Compositions and methods of vascular injury repair
Inventors
Pecora, Andrew L. • Preti, Robert A.
Assignees
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Publication Number
US-7794705-B2
Publication Date
2010-09-14
Expiration Date
Abstract
The present invention relates to pharmaceutical compositions comprising a chemotactic hematopoietic stem cell product comprising an enriched population of CD34+ cells containing a subpopulation of cells having chemotactic activity, methods of preparing these compositions and use of these compositions to treat or repair vascular injury, including infarcted myocardium.
Core Innovation
The invention provides a sterile pharmaceutical composition for repairing a vascular injury in a revascularized subject, where the vascular injury is an acute myocardial infarction resulting from underlying diseases. The composition comprises a therapeutically effective amount of a sterile chemotactic hematopoietic stem cell product and a stabilizing amount of serum. The chemotactic hematopoietic stem cell product is a nonexpanded, isolated population of autologous mononuclear cells enriched for CD34+ cells, and it contains a subpopulation of potent CD34+/CXCR-4+ cells having CXCR-4-mediated chemotactic activity.
The sterile pharmaceutical composition is characterized for at least 24 hours following acquisition of the chemotactic hematopoietic stem cell product when tested in vitro after passage through a catheter. These properties include maintaining at least 70% CD34+ cells, containing the potent CD34+/CXCR-4+ subpopulation with CXCR-4-mediated chemotactic activity, maintaining at least 70% viability, and being able to form hematopoietic colonies in vitro.
The invention also encompasses a method of treating or repairing acute myocardial infarction by parenterally administering, through a catheter, the sterile pharmaceutical composition that includes the chemotactic hematopoietic stem cell product stabilized with a serum content greater than 20% (v/v). The administration is performed after peak inflammatory cytokine cascade production in the infarcted area and before completion of myocardial scar formation in the infarcted area.
Claims Coverage
The provided partial content includes two independent claims: clm-00001 (composition) and clm-00025 (method). Across these independent claims, the main inventive features are centered on a sterile chemotactic hematopoietic stem cell product with a potent CD34+/CXCR-4+ subpopulation, serum stabilization greater than 20% (v/v), preserved in vitro performance for at least 24 hours after catheter passage, and treating acute myocardial infarction with catheter-based parenteral administration during a defined inflammatory-to-scar formation interval.
Sterile chemotactic hematopoietic stem cell product in a sterile pharmaceutical composition
The sterile pharmaceutical composition comprises a therapeutically effective amount of a sterile chemotactic hematopoietic stem cell product that includes a nonexpanded, isolated population of autologous mononuclear cells enriched for CD34+ cells, further containing a subpopulation of potent CD34+/CXCR-4+ cells that have CXCR-4-mediated chemotactic activity.
Serum stabilization greater than 20% (v/v)
The sterile pharmaceutical composition comprises a stabilizing amount of serum, wherein the stabilizing amount of serum is greater than 20% (v/v).
Maintaining CD34+ purity, potency, viability, and hematopoietic colony formation after catheter passage
For at least 24 hours following acquisition of the chemotactic hematopoietic stem cell product when tested in vitro after passage through a catheter, the pharmaceutical composition is characterized as having at least 70% CD34+ cells, containing a subpopulation of potent CD34+/CXCR-4+ cells with CXCR-4-mediated chemotactic activity, being at least 70% viable, and being able to form hematopoietic colonies in vitro.
Catheter-based parenteral administration during the defined cytokine-to-scar interval
A method of treating or repairing acute myocardial infarction comprises parenterally administering through a catheter a sterile pharmaceutical composition during a specific time interval defined as being after peak inflammatory cytokine cascade production in the infarcted area and before completion of myocardial scar formation in the infarcted area.
Overall, the claim coverage requires a sterile pharmaceutical composition and a treatment method using catheter-based parenteral administration for acute myocardial infarction in a revascularized subject, with key requirements tied to a nonexpanded autologous mononuclear CD34+ enriched product containing a potent CD34+/CXCR-4+ chemotactic subpopulation, serum stabilization greater than 20% (v/v), and preservation of CD34 content, CXCR-4-mediated chemotactic potency, viability, and hematopoietic colony-forming ability for at least 24 hours after catheter passage, plus a defined timing relative to inflammatory cytokines and scar formation.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Repairing acute myocardial infarction in a revascularized subject using a sterile pharmaceutical composition administered through a catheter.
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