. Acad. Sci. USA 88:10921 (noted in particular V.beta. 3, 14, and 17 T cell V region gene usage in IL 2R+ cells from synovial fluid of rheumatoid arthritis patients); Uematsu et al., Proc. Natl. Acad. Sci. USA 88:8534 (showed oligoclonal T cell V region gene usage in synovial fluid T cells of a single RA individual); and International Patent Application No. WO90/06758 (implicating V.beta. 3, 9, and 10 in RA).
Inflammatory bowel disease has also been extensively studied. Several groups have noted expanded T cell populations or preferential T cell receptor V region gene usage as for instance: Posnett et al., (1990) J. Clin. Invest. 85:1770; Spencer et al., (1991) J. Clin. Pathol. 44:915; Trejjdosiewicz et al., (1991) Clin. Exp. Immunol. 84:440; and Van Kerckhove et al., (1992) J. Exp. Med. 175:57. Still others have reported preferential T cell V gene usage in Mycobacterium leprae (van Shooten et al., (1992) Proc. Natl. Acad. Sci. USA 89:11244; Wang et al., (1993) Proc. Natl. Acad. Sci. USA 90:188.
In humans, expansio
REFERENCES:
Bel let al., T Cell Receptors, p. 123, Oxford University Press, Jan. 1995.
Abe et al., J. Exp. Med., 177:791-796 (1993).
Abe et al, Proc. Nati. Acad Sci. USA 89: 4066-4070 (1992).
Acha-Orbea et al., Cell, 54: 263-273 (1988).
Baranov et al., Gene, 84: 463-466 (1989).
Bernard et al., "The Epitopic Dissection . . . " 53-66 (Springer Verlag, New York (1984).
Bolivar et al., Gene, 2: 95-113 (1977).
Boylston et al., J. Immunol., 137: 741-744 (1986).
Brennan et al., Clin. Exp. Immunol., 73: 417-423 (1988).
Chang et al., Nature, 275: 617-624 (1978).
DerSimonian et al., J. Exp. Med., 177: 1623-1631 (1993).
Elian et al., Disease Markers, 5: 89-99 (1987).
Fiers et al., Nature, 273: 113-120 (1978).
Foote et al., J. Mol. Biol., 224: 487-499 (1992).
Francis et al., Lancet., 1: 211 (1986).
Goedell et al., Nature, 281: 544-548 (1979).
Goedell et al., Nuc. Acids Res., 8; 4057-4074 (1980).
Grunewald et al., Eur. J. Immunol, 22: 129-135 (1992).
Hakimi et al., J. Immunol., 151: 1075-1085 (1993).
Hess et al., J. Adv. Enzyme Reg., 7: 149-167 (1968).
Higuchi. et al., Nuc. Acids Res., 16: 7351-7367 (1988).
Ho et al., Gene, 77: 51-59 (1989).
Ho et al., Immunogenetics, 15: 509-517 (1982).
Holland et al., Biochemistry, 17: 4900-4907 (1978).
Horton et al., Gene, 77: 61-68 (1989).
Howell et al., Proc. Natl. Acad. Sci. USA, 88: 10921-10925 (1991).
Howell et al. Science, 246: 668-670 (1989).
Itakura et al., Science., 198:1056-1063 (1978).
Jaffers et al., Transplanations,41: 572-578 (1986).
Jones, Genetics, 85: 23-33 (1977).
Jones et al., Nature, 321: 522-525 (1986).
Kabat et al., U.S. Dept. Of Health and Human Services, 5th ed. NIH Publication No. 91, 3242 (1991).
Kanasawa et al, Diabetologia, 27: 133-155 (1984).
Kingsman et al., Gene, 7: 141-152 (1979).
Knight et al., J. Exp. Med., 147:1653-1660 (1978).
Kohler et al., Nature, 256: 495-497 (1975).
Kotzin et al., Proc. Natl. Acad. Sci. USA, 88: 9161-9165 (1991).
Kramer et al., Nuc. Acids Res., 10: 6475-6485 (1982).
Lin et al., Science, 249: 677-679 (1990).
Lindstrom et al., Adv. Immunol., 42: 233-284 (1988).
Maron et al., J. Exp. Med., 152: 1115-1120 (1980).
McFarlin et al., Science, 179: 478-480 (1973).
Mullis et al., Meth. Enz., 155: 335-350 (1987).
Norris et al., Nuc. Acids Res., 11: 5103-5112 (1983).
Oksenberg et al., Nature, 345: 344-346 (1990).
Oksenberg et al., Nature, 362: 68-70 (1993).
Orlandi et al., Proc. Natl. Acad. Sci. USA, 86: 3833-3837 (1989).
Paliard et al., Science, 253: 325-329 (1991).
Paterson, Textbook of Immunopathology, pp. 179-188 (Mischer et al., eds.) (Grune & Stratton, NY 1986).
Paul et al., Science, 195: 1293-1300 (1987).
Posnett et al. J. Clin. Invest., 85: 1770-1776 (1990).
Queen et al., Proc. Natl. Acad. Sci. USA, 86: 10029-10033 (1989).
Ralfkiaer et al., Brit. J. Derm., 125: 409-412 (1991).
Reichmann et al, Nature, 332: 323-327 (1988).
Reinersten et al., New Eng. J. Med., 299: 515-518 (1978).
Sanger et al., Proc. Natl. Acad. Sci. USA, 74: 5463-5467 (1977).
Satoh et al., J. Immunol., 138: 179-184 (1987).
Schmidt et al, Hoppe-Seyler's Z. Phsiol. Chem., 364:713-747 (1983).
Shalon, et al., Autoimmunity, 17:301-307 (1994).
Siebenlist et al., Cell, 20: 269-281 (1980).
Smith et al., Nature, 337: 181-184 (1989).
Spencer et al., J. Clin. Pathol., 44: 915-918 (1991).
Spielman et al., Epidemiol. Rev., 4: 46-65 (1982).
Stamenkovic et al., Proc. Natl. Acad. Sci. USA, 85: 1179-1183 (1988).
Stinchcomb et al., Nature, 282: 39-43 (1979).
Stuart et al., Ann. Rev. Immunol., 42: 199-218 (1984).
Takebe et al., Mol. Cell. Biol., 8: 466-472 (1988).
Teraski et al., Science, 1933: 1244-1247 (1976).
Trejdosiewicz et al., Clin. Exp. Immunol., 84: 440-444 (1991).
Tschemper et al., Gene, 19: 157 (1980).
Uematsu et al., Proc. Natl. Acad. Sci. USA, 88:8534-8538 (1991).
Urban et al., Cell, 54:577-592 (1988).
Van Eden et al., Nature, 331: 171-173 (1988).
Van Kerckhove et al., J. Exp. Med., 175: 57-63 (1992).
van Shooten et al., Proc. Natl. Acad. Sci. USA, 89: 11244-11248 (1992).
Vandenbark et al., Nature, 341: 541-544 (1989).
Astra AB
Eisenschenk Frank C.
Nolan Patrick
Williams Kathleen Madden
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