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US 10,780,179 B2Granted
Conjugates for the treatment of cancer targeted at intracellular tumor-associated antigens
AssigneeImmunobiochem Corporation
InventorAnton Neschadim
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Abstract
The present disclosure relates to conjugates, preferably, antibody-drug conjugates, directed against select non-transmembrane tumor antigens that are normally intracellular but can be secreted from cancer cells, such as human cathepsin D, and can be targeted in a way that enables the selective delivery of the conjugate to cancer cells. The design and mechanism of action disclosed enable the preferential delivery of the conjugate prodrug to cancer cells over normal cells for the purpose of selectively killing cancer cells. The uses of such conjugates for the treatment of cancer are described.
Claims12
A conjugate comprising:
- I. a. an antibody that specifically binds human cathepsin D;
- b. a cytotoxic moiety linked indirectly to the antibody, the cytotoxic moiety selected from the group consisting of an auristatin, a dolastatin, a maytansinoid, a tubulysin, a cryptophycins, and a calicheamicin;
- c. and a labile linker linking the antibody and cytotoxic moiety, the labile linker derived from a cross-linking reagent selected from the group consisting of N-succinimydyl-3-(2-pyridyldithio)propionate (SPDP), N-succinimidyl 4-(2-(SPDB), and N-succinimidyl-4-(2-pyridyldithio)2-sulfo-butanoate (sulfo-SPDB);
- wherein the antibody is selected from anti-cathepsin D antibody clone 185111, anti-cathepsin D antibody clone 3F12-1B9 and anti-cathepsin D antibody clone M1G8 or a binding fragment of any of the foregoing;
- and
- wherein the conjugate is able to bind extracellular cathepsin D and selectively target cancer cells.
3 more elements
Dependencies are inferred from the claim text.