Compositions containing ambient-temperature stable, inactivated but therapeutically active biopharmaceuticals and methods for formulation thereof
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Publication Number
US-9744227-B2
Publication Date
2017-08-29
Expiration Date
Abstract
The disclosure concerns compositions containing inactivated but therapeutically active biopharmaceuticals, and methods for formulation thereof. Biopharmaceuticals are encapsulated and immobilized in dry amorphous carbohydrate-glass and irradiated for inactivation while in the dry state. The resulting compositions provide ambient-temperature stable, therapeutically active but inactivated biopharmaceuticals for use in vaccines and other applications.
Core Innovation
The invention relates to ambient-temperature stable, inactivated but therapeutically active (IBTA) biopharmaceuticals and formulations for inactivated but potent (TIBP) vaccines. It preserves one or more vaccines or biopharmaceuticals in a dry amorphous carbohydrate-glass matrix that supports storage and distribution without refrigeration.
The dry-state preservation immobilizes or encapsulates the vaccines or biopharmaceuticals within the carbohydrate-glass. The preserved material is then inactivated while maintaining therapeutic or immunological activity.
Inactivation is performed by irradiating the dry amorphous carbohydrate-glass matrix using permeated ionizing radiation, including electron beam, at a dose above 12.5 kGy or at least 12 kGy. Documented examples include rabies ERAg333 preserved by vaporization and irradiated to achieve complete inactivation while preserving antigen/metabolic activity and maintaining immunogenicity.
Claims Coverage
The independent claims include three inventive methods, with a consistent theme of dry amorphous carbohydrate-glass immobilization or encapsulation followed by inactivation by ionizing radiation at a dose threshold of at least 12 kGy or above 12.5 kGy.
Dry carbohydrate-glass preservation followed by permeated ionizing radiation inactivating step for thermostable vaccines
Preserving one or more vaccines in a dry carbohydrate-glass, configuring the preserved vaccines for storage and distribution without a need for refrigeration, and then inactivating the thermostable vaccines by irradiating the dry carbohydrate-glass containing the thermostable vaccines using a permeated ionizing radiation dose above 12.5 kGy.
Vaporized dry foam amorphous carbohydrate-glass matrix encapsulation followed by electron beam irradiation and therapeutic composition formation
Preserving one or more biopharmaceuticals in a dry state by providing the biopharmaceuticals in an aqueous solution or hydrogel, partially freezing to form an ice-and-liquid two-phase state, vaporizing to transform the composition into a dry foam that forms an amorphous carbohydrate-glass matrix with the biopharmaceuticals encapsulated and immobilized, and irradiating the biopharmaceuticals encapsulated and immobilized in the dry state by subjecting the matrix to an electron beam to yield IBTA biopharmaceuticals at a radiation dose of at least 12 kGy, wherein forming the IBTA biopharmaceuticals into the composition comprises at least one of reconstituting, combining with a dry compound, or micronizing to form a therapeutic powder.
Immobilization in dry amorphous carbohydrate-glass and irradiation to inactivate while forming an IBTA therapeutic composition
Immobilizing one or more biopharmaceuticals in a dry amorphous carbohydrate-glass matrix, irradiating the immobilized biopharmaceuticals to inactivate yielding immobilized IBTA biopharmaceuticals, and forming the immobilized IBTA biopharmaceuticals into the therapeutic composition, wherein the irradiating comprises a radiation dose of at least 12 kGy.
Across the independent claims, the main inventive features are dry amorphous carbohydrate-glass preservation that immobilizes or encapsulates vaccines or biopharmaceuticals, followed by dry-state inactivation using permeated ionizing radiation, including an electron beam embodiment, and subsequent formation into a therapeutic composition by reconstitution, combining with a dry compound, or micronizing.
Stated Advantages
Ambient-temperature stable storage and distribution without refrigeration of the preserved vaccines.
Inactivation while preserving therapeutic or immunological activity, characterized as inactivated but potent (TIBP) vaccines and inactivated but therapeutically active (IBTA) biopharmaceuticals.
Complete inactivation at a stated dose while preserving antigen/metabolic activity and maintaining immunogenicity in mice.
Documented Applications
Formulation of an inactivated but potent (TIBP) vaccine using ambient-temperature stable dry carbohydrate-glass preservation followed by permeated ionizing radiation inactivation.
Rabies vaccine example using rabies virus ERAg333 preserved by vaporization and then irradiated to achieve complete inactivation while preserving antigen/metabolic activity and maintaining immunogenicity.
Bacterial and microbial inactivation examples including Bacillus anthracis Sterne strain and Lactobacillus acidophilus preserved in dry state and evaluated for reduction in survival and metabolic activity after electron beam irradiation.
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