Drug – bio-affecting and body treating compositions – Enzyme or coenzyme containing – Stabilized enzymes or enzymes complexed with nonenzyme
Patent
1988-06-29
1990-12-04
Stone, Jacqueline
Drug, bio-affecting and body treating compositions
Enzyme or coenzyme containing
Stabilized enzymes or enzymes complexed with nonenzyme
424 8591, 424 941, 424 946, 514 27, 514 33, 514 34, 514 80, 530387, 530389, 530391, 435188, 435196, 435200, 435212, 435219, 536 64, 536 181, A61K 3748, A61K 39395, C12N 1116, C12N 996
Patent
active
049752782
ABSTRACT:
This invention relates to a novel method for the delivery of cytotoxic drugs to tumor cells by the administration of a tumor-specific antibody-enzyme conjugate that binds to the tumor cells, and the additional administration of a prodrug that is converted at the tumor site, in the presence of the antibody-bound enzyme, to an active cytotoxic drug. According to preferred embodiments of this invention, antibody-enzyme conjugates containing the enzyme, alkaline phosphatase ("AP"), have been used in conjunction with the novel prodrug, etoposide-4'-phosphate or 7-(2'-aminoethyl phosphate)mitomycin or a combination thereof, to effect killing of tumor cells. According to another embodiment of the invention, an antibody-enzyme conjugate containing the enzyme, penicillin V amidase ("PVA"), has been used in conjunction with a novel prodrug, N-(p-hydroxyphenoxyacetyl)adriamycin to effect killing of tumor cells. Still another embodiment of the invention relates to the use of an antibody-enzyme conjugate containing the enzyme, cytosine deaminase ("CD"), in combination with the prodrug, 5-fluorocytosine, to effect killing of tumor cells. The method, antibody-enzyme conjugates, prodrugs, pharmaceutical compositions and combinations of this invention provide for enhanced selective killing of tumor cells and are thus useful in the treatment of cancers and other tumors.
REFERENCES:
patent: 4185111 (1980-01-01), Ducep et al.
patent: 4564675 (1986-01-01), Kurabayashi et al.
patent: 4675187 (1987-06-01), Konishi et al.
patent: 4762707 (1988-08-01), Jansen et al.
Hellstrom et al., Cancer Research, 46, (Aug. 1986), 3917-3923.
Philpott et al., Cancer Research, 34, (1974), 2159-2164.
Hellstrom et al., J. Immunol., 127(1), (1981), 157-160.
Stella et al., in Directed Drug Delivery, (1985), pp. 247-267.
Nishiyama et al., Cancer Research, 45, (1985), 1753-1761.
Wilman, Biochem. Soc. Trans., 14, (615th Meeting, Belfast, 1986), 375-382.
O'Dwyer et al., N. Eng. J. Med., 312, (1985), 692-700.
A. P. Albino et al., "Heterogeneity in Surface Antigen and Glycoprotein Expression of Cell Lines Derived from Different Melanoma Metastases of the Same Patient", J. Exp. Med., 154, pp. 1764-1778, (1981).
R. Arnon et al., "In Vitro and In Vivo Efficacy of Conjugates of Daunomycin with Anti-Tumor Antibodies", Immunological Rev., 62, pp. 5-27, (1982).
K. D. Bagshawe, "Antibody Directed Enzymes Revive Anti-Cancer Prodrugs Concept", Br. J. Cancer, 56, (No. 5), pp. 531-532, (Nov. 1987), (Bagshawe I).
K. D. Bagshawe et al., "A Novel Approach to Prodrug Activation Using a Monoclonal Antibody Conjugated to Carboxypeptidase G.sub.2 ", from the Third International Conference on Monoclonal Antibody Immunoconjugates for Cancer, Abstract #43, p. 70, (San Diego, Feb. 4-6, 1988) (Bagshawe II).
R. W. Baldwin et al., "Design and Therapeutic Evaluation of Monoclonal Antibody 791T/36-Methotrexate Conjugates", in Monoclonal Antibodies and Cancer Therapy, pp. 215-231, (Alan R. Liss, Inc., 1985), (Baldwin I).
R. W. Baldwin et al., "Monoclonal Antibodies in Cancer Treatment", Lancet, pp. 603-605, (Mar. 15, 1986), (Baldwin II).
R. W. Baldwin et al., "Monoclonal Antibody Drug Conjugates for Cancer Therapy", in Monoclonal Antibodies in Cancer: Advances in Diagnosis and Treatment, Jack A. Roth (ed)., pp. 215-257, (Futura Publishing Co., 1986), (Baldwin III).
J. P. Brown et al., "Structural Characterization of Human Melanoma-Associated Antigen p97 with Monoclonal Antibodies", J. Immunol., 127, (No. 2), pp. 539-546, (1981).
E. A. Clark et al., "Role of the Bp35 Cell Surface Polypeptide in Human B-Cell Activation", Proc. Natl. Acad. Sci., 82, pp. 1766-1770, (1985).
S. T. Crooke et al. (eds.), Antiracyclines: Current Status and New Developments, Academic Press, (New York, 1980).
R. A. DeWeger et al., "Eradication of Murine Lymphoma and Melanoma Cells by Chlorambucil-Antibody Complexes", Immunological Rev., 62, pp. 29-45, (1982).
M. J. Embleton et al., "Antibody Targeting of Anti-Cancer Agents", in Monoclonal Antibodies for Cancer Detection and Therapy, R. W. Baldwin and V. S. Byers (eds.), pp. 321-322, (Academic Press, 1985), (Embleton I).
M. J. Embleton, "Targeting of Anti-Cancer Therapeutic Agents by Monoclonal Antibodies", Biochemical Society Transactions, 14, pp. 393-395, (615th Meeting, Belfast, 1986), (Embleton II).
N. Endo et al., "In Vitro Cytotoxicity of a Human Serum Albumin-Mediated Conjugate of Methotrexate with Anti-MM46 Monoclonal Antibody", Cancer Research, 47, pp. 1076-1080, (Feb. 1987).
P. J. Fraker et al., "Protein and Cell Membrane Iodinations with a Sparingly Soluble Chloroamide, 1,3,4,6-Tetrachloro-3a,6a-Diphenylglycoluril", Biochem. Biophys. Res. Commun., 80, (No. 4), pp. 849-857, (1978).
I. Hellstrom et al., "Antitumor Effect of L6, an IgG.sub.2 a Antibody that Reacts with Most Human Carcinomas", Proc. Natl. Acad. Sci. U.S.A., 83, pp. 7059-7063, (1986).
I. Hellstrom et al., "Antibodies for Drug Delivery", in Controlled Drug Delivery, (2nd ed.), Robinson and Lee (eds.), p. 639, (1987), (Hellstrom IV).
P. L. Ipata et al., "Baker's Yeast Cytosine Deaminase. Some Enzymatic Properties and Allosteric Inhibition by Nucleosides and Nucleotides", Biochemistry, 10, pp. 4270-4276, (1971).
T. Katsuragi et al., "Affinity Chromatography of Cytosine Deaminase from Escherichia coli with Immobilized Pyrimidine Compounds", Agric. Biol. Chem., 50, (No. 7), pp. 1713-1719, (1986).
J. M. Lambert et al., "Purified Immunotoxins That Are Reactive with Human Lymphoid Cells", J. Biol. Chem., 260, (No. 22), pp. 12035-12041, (1985).
J. P. Mach et al., "Improvement of Colon Carcinoma Imaging: from Polyclonal Anti-CEA Antibodies and Static Photoscanning to Monoclonal Fab Fragements and ECT", in Monoclonal Antibodies for Cancer Detection and Therapy, R. W. Baldwin et al. (eds.), pp. 53-64, (Academic Press, 1985).
R. B. McComb et al. (eds.), Alkaline Phosphatase, Plenum Press, (New York, 1979).
R. G. Melton et al., "In Vivo Localization of Carboxypeptidase G.sub.2 : Antibody Conjugates in Human Colon Carcinoma Xenografts", from the Third International Conference on Monoclonal Antibody Immunoconjugates for Cancer, Abstract #83, p. 110, (San Diego, Feb. 4-6, 1988).
S. Monfardini et al. (eds), Manual of Cancer Chemotherapy, (3rd ed.), UICC Technical Report Series, vol. 56, (Geneva, 1981).
F. L. Moolten et al., "Antibodies Conjugated to Potent Cytotoxins as Specific Antitumor Agents", Immunological Rev., 62, pp. 47-73, (1982).
K. Ohkawa et al., "Selective In Vitro and In Vivo Growth Inhibition Against Human Yolk Sac Tumor Cell Lines by Purified Antibody Against Human .alpha.-Fetoprotein Conjugated with Mitomycin C via Human Serum Albumin", Cancer Immunol. Immunother., 23, pp. 81-86, (1986).
C. W. Parker et al., "Enzymatic Activation and Trapping of Luminol-Substituted Peptides and Proteins. A Possible Means of Amplifying the Cytotoxicity of Anti-Tumor Antibodies", Proc. Natl. Acad. Sci. U.S.A., 72, (No. 1), 338-342, (1975).
G. W. Philipott et al., "Selective Iodination and Cytotoxicity of Tumor Cells with an Antibody-Enzyme Conjugate", Surgery, 74, pp. 51-58, (1973), (Philpott I).
G. W. Philpott et al., "Selective Cytotoxicity of Hapten-Substituted Cells with an Antibody-Enzyme Conjugate", J. Immunol., 111, (No. 3), pp. 921-929, (1973), (Philpott II).
M. J. Robins et al., "Nucleic Acid Related Compounds. 16. Direct Fluorination of Uracil Nucleotides Using Trifluoromethyl Hypofluorite", Can. J. Chem., 53, pp. 1302-1306, (1975).
G. F. Rowland et al., "Drug Localization and Growth Inhibition Studies of Vindesine-Monoclonal Anti-CEA Conjugates in a Human Tumour Xenograft", Cancer Immunol. Immunother., 21, pp. 183-187, (1986).
F. Searle et al., "Antibody Carboxypeptidase G.sub.2 Conjugates as Anti-Tumor Agent", Tumor Biology, 6, (No. 4), p. 355, (1985), (Searle I).
F. Searle et al., "Carboxypeptidase G.sub.2 Conjugates with Localizing Anti-Tumour Antibodies: Potential Therapeutic Agents", Tumor Biology, 7, (No. 4), p. 320, (1986), (Searle II).
F. Searle et al., "The Potential of Carboxypeptides G.sub.2 -Antibody Conjugates as Anti-Tumour Agents. I. Preparation of Antihu
Brown Joseph P.
Kerr David E.
Saulnier Mark G.
Senter Peter D.
Barnett Deborah J.
Bristol-Myers Company
Stone Jacqueline
LandOfFree
Antibody-enzyme conjugates in combination with prodrugs for the does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Antibody-enzyme conjugates in combination with prodrugs for the , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antibody-enzyme conjugates in combination with prodrugs for the will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-882428