Systems, compositions, and methods for transplantation
Inventors
HANNA, Lewis • Laughlin, John David • BROWNING, Shawn Robert
Assignees
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Publication Number
US-11040092-B2
Publication Date
2021-06-22
Expiration Date
Abstract
Systems and methods for purification and concentration of autologous alpha-2-macroglobulin (A2M) from whole blood are provided. Also provided are diagnostic methods for identifying sites in the synovial joints, spine, tendons or ligaments for treatment of pain, degeneration, or inflammation with autologous A2M. Methods for utilizing autologous A2M in combination with other autologous treatments (e.g. platelets and other growth factors) are provided in addition to combinations with exogenous drugs or carriers. Also provided is a method of producing recombinant A2M wild type or variants thereof where the bait region was modified to enhance the inhibition characteristics of A2M and/or to prolong the half life of the protein in joints and spine disc or epidural space.
Core Innovation
The invention relates to methods of treating a disease or condition in a subject by administering at an anatomic site in need of treatment a liquid composition comprising alpha-2-macroglobulin (A2M) and platelet-rich plasma (PRP), where the A2M is present at a concentration at least 3.5 times higher than the concentration of the A2M in the blood sample from the subject. The liquid composition includes specific non-A2M protein molecular-weight constraints and immunogenicity and white blood cell constraints.
The disease or condition is associated with inflammation in a joint, spinal disc, bone, tendon, or ligament, and/or degeneration in a joint, spinal disc, bone, tendon, or ligament, and/or injury of a joint, spinal disc, bone, tendon, or ligament, and/or wound healing. The platform includes enrichment and concentration of autologous alpha-2-macroglobulin (A2M) from mammalian blood using filtration to enrich A2M while reducing low-molecular-weight proteins and removing cells and leukocytes.
The liquid composition is substantially non-immunogenic and substantially free of white blood cells, while comprising non-A2M protein with a molecular weight of less than 500 kDa at a concentration of at most 90% of the concentration of the non-A2M protein with a molecular weight less than 500 kDa in the blood sample, wherein the non-A2M protein with a molecular weight less than 500 kDa is fibrinogen. Additional refinement includes a non-A2M protein with a molecular weight of less than 100 kDa present at a concentration of at most 90% of the concentration of that protein in the blood sample, where the non-A2M protein with a molecular weight less than 100 kDa is ATP Binding Cassette Subfamily F Member 1 (ABCF1).
Claims Coverage
The independent claims cover two inventive features centered on administering an anatomic-site liquid composition containing autologous alpha-2-macroglobulin (A2M) enriched relative to the subject’s blood and platelet-rich plasma (PRP), with substantially non-immunogenic and substantially white-cell-free properties, and with molecular-weight-constrained non-A2M proteins.
Treating inflammation, degeneration, injury, or wound healing at an anatomic site with enriched autologous A2M and PRP liquid composition
Administering to the subject at an anatomic site in need of treatment a liquid composition comprising an alpha-2-macroglobulin polypeptide (A2M) from a blood sample from the subject at a concentration at least 3.5 times higher than the concentration of the A2M in the blood sample, and platelet-rich plasma from the blood sample, wherein the liquid composition comprises a non-A2M protein with a molecular weight of less than 500 kDa present at at most 90% of the concentration of that protein in the blood sample, and wherein the non-A2M protein with a molecular weight of less than 500 kDa is fibrinogen, and wherein the liquid composition is substantially non-immunogenic and substantially free of white blood cells.
Treating with enriched autologous A2M and PRP while constraining <500 kDa and <100 kDa non-A2M proteins
Administering to the subject at an anatomic site in need of treatment a liquid composition comprising an alpha-2-macroglobulin polypeptide (A2M) from a blood sample from the subject at a concentration at least 3.5 times higher than the concentration of the A2M in the blood sample, and platelet-rich plasma from the blood sample, wherein the liquid composition comprises a non-A2M protein with a molecular weight of less than 500 kDa present at at most 90% of the concentration of that protein in the blood sample, and comprises a non-A2M protein with a molecular weight of less than 100 kDa present at at most 90% of the concentration of that protein in the blood sample, where the non-A2M protein with a molecular weight less than 100 kDa is ATP Binding Cassette Subfamily F Member 1 (ABCF1), and wherein the liquid composition is substantially non-immunogenic and substantially free of white blood cells.
Across the independent claims, coverage centers on administering an anatomic-site liquid composition that combines autologous A2M enriched at least 3.5-fold relative to the subject’s baseline blood with platelet-rich plasma, while maintaining substantially non-immunogenic and substantially white-cell-free characteristics and limiting non-A2M proteins by molecular weight, including fibrinogen as the <500 kDa non-A2M protein and ABCF1 as the <100 kDa non-A2M protein in one claim.
Stated Advantages
Substantially non-immunogenic liquid composition
Substantially free of white blood cells liquid composition
Enrichment of alpha-2-macroglobulin (A2M) in a liquid composition for treatment at an anatomic site
Reduction of non-A2M protein concentrations for specific molecular-weight fractions, including <500 kDa and, in one independent claim, <100 kDa, to at most 90% relative to the blood sample
Documented Applications
Treating a disease or condition associated with inflammation, degeneration, injury, or wound healing in a joint, spinal disc, bone, tendon, or ligament by administering an anatomic-site liquid composition comprising enriched A2M and platelet-rich plasma (PRP).
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