Crosslinked polysaccharide based absorbents for removal of anti-A and/or anti-B antibodies from human plasma and whole blood
Inventors
Guliashvili, Tamaz • Gruda, Maryann • Golobish, Thomas • James, David • RUGGEBERG, Karl-Gustav • O'SULLIVAN, Pamela • PATTERSON, SARAH
Assignees
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Publication Number
US-12121879-B2
Publication Date
2024-10-22
Expiration Date
Abstract
The invention concerns polymeric media based on modified natural polysaccharides for removing one or both of Anti-A Antibodies and Anti-B Antibodies from human blood or plasma, the media comprising one or both of (i) a polymeric solid support with a blood group A Antigen ligand attached to the solid support at a ligand loading between 1-5 mg/mL of solid support, and wherein the media is stable under physiological pH conditions, and (ii) a polymeric solid support with a blood group B Antigen ligand attached to the solid support at a ligand loading between 1-5 mg/mL of solid support, and wherein the media is stable under physiological pH conditions.
Core Innovation
The polymeric media removes one or both of Anti-A Antibodies and Anti-B Antibodies from human blood or plasma. The media includes one or both polymeric solid supports, each comprising a blood group A antigen ligand or a blood group B antigen ligand attached to the solid support at a ligand loading between 1-5 mg/mL of solid support, and the media is stable under physiological pH conditions.
Prior to ligand attachment, each solid support is functionalized with NaIO4 oxidation followed by secondary crosslinking with appropriate di, tri or polyamines. The functionalized solid support is provided in a beaded form of functional polysaccharide, and embodiments specify that the beaded matrix is stable under physiological pH conditions while bearing the blood group antigen ligands.
The ligand-bearing solid supports include blood group antigen ligands, including tetra-saccharides. In certain embodiments, the solid support comprises partially unreacted aldehyde functional groups for coupling additional amino-group-containing ligands. The disclosure also presents example polymers and comparative results, including antibody reduction and evaluation using antibody titer determination.
Claims Coverage
The independent claim covers modified natural polysaccharide media for removing Anti-A and/or Anti-B antibodies from human blood or plasma, with blood group A and/or blood group B antigen ligands, 1-5 mg/mL ligand loading, physiological pH stability, NaIO4 oxidation, secondary crosslinking with di/tri/polyamines, and a beaded form of functional polysaccharide. Dependent claims add partial crosslinking, a named crosslinker, residual aldehyde groups, defined bead and pore sizes, and selected polysaccharide polymers.
Blood group antigen ligand-functionalized beaded polysaccharide for antibody removal
A polymeric media based on modified natural polysaccharides for removing one or both of Anti-A Antibodies and Anti-B Antibodies from human blood or plasma, the media comprising one or both of a polymeric solid support comprising a blood group A Antigen ligand or a polymeric solid support comprising a blood group B Antigen ligand attached to the solid support at a ligand loading between 1-5 mg/mL of solid support, wherein the media is stable under physiological pH conditions.
NaIO4 oxidation followed by secondary crosslinking of solid supports
Prior to ligand attachment, each solid support is functionalized with NaIO4 oxidation followed by secondary crosslinking with appropriate di, tri or polyamines.
Beaded form of functional polysaccharide
Each solid support comprises a beaded form of functional polysaccharide.
Partial crosslinking with multi-amines for pH stability
The solid support is stable across a pH range of 1–14 by partial crosslinking with di-, tri-, tetra-, or polyfunctional primary or secondary amines.
Tris(2-aminoethyl)amine as a crosslinking component
The trifunctional amine is tris(2-aminoethyl)amine (TREN).
Partially unreacted aldehyde functional groups for coupling amino-containing ligands
The solid support contains partially unreacted aldehyde functional groups for coupling various amino-group-containing ligands.
Defined bead size and pore size ranges
The beaded form has a bead size range of 45–1,000 microns and pore size ranging from non-porous to 1–20,000 angstrom pore diameter.
Selected polysaccharide solid-support polymers
The solid supports include polymers made from at least one of cellulose, dextran, starch, agarose, and chitosan.
The inventive concept centers on modified natural polysaccharide beaded solid supports functionalized by NaIO4 oxidation and secondary crosslinking with di/tri/polyamines, then bearing blood group A and/or blood group B antigen ligands at 1–5 mg/mL and remaining stable under physiological pH conditions for removing Anti-A and/or Anti-B antibodies. Dependent claims further refine the chemistry and physical form by specifying multi-amine partial crosslinking, a named crosslinker, residual aldehyde groups for coupling, and defined bead/pore size ranges, while narrowing the polysaccharide options.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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