Blood plasma fractions for use in liver regeneration
Inventors
Kheifets, Viktoria • Lu, Benson
Assignees
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Publication Number
US-12053489-B2
Publication Date
2024-08-06
Expiration Date
Abstract
Methods and compositions for treating aging-related diseases as well as liver regeneration, prevention of liver degeneration, and maintenance of liver are described. The compositions used in the methods include blood plasma and blood plasma fractions derived from blood plasma with efficacy in treating and/or preventing disease.
Core Innovation
The invention relates to using blood plasma fractions, including a plasma protein fraction (PPF1) and an albumin-related Fraction IV paste, to treat liver disorders and liver failure with the goal of promoting liver growth, regeneration, and recovery. The disclosed fractions include a plasma protein fraction (PPF1) and Fraction IV-1 and Fraction IV-4 paste suspensions, including a Fraction IV-1 paste suspension.
The document positions liver disorders and liver failure, including acute liver failure, chronic liver failure, and acute-on-chronic liver failure, as conditions addressed by administering these plasma fraction suspensions to a subject. The described approach aims to support liver growth and regeneration following the relevant disease state or surgical intervention.
The document reports that PPF1 and Fraction IV-4 paste suspension increase hepatocyte/proliferation markers after liver injury associated with hepatectomy, including increased EdU- and Ki67-positive cells and changes in cell cycle-associated gene expression. It also reports reduced serum ALT in remnant livers and effects on regeneration even in non-steatotic aged livers.
The document further reports that PPF1 is associated with increased TNFα expression and down-regulation of senescence markers (p53, p21, p16Ink4a). Comparative results versus recombinant human albumin are reported to indicate that the proliferative effects are driven by non-albumin “contaminant” components of plasma fractions.
Claims Coverage
The provided independent claims are clm-00001, clm-00007, and clm-00010. Across these independent claims, the core inventive features include administering an effective amount of a Fraction IV-1 paste suspension for liver disorder treatment and for improving recovery after liver resection and liver transplantation surgery.
Fraction IV-1 paste suspension for treating a diagnosed liver disorder
A method of treating a subject diagnosed with a liver disorder by administering an effective amount of a Fraction IV-1 paste suspension.
Fraction IV-1 paste suspension to improve recovery after liver resection surgery
A method of improving recovery from liver resection surgery in a subject by administering an effective amount of a Fraction IV-1 paste suspension.
Fraction IV-1 paste suspension to improve recovery after liver transplantation surgery
A method of improving recovery from liver transplantation surgery in a subject by administering an effective amount of a Fraction IV-1 paste suspension.
In the provided claim set, the inventive subject matter consistently centers on administering an effective amount of a Fraction IV-1 paste suspension, used either to treat a diagnosed liver disorder or to improve recovery after liver resection or liver transplantation surgery. The related dependent claim refinements include postoperative timing and a 10% w/v suspension concentration, and for liver disorder treatment, refinements specify acute liver failure, chronic liver failure, or acute-on-chronic liver failure.
Stated Advantages
Promotes liver growth and liver regeneration and recovery.
Increases hepatocyte/proliferation markers, including EdU- and Ki67-positive cells.
Improves liver regeneration outcomes, including after hepatectomy, including in non-steatotic aged livers.
Reduces serum ALT in remnant livers.
Improves recovery from liver resection surgery.
Improves recovery from liver transplantation surgery.
Documented Applications
Treating a subject diagnosed with a liver disorder, including liver failure (acute, chronic, and acute-on-chronic liver failure).
Improving recovery from liver resection surgery in a subject.
Improving recovery from liver transplantation surgery in a subject.
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