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filingDate 2014-03-14-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_f5cb0938379efb264846f5ab973c38db
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publicationDate 2018-04-30-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber SI-2970497-T1
titleOfInvention Variants of anti-TFPI antibodies with differential binding over the pH range for improved pharmacokinetic properties
abstract Antibodies are disclosed that bind to and inhibit the anti-coagulant function of TFPI and have a lower affinity for TFPI at pH 6.0 than at pH 7.4. The lower affinity at pH 6 improves circulating half-life (T½) due to reduced target mediated clearance, a process by which an antibody/antigen complex is endocytosed and trafficked to the lysosome where both components are degraded. The lower affinity at pH 6.0 results in disruption of the complex prior to lysosome targeting and allows for re-circulation of the antibody. Specific modifications to antibody binding by histidine residue substitution are disclosed along with methods of use.
priorityDate 2013-03-15-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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