Platelet derivative compositions, and methods of making and using such compositions
AssigneeCellphire, Inc.
InventorsJoshua Donald MONTGOMERY, Braden Carl ISHLER, Stephen Edward AMOS, Keith Andrew MOSKOWITZ, Amber Nicole LEE, Rafael JORDA, Glen Michael FITZPATRICK, Michael Alexander MATHEWS
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Abstract
Provided herein are materials and methods for the preparation of blood products. In some aspects, provided herein are compositions that include populations of platelet derivatives, including freeze-dried platelet derivatives, methods of producing the same, as well as methods of using the same to treat a subject. Such platelet derivatives have improved properties, as disclosed herein.
Claims20
A platelet derivative composition in the form of a powder, comprising
- a population of platelet derivatives having a compromised plasma membrane and a reduced propensity to aggregate as compared to platelets under in vitro aggregation conditions consisting of 1 mg/ml ristocetin, a buffer, and citrated plasma, as measured by light transmission aggregometry 5 minutes after ristocetin addition, such that no more than 5% of the platelet derivatives in the population aggregate under the in vitro aggregation conditions,
- wherein the platelet derivatives in the platelet derivative composition:
- have a CD41 positivity of at least 70% when measured using flow cytometry,
- have a phosphatidylserine positivity of at least 70%, when measured using Annexin V binding in flow cytometry,
- have less than 4.5% microparticles,
- have less than 2% crosslinking of platelet membranes via proteins and/or lipids present on the membranes,
- are capable of generating thrombin in an in vitro thrombin formation assay,
- are capable of producing occlusion by attaining a pressure of 80 kPa in less than 14 minutes when used at a concentration of about 70×103 platelet derivatives/μl in platelet-reduced citrated whole blood in an in vitro total thrombus-formation analysis system (T-TAS).
A platelet derivative composition in a vial, comprising
- a population of platelet derivatives having a compromised plasma membrane and a reduced propensity to aggregate as compared to platelets under in vitro aggregation conditions consisting of 1 mg/ml ristocetin, a buffer, and citrated plasma, as measured by light transmission aggregometry 5 minutes after ristocetin addition, such that no more than 5% of the platelet derivatives in the population aggregate under the in vitro aggregation conditions,
- wherein the platelet derivative composition in the vial is present in a volume of at least 10 ml, and
- wherein the platelet derivatives in the platelet derivative composition:
- have a CD41 positivity of at least 70% when measured using flow cytometry,
- have a phosphatidylserine positivity of at least 70%, when measured using Annexin V binding in flow cytometry,
- have less than 4.5% microparticles,
- have less than 2% crosslinking of platelet membranes via proteins and/or lipids present on the membranes,
- are capable of generating thrombin in an in vitro thrombin formation assay,
- are capable of producing occlusion by attaining a pressure of 80 kPa in less than 14 minutes when used at a concentration of about 70×103 platelet derivatives/μl in platelet-reduced citrated whole blood in an in vitro total thrombus-formation analysis system (T-TAS), and
- have a concentration of at least 5,250×103 platelet derivatives/μl.
Dependencies are inferred from the claim text.