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1. 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。

2. 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。

3. 发明授权

US08333970B2 Methods of monitoring the efficacy of anti-CD40 antibodies in treating a subject having an inflammatory or autoimmune disease 有权
标题翻译：监测抗CD40抗体在治疗具有炎性或自身免疫疾病的受试者中的功效的方法
公开(公告)号：US08333970B2
公开(公告)日：2012-12-18
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 , C12Q1/00 , C12Q1/68 , G01N33/53
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。

4. 发明授权

US08337851B2 Methods of monitoring the efficacy of anti-CD40 antibodies in treating a subject for a CD40-expressing cancer 失效
标题翻译：监测抗CD40抗体在治疗受试者表达CD40的癌症中的功效的方法
公开(公告)号：US08337851B2
公开(公告)日：2012-12-25
申请号：US11914714
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 , C12Q1/00 , C12Q1/68 , G01N33/53
CPC分类号： G01N33/6863 , A61K39/39558 , A61K2039/505 , C07K16/2878 , C07K2317/21 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C12Q1/6886 , G01N33/5091 , G01N33/574 , G01N2333/70575
摘要： Methods for identifying subjects having a cancer or pre-malignant condition 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 neoplastic 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治疗剂的癌症或恶性前病症的受试者的方法。该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信号通路来监测对调节表达CD40的肿瘤细胞上的CD40信号传导的一种或多种感兴趣的抗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。

5. 发明申请

US20090117111A1 USES OF ANTI-CD40 ANTIBODIES 有权
标题翻译：抗CD40抗体的使用
公开(公告)号：US20090117111A1
公开(公告)日：2009-05-07
申请号：US12092247
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： C12Q1/6881 , A61K2039/505 , C07K16/2878 , C07K2317/732 , C12Q2600/106 , C12Q2600/158
摘要： Methods for treating a human patient for a cancer or pre-malignant condition 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 a cancer or pre-malignant condition that is treatable with an anti-CD40 antibody and which is refractory to treatment with rituximab (Rituxan®), as well as methods and kits for selecting an antibody therapy for treatment of a human patient having a cancer or pre-malignant condition that is refractory to treatment with rituximab (Rituxan®), are also provided. The methods of the present invention find use in treatment of cancers and pre-malignant conditions that are associated with CD40-expressing cells. These methods are particularly advantageous with respect to cancers and pre-malignant conditions that are associated with cells expressing both CD40 and CD20, as the methods enable the treatment of patients having a cancer or pre-malignant condition that is refractory to therapy with other oncotherapeutic agents such as anti-CD20 antibodies.
摘要翻译：提供了用于治疗与患有CD40的细胞相关的癌症或恶性前状况的人类患者的方法，其中人类患者是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抗体治疗且难以用利妥昔单抗治疗的癌症或恶性前病症的人类患者的方法和试剂盒，以及用于选择抗体的方法和试剂盒还提供了治疗患有利妥昔单抗（Rituxan）治疗难治性的癌症或恶性前病症的人类患者的治疗。本发明的方法可用于治疗与CD40表达细胞相关的癌症和恶性前恶性病症。这些方法对于与表达CD40和CD20的细胞相关的癌症和恶性前病症是特别有利的，因为该方法能够治疗具有与其它治疗剂治疗难治的癌症或恶变前病症的患者如抗CD20抗体。

6. 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。

7. 发明授权

US08926979B2 Treatment of cancer or pre-malignant conditions using anti-CD40 antibodies 有权
标题翻译：使用抗CD40抗体治疗癌症或恶性前病症
公开(公告)号：US08926979B2
公开(公告)日：2015-01-06
申请号：US12092247
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 , C07K16/28 , A61K39/00
CPC分类号： C12Q1/6881 , A61K2039/505 , C07K16/2878 , C07K2317/732 , C12Q2600/106 , C12Q2600/158
摘要： Methods for treating a human patient for a cancer or pre-malignant condition 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 a cancer or pre-malignant condition that is treatable with an anti-CD40 antibody and which is refractory to treatment with rituximab (Rituxan®), as well as methods and kits for selecting an antibody therapy for treatment of a human patient having a cancer or pre-malignant condition that is refractory to treatment with rituximab (Rituxan®), are also provided. The methods of the present invention find use in treatment of cancers and pre-malignant conditions that are associated with CD40-expressing cells. These methods are particularly advantageous with respect to cancers and pre-malignant conditions that are associated with cells expressing both CD40 and CD20, as the methods enable the treatment of patients having a cancer or pre-malignant condition that is refractory to therapy with other oncotherapeutic agents such as anti-CD20 antibodies.
摘要翻译：提供了用于治疗人类患者与CD40表达细胞相关的癌症或恶性前病症的方法，其中人类患者是FcγRIIIa-158F（基因型V / F或F / F）是杂合的或纯合的。还提供了抑制对FcγRIIIa-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抗体治疗且难以用利妥昔单抗治疗的癌症或恶性前病症的人类患者的方法和试剂盒，以及用于选择抗体治疗的方法和试剂盒还提供了治疗患有利妥昔单抗治疗难治的癌症或恶性前病症的人类患者。本发明的方法可用于治疗与CD40表达细胞相关的癌症和恶性前恶性病症。这些方法对于与表达CD40和CD20的细胞相关的癌症和恶性前病症是特别有利的，因为该方法能够治疗具有与其它治疗剂治疗难治的癌症或恶变前病症的患者如抗CD20抗体。

8. 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。

9. 发明申请

US20090041773A1 METHODS FOR DIAGNOSIS AND TREATMENT OF PROLIFERATIVE DISORDERS MEDIATED BY CD40 SIGNALING 失效
标题翻译：诊断和治疗CD40信号传导的增殖性疾病的方法
公开(公告)号：US20090041773A1
公开(公告)日：2009-02-12
申请号：US11914714
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 , G01N33/574 , C12Q1/68 , C12Q1/37 , A61P31/00 , C12Q1/18 , G01N33/53
CPC分类号： G01N33/6863 , A61K39/39558 , A61K2039/505 , C07K16/2878 , C07K2317/21 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C12Q1/6886 , G01N33/5091 , G01N33/574 , G01N2333/70575
摘要： Methods for identifying subjects having a cancer or pre-malignant condition 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 neoplastic 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治疗剂的癌症或恶性前病症的受试者的方法。该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信号通路来监测对调节表达CD40的肿瘤细胞上的CD40信号传导的一种或多种感兴趣的抗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。

10. 发明授权

US5858977A Method of treating diabetes mellitus using KGF 失效
标题翻译：使用KGF治疗糖尿病的方法
公开(公告)号：US5858977A
公开(公告)日：1999-01-12
申请号：US817260
申请日：1997-04-11
申请人： Sharon Lea Aukerman , Glenn Francis Pierce
发明人： Sharon Lea Aukerman , Glenn Francis Pierce
IPC分类号： A61K38/00 , A61K38/18 , C07K14/50 , C07K14/475
CPC分类号： A61K38/1825 , C07K14/50 , Y10S514/866
摘要： A method and pharmaceutical compositions are described for the use of keratinocyte growth factor to treat diabetes mellitus in mammals.
摘要翻译： PCT No.PCT / IB95 / 00992 Sec。 371日期1997年04月11日 102（e）日期1997年4月11日PCT提交1995年10月12日PCT公布。出版物WO96 / 11950 PCT 日期1996年4月25日描述了使用角质细胞生长因子治疗哺乳动物糖尿病的方法和药物组合物。

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