公开(公告)号：US10648970B2

公开(公告)日：2020-05-12

申请号：US14356735

申请日：2012-11-08

Applicant: DAKO DENMARK A/S

Inventor： Jesper Lohse ,  Kristian Jensen ,  Rikke Malene Krusenst Jerna-Hafstrom ,  Kirsten Damgaard Hoff ,  Lars Christian Jacobsen

IPC: G01N33/53 ,  G01N33/68 ,  G01N33/58

Abstract: The present invention lies in the field of visualization and quantification of immobilized targets in samples using immunochemical means. In particular, the invention relates to a method and reagents for detection, visualization and quantification of a molecular target in immunostained histological samples using particular compositions of the target specific binding agent. Methods and compositions of the invention are suitable for any assay that uses a target visualization system in histological samples based on detection of the target by the target specific binding agent. The methods and compositions are useful for evaluation of targets that are biomarkers of diseases in medical diagnostic.

公开(公告)号：US20160274122A1

公开(公告)日：2016-09-22

申请号：US15166133

申请日：2016-05-26

Applicant: Dako Denmark A/S

Inventor： Jesper Lohse ,  Galina Skladchikova

IPC: G01N33/58 ,  C12Q1/26

CPC classification number: G01N33/581 ,  C12Q1/26 ,  C12Q1/28 ,  G01N33/57492

Abstract: The present invention relates to methods and compounds for enzyme-mediated amplification of target-associated signals for visualization of biological or chemical targets in samples, wherein the targets are immobilized, in particular the invention relates to the oxidoreductase-mediated signal amplification for visualization of targets in samples comprising cells. The methods of the invention are particular useful for qualitative and quantitative evaluation of biological markers relating to medical diagnostic and therapy.

Abstract translation: 本发明涉及用于酶介导扩增靶标相关信号的方法和化合物，用于在样品中生物或化学靶标的可视化，其中靶标被固定，特别是本发明涉及用于目标可视化的氧化还原酶介导的信号放大 在包含细胞的样品中。 本发明的方法对于与医学诊断和治疗有关的生物学标记的定性和定量评估特别有用。

公开(公告)号：US20190085048A1

公开(公告)日：2019-03-21

申请号：US16015955

申请日：2018-06-22

Applicant: Dako Denmark A/S

Inventor： Liselotte Brix ,  Henrik Pedersen ,  Tina Jakobsen ,  Jørgen Schøller ,  Jesper Lohse ,  Katja Brunstedt ,  Kivin Jacobsen

IPC: C07K14/74 ,  A61K47/66 ,  A61K47/64 ,  B82Y5/00

Abstract: The present invention describes novel methods to generate MHC multimers and methods to improve existing and new MHC multimers. The invention also describes improved methods for the use of MHC multimers in analysis of T-cells in samples including diagnostic and prognostic methods. Furthermore, the use of MHC multimers in therapy are described, e.g. anti-tumour and anti-virus therapy, including isolation of antigen specific T-cells capable of inactivation or elimination of undesirable targeT-cells or isolation of specific T-cells capable of regulation of other immune cells.

公开(公告)号：US08999639B2

公开(公告)日：2015-04-07

申请号：US13856569

申请日：2013-04-04

Applicant: DAKO Denmark A/S

Inventor： Jesper Lohse

IPC: C12Q1/68 ,  C08G63/672 ,  C08G69/40 ,  C08G69/48 ,  C12Q1/28 ,  G01N33/543 ,  C07H21/02 ,  C07H19/04

CPC classification number: G01N33/54393 ,  C08G63/672 ,  C08G69/40 ,  C08G69/48 ,  C12Q1/28

Abstract: The present invention relates to methods and compounds for detection of molecular targets, such as biological or chemical molecules, or molecular structures, in samples using a host of experimental schemes for detecting and visualizing such targets, e.g. immunohistochemistry (IHC), in situ hybridization (ISH), ELISA, Southern, Northern, and Western blotting, etc.

Abstract translation: 本发明涉及用于检测分子靶标的方法和化合物，例如生物或化学分子或分子结构，使用大量用于检测和可视化这些靶标的实验方案的样品。 免疫组化（IHC），原位杂交（ISH），ELISA，Southern，Northern和Western blotting等。

公开(公告)号：US10526646B2

公开(公告)日：2020-01-07

申请号：US15383996

申请日：2016-12-19

Applicant: Dako Denmark A/S

Inventor： Jesper Lohse ,  Mike Paw Maischnack Hansen

IPC: C07D311/82 ,  C12Q1/6841 ,  C07D311/90 ,  C07D493/10 ,  C12N9/08 ,  C12N9/96 ,  C12Q1/28 ,  G01N33/58 ,  C12Q1/68

Abstract: Chromogenic conjugates for color-based detection of targets are described. The conjugates comprise a chromogenic moiety such as rhodamine, rhodol or fluorescein. The chromogenic moiety is linked to a peroxidase substrate. The chromogenic conjugates can be used in immunohistochemical analysis and in situ hybridization. The conjugates can be used to detect 1, 2, 3 or more targets in a sample by color.

公开(公告)号：US10168335B2

公开(公告)日：2019-01-01

申请号：US15165823

申请日：2016-05-26

Applicant: Dako Denmark A/S

Inventor： Jesper Lohse ,  Kenneth Heesche Petersen

IPC: G01N33/58 ,  C12Q1/28 ,  C12Q1/68 ,  C12Q1/6806

Abstract: The present invention relates to a method of biological labeling that occurs via a free radical chain reaction. The labeling occurs due to deposition of a detectable reporter molecule from a media comprising a substance comprising at least two moieties of a peroxidase enzyme substrate (termed herein ‘cross-linker’) in a target site comprising peroxidase activity and a biological marker. The labeling reaction described herein may generally be used to detect targets in a host of experimental schemes for detecting and visualizing a biological or chemical target, including immunohistochemistry (IHC), in situ hybridization (ISH), antibody-based staining methods such as ELISA, Southern, Northern, and Western blotting, and others.

公开(公告)号：US10036066B2

公开(公告)日：2018-07-31

申请号：US14659847

申请日：2015-03-17

Applicant: DAKO DENMARK A/S

Inventor： Lars Winther ,  Jesper Lohse ,  Susanne Gabs ,  Kenneth Heesche Petersen

IPC: C12Q1/68 ,  C12Q1/6876 ,  C12Q1/6841

CPC classification number: C12Q1/6876 ,  C12Q1/6841 ,  C12Q2525/161 ,  C12Q2565/40

Abstract: The invention provides compositions and methods for the detection of targets in a sample; in particular, an in situ hybridization (ISH) sample. Probes and detectable labels may be provided in multiple layers in order to increase the flexibility of a detection system, and to allow for amplification to enhance the signal from a target. The layers may be created by incorporating probes and detectable labels into larger molecular units that interact through nucleic acids base-pairing, including peptide-nucleic acid (PNA) base-pairing. Optional non-natural bases allow for degenerate base pairing schemes. The compositions and methods are also compatible with immunohistochemistry (IHC), immunocytochemistry (ICC), flow cytometry, enzyme immuno-assays (EIA), enzyme linked immuno-assays (ELISA), blotting methods (e.g. Western, Southern, and Northern), labeling inside electrophoresis systems or on surfaces or arrays, and precipitation, among other general detection assay formats. The invention is also compatible with many different types of targets, probes, and detectable labels.

公开(公告)号：US20170175178A1

公开(公告)日：2017-06-22

申请号：US15383996

申请日：2016-12-19

Applicant: Dako Denmark A/S

Inventor： Jesper Lohse ,  Mike Paw Maischnack Hansen

IPC: C12Q1/68 ,  C12N9/96 ,  C07D493/10 ,  C07D311/82 ,  C07D311/90 ,  C12N9/08 ,  C12Q1/28

CPC classification number: C12Q1/6841 ,  C07D311/82 ,  C07D311/90 ,  C07D493/10 ,  C12N9/0065 ,  C12N9/96 ,  C12Q1/28 ,  G01N33/581

Abstract: Chromogenic conjugates for color-based detection of targets are described. The conjugates comprise a chromogenic moiety such as rhodamine, rhodol or fluorescein. The chromogenic moiety is linked to a peroxidase substrate. The chromogenic conjugates can be used in immunohistochemical analysis and in situ hybridization. The conjugates can be used to detect 1, 2, 3 or more targets in a sample by color.

公开(公告)号：US20160370375A1

公开(公告)日：2016-12-22

申请号：US15165823

申请日：2016-05-26

Applicant: Dako Denmark A/S

Inventor： Jesper Lohse ,  Kenneth Heesche Petersen

IPC: G01N33/58 ,  C12Q1/68 ,  C12Q1/28

CPC classification number: G01N33/581 ,  C12Q1/28 ,  C12Q1/6806 ,  G01N2333/908

Abstract: The present invention relates to a method of biological labeling that occurs via a free radical chain reaction. The labeling occurs due to deposition of a detectable reporter molecule from a media comprising a substance comprising at least two moieties of a peroxidase enzyme substrate (termed herein ‘cross-linker’) in a target site comprising peroxidase activity and a biological marker. The labeling reaction described herein may generally be used to detect targets in a host of experimental schemes for detecting and visualizing a biological or chemical target, including immunohistochemistry (IHC), in situ hybridization (ISH), antibody-based staining methods such as ELISA, Southern, Northern, and Western blotting, and others.

Abstract translation: 本发明涉及通过自由基链反应发生的生物标记方法。 标记发生是由于可检测的报道分子从包含过氧化物酶底物（称为“交联剂”）至少两个部分的物质的介质沉积在包含过氧化物酶活性的靶位点和生物标记物中。 本文描述的标记反应通常可用于检测用于检测和可视化生物或化学靶的主要实验方案中的靶标，包括免疫组织化学（IHC），原位杂交（ISH），基于抗体的染色方法如ELISA， 南，北，西印迹等。

公开(公告)号：US09340824B2

公开(公告)日：2016-05-17

申请号：US14251934

申请日：2014-04-14

Applicant: Dako Denmark A/S

Inventor： Lars Winther ,  Jesper Lohse ,  Susanne Gabs ,  Kenneth Heesche Petersen

IPC: C07H21/04 ,  C12Q1/68 ,  A61K47/48 ,  A61K49/00 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C08G69/02 ,  C07C231/02 ,  C07C233/36 ,  G01N33/53

CPC classification number: C12Q1/6804 ,  A61K47/61 ,  A61K47/6843 ,  A61K47/6889 ,  A61K49/0041 ,  A61K49/0043 ,  A61K49/0056 ,  C07C231/02 ,  C07C233/36 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C08G69/02 ,  C12Q1/6876 ,  G01N33/5306

Abstract: The invention provides compositions and methods for the detection of targets in a sample; in particular, an immunohistochemistry (IHC) sample. Probes and detectable labels may be provided in multiple layers in order to increase the flexibility of a detection system, and to allow for amplification to enhance the signal from a target. The layers may be created by incorporating probes and detectable labels into larger molecular units that interact through nucleic acids base-pairing, including peptide-nucleic acid (PNA) base-pairing. Optional non-natural bases allow for degenerate base pairing schemes. The compositions and methods are compatible with immunohistochemistry (IHC), but also could be used in immunocytochemistry (ICC), in situ hybridization (ISH), flow cytometry, enzyme immuno-assays (EIA), enzyme linked immuno-assays (ELISA), blotting methods (e.g. Western, Southern, and Northern), labeling inside electrophoresis systems or on surfaces or arrays, and precipitation, among other general detection assay formats. The invention is also compatible with many different types of targets, probes, and detectable labels.

Abstract translation: 本发明提供用于检测样品中靶标的组合物和方法; 特别是免疫组织化学（IHC）样品。 可以以多层提供探针和可检测标记，以便增加检测系统的灵活性，并允许放大以增强来自靶的信号。 可以通过将探针和可检测标记掺入通过核酸碱基配对（包括肽 - 核酸（PNA）碱基配对）相互作用的较大分子单元中来产生层。 可选的非天然碱基允许简并碱基配对方案。 组合物和方法与免疫组织化学（IHC）相容，但也可用于免疫细胞化学（ICC），原位杂交（ISH），流式细胞术，酶免疫分析（EIA），酶联免疫分析（ELISA） 印迹方法（如西方，南方和北方），电泳系统或表面或阵列内标记，以及其他一般检测方法中的沉淀。 本发明还与许多​​不同类型的靶，探针和可检测标记相兼容。