Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1990-05-14
1992-08-11
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514345, 514346, 514347, 514581, 514590, 514614, 536 64, 544791, 544794, 544795, 546295, 546294, 564 18, 564 34, 564 35, 564140, A61K 39395, A61K 4700, C07H 15252, C07C28106
Patent
active
051378779
ABSTRACT:
The present invention provides novel N-substituted hydrazine bifunctional compounds, novel N-subhstituted hydrazone derivatives of a cytotoxic reagent incorporating the bifunctional compounds, novel conjugates containing at least one cytotoxic reagent molecule reacted with the bifunctional compound and bound to a molecule reactive with a target cell population, methods for their production, and pharmaceutical compositions and methods for delivering cytotoxic reagents to a target population of cells. The hydrazone bonds of the conjugates of the invention permit the release of free cytotoxic reagent from the conjugates in the acidic external or internal environment of the target cells. The bifunctional compounds, derivatives, conjugates and methods of the invention are useful in antibody-or ligand-mediated drug delivery systems for the perferential killing of a target cell population to treat diseases such as cancers, infections and autoimmune disorders.
REFERENCES:
patent: 3324140 (1967-06-01), Schorre
patent: 4112217 (1978-09-01), Henry
patent: 4130562 (1978-12-01), Dubs et al.
patent: 4202967 (1980-05-01), Tong et al.
patent: 4250303 (1981-02-01), Wu et al.
patent: 4258193 (1981-03-01), Fujii et al.
patent: 4301277 (1981-11-01), Acton et al.
patent: 4303785 (1981-12-01), Umezawa et al.
patent: 4314054 (1982-02-01), Acton
patent: 4464529 (1984-08-01), Mosher et al.
patent: 4522750 (1985-06-01), Ades et al.
patent: 4545985 (1985-10-01), Pastan et al.
patent: 4568694 (1986-02-01), Griffin et al.
patent: 4590001 (1985-05-01), Skjernholm
patent: 4591637 (1986-05-01), Acton et al.
patent: 4675382 (1987-06-01), Murphy
Peterson et al., "Transport and Storage of Anthracyclines in Experimental Systems and Human Leukemia", Anthracycline Antibiotics in Cancer Therapy, Muggia et al., (Eds), p. 132 (Nijhoff Publ., 1982).
Wiernik, "Current Status of Adriamycin and Daunomycin in Cancer Treatment", in Anthracyclines: Current Status and New Developments, Crooke et al., (Eds.), pp. 273-94 (Academic Press 1980).
Hermentin and Seiler, "Investigations with Monoclonal Antibody Drug (Anthracycline) Conjugates", Behring Inst. Mitl. 82:197-215 (1988).
Gallego et al., "Preparation of Four Daunomucin-Monoclonal Antibody 791T/36 Conjugates with Anti-Tumour Activity", Int. J. Cancer 33:737-44 (1984).
Arnon et al., "In vitro and in vivo efficacy of conjugates of Daunomycin with Anti-Tumor Antibodies", Immunological Rev. 62:5-27 (1982).
Hurwitz et al., "The Covalent Binding of Daunomycin and Adriamycin to Antibodies, with Retention of both Drug and Antibody Activities", Cancer Res. 35:1175-1181 (1975).
Hurwitz et al., "The effect in vivo of chemotherapeutic drug-antibody conjugates in two murine experimental tumor systems", Int. J. Cancer 21:747-755 (1978).
Belles-Isles et al., "In vitro activity of Daunomycin -anti-Alphafoetoprotein conjugate on mouse hepatoma cells", Br. J. Cancer 41: pp. 841-42 (1980).
Yamamoto et al., "Antitumor Activity of some Derivatives of Daunorubicin at the Amino and Methyl Ketone Functions", J. Med. Chem. 15:872-75 (1972).
Tong et al., "Antitumor Antrhacycline Antibiotics. Structure-Activity and Structure-Cardiotoxicity Relationships of Rubidazone Analogues", J. Med. Chem., 21(8):732-737 (1978).
Smith et al., "Adriamycin Analogues, 2, Synthesis of 13-Deoxyanthracyclines", J. Med. Chem., 21(3): 280-283 (1978).
Brownlee, "Synthesis and Characterization of a Series of Bis-intercalating Bis-anthracyclines", J. Chem. Soc., pp. 659-61 (1986).
Hurwitz et al., "Soluble Macromolecules as Carriers for Daunorubicin", J. Appl. Biochem., 2:25-35 (1980).
Arnon and Hurwitz, "Monoclonal Antibodies as Carriers for Immunotargeting of Drugs", in Monoclonal Antibodies for Cancer Detection and Therapy, pp. 365-383 (1985), publ. Academic Press Inc. (London).
Hurwitz et al., "A Conjugate of Adriamycin and monoclonal antibodies to THY-1 antigen inhibits human neuroblastoma cells in vitro", Ann. NY Acad. of Sci. vol. 417:125-136 (1983).
Dillman et al., "Preclinical Trials with Combinations and Conjugates of T101 Monoclonal Antibody and Doxorubicin", Cancer Res. 46:4886-4891 (1986).
Embleton, "Antibody Targeting of Anti-cancer Agents", in Monoclonal Antibodies for Cancer Detection and Therapy, Academ. Press., pp.317-344 (1985).
Ford et al., "Localisation and toxicity study of a vindesine-anti-CEA conjugate in patients with advanced cancer", Br. J. Cancer, 47:35-42 (1983).
Cawley et al., "Epidermal Growth Factor-Toxin A Chain Conjugates: EGF-Ricin A is a Potent Toxin While EGF-Diptheria Fragment A in Nontoxic", Cell 22:563-570 (1980).
Shimizu et al., "A Cytotoxic Epidermal Growth Factor Cross-Linked to Diptheria Toxin A-Fragment", FEBS Letters, 118(2):274-278 (1980).
Pastan and Fitzgerald, "New Cytotoxic Agents Created by the Fusion of Growth Factor and Modified Pseudomonas Exotoxin Genes", Proceed. Amer. Assoc. Cancer Res., 4th Ann. Conf. on Monoclonal Antibodies, 30:667 (1989).
Lorberbaum et al., "Cytotoxic activity of an interleukin 2-Pseudomonas exotoxin chimeric protein produced in Escherichia coli", Proc. Natl. Acad. Sci. USA, 85:1922-1926 (1988).
Chaudhary et al., "Activity of a recombinant fusion protein between transforming growth factor type and Pseudomonas toxin", Proc. Natl. Acad. Sci. USA, 84:4538-4542 (1987).
Siegall et al., "Cytotoxic activity of an interleukin 6-Pseudomonas exotoxin fusion protein on human myeloma cells", Proc. Natl. Acad. Sci. USA, 85:9738-9742 (1988).
Chaudhary et al., "Selective killing of HIV-infected cells by recombinant human CD4-Pseudomonas exotoxin hybrid protein", Nature:335:369-372 (1988).
Murphy et al., "Genetic construction, expression, and melanoma-selective cytotoxicity of a diptheria toxin-related -melanocyte-stimulating hormone fusion protein", Proc. Natl. Acad. Sci. USA, 83:8258-8262 (1986).
Varga et al., "Malanotropin-daunomycin conjugate shows receptor-mediated cytotoxicity in cultured murine melanoma cells", Nature, 267:56-58 (1977).
deDuve, "Lysosomes revisited", Eur. J. Bioch., 137:391-397 (1983).
Poznansky and Juliano, "Biological Approaches to the Controlled Delivery of Drugs: A Critical Review", Pharm. Rev., 36:277-336 (1984).
Shen and Ryser, "Cis-aconityl spacer between daunomycin and macromolecular carriers: A model of PH-sensitive linkage releasing drug from a lysosomotropic conjugate", Biochem. Biophys. Res. Comm., 102(3) 1048-1054 (1981).
Yang and Reisfeld, "Doxorubicin conjugated with a monoclonal antibody directed to a human melanoma-associated proteoglycan suppresses the growth of established tumor xenografts in nude mice", Proc. Natl. Acad. Sci. USA, 85:1189-1193 (1988).
Strinivasachar and Neville, "New protein cross-linking reagents that are cleaved by mild acid", Biochem., 28:2501-2509 (1989).
Hardy, "Purification and coupling of fluorescent proteins for use in flow cytometry", in Immunochemistry, vol. 1, Ed. Weir et al., Blackwell Sci. Publ., London (1967).
Casazza, "Experimental Studies on New Anthracyclines", in Adriamycin: Its Expanding Role in Cancer Treatment, Eds. Ogawa et al., Excerpta Medica. Publ., pp. 439-52 (1984).
DeWeger et al., "Eradication of Murine Lymphoma and Melanoma Cells by Chlorambucil-Antibody Complexes", Immunol. Rev., 62:29-45 (1982).
Brown et al., "Structural Characterization of Human Melanoma-Associated Antigen p. 97 with Monoclonal Antibodies", J. Immunol., 127(2): 539-46 (1981).
Pastan and Willingham, "the Pathway of Endocytosis", in Endocytosis, I: pp. 1-44 (1985).
Hellstrom et al., "Monoclonal Antibodies to Two Determinants of Melanoma-Antigen p. 97 Act Synergistically in Complement-Dependent Cytotoxicity", J. Immunol., 127(1):157-160 (1981).
Zumach et al., "Chlorosulfenylated Carbonic Acid Derivatives", Agnew Chem. Inter. Edit., 9:54-63 (1970).
Field et al., "Organic Disulfides and Related Substances, VIII, Preparation and Oxidation of Some Unsymmetrical Dialkyl and Alkyl Pyridinium Disulfides", J. Organ. Chem., 29:1632 (1964).
Connor and Schroit, "Transbilayer Movement of Phosphatidylserine in Erythrocytes: Inhibition of Transport and Preferential Labeling of a 31 000-Dalton Protein by Sulthydryl Reactiv
Braslawsky Gary R.
Greenfield Robert S.
Kaneko Takushi
Monkovic Ivo
Willner David
Bristol-Myers Squibb
Covington Raymond
Ivy C. Warren
Mandel SaraLynn
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