Methods for handling biological drugs containing living cells
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Assignees
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Publication Number
US-11648273-B2
Publication Date
2023-05-16
Expiration Date
Abstract
The present invention includes methods for handling live cell compositions in non-nutritive buffer. The cells in the compositions maintain their identity and functional characteristics after being stored in non-nutritive media up to about 72 hours. The storage method enables the cells to be manufactured at a processing facility and shipped to a point of care site. The invention also includes compositions that have been stored in non-nutritive buffer at storage temperatures while maintaining the functional characteristics.
Core Innovation
The invention relates to providing living cell compositions to a point of care facility by formulating living CD4+ T-cells in a non-nutritive buffer. The living CD4+ T-cells are reactivated to a state of activation by cross-linking CD3 and CD28 cell surface moieties using anti-CD3 and anti-CD28 monoclonal antibodies, and the living cells are more than minimally manipulated, cryopreserved and thawed prior to reactivation at a processing facility.
The method further includes transporting the reactivated cells to a point of care facility in a package equipped to maintain a storage temperature at 20° C. or below. After transportation, the reactivated living cells are stored with the agents in the state of activation in the non-nutritive buffer at a storage temperature of 20° C. or below, and transportation and storage time is greater than 24 hours while maintaining cell marker(s) indicative of the living cells identity.
The invention is directed to maintaining at least one functional characteristic exhibited by the living cells during transportation and storage for greater than 24 hours in the state of activation in the non-nutritive buffer, such that the reactivated living cells are useful for immunotherapy. The described functional characteristics include at least one cell functional characteristic exhibited by the living cells, with examples including CD40L expression and IFN-γ secretion.
Claims Coverage
The partial claims content identifies one independent claim, supported by dependent claims that add quantitative retention thresholds for viability, CD40L expression, and IFN-γ secretion, as well as optional constraints related to storage temperature range and pre-packaging container formats. Across the independent claim and dependents, the core coverage centers on reactivating cryopreserved, more-than-minimally-manipulated living CD4+ T-cells via CD3/CD28 cross-linking in a non-nutritive buffer, and preserving identity markers and functional characteristics for immunotherapy after transport and storage exceeding 24 hours at 20° C. or below.
Reactivating cryopreserved CD4+ T-cells in non-nutritive buffer by CD3/CD28 cross-linking
Formulating living CD4+ T-cells in a non-nutritive buffer by reactivating the living CD4+ T-cells to a state of activation by cross-linking the CD3 and CD28 cell surface moieties by anti-CD3 and anti-CD28 monoclonal antibodies, wherein the living CD4+ T-cells have been activated by cross-linking CD3 and CD28 cell surface moieties by anti-CD3 and anti-CD28 monoclonal antibodies and wherein the living cells have been more than minimally manipulated, cryopreserved and thawed prior to reactivation at a processing facility.
Transporting and storing reactivated cells at 20°c or below for more than 24 hours
Transporting the reactivated cells to a point of care facility in a package equipped to maintain a storage temperature at 20° C. or below; and storing the reactivated living cells with the agents in the state of activation in a non-nutritive buffer at a storage temperature of 20° C. or below, wherein the transportation and storage time is greater than 24 hours.
Maintaining identity markers and functional characteristics for immunotherapy after transport and storage
The reactivated living cells with the agents maintain a cell marker indicative of the living cells identity, maintain at least one functional characteristic exhibited by the living cells and are useful for immunotherapy after transportation and storage in the non-nutritive buffer for greater than 24 hours in the state of activation in the non-nutritive buffer.
Overall, the claim coverage requires a point-of-care workflow in which cryopreserved, more-than-minimally-manipulated living CD4+ T-cells are reactivated by CD3/CD28 cross-linking in a non-nutritive buffer, transported and stored at 20° C. or below for greater than 24 hours, and retain identity marker(s) and at least one functional characteristic for immunotherapy. Dependent claims further specify particular functional outputs and/or quantitative retention thresholds, and may constrain storage temperature and packaging/container formats.
Stated Advantages
Maintains cell marker indicative of the living cells identity after transportation and storage in the non-nutritive buffer for greater than 24 hours.
Maintains at least one functional characteristic exhibited by the living cells after transportation and storage in the non-nutritive buffer for greater than 24 hours.
Retained reactivated living cells are useful for immunotherapy after transportation and storage in the non-nutritive buffer for greater than 24 hours.
Documented Applications
Providing reactivated living CD4+ T-cell compositions to a point of care facility for use in immunotherapy after transportation and refrigerated storage.
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