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1. 发明申请

WO2014072305A1 ANTI-HER3/HER4 ANTIGEN BINDING PROTEINS BINDING TO THE BETA-HAIRPIN OF HER3 AND THE BETA-HAIRPIN OF HER4 审中-公开
标题翻译：抗HER3 / HER4抗原结合蛋白与HER3的BETA-HAIRPIN和HER4的BETA-HAIRPIN结合
公开(公告)号：WO2014072305A1
公开(公告)日：2014-05-15
申请号：PCT/EP2013/073093
申请日：2013-11-06
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： BOSSENMAIER, Birgit , GEORGES, Guy , GERG, Michael , NIEDERFELLNER, Gerhard , SCHOLZ, Christian , SCHRAEML, Michael
IPC分类号： C07K16/32 , A61K39/395 , A61P35/00 , A61K39/00
CPC分类号： C07K16/2863 , A61K47/6803 , A61K47/6829 , A61K47/6851 , A61K47/6855 , A61K2039/505 , C07K16/32 , C07K2317/24 , C07K2317/33 , C07K2317/34 , C07K2317/55 , C07K2317/73 , C07K2317/75 , C07K2317/77
摘要： The disclosure relates to anti-HER3/HER4 antigen binding proteins, e.g. anti-HER3/HER4 antibodies, that bind to the beta-hairpin of HER3 and the beta-hairpin of HER4, methods for selecting these antigen binding proteins, their preparation and use as medicament.
摘要翻译：本公开涉及抗HER3 / HER4抗原结合蛋白，例如抗HER3 / HER4抗体，其结合HER3的β发夹和HER4的β-发夹，选择这些抗原结合蛋白的方法，其制备和用作药物。

2. 发明申请

WO2014001326A1 METHOD FOR THE SELECTION AND PRODUCTION OF TAILOR-MADE, SELECTIVE AND MULTI-SPECIFIC THERAPEUTIC MOLECULES COMPRISING AT LEAST TWO DIFFERENT TARGETING ENTITIES AND USES THEREOF 审中-公开
标题翻译：用于选择和生产包含至少两个不同目标实体的选择性和选择性和多特异性治疗分子的方法及其用途
公开(公告)号：WO2014001326A1
公开(公告)日：2014-01-03
申请号：PCT/EP2013/063260
申请日：2013-06-25
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： HEINDL, Dieter , HUELSMANN, Peter, Michael , KALUZA, Brigitte , KOPETZKI, Erhard , NIEDERFELLNER, Gerhard , TIEFENTHALER, Georg
IPC分类号： C07K16/00 , C07K16/46 , A61K39/395
CPC分类号： C07K16/00 , C07K16/32 , C07K16/468 , C12Q1/26 , C12Q1/58 , C12Q1/66 , G01N33/53 , G01N33/563
摘要： Herein is reported a method for determining a combination of antigen binding sites comprising the steps of (i) determining the binding specificity and/or affinity and/or effector function and/or in vivo half-life of a multitude of bispecific antibodies prepared by combining each member of a first multitude of antibody Fab fragments or scFv antibody fragments with each member of a second multitude of antibody Fab fragments or scFv antibody fragments, and a linker comprising at one of its termini the second member of the first binding pair and at the respective other terminus the second member of the second binding pair, whereby the first multitude specifically binds to a first cell surface molecule and the second multitude specifically binds to a second cell surface molecule, and (ii) choosing the bispecific antibody with suitable binding specificity and/or affinity and/or effector function and/or in vivo half-life and thereby determining a combination of antigen binding sites.
摘要翻译：本文报道了用于确定抗原结合位点的组合的方法，包括以下步骤：（i）测定通过组合制备的大量双特异性抗体的结合特异性和/或亲和力和/或效应子功能和/或体内半衰期每个成员具有第二大量抗体Fab片段或scFv抗体片段的每个成员的第一大量抗体Fab片段或scFv抗体片段，以及在其末端包含第一结合对的第二个成员和相应的另一个末端是第二结合对的第二个成员，其中第一个人特异性结合第一细胞表面分子，第二个人特异性结合第二细胞表面分子，和（ii）选择具有合适结合特异性的双特异性抗体， /或亲和力和/或效应子功能和/或体内半衰期，从而确定抗原结合位点的组合。

3. 发明申请

WO2018002358A1 IMPROVED ADOPTIVE T-CELL THERAPY 审中-公开
标题翻译：改善采用的T细胞疗法
公开(公告)号：WO2018002358A1
公开(公告)日：2018-01-04
申请号：PCT/EP2017/066375
申请日：2017-06-30
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC. , LUDWIG-MAXIMILIANS-UNIVERSITÄT MÜNCHEN
发明人： KLEIN, Christian , SUSTMANN, Claudio , NIEDERFELLNER, Gerhard , GEIGER, Martina , ENDRES, Stefan , KOBOLD, Sebastian
IPC分类号： C07K16/28 , C07K16/30 , C07K14/71 , C12N5/0783 , A61P35/00
摘要： The present invention generally relates to T-cells, such as CD8+ T-cells, CD4+ T-cells, CD3+ T-cells, γδ T-cells or natural killer (NK) T-cells, transfected / transduced with a fusion protein which is recruited by the use of trivalent, bispecific antibody molecule which specifically binds to / interacts with the extracellular domain of the fusion protein. More precisely, the present invention relates to a kit comprising the nucleic acid molecules, vectors and/or the fusion proteins of the present invention and the trivalent, bispecific antibody molecules of the present invention. Further aspects of the inventions are expression vectors comprising nucleic acid molecules encoding the fusion proteins as well as the trivalent, bispecific antibody molecules. Further, a process for the production of the trivalent, bispecific antibody molecules of the invention and a medicament / pharmaceutical composition comprising said trivalent, bispecific antibody molecules are described. The invention also provides the use of said trivalent, bispecific antibody molecules in a method for the treatment of particular diseases as well as a pharmaceutical compositions / medicament comprising said trivalent, bispecific antibody molecules, wherein said trivalent, bispecific antibody molecule(s) is (are) to be administered in combination with transduced T-cells comprising the fusion protein of the invention. The invention also provides a method for the treatment of particular diseases.
摘要翻译：本发明一般涉及转染的T细胞，如CD8 + T细胞，CD4 + T细胞，CD3 + T细胞，γδT细胞或天然杀伤（NK）T细胞 /用融合蛋白转导，所述融合蛋白通过使用与融合蛋白的细胞外结构域特异性结合/相互作用的三价双特异性抗体分子募集。更确切地说，本发明涉及包含本发明的核酸分子，载体和/或融合蛋白以及本发明的三价双特异性抗体分子的试剂盒。本发明的其他方面是包含编码融合蛋白的核酸分子以及三价双特异性抗体分子的表达载体。此外，描述了生产本发明的三价双特异性抗体分子的方法和包含所述三价双特异性抗体分子的药物/药物组合物。本发明还提供了所述三价双特异性抗体分子在治疗特定疾病的方法中的用途以及包含所述三价双特异性抗体分子的药物组合物/药物，其中所述三价双特异性抗体分子是（）与包含本发明融合蛋白的转导的T细胞组合施用。本发明还提供了治疗特定疾病的方法。

4. 发明申请

WO2016207324A1 BIOMARKERS FOR NAD(+)−DIPHTHAMIDE ADP RIBOSYLTRANSFERASE SENSITIVITY AND RESISTANCE 审中-公开
标题翻译： NAD（+） - DIPHTHAMIDE ADP RIBOSYLTRANSFERASE敏感性和抗性的生物标记
公开(公告)号：WO2016207324A1
公开(公告)日：2016-12-29
申请号：PCT/EP2016/064629
申请日：2016-06-23
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE, INC. , THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
发明人： BRINKMANN, Ulrich , GERG, Michael , STAHL, Sebastian , NIEDERFELLNER, Gerhard , DUCRET, Axel , PASTAN, Ira H.
IPC分类号： G01N33/68 , G01N33/574 , A61K38/00 , A61K47/48
CPC分类号： G01N33/574 , A61K38/45 , A61K47/6815 , C12Y204/02036 , G01N2333/91142 , G01N2800/52
摘要： The invention is based on the finding that cells containing eukaryotic elongation factor 2 (eEF2) that lacks the diphthamide modification at the His715 residue remain sensitive to killing by PE when the cells also contain eEF2 with the diphthamide modification at the His715 residue. Accordingly, the invention provides methods for assessing sensitivity and/or resistance of diseased cells in a patient to treatment with a NAD (+) −diphthamide ADP-ribosyltransferase, the method comprising assaying for the presence of eEF2 protein having diphthamide modification at the His715 residue in a sample containing the diseased cells, wherein the presence of eEF2 protein having diphthamide modification at the His715 residue is indicative that the diseased cells are sensitive to treatment with a NAD (+) −diphthamide ADP-ribosyltrans ferase and/or wherein the absence of eEF2 protein having diphthamide modification at the His715 residue is indicative that the diseased cells are resistant to treatment with a NAD (+) −diphthamide ADP-ribosyltransferase. Also provided are NAD (+) −diphthamide ADP ribosylatransferases for use in methods of medical treatment, monoclonal anti-eEF2 antibodies, methods for assessing increased sensitivity of diseased cells in a patient to treatment with TNFα or other inducer of NFkappaB-signalling pathways or related signalling pathways; and TNFα or other inducers for use in methods of medical treatment.
摘要翻译：本发明是基于以下发现：当His715残基上的细胞也含有二氢叶酸修饰时，细胞也含有eEF2而在His715残基处缺少二硫代叶酸修饰的细胞对PE杀死仍然敏感。因此，本发明提供了用于评估患者中用NAD（+） - 二硫代氨基 - 核糖基转移酶进行治疗的患病细胞的敏感性和/或耐药性的方法，该方法包括在His715残基中测定具有二硫代氨基修饰的eEF2蛋白的存在在含有病变细胞的样品中，其中在His715残基处具有二硫代氨基修饰的eEF2蛋白的存在表明患病细胞对用NAD（+） - 二硫代酰胺ADP-核糖基转移酶处理敏感，和/或其中不存在在His715残基处具有二硫代叶酸修饰的eEF2蛋白表明患病细胞对用NAD（+） - 二硫代氨基酸 - 核糖基转移酶进行治疗具有抗性。还提供了用于医学治疗方法的NAD（+） - 二硫代酰胺ADP核糖基转移酶，单克隆抗eEF2抗体，用于评估患者中患病细胞对TNFα或NFκB信号通路或其他诱导因子治疗的敏感性增加的方法信号通路; 和TNFα或其他诱导剂，用于治疗方法。

5. 发明申请

WO2014072306A1 HER3 ANTIGEN BINDING PROTEINS BINDING TO THE BETA-HAIRPIN OF HER3 审中-公开
标题翻译： HER3抗原结合蛋白与HER3的BETA-HAIRPIN结合
公开(公告)号：WO2014072306A1
公开(公告)日：2014-05-15
申请号：PCT/EP2013/073094
申请日：2013-11-06
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： BOSSENMAIER, Birgit , CASAGOLDA VALLRIBERA, David , GEORGES, Guy , GERG, Michael , NIEDERFELLNER, Gerhard , SCHOLZ, Christian , SCHRAEML, Michael
IPC分类号： C07K16/32 , A61K47/48 , C07K14/195 , C07K14/705
CPC分类号： C07K16/2863 , A61K47/6803 , A61K47/6817 , A61K47/6851 , A61K47/6855 , C07K14/195 , C07K14/71 , C07K16/32 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/70 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C07K2319/00 , C07K2319/55 , C07K2319/70
摘要： The invention relates to anti-HER3 antigen binding proteins, e.g. anti-HER3 antibodies, that bind to the beta-hairpin of HER3, methods for selecting these antigen binding proteins, their preparation and use as medicament.
摘要翻译：本发明涉及抗HER3抗原结合蛋白，例如，抗HER3抗体，其结合HER3的β-发夹，选择这些抗原结合蛋白的方法，其制备和用作药物。

6. 发明申请

WO2015173249A1 HER1 ANTIGEN BINDING PROTEINS BINDING TO THE BETA-HAIRPIN OF HER1 审中-公开
标题翻译： HER1抗原结合蛋白与HER1的BETA-HAIRPIN结合
公开(公告)号：WO2015173249A1
公开(公告)日：2015-11-19
申请号：PCT/EP2015/060491
申请日：2015-05-12
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： BOSSENMAIER, Birgit , GERG, Michael , NIEDERFELLNER, Gerhard , SCHRAEML, Michael , PEESS, Carmen
IPC分类号： C07K16/28 , A61K39/00
CPC分类号： C07K16/3076 , A61K2039/505 , A61K2039/6068 , C07K14/71 , C07K16/2863 , C07K2317/34 , C07K2317/55 , C07K2317/76 , C07K2317/77 , G01N33/6854
摘要： The disclosure relates to anti-HERI antigen binding proteins, e.g. anti-HERI antibodies, that bind to the beta-hairpin of HER1, methods for selecting these antigen binding proteins, their preparation and use as medicament.
摘要翻译：本公开涉及抗HERI抗原结合蛋白，例如结合HER1的β-发夹的抗HERI抗体，选择这些抗原结合蛋白的方法，其制备和用作药物。

7. 发明申请

WO2017055391A1 BISPECIFIC T CELL ACTIVATING ANTIGEN BINDING MOLECULES BINDING MESOTHELIN AND CD3 审中-公开
标题翻译： BISPECIFIC T细胞激活抗体结合分子结合MESOTHELIN和CD3
公开(公告)号：WO2017055391A1
公开(公告)日：2017-04-06
申请号：PCT/EP2016/073173
申请日：2016-09-29
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： BACAC, Marina , FAUTI, Tanja , FREIMOSER-GRUNDSCHOBER, Anne , IMHOF-JUNG, Sabine , KLEIN, Christian , KLOSTERMANN, Stefan , MOLHOJ, Michael , NIEDERFELLNER, Gerhard , REGULA, Joerg Thomas , SCHAEFER, Wolfgang , UMAÑA, Pablo
IPC分类号： C07K16/30 , C07K16/28 , C07K16/46
CPC分类号： C07K16/28 , C07K16/2809 , C07K16/30 , C07K2317/24 , C07K2317/31 , C07K2317/52 , C07K2317/522 , C07K2317/55 , C07K2317/56 , C07K2317/64 , C07K2317/66 , C07K2317/71 , C07K2317/73 , C07K2317/92 , C07K2317/94 , C07K2319/00
摘要： The present disclosure generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present disclosure relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The disclosure further relates to methods for producing the bispecific antigen binding molecules of the disclosure, and to methods of using these bispecific antigen binding molecules in the treatment of disease.
摘要翻译：本公开通常涉及用于T细胞活化和对特异性靶细胞的重新定向的新型双特异性抗原结合分子。此外，本公开涉及编码这种双特异性抗原结合分子的多核苷酸，以及包含这种多核苷酸的载体和宿主细胞。本公开还涉及用于产生本公开内容的双特异性抗原结合分子的方法，以及在治疗疾病中使用这些双特异性抗原结合分子的方法。

8. 发明申请

WO2016146833A1 BIOMARKERS FOR NAD(+)-DIPHTHAMIDE ADP RIBOSYLTRANSFERASE RESISTANCE 审中-公开
标题翻译：生物标记NAD（+） - 二苯胺ADP抗氧化剂耐药性
公开(公告)号：WO2016146833A1
公开(公告)日：2016-09-22
申请号：PCT/EP2016/056028
申请日：2016-03-18
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： BRINKMANN, Ulrich , DENGL, Stefan , NIEDERFELLNER, Gerhard , DA SILVA MATEUS SEIDL, Ana Rita , STAHL, Sebastian
IPC分类号： G01N33/68
CPC分类号： G01N33/68 , G01N2333/91142 , G01N2440/14 , G01N2800/52
摘要： Phosphorylation of the serine residue at position 615 of eukaryotic elongation factor 2 (eEF2) protein is associated with resistance to NAD(+)-diphthamide ADP-ribosyltransferase enzymes such as Pseudomonas exotoxin, diphtheria toxin and cholix toxin, which are used in targeted immunotherapies. Methods of determining resistance and related treatments are provided.
摘要翻译：真核延伸因子2（eEF2）蛋白的615位丝氨酸残基的磷酸化与NAD（+） - 二硫代酰胺ADP-核糖基转移酶（如假单胞菌外毒素，白喉毒素和胆固醇毒素）的抗性相关，用于靶向免疫疗法。提供了确定抵抗力和相关治疗方法。

9. 发明申请

WO2015173250A1 ANTI-HER3 ANTIBODIES BINDING TO THE BETA-HAIRPIN OF HER3 审中-公开
标题翻译：抗HER3抗体与HER3的BETA-HAIRPIN结合
公开(公告)号：WO2015173250A1
公开(公告)日：2015-11-19
申请号：PCT/EP2015/060492
申请日：2015-05-12
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： BOSSENMAIER, Birgit , GERG, Michael , KRONER, Frank , NIEDERFELLNER, Gerhard , SCHRAEML, Michael , PEESS, Carmen , BUICK, Richard
IPC分类号： C07K16/32 , C07K16/34 , A61K39/395 , A61P35/00
CPC分类号： C07K16/2863 , A61K47/6871 , A61K2039/505 , A61K2039/6068 , C07K16/32 , C07K16/34 , C07K2317/24 , C07K2317/33 , C07K2317/34 , C07K2317/55 , C07K2317/73 , C07K2317/76 , C07K2317/77 , C07K2317/92
摘要： The disclosure relates to specific anti-HER3 antibodies, that bind to the beta-hairpin of HER3, their preparation and use as medicament.
摘要翻译：本公开涉及结合HER3的β-发夹的特异性抗HER3抗体，其制备和用作药物。

10. 发明申请

WO2015082446A1 TREATMENT OF CANCER USING AN ANTI-CDCP1 ANTIBODY AND A TAXANE 审中-公开
标题翻译：使用抗CDCP1抗体和TAXANE治疗癌症
公开(公告)号：WO2015082446A1
公开(公告)日：2015-06-11
申请号：PCT/EP2014/076200
申请日：2014-12-02
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： BOSSENMAIER, Birgit , LIFKE, Alexander , NIEDERFELLNER, Gerhard , NOPORA, Adam , KOLLMORGEN, Gwendlyn , KRIETER, Oliver
IPC分类号： A61K39/395 , C07K16/28 , C07K16/30
CPC分类号： A61K45/06 , A61K31/337 , A61K39/39558 , C07K16/2896 , C07K16/30 , C07K2319/00 , A61K2300/00
摘要： The present invention relates to the use of an anti-CDCP1 antibody for the treatment of cancer, in combination with a taxane. The invention also relates to methods of treating cancer using an anti-CDCP1 antibody and a taxane.
摘要翻译：本发明涉及抗CDCP1抗体与紫杉烷联合治疗癌症的用途。本发明还涉及使用抗CDCP1抗体和紫杉烷治疗癌症的方法。

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