公开(公告)号：US11377698B2

公开(公告)日：2022-07-05

申请号：US16560504

申请日：2019-09-04

Applicant: Inivata Ltd.

Inventor： Clive Morris ,  Vincent Plagnol ,  Tim Forshew

IPC: C12Q1/6886 ,  C12Q1/6827

Abstract: Provided herein, among other things, is a method of treating a cancer patient without the need for a tissue biopsy. In some embodiments, the method may comprise (a) performing or having performed a sequencing assay on cell-free DNA (cfDNA) from a sample of blood from the patient to determine if the cell-free DNA comprises actionable and/or non-actionable sequence variations in one or more target genes, and (b) treating the patient using the following method: i. administering a therapy that is targeted to an actionable sequence variation if the patient is identified as having the actionable sequence variation, and ii. administering a non-targeted therapy in the absence of any follow-up genetic testing on DNA extracted from a tissue biopsy if one or more non-actionable sequence variations and no actionable sequence variations are identified.

公开(公告)号：US20220162707A1

公开(公告)日：2022-05-26

申请号：US17494669

申请日：2021-10-05

Applicant: Inivata Ltd.

Inventor： Samuel Woodhouse ,  Stefanie Lensing ,  Tim Forshew ,  Vincent Plagnol ,  Matthew Edward Smith ,  Karen Howarth ,  Michael Epstein

IPC: C12Q1/6886 ,  C12Q1/6853 ,  C12Q1/6806 ,  C12Q1/686

Abstract: The present disclosure relates to methods for detecting and targeting genomic rearrangements, in particular gene fusion events, by targeting a DNA molecule of interest with a set or pool of primers, wherein the forward primers and reverse primers produce a PCR amplification product when a genomic rearrangement is present. The present disclosure also relates to methods of bioinformatic analysis to determine whether or not the detection of an amplification product from the selective PCR is actually indicative of the presence of a gene fusion. The present disclosure also related to related methods of diagnosis and treatment of diseases and conditions associated with such genomic rearrangements, in particular cancers, such as lung cancer.

公开(公告)号：US20210040564A1

公开(公告)日：2021-02-11

申请号：US16979832

申请日：2019-04-19

Applicant: Inivata Ltd.

Inventor： John Beeler ,  Vincent Plagnol ,  Greg Jones ,  Giovanni Marsico

IPC: C12Q1/6886 ,  C07K16/28 ,  A61P35/00

Abstract: A method for analyzing cell free DNA (cfDNA) from the bloodstream of a cancer patient is provided. In some embodiments, the method may comprise sequencing at least part of the coding sequences of TP53 and KRAS in a sample of the cfDNA, analyzing the sequences to identify nucleotide transversions in the coding sequences of the genes, relative to reference sequences of the genes. In some embodiments, the method may comprise counting the total number of identified nucleotide transversions. The presence of nucleotide transversions indicates that the patient will be more responsive to the immune checkpoint inhibitor, whereas a decreased number of transversions or no transversios indicates that the patient will be less responsive to the immune checkpoint inhibitor.

公开(公告)号：US20200010905A1

公开(公告)日：2020-01-09

申请号：US16491141

申请日：2018-06-18

Applicant: Inivata Ltd.

Inventor： Samuel Woodhouse ,  Stefanie Lensing ,  Tim Forshew ,  Vincent Plagnol ,  Matthew Edward Smith ,  Karen Howarth ,  Michael Epstein

IPC: C12Q1/6886

Abstract: The present disclosure relates to methods for detecting and targeting genomic rearrangements, in particular gene fusion events, by targeting a DNA molecule of interest with a set or pool of primers, wherein the forward primers and reverse primers produce a PCR amplification product when a genomic rearrangement is present. The present disclosure also relates to methods of bioinformatic analysis to determine whether or not the detection of an amplification product from the selective PCR is actually indicative of the presence of a gene fusion. The present disclosure also related to related methods of diagnosis and treatment of diseases and conditions associated with such genomic rearrangements, in particular cancers, such as lung cancer.

公开(公告)号：US10329627B1

公开(公告)日：2019-06-25

申请号：US16013869

申请日：2018-06-20

Applicant: Inivata Ltd.

Inventor： John Beeler ,  Vincent Plagnol ,  Greg Jones

IPC: C07H21/04 ,  C12Q1/68 ,  C12Q1/6886 ,  A61K39/395 ,  C07K16/28 ,  A61P35/00 ,  C12Q1/6806

Abstract: A method for analyzing cell free DNA (cfDNA) from the bloodstream of a cancer patient is provided. In some embodiments, the method may comprise sequencing at least part of the coding sequences of TP53 and KRAS in a sample of the cfDNA, analyzing the sequences to identify nucleotide transversions in the coding sequences of the genes, relative to reference sequences of the genes. In some embodiments, the method may comprise counting the total number of identified nucleotide transversions. The presence of nucleotide transversions indicates that the patient will be more responsive to the immune checkpoint inhibitor, whereas a decreased number of transversions or no transversions indicates that the patient will be less responsive to the immune checkpoint inhibitor.

公开(公告)号：US20190112645A1

公开(公告)日：2019-04-18

申请号：US16230609

申请日：2018-12-21

Applicant: Inivata Ltd.

Inventor： Samuel Woodhouse ,  Giovanni Marsico ,  Vincent Plagnol ,  Stefanie Lensing

IPC: C12Q1/6827

CPC classification number: C12Q1/6827 ,  C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2525/151 ,  C12Q2531/113 ,  C12Q2535/122

Abstract: Provided herein is method for, among other things, estimating the number of sequence variations in a sample of DNA. In some embodiments, the method can be used to estimate the mutational load of a sample. In some embodiments, the method makes use of a set of primers that have 3′ ends that specifically hybridizes to a sequence that is repeated multiple times in the genome. Thermocycling a reaction mix containing the primers may produce a reaction product comprising at least 50 amplicons having a total length of at least 100 kb. This product can be sequenced to provide an estimate of the number of sequence variations in the sample, and thus the mutational load of the sample.

公开(公告)号：US12195807B2

公开(公告)日：2025-01-14

申请号：US17831345

申请日：2022-06-02

Applicant: Inivata Ltd.

Inventor： Clive Morris ,  Vincent Plagnol ,  Tim Forshew

IPC: C12Q1/6886 ,  C12Q1/6827

Abstract: Provided herein, among other things, is a method of treating a cancer patient without the need for a tissue biopsy. In some embodiments, the method may comprise (a) performing or having performed a sequencing assay on cell-free DNA (cfDNA) from a sample of blood from the patient to determine if the cell-free DNA comprises actionable and/or non-actionable sequence variations in one or more target genes, and (b) treating the patient using the following method: i. administering a therapy that is targeted to an actionable sequence variation if the patient is identified as having the actionable sequence variation, and ii. administering a non-targeted therapy in the absence of any follow-up genetic testing on DNA extracted from a tissue biopsy if one or more non-actionable sequence variations and no actionable sequence variations are identified.

公开(公告)号：US11788116B2

公开(公告)日：2023-10-17

申请号：US18123235

申请日：2023-03-17

Applicant: Inivata Ltd.

Inventor： Vincent Plagnol ,  Tim Forshew ,  Samuel Woodhouse ,  Andrew Lawson ,  Matthew Smith

IPC: C12P19/34 ,  C12Q1/6806 ,  G16B50/00 ,  G06F17/18

CPC classification number: C12Q1/6806 ,  G06F17/18 ,  G16B50/00 ,  C12Q2600/158 ,  C12Q2600/16

Abstract: A method for the analysis of minimal residual disease is provided. In some embodiments, the method comprises obtaining multiple pairs of primers designed to amplify sequences that contain a plurality of sequence variations that have been previously identified in a patient's tumor. Amplicons are then obtained through a targeted multiplex amplification that amplifies those sequences from cell-free DNA isolated from a plasma sample. The amplicons are sequenced and two or more of the sequence variations are detected from sequence reads, wherein the detecting comprises comparing a quantity of sequence reads containing a sequence variation against a threshold value. A score is then calculated for the patient sample based on the combined allele frequencies of the detected two or more sequence variations, wherein the score indicates the presence of minimal residual disease.

公开(公告)号：US20230304084A1

公开(公告)日：2023-09-28

申请号：US17424708

申请日：2020-02-26

Applicant: Inivata Ltd.

Inventor： Samuel Woodhouse ,  Warren Emmett ,  Tim Forshew ,  Vincent Plagnol ,  Stefanie Lensing ,  Matthew Edward Smith ,  Giovanni Marsico ,  Mikidache Madi

IPC: C12Q1/6869

CPC classification number: C12Q1/6869 ,  C12Q2600/166 ,  C12Q1/6844

Abstract: Provided herein is method for quantifying a target sequence in a sample. In some embodiments, the method may comprise: adding a known amount of a first nucleic acid to a sample, wherein the longest contiguous sequence that the first spike-in sequence and the first target sequence have in common is no more than 40 contiguous nucleotides. After amplification and sequencing the reads from first nucleic acid can be used to quantify the amount of target sequence, or a variant thereof in the sample.

公开(公告)号：US11566274B2

公开(公告)日：2023-01-31

申请号：US16749858

申请日：2020-01-22

Applicant: Inivata Ltd.

Inventor： Vincent Plagnol ,  Tim Forshew ,  Samuel Woodhouse ,  Andrew Lawson ,  Matthew Smith

IPC: C12P19/34 ,  C12Q1/6806 ,  G16B50/00 ,  G06F17/18

Abstract: Provided herein is a method for sequence analysis that comprises analyzing PCR reactions that each contain different portions of the same sample, wherein at least some of the primer pairs are in more than one PCR reaction and at least one of the PCR reactions contains some but not all of the primer pairs of the other reaction(s).