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1. 发明申请

US20130011405A1 ANTAGONIST ANTI-CD40 MONOCLONAL ANTIBODIES AND METHODS FOR THEIR USE 有权
标题翻译： ANTAGONIST抗CD40单克隆抗体及其使用方法
公开(公告)号：US20130011405A1
公开(公告)日：2013-01-10
申请号：US13612070
申请日：2012-09-12
申请人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror , Bao-Lu Chen , Xiaofeng Lu , Sang Hoon Lee , Deborah Hurst , Sharon Lea Aukerman , Daniel E. Lopes de Menezes
发明人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror , Bao-Lu Chen , Xiaofeng Lu , Sang Hoon Lee , Deborah Hurst , Sharon Lea Aukerman , Daniel E. Lopes de Menezes
IPC分类号： A61K39/395 , A61P29/00 , A61P19/04 , A61P35/00 , A61P19/02 , A61P19/08 , A61P37/06 , A61P25/00 , A61P1/16 , A61P1/00 , A61P7/06 , A61P31/14 , A61P17/06 , A61P21/04 , A61P5/14 , A61P37/00 , A61P7/02 , A61P9/00 , A61P3/10 , A61P37/08 , A61P11/06 , A61P25/28 , C12N5/0781 , A61K39/44
CPC分类号： C07K16/2878 , A61K39/395 , A61K39/3955 , A61K45/06 , A61K47/6849 , A61K2039/505 , A61K2039/507 , A61N5/10 , C07K2317/14 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/92 , A61K2300/00
摘要： Compositions and methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing cells, such as B cells.
摘要翻译：提供了用于治疗通过CD40表达细胞刺激CD40信号传导介导的疾病的组合物和方法。所述方法包括向有需要的患者施用治疗有效量的拮抗性抗CD40抗体或其抗原结合片段。拮抗性抗CD40抗体或其抗原结合片段没有显着的激动剂活性，但当抗体结合表达人CD40的细胞上的CD40抗原时，其表现出拮抗剂活性。抗CD40抗体或其抗原结合片段的拮抗作用有利地抑制人CD40表达细胞如B细胞的增殖和/或分化。

2. 发明申请

US20080254026A1 ANTAGONIST ANTI-CD40 MONOCLONAL ANTIBODIES AND METHODS FOR THEIR USE 有权
标题翻译： ANTAGONIST抗CD40单克隆抗体及其使用方法
公开(公告)号：US20080254026A1
公开(公告)日：2008-10-16
申请号：US11932472
申请日：2007-10-31
申请人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror , Bao-Lu Chen , Xiaofeng Lu , Sang Hoon Lee , Deborah Hurst , Sharon Lea Aukerman , Daniel E. Lopes de Menezes
发明人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror , Bao-Lu Chen , Xiaofeng Lu , Sang Hoon Lee , Deborah Hurst , Sharon Lea Aukerman , Daniel E. Lopes de Menezes
IPC分类号： A61K39/395 , C07K16/18 , C12N5/06 , A61P1/00 , A61P37/00 , G01N33/574 , C07H21/00
CPC分类号： C07K16/2878 , A61K39/395 , A61K39/3955 , A61K45/06 , A61K47/6849 , A61K2039/505 , A61K2039/507 , A61N5/10 , C07K2317/14 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/92 , A61K2300/00
摘要： Compositions and methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing cells, such as B cells.
摘要翻译：提供了用于治疗通过CD40表达细胞刺激CD40信号传导介导的疾病的组合物和方法。所述方法包括向有需要的患者施用治疗有效量的拮抗性抗CD40抗体或其抗原结合片段。拮抗性抗CD40抗体或其抗原结合片段没有显着的激动剂活性，但当抗体结合表达人CD40的细胞上的CD40抗原时，其表现出拮抗剂活性。抗CD40抗体或其抗原结合片段的拮抗作用有利地抑制人CD40表达细胞如B细胞的增殖和/或分化。

3. 发明授权

US08277810B2 Antagonist anti-CD40 antibodies 有权
标题翻译：拮抗剂抗CD40抗体
公开(公告)号：US08277810B2
公开(公告)日：2012-10-02
申请号：US11932472
申请日：2007-10-31
申请人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror , Bao-Lu Chen , Xiaofeng Lu , Sang Hoon Lee , Deborah Hurst
发明人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror , Bao-Lu Chen , Xiaofeng Lu , Sang Hoon Lee , Deborah Hurst
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K16/2878 , A61K39/395 , A61K39/3955 , A61K45/06 , A61K47/6849 , A61K2039/505 , A61K2039/507 , A61N5/10 , C07K2317/14 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/92 , A61K2300/00
摘要： Compositions and methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing cells, such as B cells.
摘要翻译：提供了用于治疗通过CD40表达细胞刺激CD40信号传导介导的疾病的组合物和方法。所述方法包括向有需要的患者施用治疗有效量的拮抗性抗CD40抗体或其抗原结合片段。拮抗性抗CD40抗体或其抗原结合片段没有显着的激动剂活性，但当抗体结合表达人CD40的细胞上的CD40抗原时，其表现出拮抗剂活性。抗CD40抗体或其抗原结合片段的拮抗作用有利地抑制人CD40表达细胞如B细胞的增殖和/或分化。

4. 发明申请

US20080057070A1 Antagonist Anti-Cd40 Monoclonal Antibodies and Methods for Their Use 审中-公开
标题翻译：拮抗剂抗Cd40单克隆抗体及其使用方法
公开(公告)号：US20080057070A1
公开(公告)日：2008-03-06
申请号：US10577390
申请日：2004-11-04
申请人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror , Bao-Lu Chen , Xiaofeng Lu , Sang Hoon Lee , Deborah Hurst
发明人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror , Bao-Lu Chen , Xiaofeng Lu , Sang Hoon Lee , Deborah Hurst
IPC分类号： A61K39/395 , A61P19/02 , A61P35/00 , A61P35/02 , A61P35/04 , A61P37/00 , C07K16/28 , C12N15/13 , C12N5/20
CPC分类号： C07K16/2878 , A61K2039/505 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/92
摘要： Methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40 expressing cells, such as B cells.
摘要翻译：提供了通过CD40表达细胞上的CD40信号传导介导的治疗疾病的治疗方法。所述方法包括向有需要的患者施用治疗有效量的拮抗性抗CD40抗体或其抗原结合片段。拮抗性抗CD40抗体或其抗原结合片段没有显着的激动剂活性，但当抗体结合表达人CD40的细胞上的CD40抗原时，其表现出拮抗剂活性。抗CD40抗体或其抗原结合片段的拮抗作用有利地抑制人CD40表达细胞如B细胞的增殖和/或分化。

5. 发明授权

US08637032B2 Antagonist anti-CD40 monoclonal antibodies and methods for their use 有权
标题翻译：拮抗剂抗CD40单克隆抗体及其使用方法
公开(公告)号：US08637032B2
公开(公告)日：2014-01-28
申请号：US13612070
申请日：2012-09-12
申请人： Li Long , Asha Yabannavar , Isabel Zaror , Sang Hoon Lee , Deborah Hurst
发明人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror , Sang Hoon Lee , Deborah Hurst
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K16/2878 , A61K39/395 , A61K39/3955 , A61K45/06 , A61K47/6849 , A61K2039/505 , A61K2039/507 , A61N5/10 , C07K2317/14 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/92 , A61K2300/00
摘要： Compositions and methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing cells, such as B cells.
摘要翻译：提供了用于治疗通过CD40表达细胞刺激CD40信号传导介导的疾病的组合物和方法。所述方法包括向有需要的患者施用治疗有效量的拮抗性抗CD40抗体或其抗原结合片段。拮抗性抗CD40抗体或其抗原结合片段没有显着的激动剂活性，但当抗体结合表达人CD40的细胞上的CD40抗原时，其表现出拮抗剂活性。抗CD40抗体或其抗原结合片段的拮抗作用有利地抑制人CD40表达细胞如B细胞的增殖和/或分化。

6. 发明申请

US20070218060A1 Use of Antagonist Anti-Cd40 Monoclonal Antibodies for Treatment of Multiple Myeloma 审中-公开
标题翻译：使用拮抗剂抗Cd40单克隆抗体治疗多发性骨髓瘤
公开(公告)号：US20070218060A1
公开(公告)日：2007-09-20
申请号：US10578387
申请日：2004-11-04
申请人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror
发明人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror
IPC分类号： C07K16/00
CPC分类号： C07K16/2878 , A61K38/2013 , A61K39/39558 , A61K2039/505 , C07K2317/21 , C07K2317/34 , C07K2317/73 , C07K2317/732 , C07K2317/76 , A61K2300/00
摘要： Methods of therapy for treating a subject for multiple myeloma are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40 expressing multiple myeloma cells.
摘要翻译：提供了治疗多发性骨髓瘤受试者的治疗方法。所述方法包括向有需要的患者施用治疗有效量的拮抗性抗CD40抗体或其抗原结合片段。拮抗性抗CD40抗体或其抗原结合片段没有显着的激动剂活性，但当抗体结合表达人CD40的细胞上的CD40抗原时，其表现出拮抗剂活性。抗体抗体或其抗原结合片段的拮抗作用有利地抑制人CD40表达多发性骨髓瘤细胞的增殖和/或分化。

7. 发明申请

US20070098718A1 Methods of therapy for b cell-related cancers 审中-公开
标题翻译： b细胞相关癌症治疗方法
公开(公告)号：US20070098718A1
公开(公告)日：2007-05-03
申请号：US10578401
申请日：2004-11-04
申请人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror
发明人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabel Zaror
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K16/2878 , A61K2039/507 , C07K16/2887 , C07K2317/21 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/56 , C07K2317/73 , C07K2317/76 , C07K2317/92
摘要： Methods of treating a human subject for a cancer characterized by neoplastic B cell growth are provided. The methods comprise administering combination antibody therapy to the subject, where an effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof in combination with an anti-CD20 antibody or antigenbinding fragment thereof is administered to the subject. The invention further comprises pharmaceutical compositions with combinations of these antibodies in a pharmaceutically acceptable carrier.
摘要翻译：提供了治疗人受试者以肿瘤B细胞生长为特征的癌症的方法。所述方法包括向受试者施用组合抗体治疗，其中将有效量的抗CD40抗体或其抗原结合片段与抗CD20抗体或其抗原结合片段组合施用于受试者。本发明进一步包括在药学上可接受的载体中具有这些抗体的组合的药物组合物。

8. 发明申请

US20070110754A1 Use of antagonist anti-cd40 antibodies for treatment of chronic lymphocytic leukemia 审中-公开
标题翻译：使用拮抗剂抗CD40抗体治疗慢性淋巴细胞性白血病
公开(公告)号：US20070110754A1
公开(公告)日：2007-05-17
申请号：US10577642
申请日：2004-11-04
申请人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabet Zaror , Sharon Aukerman
发明人： Li Long , Mohammad Luqman , Asha Yabannavar , Isabet Zaror , Sharon Aukerman
IPC分类号： A61K39/395 , C07K16/30
CPC分类号： C07K16/2878 , A61K2039/505 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/92
摘要： Methods of therapy for treating a subject for chronic lymphocytic leukemia are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CN40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing chronic lymphocytic leukemia cells.
摘要翻译：提供了治疗慢性淋巴细胞性白血病受试者的治疗方法。所述方法包括向有需要的患者施用治疗有效量的拮抗性抗CN40抗体或其抗原结合片段。拮抗性抗CD40抗体或其抗原结合片段没有显着的激动剂活性，但当抗体结合表达人CD40的细胞上的CD40抗原时，其表现出拮抗剂活性。抗CD40抗体或其抗原结合片段的拮抗作用有益地抑制人CD40表达慢性淋巴细胞白血病细胞的增殖和/或分化。

9. 发明申请

US20090202531A1 USES OF ANTI-CD40 ANTIBODIES 审中-公开
标题翻译：抗CD40抗体的使用
公开(公告)号：US20090202531A1
公开(公告)日：2009-08-13
申请号：US12092256
申请日：2006-11-01
申请人： Sharon Lea Aukerman , Mohammad Luqman
发明人： Sharon Lea Aukerman , Mohammad Luqman
IPC分类号： A61K39/395 , C12Q1/68
CPC分类号： C07K16/2878 , C07K16/2887 , C07K2317/732 , C07K2317/77
摘要： Methods for treating a human patient for an inflammatory or autoimmune disease that is associated with CD40-expressing cells are provided, where the human patient is heterozygous or homozygous for FcγRIIIa-158F (genotype V/F or F/F). Also provided are methods of inhibiting antibody production by B cells in a human patient who is heterozygous or homozygous for FcγRIIIa-158F (genotype V/F or F/F). The methods comprise administering to the human patient a therapeutically or prophylactically effective amount of an anti-CD40 antibody. Methods and kits for identifying a human patient with an inflammatory or autoimmune disease that is treatable with an anti-CD40 antibody and which is non-responsive or refractory to treatment with rituximab (Rituxan®), as well as methods and kits for selecting an antibody therapy for treatment of a human patient having an inflammatory or autoimmune disease that is non-responsive or refractory to treatment with rituximab (Rituxan®), are also provided. The methods of the present invention find use in treatment of inflammatory diseases and autoimmune diseases that are associated with CD40-expressing cells. These methods are particularly advantageous with respect to inflammatory diseases and autoimmune diseases that are associated with cells expressing both CD40 and CD20, as the methods enable the treatment of patients having an inflammatory or autoimmune disease that is non-responsive or refractory to therapy with other therapeutic agents such as anti-CD20 antibodies.
摘要翻译：提供了用于治疗患有与表达CD40的细胞相关的炎性或自身免疫性疾病的人类患者的方法，其中人类患者对于FcgammaRIIIa-158F（基因型V / F或F / F）是杂合的或纯合的。还提供了抑制对FcgammaRIIIa-158F（基因型V / F或F / F）是杂合的或纯合的人类患者中B细胞的抗体产生的方法。所述方法包括向人类患者施用治疗或预防有效量的抗CD40抗体。用于鉴定具有可用抗CD40抗体治疗并且对利妥昔单抗治疗无反应或难治性的炎性或自身免疫性疾病的人类患者的方法和试剂盒以及用于选择的方法和试剂盒还提供了用于治疗具有对利妥昔单抗治疗无反应或难治的炎性或自身免疫性疾病的人类患者的抗体疗法（Rituxan）。本发明的方法可用于治疗与CD40表达细胞相关的炎性疾病和自身免疫性疾病。这些方法对于与表达CD40和CD20的细胞相关的炎性疾病和自身免疫性疾病是特别有利的，因为该方法能够治疗患有对其他治疗无效或难治的炎性或自身免疫性疾病的患者药物如抗CD20抗体。

10. 发明申请

US20080274118A1 Methods for Diagnosis and Treatment of Diseases Having an Autoimmune and/or Inflammatory Component 有权
标题翻译：具有自身免疫和/或炎症成分的疾病的诊断和治疗方法
公开(公告)号：US20080274118A1
公开(公告)日：2008-11-06
申请号：US11914710
申请日：2006-05-18
申请人： Sharon Lea Aukerman , Bahija Jallal , Mohammad Luqman
发明人： Sharon Lea Aukerman , Bahija Jallal , Mohammad Luqman
IPC分类号： A61K39/395 , G01N33/567 , A61P1/00 , A61P3/00 , A61P19/00 , A61P29/00 , A61P37/00 , A61P25/00
CPC分类号： G01N33/564 , G01N33/5091 , G01N33/533 , G01N33/57484 , G01N33/582 , G01N2800/24 , G01N2800/52
摘要： Methods for identifying subjects having an inflammatory disease and/or autoimmune disease that will benefit from anti-CD40 therapeutic agents that modulate CD40L-mediated CD40 signaling are provided. The methods comprise the use of biomarkers of cellular apoptosis, cell proliferation and survival, and CD40 signaling pathways to monitor ex vivo response to one or more anti-CD40 therapeutic agents of interest that modulate CD40 signaling on CD40-expressing cells. The ex vivo prognostic assays can be used alone or in conjunction with other prognostic assays to identify candidate subjects who will benefit from treatment with anti-CD40 therapeutic agents. Methods of the invention also comprise the use of these biomarkers to monitor in vivo efficacy of treatment with an anti-CD40 therapeutic agent.
摘要翻译：提供了用于鉴定将受益于调节CD40L介导的CD40信号传导的抗CD40治疗剂的炎性疾病和/或自身免疫性疾病的受试者的方法。所述方法包括使用细胞凋亡，细胞增殖和存活的生物标志物，以及CD40信号通路来监测对一种或多种调节CD40表达细胞上的CD40信号传导的抗CD40治疗剂的离体反应。离体预后测定可以单独使用或与其他预后测定结合使用，以鉴定将受益于抗CD40治疗剂治疗的候选受试者。本发明的方法还包括使用这些生物标志物来监测用抗CD40治疗剂治疗的体内功效。

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