Настройки

Укажите год
-

Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

Подробнее
-

Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

Подробнее

Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
Ведите корректный номера.
Ведите корректный номера.
Ведите корректный номера.
Ведите корректный номера.
Укажите год
Укажите год

Применить Всего найдено 7393. Отображено 100.
02-02-2012 дата публикации

Method and compositions for cancer prognosis

Номер: US20120027750A1

Methods are provided to determine the cancer prognosis of subjects and/or to adapt the treatment protocol of subjects having or susceptible to cancer. Embodiments include the steps of determining in vitro the genotype of said subject at a polymorphism in the C3-ITGAM axis, making a cancer prognosis of the subject based on said genotype and selecting an anti-cancer treatment for the subject.

Подробнее
16-02-2012 дата публикации

Lung cancer diagnostic polypeptide, method for detecting lung cancer, and method for evaluating therapeutic effect

Номер: US20120040376A1

A novel biomarker for use in lung cancer diagnosis is provided.

Подробнее
23-02-2012 дата публикации

ANTI-lgSF4 ANTIBODY AND UTILIZATION OF THE SAME

Номер: US20120046451A1
Принадлежит: Institute for Antibodies Co Ltd

It is intended to clarify a molecule which is available as a target in treating or diagnosing cancer and utilize the molecule in the medical field or the research field. By treating IgSF4, which has been identified as a molecule specifically expressed in lung cancer cells, with an antibody, and ADCC activity is exerted. Based on this finding, an anti-IgSF4 antibody is provided as a means efficacious in treating cancer, etc.

Подробнее
15-03-2012 дата публикации

Il-17 homologous polypeptides and therapeutic uses thereof

Номер: US20120064073A1
Принадлежит: Individual

The present invention is directed to novel polypeptides having sequence identity with IL-17, IL-17 receptors and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders and other inflammatory diseases.

Подробнее
15-03-2012 дата публикации

Identification of a jak2 mutation involved in vaquez polyglobulia

Номер: US20120066776A1

The present invention concerns the V617F variant of the protein-tyrosine kinase JAK2, said variant being responsible for Vaquez Polyglobulia. The invention also relates to a first intention diagnostic method for erythrocytosis and thrombocytosis allowing their association with myeloproliferative disorders, or to the detection of the JAK2 V617F variant in myeloproliferative disorders allowing their reclassification in a new nosological group.

Подробнее
22-03-2012 дата публикации

Methods And Marker Combinations For Screening For Predisposition To Lung Cancer

Номер: US20120071334A1
Принадлежит: ABBOTT LABORATORIES

The present invention relates to rapid, sensitive methods for determining whether a subject has or is at risk of developing lung cancer based on certain combinations of biomarkers, or biomarkers and biometric parameters. The methods consist of: a) quantifying in a test sample obtained from a subject, the amount of two or more biomarkers in a panel, the panel comprising at least one antibody and at least one antigen: b) comparing the amount of each biomarker quantified in the panel to a predetermined cutoff for said biomarker and assigning a score for each biomarker based on said comparison: c) combining the assigned score for each biomarker quantified in step b to obtain a total score for said subject: d) comparing the total score in step c with a predetermined total score and e) determining whether said subject has a risk of lung cancer based on the comparison in step d.

Подробнее
19-04-2012 дата публикации

Ipp complex as marker for erlotinib treatment

Номер: US20120095029A1
Принадлежит: Hoffmann La Roche Inc

The present invention provides biomarkers which are predictive for the clinical benefit of erlotinib hydrochloride treatment in cancer patients.

Подробнее
24-05-2012 дата публикации

Diagnosis and treatment of cancer using anti-tmprss11e antibody

Номер: US20120128678A1

[Problem to be Solved] An object of the present invention is to provide novel means for the treatment and diagnosis of cancer. [Solution] The present inventors have obtained a monoclonal antibody against TMPRSS11E and found that this antibody binds to a native form of TMPRSS11E, and TMPRSS11E is highly expressed on the cell membranes of cancer cell lines in flow cytometry. This antibody exhibits antibody-dependent cell-mediated cytotoxicity activity (ADCC activity) and antitumor effect based on internalization activity and is promising as a therapeutic target. Moreover, this antibody has neutralization activity against protease activity and is also expected to have effect brought about by the inhibition of TMPRSS11E functions.

Подробнее
24-05-2012 дата публикации

Truncated cd20 protein, deltacd20

Номер: US20120129167A1
Принадлежит: Francais du Sang Ets

The present invention relates in particular to a protein from an alternative splicing of the gene encoding CD20, the nucleic acid sequences encoding the protein according to the invention, a mutated form of the CD20 gene as well as drugs, diagnostic tools, diagnostic methods and treatment methods using the protein and the nucleic acid sequences according to the invention.

Подробнее
02-08-2012 дата публикации

Cybp as a marker for lung cancer

Номер: US20120196303A1
Принадлежит: Roche Diagnostics Operations Inc

The present invention relates to the assessment of lung cancer. It discloses the use of protein CYBP in the assessment of lung cancer. It also relates to a method for assessing lung cancer in vitro using a liquid sample, derived from an individual by measuring CYBP in said sample. Measurement of CYBP can, e.g., be used in the early detection or in the follow-up of patients with lung cancer.

Подробнее
16-08-2012 дата публикации

Folate receptor alpha as a diagnostic and prognostic marker for folate receptor alpha-expressing cancers

Номер: US20120207771A1
Принадлежит: Morphotek Inc

The present invention provides methods and kits for assessing whether a subject is afflicted with an FRα-expressing cancer, methods and kits for predicting the progression of ovarian cancer in a subject afflicted with an FRα-expressing cancer, methods and kits for assessing the level of risk that a subject will develop an FRα-expressing cancer, and methods of stratifying a subject with an FRα-expressing cancer into cancer therapy groups. The methods involve determining the level of folate receptor alpha (FRα) which is not bound to a cell in a sample derived from the subject and comparing this level with the level of FRα in a control sample.

Подробнее
23-08-2012 дата публикации

Method of predicting response to thalidomide in multiple myeloma patients

Номер: US20120214710A1
Принадлежит: DUBLIN CITY UNIVERSITY

A method of predicting response to thalidomide, or thalidomide analogs, in an individual with cancer, especially cancers for which thalidomide has been implicated as a treatment, such as Multiple Myeloma (MM) employs one or more of a panel of biomarkers that have been shown to be differentially expressed in cancer patients that respond to thalidomide (hereafter “Responders”) relative to cancer patients that do not respond to thalidomide (hereafter “Non-responders). The method involves assaying a biological sample from the individual to determine the abundance of at least three biomarkers including Vitamin-D binding protein precursor (VDB) (Sequence ID 1) and Serum amyloid A protein (SAA) (Sequence ID 3), and at least one of beta-2-microglobulin (B2M) (Sequence ID 4), Haptoglobin (Hp) precursor (fragment) (Sequence ID 5), and zinc-alpha-2-glycoprotein (ZAG) (Sequence ID 2). Correlation of the abundance value for the at least three biomarkers with a reference abundance value from a Responder or Non-responder enables predication of response to thalidomide for the patient.

Подробнее
08-11-2012 дата публикации

Prognostic,. screening and treatment methods and agents for treatment of metastasis and inflammation using 5t4 oncofoetal glycoprotein

Номер: US20120282183A1
Принадлежит: Cancer Research Technology LTD

Methods and agents are disclosed based on the finding that 5T4 interacts with CXCR4 in the cell membrane to form a complex, and that the 5T4 transmembrane region is involved in the promotion of CXCR4 membrane expression and chemotactic response.

Подробнее
29-11-2012 дата публикации

Methods of identification, assessment, prevention and therapy of lung diseases and kits thereof

Номер: US20120302455A1
Принадлежит: Cancer Prevention and Cure Ltd

The invention provides biomarkers and combinations of biomarkers useful in diagnosing lung diseases such as non-small cell lung cancer or reactive airway disease. The invention also provides methods of differentiating lung disease, methods of monitoring therapy, and methods of predicting a subjects response to therapeutic intervention based on the extent of expression of the biomarkers and combinations of biomarkers. Kits comprising agents for detecting the biomarkers and combination of biomarkers are also provided.

Подробнее
06-12-2012 дата публикации

Methods for diagnosis, prognosis and methods of treatment

Номер: US20120309029A1
Принадлежит: Nodality Inc

This invention is directed to methods and compositions for diagnosis, prognosis and for determining methods of treatment. The physiological status of cells present in a sample (e.g. clinical sample) can be used in diagnosis or prognosis of a condition (e.g. Chronic Lymphocytic Leukemia), in patient selection for therapy, to monitor treatment and to modify or optimize therapeutic regimens. The physiological status of a cell can be determined by comparing the intracellular status of one or more activation elements (e.g. the phosphorylation status of a signaling molecule) in a cell (e.g. a cancer cell) to that of another cell (e.g. a normal cell). The physiological status of a cell can be further classified by adding one or more modulators (e.g. an inhibitor or activator) to the cell in question. In some embodiments, the invention is directed to methods of determining a phenotypic profile of a population of cells.

Подробнее
31-01-2013 дата публикации

Diagnostic marker for effect of anticancer agent

Номер: US20130029357A1
Принадлежит: FUJIREBIO INC

The present invention enables to realize a convenient determination of a therapeutic effect of an anticancer agent on a cancer. Specifically, the present invention provides a diagnostic marker for an effect of an anticancer agent on a cancer, comprising a substance having an affinity for a fragment of an extracellular domain of c-MET; a diagnostic reagent for an effect of an anticancer agent on a cancer, comprising a substance having an affinity for a fragment of an extracellular domain of c-MET and the fragment of the extracellular domain of c-MET; and a method of testing an effect of an anticancer agent on a cancer, comprising (a) measuring a concentration of a fragment of an extracellular domain of c-MET in a biological sample from a subject, and (b) comparing the measured concentration of the fragment of the extracellular domain of c-MET with an indicator which presents a relationship between a concentration of the fragment of the extracellular domain of c-MET and the effect of the anticancer agent on the cancer.

Подробнее
07-02-2013 дата публикации

Methods for diagnosis, prognosis and methods of treatment

Номер: US20130035253A1
Принадлежит: Nodality Inc

The present invention provides an approach for the determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, expression markers and other criteria, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of modulators of cellular activation allows for characterization of pathways and cell populations.

Подробнее
07-03-2013 дата публикации

Translocation and mutant ros kinase in human non-small cell lung carcinoma

Номер: US20130059305A1
Принадлежит: Cell Signaling Technology Inc

In accordance with the invention, a novel gene translocation, (4p15, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of Sodium-dependent Phosphate Transporter Isoform NaPi-3b protein (SLC34A2) with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The SLC34A2-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of the new fusion protein enables new methods for determining the presence of these mutant ROS kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

Подробнее
07-03-2013 дата публикации

Global analysis of serum micro rnas as potential biomarkers for lung adenocarcinoma

Номер: US20130059742A1

A diagnostic kit to detect lung adenocarcinoma, or to stratify patients according to expected prognosis comprising at least one oligonucleotide probe capable of binding to at least a portion of a circulating miRNA selected from the group comprising miR-556, -550, -939, -616*, 146b-3p and -30c-1* biomarkers.

Подробнее
28-03-2013 дата публикации

Methods for identifying leukemia stem cells and distinguishing them from normal hematopietic stem cells in patients with acute myeloid leukemia: uses in diagnosis, treatment, and research

Номер: US20130079424A1
Принадлежит: JOHNS HOPKINS UNIVERSITY

Using the methods of the present invention, intermediate (int) levels of aldehyde dehydrogenase (ALDH) activity reliably distinguished leukemic CD34 + CD38 − cells capable of engrafting immunodeficient mice, from residual normal hematopoietic stem cells that exhibited relatively higher ALDH activity. Minimal residual disease (MRD) detected during complete remission was enriched for the CD34 + CD38 − ALDH int leukemic cells, and the presence of these cells after therapy highly correlated with subsequent clinical relapse. The methods of the present invention can distinguish normal from leukemic CD34 + CD38 − cells, and identifies those AML cells associated with relapse. Methods of prediction of relapse of AML patients and methods of treatment are also provided.

Подробнее
18-04-2013 дата публикации

Methods and compositions for treatment and diagnosis of fibrosis, tumor invasion, angiogenesis, and metastasis

Номер: US20130095101A1
Принадлежит: Gilead Biologics Inc

Provided are methodology, compositions and kits to prevent and treat diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, using processed lysyl oxidase or lysyl oxidase-like protein inhibitors, LOX inhibitors and LOXL inhibitors, or synergistic combinations of such inhibitors with therapeutic agents. Provided are methods for selecting tumor invasion, angiogenesis and metastasis inhibiting agents, by contacting cells in EMT states with candidate agents and detecting changes in such states; and methods, compositions, and kits for diagnosing or monitoring diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, using molecules or agents specifically recognizing processed LOX or LOXL. Provided are methods, compositions, medical devices, systems and kits for preventing or treating diseases and conditions associated with fibrosis, including pathological cardiovascular conditions and diseases, e.g., hypertension, hypertensive heart disease, myocardial infarction, atherosclerosis, restenosis, liver fibrosis, kidney fibrosis, lung fibrosis, dermal scaring, keloid formation, and Alzheimer's disease, with LOX or LOXL inhibitors.

Подробнее
18-04-2013 дата публикации

Serum spla2-iia as diagnosis marker for prostate and lung cancer

Номер: US20130095503A1
Автор: Shan Lu
Принадлежит: University of Cincinnati

Kits for assessing lung cancer in patients with solitary pulmonary nodules and methods for assessing lung cancer. The kit includes reagents for detection and/or quantification of serum secretory phospholipase A 2 -IIA in plasma, reagents for detection and/or quantification of carcinoembryonic antigen in plasma, and reagents for detection and/or quantification of cytokeratin-19 fragment in plasma. The method includes contacting a sample with a specific binding agent for serum secretory phospholipase A 2 -IIA, a specific binding agent for carcinoembryonic antigen, and a specific binding agent for cytokeratin-19 fragment, calculating levels of serum secretory phospholipase A 2 -IIA, carcinoembryonic antigen, and cytokeratin-19 fragment, and assessing as indicating lung cancer in the patient if the calculated levels are elevated.

Подробнее
25-04-2013 дата публикации

Bcma-based stratification and therapy for multiple myeloma patients

Номер: US20130101599A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to methods for the stratification of a multiple myeloma (MM) patient comprising determining whether or not B-cells, preferably malignant B-cells of said patient express BCMA protein on their surface. Also, methods for selecting an antibody-based multiple myeloma (MM) therapy is based on whether or not BCMA is expressed on the cell surface of B-cells, preferably malignant B-cells of a patient. Furthermore, antibody-based therapies for patients who have BCMA positive malignant B-cells are provided.

Подробнее
02-05-2013 дата публикации

Blockade of ccl18 signaling via ccr6 as a therapeutic option in fibrotic diseases and cancer

Номер: US20130109629A1
Принадлежит: Universitaetsklinikum Freiburg

The present invention relates to an isolated soluble CCR6 receptor polypeptide capable of binding to CCL18 and/or CCL20 and to a method for quantifying the concentration of a soluble CCR6 receptor polypeptide in a liquid sample from a subject. The present invention also relates to a method for detecting and/or prognosticating an interstitial lung disease or a cancer in a subject by determining the level of a soluble CCR6 receptor polypeptide in a sample from said subject and further provides a pharmaceutical composition comprising a compound capable of inhibiting the activity and/or the expression of CCL18 or CCL20 for the treatment of said diseases. The present invention further relates to an isolated polypeptide capable of binding to and inhibiting the activity of the chemokine receptor CCR6 and to a method for identifying further inhibitors of CCR6 receptor activity. The present invention also relates to a method for detecting an interstitial lung disease or a cancer in a subject by determining the level of CCR6 gene expression in a sample from said subject and further provides pharmaceutical compositions comprising inhibitors of CCR6 receptor activity and/or expression for the treatment of said diseases.

Подробнее
23-05-2013 дата публикации

Composition and methods for the diagnosis, prognosis and treatment of leukemia

Номер: US20130129734A1
Принадлежит: Newcastle Innovation Ltd

The present disclosure relates generally to compositions and methods for the diagnosis, prognosis and treatment of leukemia, in particular leukemia in which leukemic cells, or neoplastic precursors thereof, express Fat1 or a homolog of Fat1 that is substantially not expressed on normal blood cells.

Подробнее
13-06-2013 дата публикации

BARD1 Isoforms in Lung and Colorectal Cancer and Use Thereof

Номер: US20130149711A1

The present invention relates to new BARD1 isoforms specific to lung cancer and colorectal cancer, a method for detecting thereof and a method for treating and/or preventing lung cancer and colorectal cancer.

Подробнее
13-06-2013 дата публикации

Risk factors of cigarette smoke-induced spirometric phenotypes

Номер: US20130150250A1
Принадлежит: Individual

The technology provided herein relates to the SNPs identified as described herein, both singly and in combination, as well as to the use of these SNPs, and others in linkage disequilibrium with these SNPs, for diagnosis, prediction of clinical course, and/or treatment response for pulmonary disease such as COPD, development of new treatments for pulmonary disease such as COPD based upon comparison of the variant and normal versions of the gene or gene product, and development of cell-culture based and animal models for research and treatment of pulmonary disease such as COPD. The technology provided herein further relates to novel compounds, pharmaceutical compositions, and kits for use in the diagnosis, treatment, and evaluation of such disorders.

Подробнее
15-08-2013 дата публикации

Complex phosphoprotein activation profiles

Номер: US20130210034A1
Принадлежит: Beckman Coulter Inc

The present specification discloses methods for determining a phosphoprotein activation profile in hematopoietic cells, methods for detecting a signal transduction activation state in an individual having or suspected of having a disease or condition associated with activation of a signal transduction pathway, methods for detecting leukemia, and kits for determining a phosphoprotein activation profile in a sample containing hematopoietic cells.

Подробнее
29-08-2013 дата публикации

Modulation of NR2F6 and methods and uses thereof

Номер: US20130225425A1
Принадлежит: Individual

The application provides methods of modulating NR2F6 in a cell or animal in need thereof by administering an effective amount of a NR2F6 modulator.

Подробнее
29-08-2013 дата публикации

Lung Cancer Tests

Номер: US20130225442A1
Автор: Jeffrey A. Borgia
Принадлежит: RUSH UNIVERSITY MEDICAL CENTER

Methods for the diagnosis of lung cancer and more specifically, non-small cell lung cancer are described. An assortment of biomarkers with diagnostic or prognostic value for non-small cell lung cancer (NSCLC) are used to establish a multi-analyte serum test capable of diagnosing patients with lung cancer. A first method assesses an elevated level of expression of one or more nucleic acids, a polypeptide encoded by the nucleic acid or an autoantibody to said polypeptide. An alternative method includes (a) determining whether or not a patient has NSCLC versus a non-NSCLC lung cancer, and (b) classifying the patient as susceptible to specific treatments if the patient has a NSCLC profile and classifying the patient as not susceptible to a specific treatment if the patient does not have a NSCLC profile.

Подробнее
05-09-2013 дата публикации

Tumor-Targeting Monoclonal Antibodies to FZD10 and Uses Thereof

Номер: US20130230521A1
Принадлежит: Individual

The present invention relates to an antibody or a fragment thereof which is capable of binding to a Frizzled homologue 10 (FZD10) protein, such as a mouse monoclonal antibody, a chimeric antibody and a humanized antibody. Also, the present invention relates to a method for treating and/or preventing FZD10-associated disease; a method for diagnosis or prognosis of FZD10-associated disease; and a method for in vivo imaging of FZD10 in a subject.

Подробнее
19-09-2013 дата публикации

Method for discriminating between early and advanced stage lung carcinoma

Номер: US20130244260A1
Автор: Hendrik Jan Ankersmit
Принадлежит: Aposcience AG

The present invention relates to a method for discriminating between early and advanced stage lung carcinoma in an individual suffering from lung carcinoma comprising the steps of a) providing a sample of an individual suffering from lung carcinoma, b) determining the level of heat shock protein 27 (HSP27) in said sample, c) comparing the determined level of HSP27 in said sample with a reference range of HSP27 measured in samples of control individuals with an early stage lung carcinoma and/or with advanced stage lung carcinoma, d) diagnosing early stage lung carcinoma in said individual when the level of HSP27 in sample a) is below the reference range of HSP27 in samples of control individuals with advanced stage lung carcinoma or within the reference range of control individuals with early stage lung carcinoma and diagnosing advanced stage lung carcinoma when the level of HSP27 in sample a) is above the reference range of HSP27 in samples of control individuals with early stage lung carcinoma or within the reference range of control individuals with advanced stage lung carcinoma.

Подробнее
26-09-2013 дата публикации

Method of diagnosing early stage non-small cell lung cancer

Номер: US20130252831A1
Автор: Dung-Tsa Chen

A “malignancy-risk” (MR) gene signature score was developed with abundant proliferative genes using principal component analysis. This MR gene signature was shown to be a predictive and prognostic factor of overall survival in early-stage NSCLC. The malignancy-risk signature showed a significant association with OS, with poor survival seen in patients having a higher MR score and better survival seen in patients having a low MR score. As a prognostic factor, the MR gene signature showed a positive correlation with TNM stage, histologic grade, and smoking status. Combination of the MR signature with each clinical parameter often showed the best survival in the low MR group with good clinical outcome. The MR gene profile, tested with a PCA scoring method, discriminated overall survival in lung cancer patients was a predictor independent of pathological staging and other clinical parameters.

Подробнее
17-10-2013 дата публикации

Socs-3 promoter methylation in cancer

Номер: US20130273534A1
Принадлежит: UNIVERSITY OF CALIFORNIA

This invention provides compositions and methods for the diagnosis and treatment of cancers that exhibit decreased SOCS-3 expression.

Подробнее
07-11-2013 дата публикации

Diagnostic tests using gene expression ratios

Номер: US20130296198A1
Принадлежит: Brigham and Womens Hospital Inc

The invention provides methods for diagnosing biological states or conditions based on ratios of gene expression data from cell or tissue samples, such as cancer cell or tissue samples. The invention also provides sets of genes that are expressed differentially in normal and cancer lung cells and tissues. These sets of genes can be used to discriminate between normal and malignant cells or tissues, and between classes of malignant cells or tissues. Accordingly, diagnostic assays for classification of tumors, prediction of tumor outcome, selecting and monitoring treatment regimens and monitoring tumor progression/regression also are provided.

Подробнее
14-11-2013 дата публикации

Inhibitors of Human EZH2 and Methods of Use Thereof

Номер: US20130303555A1
Принадлежит: Epizyme Inc

The invention relates to determining the presence of an EZH2 gene mutation in a sample from a subject and inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono-through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.

Подробнее
05-12-2013 дата публикации

Lox and loxl2 inhibitors and uses thereof

Номер: US20130324705A1
Принадлежит: Gilead Biologics Inc

The present application relates to anti-LOX and anti-LOXL2 antibodies and their use in purification, diagnostic and therapeutic methods. Antibodies include monoclonal antibodies, humanized antibodies and functional fragments thereof. Anti-LOX and anti-LOXL2 antibodies can be used to identify and treat conditions such as a fibrotic condition, angiogenesis, or to prevent a transition from an epithelial cell state to a mesenchymal cell state.

Подробнее
19-12-2013 дата публикации

Detection of acute myeloid leukaemia

Номер: US20130337474A1
Принадлежит: Oxford University Innovation Ltd

The present invention relates to diagnostic screens, antibodies, methods and kits for detection/prognosis of acute myeloid leukaemia. The diagnostic screen detects the presence (+) or absence (−) of the cell surface polypeptide markers i) CD34+; ii) CD45RA+; and iii) CD90− and/or CD123+. Antibodies specific for one or more of said cell surface polypeptide markers may be used in the diagnostic screen of the invention. Diagnostic and prognostic methods for detecting and monitoring minimal residual disease based on said screen also form part of the invention.

Подробнее
23-01-2014 дата публикации

METHODS OF IDENTIFICATION AND DIAGNOSIS OF LUNG DISEASES USING CLASSIFICATION SYSTEMS AND KITS THEREOF

Номер: US20140024553A1
Принадлежит: Cancer Prevention and Cure, Ltd.

The invention provides biomarkers and combinations of biomarkers useful in diagnosing lung diseases such as non-smail cell lung cancer or reactive airway disease. Measurements of these biomarkers are inputted into a classification system such as a support vector machine or AdaBoost to assist in determining the likelihood that an individual has a lung disease. Kits comprising agents for detecting the biomarkers and combination of biomarkers, as well as systems that assist in diagnosing lung diseases are also provided. 1. A method of physiological characterization in a subject comprising (a) obtaining a physiological sample of the subject; (b) determining biomarker measures of a plurality of biomarkers in said sample; and (c) classifying the sample based on the biomarker measures using a classification system , wherein the classification of the sample correlates to a physiologic state or condition , or changes in a disease state in the subject.2. A method according to for diagnosing non-small cell lung cancer in a subject comprising claim 1 , (a) obtaining a physiological sample of the subject; (b) determining biomarker measures of a plurality of biomarkers in said sample; and (c) classifying the sample based on the biomarker measures using a classification system claim 1 , wherein the classification of the sample is indicative of the presence or development of non-small cell lung cancer in the subject.3. A method according to for diagnosing reactive airway disease in a subject comprising claim 1 , (a) obtaining a physiological sample of the subject; (b) determining biomarker measures of a plurality of biomarkers in said sample; and (c) classifying the sample based on the biomarker measures using a classification system claim 1 , wherein the classification of the sample is indicative of reactive airway disease in the subject.4. A method according to for diagnosing a lung disease in a subject comprising claim 1 ,(a) obtaining a physiological sample of the subject;(b) ...

Подробнее
06-03-2014 дата публикации

LUNG CANCER DIAGNOSTIC ASSAY

Номер: US20140066329A1

A method for selecting a person at risk for lung cancer to undergo radiographic testing is provided. The method provides for the identification of markers for lung cancer in a population of patients that have not previously diagnosed with the disease. The markers identify autoantibodies present in a fluid sample of a patient who may not show other symptoms of lung cancer. 1. A method for reducing the number of false positives associated with radiographic screening for lung cancer , comprising:(a) providing a test to an asymptomatic patient with a smoking history that measures a panel of two or more autoantibody biomarkers demonstrated to distinguish stage I lung cancer and/or occult disease from risk-matched control samples;(b) obtaining a blood sample from the patient;(c) measuring the panel of biomarkers in the blood sample;(d) determining an amount of the measured autoantibodies in the sample;(e) calculating a probability the patient is positive for lung cancer using a specificity of at least 65% for the panel as a threshold; and,(f) selecting for radiographic testing those patients positive for lung cancer according to step (e) whereby the number of false positives associated with radiographic screening for lung cancer have been reduced.2. The method of claim 1 , wherein said radiographic screening is by CT scanning or X-ray.3. The method of claim 1 , wherein the patient is at least 50 years of age.4. The method of claim 1 , wherein the patient has a minimum 20 pack year smoking history.5. The method of claim 1 , wherein said patient is a high risk patient without radiographically detectable lung cancer.6. The method of claim 1 , wherein the panel has a positive predictive value of at least 0.70 as measured by area under the curve (AUC) of receiver operating characteristic (ROC) curves7. The method of claim 1 , further comprising measuring at least three biomarkers claim 1 , at least four biomarkers claim 1 , at least five biomarkers claim 1 , at least six ...

Подробнее
02-01-2020 дата публикации

Method for Treating Cancer

Номер: US20200000903A1
Принадлежит:

The present invention relates to a method for identifying a truncal neo-antigen in a tumour from a subject which comprises the steps of: i) determining mutations present in a sample isolated from the tumour; and ii) identifying a truncal mutation which is a mutation present in essentially all tumour cells; and iii) identifying a truncal neo-antigen, which is an antigen encoded by a sequence which comprises the truncal mutation. 154-. (canceled)55. A T cell composition comprising an engineered T cell expressing a chimeric antigen receptor (CAR) or a T cell receptor (TCR) which specifically binds a clonal neoantigen or a clonal neoantigen peptide.56. The T cell composition according to claim 55 , wherein the TCR is an affinity-enhanced TCR which specifically binds a clonal neoantigen or a clonal neoantigen peptide.57. The T cell composition according to claim 55 , wherein the T cells comprise CD8+ T cells claim 55 , CD4+ T cells or CD8+ and CD4 T+ cells.58. The T cell composition according to claim 55 , wherein the TCR is expressed in autologous T cells from a subject.59. The T cell composition according to which is enriched with engineered T cells that are specific to clonal neoantigens.60. A method for producing a composition comprising engineered T cells claim 55 , the method comprising: ["i) determining mutations present in a sample isolated from the subject's tumour;", 'ii) identifying a clonal mutation which is a mutation present in essentially all tumour cells;', 'iii) identifying a clonal neoantigen, which is an antigen encoded by a sequence which comprises the clonal mutation;', 'vi) identifying a T cell from a sample isolated from the subject which is capable of specifically recognising the clonal neoantigen as a clonal neoantigen-specific T cell;, '(a) identifying a clonal neoantigen-specific T cell from a subject which comprises the steps of(b) isolating a TCR gene that encodes a TCR from the clonal neoantigen-specific T cell; and(c) engineering a T cell ...

Подробнее
02-01-2020 дата публикации

NEO-ANTIGEN SPECIFIC T CELLS

Номер: US20200000904A1
Принадлежит:

The present invention relates to a method for identifying a truncal neo-antigen in a tumour from a subject which comprises the steps of: i) determining mutations present in a sample isolated from the tumour; and ii) identifying a truncal mutation which is a mutation present in essentially all tumour cells; and iii) identifying a truncal neo-antigen, which is an antigen encoded by a sequence which comprises the truncal mutation. 154-. (canceled)55. A method for identifying a clonal neoantigen-specific T cell which comprises steps of:i) determining mutations present in a sample isolated from a tumour from a subject;ii) identifying a clonal mutation which is a mutation present in essentially all tumour cells;iii) identifying a clonal neoantigen, which is an antigen encoded by a sequence which comprises the clonal mutation; andiv) identifying a T cell from a sample isolated from a subject which is capable of specifically recognising the clonal neoantigen as a clonal neoantigen-specific T cell.56. The method according to wherein the clonal neoantigen-specific T cell is identified using a MHC multimer comprising a clonal neoantigen.57. A method for providing a T cell population which targets a clonal neoantigen in a tumour claim 55 , the method comprising:{'claim-ref': {'@idref': 'CLM-00055', 'claim 55'}, 'i) identifying a T cell from a sample isolated from a subject which is capable of specifically recognising a clonal neoantigen peptide by the method according to ; and'}ii) expanding the T cell to provide a T cell population which targets the clonal neoantigen.58. The method according to claim 57 , wherein in step ii) the T cell is expanded by ex vivo culture with IL-2 or anti-CD3 and/or CD28 antibodies.59. The method according to wherein in step ii) the T cell is co-cultured with irradiated antigen-presenting cells (APCs) claim 57 , artificial antigen presenting cells (aAPCs) or autologous peripheral blood mononuclear cells (PBMCs).60. The method according to claim 57 ...

Подробнее
07-01-2016 дата публикации

A compound that specifically binds to kir3dl2 for use in the treatment of peripheral t cell lymphoma

Номер: US20160002345A1
Принадлежит: Innate Pharma SAS

The present disclosure relates to methods for the treatment, prevention and diagnostic of peripheral T cell lymphoma using compounds that specifically bind KIR3DL2. The disclosure also relates to use of antibodies that specifically bind KIR3DL2 in diagnostic and theranostic assays in the detection and treatment of peripheral T cell lymphoma.

Подробнее
04-01-2018 дата публикации

Prognostic Marker For Cryoglobulinemic Vasculitis And B Cell Malignancies In HCV Infected Patients

Номер: US20180002763A1
Автор: Vincent Agnello
Принадлежит: Individual

The invention provides methods and compositions for early diagnosis and treatment of a disease associated with a specific antibody by employing the detection of a cross-idiotypic epitope on the specific antibody to detect the cells that produce the antibody before the development of clinical symptoms of the disease.

Подробнее
01-01-2015 дата публикации

METHOD FOR PREDICTING THE CLINICAL RESPONSE TO CHEMOTHERAPY IN A SUBJECT WITH CANCER

Номер: US20150004252A1
Принадлежит: TRASLATIONAL CANCER DRUGS PHARMA, S.L

The invention relates to the use of choline kinase alpha as predictive marker for the determination of the response to a chemotherapeutic treatment in a subject suffering from cancer, particularly for predicting the clinical response of a subject suffering from non-small cell lung cancer to a platinum-based chemotherapeutic treatment. The invention relates to methods for designing a personalised therapy for subjects suffering from cancer, particularly from non-small cell lung cancer, based on the expression levels of choline kinase alpha as well as to methods for the treatment of non-small cell lung cancer using a platinum-based chemotherapeutic treatment based in a subject wherein the subject is selected based on the expression levels of choline kinase alpha. 141.-. (canceled)42. An in vitro method for predicting the clinical response of a subject suffering from cancer to a chemotherapeutic treatment comprising determining the expression level of choline kinase alpha (ChoKα) gene in a sample from the subject.43. The method according to claim 42 , wherein the method further comprises comparing the expression level of ChoKα with a reference value claim 42 , wherein an alteration in the expression level of ChoKα gene in said sample with respect to said reference value is indicative of a poor clinical response of the subject to said chemotherapeutic treatment or of a good clinical response of the subject to said chemotherapeutic treatment.44. The method according to claim 43 , wherein the alteration in the expression levels of ChoKα is an increase in said expression level with respect to said reference value and wherein the increase in said expression level is indicative of a poor clinical response or wherein the alteration in the expression levels of ChoKα is an decrease in said expression level with respect to said reference value and wherein the decrease in said expression level is indicative of a good clinical response.45. The method according to claim 42 , wherein ...

Подробнее
01-01-2015 дата публикации

METHODS FOR TREATING HEMATOPOIETIC MALIGNANCIES

Номер: US20150004613A1
Принадлежит:

The present invention relates to methods for treating neoplasias in a mammalian subject. In particular, the invention provides methods for treating lymphomas, including forms of non-Hodgkin lymphoma. In one embodiment, these methods involve reducing tumor necrosis factor signaling. 125-. (canceled)26. A method for diagnosing a subject as having diffuse large B cell lymphoma (DLBCL) , comprising i) a test sample from said subject, and', 'ii) a control sample selected from the group consisting of chronic lymphocytic leukemia (CLL) sample and follicular lymphoma (FL) sample,, 'a) providing'}b) measuring the level of at least one marker of DLBCL in said test sample and in said control sample, wherein said marker is selected from the group consisting of inositol polyphosphate-5-phosphatase (SHIP-1) and miR-155, and wherein said measuring comprises contacting said test sample and said control sample with a recombinant polymerase chain reaction (PCR) primer,c) comparing the level of said at least one marker in said test sample and in said control sample, wherein at least one of reduced expression of said SHIP-1 and increased expression of said miR-155 in said test sample compared to said control sample correlates with DLBCL in said test sample, andd) diagnosing said subject as having DLBCL.27. The method of claim 26 , further comprising step e) generating a prognosis for the subject that is diagnosed in step d) as having DLBCL.28. A method for diagnosing a subject as having diffuse large B cell lymphoma (DLBCL) claim 26 , comprising iii) a test sample from said subject, and', 'iv) a control sample selected from the group consisting of chronic lymphocytic leukemia (CLL) sample and follicular lymphoma (FL) sample,, 'e) providing'}f) measuring the level of at least one marker of DLBCL in said test sample and in said control sample, wherein said marker is selected from the group consisting of inositol polyphosphate-5-phosphatase (SHIP-1) and miR-155, and wherein said measuring ...

Подробнее
04-01-2018 дата публикации

BCR-ABL VARIANTS

Номер: US20180003714A1
Автор: Albitar Maher

A splice variant of bcr-abl mRNA that produces BCR-ABL protein with a truncated C-terminus and its role in resistance to treatment with kinase inhibitors is disclosed. Vectors for expressing the truncated gene product are provided as well as recombinant cells that express the truncated gene product from a cDNA construct. Also provided are methods compositions and kits for detecting the BCR-ABL splice variant. Additionally, methods for screening BCR-ABL kinase domain inhibitors which rely on the recombinant cells and methods of predicting likelihood for resistance of a CML patient with a BCR/ABL translocation respond to treatment with one or more BCR-ABL kinase inhibitors are also disclosed. 113.-. (canceled)14. A kit for detecting the presence of bcr-abl splice variant mRNA comprising:a) a first primer and a second primer, wherein said first primer anneals to a portion of bcr exon b2 and said second primer anneals to a region at the junction of abl exon 9 and 10, wherein the use of said first and second primers in an amplification reaction is capable of generating an amplicon; andb) a detectably labeled probe capable of hybridizing to said amplicon, wherein said probe hybridizes to at least 10 contiguous nucleotides of SEQ ID NO: 4 or a complement thereof.15. The kit of claim 14 , wherein said first primer is SEQ ID NO: 5 or a complement thereof.16. The kit of claim 14 , wherein said second primer is SEQ ID NO: 6 or a complement thereof.17. The kit of further comprising a third and a fourth primer claim 14 , wherein said third primer anneals to a portion of abl exon 8 and said fourth primer anneals to a portion of abl exon 9 claim 14 , wherein the use of said first and second primers in an amplification reaction is capable of generating a second amplicon.18. The kit of claim 17 , wherein said third primer is SEQ ID NO: 22 or a complement thereof.19. The kit of claim 17 , wherein said fourth primer is SEQ ID NO: 23 or a complement thereof.2039.-. (canceled)40. The ...

Подробнее
02-01-2020 дата публикации

MOLECULAR PROFILING OF TUMORS

Номер: US20200003796A1
Принадлежит:

Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease. 1. A system for generating a report identifying at least one therapeutic agent for an individual with a cancer comprising:a. at least one device configured to assay a plurality of molecular targets in a biological sample from the individual to determine molecular profile test values for each of the plurality of molecular targets, wherein the molecular targets comprise ERBB2, PTEN, TOP2A, TOPO1 and TS; and i. a reference value for each of the plurality of molecular targets; and', 'ii. a listing of therapeutic agents with efficacy linked to a biological state of at least one member of the plurality of molecular targets;, 'b. at least one computer database comprisingc. a computer-readable program code comprising instructions to input the molecular profile test values and to compare each molecular profile test value with a corresponding reference value in (b)(i) to identify a biological state for each member of the plurality of molecular targets;d. a computer-readable program code comprising instructions to identify at least one therapeutic agent from the listing of therapeutic agents in (b)(ii), wherein the biological state identified in (c) for at least one member of the plurality of molecular targets provides an indication of likely benefit of the at least one therapeutic agent for treating the cancer; ande. a computer-readable program code comprising instructions to generate a report that comprises a listing of the at least one therapeutic agent identified in (d) and the biological state of each molecular target with efficacy linked thereto.2. The system of claim 1 , wherein the molecular profile test values are input into the system from a ...

Подробнее
07-01-2021 дата публикации

IMMUNOLOGICAL COMPOSITION FOR DIAGNOSIS OF LUNG CANCER BY USING AUTOANTIBODY-ANTIGEN COMPLEX, DIAGNOSIS METHOD FOR LUNG CANCER BY USING SAME, AND LUNG CANCER DIAGNOSIS KIT COMPRISING SAME

Номер: US20210003576A1
Принадлежит: BIOMETRIX TECHNOLOGY INC.

The present disclosure provides an immunological composition for diagnosing lung cancer comprising: an antibody composition A containing an anti-CYFRA21-1 primary antibody-gene and an anti-CYFRA21-1 secondary antibody-detection marker; and an antibody composition B containing an anti-CYFRA 21-1 primary antibody-gene and an anti-human IgG antibody-detection marker; a method for diagnosing lung cancer in a human biological specimen using the same, and a diagnostic kit for lung cancer using the same. 1. A immunological composition for diagnosing lung cancer comprising:an antibody composition A containing an anti-CYFRA21-1 primary antibody-gene and an anti-CYFRA21-1 secondary antibody-detection marker; andan antibody composition B containing an anti-CYFRA 21-1 primary antibody-gene and an anti-human IgG antibody-detection marker.2. The immunological composition for diagnosing lung cancer according to claim 1 , wherein the detection marker is any one selected from the group consisting of a chromogenic enzyme claim 1 , a fluorescent material claim 1 , a fluorescent bead claim 1 , a radioactive isotope claim 1 , and a colloid.3. The immunological composition for diagnosing lung cancer according to claim 2 , wherein the detection marker is selected from a fluorescent material.4. A method for diagnosing lung cancer in a human biological specimen using the immunological composition for diagnosing lung cancer according to claim 1 , the method comprising the steps of:(A) measuring a presence or absence or a concentration of in the biological specimen by using an antibody composition A containing and ,(B) measuring a presence or absence or a concentration of in the biological specimen by using an antibody composition B containing and ; and( ...

Подробнее
03-01-2019 дата публикации

METHODS FOR DETERMINING DRUG EFFICACY FOR THE TREATMENT OF DIFFUSE LARGE B-CELL LYMPHOMA, MULTIPLE MYELOMA, AND MYELOID CANCERS

Номер: US20190004033A1
Принадлежит:

Provided herein, in some embodiments, are methods of using certain cereblon-associated proteins, such as Aiolos, Ikaros, interferon (IFN), and IFN pathway proteins, casein kinase 1, alpha 1 (CSNK1A1), and ZFP9, as biomarkers for use in predicting and monitoring clinical sensitivity and therapeutic response to certain compounds in patients having various diseases and disorders, such as cancers (e.g., diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), myelodysplasia syndromes (MDS) and acute myeloid leukemia (AML)) and IFN-associated disorders. Also provided herein, in certain embodiments, are methods of determining the efficacy of an immunomodulatory compound. 1. A method of determining whether a compound is effective as an immunomodulatory compound or anti-tumor agent , or treating a cancer , comprising: wherein optionally the cell is a cancer cell, or', 'wherein optionally the cell is an immune cell;, '(a) contacting a first cell with the compound;'}(b) obtaining a first sample from the first cell from step (a);(c) determining the level of a biomarker in the first sample,(d) comparing the level of the biomarker from step (c) to the level of the same protein obtained from a reference sample, wherein a change in the biomarker level as compared to the reference sample is indicative of the efficacy of the compound as an immunomodulatory compound or an anti-tumor agent; and(e) administering to the subject a therapeutically effective amount of the compound when the compound is indicated as likely to be efficacious as an immunomodulatory compound or an anti-tumor agent, or administering to the subject a therapeutically effective amount of a therapy other than the compound when the compound is indicated as unlikely to be efficacious as an immunomodulatory compound or an anti-tumor agent;wherein the biomarker is a cereblon (CRBN)-associated protein (CAP); andwherein the compound is a cereblon-binding compound.2. The method of claim 1 , wherein an increased level ...

Подробнее
03-01-2019 дата публикации

PLASMA AUTOANTIBODY BIOMARKERS FOR DIAGNOSIS OF LUNG CANCER

Номер: US20190004051A1
Принадлежит:

An immune-proteomic screening of AAb responses using protein arrays has identified two panels of Aab (antigen/antibody complexes) that can potentially differentiate lung adenocarcinoma from smoker controls as well as CT positive benign lung disease. The resulting biomarkers appear to have high specificity so that high risk subjects with a positive CT screen and a positive serum test should get more invasive test such as needle biopsy for a timely cancer diagnosis, among other advantages. 1. A method for detecting lung cancer , comprising the steps of:contacting a patient sample capable of containing an auto antibody (AAb) with a panel of antigens, thereby forming an antigen/AAb complex in vitro if said AAb binds an antigen on said panel, wherein said panel of antigens is selected from the group consisting of one or more of TTL14, VPS72, CTTNBP2NL, TSPYL2, ACTL6B, ACVR2B, BRAF, KLF8, BAT4, C12ORF50, IQCE, CSPP1, KRT8, MORC2, FAM76A, NF2, TLK1, P53 (TP53), and NYESO1 (CTAG1B); anddetecting any of said antigen/AAb complex in comparison with a control.2. The method of claim 1 , wherein said panel of antigens comprises TTC14 claim 1 , BRAF claim 1 , ACTL6B claim 1 , MORC2 claim 1 , and CTAG1B.3. The method of claim 1 , wherein said panel of antigens comprises TTC14 claim 1 , BRAF claim 1 , KLF8 claim 1 , TLK1 claim 1 , and KRT8.4. The method of claim 3 , wherein said panel of antigens and said control provides discrimination between lung adenocarcinoma and benign cells.5. The method of claim1 claim 3 , further including an additional claim 3 , more invasive test if a patient has both a positive CT screen and a positive serum test for lung cancer.6. A method of confirming or questioning a lung cancer diagnosis claim 3 , comprising the step of:using a patient sample, comparing an AAb response to a panel of antigens with those of lung cancer patients and patients with CT positive pulmonary nodules, wherein said panel of antigens comprises TTC14, BRAF, KLF8, TLK1, and KRT8.7 ...

Подробнее
03-01-2019 дата публикации

METHODS OF DETECTING AND REDUCING CANCER CELL CENTRAL NERVOUS SYSTEM COLONIZATION

Номер: US20190004053A1
Принадлежит:

The present invention is related to novel methods for detecting and reducing cancer cell central nervous system colonization and methods of treating subjects having cancers that colonize in the central nervous system. 1. A method of treating cancer comprising administering to a subject in need thereof , a Protocadherin-9 (PCDH9) inhibitor.2. The method of claim 1 , wherein the cancer is leukemia or lymphoma.3. The method of claim 2 , wherein the leukemia is Acute Lymphoblastic Leukemia (ALL) or Acute Myeloid Leukemia (AML).4. The method of claim 1 , wherein the PCDH9 inhibitor is selected from the group consisting of an antibody claim 1 , an antisense molecule claim 1 , an siRNA molecule claim 1 , an shRNA molecule claim 1 , a receptor antagonist claim 1 , a chemical entity claim 1 , a nucleotide claim 1 , a peptide claim 1 , and a protein.5. The method of claim 4 , wherein the PCDH9 inhibitor is a PCDH9 antibody.6. The method of claim 1 , wherein the subject is further administered a systemic therapy selected from the group consisting of chemotherapy claim 1 , radiation claim 1 , and tyrosine kinase inhibitor (TKI) therapy.7. The method of claim 1 , wherein the subject is human.8. A method to identify a subject at risk for leukemia cell colonization of the central nervous system (CNS) in a subject having leukemia claim 1 , the method comprising:a. obtaining a blood sample from the subject;b. detecting the expression level of PCDH9 in the sample; andc. identifying the subject as at risk for leukemia cell colonization of the CNS when either the presence of PCDH9 expression is detected above a control threshold level or the expression level of PCDH9 in the sample is higher than the expression level of PCHD9 from a control.9. The method of claim 8 , wherein the subject identified as being at risk is administered a PCDH9 inhibitor.10. The method of claim 9 , wherein the PCDH9 inhibitor is selected from the group consisting of an antibody claim 9 , an antisense molecule ...

Подробнее
12-01-2017 дата публикации

ACTIVATORS OF PYRUVATE KINASE M2 AND METHODS OF TREATING DISEASE

Номер: US20170007608A1
Автор: Kung Charles
Принадлежит:

The invention described herein features methods, compositions, and kits that utilize activators of pyruvate kinase M2 (PKM2) for the treatment or amelioration of disorders related to PKM2 function and characterized by abnormally low levels of serine. 1. A method of diagnosing and treating a patient who has a cell proliferative-related disorder that is a candidate for treatment with a compound that activates PKM2 , the method comprising:diagnosing the patient as a candidate for treatment with a compound that activates PKM2 based on abnormally low levels of phosphoserine phosphatase mRNA or protein, or abnormally low levels of phosphoserine phosphatase activity, determined to be present in a sample from the subject, as compared to a reference standard, thereby measuring serine levels in the sample, to thereby diagnose the patient; andadministering an effective amount of a compound that activates PKM2.2. The method of claim 1 , wherein the compound is a small molecule.3. The method of claim 1 , wherein the sample comprises a serum sample or a tissue sample.4. The method of claim 3 , wherein the tissue sample is a sample from a tumor sample or from a tissue suspected of having cancerous cells.5. The method of claim 1 , wherein the cell proliferative-related disorder is cancer.6. The method of claim 5 , wherein the cancer is selected from the group consisting of a leukemia claim 5 , polycythemia vera claim 5 , lymphoma claim 5 , Waldenstrom's macroglobulinemia claim 5 , multiple myeloma claim 5 , heavy chain disease claim 5 , and a solid tumor.7. The method of claim 6 , wherein the leukemia is selected from the group consisting of acute leukemia claim 6 , acute lymphocytic leukemia claim 6 , acute myelocytic leukemia claim 6 , acute myeloblasts leukemia claim 6 , acute promyelocyte leukemia claim 6 , acute myelomonocytic leukemia claim 6 , acute monocytic leukemia claim 6 , acute erythroleukemia claim 6 , chronic leukemia claim 6 , chronic myelocytic leukemia claim 6 , ...

Подробнее
08-01-2015 дата публикации

Rspo binding agents and uses thereof

Номер: US20150010565A1
Принадлежит: OncoMed Pharmaceuticals Inc

The present invention relates to RSPO-binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human RSPO proteins and modulate β-catenin activity. The present invention further provides methods of using agents that modulate the activity of RSPO proteins, such as antibodies that specifically bind RSPO1, RSPO2, and/or RSPO3 and inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

Подробнее
14-01-2016 дата публикации

THERAPEUTIC AND DIAGNOSTIC METHODS RELATING TO CANCER STEM CELLS

Номер: US20160009804A1
Принадлежит: THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

The present invention relates in part to the discovery of genes that are deregulated in cancer stem cells (e.g., melanoma stem cells). In some aspects, methods for treating individuals having melanoma are provided; the methods involve modulating (e.g., inducing, inhibiting, etc.) the activity of the cancer stem cell associated genes. In other aspects, cell surface genes that are upregulated in melanoma stem cells are targeted for the selective isolation, detection, and killing of cancer stem cells in melanoma. Other aspects of the invention relate to reagents, arrays, compositions, and kits that are useful for diagnosing and treating melanoma. 1. A method , comprising:determining an expression level of a cancer stem cell (CSC)-associated gene in an ABCB5+ stem cell sample of an individual, wherein the CSC-associated gene is PD-1;comparing the expression level of the CSC-associated gene to a reference value; andadministering to the individual a PD-1 antibody based on the PD-1 levels in the ABCB5+ stem cell.23-. (canceled)4. The method of claim 1 , wherein the determining step comprises detecting in the ABCB5+ stem cell sample a mRNA that is encoded by the CSC-associated gene.5. The method of claim 1 , wherein the determining step comprises detecting in the ABCB5+ stem cell sample a polypeptide that is encoded by the CSC-associated gene.612-. (canceled)13. The method of claim 1 , wherein the reference value is the expression level of the CSC-associated gene in a non-cancer reference sample claim 1 , and wherein the expression level of the CSC-associated gene in the ABCB5+ stem cell sample is greater than the expression level of the CSC-associated gene in the non-cancer reference sample.14. (canceled)15. The method of claim 1 , wherein the reference value is the expression level of the CSC-associated gene in a cancer reference sample claim 1 , and wherein claim 1 , the expression level of the CSC-associated gene is about equal to the expression level of the CSC- ...

Подробнее
27-01-2022 дата публикации

METHODS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA BY ERADICATING LEUKEMIC STEM CELLS

Номер: US20220025058A1
Принадлежит:

After intensive chemotherapy, the emergence of cells with dmg resistant and/or stem cell features might explain frequent relapses and the poor outcome of patients with acute myeloid leukemia (AML). Herein the inventors first uncovered that the adrenomedullin receptor CALCRL is overexpressed in AML patients comparing with normal cells and preferentially in the immature CD34 CD38 compartment. Then they demonstrated its role in the maintenance of leukemic stem cell function in vivo. Moreover, CALCRL depletion strongly affected leukemic growth in xenograft models and sensitized to chemotherapeutic agent cytarabine in vivo. It Accordingly, the inventors showed that ADM-CALCRL axis drove cell cycle, DNA integrity, and high OxPHOS status of chemoresistant AML stem cells in an E2F1- and BCL2-dependent manner. Furthermore, CALCRL depletion sensitizes cells to cytarabine and its CT expression predicted the response to chemotherapy in vivo in mice. Further, using the combination of limiting dilution assays, single-cell RNA-seq analysis of primary AMF samples at diagnosis and relapse and before and after transplantation in NSG mice, the inventors revealed the pre-existence of a chemoresistant leukemic stem cell sub-population harboring a CALCRL-driven gene signature. Finally the inventors strongly demonstrated that chemoresistant LSC are dependent for CALCRL. All of these data highlight the critical role of CALCRL in stem cell survival, proliferation and metabolism and identify this receptor as a new marker of chemoresistant leukemic stem cell population and a promising therapeutic target to specifically eradicate them and overcome relapse in AML. 1. A method of depleting leukemic stem cells in a subject suffering from acute myeloid leukemia comprising administering to the subject a therapeutically effective amount of an antibody that specifically binds to CALCRL thereby depleting said leukemic stem cells.2. A method of depleting leukemic stem cells in a subject suffering from ...

Подробнее
11-01-2018 дата публикации

ANTI-CLL-1 ANTIBODIES AND IMMUNOCONJUGATES

Номер: US20180009894A1
Принадлежит: Genentech, Inc.

The invention provides anti-CLL-1 antibodies and immunoconjugates and methods of using the same. 150.-. (canceled)51. A method of treating an individual having acute myeloid leukemia (AML) , comprising administering to the individual an effective amount of an immunoconjugate comprising a monoclonal anti-CLL-1 antibody and a cytotoxic drug , wherein the antibody comprises(a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:8;(b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:11;(c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:10;(d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5;(e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6; and(f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:7.52. The method of claim 51 , wherein the antibody comprises one or more engineered free cysteine amino acid residues.53. The method of claim 52 , wherein the one or more engineered free cysteine amino acid residues is located in the light chain.54. The method of claim 53 , wherein the one or more engineered free cysteine amino acid residues in the light chain comprises K149C according to Kabat numbering.55. The method of claim 51 , wherein the antibody is a humanized antibody.56. The method of claim 51 , wherein the antibody is an antibody fragment that binds CLL-1.57. The method of claim 51 , wherein the antibody is an IgG1 claim 51 , IgG2a claim 51 , or IgG2b antibody.58. The method of claim 51 , wherein the antibody is an IgG1 antibody.59. The method of claim 54 , wherein the antibody is an IgG1 antibody.60. The method of claim 51 , wherein the AML claim 51 , is CLL-1 positive AML.61. A method of treating an individual having acute myeloid leukemia (AML) claim 51 , comprising administering to the individual an effective amount of an immunoconjugate comprising a monoclonal anti-CLL-1 antibody and a cytotoxic drug claim 51 , wherein the antibody comprises (a) a heavy chain variable region comprising the amino acid sequence of SEQ ID ...

Подробнее
27-01-2022 дата публикации

METHOD FOR IDENTIFICATION OF CANCER PATIENTS WITH DURABLE BENEFIT FROM IMMUNOTEHRAPY IN OVERALL POOR PROGNOSIS SUBGROUPS

Номер: US20220026416A1
Принадлежит: BIODESIX, INC.

A blood-based sample from a cancer patient is subject to mass spectrometry and the resulting mass spectral data is classified with the aid of a computer to see if the patient is a member of a class of patients having a poor prognosis. If so, the mass spectral data is further classified with the aid of the computer by a second classifier which identifies whether the patient is nevertheless likely to obtain durable benefit from immunotherapy drugs, e.g., immune checkpoint inhibitors, anti-CTLA4 drugs, and high dose interleukin-2. 1. A method of detecting a class label in a lung cancer patient , a renal cell carcinoma patient , or a melanoma patient comprising:(a) conducting a mass spectrometer test on a blood-based sample of the cancer patient to obtain a mass spectrum; obtaining integrated intensity values of selected features in the mass spectrum at one or more m/z ranges from a multitude of mass-spectral features listed in Table 25; using the integrated intensity values in a first stage classification algorithm using a training set comprising class-labeled spectra produced from blood-based samples from the same type of cancer patients to identify the patient as being in a class of patients determined to be a poor prognosis subgroup, and(b) identifying the cancer patient as being in the class of patients determined to be a poor prognosis subgroup, and operating on the mass spectral data with a programmed computer implementing a second stage classification algorithm; wherein in the operating step the classifier compares the integrated intensity values with feature values of a reference set of class-labeled mass spectral data obtained from blood-based samples from a multitude of patients having the same type of cancer treated with an immunotherapy drug and detecting a class label for the sample.2. The method of claim 1 , wherein the immunotherapy drug comprises an antibody drug blocking ligand activation of the PD-1 checkpoint protein claim 1 , anti-CTLA4 drugs claim ...

Подробнее
12-01-2017 дата публикации

METHODS FOR ANALYZING RARE CIRCULATING CELLS

Номер: US20170010268A1
Автор: Marrinucci Dena
Принадлежит:

The disclosure provides methods for analyzing rare circulating cells (RCCs) at cellular and molecular level following their detection in non-enriched blood samples, methods of this disclosure serve as diagnostic methods for several disease conditions, including cardiovascular diseases and cancer. 1. A method for analyzing rare circulating cells (RCCs) in a non-enriched blood sample , comprising: (a) detecting RCCs in the non-enriched blood sample , comprising i) determining presence or absence of one or more immunofluorescent RCC detection markers in nucleated cells in the non-enriched blood sample , and ii) assessing the morphology of the nucleated cells , wherein RCCs are detected among the nucleated cells based on a combination of distinct immunofluorescent staining and morphological characteristics; (b) quenching the immunofluorescence of the one or more immunofluorescent RCC detection markers comprising contacting the RCCs with a quenching buffer , wherein the immunofluorescence is quenched by more than 50% , 60% , 70% , 80% , 90% , 95% , 99% , 99.9% or 99.99%; and (c) analyzing the detected RCCs , comprising determining presence or absence of one or more fluorescent RCC analysis markers.2. The method of claim 1 , wherein the fluorescent RCC analysis markers are fluorescence in situ hybridization (FISH) markers.3. The method of claim 1 , wherein more than 25% claim 1 , 30% claim 1 , 35% claim 1 , 40% claim 1 , 45% claim 1 , 50% claim 1 , 55% claim 1 , 60% claim 1 , 65% claim 1 , 70% claim 1 , 75% claim 1 , 80% claim 1 , 85% claim 1 , 90% claim 1 , 95% or 99% of RCCs detected in (a) are retained in (c).4. The method of claim 1 , wherein the fluorescent RCC analysis markers are positive control markers.5. The method of claim 4 , wherein the positive control markers are present in more than 25% claim 4 , 30% claim 4 , 35% claim 4 , 40% claim 4 , 45% claim 4 , 50% claim 4 , 55% claim 4 , 60% claim 4 , 65% claim 4 , 70% claim 4 , 75% claim 4 , 80% claim 4 , 85% ...

Подробнее
14-01-2016 дата публикации

REPLICATION PROTEIN

Номер: US20160011200A1
Автор: Coverley Dawn
Принадлежит: Cizzle Biotechnology Limited

This invention relates to a screening method for the identification of agents which modulate the activity of a DNA replication protein as a target for intervention in cancer therapy and includes agents which modulate said activity. The invention also relates to the use of the DNA replication protein, and its RNA transcripts in the prognosis and diagnosis of proliferative disease e.g., cancer. 133-. (canceled)34. A method for determining whether the subject has cancer , the method comprising:a) providing a biological sample from the patient;b) contacting the biological sample with an antibody that specifically binds to an epitope in the N-terminal region of a Ciz1 polypeptide isoform thereby forming a Ciz1 polypeptide isoform-antibody complex;c) detecting the complexes and thereby measuring the protein expression level of a Ciz1 polypeptide isoform in the sample; andd) comparing the protein expression level of the Ciz1 polypeptide isoform in the sample with the protein expression level of the Ciz1 polypeptide isoform in a control sample, wherein an elevated protein expression level of the Ciz1 polypeptide isoform indicates an increased likelihood that the subject has cancer.35. The method of claim 34 , wherein the antibody comprises a polyclonal antibody.36. The method of claim 34 , wherein the antibody comprises a monoclonal antibody.37. The method of claim 34 , wherein the Ciz1 polypeptide isoform comprises an amino-acid sequence selected from the group consisting of SEQ ID NO: 29-44 claim 34 , 47 claim 34 , 48 claim 34 , 58-64 and 65.38. The method of claim 34 , wherein said Ciz1 polypeptide isoform comprises an amino-acid sequence selected from the group consisting of SEQ ID NO: 58-64 and 65.39. The method of claim 38 , wherein said Ciz1 polypeptide isoform comprises an amino-acid sequence of SEQ ID NO: 64.40. The method of claim 34 , wherein the cancer is a pediatric cancer selected from the group consisting of retinoblastoma claim 34 , neuroblastoma claim 34 , ...

Подробнее
11-01-2018 дата публикации

METHODS AND KITS FOR ANALYSIS OF HMGB1 ISOFORMS

Номер: US20180011098A1
Принадлежит: UNIVERSITY OF HAWAII

In accordance with some embodiments herein, methods of determining signatures of HMGB1 isoforms in a subject are provided. In some embodiments, antibodies that bind specifically to HMGB1 isoforms are provided. In some embodiments, immunoassay kits are provided. 1. A method of detecting an HMGB1 isoform signature in a sample of a subject , the method comprising:providing a sample of a subject; (a) an antibody that binds specifically to hyper-acetylated HMGB1;', '(b) an antibody that binds specifically to disulfide HMGB1 (HMGB1C23-C45);', '(c) an antibody that binds specifically to hypo-acetylated HMGB1;', '(d) an antibody that binds specifically to fully reduced HMGB1;', '(e) an antibody that binds specifically to hyper-acetylated disulfide HMGB1;', '(f) an antibody that binds specifically to hyper-acetylated fully reduced HMGB1;', '(g) an antibody that binds specifically to hypo-acetylated disulfide HMGB1; or', '(h) an antibody that binds specifically to hypo-acetylated fully-reduced HMGB1; and detecting a level of the antibody bound to HMGB1 in the sample., 'contacting the sample with at least one of2. The method of claim 1 , wherein the method is performed in vitro.3. The method of any one of - claim 1 , further comprising comparing the level of bound antibody to a predetermined level.4. The method of claim 3 , wherein binding of any of (a)-(h) below the predetermined level identifies an HMGB1 isoform signature characteristic of a healthy subject.5. The method of claim 3 , wherein binding of any of (a)-(h) above the predetermined level identifies an HMGB1 isoform characteristic of a subject that has at least one of asbestos exposure claim 3 , malignant mesothelioma or an inflammatory cancer.6. The method of claim 3 , wherein the sample is contacted with (a) and (c) claim 3 , and wherein binding of (c) above a first predetermined level and binding of (a) above a second predetermined level identifies an HMGB1 isoform characteristic of a subject that has malignant ...

Подробнее
11-01-2018 дата публикации

Compositions, Methods and Kits for Diagnosis of Lung Cancer

Номер: US20180011099A1
Принадлежит:

The present invention provides methods for identifying biomarker proteins that exhibit differential expression in subjects with a first lung condition versus healthy subjects or subjects with a second lung condition. The present invention also provides compositions comprising these biomarker proteins and methods of using these biomarker proteins or panels thereof to diagnose, classify, and monitor various lung conditions. The methods and compositions provided herein may be used to diagnose or classify a subject as having lung cancer or a non-cancerous condition, and to distinguish between different types of cancer (e.g., malignant versus benign, SCLC versus NSCLC). 1. A method of determining that a lung condition in a subject is cancer comprising:(a) assessing the expression of a plurality of proteins comprising determining the protein expression level of at least each of ALDOA_HUMAN, FRIL_HUMAN, LG3BP_HUMAN, TSP1_HUMAN and COIA1_HUMAN from a biological sample obtained from the subject;(b) calculating a score from the protein expression of at least each of ALDOA_HUMAN, FRIL_HUMAN, LG3BP_HUMAN, TSP1_HUMAN and COIA1_HUMAN from the biological sample determined in step (a); and(c) comparing the score from the biological sample to a plurality of scores obtained from a reference population, wherein the comparison provides a determination that the lung condition is not cancer.2. The method of claim 1 , wherein the subject has a pulmonary nodule.3. The method of claim 2 , wherein the pulmonary nodule is 30 mm or less.4. The method of claim 3 , wherein the pulmonary nodule is between 8-30 mm.5. The method of claim 1 , wherein said lung condition is cancer or a non-cancerous lung condition.6. The method of claim 1 , wherein said cancer is non-small cell lung cancer.7. The method of claim 1 , wherein said non-cancerous lung condition is chronic obstructive pulmonary disease claim 1 , hamartoma claim 1 , fibroma claim 1 , neurofibroma claim 1 , granuloma claim 1 , sarcoidosis ...

Подробнее
11-01-2018 дата публикации

METHODS OF SELECTING AND ISOLATING CANCER STEM CELLS

Номер: US20180011100A1
Автор: Nitin Nitin, Satake Noriko

Provided herein are methods for selecting/identifying and/or isolating cancer stem cells from a biological sample or a cell culture sample using a fluorescent glucose analog. Also provided herein are methods for selecting/identifying and/or isolating leukemia stem cells and subpopulations thereof. The present invention is based, in part, on the discovery that cancer stem cells can be selected/identified based upon a lower level of fluorescence of the fluorescent glucose analog compared to non-cancer stem cells and that specific genes are differentially expressed in leukemia stem cells compared to non-leukemia stem cells. 1. A method for selecting cancer stem cells from a sample , the method comprising:(a) incubating the sample with a fluorescent glucose analog under suitable conditions, wherein the sample comprises cancer stem cells and non-cancer stem cells; and(b) selecting the cancer stem cells from the sample based upon a lower level of fluorescence compared to the non-cancer stem cells.2. The method of claim 1 , further comprising isolating the cancer stem cells.3. The method of claim 1 , wherein the cancer stem cells are capable of initiating cancer in an animal model.4. The method of claim 1 , wherein the non-cancer stem cells have highly efficient glucose uptake.5. The method of claim 1 , wherein the sample is a biological sample or a cell culture sample.6. The method of claim 5 , wherein the biological sample is selected from the group consisting of bone marrow claim 5 , blood claim 5 , plasma claim 5 , serum claim 5 , cerebrospinal fluid claim 5 , a tumor biopsy claim 5 , a tissue biopsy claim 5 , a fine needle aspirate claim 5 , circulating tumor cells claim 5 , and combinations thereof.7. The method of claim 5 , wherein the biological sample is obtained from a subject with cancer.8. The method of claim 7 , wherein the cancer is selected from the group consisting of a hematologic malignancy claim 7 , bladder cancer claim 7 , neuroblastoma claim 7 , ...

Подробнее
14-01-2021 дата публикации

MPL MUTATIONS IN JAK2 V617F NEGATIVE PATIENTS WITH MYELOPROLIFERATIVE DISEASE

Номер: US20210011019A1
Автор: Albitar Maher, Ma Wanlong
Принадлежит: Quest Diagnostics Investments LLC

The invention provides compositions and methods for diagnosing a patient as having a myeloproliferative disease by identifying mutations in the MPL gene or gene products. 1. A method of assessing the myeloproliferative disease status of an individual , comprising:(a) processing a sample comprising MPL protein from the individual to generate a processed sample; and(b) evaluating the processed sample for the presence or absence of one or more MPL protein mutations and the wild type MPL protein, wherein said MPL protein mutations are selected from the group consisting of: W515_P518 del/insKT, T496_A497 insATVI, and R525C fs*14; (i) when the sample shows the presence of one or more of said protein mutations and the absence wild type MPL protein is indicative of the individual having a myeloproliferative disease or being predisposed to myeloproliferative disease,', '(ii) when the sample shows the presence of wild type MPL protein and the presence of one or more of said protein mutations is indicative of the individual as being predisposed to a myeloproliferative disease, or', '(iii) when the sample shows the absence of each of said protein mutations is indicative of the individual as having no predisposition to a myeloproliferative disease., 'wherein'}2. The method of claim 1 , wherein said sample is selected from the group consisting of blood claim 1 , serum claim 1 , and plasma.3. The method of claim 1 , wherein said myeloproliferative disease is selected from the group consisting of polycythemia vera (PV) claim 1 , essential thrombocythemia (ET) claim 1 , and idiopathic myelofibrosis (IMF).4. The method of claim 1 , wherein evaluating comprises using antibodies against wild type MPL protein and each of the protein mutations.5. The method of claim 1 , wherein evaluating comprises protein sequencing.6. The method of claim 1 , wherein said individual does not have a pathologic mutation in the JAK2 gene.7. The method of claim 1 , wherein said individual does not have a ...

Подробнее
03-02-2022 дата публикации

ANTIBODY BINDING TO CARBONIC ANHYDRASE AND USE THEREOF

Номер: US20220033523A1
Принадлежит:

Provided is an antibody that recognizes and binds to carbonic anhydrase or antigen-binding fragment, a nucleic acid molecule coding for the antibody or antigen-binding fragment, a vector carrying the nucleic acid molecule, a host cell including the nucleic acid molecule or the vector, and use of the antibody or antigen-binding fragment thereof in the alleviation, prevention, treatment or diagnosis of solid cancers. 1. A method of preventing , alleviating or treating a solid cancer , comprising administering an effective amount of an antibody or antigen-binding fragment to a subject in need of preventing , alleviating or treating the solid cancer ,wherein the antibody or antigen-binding fragment comprises a VH-CDR1 having the amino acid sequence of SEQ ID NO: 14, a VH-CDR2 having the amino acid sequence of SEQ ID NO: 15, a VH-CDR3 having the amino acid sequence of SEQ ID NO: 28, a VL-CDR1 having the amino acid sequence of SEQ ID NO: 32 or 33, a VL-CDR2 having the amino acid sequence selected from the group consisting of SEQ ID NO: 34 to 42, and a VL-CDR3 having the amino acid sequence of SEQ ID NO: 31.2. The method to claim 1 , wherein the antibody further comprises VH-framework sequence comprising the amino acid sequences of SEQ ID NOs: 43 to 46.3. The method to claim 1 , wherein the antibody further comprises VL-framework sequence comprising the amino acid sequences of SEQ ID NOs: 47 claim 1 , 48 claim 1 , 51 and 52.4. The method to claim 1 , wherein the antibody further comprises VL-framework sequences comprising the amino acid sequence of SEQ ID NO: 48 which comprises the amino acid sequence of SEQ ID NO: 49 or 50.5. The method to claim 1 , wherein the antibody comprises VH-region amino acid sequence comprising the amino acid sequence of SEQ ID NO: 53 claim 1 , and VL-region amino acid sequence comprising the amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NOs: 54 to 63.6. The method to claim 1 , wherein the antigen- ...

Подробнее
15-01-2015 дата публикации

METHODS FOR DIAGNOSIS, PROGNOSIS AND METHODS OF TREATMENT

Номер: US20150017119A1
Принадлежит: NODALITY, INC.

The present invention provides an approach for the determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, expression markers and other criteria, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of modulators of cellular activation allows for characterization of pathways and cell populations. Several exemplary diseases that can be analyzed using the invention include AML, MDS, and MPN. 170-. (canceled)71. A method of determining whether an individual suffering from acute myeloid leukemia will respond to treatment comprising:(i) subjecting a cell population comprising said one or more hematopoietic cells from said individual to an apoptosis-inducing agent;(ii) determining a level of an activatable element within the apoptosis pathway in single cells from the cell population; and(iii) determining whether or not the individual will respond to treatment based on the level of the activatable element in the population.72. The method of further comprising comparing the level of the activatable element to a threshold value claim 71 , and determining whether or not the individual will respond to treatment based on the comparison.73. The method of wherein the apoptosis-inducing agent is selected from the group consisting of Staurosporine claim 71 , Etoposide claim 71 , Mylotarg claim 71 , Daunorubicin claim 71 , and AraC.74. The method of wherein the apoptosis-inducing agent comprises etoposide.75. The method of wherein the cell population is subjected to 2 apoptosis-inducing agents.76. The method of wherein the cell population is subjected to 2 apoptosis-inducing agents and the agents comprise Daunorubicin and AraC.77. The method of wherein the activatable element ...

Подробнее
03-02-2022 дата публикации

IGF2BP3 FUNCTIONAL ALTERATIONS AND OVEREXPRESSION AS A MARKER FOR CANCER DIAGNOSIS AND THERAPEUTIC RESPONSE TO IGF1R INHIBITORS

Номер: US20220033914A1
Принадлежит:

The present disclosure provides systems and methods for the highly sensitive and effective treatment and diagnosis of cancer. The methods disclosed herein take advantage of the discovery of a series of newly identified, inter-chromosomal genetic fusion events that occur upstream from the IGF2BP3 gene, which result in elevated expression of IGF2BP3 protein. The present disclosure utilizes biomarkers developed using this set of newly discovered genetic fusion events and elevated expression of IGF2BP3 protein to not only diagnosis cancer with high sensitivity and reliability, but also to pre-select patient populations that are expected to display an elevated likelihood of success when treated with any of numerous inhibitors of IGF1R-mediated signaling. 120-. (canceled)21. A method of detecting a thyroid adenoma associated (THADA) gene fusion cancer in a human patient , comprising the steps of:obtaining a tissue sample from a tumor or a suspected tumor in the human patient;extracting chromosomal DNA, mRNA, or combinations thereof from the tissue sample;assaying the chromosomal DNA and/or mRNA for the presence of a genetic fusion event between THADA exons 28, 29, 30, or 36 and a breakpoint located upstream of the Insulin-like growth factor 2 binding protein 3 (IGF2BP3) gene at LOC389473 including chromosome position 23,521,997; wherein the presence of the THADA-LOC389473 fusion event indicates that the human patient has a THADA gene fusion cancer; andsurgically removing tissue comprising said THADA gene fusion event.22. The method of claim 21 , wherein the cancer is selected from the group consisting of thyroid cancer claim 21 , pancreatobiliary cancer claim 21 , gastric cancer claim 21 , ovarian cancer claim 21 , colon cancer claim 21 , and lung cancer.23. The method of claim 22 , wherein the thyroid cancer is papillary thyroid carcinoma.24. The method of claim 21 , wherein the obtaining step is accomplished by fine needle aspiration or biopsy.25. The method of claim 21 ...

Подробнее
18-01-2018 дата публикации

Crenolanib for Treating FLT3 Mutated Proliferative Disorders

Номер: US20180015081A1
Автор: Jain Vinay K.
Принадлежит:

The present invention relates to the use of crenolanib, in a pharmaceutically acceptable salt form for the treatment of FLT3 mutated proliferative disorders driven by constitutively activated mutant FLT3, and to a method of treatment of warm-blooded animals, preferably humans, in which a therapeutically effective dose of crenolanib is administered to an animal suffering from said disease or condition: 1. A method for treating a FLT3 mutated proliferative disorder in a patient that comprises administering to the patient a therapeutically effective amount of crenolanib or a pharmaceutically acceptable salt thereof.2. The method of claim 1 , wherein the proliferative disorder is selected from at least one of a leukemia claim 1 , myeloma claim 1 , myeloproliferative disease claim 1 , myelodysplastic syndrome claim 1 , idiopathic hypereosinophilic syndrome (HES) claim 1 , bladder cancer claim 1 , breast cancer claim 1 , cervical cancer claim 1 , CNS cancer claim 1 , colon cancer claim 1 , esophageal cancer claim 1 , head and neck cancer claim 1 , liver cancer claim 1 , lung cancer claim 1 , nasopharyngeal cancer claim 1 , neuroendocrine cancer claim 1 , ovarian cancer claim 1 , pancreatic cancer claim 1 , prostate cancer claim 1 , renal cancer claim 1 , salivary gland cancer claim 1 , small cell lung cancer claim 1 , skin cancer claim 1 , stomach cancer claim 1 , testicular cancer claim 1 , thyroid cancer claim 1 , uterine cancer claim 1 , and hematologic malignancy.3. The method of claim 1 , wherein the therapeutically effective amount of crenolanib or a pharmaceutically acceptable salt thereof are from about 50 to 500 mg per day claim 1 , 100 to 450 mg per day claim 1 , 200 to 400 mg per day claim 1 , 300 to 500 mg per day claim 1 , 350 to 500 mg per day claim 1 , or 400 to 500 mg per day.4. The method of claim 1 , wherein the mutated FLT3 is defined further as a constitutively active FLT3 mutant.5. The method of claim 1 , wherein the therapeutically effective amount ...

Подробнее
15-01-2015 дата публикации

Gene Signature Predicts Adenocarcinoma Prognosis and Therapeutic Response

Номер: US20150017210A1
Принадлежит:

The present invention is drawn to methods of predicting prognosis of, and therapeutic response in, carcinoma of the lung. 1. A method of predicting the survival of a human subject diagnosed with carcinoma tumor of the lung comprising obtaining expression information for 9 or more of the following genes in a lung carcinoma cancer sample obtained from said subject:RPM2, ARUKA, CDKN3, PRC1, HOPX, DPP4, ATP8A1, CYP2B6, DOCKS, COL4A3, Clorf116, TTC37, IFT57, HSD17B6, NKX2-1, GPR116, MBIP, and/or SLC35A5,wherein an alteration in the expression 9 or more of said genes, as compared to the average expression in an carcinoma of the lung, indicates that said subject has a worse than average survival.2. The method of claim 1 , wherein the decrease and/or increase of expression is at least 0.2-fold.3. The method of claim 1 , further comprising treating said patient with an aggressive therapy if predicted to have a worse than average prognosis for survival.4. The method of claim 1 , wherein obtaining expression information comprises assessing protein expression.5. (canceled)6. The method of claim 1 , wherein obtaining expression information expression comprises assessing mRNA expression.79-. (canceled)10. The method of claim 1 , further comprising resecting said tumor.11. The method of claim 3 , wherein aggressive therapy comprises chemotherapy and/or radiotherapy.12. The method of claim 11 , wherein chemotherapy comprises a platin compound and/or a taxane compound.13. The method of claim 1 , further comprising obtaining expression information for 10 claim 1 , 11 claim 1 , 12 claim 1 , 13 claim 1 , 14 claim 1 , 15 claim 1 , 16 claim 1 , 17 claim 1 , or all 18 of said genes.14. The method of claim 1 , wherein said carcinoma of the lung is early stage adenocarcinoma.15. The method of claim 1 , wherein the expression of each of the following genes is assessed:RPM2, ARUKA, HOPX, ATP8A1, DOCK9, COL4A3, Clorf116, TTC37, IFT57, HSD17B6, NKX2-1 and MBIP.16. A method of predicting the ...

Подробнее
18-01-2018 дата публикации

ANTI-DLL3 ANTIBODY DRUG CONJUGATES AND METHODS OF USE

Номер: US20180015178A1
Принадлежит: ABBVIE STEMCENTRX LLC

Novel modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat proliferative disorders are provided. 120.-. (canceled)22. The method of claim 21 , wherein the cancer is lung cancer.23. The method of claim 22 , wherein the lung cancer is small cell lung cancer.24. The method of claim 21 , wherein the cancer comprises a neuroendocrine tumor.25. The method of claim 21 , wherein the cancer is large cell neuroendocrine carcinoma.26. The method of claim 21 , wherein the cancer is thyroid cancer.27. The method of claim 21 , wherein the cancer is prostate cancer.28. The method of claim 21 , wherein the subject has relapsed from chemotherapy.29. The method of claim 21 , wherein the linker comprises a cleavable linker.30. The method of claim 21 , wherein:{'sup': '2', 'sub': '5-20', 'Ris R, wherein R is a Caryl group;'}{'sup': 6', '9, 'Rand Rare H;'}{'sup': '7', 'sub': '1', 'Ris OR, and wherein R is a Calkyl;'}{'sup': '11', 'Q is O, and wherein Ris H; and/or'}X and X″ are O.32. The method of claim 31 , wherein the tumor shows suppressed Notch signaling.33. The method of claim 31 , wherein the tumor shows elevated levels of DLL3 and/or HES6 as compared to normal tissue or non-tumorigenic cells.34. The method of claim 31 , wherein the tumor is characterized by a poorly differentiated neuroendocrine phenotype.35. The method of claim 31 , wherein the tumor occurs in lung claim 31 , genitourinary tract claim 31 , gastrointestinal tract claim 31 , thyroid claim 31 , or kidney.36. The method of claim 35 , wherein the tumor comprises small cell lung cancer.37. The method of claim 35 , wherein the tumor is a large cell neuroendocrine carcinoma.38. The method of claim 35 , wherein the tumor comprises ovarian cancer.39. The method of claim 35 , wherein the tumor comprises prostate cancer.40. The method of claim 35 , wherein the tumor comprises medullary thyroid cancer.41. The method of claim 35 , wherein the tumor comprises renal cancer.42. ...

Подробнее
03-02-2022 дата публикации

USE OF CIRCULATING TUMOR CELL MITOTIC INDEX IN CANCER STRATIFICATION AND DIAGNOSTICS

Номер: US20220034888A1
Автор: ADAMS Daniel, Tang Cha-Mei
Принадлежит: CREATV MICROTECH INC.

Circulating tumor cells (CTCs) are associated with metastasis of malignant solid tumors in a patient. Presented here is evidence that CTCs exhibit cell cycle phase variability and that there is a strong correlation between the number of CTCs in a mitotic cell cycle phase and the prospects for long term survival of the subject from which the cells were obtained. Also presented herein are methods of determining the mitotic cell cycle phase of CTCs from a patient having cancer and using the information in grading malignant solid tumors and predicting the likelihood of survival of the patient. 1. A method for monitoring the effectiveness of treatment in a subject having cancer , wherein the method comprises:(a) obtaining a first population of CTCs from a first biological sample of a subject having cancer,(b) screening the first population for cells in a mitotic cell cycle phase,(c) administering a cancer treatment to the subject,(d) obtaining a second population of CTCs from a second biological sample of the subject after treatment, and(e) screening the second population for cells in a mitotic cell cycle phase,wherein an increase in the number of mitotic CTCs in the second population versus the first population, or an increase in the mitotic index calculated for the second population versus the first population, suggests the treatment is ineffective.2. The method of claim 1 , wherein the biological sample is selected from the group consisting of peripheral blood claim 1 , blood claim 1 , lymph nodes claim 1 , bone marrow claim 1 , cerebral spinal fluid claim 1 , and urine claim 1 , and wherein the first and second biological samples are from the same source.3. The method of claim 2 , wherein the first and second biological samples are at least about 7.5 mL of peripheral blood.4. The method of claim 1 , wherein the cancer is carcinoma and the CTCs are characterized by one or more of the following characteristics:(a) diameter of between about 7 and 25 microns,(b) presence ...

Подробнее
15-01-2015 дата публикации

CELL ADHESION INHIBITOR, CELL PROLIFERATION INHIBITOR, AND METHOD AND KIT FOR EXAMINING CANCER

Номер: US20150018225A1
Принадлежит:

PROBLEM 1. A cell adhesion inhibitor for a leukemia cell , comprising an antibody to a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID No: 2 or a partial peptide thereof.2. A cell adhesion inhibitor for a leukemia cell , comprising an antisense polynucleotide comprising a complementary or substantially complementary base sequence to a base sequence of a polynucleotide encoding a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID No: 2 or a part thereof.3. A cell adhesion inhibitor for a leukemia cell , comprising a substance to inhibit expression and/or activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID No: 2.4. (canceled)5. (canceled)6. (canceled)7. The inhibitor according to claim 1 , wherein the leukemia is acute myelogenous leukemia.814-. (canceled)15. A cell proliferation inhibitor for a leukemia cell claim 1 , comprising an antibody to a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID No: 2 or a partial peptide thereof.16. The inhibitor according to claim 15 , wherein the antibody is an antibody having cytotoxicity activity.17. The inhibitor according to claim 16 , wherein the cytotoxicity activity is antibody-dependent cellular cytotoxicity activity (ADCC activity).18. (canceled)19. (canceled)20. The inhibitor according to claim 15 , wherein the leukemia is acute myelogenous leukemia.21. (canceled)22. A method for examining leukemia claim 15 , comprising as follows:(a) a step of collecting a sample from a subject; and(b) a step of detecting a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID No: 2 or a partial peptide thereof, or a polynucleotide encoding a protein comprising the same ...

Подробнее
21-01-2016 дата публикации

METHOD FOR PROGNOSING THE SURVIVAL OF PATIENTS SUFFERING FROM CHRONIC MYELOMONOCYTIC LEUKAEMIA

Номер: US20160017429A1
Принадлежит:

The present invention relates to a method of prognostic of the survival of human subject suffering from chronic myelomonocytic leukemia (CMML) based on the differential expression of six genes in a test sample of PBMC cells obtained from said human subject and in a control sample of normal cells, wherein said expression level indicates if the human subject from which the test sample has been obtained will have long-term or short-term survival.

Подробнее
16-01-2020 дата публикации

INHIBITORS OF HUMAN EZH2, AND METHODS OF USE THEREOF

Номер: US20200016162A1
Принадлежит:

The invention relates to inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono- through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject. 1. A method comprisingdetecting the presence of a mutation in the EZH2 substrate pocket domain as defined in SEQ ID NO: 7 in a sample from a subject having a cancer or a precancerous condition by contacting the sample with at least one primer that specifically hybridizes to a portion of the nucleic acid encoding SEQ ID NO: 7, wherein the mutation increases EZH2 trimethylation of Lys27 of histone H3 (H3-K27);identifying the subject as a candidate for treatment with an EZH2 inhibitor based on the presence of said EZH2 mutation; andadministering a therapeutically effective amount of an EZH2 inhibitor to the identified subject.2. (canceled)3. A method comprisingdetecting the presence of a mutation in the EZH2 substrate pocket domain as defined in SEQ ID NO: 7 in a sample from a subject having a cancer or a precancerous condition by contacting the sample with at least one primer that specifically hybridizes to a portion of the nucleic acid encoding SEQ ID NO: 7, wherein the mutation increases EZH2 trimethylation of Lys27 of histone H3 (H3-K27);identifying the subject as a candidate for treatment with an EZH2 inhibitor based on the presence of said EZH2 mutation, andselecting a therapy that includes the administration of a therapeutically effective amount of an EZH2 ...

Подробнее
19-01-2017 дата публикации

METHOD OF TREATING AND REDUCING THE RISK OF ACUTE MYELOGENOUS LEUKEMIA

Номер: US20170016902A1
Автор: Nimer Stephen D., Wang Lan
Принадлежит:

The present invention relates to methods and compositions for treating and reducing the risk of Acute Myelogenous Leukemia (AML). In particular, the invention provides methods for identifying novel treatments for AML based on reproducible and detectable changes in AMLI-ETO acetylation. The present invention further provides methods of using these treatments. 117.-. (canceled)18. A method of treating or reducing risk for acute myelogenous leukemia comprising administering to a subject one or more AML1-ETO acetylation inhibitors.19. The method of wherein the one or more AML1-ETO acetylation inhibitors are identified by:determining transcription levels of one or more targets of AML1-ETO transcriptional activation contacted to a test agent; andidentifying the test agent as treating or reducing risk for acute myelogenous leukemia if the transcription levels are reduced relative to transcription levels in comparable conditions lacking the test agent.20. The method of claim 19 , wherein one or more targets of AML1-ETO transcriptional activation comprises Id1 claim 19 , p21 or Egr1.21. The method of claim 18 , wherein administering to a subject one or more AML1-ETO acetylation inhibitors characterized in that transcription levels of one or more targets of AML1-ETO transcriptional activation are lower in the presence of the one or more AML1-ETO acetylation inhibitors as compared with in its absence.22. The method of claim 18 , wherein the one or more AML1-ETO acetylation inhibitors is or was identified or characterized by a method comprising steps of:(a) providing a system in which AML1-ETO acetylation level is determinable;(b) contacting the system with a test agent;(c) determining AML1-ETO acetylation level when the test agent is present;(d) comparing the determined AML1-ETO acetylation level with a reference AML1-ETO acetylation level so that any difference between the reference level and the determined level is detected; and(e) identifying or characterizing the test ...

Подробнее
21-01-2016 дата публикации

METHODS AND MATERIALS FOR IDENTIFYING AND TREATING MAMMALS HAVING LUNG ADENOCARCINOMA CHARACTERIZED BY NEUROENDOCRINE DIFFERENTIATION

Номер: US20160018399A1
Принадлежит:

This document provides methods and materials involved in identifying mammals having lung adenocarcinoma characterized by neuroendocrine differentiation as well as methods and materials involved in treating mammals having lung adenocarcinoma characterized by neuroendocrine differentiation. For example, methods and materials for using ASCL1 and RET expression levels to identify lung cancer patients having lung adenocarcinoma characterized by neuroendocrine differentiation are provided.

Подробнее
18-01-2018 дата публикации

Use of isocitrate dehydrogenase 1 as a diagnostic and prognostic biomarker and therapeutic target for lung cancers

Номер: US20180017563A1

The present invention relates to a method for diagnosing lung cancers such as non-small lung cancer in a subject by using isocitrate dehydrogenase 1 as a diagnostic biomarker. The present invention also relates to a method for predicting the prognosis of the lung cancers such as non-small lung cancer in a subject by using isocitrate dehydrogenase 1 as a prognostic biomarker. The present invention further relates to a method of suppressing proliferation of lung tumor cells in a subject, decreasing growth of lung tumor cells in a subject, or improving survival of a subject with lung cancer by using isocitrate dehydrogenase 1 as a therapeutic target.

Подробнее
18-01-2018 дата публикации

EVALUATING METHOD, EVALUATING APPARATUS, EVALUATING PROGRAM PRODUCT, EVALUATING SYSTEM, AND TERMINAL APPARATUS

Номер: US20180017570A1
Принадлежит: AJINOMOTO CO., INC.

An evaluating method includes an evaluating step of evaluating a state of lung cancer for a subject to be evaluated using a concentration value of at least one of Homoarginine, GABA, 3-Me-His, ADMA, Spermine, Spermidine, Cystathionine, Sarcosine, aAiBA, bAiBA, Putrescine, N-Acetyl-L-lys, Hypotaurine, bABA, and Ethylglycine in blood of the subject. 1. An evaluating method comprising:an evaluating step of evaluating a state of lung cancer for a subject to be evaluated using a concentration value of at least one of Homoarginine, GABA, 3-Me-His, ADMA, Spermine, Spermidine, Cystathionine, Sarcosine, aAiBA, bAiBA, Putrescine, N-Acetyl-L-lys, Hypotaurine, bABA, and Ethylglycine in blood of the subject.2. The evaluating method according to claim 1 , wherein the evaluating step further uses a concentration value of at least one of Asn claim 1 , His claim 1 , Thr claim 1 , Ala claim 1 , Cit claim 1 , Arg claim 1 , Tyr claim 1 , Val claim 1 , Met claim 1 , Lys claim 1 , Trp claim 1 , Gly claim 1 , Pro claim 1 , Orn claim 1 , Ile claim 1 , Leu claim 1 , Phe claim 1 , Ser claim 1 , and Gln in blood of the subject.3. The evaluating method according to claim 1 , wherein the evaluating step evaluates the state of lung cancer for the subject by calculating a value of a formula further using the formula including an explanatory variable to be substituted with the concentration value of at least one of Homoarginine claim 1 , GABA claim 1 , 3-Me-His claim 1 , ADMA claim 1 , Spermine claim 1 , Spermidine claim 1 , Cystathionine claim 1 , Sarcosine claim 1 , aAiBA claim 1 , bAiBA claim 1 , Putrescine claim 1 , N-Acetyl-L-lys claim 1 , Hypotaurine claim 1 , bABA claim 1 , and Ethylglycine.4. The evaluating method according to claim 3 , wherein the evaluating step further uses a concentration value of at least one of Asn claim 3 , His claim 3 , Thr claim 3 , Ala claim 3 , Cit claim 3 , Arg claim 3 , Tyr claim 3 , Val claim 3 , Met claim 3 , Lys claim 3 , Trp claim 3 , Gly claim 3 , Pro ...

Подробнее
16-01-2020 дата публикации

ANTI-VISTA ANTIBODIES AND FRAGMENTS

Номер: US20200017589A1
Принадлежит:

The present invention relates to novel antibodies and fragments that bind to a V-domain Ig Suppressor of T cell Activation (VISTA), and methods of making and using same. Methods of use include methods of treatment of cancer, including leukemias, lymphomas, solid tumors and melanomas. 1103-. (canceled)104. An isolated antibody or antibody fragment thereof comprising an antigen binding region that binds to a V-domain Ig Suppressor of T cell Activation (VISTA) , wherein binding of the antibody or antibody fragment to VISTA modulates or enhances an immune response and which antibody:(i) comprises a VH domain comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 19, a VH CDR2 having the amino acid sequence of SEQ ID NO:20 and a VH CDR3 having the amino acid sequence of SEQ ID NO:21, and further comprises a VL domain comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:22, a VL CDR2 having the amino acid sequence of SEQ ID NO: 23 and a VL CDR3 having the amino acid sequence of SEQ ID NO:24; or(ii) comprises a VH domain comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 25, a VH CDR2 having the amino acid sequence of SEQ ID NO:26 and a VH CDR3 having the amino acid sequence of SEQ ID NO:27, and which further comprises a VL domain comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:28, a VL CDR2 having the amino acid sequence of SEQ ID NO: 29 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 30.105. A method for treating or preventing cancer in a subject in need thereof claim 104 , said method comprising administering to the subject an effective amount of an antibody or antibody fragment according to .106. A method for suppressing tumor growth in a subject in need thereof claim 104 , said method comprising administering to the subject an effective amount of an antibody or antibody fragment according to .107. A method for eliciting a biological response in a subject in need thereof claim 104 , said method ...

Подробнее
21-01-2021 дата публикации

ANTI-CD33 CHIMERIC ANTIGEN RECEPTORS AND THEIR USES

Номер: US20210017277A1
Автор: Fry Terry J., Qin Haiying

Embodiments of the invention provide chimeric antigen receptors (CARs) having antigenic specificity for CD33. Nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed. 1. A chimeric antigen receptor (CAR) comprising an antigen binding domain having antigenic specificity for CD33 , a transmembrane domain , and an intracellular T cell signaling domain , whereinthe antigen binding domain comprises from N-terminus to C-terminus the amino acid sequences of (a) SEQ ID NOS: 15, 4, and 16 or (b) SEQ ID NOS: 13, 4, and 14.28.-. (canceled)9. A chimeric antigen receptor (CAR) comprising an antigen binding domain having antigenic specificity for CD33 , a transmembrane domain , and an intracellular T cell signaling domain , wherein(a) the antigen binding domain comprises the light chain variable CDR1, CDR2, and CDR3 regions of hP67.6; and/or(b) the antigen binding domain comprises the heavy chain variable CDR1, CDR2, and CDR3 regions of hP67.6wherein the CDR regions are the amino acid sequences of SEQ ID NOS: 47-52.10. The CAR according to claim 9 , wherein the antigen binding domain comprises the amino acid sequence of SEQ ID NO: 3.11. The CAR according to claim 9 , wherein the antigen binding domain comprises the amino acid sequence of SEQ ID NO: 5.12. The CAR according to claim 9 , wherein the antigen binding domain comprises the amino acid sequence of SEQ ID NO: 4.13. The CAR according to claim 9 , wherein the antigen binding domain comprises the amino acid sequences of SEQ ID NOS: 3 claim 9 , 4 claim 9 , and 5.14. The CAR according to claim 1 , wherein the CAR comprises (i) the amino acid sequence of SEQ ID NO: 7 and the amino acid sequence of SEQ ID NO: 6 claim 1 , or (ii) the amino acid sequence of SEQ ID NO: 11 and the amino acid sequence of SEQ ID NO ...

Подробнее
21-01-2021 дата публикации

MARKER COMPOSITION FOR DIAGNOSING OR PREDICTING PROGNOSIS OF LUNG CANCER BASED ON EXOSOME OVEREXPRESSING GCC2 GENE OR PROTEIN

Номер: US20210018505A1
Принадлежит:

Described herein is a composition for diagnosing or predicting the prognosis of lung cancer. The composition includes a primer, probe, or antibody that specifically binds to a GRIP and coiled-coil domain-containing protein (GCC2) gene or protein in an exosome. 1. A marker composition for diagnosing or prognosing lung cancer , the composition containing exosome overexpressing a GCC2 (GRIP and coiled-coil domain-containing protein) protein.2. A composition for diagnosing or prognosing lung cancer , the composition containing a primer or a probe that specifically binds to a GCC2 (GRIP and coiled-coil domain-containing protein) gene in exosome.3. A composition for diagnosing or prognosing lung cancer , the composition containing an antibody that specifically binds to a GCC2 (GRIP and coiled-coil domain-containing protein) protein in exosome.4. A kit for diagnosing or prognosing lung cancer claim 2 , the kit containing the composition of .5. The kit of claim 4 , wherein the kit includes at least one selected from a group consisting of an RT-PCR kit claim 4 , a microarray chip kit claim 4 , a DNA kit and a protein chip kit.6. A method for providing information needed to diagnose or prognose lung cancer claim 4 , the method including:(a) separating an exosome from a biological sample; and(b) measuring an expression level of a GCC2 (GRIP and coiled-coil domain-containing protein) gene or protein in the exosome.7. The method of claim 6 , wherein the biological sample includes at least one selected from a group consisting of whole blood claim 6 , serum claim 6 , plasma claim 6 , saliva claim 6 , urine claim 6 , sputum claim 6 , lymph and cell.8. A method for screening a lung cancer therapeutic agent claim 6 , the method including:(a) treating a biological sample collected from a lung cancer patient with a candidate substance for a lung cancer therapeutic agent;(b) separating exosome from the biological sample; and(c) measuring an expression level of a GCC2 (GRIP and coiled- ...

Подробнее
21-01-2021 дата публикации

AUTOANTIBODIES AND AUTOANTIBODY-AUTOANTIGEN COMPLEXES AS BIOMARKERS OF SMALL CELL LUNG CANCER

Номер: US20210018506A1
Принадлежит:

Disclosed herein are high performance biomarkers and panel for small cell lung cancer (SCLC) early detection useful for identifying, diagnosing and treating SCLC patients at an early stage. The method of detecting and diagnosing small cell lung cancer (SCLC) includes contacting a sample from a subject suspected of being at-risk of acquiring or having SCLC with at least two SCLC-specific autoantibody molecules and detecting binding of four different protein types—SCLC autoantibody-antigen complexes, SCLC uncomplexed autoantibodies, SCLC associated proteins and SCLC glycoproteins—in the sample, thereby detecting SCLC in the subject. 1. A biomarker detection panel for small cell lung cancer (SCLC) comprising two or more SCLC autoantibody molecules capable of detecting autoantibody molecules of Tables 3 , 1B , 2A , 2B and 4 , wherein the autoantibody molecules complexed or not complexed with cognate autoantigen are capable of detecting SCLC with a sensitivity and specificity of at least 75%.2. The biomarker detection panel of claim 1 , wherein the sensitivity and specificity is at least 95%.3. The biomarker detection panel of claim 1 , wherein the sensitivity and specificity is between 98% to 100%.4. The biomarker detection panel of - claim 1 , wherein the at least two SCLC autoantibody molecules comprise at least PNMA1 and PNMA2 autoantibody molecules.5. The biomarker detection panel of claim 1 , wherein the at least two SCLC autoantibody molecules comprise at least PNMA1 claim 1 , PNMA2 claim 1 , and GAD65 autoantibody molecules.6. The biomarker detection panel of claim 1 , wherein the at least two SCLC autoantibody molecules comprise at least PNMA1 claim 1 , PNMA2 claim 1 , GAD65 and CRMP5 autoantibodies.7. A method of detecting small cell lung cancer (SCLC) claim 1 , comprising:contacting a sample from a subject suspected of being at-risk of acquiring or having SCLC with at least two autoantibody molecules capable of detecting molecules provided in Tables 3, 1B, 2A, ...

Подробнее
28-01-2016 дата публикации

BET INHIBITOR AND BRUTON'S TYROSINE KINASE INHIBITOR COMBINATIONS

Номер: US20160022684A1
Принадлежит:

Disclosed herein are methods, compositions, and kits for treating a B-cell malignancy comprising administering a combination of a BTK inhibitor (e.g., ibrutinib) and a BET inhibitor. Also disclosed herein are methods, compositions, and kits for treating a BTK-resistant B cell malignancy, or a MYC-driven B cell malignancy comprising administering a combination of a BTK inhibitor (e.g., ibrutinib) and a BET inhibitor. Further disclosed herein are methods of evaluating a patient having a B-cell malignancy for treatment with a combination of a BTK inhibitor (e.g., ibrutinib) and a BET inhibitor based on the MYC expression level of the patient. 1. A method of treating a B-cell malignancy in a subject in need thereof , comprising administering to the subject a therapeutically effective amount of a combination comprising a BTK inhibitor and a BET inhibitor.2. The method of claim 1 , wherein the combination provides a synergistic therapeutic effect compared to administration of the BTK inhibitor or the BET inhibitor alone.3. The method of claim 1 , wherein the combination sensitizes a B-cell malignancy to the BTK inhibitor.4. The method of claim 1 , wherein the BET inhibitor comprises CPI-0610 claim 1 , DUAL946 claim 1 , GSK525762 claim 1 , I-BET151 claim 1 , JQ1 claim 1 , OTX015 claim 1 , PFI-1 claim 1 , RVX-208 claim 1 , RVX2135 claim 1 , TEN-010 claim 1 , or a combination thereof.5. The method of claim 1 , wherein the BTK inhibitor is ibrutinib.6. The method of claim 1 , wherein the B-cell malignancy is acute lymphoblastic leukemia (ALL) claim 1 , acute myelogenous leukemia (AML) claim 1 , chronic myelogenous leukemia (CML) claim 1 , acute monocytic leukemia (AMoL) claim 1 , chronic lymphocytic leukemia (CLL) claim 1 , small lymphocytic lymphoma (SLL) claim 1 , high-risk small lymphocytic lymphoma (SLL) claim 1 , follicular lymphoma (FL) claim 1 , diffuse large B-cell lymphoma (DLBCL) claim 1 , mantle cell lymphoma (MCL) claim 1 , Waldenstrom's macroglobulinemia claim 1 ...

Подробнее
22-01-2015 дата публикации

Molecular diagnosis and typing of lung cancer variants

Номер: US20150024399A1

Compositions and methods useful in determining the major morphological types of lung cancer are provided. The methods include detecting expression of at least one gene or biomarker in a sample. The expression of the gene or biomarker is indicative of the lung tumor subtype. The compositions include subsets of genes that are monitored for gene expression. The gene expression is capable of distinguishing between normal lung parenchyma and the major morphological types of lung cancer. The gene expression and somatic mutation data are useful in developing a complete classification of lung cancer that is prognostic and predictive for therapeutic response. The methods are suited for analysis of paraffin-embedded tissues. Methods of the invention include means for monitoring gene or biomarker expression including PCR and antibody-based detection. The biomarkers of the invention are genes and/or proteins that are selectively expressed at a high or low level in certain tumor subtypes. Biomarker expression can be assessed at the protein or nucleic acid level.

Подробнее
24-01-2019 дата публикации

NOVEL SEZ6 MODULATORS AND METHODS OF USE

Номер: US20190022241A1
Принадлежит: ABBVIE STEMCENTRX LLC

Novel modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat proliferative disorders are provided. 119.-. (canceled)20. A method of treating (i) chemoresistant small cell lung cancer or (ii) medullary thyroid cancer , comprising administering to a subject in need thereof an antibody drug conjugate comprising a monoclonal antibody conjugated , linked , or otherwise associated with a cytotoxic agent , wherein the monoclonal antibody binds to a human SEZ6 protein.21. The method of claim 20 , wherein the monoclonal antibody is selected from the group consisting of a chimeric antibody claim 20 , humanized antibody claim 20 , and CDR-grafted antibody.22. The method of claim 20 , wherein the monoclonal antibody comprises three complementarity determining regions of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 190 claim 20 , and three complementarity determining regions of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 191.23. The method of claim 22 , wherein the monoclonal antibody comprises residues 23-34 of SEQ ID NO: 190 for CDR-L1 claim 22 , residues 50-56 of SEQ ID NO: 190 for CDR-L2 claim 22 , residues 89-97 of SEQ ID NO: 190 for CDR-L3 claim 22 , residues 26-32 of SEQ ID NO: 191 for CDR-H1 claim 22 , residues 50-58 of SEQ ID NO: 191 for CDR-H2 and residues 95-102 of SEQ ID NO: 191 for CDR-H3 claim 22 , wherein the residues are numbered according to Chothia.24. The method of claim 22 , wherein the monoclonal antibody comprises residues 30-36 of SEQ ID NO: 190 for CDR-L1 claim 22 , residues 46-55 of SEQ ID NO: 190 for CDR-L2 claim 22 , residues 89-96 of SEQ ID NO: 190 for CDR-L3 claim 22 , residues 30-35 of SEQ ID NO: 191 for CDR-H1 claim 22 , residues 47-58 of SEQ ID NO: 191 for CDR-H2 and residues 93-101 of SEQ ID NO: 191 for CDR-H3 claim 22 , wherein the residues are numbered according to MacCallum.25. The method of claim 22 , wherein ...

Подробнее
25-01-2018 дата публикации

MARKERS OF ACUTE MYELOID LEUKEMIA STEM CELLS

Номер: US20180022806A1
Принадлежит:

Markers of acute myeloid leukemia stem cells (AMLSC) are identified. The markers are differentially expressed in comparison with normal counterpart cells, and are useful as diagnostic and therapeutic targets. 1. A method for characterizing an acute myeloid leukemia from a patient , the method comprising:contacting a patient sample with reagents specific for a differentially expressed marker or combination of markers set forth in Table 1;quantitating the number of marker expressing cancer cells,wherein the presence of marker expressing cancer cells is indicative of the presence of AML stem cells (AMLSC).2. The method of claim 1 , wherein the quantitating is performed by flow cytometry.3. The method of claim 1 , wherein the quantitating is performed by immunohistochemistry.4. The method of claim 1 , wherein the sample is a blood sample.5. The method of claim 1 , wherein the patient has been diagnosed as having AML.6. The method of claim 5 , wherein the patient is undergoing treatment for AML.7. The method according to claim 1 , wherein said patient is a human.8. The method of claim 1 , wherein the marker is selected from CD97 claim 1 , CD99 claim 1 , CD180 and TIM3.9. A kit for use in the method of .10. A method of screening a candidate chemotherapeutic agent for effectiveness against an AMLSC claim 1 , the method comprising:contacting an AMLSC expressing a polypeptide set forth in Table 1 with a candidate agent, anddetermining the effectiveness of said agent against said AMLSC.11. A method of targeting or depleting AML cancer stem cells claim 1 , the method comprising contacting reagent blood cells with an agent that specifically binds a marker or combination of markers set forth in Table 1 in order to target or deplete AMLSC.12. The method of claim 11 , wherein the agent is an antibody.13. The method of claim 11 , wherein the the marker is selected from CD97 claim 11 , CD99 claim 11 , CD180 and TIM3.14. The method of claim 12 , wherein the agent is a bispecific ...

Подробнее
28-01-2016 дата публикации

POLYMER BACKBONE ELEMENT TAGS

Номер: US20160025731A1
Принадлежит:

Element tags based on novel metal-polymer conjugates are provided for elemental analysis of analytes, including ICP-MS. A polymer backbone is functionalized to irreversibly bind metals that are selected prior to use by the user. The polymer is further functionalized to attach a linker which allows for attachment to antibodies or other affinity reagents. The polymer format allows attachment of many copies of a given isotope, which linearly improves sensitivity. The metal-polymer conjugate tags enable multiplexed assay in two formats: bulk assay, where the average biomarker distribution in the sample is diagnostic, and single cell format to distinguish a rare (for example a diseased) cell in a complex sample (for example, blood). 165-. (canceled)66. A method for the analysis of an analyte , comprising:(i) incubating an element tagged affinity reagent with an analyte, the element tagged affinity reagent comprising an affinity reagent tagged with an element tag, the element tag comprising a polymer having at least one metal-binding pendant group that includes at least one metal atom or is capable of binding at least one metal atom, and wherein the affinity reagent binds with the analyte;(ii) separating unbound element tagged affinity reagent from bound element tagged affinity reagent;(iii) analyzing the element tag bound to the affinity reagent attached to the analyte by elemental analysis.67. The method of claim 66 , wherein two or more analytes are analyzed in a multiplex reaction claim 66 , comprising:(i) incubating two or more differential element tagged affinity reagents with two or more analytes, wherein the element tagged affinity reagents bind with the two or more analytes to produce two or more differentially tagged analytes;(ii) separating unbound element tagged affinity reagents from bound element tagged affinity reagents; and(iii) analyzing the differential element tags bound to the two or more analytes by elemental analysis.68. The method of claim 66 , ...

Подробнее
26-01-2017 дата публикации

Methods and compositions for immunomodulation

Номер: US20170023573A1
Принадлежит: Nodality Inc

The invention relates to immunomodulation of cells and the detection and use thereof, for example, in drug screening, including methods, compositions and systems therefor, or in an aspect of healthcare, such as prognosis, diagnosis, an aspect of treatment, monitoring, and the like, and methods, compositions, and systems thereof.

Подробнее
10-02-2022 дата публикации

BINDING DOMAIN

Номер: US20220041718A1
Принадлежит:

The present invention provides a variant antigen-binding domain which comprises at least one mutation in the VH domain compared to a reference antibody and which displays an increased affinity for TRBC2 over the reference antibody. It further provides an antibody, a chimeric antigen receptor (CAR), and a bispecific T-cell engager (BiTE), a cell which comprises said CAR, and a conjugate comprising said variant antigen-binding domain or said antibody. Additionally, it provides medical uses, diagnostic methods and methods of personalised medicine that exploit the products of the invention. 1. A variant antigen-binding domain which comprises at least one mutation in the VH domain compared to a reference antibody having a VH domain with the sequence shown in SEQ ID NO: 1 and a VL domain with the sequence shown in SEQ ID NO: 2 , in which at least one mutation in the VH domain is selected from T28K , Y32K and A100N , and wherein the variant antigen-binding domain displays an increased affinity for TRBC2 over the reference antibody.2. A variant antigen-binding domain according to claim 1 , which comprises at least two mutations in the VH domain selected from T28K claim 1 , Y32K and A100N.3. The variant antigen-binding domain according to claim 2 , wherein the at least two mutations in the VH domain are Y32K and A100N.4. The variant antigen-binding domain according to claim 3 , further comprising mutation T28R in the VH domain.5. The variant antigen-binding domain according to claim 3 , further comprising mutation G31K in the VH domain.6. The variant antigen-binding domain according to any of to claim 3 , which comprises T28K claim 3 , Y32K and A100N mutations.7. The variant antigen-binding domain according to claim 6 , further comprising at least one mutation at a position selected from the group consisting of V2 claim 6 , Y27 claim 6 , G31 claim 6 , R98 claim 6 , Y102 claim 6 , N103 claim 6 , and A107 in the VH domain claim 6 , N35 in the VL domain claim 6 , and R55 in the ...

Подробнее
10-02-2022 дата публикации

Identification of a JAK2 Mutation in Polycythemia Vera

Номер: US20220042016A1
Принадлежит:

The present invention concerns the V617F variant of the protein-tyrosine kinase JAK2, said variant being responsible for Vaquez Polyglobulia. The invention also relates to a first intention diagnostic method for erythrocytosis and thrombocytosis allowing their association with myeloproliferative disorders, or to the detection of the JAK2 V617F variant in myeloproliferative disorders allowing their reclassification in a new nosological group. 110.-. (canceled)21. An isolated nucleic acid comprising a complement of at least 12 consecutive nucleotides of sequence SEQ ID NO: 3 or 4 , wherein the isolated nucleic acid comprises a thymine (t) in position 261 in SEQ ID NO: 3 or a thymine (t) at position 50 in SEQ ID NO: 4 , and wherein the isolated nucleic acid further comprises a radioactive , fluorescent or enzymatic label.22. The isolated nucleic acid according to claim 21 , wherein said nucleic acid is SEQ ID NO: 11 with a G21T mutation.23. The isolated nucleic acid according to claim 21 , wherein the label is a radioactive label.24. The isolated nucleic acid according to claim 21 , wherein the label is a fluorescent label.25. The isolated nucleic acid according to claim 21 , wherein the label is an enzymatic label.26. A kit for detecting a G1849T mutation in a human Janus kinase 2 (JAK2) gene in a human tumor claim 21 , wherein the kit comprises one or more primers or probes comprising a complement of an isolated nucleic acid comprising at least 12 consecutive nucleotides of sequence SEQ ID NO 3 or 4 claim 21 , or having at least 95% homology to at least 17 consecutive nucleotides of sequence SEQ ID NO 3 or 4 claim 21 , wherein the isolated nucleic acid comprises the nucleotide tin SEQ ID NO 3 or tin SEQ ID NO 4 claim 21 ,wherein the isolated nucleic further comprises a radioactive, fluorescent or enzymatic label], for the specific detection of the presence or absence of the G1849T mutation in the human JAK2 gene,{'sup': 261', '50, 'wherein the G1849T mutation is ...

Подробнее
10-02-2022 дата публикации

CAPTURE, IDENTIFICATION AND USE OF A NEW BIOMARKER OF SOLID TUMORS IN BODY FLUIDS

Номер: US20220042970A1
Автор: ADAMS Daniel, Tang Cha-Mei
Принадлежит: Creatv MicroTech, Inc.

A new sensitive cell biomarker of solid tumors is identified in blood. This biomarker can be used to determine presence of solid tumors, rapid determination of treatment response, early detection of cancer, early detection of cancer recurrence, and may be used to determine therapy. 1. A method of screening a subject for cancer , comprising detecting circulating Cancer Associated Macrophage-Like cells (CAMLs) in blood of a subject , wherein said detecting comprises:(a) isolating intact cells of between 20 and 300 micron in size from a biological sample obtained from a subject using a means selected from the group consisting of size exclusion methodology, immunocapture, red blood cell lysis, white blood cell depletion, FICOLL separation, electrophoresis, dielectrophoresis, flow cytometry, magnetic levitation, microfluidic chip, and a combination thereof, and (i) a large atypical polyploid nucleus of about 14-64 μm in size or multiple nuclei, and', '(ii) a morphological shape selected from the group consisting of spindle, tadpole, round, oblong, two legs, more than two legs, thin legs, and amorphous,, '(b) selecting cells isolated in (a) having'}thereby detecting CAMLs in a biological sample from a subject,wherein when CAMLs are detected in the biological sample, the subject is determined to have cancer.2. The method of claim 1 , wherein the cancer is carcinoma or solid tumor.3. The method of claim 1 , wherein the cancer is breast claim 1 , prostate claim 1 , lung claim 1 , pancreatic claim 1 , or colorectal.4. The method of claim 1 , further comprising detecting circulating tumor cells (CTCs) in the biological sample.5. The method of claim 1 , wherein the cells are isolated in (a) using size exclusion methodology.6. The method of claim 5 , wherein the size exclusion methodology is use of a microfilter having pores ranging in size from 5 to 20 microns.7. The method of claim 1 , wherein the blood is peripheral blood.8. A method for confirming a diagnosis of cancer in a ...

Подробнее
10-02-2022 дата публикации

COMPOSITIONS AND METHODS RELATED TO LATROPHILINS AS BIOMARKERS FOR HAEMATOPOIETIC CELL CANCER

Номер: US20220042996A1
Принадлежит: University of Kent, School of Pharmacy

Disclosed is the use of latrophilin expression as a biomarker for the diagnosis of haematopoietic cell cancer in a subject, together with methods for diagnosis and a kit for the detection of latrophilin expression on white blood cells collected from a subject. 128-. (canceled)29. A kit for the detection of one or more latrophilin isoforms on white blood cells collected from a subject , the kit comprising:i) a latrophilin capture agent;ii) one or more factors to enhance latrophilin expression;iii) one or more latrophilin ligand; andiv) means to visualise products of exocytosis from the white blood cells.30. The kit according to claim 29 , wherein the latrophilin capture agent is an antibody against latrophilin.31. The kit according to claim 30 , wherein the antibody against latrophilin is specific for latrophilin 1 claim 30 , latrophilin 2 or latrophilin 3 claim 30 , or any combination thereof.32. The kit according to claim 29 , wherein the kit further comprises one or more reagent to visualise captured cells.33. The kit according to claim 32 , wherein the one or more reagent to visualise captured cells is an antibody against a cell-surface protein or a cell detection reagent.34. The kit according to claim 29 , wherein the latrophilin capture agent is coated on at least one surface.35. The kit according to claim 34 , wherein the at least one surface is an internal surface of a well in a microtitre plate.36. The kit according to claim 29 , wherein the one or more factor to enhance latrophilin expression is a pro-inflammatory factor.37. The kit according to claim 29 , wherein the one or more factor to enhance latrophilin expression is selected from a lipopolysaccharide (LPS) claim 29 , stem cell factor (SCF) or anti-Tim-3 antibody.38Pseudomonas aeruginosa.. The kit according to claim 37 , wherein the lipopolysaccharide is derived from39. The kit according to claim 29 , wherein the one or more latrophilin ligand induces exocytosis.40. The kit according to claim 29 , ...

Подробнее
24-01-2019 дата публикации

METHODS FOR DETECTION OF PLASMA CELL DYSCRASIA

Номер: US20190025311A1
Принадлежит:

The present invention is directed to methods for detecting a plasma cell dyscrasia like myeloma or MGUS, methods for determining whether a plasma cell dyscrasiais stable or progressive, methods for determining a risk for disease relapse, and methods for determining a response by a subject having a plasma cell dyscrasia to a therapy. 1. A method for detecting a plasma cell dyscrasia in a subject in need thereof , comprising:determining the expression level of at least 32 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 32 biomarkers, wherein the at least 32 biomarkers comprise ASXL1, BHLHE40, BTG2, COPA, FBXW7, GNA13, IL8, JMJD1C, LARS2, MALAT1,MBNL1,MCL1, NFKBIZ (2 splice variants), NR4A1 (2 splice variants), PDE4B, P1AS2, PRKAA1 (2 splice variants), SCYL2 (2 splice variants), SMARCD2, SP1 (2 splice variants), SRSF5, TAGAP, TANK, TLE4, TSC22D3, UBE2J1, and at least one housekeeping gene;normalizing the expression level of each of ASXL1, BHLHE40, BTG2, COPA, FBXW7, GNA13, IL8, JMJD1C, LARS2, MALAT1, MBNL1, MCL1, NFKBIZ (2 splice variants), NR4A1 (2 splice variants), PDE4B, PJAS2, PRKAA1 (2 splice variants), SCYL2 (2 splice variants), SMARCD2, SP1 (2 splice variants), SRSF5, TAGAP, TANK, TLE4, TSC22D3, and UBE2J1 to the expression level of the at least one housekeeping gene, thereby obtaining a normalized expression level of each of ASXL1, BHLHE40, BTG2, COPA, FBXW7, GNA13, IL8, JMJD1C, LARS2, MALAT1,MBNL1,MCL1, NFKBIZ (2 splice variants), NR4A1 (2 splice variants), PDE4B, PJAS2, PRKAA1 (2 splice variants), SCYL2 (2 splice variants), SMARCD2, SP1 (2 splice variants), SRSF5, TAGAP, TANK, TLE4, TSC22D3, and UBE2J1;inputting each normalized expression level into an algorithm to generate a score;comparing the score with a first predetermined cutoff value; andproducing a report, wherein the report identifies the presence of a plasma cell dyscrasia in the subject when ...

Подробнее
23-01-2020 дата публикации

IN VITRO METHOD FOR THE DIAGNOSIS OF LUNG CANCER

Номер: US20200025765A1
Принадлежит:

In vitro method for the diagnosis of lung cancer. The present invention is generally related to diagnostic assays. In particular, the present invention refers to the use of at least C4c fragment as diagnostic and prognostic lung cancer marker. C4c fragment can also be useful to estimate lung cancer risk and to decide whether a medical regimen has to be initiated and to determine whether the medical regimen initiated is efficient. 1. In vitro method for the diagnosis or screening of lung cancer in a subject which comprises:a. Determining the level of at least C4c fragment in a plasma sample isolated from the subject; andb. Comparing the C4c fragment level determined in step (a) with a reference control level of said C4c fragment, andc. Wherein if the C4c fragment level determined in step (a) is higher than the reference control level, it is indicative that the subject suffers from lung cancer.2. In vitro method claim 1 , according to claim 1 , wherein indeterminate pulmonary nodules have been previously identified in the subject to be diagnosed and wherein if the C4c fragment level determined in step (a) is higher than the reference control level claim 1 , it is indicative that the indeterminate pulmonary nodules identified in the subject are malignant.3. In vitro method for deciding whether to administer a medical treatment to a subject suspected of suffering from lung cancer which comprises:a. Determining the level of at least C4c fragment in a plasma sample isolated from the subject; andb. Comparing the C4c fragment level determined in step (a) with a reference control level of said C4c fragment, andc. Wherein if the C4c fragment level determined in step (a) is higher than the reference control level, a medical treatment suitable for the treatment of lung cancer is selected to be administered to the patient.4. In vitro method claim 3 , according to claim 3 , wherein indeterminate pulmonary nodules have been previously identified in the subject and wherein if the ...

Подробнее
23-01-2020 дата публикации

METHODS FOR THE DETECTION AND TREATMENT OF LUNG CANCER

Номер: US20200025766A1
Принадлежит:

Provided are methods and related kits for detection of early stage lung cancer, and determination of risk of harboring lung cancer. 1. A method of determining the risk of a subject for harboring lung cancer , comprising obtaining a biological sample from the subject;measuring the level of CEA in the biological sample;measuring the level of CA125 in the biological sample;measuring the level of CYFRA21-1 in the biological sample;measuring the level of Pro-SFTPB in the biological sample;wherein the amount of CEA, CA125, CYFRA21-1, and Pro-SFTPB classifies the subject as being at risk of harboring lung cancer or not at risk of harboring lung cancer.2. A method of determining the risk of a subject for harboring lung cancer , comprising obtaining a biological sample from the subject;contacting the sample with a first reporter molecule that binds CEA;contacting the sample with a second reporter molecule that binds CA125;contacting the sample with a third reporter molecule that binds CYFRA21-1;contacting the sample with a fourth reporter molecule that binds Pro-SFTPB;wherein the amount of the first reporter molecule, the second reporter molecule, the third reporter molecule, and the fourth reporter molecule classifies the subject as being at risk of harboring lung cancer or not at risk of harboring lung cancer.3. A method of determining the risk of a subject for harboring lung cancer , comprising obtaining a biological sample from the subject;providing a surface that binds CEA, CA125, CYFRA21-1, and Pro-SFTPB;incubating the surface with the biological sample;contacting the surface with a first reporter molecule that binds CEA;contacting the surface with a second reporter molecule that binds CA125;contacting the surface with a third reporter molecule that binds CYFRA21-1;contacting the surface with a fourth reporter molecule that binds Pro-SFTPB;measuring the amount of the first reporter molecule that is associated with the surface;measuring the amount of the second reporter ...

Подробнее
29-01-2015 дата публикации

COMPOSITIONS, METHODS AND KITS FOR DIAGNOSIS OF LUNG CANCER

Номер: US20150031065A1
Принадлежит:

The present invention provides methods for identifying biomarker proteins that exhibit differential expression in subjects with a first lung condition versus healthy subjects or subjects with a second lung condition. The present invention also provides compositions comprising these biomarker proteins and methods of using these biomarker proteins or panels thereof to diagnose, classify, and monitor various lung conditions. The methods and compositions provided herein may be used to diagnose or classify a subject as having lung cancer or a non-cancerous condition, and to distinguish between different types of cancer (e.g., malignant versus benign, SCLC versus NSCLC). 1. A method of determining that a lung condition in a subject is cancer comprising:(a) assessing the expression of a plurality of proteins comprising determining the protein expression level of at least each of ALDOA_HUMAN, FRIL_HUMAN, LG3BP_HUMAN, TSP1_HUMAN and COIA1_HUMAN from a biological sample obtained from the subject;(b) calculating a score from the protein expression of at least each of ALDOA_HUMAN, FRIL_HUMAN, LG3BP_HUMAN, TSP1_HUMAN and COIA1_HUMAN from the biological sample determined in step (a); and(c) comparing the score from the biological sample to a plurality of scores obtained from a reference population, wherein the comparison provides a determination that the lung condition is not cancer.2. The method of claim 1 , wherein the subject has a pulmonary nodule.3. The method of claim 2 , wherein the pulmonary nodule is 30 mm or less.4. The method of claim 3 , wherein the pulmonary nodule is between 8-30 mm.5. The method of claim 1 , wherein said lung condition is cancer or a non-cancerous lung condition.6. The method of claim 1 , wherein said cancer is non-small cell lung cancer.7. The method of claim 1 , wherein said non-cancerous lung condition is chronic obstructive pulmonary disease claim 1 , hamartoma claim 1 , fibroma claim 1 , neurofibroma claim 1 , granuloma claim 1 , sarcoidosis ...

Подробнее
29-01-2015 дата публикации

ANTI-MESOTHELIN CHIMERIC ANTIGEN RECEPTORS

Номер: US20150031624A1
Принадлежит:

The invention provides a chimeric antigen receptor (CAR) (a) an antigen binding domain of HN1 or SS, a transmembrane domain, and an intracellular T cell signaling domain, or (b) an antigen binding domain of SS1, a transmembrane domain, an intracellular T cell signaling domain, and a granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor 2 leader. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed. 1. A chimeric antigen receptor (CAR) comprising:(a) an antigen binding domain of HN1 or SS, a transmembrane domain, and an intracellular T cell signaling domain, or(b) an antigen binding domain of SS 1, a transmembrane domain, an intracellular T cell signaling domain, and a granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor 2 leader.2. The CAR according to claim 1 , wherein the antigen binding domain comprises a light chain variable region comprising any one of SEQ ID NOs: 1-3.3. The CAR according to claim 1 , wherein the antigen binding domain comprises a heavy chain variable region comprising any one of SEQ ID NOs: 4-6.4. The CAR according to claim 1 , wherein the antigen binding domain comprises a linker comprising SEQ ID NO: 7 or 8.5. The CAR according to claim 1 , wherein the antigen binding domain comprises a leader sequence comprising SEQ ID NO: 9.6. The CAR according to claim 1 , wherein the antigen binding domain comprises any one of SEQ ID NOs: 10-12.7. The CAR according to claim 1 , wherein the transmembrane domain comprises i) CD8 and/or ii) CD28.8. The CAR according to claim 1 , wherein the transmembrane domain comprises a CD8 amino acid sequence comprising SEQ ID NO: 13 and/or a CD28 amino acid sequence comprising SEQ ID NO: 14.9. The CAR according to claim ...

Подробнее
04-02-2016 дата публикации

DRUG SELECTION FOR NON-SMALL CELL LUNG CANCER THERAPY

Номер: US20160032403A1
Принадлежит: NESEC S.A,

The present invention provides methods for selecting a suitable anticancer drug for the treatment of patient with non-small cell lung cancer (NSCLC). The present invention also provides methods for determining drug resistance in NSCLC patients receiving EGFR inhibitor therapy. 1. A method for selecting a suitable anticancer drug for the treatment of non-small cell lung cancer (NSCLC) in a subject , the method comprising:(a) determining and/or quantifying the activation and/or expression level of EGFR in a cellular extract produced from an isolated cancer cell from the subject;(b) determining and/or quantifying the activation and/or expression level of c-Met in the cellular extract produced from an isolated cancer cell from the subject;(c) calculating a EGFR/c-MET index based upon the measurement of steps (a) and (b); and(d) selecting a suitable anticancer drug(s) for the treatment of NSCLC based upon the a EGFR/c-MET index.2. The method of claim 1 , wherein the expression levels of EGFR and cMet are used in calculating the EGFR/c-MET index.3. The method of claim 1 , wherein the activation levels of EGFR and cMet are used in calculating the EGFR/c-MET index.4. The method of claim 1 , wherein the expression levels and/or activation levels of EGFR and cMet are determined by CEER™.5. The method of claim 1 , wherein the expression levels of EGFR and cMet are determined by mRNA.6. The method of claim 5 , wherein the mRNA levels are measured using Northern blotting claim 5 , Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) claim 5 , or quantitative RT-PCR (qRT-PCR).7. The method of claim 1 , wherein the EGFR/c-MET index is between 0-20.8. The method of claim 7 , wherein when the EGFR/c-MET index is between 2 and 20 claim 7 , the subject is administered an EGFR inhibitor.9. The method of claim 8 , wherein the EGFR inhibitor is selected from the group consisting of Cetaximab claim 8 , Panitumumab claim 8 , Matuzumab claim 8 , Nimotuzumab claim 8 , ErbB1 vaccine claim ...

Подробнее
01-02-2018 дата публикации

THERAPEUTIC AND DIAGNOSTIC METHODS FOR CANCER

Номер: US20180030138A1
Автор: KOWANETZ Marcin
Принадлежит:

The present invention provides therapeutic and diagnostic methods and compositions for cancer, for example, non-small cell lung cancer (NSCLC). The invention provides methods of treating NSCLC, methods of determining whether a patient suffering from NSCLC is likely to respond to treatment comprising a PD-L1 axis binding antagonist, methods of predicting responsiveness of a patient suffering from NSCLC to treatment comprising a PD-L1 axis binding antagonist, and methods of selecting a therapy for a patient suffering from NSCLC, based on expression levels of a biomarker of the invention (e.g., PD-L1 expression levels in tumor cells and/or tumor-infiltrating immune cells). 1. A method of treating a patient suffering from a non-small cell lung cancer , the method comprising administering to the patient a therapeutically effective amount of a PD-L1 axis binding antagonist , wherein a tumor sample obtained from the patient has been determined to have a detectable expression level of PD-L1 in 5% or more of the tumor cells in the tumor sample.2. The method of claim 1 , wherein the tumor sample obtained from the patient has been determined to have a detectable expression level of PD-L1 in 10% or more of the tumor cells in the tumor sample.3. The method of claim 2 , wherein the tumor sample obtained from the patient has been determined to have a detectable expression level of PD-L1 in 20% or more of the tumor cells in the tumor sample.4. The method of claim 3 , wherein the tumor sample obtained from the patient has been determined to have a detectable expression level of PD-L1 in 50% or more of the tumor cells in the tumor sample.5. The method of any one of - claim 3 , wherein the tumor sample obtained from the patient has a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise less than 10% of the sample.6. A method of treating a patient suffering from a non-small cell lung cancer claim 3 , the method comprising administering to the patient a ...

Подробнее
01-02-2018 дата публикации

COMPOSITIONS AND METHODS FOR THE DETECTION DIAGNOSIS AND THERAPY OF HEMATOLOGICAL MALIGNANCIES

Номер: US20180030148A1
Принадлежит:

Disclosed are methods and compositions for the detection, diagnosis, prognosis, and therapy of hematological malignancies, and in particular, B cell leukemias, lymphomas and multiple myelomas. Disclosed are compositions, methods and kits for eliciting immune and T cell responses to specific malignancy-related antigenic polypeptides and antigenic polypeptide fragments thereof in an animal. Also disclosed are compositions and methods for use in the identification of cells and biological samples containing one or more hematological malignancy-related compositions, and methods for the detection and diagnosis of such diseases and affected cell types. Also disclosed are diagnostic and therapeutic kits, as well as methods for the diagnosis, therapy and/or prevention of a variety of leukemias and lymphomas. 116-. (canceled)17. A method for treating non-Hodgkin's lymphoma (NHL) in a mammalian subject wherein a B-cell from said subject overexpresses SEQ ID NO:4 , comprising administering to said subject an effective amount of an isolated monoclonal antibody that specifically binds to a polypeptide comprising the sequence set forth in SEQ ID NO: 4 , wherein said monoclonal antibody has a binding constant for SEQ ID NO:4 that exceeds 10L/mol.18. The method of claim 17 , wherein said antibody is a humanized antibody.197. The method of claim claim 17 , wherein said antibody is a chimeric antibody.20. The method of claim 17 , wherein said antibody is a Fab fragment.21. The method of claim 17 , wherein said antibody is a Fv fragment.22. The method of claim 17 , wherein said antibody is a scFv.23. The method of claim 17 , wherein said antibody further comprises a therapeutic moiety.24. The method of claim 23 , wherein the therapeutic moiety is a radionuclide.25. The method of claim 24 , wherein the radionuclide is chosen from: Y claim 24 , I claim 24 , I claim 24 , I claim 24 , Re claim 24 , At claim 24 , and Bi.26. The method of claim 17 , wherein the mammalian subject is a human. ...

Подробнее