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1. 发明申请

WO2007076927A1 ANTI-IL-6 ANTIBODIES PREVENTING THE BINDING OF IL-6 COMPLEXED WITH IL-6RALPHA TO GP130 审中-公开
标题翻译：抗IL-6抗体，预防与IL-6RALPHA复合的IL-6与GP130的结合
公开(公告)号：WO2007076927A1
公开(公告)日：2007-07-12
申请号：PCT/EP2006/012236
申请日：2006-12-19
申请人： MERCK PATENT GMBH , WAY, Jeffrey, C. , GILLIES, Stephen, D. , LO, Kin-Ming , LIU, Yuan
发明人： WAY, Jeffrey, C. , GILLIES, Stephen, D. , LO, Kin-Ming , LIU, Yuan
IPC分类号： C07K16/24 , A61K39/395 , A61P35/00 , C12N15/13 , C07K19/00 , C07K14/54
CPC分类号： C07K14/5412 , A61K2039/505 , C07K14/7155 , C07K16/248 , C07K16/2866 , C07K16/3023 , C07K16/3053 , C07K16/3061 , C07K2317/24 , C07K2317/32 , C07K2317/56 , C07K2317/73 , C07K2317/76 , C07K2319/30
摘要： The present invention provides anti IL-6 antibodies including an antibody variable region that prevents IL-6 from binding to gp130. The present invention also provides compositions and methods for treating IL-6 related diseases based on the IL-6 antagonists of the invention.
摘要翻译：本发明提供抗IL-6抗体，其包括防止IL-6与gp130结合的抗体可变区。本发明还提供了基于本发明的IL-6拮抗剂治疗IL-6相关疾病的组合物和方法。

2. 发明申请

WO2004055056A1 HUMANIZED ANTIBODY (H14.18) OF THE MOUSE 14.18 ANTIBODY BINDING TO GD2 AND ITS FUSION WITH IL-2 审中-公开
标题翻译：小鼠的人体抗体（H14.18）14.18与GD2的抗体结合及其与IL-2的融合
公开(公告)号：WO2004055056A1
公开(公告)日：2004-07-01
申请号：PCT/EP2003/014295
申请日：2003-12-16
申请人： MERCK PATENT GMBH , GILLIES, Stephen, D. , LO, Kin-Ming
发明人： GILLIES, Stephen, D. , LO, Kin-Ming
IPC分类号： C07K16/30
CPC分类号： C07K16/3084 , A61K48/00 , C07K16/30 , C07K16/467 , C07K2317/24 , C07K2317/732
摘要： The invention provides humanized antibody H14.18 binding the human cell surface glycosphingolipid GD2. The antibody comprises modified variable regions, more specially, modified framework regions, which reduce their immunogenitity when administered to a human. The antibody may be coupled to the therapeutic agent such as IL-2 and used in the treatment of cancer.
摘要翻译：本发明提供人源化抗体H14.18结合人细胞表面的鞘糖脂GD2。抗体包含修饰的可变区，更特别地，修饰的框架区，当施用于人时降低其免疫原性。抗体可以与治疗剂例如IL-2偶联并用于治疗癌症。

3. 发明申请

WO2007076933A1 INTERLEUKIN-12P40 VARIANTS WITH IMPROVED STABILITY 审中-公开
标题翻译：具有改进稳定性的INTERLEUKIN-12P40变量
公开(公告)号：WO2007076933A1
公开(公告)日：2007-07-12
申请号：PCT/EP2006/012301
申请日：2006-12-20
申请人： MERCK PATENT GMBH , WEBSTER, Gordon, D. , MCKENZIE, Suzanne, P. , LO, Kin-Ming , STEIN, Pascal, André
发明人： WEBSTER, Gordon, D. , MCKENZIE, Suzanne, P. , LO, Kin-Ming , STEIN, Pascal, André
IPC分类号： C07K14/54 , A61K38/20 , C12N15/24 , C12N15/62 , C12N5/00
CPC分类号： H04N21/4353 , A61K38/00 , C07K14/5434 , G06Q20/10 , G06Q30/0215 , G06Q30/0226 , G06Q30/04 , G06Q40/12 , H04L41/32 , H04L41/5019 , H04L47/2491 , H04N21/462 , H04N21/6106 , H04N21/8549
摘要： Modified interleukin-12 (IL-12) p40 polypeptides are disclosed. The modified polypeptides have alterations in the IL-12p40 subunit to eliminate the protease site between positions Lys260 and Arg261. The modified IL-12p40 polypeptides according to the invention have improved stability compared to wild-type mature human IL-12p40 polypeptides.
摘要翻译：公开了修饰的白细胞介素-12（IL-12）p40多肽。修饰的多肽在IL-12p40亚基中具有改变以消除Lys260和Arg261之间的蛋白酶位点。与野生型成熟人IL-12p40多肽相比，根据本发明的修饰的IL-12p40多肽具有改善的稳定性。

4. 发明申请

WO2010121766A1 ANTIBODY FUSION PROTEINS WITH MODIFIED FCRN BINDING SITES 审中-公开
标题翻译：具有修饰的FCRN结合位点的抗体融合蛋白
公开(公告)号：WO2010121766A1
公开(公告)日：2010-10-28
申请号：PCT/EP2010/002377
申请日：2010-04-19
申请人： MERCK PATENT GMBH , LO, Kin-Ming , STEIN, Pascal André
发明人： LO, Kin-Ming , STEIN, Pascal André
IPC分类号： C07K16/00
CPC分类号： C07K14/565 , C07K16/00 , C07K2317/52 , C07K2317/53 , C07K2319/02 , C07K2319/30
摘要： Disclosed are antibody fusion proteins with a modified FcRn binding site and nucleic acid molecules encoding them. The antibody fusion protein include two polypeptide chains, wherein the first polypeptide chain includes a biologically, preferably therapeutically active molecule linked to at least a portion of an immunoglobulin constant region. The second polypeptide chain includes at least a portion of an immunoglobulin constant region. One of the polypeptide chains includes a mutation in the constant region that results in reduction or loss of FcRn binding but does not cause substantial reduction of serum half-life of said antibody fusion protein. In a preferred embodiment the invention relates to respectively constructed Fc-IFNβ molecules. Also disclosed are methods of producing the fusion proteins and methods of using the fusion proteins for treating diseases and conditions alleviated by the administration of the fusion proteins.
摘要翻译：公开了具有修饰的FcRn结合位点和编码它们的核酸分子的抗体融合蛋白。抗体融合蛋白包括两条多肽链，其中第一多肽链包括连接至免疫球蛋白恒定区的至少一部分的生物学优选的治疗活性分子。第二多肽链包括免疫球蛋白恒定区的至少一部分。多肽链中的一个包括导致FcRn结合的减少或丧失的恒定区中的突变，但不会导致所述抗体融合蛋白的血清半衰期的显着降低。在优选的实施方案中，本发明涉及分别构建的Fc-IFNβ分子。还公开了产生融合蛋白的方法和使用融合蛋白治疗通过施用融合蛋白而减轻的疾病和病症的方法。

5. 发明申请

WO2009010290A2 ENGINEERED ANTI-ALPHA V- INTEGRIN HYBRID ANTIBODIES 审中-公开
标题翻译：工程抗αV整合杂合抗体
公开(公告)号：WO2009010290A2
公开(公告)日：2009-01-22
申请号：PCT/EP2008/005852
申请日：2008-07-17
申请人： MERCK PATENT GMBH , GOODMAN, Simon , HAHN, Diane , MITJANS, Francesc , ADAN, Jaume , LO, Kin-Ming
发明人： GOODMAN, Simon , HAHN, Diane , MITJANS, Francesc , ADAN, Jaume , LO, Kin-Ming
IPC分类号： A61K39/395 , A61P35/00 , C07K16/28
CPC分类号： C07K16/2842 , A61K39/3955 , A61K2039/505 , A61K2039/507 , C07K2317/24 , C07K2317/565 , C07K2317/567 , C07K2317/72 , C07K2317/76 , C07K2317/90 , C07K2317/92 , A61K2300/00
摘要： The invention relates to engineered antibodies which specifically bind to integrin receptors, especially the alpha V integrin receptor subunit. The antibodies comprise the antigen binding sites (CDRs) of a known mouse anti-integrin antibody, as well as hybrid light chain variable sequences, mutated heavy chain variable sequences (Frs) and modified heavy chain constant sequences. The novel antibodies have improved immunogenic and expression properties and elicit excellent anti-angiogenic as well as anti-tumor activities in humans in monotherapy but also and above all in combination with other angiogenesis and tumor inhibiting agents.
摘要翻译：本发明涉及特异性结合整联蛋白受体，特别是αV整联蛋白受体亚基的工程化抗体。抗体包含已知的小鼠抗整联蛋白抗体的抗原结合位点（CDR），以及杂合轻链可变序列，突变的重链可变序列（Frs）和修饰的重链恒定序列。新型抗体具有改善的免疫原性和表达特性，并且在单一疗法中引起人类优异的抗血管生成以及抗肿瘤活性，并且最重要的是与其他血管生成和肿瘤抑制剂联合。

6. 发明申请

WO2005066348A2 COMPOUNDS FOR TARGETING 审中-公开
标题翻译：目标化合物
公开(公告)号：WO2005066348A2
公开(公告)日：2005-07-21
申请号：PCT/GB2005/000007
申请日：2005-01-05
申请人： EMD LEXIGEN RESEARCH CENTER CORP. , ANTISOMA PLC , GILLIES, Stephen , LO, Kin-Ming , LAN, Yan , VERMA, Rakesh
发明人： GILLIES, Stephen , LO, Kin-Ming , LAN, Yan , VERMA, Rakesh
IPC分类号： C12N15/62
CPC分类号： C07K14/5434 , A61K47/6813 , A61K47/6851 , C07K16/244 , C07K16/30 , C07K2317/21 , C07K2317/24 , C07K2319/00 , C07K2319/30
摘要： The invention provides a compound comprising a target specific portion and an effector portion wherein the target specific portion comprises or consists of a monoclonal antibody having specificity for oncofoetal fibronectin, or a fragment or variant thereof which retains the antigen binding specificity of the parent monoclonal antibody and the effector portion comprises or consists of interleukin-12, or a functional fragment or variant thereof, characterised in the monoclonal antibody having specificity for oncofoetal fibronectin binds to a region of oncofoetal fibronectin other than the ED-B region. The invention further provides nucleic acids encoding the compounds of the invention, and the use of such compounds in medicine, e.g. in the treatment of cancer.
摘要翻译：本发明提供了包含目标特异性部分和效应部分的化合物，其中靶特异性部分包含具有对母体纤连蛋白特异性的单克隆抗体或其保留亲本单克隆抗体的抗原结合特异性的片段或变体，效应部分包含白细胞介素-12或其功能片段或变体，其特征在于具有结合除ED-B区域以外的纤维结合蛋白结合区域的纤维结合蛋白的特异性的单克隆抗体。本发明还提供了编码本发明化合物的核酸，以及这些化合物在医学中的用途，例如，在治疗癌症。

7. 发明申请

WO2018029367A1 COMBINATION THERAPY FOR CANCER 审中-公开
标题翻译：癌症联合治疗
公开(公告)号：WO2018029367A1
公开(公告)日：2018-02-15
申请号：PCT/EP2017/070513
申请日：2017-08-11
申请人： MERCK PATENT GMBH
发明人： LO, Kin-Ming , LAN, Yan
IPC分类号： C07K16/28 , A61K38/17 , C07K14/71 , A61P35/00 , A61K31/282 , A61K31/513 , A61K39/395
摘要： This invention relates generally to a combination therapy for the treatment of cancer, particularly to a combination of (i) a bifunctional molecule comprising a TGFßRII or fragment thereof capable of binding TGFß and an antibody, or antigen binding fragment thereof, that binds to an immune checkpoint protein, such as Programmed Death Ligand 1 (PD-L1) and (ii) at least one additional anti-cancer therapeutic agent.
摘要翻译：本发明一般涉及用于治疗癌症的组合疗法，特别涉及（i）包含能够结合TGF-β1的TGF-β1; RII或其片段的双功能分子的组合; 和结合免疫关卡蛋白如程序性死亡配体1（PD-L1）和（ii）至少一种另外的抗癌治疗剂的抗体或其抗原结合片段。

8. 发明申请

WO2015118175A2 TARGETED TGFβ INHIBITION 审中-公开
标题翻译：靶向TGFβ抑制剂
公开(公告)号：WO2015118175A2
公开(公告)日：2015-08-13
申请号：PCT/EP2015/052781
申请日：2015-02-10
申请人： MERCK PATENT GMBH
发明人： LO, Kin-Ming
IPC分类号： C07K14/435
CPC分类号： C07K16/2896 , A61K38/177 , A61K39/3955 , A61K2039/505 , C07K14/495 , C07K14/71 , C07K16/2827 , C07K16/2863 , C07K16/2866 , C07K2319/00 , C07K2319/33
摘要： This invention relates generally to bifunctional molecules including (a) a TGFβRII or fragment thereof capable of binding TGFβ and (b) an antibody, or antigen binding fragment thereof, that binds to an immune checkpoint protein, such as Programmed Death Ligand 1 (PD-L1), uses of such molecules (e.g., for treating cancer), and methods of making such molecules.
摘要翻译：本发明一般涉及双功能分子，包括（a）能够结合TGFβ的TGFβRII或其片段和（b）结合免疫关卡蛋白的抗体或其抗原结合片段，例如作为程序性死亡配体1（PD-L1），这些分子（例如，用于治疗癌症）的用途以及制造这种分子的方法。

9. 发明申请

WO2016024021A1 SIRP-ALPHA IMMUNOGLOBULIN FUSION PROTEINS 审中-公开
标题翻译： SIRP-ALPHA免疫调节蛋白融合蛋白
公开(公告)号：WO2016024021A1
公开(公告)日：2016-02-18
申请号：PCT/EP2015/068798
申请日：2015-08-14
申请人： MERCK PATENT GMBH
发明人： LO, Kin-Ming , ZIZLSPERGER, Nora , SIRCAR, Aroop
IPC分类号： C07K16/46
CPC分类号： C12N9/16 , A61K38/00 , C07K14/70596 , C07K16/2803 , C07K16/2827 , C07K16/2863 , C07K16/2887 , C07K16/30 , C07K16/32 , C07K2317/31 , C07K2317/622 , C07K2319/33 , C07K2319/74 , C12Y301/03048
摘要： The invention discloses immunoglobulin fusion proteins designed to bind both CD47 and a tumor cell antigen. The immunoglobulin fusion proteins include a SIRPα moiety that binds CD47 and an antigen binding site for a tumor cell antigen.
摘要翻译：本发明公开了设计用于结合CD47和肿瘤细胞抗原的免疫球蛋白融合蛋白。免疫球蛋白融合蛋白包括结合CD47的SIRPα部分和肿瘤细胞抗原的抗原结合位点。

10. 发明授权

EP1966244B1 ANTI-IL-6 ANTIBODIES PREVENTING THE BINDING OF IL-6 COMPLEXED WITH IL-6RALPHA TO GP130 有权
标题翻译：用IL-6RALPHA的结合复合的IL-6与gp130避免抗IL-6抗体
公开(公告)号：EP1966244B1
公开(公告)日：2012-03-21
申请号：EP06829726.6
申请日：2006-12-19
申请人： Merck Patent GmbH
发明人： WAY, Jeffrey C. , GILLIES, Stephen D. , LO, Kin-Ming , LIU, Yuan
IPC分类号： C07K16/24 , A61K39/395 , A61P35/00 , C12N15/13 , C07K19/00 , C07K14/54
CPC分类号： C07K14/5412 , A61K2039/505 , C07K14/7155 , C07K16/248 , C07K16/2866 , C07K16/3023 , C07K16/3053 , C07K16/3061 , C07K2317/24 , C07K2317/32 , C07K2317/56 , C07K2317/73 , C07K2317/76 , C07K2319/30
摘要： The present invention provides anti IL-6 antibodies including an antibody variable region that prevents IL-6 from binding to gp130. The present invention also provides compositions and methods for treating IL-6 related diseases based on the IL-6 antagonists of the invention.

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