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filingDate 2020-08-27-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_f25b23a2e0d5335f43058bfe153c1037
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publicationDate 2022-05-04-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber EP-3990662-A1
titleOfInvention Method for determining the presence or absence of minimal residual disease (mrd) in a subject who has been treated for a disease
abstract The present invention is focused on a method, kit and system for determining the presence or absence of minimal residual disease in a subject who has been treated for a proliferative disease wherein said method, kit and system comprise: (A) amplifying and sequencing at least one nucleotide sequence comprised in genomic DNA from a biological sample obtained from said subject prior to treatment for said disease, to obtain a first list of characters reading from left to right; (B) amplifying and sequencing at least one nucleotide sequence comprised in genomic DNA from a biological sample obtained from said subject after treatment for said disease, to obtain a second list of characters reading from left to right, wherein when a nucleotide sequence is mutated it is a genetic marker for said proliferative disease; (C) determining, for each second list of characters obtained in step (B), the degree of similarity, DS, with each first list of characters obtained in step (A); (D) selecting, for each second list of characters obtained in step (B), the DS of highest value, DSHV; (E) adding up the number of second lists of characters which have a DSHV that is greater than a threshold value, T, to obtain Lc, (F) adding up the total number of second lists of characters, Lt; (G) calculating the level of minimal residual disease, MRD, according to any of the following formulae: MRD = (Lc x k) / (Lt x D) or MRD = Lc / Lt or MRD = g x Lc x (D / k) / Lt 2; (H) determining (i) the minimum variant read frequency, minVRF, of said genetic marker, (ii) the limit ofdetection, D-limit, of said genetic marker (iii) the average mutation noise, avMut and (iv) the average position noise, avPos; (I) determining the experimental sensitivity, ES, from the greater of the minVRF, D-limit, avMut and avPos or from the greater of minVRF and D-limit; (J) determining the presence or absence of minimal residual disease in said subject by comparing the value of the level of minimal residual disease with the value of ES, the values of minVRF, D-limit, avMut and avPos, or the values of minVRF and D-limit; wherein when said level of minimal residual disease is equal to or greater than said ES, minVRF, D-limit, avMut or avPos values, minimal residual disease is present in said subject.
priorityDate 2019-08-27-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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