G01N2333/91017

Fusion proteins for the detection of apoptosis

The present invention relates to fusion proteins which are capable of binding to phosphatidylserine comprising a phosphatidylserene binding ligand and a modified O6-alkylguanine-DNA alkyltransferase which is capable of autoconjugation to an O6-benzylguanine-modified label, the fusion proteins being capable of binding to phosphatidylserine on the surface of a cell undergoing apoptosis. The invention also relates to recombinant polypeptide precursors of the fusion proteins which comprise a secretion leader sequence, purification tag, protease cleavage site and the fusion protein. Also included in the scope of the invention are nucleic acids encoding the recombinant polypeptide precursor, vectors comprising the nucleic acids, host cells comprising the vectors, methods of production of the fusion proteins, kits and assays for detecting apoptosis.

Clonal haematopoiesis

The present invention relates to clonal expansion of somatic cells in subjects, and acquired selective advantage of cell clones during the lifetime of a subject. In particular, the invention relates to methods for predicting the development of cancer based on the observation of specific genetic mutations in somatic cell clones, as well as to methods for treating or preventing cancer in a subject, in which clonal expansion of cells comprising specific modifications is observed.

Methods of detecting modified and unmodified DNA

Methods and kits for detecting the presence of at least one target DNA sequence with or without a modification in a DNA molecule are provided.

Methods of treating cancer

This invention relates to methods of treating cancer in a subject such as a human and determining at least one of the following in a sample from the subject, such as a human: (a) the presence or absence of a mutation at the alanine 677 (A677) residue in EZH2; or (b) the presence or absence of a mutation at the tyrosine 641 (Y641) residue in EZH2; or (c) the presence or absence of an increased level of H3K27me3 as compared to a control, and administering to said human an effective amount of an EZH2 inhibitor or a pharmaceutically acceptable salt thereof if at least one of the A677 mutation, Y641 mutation, or increased level of H3K27me3 is present in the sample.

EPIGENETIC COMPOUND SCREENING PLATFORM

Epigenetic compound screening platform, including methods and cell lines. In an exemplary screening method, ADK-null, ADK-L, and ADK-S cell lines may be selected. The ADK-null cell line may express no ADK protein. The ADK-L cell line may express only the long (L), nuclear isoform of a mammalian ADK protein from an exogenous construct. The ADK-S cell line may express only the short (S), cytoplasmic isoform of a mammalian ADK protein from an exogenous construct. Each of the cell lines may be exposed to the same test compound. A level of DNA or histone methylation, or DNA or histone methyltransferase activity for each of the exposed cell lines may be measured. The level for each exposed cell line may be compared to a corresponding level measured without exposure to the test compound, to determine whether the test compound affects DNA or histone methylation, or DNA or histone methyltransferase activity, in any of the cell lines.

CLONAL HAEMATOPOIESIS

The present invention relates to clonal expansion of somatic cells in subjects, and acquired selective advantage of cell clones during the lifetime of a subject. In particular, the invention relates to methods for predicting the development of cancer based on the observation of specific genetic mutations in somatic cell clones, as well as to methods for treating or preventing cancer in a subject, in which clonal expansion of cells comprising specific modifications is observed.

Method for treating and prognosing cancer

The present invention relates to an in vitro method for determine the prognosis of the survival time of a patient suffering from a cancer comprising the steps consisting of i) determining the expression level of the couple DNMT3A/ISGF3γ in a sample from said patient, ii) comparing said expression level with a predetermined reference value and iii) providing a good prognosis when the expression level is lower than the predetermined reference value and a poor prognosis when the expression level is higher than the predetermined reference value. The invention also relates a compound which is a DNMT3A/ISGF3γ antagonist or a compound which is a DNMT3A/ISGF3γ gene expression inhibitor for use in the treatment and prevention of cancer.

Process for in vitro diagnosis of hepatic disorders

Process for in vitro diagnosis and/or monitoring and/or prognosis and/or theranosis of hepatic disorders from a biological sample originating from a subject, in which process the presence and/or the concentration of the marker ADH1B (SEQ ID NO.2) and/or the presence and/or the concentration of the combination of the markers ADH1B (SEQ ID NO.2) and ADH1A (SEQ ID NO.1) is determined.

BIOMARKERS FOR CANCER THERAPY

This invention relates generally to biomarkers that are useful for determining whether a subject with cancer is likely to respond to cancer therapy. The invention therefore relates to methods, kits and compositions for determining whether a subject is likely to respond to cancer therapy, and to methods of treatment based on a determination that a subject with cancer is likely to respond to cancer therapy. The invention also relates to methods for sensitizing a subject with cancer to cancer therapy.

AGENT FOR THE TREATMENT OF PSORIASIS

The present invention relates to the use of EZH2 inhibitors for the treatment of psoriasis, a pharmaceutical composition for the treatment of psoriasis comprising said EZH2 inhibitors, a method for the preparation of said pharmaceutical composition, a method for the therapeutic treatment of a living being against psoriasis, a method for the screening of active agents against psoriasis, and the use in vitro of a EZH2 inhibitor for the suppression of the cellular IκBζ expression.