Diaryl trehalose compounds and uses thereof
Inventors
Burkhart, David • ETTENGER, GEORGE • Evans, Jay • Ryter, Kendal T. • Smith, Alyson
Assignees
University of Montana Missoula
Publication Number
US-11912736-B2
Publication Date
2024-02-27
Expiration Date
2039-02-21
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Abstract
Disclosed herein are diaryl trehalose compounds and methods of use thereof, for example as vaccine adjuvants.
Core Innovation
The invention discloses diaryl trehalose (DAT) compounds and their pharmaceutically acceptable salts, with specific structural features as described by various formulas, such as (I) and (II). These compounds are characterized by aryl or heteroaryl groups attached to the trehalose core and specifically exclude a list of known compounds, ensuring novelty. The DAT compounds can be further incorporated into adjuvant and vaccine compositions for biological and therapeutic use.
This invention addresses the problem that, despite the availability of antigens for some bacterial and fungal pathogens, there is a lack of effective Th17-inducing vaccine adjuvants. Currently, adjuvants available for human use induce mainly Th2 or Th1 responses, with only CAF01 being known to promote Th17-mediated immunity, and it has not progressed beyond early clinical trials. There is a pressing need for adjuvants with improved efficacy and safety for use in vaccines against infectious diseases, autoimmunity, and cancer.
Through the identification and synthesis of new diaryl trehalose compounds, this disclosure provides a new class of potential Th17-inducing adjuvants. These compounds have been demonstrated to stimulate Th17-type cytokine production, such as IL-6, IL-1β, IL-23, and TNFα, in human and murine cells. As such, the compounds and their compositions are intended to modulate immune responses, enhance immunogenicity of co-administered antigens, and may serve in immunotherapies for cancer, infectious diseases, and autoimmune disorders.
Claims Coverage
The patent contains one independent claim defining five specific diaryl trehalose compounds or their pharmaceutically acceptable salts, as well as dependent claims covering adjuvant and vaccine compositions comprising these compounds.
Diaryl trehalose compounds with defined aryl substitution patterns
The independent claim specifically covers compounds selected from the group consisting of: - 6,6′-bis(3,5-diethoxybenzoyl)-α,α-D-trehalose - 6,6′-bis(2-hydroxy-3,5-di-tert-butylbenzoyl)-α,α-D-trehalose - 6,6′-bis(3,5-dipentyloxybenzoyl)-α,α-D-trehalose - 6,6′-bis(3,4,5-triethoxybenzoyl)-α,α-D-trehalose - 6,6′-bis(2,6-hydroxy-3,5-di-tert-butylbenzoylamino)-α,α-D-trehalose or a pharmaceutically acceptable salt thereof. These compounds are characterized by specific patterns of ethoxy, hydroxy, tert-butyl, pentyloxy, or triethoxy substitutions on the benzoyl or benzoylamino groups attached at the 6,6′-positions of the trehalose structure.
Adjuvant composition comprising an effective amount of any of the specified compounds
Dependent claims extend coverage to adjuvant compositions that include an effective amount of any one of the claimed diaryl trehalose compounds, or their pharmaceutically acceptable salts.
Vaccine composition comprising an antigen and the specified adjuvant composition
Dependent claims further include a vaccine composition comprising: - (a) an antigen; and - (b) an adjuvant composition comprising an effective amount of any one of the specified diaryl trehalose compounds or their pharmaceutically acceptable salts.
In summary, the claims cover five structurally defined diaryl trehalose compounds or their pharmaceutically acceptable salts, adjuvant compositions containing these compounds, and vaccine formulations comprising both an antigen and the adjuvant composition.
Stated Advantages
The compounds provide a new class of Th17-inducing adjuvants for vaccines targeting bacterial and fungal pathogens, certain cancers, and autoimmune diseases.
The disclosed compounds can stimulate production of Th17-type cytokines, such as IL-6, IL-1β, IL-23, and TNFα, in human and murine cells.
The adjuvant compositions may promote immune responses predominantly of the Th17 type, which is not achieved by most currently approved adjuvants.
The compounds and compositions offer potential utility in the treatment of cancer by inhibiting or reducing the growth or proliferation of cancer cells.
Documented Applications
Use as adjuvants in vaccine compositions to enhance immunogenicity of antigens for infectious diseases, including bacterial and fungal pathogens.
Use in methods for inducing an enhanced immune response, particularly Th17-type responses, in a subject.
Use in immunomodulatory compositions for modulating the immune response, either as monotherapy or in combination with an antigen.
Use in the treatment of cancer or inhibition/reduction of cancer cell proliferation.
Use in treatment and prevention of autoimmune disorders.
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