Targeted enzyme prodrug therapy
OwnerVolker Schellenbergerinventor
Life of this patent
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Abstract
The present invention provides targeted enzymes that bind to targets better than the corresponding pre-targeted enzymes bind the target under like conditions, methods of making targeted enzymes, methods of using targeted enzymes to treat diseases, and pharmaceutical compositions comprising targeted enzymes.
Claims29
A pharmaceutical composition comprising a targeted enzyme (TE) and a pharmaceutically acceptable carrier, excipient or diluent, said TE exhibiting a catalytic activity that converts a prodrug to a product and comprising:
- a) a substrate recognition site;
- and
- b) a targeting site that binds a target;
- wherein
- i) the targeting site comprises a variant sequence that is derived from a variation-tolerant sequence of a corresponding pre-targeted enzyme that does not bind the target,
- ii) the target is bound by the TE but not by the pre-targeted enzyme under like conditions;
- and
- iii) the target is not an isolated monoclonal antibody.
A targeted enzyme exhibiting a catalytic activity that converts a prodrug into a product, comprising:
- a) a substrate recognition site;
- b) a first targeting site that binds a first target;
- and
- c) a second targeting site that binds a second target,
- wherein
- i) each targeting site comprises a variant sequence derived from variation-tolerant sequences of a corresponding pre-targeted enzyme, and
- ii) the affinity of the targeted enzyme for the first and second target is greater than the affinity of the pre-targeted enzyme for the first and second target under like conditions.
A targeted enzyme exhibiting a catalytic activity that converts a prodrug to a product, comprising:
- a) a substrate recognition site;
- and
- b) a targeting site that binds a target,
- wherein
- i) the targeting site comprises two variant sequences derived from variation-tolerant sequences of a corresponding pre-targeted enzyme,
- ii) the affinity of the targeted enzyme for the target is greater than the affinity of the pre-targeted enzyme for the target under like conditions;
- and
- iii) the target is not an isolated monoclonal antibody.
A targeted enzyme exhibiting a catalytic activity that converts a prodrug to a product, comprising:
- a) a substrate recognition site;
- and
- b) a targeting site that binds a target;
- wherein
- i) the targeting site comprises three variant sequences, wherein each of the variant sequences is derived from variation-tolerant sequences of a corresponding pre-targeted enzyme;
- and
- ii) the affinity of the targeted enzyme for the target is greater than the affinity of the pre-targeted enzyme for the target under like conditions.
A targeted β-lactamase enzyme exhibiting a catalytic activity that converts a prodrug to a product, comprising:
- a) a substrate recognition site;
- b) a first targeting site that binds a first target;
- c) a second targeting site that binds a second target;
- and
- d) a sequence KTXS at its substrate recognition site,
- wherein
- i) each targeting site comprises a variant sequence derived from a variation-tolerant sequence of a corresponding pre-targeted enzyme, and
- ii) the affinity of the targeted enzyme for the first and second target is greater than the affinity of the pre-targeted enzyme for the first and second target under like conditions.
A targeted β-lactamase enzyme exhibiting a catalytic activity that converts a prodrug to a product, comprising:
- a) a prodrug recognition site;
- b) a targeting site that binds a target, and
- c) a sequence KTXS at its substrate recognition site,
- wherein
- i) the targeting site comprises three variant sequences, wherein each of the variant sequences is derived from variation-tolerant sequences of a corresponding pre-targeted β-lactamase enzyme;
- and
- ii) the affinity of the targeted β-lactamase enzyme for the target is greater than the affinity of the pre-targeted β-lactamase enzyme for the target under like conditions.
A targeted β-lactamase enzyme exhibiting a catalytic activity that converts a prodrug to a product, comprising:
- a) a substrate recognition site;
- b) a targeting site that binds a target, and
- c) a sequence KTXS at its substrate recognition site,
- wherein
- i) the targeting site comprises two variant sequences, wherein each of the variant sequences is derived from variation-tolerant sequences of a corresponding pre-targeted β-lactamase enzyme,
- ii) the affinity of the targeted β-lactamase enzyme for the target is greater than the affinity of the pre-targeted β-lactamase enzyme for the target, and
- iii) the target is not an isolated monoclonal antibody.
A pharmaceutical composition comprising a targeted β-lactamase enzyme and a pharmaceutically acceptable carrier, excipient, or diluent, said enzyme exhibiting a catalytic activity that converts a prodrug to a product and comprising:
- a) a substrate recognition site;
- b) a targeting site that binds a target;
- and
- c) a sequence KTXS at its substrate recognition site,
- wherein
- i) the targeting site comprises a variant sequence that is derived from a variation-tolerant sequence of a corresponding pre-targeted enzyme that does not bind the target,
- ii) the target is bound by the targeted β-lactamase enzyme but not by the pre-targeted β-lactamase enzyme under like conditions, and
- iii) the target is not an isolated monoclonal antibody.
Dependencies are inferred from the claim text.