Methods of inducing liver regeneration by administering a plasma protein fraction
Inventors
Kheifets, Viktoria • Lu, Benson
Assignees
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Publication Number
US-11660316-B2
Publication Date
2023-05-30
Expiration Date
Abstract
Provided herein are methods of inducing liver regeneration in a subject diagnosed with a liver disorder. The method comprises administering a Plasma Protein Fraction (PPF) to the subject. In certain embodiments, the PPF comprises between 83% and 95% albumin in relation to total proteins. The PPF can be produced from plasma obtained from young individuals, for example, humans 40 years of age or younger.
Core Innovation
The invention relates to a method of inducing liver regeneration in a subject diagnosed with a liver disorder, including liver disorders and liver failure. The method administers an effective amount of a Plasma Protein Fraction (PPF), where the PPF comprises between 83% and 95% albumin in relation to total proteins.
The described PPF embodiments are plasma-derived fractions formulated with defined albumin and globulin contents. In some embodiments, the plasma used to produce the PPF is from human donors aged 40 years or younger.
In the described preclinical context, administration of PPF1 is reported to increase remnant liver and resected liver growth and to support hepatoprotective effects, including decreased serum ALT after hepatectomy. Proliferation and regenerative responses are reported using markers including EdU, Ki67, Cyclin B1, and Cyclin A2.
Claims Coverage
The independent claim covers a method of inducing liver regeneration by administering an effective amount of a Plasma Protein Fraction (PPF) with a defined albumin-to-total-protein ratio. The claim set includes refinements that add a Pulse Dose regimen, specify acute and chronic liver failure contexts, and impose quantitative limits on globulins and other plasma proteins and on gamma globulin.
PPF with defined albumin proportion for liver regeneration
A method of inducing liver regeneration in a subject diagnosed with a liver disorder by administering an effective amount of a Plasma Protein Fraction (PPF), where the PPF comprises between 83% and 95% albumin in relation to total proteins.
Pulse Dose administration for liver regeneration
The method further specifies that administering the PPF is carried out using a Pulse Dose dosing regimen.
Acute liver failure treatment context
The method is configured for a liver disorder that is acute liver failure.
Chronic liver failure treatment context
The method is further defined as being used for treating a chronic liver failure condition.
Globulins and other plasma proteins upper limit
The method is configured such that the PPF includes no more than 17% globulins and other plasma proteins.
Gamma globulin upper limit
The method is such that the PPF contains no more than 1% gamma globulin.
Overall, the claim coverage centers on liver regeneration induction by administering a plasma-derived PPF with an 83% to 95% albumin proportion relative to total proteins, with further claim refinements adding Pulse Dose administration, selecting acute or chronic liver failure contexts, and imposing quantitative constraints on globulins and other plasma proteins and gamma globulin.
Stated Advantages
Induces liver regeneration in subjects with liver disorders and liver failure.
Increases remnant liver and resected liver growth.
Provides hepatoprotective effects, including decreased serum ALT after hepatectomy.
Enhances liver cell proliferation and regenerative marker expression (EdU, Ki67, Cyclin B1, Cyclin A2).
Supports a mechanism involving liver sinusoidal endothelial cell proliferation and TNFα upregulation.
Reported to show stronger proliferation/regenerative effects compared to recombinant human albumin (rhAlbumin) and human albumin solution (HAS), including HAS1.
Documented Applications
Methods for inducing liver regeneration in a subject diagnosed with a liver disorder, including acute liver failure, chronic liver failure, and acute-on-chronic liver failure.
Use of plasma-derived Plasma Protein Fraction (PPF) compositions, including albumin- and globulin-constrained PPF embodiments, to promote liver cell proliferation and regeneration in the stated liver failure contexts.
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