Therapeutic apoptotic cell preparations, method for producing same and uses thereof
Inventors
Assignees
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Publication Number
US-10927343-B2
Publication Date
2021-02-23
Expiration Date
Abstract
The present application provides pharmaceutical compositions comprising a population of mononuclear-enriched cells in an early-apoptotic state, methods for the production of said compositions and uses thereof in the treatment of diseases characterized by pathological immune responses. The pharmaceutical compositions may be used in treatment of conditions such as, but not limited to, graft versus host disease (GVHD) and autoimmune diseases including but not limited to inflammatory bowel disease, gout and arthritis.
Core Innovation
The described invention relates to treating, preventing, or ameliorating an immune disease, an autoimmune disease, or an inflammatory disease by administering a pharmaceutical composition. The composition comprises a stable, high-yield, early-apoptotic mononuclear-enriched cell population that includes at least 30% early apoptotic mononuclear-enriched cells. The early-apoptotic cell population is stable for more than 24 hours and is produced for therapeutic administration as an early-apoptotic mononuclear-enriched cell product.
The invention targets immune and inflammatory indications in which the immune disease is selected from graft versus host disease (GVHD), high grade GVHD, acute GVHD, or any combination thereof. The inflammatory disease is selected from gout, inflammatory bowel disease, Crohn’s disease, and ulcerative colitis, or any combination thereof. The described approach includes early-apoptotic mononuclear-enriched cells for use in a subject in need thereof, including contexts associated with HSCT in the provided description.
Production of the pharmaceutical composition comprises freezing a mononuclear-enriched cell population in a freezing medium comprising an anticoagulant, thawing the mononuclear-enriched cell population, and inducing apoptosis in the thawed mononuclear-enriched cell population. Inducing apoptosis is described as incubating the population in a medium comprising methylprednisolone and an anticoagulant. The provided document description further emphasizes stable, high-yield manufacturing and references production improvements associated with adding anticoagulants during apoptosis induction stages.
Claims Coverage
The independent claim set is grounded in one independent claim (clm-00001). The claim contains inventive features covering therapeutic use conditions and disease selection, a stable early-apoptotic mononuclear-enriched cell composition with defined early-apoptotic content and stability window, and production by freezing with an anticoagulant, thawing, and methylprednisolone-plus-anticoagulant apoptosis induction.
Stable, high-yield early-apoptotic mononuclear-enriched cell population for immune/inflammatory disease treatment
Administering to the subject a pharmaceutical composition comprising a stable, high-yield, early-apoptotic mononuclear-enriched cell population comprising at least 30% early apoptotic mononuclear-enriched cells, wherein said early-apoptotic cell population is stable for more than 24 hours.
Disease selection for GVHD and inflammatory disease indications
Treating, preventing, or ameliorating an immune disease, an autoimmune disease, or an inflammatory disease in a subject in need thereof, wherein said immune disease is selected from graft versus host disease (GVHD), high grade GVHD, acute GVHD, or any combination thereof, and wherein said inflammatory disease is selected from gout, inflammatory bowel disease, Crohn's disease, and ulcerative colitis, or any combination thereof.
Freeze–thaw with anticoagulant and methylprednisolone-induced apoptosis production
Producing said cell population by freezing a mononuclear-enriched cell population in a freezing medium comprising an anticoagulant, thawing said mononuclear-enriched cell population, and inducing apoptosis in said thawed mononuclear-enriched cell population by incubating said population in a medium comprising methylprednisolone and an anticoagulant.
Across the independent claim, the inventive scope centers on a stable, high-yield, early-apoptotic mononuclear-enriched cell composition (≥30% early apoptotic cells; stability >24 hours) administered to treat selected GVHD and inflammatory disease indications, with production requiring anticoagulant-containing freezing, thawing, and methylprednisolone-plus-anticoagulant apoptosis induction.
Stated Advantages
High-yield production of the stable early-apoptotic mononuclear-enriched cell population.
Stability of the early-apoptotic cell population for more than 24 hours.
Documented Applications
Treating, preventing, or ameliorating graft versus host disease (GVHD), high grade GVHD, and acute GVHD.
Treating, preventing, or ameliorating inflammatory bowel disease, including Crohn’s disease and ulcerative colitis.
Treating, preventing, or ameliorating gout.
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