Systems, compositions, and methods for transplantation
Inventors
HANNA, Lewis • Laughlin, John David • BROWNING, Shawn Robert
Assignees
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Publication Number
US-10265388-B2
Publication Date
2019-04-23
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 concerns a liquid composition that includes an alpha-2-macroglobulin polypeptide (A2M) obtained from a biological sample that is blood or bone marrow aspirate from an individual mammal. The liquid composition is not coagulated and is substantially free of white blood cells, while the concentration of A2M is at least 1.1 times higher than in the biological sample. The composition includes a fluid from the blood or bone marrow aspirate and an effective amount of an anti-coagulant selected from EDTA, tri-sodium citrate, acid-citrate-dextrose (ACD), CPD, CP2D, or CPDA1.
The liquid composition further defines targeted removal of non-A2M proteins by molecular-weight limitation. It includes a non-A2M protein with a molecular weight of less than 500 kDa, specifically fibrinogen, and a non-A2M protein with a molecular weight of less than 100 kDa, specifically CXCR2 or ABCF1, wherein the concentration of each non-A2M protein is less than in the biological sample.
The invention recites that the composition is prepared by passing a blood sample or bone marrow aspirate sample substantially free of white blood cells through a filter, retaining the retentate, and adding the effective amount of the anti-coagulant to the retentate. The filter has a molecular weight cut-off of about 500 kDa or less, and the disclosed context frames this preparation to yield a non-coagulated liquid with reduced non-A2M proteins.
Claims Coverage
The consolidated content identifies one independent claim. It covers a liquid composition with specified A2M enrichment, reduction of specific non-A2M proteins by molecular weight, and a preparation process using a filter with a defined molecular weight cut-off plus anti-coagulant addition, while maintaining a non-coagulated, substantially white-blood-cell-free condition.
A liquid composition with enriched A2M and reduced non-A2M proteins
A liquid composition comprising an alpha-2-macroglobulin polypeptide (A2M) from blood or bone marrow aspirate with a concentration at least 1.1 times higher than in the biological sample, including reduced concentrations of non-A2M proteins with molecular weight less than 500 kDa (fibrinogen) and less than 100 kDa (CXCR2 or ABCF1), and containing a fluid from the blood or bone marrow aspirate while being not coagulated and substantially free of white blood cells.
Anti-coagulant included in the A2M liquid composition
The liquid composition further comprises an effective amount of an anti-coagulant selected from EDTA, tri-sodium citrate, ACD, CPD, CP2D, and CPDA1.
Filtering-based preparation with a molecular weight cut-off filter
The liquid composition is prepared by passing a blood sample or bone marrow aspirate sample substantially free of white blood cells through a filter, retaining the retentate, and adding the effective amount of the anti-coagulant to the retentate, wherein the filter has a molecular weight cut-off of about 500 kDa or less.
The independent claim is directed to producing a non-coagulated, substantially white-blood-cell-free liquid containing enriched A2M together with reduced fibrinogen and reduced CXCR2 or ABCF1, using a filter-based preparation with a molecular weight cut-off of about 500 kDa or less and incorporating a specified anti-coagulant.
Stated Advantages
Not explicitly described in patent.
Documented Applications
For autologous delivery into joints (including synovial/diarthrodial etc.) to treat pain/inflammation and ECM degradation, as described in the partial content.
For autologous delivery into the spine (including disc/epidural space) to treat pain/inflammation and ECM degradation, as described in the partial content.
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