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1. 发明授权

US09688768B2 Silent Fc variants of anti-CD40 antibodies 有权
公开(公告)号：US09688768B2
公开(公告)日：2017-06-27
申请号：US14946170
申请日：2015-11-19
申请人： Christoph Heusser , James Rush , Karen Vincent
发明人： Christoph Heusser , James Rush , Karen Vincent
IPC分类号： A61K39/395 , C07K16/28 , A61K39/00
CPC分类号： C07K16/2878 , A61K2039/505 , C07K16/2866 , C07K2317/52 , C07K2317/565 , C07K2317/60 , C07K2317/71
摘要： The present invention relates to silent Fc variants of anti-CD40 antibodies and compositions and methods of use of said antibodies for treating pathological disorders such as autoimmune and inflammatory disorders and/or for preventing or reducing the risk of graft rejection in transplantation.

2. 发明授权

US09221913B2 Silent Fc variants of anti-CD40 antibodies 有权
标题翻译：抗CD40抗体的沉默Fc变体
公开(公告)号：US09221913B2
公开(公告)日：2015-12-29
申请号：US14452647
申请日：2014-08-06
申请人： Christoph Heusser , James Rush , Karen Vincent
发明人： Christoph Heusser , James Rush , Karen Vincent
IPC分类号： A61K39/395 , C07K16/28 , A61K39/00
CPC分类号： C07K16/2878 , A61K2039/505 , C07K16/2866 , C07K2317/52 , C07K2317/565 , C07K2317/60 , C07K2317/71
摘要： Anti-CD40 antibodies have not been reported to induce hemostatic events in patients, however elevations in pancreatic enzymes in B cell lymphoma patients receiving the anti-CD40 Ab Chir12.12 and the possible risk of pancreatitis precludes the use of this Fc-competent anti-CD40 antibody in chronic autoimmune disease and transplantation for safety reasons. We therefore generated Fc-silent IgG1 anti-CD40 antibodies (mAb1, mAb2 and mAb3) unable to mediate antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) both in vitro and in vivo. mAb1 was able to prolong non-human primate renal allograft survival in combination with sub-therapeutic doses of cyclosporine. In addition, mAb1 was able to completely suppress primary and secondary antibody responses to immunization with a T cell-dependent antigen. Crucially, there was no evidence of hemostatic events or abnormal pancreatic histology in either the transplant or immunization study. Collectively these results suggest mAb1 would be a safe and efficacious therapeutic, and could be used to treat patients suffering from B lymphocyte and antigen presenting cell driven autoimmune disease or undergoing allograft transplant where CD4O-CD154 interactions are involved in contributing to pathology.
摘要翻译：抗CD40抗体尚未报道在患者中诱导止血事件，但是接受抗CD40 Ab Chir12.12的B细胞淋巴瘤患者胰腺酶升高以及胰腺炎的可能风险可能导致使用此抗Fc抗体抗体， CD40抗体在慢性自身免疫性疾病和移植中的安全性原因。因此，我们在体外和体内产生了不能介导抗体依赖性细胞毒性（ADCC）或补体依赖性细胞毒性（CDC）的Fc-沉默IgG1抗CD40抗体（mAb1，mAb2和mAb3）。 mAb1与亚治疗剂量的环孢菌素组合能够延长非人灵长类动物肾同种异体移植物存活。此外，mAb1能够完全抑制用T细胞依赖性抗原免疫的一抗和二抗。至关重要的是，在移植或免疫研究中没有止血事件或异常胰组织学的迹象。总体而言，这些结果表明，mAb1将是一种安全有效的治疗方法，可用于治疗患有B淋巴细胞和抗原呈递细胞驱动的自身免疫性疾病或进行同种异体移植的患者，其中CD4O-CD154相互作用涉及病理学。

3. 发明授权

US08828396B2 Silent Fc variants of anti-CD40 antibodies 有权
标题翻译：抗CD40抗体的沉默Fc变体
公开(公告)号：US08828396B2
公开(公告)日：2014-09-09
申请号：US13295141
申请日：2011-11-14
申请人： Christoph Heusser , James Rush , Karen Vincent
发明人： Christoph Heusser , James Rush , Karen Vincent
IPC分类号： A61K39/395 , C07K16/28 , A61K39/00
CPC分类号： C07K16/2878 , A61K2039/505 , C07K16/2866 , C07K2317/52 , C07K2317/565 , C07K2317/60 , C07K2317/71
摘要： The present invention relates to silent Fc variants of anti-CD40 antibodies and compositions and methods of use of said antibodies for treating pathological disorders such as autoimmune and inflammatory disorders and/or for preventing or reducing the risk of graft rejection in transplantation.
摘要翻译：本发明涉及抗CD40抗体的沉默性Fc变体，以及所述抗体用于治疗诸如自身免疫性和炎症性疾病等病理性疾病和/或预防或降低移植排斥反应风险的组合物和方法。

4. 发明授权

US6020153A Chimeric antibodies 失效
标题翻译：嵌合抗体
公开(公告)号：US6020153A
公开(公告)日：2000-02-01
申请号：US307087
申请日：1994-09-16
申请人： Norman Hardman , Laura Lee Gill , Ronald F. J. de Winter , Kathrin Wagner , Christoph Heusser
发明人： Norman Hardman , Laura Lee Gill , Ronald F. J. de Winter , Kathrin Wagner , Christoph Heusser
IPC分类号： C07K16/30 , C07K16/46 , C12P21/08 , G01N33/574 , C12N15/00 , C07H21/04 , C12N5/00 , C12P21/06 , C12D21/08
CPC分类号： C07K16/3007 , C07K16/462 , A61K2039/505 , C07K2317/24 , C07K2319/00 , C07K2319/02 , C07K2319/33
摘要： The invention relates to murine/human chimeric monoclonal antibodies with high specificity to and affinity for human carcinoembryonic antigen (CEA), derivatives thereof, processes for the preparation of these antibodies and their derivatives, DNAs coding for heavy and light chains of these antibodies, processes for the preparation of said DNAs, mammalian cell lines that produce and secrete the antibodies and processes for the preparation of said cell lines. The chimeric antibodies and their derivatives are used for clinical purposes in vitro and in vivo, especially for the diagnosis of cancer, for localization and in vivo imaging of tumors, for therapy, e.g. site-directed delivery of cytotoxins, and similar purposes. The invention also concerns test kits and pharmaceutical compositions containing said chimeric monoclonal antibodies and/or derivatives thereof.
摘要翻译：本发明涉及对人癌胚抗原（CEA）具有高特异性和亲和力的鼠/人嵌合单克隆抗体，其衍生物，制备这些抗体及其衍生物的方法，编码这些抗体重链和轻链的DNA，过程用于制备所述DNA，产生和分泌抗体的哺乳动物细胞系和用于制备所述细胞系的方法。嵌合抗体及其衍生物在体外和体内用于临床目的，特别是用于诊断癌症，用于肿瘤的定位和体内成像，用于治疗，例如癌症。细胞毒素的定点递送和类似目的。本发明还涉及含有所述嵌合单克隆抗体和/或其衍生物的测试试剂盒和药物组合物。

5. 发明授权

US08574573B2 Anti-IL12Rbeta1 antibodies and their use in treating autoimmune and inflammatory disorders 失效
标题翻译：抗IL12Rbeta1抗体及其在治疗自身免疫性和炎症性疾病中的应用
公开(公告)号：US08574573B2
公开(公告)日：2013-11-05
申请号：US13252721
申请日：2011-10-04
申请人： José M. Carballido Herrera , Stefan Hartle , Christoph Heusser , Ingo Klagge , Andrea Polzer , Christoph Schwaerzler , Gabriela Wochnik-Veltrup
发明人： José M. Carballido Herrera , Stefan Hartle , Christoph Heusser , Ingo Klagge , Andrea Polzer , Christoph Schwaerzler , Gabriela Wochnik-Veltrup
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C12N9/0069 , C07K16/2866 , C07K2317/33 , C07K2317/34 , C07K2317/55 , C07K2317/76 , C07K2317/92 , C12Q1/66
摘要： The present invention relates to antibodies that specifically bind to IL12Rβ1, the non-signal transducing chain of both the heterodimeric IL12 and IL23 receptors. The invention more specifically relates to specific antibodies that are IL12 and IL23 receptor antagonists capable of inhibiting IL12/1L18 induced IFNγ production of blood cells and compositions and methods of use for said antibodies to treat pathological disorders that can be treated by inhibiting IFNγ production, IL12 and/IL23 signaling, such as rheumatoid arthritis, psoriasis or inflammatory bowel diseases or other autoimmune and inflammatory disorders.
摘要翻译：本发明涉及特异性结合异源二聚体IL12和IL23受体的非信号转导链IL12Rβ1的抗体。本发明更具体地涉及能够抑制IL12 / 1L18诱导的血细胞IFNγ产生的IL12和IL23受体拮抗剂的特异性抗体，以及用于所述抗体治疗可通过抑制IFNγ产生治疗的病理学障碍的组合物和方法，IL12 和/ IL23信号，例如类风湿性关节炎，牛皮癣或炎性肠病或其它自身免疫性和炎症性疾病。

6. 发明授权

US08106163B2 Compositions and methods of use for therapeutic antibodies 有权
标题翻译：用于治疗性抗体的组合物和方法
公开(公告)号：US08106163B2
公开(公告)日：2012-01-31
申请号：US12503175
申请日：2009-07-15
申请人： Christoph Heusser , Julia Neugebauer , Eveline Schaadt , Stefanie Urlinger , Maximilian Woisetschlaeger
发明人： Christoph Heusser , Julia Neugebauer , Eveline Schaadt , Stefanie Urlinger , Maximilian Woisetschlaeger
IPC分类号： C07K16/00
CPC分类号： C07K16/2878 , A61K2039/505 , C07K2317/21 , C07K2317/34 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/74 , C07K2317/76
摘要： The present invention relates to antibodies that specifically bind to the BAFF receptor (BAFFR). The invention more specifically relates to specific antibodies that are BAFFR antagonists with in vivo B cell depleting activity and compositions and methods of use for said antibodies to treat pathological disorders that can be treated by killing or depleting B cells, such as systemic lupus erythematosus or rheumatoid arthritis or other autoimmune diseases or lymphomas, leukemias and myelomas.
摘要翻译：本发明涉及特异性结合BAFF受体（BAFFR）的抗体。本发明更具体地涉及具有体内B细胞消耗活性的BAFFR拮抗剂的特异性抗体，以及用于治疗可通过杀死或消耗B细胞如系统性红斑狼疮或类风湿病治疗的病理学障碍的所述抗体的组合物和方法关节炎或其他自身免疫性疾病或淋巴瘤，白血病和骨髓瘤。

7. 发明授权

US5843708A Chimeric antibodies 失效
公开(公告)号：US5843708A
公开(公告)日：1998-12-01
申请号：US462371
申请日：1995-06-05
申请人： Norman Hardman , Laura Lee Gill , Ronald F.J. de Winter , Kathrin Wagner , Christoph Heusser
发明人： Norman Hardman , Laura Lee Gill , Ronald F.J. de Winter , Kathrin Wagner , Christoph Heusser
IPC分类号： C07K16/30 , C07K16/46 , C12P21/08 , C12N15/00 , C07K16/00 , C12P21/04 , C12P21/06
CPC分类号： C07K16/3007 , C07K16/462 , A61K2039/505 , C07K2317/24 , C07K2319/00 , C07K2319/02 , C07K2319/33
摘要： The invention relates to murine/human chimeric monoclonal antibodies with high specificity to and affinity for human carcinoembryonic antigen (CEA), derivatives thereof, processes for the preparation of these antibodies and their derivatives, DNAs coding for heavy and light chains of these antibodies, processes for the preparation of said DNAs, mammalian cell lines that produce and secrete the antibodies and processes for the preparation of said cell lines. The chimeric antibodies and their derivatives are used for clinical purposes in vitro and in vivo, especially for the diagnosis of cancer, for localization and in vivo imaging of tumors, for therapy, e.g. site-directed delivery of cytotoxins, and similar purposes. The invention also concerns test kits and pharmaceutical compositions containing said chimeric monoclonal antibodies and/or derivatives thereof.

8. 发明授权

US09458240B2 Anti-BAFFR antibody formulations 有权
标题翻译：抗BAFFR抗体制剂
公开(公告)号：US09458240B2
公开(公告)日：2016-10-04
申请号：US13991984
申请日：2011-12-08
申请人： Marta Cosenza , Christoph Heusser , Julia Neugebauer , Eveline Schaadt , Stefanie Urlinger , Maximilian Woisetschlaeger
发明人： Marta Cosenza , Christoph Heusser , Julia Neugebauer , Eveline Schaadt , Stefanie Urlinger , Maximilian Woisetschlaeger
IPC分类号： A61K39/395 , C07K16/18 , C07K16/28 , A61K9/00 , A61K9/08 , A61K9/19 , A61K47/18 , A61K47/26 , C07K14/715 , A61K39/00
CPC分类号： C07K16/2878 , A61K9/0019 , A61K9/08 , A61K9/19 , A61K39/39533 , A61K39/3955 , A61K39/39591 , A61K47/10 , A61K47/183 , A61K47/26 , A61K2039/505 , C07K2317/21 , C07K2317/56 , C07K2317/565 , C07K2317/73
摘要： Anti-BAFFR antibodies are formulated as lyophilisate or liquid formulation. The lyophilisates can be reconstituted to give a solution with a high concentration of the antibody active ingredient for delivery to a patient without high levels of antibody aggregation. The lyophilisate can be reconstituted with an aqueous reconstituent to provide an aqueous composition in which the antibody has a concentration of at least 50 mg/ml. The lyophilisate or aqueous pharmaceutical composition may include one or more of a sugar, a buffering agent, a surfactant, and/or a free amino acid.
摘要翻译：抗BAFFR抗体配制成冻干液或液体制剂。可以重构冻干物以产生具有高浓度抗体活性成分的溶液，用于递送至患者，而不需要高水平的抗体聚集。可以用水重构物重构冻干物，以提供其中抗体具有至少50mg / ml浓度的水性组合物。冻干物或水性药物组合物可以包括糖，缓冲剂，表面活性剂和/或游离氨基酸中的一种或多种。

9. 发明授权

US09382326B2 Compositions and methods of use for therapeutic antibodies 有权
标题翻译：用于治疗性抗体的组合物和方法
公开(公告)号：US09382326B2
公开(公告)日：2016-07-05
申请号：US13326569
申请日：2011-12-15
申请人： Christoph Heusser , Julia Neugebauer , Eveline Schaadt , Stefanie Urlinger , Maximilian Woisetschlaeger
发明人： Christoph Heusser , Julia Neugebauer , Eveline Schaadt , Stefanie Urlinger , Maximilian Woisetschlaeger
IPC分类号： C07K16/00 , C07K16/28 , A61K39/00
CPC分类号： C07K16/2878 , A61K2039/505 , C07K2317/21 , C07K2317/34 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/74 , C07K2317/76
摘要： The present invention relates to antibodies that specifically bind to the BAFF receptor (BAFFR). The invention more specifically relates to specific antibodies that are BAFFR antagonists with in vivo B cell depleting activity and compositions and methods of use for said antibodies to treat pathological disorders that can be treated by killing or depleting B cells, such as systemic lupus erythematosus or rheumatoid arthritis or other autoimmune diseases or lymphomas, leukemias and myelomas.
摘要翻译：本发明涉及特异性结合BAFF受体（BAFFR）的抗体。本发明更具体地涉及具有体内B细胞消耗活性的BAFFR拮抗剂的特异性抗体，以及用于治疗可通过杀死或消耗B细胞如系统性红斑狼疮或类风湿病治疗的病理学障碍的所述抗体的组合物和方法关节炎或其他自身免疫性疾病或淋巴瘤，白血病和骨髓瘤。

10. 发明授权

US09340620B2 Compositions and methods of use for therapeutic antibodies 有权
公开(公告)号：US09340620B2
公开(公告)日：2016-05-17
申请号：US13326514
申请日：2011-12-15
申请人： Christoph Heusser , Julia Neugebauer , Eveline Schaadt , Stefanie Urlinger , Maximilian Woisetschlaeger
发明人： Christoph Heusser , Julia Neugebauer , Eveline Schaadt , Stefanie Urlinger , Maximilian Woisetschlaeger
IPC分类号： A61K39/395 , C07K16/28 , A61K39/00
CPC分类号： C07K16/2878 , A61K2039/505 , C07K2317/21 , C07K2317/34 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/74 , C07K2317/76
摘要： The present invention relates to antibodies that specifically bind to the BAFF receptor (BAFFR). The invention more specifically relates to specific antibodies that are BAFFR antagonists with in vivo B cell depleting activity and compositions and methods of use for said antibodies to treat pathological disorders that can be treated by killing or depleting B cells, such as systemic lupus erythematosus or rheumatoid arthritis or other autoimmune diseases or lymphomas, leukemias and myelomas.

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