Assays to monitor bleeding disorders
Inventors
Sommer, Jurg • Jiang, Haiyan • Zhang, Xin • Yang, Buyue • Pierce, Glenn
Assignees
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Publication Number
US-11747351-B2
Publication Date
2023-09-05
Expiration Date
Abstract
The present invention provides methods of dosing Factor VIII or Factor IX chimeric and hybrid polypeptides. The present invention further provides high-sensitivity methods of quantifying an amount of activated FIX protein in a test sample.
Core Innovation
The invention provides a method for quantifying activated FIX protein in a test sample. The method measures thrombin generation activity in FIX-deficient plasma or blood in the presence of exogenous thrombin and without exogenous tissue factor. The measured thrombin generation activity is compared to a standard curve relating known activated FIX protein levels to activity; [procedural detail omitted for safety].
Reported examples show detection down to 0.5 pM and demonstrate that FIXa impurity accounts for misleading thrombin generation activity in FIX products. Calibrations relate activated FIX concentration to peak activity, including comparisons involving rFIXFc and BeneFIX. These evaluations indicate that activated FIX impurity contributes to apparent differences in product potency.
Claims Coverage
The claims identify one independent claim comprising two inventive features for quantifying activated FIX protein in a test sample.
Measurement of thrombin-generation activity
The claim element measures thrombin-generation activity for a test sample in FIX-deficient plasma or blood in the presence of exogenous thrombin and without exogenous tissue factor; [procedural detail omitted for safety].
Comparison with a standard curve
The claim element compares the measured thrombin-generation activity with a standard curve relating known activated FIX protein levels to thrombin-generation activity.
The independent claim centers on quantifying activated FIX protein through thrombin generation measurement in FIX-deficient plasma or blood without exogenous tissue factor and comparison with an activated FIX standard curve.
Stated Advantages
The assay provides high sensitivity, with reported examples showing detection down to 0.5 pM.
Documented Applications
Quantifying activated FIX protein in a test sample.
Assessing thrombin-generation activity in FIX products where FIXa impurity can confound comparisons of product potency.
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