Enzyme-directed immunostimulant and uses thereof
Inventors
Mancini, Rock Joseph • Nielsen, Amy Esther • Hantho, Joseph Daniel
Assignees
Washington State University WSU
Publication Number
US-11117918-B2
Publication Date
2021-09-14
Expiration Date
2037-10-02
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Abstract
The disclosed invention relates to the novel composition of matter that allows for the controlled release of highly active compounds to be delivered to a desired site. This novel composition utilizes the immune system to allow for the controlled release of desired compounds. The present invention can utilize a plurality of highly active compounds, with one embodiment being the use of chemotherapeutics for the treatment of cancer.
Core Innovation
The invention concerns a novel composition of matter that enables the controlled release of highly active compounds, such as immunomodulators, to specific sites within the body. This composition achieves site-specific delivery by utilizing the immune system, particularly through mechanisms that allow for controlled activation and release of the active agent. One example provided is the use of chemotherapeutic agents for targeted cancer treatment.
A key problem addressed by this invention, according to the background section, is the challenge of effectively delivering drugs like immunomodulators while minimizing off-target effects and reducing dosing frequency. Traditional methods often result in inconsistent dosing, patient inconvenience, and significant toxicities, especially when attempting systemic administration of potent immune stimulants. The invention overcomes these limitations using enzyme-directed prodrug therapy to confine the release of the active compound to the desired location, such as the tumor microenvironment.
The composition involves a compound that links an immunomodulator to an enzyme substrate through a cleavable linker. Upon exposure to the specific enzyme, the immunomodulator is released in its active form at the target site. The invention allows for controlled, selective release, potentially improving efficacy and safety compared to conventional administration. Applications described in the patent include targeting disease states involving under- or over-activation of the immune system, such as cancer, multidrug-resistant cancer, or autoimmune disorders.
Claims Coverage
The patent includes independent claims pertaining to novel compound structures and their functional components.
Compound of formula (II) with immunomodulator-enzyme substrate linkage
The invention discloses a compound of formula (II), where the structure includes: - An immunomodulator moiety capable of enhancing the immune response at the site of release. - An enzyme substrate moiety, such as a pyranose-like or furanose-like structure, wherein chiral centers may be racemic or in S or R configuration, or other substrates like serine or glutamate. - Linkage between the immunomodulator and enzyme substrate, facilitating enzyme-mediated cleavage and controlled site-specific release. - The possibility for the compound to be in the form of a pharmaceutically acceptable salt.
Compound of formula (I) with functionalized structure for controlled release
The patent also claims a compound of formula (I), encompassing: - Defined chemical structure with variable groups (X as O, S, CH2, or N; Y as substituents affecting electron density, including hydrogen, nitro, alcohol, alkyl ether, alkyl ester, or carboxylate). - R is an enzyme substrate as detailed, fitting defined structural constraints. - R1 is an immunomodulator, including but not limited to known therapeutics like interferons, Imiquimod, or cellular membrane fractions from bacteria, and chemotherapeutic agents. - The compound allows for simultaneous or sequential delivery of immune stimulation or therapeutic agent. - Includes both the structure itself and its pharmaceutically acceptable salt forms.
The claims establish proprietary coverage for enzyme-activated pro-immunostimulant compounds with defined structures targeted for controlled, site-specific release of immunomodulators or chemotherapeutics.
Stated Advantages
Allows for controlled and site-specific release of highly active compounds, thus reducing systemic toxicity.
Improves safety and efficacy profiles over traditional immunomodulatory drug delivery methods by confining activity to disease sites.
Decreases dosing frequency and improves patient compliance due to more effective pharmacokinetic properties.
Provides selective targeting of immune activation, allowing for tailored treatment of diseases involving over- or under-activation of the immune system.
Documented Applications
Treatment of cancer, including multidrug-resistant cancer.
Treatment of multidrug-resistant pathogen infections.
Treatment of disease states resulting from under-activation of the immune system.
Treatment of disease states resulting from over-activation of the immune system, such as asthma and Crohn's disease.
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