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1. 发明申请

US20120046450A1 Modulation Of Antibody Effector Function By Hinge Domain Engineering 有权
标题翻译：通过铰链域工程调制抗体效应器功能
公开(公告)号：US20120046450A1
公开(公告)日：2012-02-23
申请号：US13190199
申请日：2011-07-25
申请人： William Dall'Acqua , Herren Wu , Melissa Damschroder , Jose Casas-Finet
发明人： William Dall'Acqua , Herren Wu , Melissa Damschroder , Jose Casas-Finet
IPC分类号： C07K16/18 , C07H21/00
CPC分类号： C07K16/18 , C07K16/00 , C07K16/2866 , C07K2317/53 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/734
摘要： The present invention relates to novel molecules (Fc variants) comprising at least one antigen binding region and an Fc region that further comprises a modified hinge which alters the binding of Fc to one or more Fc ligand (e.g., FcγRs) and/or modulates effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more FcγR and/or C1q. Additionally, the Fc variants have altered antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variants particularly for therapeutic purposes.
摘要翻译：本发明涉及包含至少一个抗原结合区和Fc区的新分子（Fc变体），其还包含修饰的铰链，其改变Fc与一个或多个Fc配体（例如FcγR）的结合和/或调节效应子功能。更具体地，本发明提供了对一种或多种FcγR和/或C1q具有修饰的结合亲和力的Fc变体。另外，Fc变体具有改变的抗体依赖性细胞介导的细胞毒性（ADCC）和/或补体依赖性细胞毒性（CDC）活性。本发明还提供了用于所述Fc变体的应用的方法和方案，特别是用于治疗目的。

2. 发明申请

US20100189718A1 MOLECULES WITH EXTENDED HALF-LIVES, COMPOSITIONS AND USES THEREOF 有权
标题翻译：具有扩展的半衰期，组合物和其用途的分子
公开(公告)号：US20100189718A1
公开(公告)日：2010-07-29
申请号：US12691433
申请日：2010-01-21
申请人： William Dall'Acqua , Leslie S. Johnson , Elizabeth Sally Ward
发明人： William Dall'Acqua , Leslie S. Johnson , Elizabeth Sally Ward
IPC分类号： A61K39/395 , C07K16/00 , C07H21/04 , C12N5/10 , A61P31/12 , C12Q1/70
CPC分类号： C07K16/283 , A61K38/00 , A61K39/00 , A61K47/48507 , A61K47/6835 , A61K49/0002 , A61K49/0004 , A61K2039/505 , C07K2/00 , C07K14/70503 , C07K16/00 , C07K2317/14 , C07K2317/21 , C07K2317/24 , C07K2317/52 , C07K2317/53 , C07K2317/94 , C07K2319/00 , C07K2319/30 , Y10S435/81
摘要： The present invention provides molecules, including IgGs, non-IgG immunoglobulins, proteins and non-protein agents, that have increased in vivo half-lives due to the presence of an IgG constant domain, or a portion thereof that binds the FcRn, having one or more amino acid modifications that increase the affinity of the constant domain or fragment for FcRn. Such proteins and molecules with increased half-lives have the advantage that smaller amounts and or less frequent dosing is required in the therapeutic, prophylactic or diagnostic use of such molecules.
摘要翻译：本发明提供了由于存在IgG恒定结构域或其结合FcRn的部分而具有增加的体内半衰期的IgG，非IgG免疫球蛋白，蛋白质和非蛋白质试剂的分子，其具有一个或更多的氨基酸修饰，其增加FcRn的恒定结构域或片段的亲和力。具有增加的半衰期的这种蛋白质和分子具有在这种分子的治疗，预防或诊断使用中需要更少量和/或更低频率给药的优点。

3. 发明申请

US20100145028A1 Increasing The Production Of Recombinant Antibodies In Mammalian Cells By Site-Directed Mutagenesis 审中-公开
标题翻译：通过定点突变增加哺乳动物细胞中重组抗体的产生
公开(公告)号：US20100145028A1
公开(公告)日：2010-06-10
申请号：US12706264
申请日：2010-02-16
申请人： William DALL'ACQUA , Herren WU , Melissa DAMSCHRODER
发明人： William DALL'ACQUA , Herren WU , Melissa DAMSCHRODER
IPC分类号： C07K16/00 , C12P21/00
CPC分类号： C07K16/2866 , C07K16/00 , C07K16/2848 , C07K2317/24 , C07K2317/565 , C07K2317/567 , C07K2317/92 , C12N2510/02
摘要： The present invention relates to a reliable, reproducible method for improving the producibility of an antibody. More specifically, this invention provides a method for modifying the heavy chain of an antibody to improve its producibility in eukaryotic cells. Additionally, the method of the invention may improve both antibody producibility and one or more antigen binding characteristics. The invention further provides modified antibodies which are better produced and which have either no change in their antigen binding characteristics or exhibit improved antigen binding characteristics.
摘要翻译：本发明涉及提高抗体可生产性的可靠，可重现的方法。更具体地，本发明提供了修饰抗体重链以改善其在真核细胞中的可生产性的方法。此外，本发明的方法可以改善抗体可产生性和一种或多种抗原结合特征。本发明还提供了更好地产生并且其抗原结合特征没有变化或表现出改善的抗原结合特征的修饰抗体。

4. 发明授权

US07704497B2 Molecules with extended half-lives, compositions and uses thereof 有权
标题翻译：具有延长半衰期，组成和用途的分子
公开(公告)号：US07704497B2
公开(公告)日：2010-04-27
申请号：US11649455
申请日：2007-01-03
申请人： William Dall'Acqua , Leslie S. Johnson , Elizabeth Sally Ward
发明人： William Dall'Acqua , Leslie S. Johnson , Elizabeth Sally Ward
IPC分类号： C07K16/00 , A61K39/395 , C12P21/08 , C12N1/00
CPC分类号： C07K16/283 , A61K38/00 , A61K39/00 , A61K47/48507 , A61K47/6835 , A61K49/0002 , A61K49/0004 , A61K2039/505 , C07K2/00 , C07K14/70503 , C07K16/00 , C07K2317/14 , C07K2317/21 , C07K2317/24 , C07K2317/52 , C07K2317/53 , C07K2317/94 , C07K2319/00 , C07K2319/30 , Y10S435/81
摘要： The present invention provides molecules, including IgGs, non-IgG immunoglobulins, proteins and non-protein agents, that have increased in vivo half-lives due to the presence of an IgG constant domain, or a portion thereof that binds the FcRn, having one or more amino acid modifications that increase the affinity of the constant domain or fragment for FcRn. Such proteins and molecules with increased half-lives have the advantage that smaller amounts and or less frequent dosing is required in the therapeutic, prophylactic or diagnostic use of such molecules.
摘要翻译：本发明提供了由于存在IgG恒定结构域或其结合FcRn的部分而具有增加的体内半衰期的IgG，非IgG免疫球蛋白，蛋白质和非蛋白质试剂的分子，其具有一个或更多的氨基酸修饰，其增加FcRn的恒定结构域或片段的亲和力。具有增加的半衰期的这种蛋白质和分子具有在这种分子的治疗，预防或诊断使用中需要更少量和/或更低频率给药的优点。

5. 发明授权

US07371383B2 Recombinant anti-interleukin-9 antibodies 失效
标题翻译：重组抗白细胞介素-9抗体
公开(公告)号：US07371383B2
公开(公告)日：2008-05-13
申请号：US10412703
申请日：2003-04-11
申请人： Jennifer Lynne Reed , William Dall'Acqua , Jacques Van Snick , Jean-Christophe Renauld , Francoise Cormont , Catherine Uyttenhove
发明人： Jennifer Lynne Reed , William Dall'Acqua , Jacques Van Snick , Jean-Christophe Renauld , Francoise Cormont , Catherine Uyttenhove
IPC分类号： A61K39/395
CPC分类号： C07K16/244 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/76
摘要： The application describes neutralizing chimeric and humanized anti-human IL-9 antibodies, and the use thereof to identify neutralizing epitopes on human IL-9 and as medicaments to prevent and treat asthma, bronchial hyperresponsiveness, atopic allergy, and other related disorders. Particularly disclosed are recombinant antibodies derived from three murine anti-human IL-9 antibodies identified infra as MH9A3, MH9D1, and MH9L1.
摘要翻译：本申请描述了中和嵌合和人源化抗人IL-9抗体，以及其用于鉴定人IL-9上的中和表位以及用于预防和治疗哮喘，支气管高反应性，特应性变态反应和其它相关疾病的药物。特别公开的是衍生自以下鉴定的三种鼠抗人IL-9抗体作为MH9A3，MH9D1和MH9L1的重组抗体。

6. 发明申请

US20060115485A1 Methods of preventing and treating RSV infections and related conditions 审中-公开
标题翻译：预防和治疗RSV感染和相关病症的方法
公开(公告)号：US20060115485A1
公开(公告)日：2006-06-01
申请号：US11263230
申请日：2005-10-31
申请人： Genevieve Losonsky , Edward Connor , James Young , Herren Wu , William Dall'Acqua
发明人： Genevieve Losonsky , Edward Connor , James Young , Herren Wu , William Dall'Acqua
IPC分类号： A61K39/42
CPC分类号： C07K16/1027 , A61K2039/505 , A61K2039/543 , C07K2317/21 , C07K2317/24 , C07K2317/52 , C07K2317/55 , C07K2317/565 , C07K2317/567 , C07K2317/72 , C07K2317/92 , C07K2317/94
摘要： The present invention provides methods for preventing, managing, treating and/or ameliorating a Respiratory Syncytial Virus (RSV) infection (e.g., acute RSV disease, or a RSV upper respiratory tract infection (URI) and/or lower respiratory tract infection (LRI)), otitis media (preferably, stemming from, caused by or associated with a RSV infection, such as a RSV URI and/or LRI), and/or a symptom or respiratory condition relating thereto (e.g., asthma, wheezing, and/or reactive airway disease (RAD)) in a subject, comprising administering to said human an effective amount of one or more antibodies that immunospecifically bind to one or more RSV antigens with a high affinity and/or high avidity. In some embodiments, one or more antibodies comprise a modified IgG constant domain, or FcRn-binding fragment thereof resulting in longer in vivo serum half-life. In particular embodiments the methods of the invention comprising administering to subject an effective amount of one or more modified antibodies that immunospecifically bind to one or more RSV antigens with an association rate (kon) of at least 2×105 M−1s−1 and a dissociation rate (koff) of less than 5×10−4 s−1.
摘要翻译：本发明提供了用于预防，治疗和/或改善呼吸道合胞病毒（RSV）感染（例如急性RSV疾病或RSV上呼吸道感染（URI））和/或下呼吸道感染（LRI）的方法，），中耳炎（优选来源于，由RSV感染引起或与RSV感染相关联，例如RSV URI和/或LRI），和/或与其相关的症状或呼吸病症（例如，哮喘，喘鸣和/或反应性气道疾病（RAD）），包括向所述人施用有效量的一种或多种以高亲和力和/或高亲合力免疫特异性结合一种或多种RSV抗原的抗体。在一些实施方案中，一种或多种抗体包含修饰的IgG恒定结构域或其FcRn结合片段，导致更长的体内血清半衰期。在具体实施方案中，本发明的方法包括施用有效量的一种或多种经免疫特异性结合一种或多种RSV抗原的修饰的抗体，其具有至少2×10 6的结合速率（kNI）小于5×10-6的解离速率（k >） 4 -1 。

7. 发明授权

US08697396B2 Modulation of antibody effector function by hinge domain engineering 有权
标题翻译：通过铰链域工程调节抗体效应子功能
公开(公告)号：US08697396B2
公开(公告)日：2014-04-15
申请号：US13190199
申请日：2011-07-25
申请人： William Dall'Acqua , Herren Wu , Melissa Damschroder , Jose Casas-Finet
发明人： William Dall'Acqua , Herren Wu , Melissa Damschroder , Jose Casas-Finet
IPC分类号： C12P21/04 , C12N15/00 , C07K16/00
CPC分类号： C07K16/18 , C07K16/00 , C07K16/2866 , C07K2317/53 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/734
摘要： The present invention relates to novel molecules (Fc variants) comprising at least one antigen binding region and an Fc region that further comprises a modified hinge which alters the binding of Fc to one or more Fc ligand (e.g., FcγRs) and/or modulates effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more FcγR and/or C1q. Additionally, the Fc variants have altered antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variants particularly for therapeutic purposes.
摘要翻译：本发明涉及包含至少一个抗原结合区和Fc区的新分子（Fc变体），其还包含修饰的铰链，其改变Fc与一个或多个Fc配体（例如FcγR）的结合和/或调节效应子功能。更具体地，本发明提供了对一种或多种FcγR和/或C1q具有修饰的结合亲和力的Fc变体。另外，Fc变体具有改变的抗体依赖性细胞介导的细胞毒性（ADCC）和/或补体依赖性细胞毒性（CDC）活性。本发明还提供了用于所述Fc变体的应用的方法和方案，特别是用于治疗目的。

8. 发明授权

US08323653B2 Humanized anti-CD19 antibodies and their use in treatment of oncology, transplantation and autoimmune disease 有权
标题翻译：人源化抗CD19抗体及其在治疗肿瘤，移植和自身免疫疾病中的应用
公开(公告)号：US08323653B2
公开(公告)日：2012-12-04
申请号：US11852106
申请日：2007-09-07
申请人： Melissa Damschroder , Peter Kiener , Herren Wu , William Dall'Acqua , Ronald Herbst , Anthony Coyle
发明人： Melissa Damschroder , Peter Kiener , Herren Wu , William Dall'Acqua , Ronald Herbst , Anthony Coyle
IPC分类号： C07K16/28 , C07K16/30 , A61K39/395
CPC分类号： C07K16/2803 , A61K2039/505 , C07K16/2896 , C07K16/3061 , C07K2317/24 , C07K2317/41 , C07K2317/52 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/73 , C07K2317/732 , C07K2317/77 , C07K2317/92
摘要： The present invention provides chimeric and humanized versions of anti-CD19 mouse monoclonal antibodies. The invention further relates to pharmaceutical compositions, immunotherapeutic compositions, and methods using therapeutic antibodies that bind to the human CD19 antigen and that may mediate ADCC, CDC, and/or apoptosis for the treatment of B cell diseases and disorders, such as, but not limited to, B cell malignancies, for the treatment and prevention of autoimmune disease, and for the treatment and prevention of graft-versus-host disease (GVHD), humoral rejection, and post-transplantation lymphoproliferative disorder in human transplant recipients.
摘要翻译：本发明提供抗CD19小鼠单克隆抗体的嵌合和人源化形式。本发明进一步涉及药物组合物，免疫治疗组合物和使用结合人CD19抗原并且可介导ADCC，CDC和/或细胞凋亡以治疗B细胞疾病和病症的治疗性抗体的方法，例如但不限于B细胞恶性肿瘤，用于治疗和预防自身免疫疾病，以及用于治疗和预防人类移植受体中移植物抗宿主病（GVHD），体液排斥和移植后淋巴增殖性疾病。

9. 发明申请

US20120134984A1 MOLECULES WITH EXTENDED HALF-LIVES AND USES THEREOF 审中-公开
标题翻译：具有扩展性半衰期的分子及其用途
公开(公告)号：US20120134984A1
公开(公告)日：2012-05-31
申请号：US13375002
申请日：2010-05-28
申请人： Olga Lubman , William Dall'Acqua , Herren Wu
发明人： Olga Lubman , William Dall'Acqua , Herren Wu
IPC分类号： A61K39/395 , C12P21/06 , C12N5/10 , C07K16/18 , C07H21/04
CPC分类号： C07K16/18 , A61K39/3955 , A61K47/62 , A61K47/6835 , A61K2039/505 , C07K14/315 , C07K2317/52 , C07K2317/94 , C07K2319/21 , C07K2319/30 , C07K2319/31 , C07K2319/41
摘要： The invention is directed to a molecule comprising an albumin binding domain (ABD) and an FcRn binding moiety, wherein said molecule has enhanced pharmacologic properties in vivo.
摘要翻译：本发明涉及包含白蛋白结合结构域（ABD）和FcRn结合部分的分子，其中所述分子在体内具有增强的药理学性质。

10. 发明申请

US20080138336A1 Humanized Anti-CD19 Antibodies And Their Use In Treatment Of Oncology, Transplantation And Autoimmune Disease 有权
标题翻译：人源化抗CD19抗体及其在肿瘤，移植和自身免疫性疾病治疗中的应用
公开(公告)号：US20080138336A1
公开(公告)日：2008-06-12
申请号：US11852106
申请日：2007-09-07
申请人： Melissa Damschroder , Peter Kiener , Herren Wu , William Dall'Acqua , Ronald Herbst , Anthony Coyle
发明人： Melissa Damschroder , Peter Kiener , Herren Wu , William Dall'Acqua , Ronald Herbst , Anthony Coyle
IPC分类号： A61K39/395 , C07K16/18 , C12N15/11 , A61P37/00 , C12N5/06
CPC分类号： C07K16/2803 , A61K2039/505 , C07K16/2896 , C07K16/3061 , C07K2317/24 , C07K2317/41 , C07K2317/52 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/73 , C07K2317/732 , C07K2317/77 , C07K2317/92
摘要： The present invention provides chimeric and humanized versions of anti-CD19 mouse monoclonal antibodies. The invention further relates to pharmaceutical compositions, immunotherapeutic compositions, and methods using therapeutic antibodies that bind to the human CD19 antigen and that may mediate ADCC, CDC, and/or apoptosis for the treatment of B cell diseases and disorders, such as, but not limited to, B cell malignancies, for the treatment and prevention of autoimmune disease, and for the treatment and prevention of graft-versus-host disease (GVHD), humoral rejection, and post-transplantation lymphoproliferative disorder in human transplant recipients.
摘要翻译：本发明提供抗CD19小鼠单克隆抗体的嵌合和人源化形式。本发明进一步涉及药物组合物，免疫治疗组合物和使用结合人CD19抗原并且可介导ADCC，CDC和/或细胞凋亡以治疗B细胞疾病和病症的治疗性抗体的方法，例如但不限于B细胞恶性肿瘤，用于治疗和预防自身免疫疾病，以及用于治疗和预防人类移植受体中移植物抗宿主病（GVHD），体液排斥和移植后淋巴增殖性疾病。

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