Preparation and composition of inter-alpha inhibitor proteins from blood
Inventors
Lim, Yow-Pin • Sirya, Edward S. • Brne, Peter
Assignees
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Publication Number
US-10076559-B2
Publication Date
2018-09-18
Expiration Date
Abstract
The present invention generally provides processes for purification of Inter-alpha inhibitor proteins (IαIp) and compositions thereof from blood.
Core Innovation
The invention provides a method for treating a disease associated with increased activity of a serine protease or decreased activity of a serine protease inhibitor or a symptom thereof in a subject. The method includes administering to a human a composition comprising a first component comprising 85% to 100% IαIp proteins (IαIps) by weight admixed with a pharmaceutically acceptable carrier. The composition is defined as suitable for administration to a human.
The IαIps used in the method are characterized as having increased binding to an anti-IαIp antibody selected from MAb 69.26 and MAb 69.31 in a competitive Enzyme-Linked Immunosorbent Assay (ELISA). This increased binding is specified as compared to IαIps not exposed to a wash buffer having a pH of 4.0 or lower.
The disclosed approach is also associated with purification of inter-alpha inhibitor proteins (IαIp) from blood/plasma using chromatography combined with low-pH wash steps. The document characterizes IαIps by competitive ELISA with MAb 69.26 and MAb 69.31 and by trypsin inhibition activity, and it reports that low-pH exposure increases competitive ELISA binding without loss of biological activity in example results.
Claims Coverage
The document includes one independent claim directed to a treating method using a human-suitable composition that contains highly enriched IαIp proteins (85% to 100% by weight) and uses IαIps characterized by increased competitive ELISA binding to anti-IαIp antibodies after exposure to a wash buffer at pH 4.0 or lower. Dependent claims further refine the claim scope with additional quantitative assay-binding constraints and composition and dosing constraints.
Human treatment with high-purity IαIp composition
Administering to a human a composition comprising a first component comprising 85% to 100% IαIp proteins (IαIps) by weight admixed with a second component comprising a pharmaceutically acceptable carrier, wherein the composition is suitable for administration to a human.
IαIps defined by increased competitive ELISA binding after pH 4.0-or-lower wash exposure
Using IαIps characterized as having increased binding to an anti-IαIp antibody selected from MAb 69.26 and MAb 69.31 in a competitive ELISA as compared to IαIps not exposed to a wash buffer having a pH of 4.0 or lower.
Coverage centers on administering a human-suitable composition with 85% to 100% IαIp proteins (IαIps) by weight for treating a disease associated with increased serine protease activity or decreased serine protease inhibitor activity (or a symptom). The key defining limitation is that the IαIps show increased competitive ELISA binding to MAb 69.26 or MAb 69.31 after exposure conditions involving a wash buffer pH of 4.0 or lower, compared to IαIps not exposed to such a wash buffer.
Stated Advantages
Increased binding in competitive ELISA to MAb 69.26 and MAb 69.31 after exposure to a wash buffer having a pH of 4.0 or lower, while maintaining biological activity as reflected in example results.
Documented Applications
Therapeutic and prophylactic use of purified inter-alpha inhibitor proteins (IαIp) and compositions containing physiological mixtures of IαI and PαI for sepsis/septic shock.
Therapeutic and prophylactic use for acute inflammatory diseases and systemic inflammatory response syndrome (SIRS).
Therapeutic and prophylactic use for rheumatoid arthritis.
Therapeutic and prophylactic use for cancer and cancer metastasis.
Therapeutic and prophylactic use for infectious disease.
Therapeutic and prophylactic use for trauma/injury.
Therapeutic and prophylactic use for preterm labor.
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