Compositions and Methods for Delivery of Antitumor Agents
First Claim
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1. A method for treating a neoplastic disease in a mammal comprising:
- providing an antibody-cytotoxin conjugate with an acid-stable covalent linkage between an antibody and a cytotoxin, andadministering said antibody-cytotoxin conjugate to the mammal so that said conjugate is internalized within a cell of the mammal to treat said neoplastic disease.
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Abstract
Methods for treating a neoplastic disease with an antibody-cytotoxin conjugate molecule, methods of synthesizing an antibody-cytotoxin conjugate molecule are provided. Compounds that are useful as antibody-cytotoxin conjugate molecule or useful in the synthesis of these molecules are also provided.
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Citations
51 Claims
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1. A method for treating a neoplastic disease in a mammal comprising:
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providing an antibody-cytotoxin conjugate with an acid-stable covalent linkage between an antibody and a cytotoxin, and administering said antibody-cytotoxin conjugate to the mammal so that said conjugate is internalized within a cell of the mammal to treat said neoplastic disease. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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10. A method for treating a neoplastic disease in a mammal comprising:
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providing an antibody-cytotoxin conjugate with an acid-labile covalent linkage between an antibody and a cytotoxin, and administering said antibody-cytotoxin conjugate to the mammal so that said conjugate is internalized within a cell of the mammal to treat said neoplastic disease. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17, 18)
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19. A method of synthesizing an antibody-cytotoxin conjugate molecule comprising:
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introducing into a single vessel an antibody, a thiolating reagent, and a maleimide-derivatized cytotoxin; contacting said antibody with said thiolating reagent to form a thiolated antibody; and contacting said thiolated antibody with said maleimide-derivatized cytotoxin to form an antibody-cytotoxin conjugate molecule. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27, 28)
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29. A compound 3-[5-(1-(3-aminopropyl)indole-2-carbonyl)aminoindole-2-carbonyl]-1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole.
- 30. A compound of Formula I:
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33. The compound 3-[5-(1-(3-aminopropyl)indole-2-carbonyl)aminoindole-2-carbonyl]-1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole.
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34. The compound 3-[5-[1-{3-[3-(2,5-dioxo-2,5-dihydropyrrol-1-yl)propionylamino]propyl}indole-2-carbonyl]aminoindole-2-carbonyl]-(1-chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indole.
- 43. A compound of Formula II:
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44. A compound 1-[3-(N′
- -{1-[2-(1-Chloromethyl-5-hydroxy-1,2-dihydro-3H-benzo[e]indole-3-carbonyl)-1H-indol-5-yl]-ethylidene}-hydrazino)-3-oxo-1-propyl]maleimide.
Specification