Alteration of pharmacokinetics of proteins by charge modification
AssigneeNeoRx Corporation
InventorsAlton C. Morgan, Jr., Gowsala P. Sivam, Paul G. Abrams
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Abstract
There is disclosed charge-modified conjugates comprising a targeting protein bound to a therapeutic or diagnostic agent. Charge-modifying a conjugate to cause an acidic shift in the isoelectric point results in prolonged serum half-life upon in vivo administration and is useful to accumulate a therapeutic agent at the target site. Conversely, charge-modification to cause a basic shift in the isoelectric point of the conjugate reduces serum half-life upon in vivo use for diagnostic imaging purposes and results in higher target-to-background ratios.
Claims11
A conjugate comprising a monoclonal antibody or fragment thereof and a charge-modified polypeptide toxin, wherein the charge-modified toxin contains at least one non-native anionic group formed by reaction of at least one native amino group of unmodified toxin with an anion-forming agent.
Dependencies are inferred from the claim text.