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1. 发明申请

WO2018220236A1 POLYPEPTIDES BINDING ADAMTS5, MMP13 AND AGGRECAN 审中-公开
公开(公告)号：WO2018220236A1
公开(公告)日：2018-12-06
申请号：PCT/EP2018/064668
申请日：2018-06-04
申请人： MERCK PATENT GMBH , ABLYNX N.V.
发明人： STEFFENSEN, Soren , BESTE, Gerald , GUEHRING, Hans , TOLEIKIS, Lars , LADEL, Christoph , LINDEMANN, Sven , KELLNER, Roland , GUENTHER, Ralf
IPC分类号： C07K16/18 , C07K16/40 , C07K16/44 , A61K39/395 , A61P19/02
摘要： The present invention relates to polypeptides binding Aggrecan as well as ADAMTS5 and/or MMP13, more in particular to polypeptides that comprise or essentially consist of immunoglobulins binding Aggrecan as well as immunoglobulins binding ADAMTS5 and/or immunoglobulins binding MMP13 (also referred to herein as "polypeptides of the invention", and "immunoglobulin(s) of the invention", respectively). The invention also relates to constructs comprising such immunoglobulins, such as immunoglobulin single variable domains (ISVDs) or polypeptides as well as nucleic acids encoding such immunoglobulins or polypeptides (also referred to herein as "nucleic acid(s) of the invention"; to methods for preparing such immunoglobulins, polypeptides and constructs; to host cells expressing or capable of expressing such immunoglobulins or polypeptides; to compositions, and in particular to pharmaceutical compositions, that comprise such immunoglobulins, polypeptides, constructs, nucleic acids and/or host cells; and to uses of immunoglobulins, polypeptides, constructs, nucleic acids, host cells and/or compositions, in particular for prophylactic and/or therapeutic purposes, such as the prophylactic and/or therapeutic purposes mentioned herein. Other aspects, embodiments, advantages and applications of the invention will become clear from the further description herein.

2. 发明申请

WO2018220234A1 ADAMTS BINDING IMMUNOGLOBULINS 审中-公开
公开(公告)号：WO2018220234A1
公开(公告)日：2018-12-06
申请号：PCT/EP2018/064665
申请日：2018-06-04
申请人： MERCK PATENT GMBH , ABLYNX N.V.
发明人： BUYSE, Marie-Ange , HERMANS, Guy , LINDEMANN, Sven , GUEHRING, Hans , GUENTHER, Ralf , KELLNER, Roland
IPC分类号： C07K16/40 , A61K39/395 , A61P19/02
摘要： The present invention relates to immunoglobulins that bind ADAMTS5 and more in particular to polypeptides, that comprise or essentially consist of one or more such immunoglobulins. The invention also relates to constructs comprising such immunoglobulins, such as immunoglobulin single variable domains (ISVDs) or polypeptides as well as nucleic acids encoding such immunoglobulins or polypeptides; to methods for preparing such immunoglobulins, polypeptides and constructs; to host cells expressing or capable of expressing such immunoglobulins or polypeptides; to compositions, and in particular to pharmaceutical compositions, that comprise such immunoglobulins, polypeptides, constructs, nucleic acids and/or host cells; and to uses of immunoglobulins, polypeptides, constructs, nucleic acids, host cells and/or compositions, in particular for prophylactic and/or therapeutic purposes, such as the prophylactic and/or therapeutic purposes mentioned herein. Other aspects, embodiments, advantages and applications of the invention will become clear from the further description herein.

3. 发明公开

EP3630817A1 POLYPEPTIDES BINDING ADAMTS5, MMP13 AND AGGRECAN 审中-公开
公开(公告)号：EP3630817A1
公开(公告)日：2020-04-08
申请号：EP18730691.5
申请日：2018-06-04
申请人： Merck Patent GmbH , Ablynx N.V.
发明人： STEFFENSEN, Soren , BESTE, Gerald , GUEHRING, Hans , TOLEIKIS, Lars , LADEL, Christoph , LINDEMANN, Sven , KELLNER, Roland , GUENTHER, Ralf
IPC分类号： C07K16/18 , C07K16/40 , C07K16/44 , A61K39/395 , A61P19/02

4. 发明公开

EP4272822A3 ADAMTS BINDING IMMUNOGLOBULINS 审中-实审
公开(公告)号：EP4272822A3
公开(公告)日：2024-03-27
申请号：EP23184254.3
申请日：2018-06-04
申请人： Merck Patent GmbH , Ablynx N.V.
发明人： BUYSE, Marie-Ange , HERMANS, Guy , LINDEMANN, Sven , GUEHRING, Hans , GUENTHER, Ralf , KELLNER, Roland
IPC分类号： C07K16/40 , A61K39/395 , A61P19/02
摘要： The present invention relates to immunoglobulins that bind ADAMTSS and more in particular to polypeptides, that comprise or essentially consist of one or more such immunoglobulins (also referred to herein as "immunoglobulin(s) of the invention", and "polypeptides of the invention", respectively). The invention also relates to constructs comprising such immunoglobulins, such as immunoglobulin single variable domains (ISVDs) or polypeptides as well as nucleic acids encoding such immunoglobulins or polypeptides (also referred to herein as "nucleic acid(s) of the invention"; to methods for preparing such immunoglobulins, polypeptides and constructs; to host cells expressing or capable of expressing such immunoglobulins or polypeptides; to compositions, and in particular to pharmaceutical compositions, that comprise such immunoglobulins, polypeptides, constructs, nucleic acids and/or host cells; and to uses of immunoglobulins, polypeptides, constructs, nucleic acids, host cells and/or compositions, in particular for prophylactic and/or therapeutic purposes, such as the prophylactic and/or therapeutic purposes mentioned herein. Other aspects, embodiments, advantages and applications of the invention will become clear from the further description herein.

5. 发明公开

EP3630847A1 ADAMTS BINDING IMMUNOGLOBULINS 审中-实审转让
公开(公告)号：EP3630847A1
公开(公告)日：2020-04-08
申请号：EP18730689.9
申请日：2018-06-04
申请人： Merck Patent GmbH , Ablynx N.V.
发明人： BUYSE, Marie-Ange , HERMANS, Guy , LINDEMANN, Sven , GUEHRING, Hans , GUENTHER, Ralf , KELLNER, Roland
IPC分类号： C07K16/40 , A61K39/395 , A61P19/02

6. 发明公开

EP4272822A2 ADAMTS BINDING IMMUNOGLOBULINS 审中-实审
公开(公告)号：EP4272822A2
公开(公告)日：2023-11-08
申请号：EP23184254.3
申请日：2018-06-04
申请人： Merck Patent GmbH , Ablynx N.V.
发明人： BUYSE, Marie-Ange , HERMANS, Guy , LINDEMANN, Sven , GUEHRING, Hans , GUENTHER, Ralf , KELLNER, Roland
IPC分类号： A61P19/02
摘要： The present invention relates to immunoglobulins that bind ADAMTSS and more in particular to polypeptides, that comprise or essentially consist of one or more such immunoglobulins (also referred to herein as "immunoglobulin(s) of the invention", and "polypeptides of the invention", respectively). The invention also relates to constructs comprising such immunoglobulins, such as immunoglobulin single variable domains (ISVDs) or polypeptides as well as nucleic acids encoding such immunoglobulins or polypeptides (also referred to herein as "nucleic acid(s) of the invention"; to methods for preparing such immunoglobulins, polypeptides and constructs; to host cells expressing or capable of expressing such immunoglobulins or polypeptides; to compositions, and in particular to pharmaceutical compositions, that comprise such immunoglobulins, polypeptides, constructs, nucleic acids and/or host cells; and to uses of immunoglobulins, polypeptides, constructs, nucleic acids, host cells and/or compositions, in particular for prophylactic and/or therapeutic purposes, such as the prophylactic and/or therapeutic purposes mentioned herein. Other aspects, embodiments, advantages and applications of the invention will become clear from the further description herein.

7. 发明申请

WO2016066260A1 METHODS FOR NON-COVALENT FC-DOMAIN-CONTAINING PROTEIN DISPLAY ON THE SURFACE OF CELLS AND METHODS OF SCREENING THEREOF 审中-公开
标题翻译：在细胞表面上非共价含FC结合蛋白质显示的方法及其筛选方法
公开(公告)号：WO2016066260A1
公开(公告)日：2016-05-06
申请号：PCT/EP2015/002125
申请日：2015-10-27
申请人： MERCK PATENT GMBH
发明人： RHIEL, Laura , BECKER, Stefan , GUENTHER, Ralf , HOCK, Bjoern , HELMAN, Daniel , TOISTER-ACHITUV, Mira
IPC分类号： C12N15/10 , C12N15/31 , C12N15/62 , C12N5/10 , C12N1/19 , C07K14/315 , C07K14/36
CPC分类号： C12N15/1037 , C07K14/315 , C07K14/36 , C07K2319/00 , C07K2319/02 , C07K2319/22 , C07K2319/70
摘要： The present invention provides methods for the non-covalent surface display of proteins of interest (POI), in particular for Fc-domain containing proteins such as antibodies. The inventive method may be used to screen and select proteins of interest of a desired phenotype. The present invention further discloses polynucleotides and proteins and methods of producing the same, which may be used in carrying out the inventive method.
摘要翻译：本发明提供了非共价表面显示目标蛋白（POI）的方法，特别是用于含Fc结构域的蛋白质如抗体。本发明的方法可用于筛选和选择所需表型的目的蛋白质。本发明还公开了可用于实施本发明方法的多核苷酸和蛋白质及其制备方法。

8. 发明申请

WO2014106527A1 VERFAHREN ZUR HERSTELLUNG VON SEKRETIERBAREN ANTIKÖRPERN DURCH EXPRESSION IN SACCHAROMYCES CEREVISIAE 审中-公开
标题翻译：用于在酿酒酵母中产生抗体BY分泌表达
公开(公告)号：WO2014106527A1
公开(公告)日：2014-07-10
申请号：PCT/EP2013/003748
申请日：2013-12-11
申请人： MERCK PATENT GMBH
发明人： GUENTHER, Ralf , HOCK, Bjoern , BECKER, Stefan , RHIEL, Laura
IPC分类号： C07K16/00
CPC分类号： C12N15/1037 , C07K16/005 , C07K2317/14 , C07K2317/569 , C07K2317/624
摘要： Die Erfindung betrifft ein Verfahren zur Erzeugung und nicht-kovalenten Oberflächenpräsentation von Antikörpern und abgeleiteten Fragmenten sowie darauf basierenden Molekülbibliotheken auf der Oberfläche von S. cerevisiae Zellen. Die nicht- kovalente Weise der Oberflächenpräsentation ermöglicht die Selektion von spezifischen Varianten mittels Hochdurchsatz-Durchmusterung und die nachfolgende schaltbare Sekretion des selektierten Bindemoleküls in den Kulturüberstand zur biochemischen Charakterisierung.
摘要翻译：本发明涉及一种用于产生和抗体和衍生的片段的非共价表面展示并在其上酿酒酵母细胞的表面上的分子文库基于的方法。非共价的方式，表面显示允许特定的变体的高通量筛选和在生物化学表征培养上清液中的可切换的选择的结合分子的随后分泌的手段选择。

9. 发明申请

WO2012076191A1 APTAMER LABELED WITH F-19 NUCLEUS FOR TARGETED MOLECULAR IMAGING BY MRI 审中-公开
标题翻译：标有F-19核子的APTAMER通过MRI进行靶向分子成像
公开(公告)号：WO2012076191A1
公开(公告)日：2012-06-14
申请号：PCT/EP2011/006255
申请日：2011-12-12
申请人： MERCK PATENT GMBH , GUENTHER, Ralf , HOCK, Bjoern , GOODMAN, Simon , PIATER, Birgit
发明人： GUENTHER, Ralf , HOCK, Bjoern , GOODMAN, Simon , PIATER, Birgit
IPC分类号： A61K49/12
CPC分类号： C12N15/115 , A61K49/12 , A61K49/126
摘要： Magnetic Resonance Imaging, usually based on 1 H as the magnetic nucleus, is an important diagnostic technique that is commonly used in hospitals for the diagnosis of disease. MRI allows for the non- invasive imaging of soft tissue with a superb spatial resolution. Magnetic Resonance Imaging based on 19 F instead of 1 H opens up new diagnostic possibilities. The 19 F nucleus has a high gyromagnetic ratio (40 MHz/T) and a natural isotopic abundance ratio of 100%. In the human body, 19 F containing structures are exclusively present in the form of solid salts in e.g. teeth and bones. As a consequence, the J2 relaxation times of the endogenous 19 F atoms are extremely short and the MR signal is hardly detectable, in other words, the lack of endogenous, 19 F-based structures with relatively high transverse relaxation times assures a very low background MR signal. Therefore, exogenous 19 F-based MRI contrast agents allow for "hot spot" imaging in a way similar to other techniques such as PET (positron emission tomography). As a useful extension of its diagnostic use, MRI is also proposed for the monitoring of the delivery of bio-active agents such as therapeutic or diagnostic agents. I.e., MRI can not only be used for treatment planning, but also to control local drug delivery under image guidance.
摘要翻译：磁共振成像通常以1H为磁核，是医院常用于诊断疾病的重要诊断技术。 MRI允许具有极好的空间分辨率的软组织的非侵入性成像。基于19F而不是1H的磁共振成像开辟了新的诊断可能性。 19F核具有高回旋比（40MHz / T）和100％的天然同位素丰度比。在人体中，含有19F的结构仅以例如固体盐的形式存在。牙齿和骨头。因此，内源性19F原子的J2松弛时间非常短，并且MR信号几乎不可检测，换句话说，缺乏具有相对较高的横向弛豫时间的内源性19F基结构，确保非常低的背景MR信号。因此，外源性基于19F的MRI造影剂允许以与PET（正电子发射断层摄影）等其他技术相似的方式进行“热点”成像。作为其诊断用途的有用扩展，还提出了用于监测生物活性剂如治疗剂或诊断剂的递送的MRI。即，MRI不仅可以用于治疗计划，还可以在图像引导下控制局部药物传播。

10. 发明申请

WO2016000813A1 ANTI-TNFA ANTIBODIES WITH PH-DEPENDENT ANTIGEN BINDING 审中-公开
标题翻译：具有PH依赖性抗原结合的抗TNFA抗体
公开(公告)号：WO2016000813A1
公开(公告)日：2016-01-07
申请号：PCT/EP2015/001296
申请日：2015-06-26
申请人： MERCK PATENT GMBH
发明人： GUENTHER, Ralf , BECKER, Stefan , RHIEL, Laura , HOCK, Bjoern , SCHROETER, Christian
IPC分类号： C07K16/08
CPC分类号： C07K16/241 , A61K2039/505 , C07K2317/55 , C07K2317/565 , C07K2317/72 , C07K2317/92 , C07K2317/94
摘要： The invention relates to anti-TNFa antibodies which are engineered to exhibit a pH-sensitive antigen binding. The invention is preferably directed to anti-TNFa antibody adalimumab (Humira®) or biologically active variants and fragments thereof, wherein the original adalimumab antibody or variant or fragment thereof is engineered by modifications of amino acid sequence within the variable regions. Specifically, the invention relates to adalimumab or biologically active variants or fragments thereof, wherein the CDR domains are modified by replacing one or more amino acid residues by histidine residues.
摘要翻译：本发明涉及经过工程改造以显示pH敏感抗原结合的抗TNFα抗体。本发明优选针对抗TNFα抗体阿达木单抗或其生物活性变体及其片段，其中原始阿达木单抗抗体或其变体或片段通过在可变区内的氨基酸序列的修饰来工程化。具体地，本发明涉及阿达木单抗或生物活性变体或其片段，其中通过用组氨酸残基替换一个或多个氨基酸残基来修饰CDR结构域。

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