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1. 发明申请

WO2005044294A3 METHOD OF THERAPY FOR CANCERS EXPRESSING THE CD40 ANTIGEN 审中-公开
标题翻译：表达CD40抗原的癌症治疗方法
公开(公告)号：WO2005044294A3
公开(公告)日：2005-09-15
申请号：PCT/US2004036958
申请日：2004-11-04
申请人： CHIRON CORP , LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL , HURST DEBORAH , LOPES DE MENEZES DANIEL E
发明人： LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL , HURST DEBORAH , LOPES DE MENEZES DANIEL E
IPC分类号： A61K38/20 , A61K39/395 , C07K16/28 , A61P35/02
CPC分类号： C07K16/2878 , A61K38/2013 , A61K39/39558 , A61K2039/505 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/92 , A61K2300/00
摘要： Methods of treating a subject for a cancer comprising neoplastic cells expressing the CD40 cell surface antigen are provided. The methods comprise combination therapy with interleukin-2 (IL-2) or biologically active variant thereof and at least one antagonist anti-CD40 antibody or antigen-binding fragment thereof. In some embodiments, these two therapeutic agents are concurrently administered as two separate pharmaceutical compositions, one containing IL-2 or biologically active variant thereof, which is administered according to a constant IL-2 dosing regimen or a two-level IL-2 dosing regimen, the other containing the antagonist anti-CD40 antibody or suitable antigen binding fragment thereof, which is administered according to a weekly dosing regimen, or alternatively is dosed once every two, three, or four weeks. Administering of these two agents together potentiates their effectiveness in promoting a positive therapeutic response. The methods find use in treating CD40-expressing cancers, including B-cell related cancers and solid tumors.
摘要翻译：提供了治疗受试者的包含表达CD40细胞表面抗原的肿瘤细胞的癌症的方法。该方法包括用白细胞介素-2（IL-2）或其生物活性变体和至少一种拮抗性抗-CD40抗体或其抗原结合片段的组合疗法。在一些实施方案中，这两种治疗剂作为两种独立的药物组合物同时施用，一种包含IL-2或其生物活性变体，其根据恒定的IL-2给药方案或两级IL-2给药方案，另一种含有拮抗性抗-CD40抗体或其合适的抗原结合片段，其根据每周给药方案给药，或者每两周，三周或四周给药一次。共同施用这两种药物增强了其促进积极治疗反应的有效性。该方法可用于治疗表达CD40的癌症，包括B细胞相关的癌症和实体瘤。

2. 发明申请

WO2005044304A2 USE OF ANTAGONIST ANTI-CD40 ANTIBODIES FOR TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA 审中-公开
标题翻译：拮抗剂抗CD40抗体用于治疗慢性淋巴细胞白血病
公开(公告)号：WO2005044304A2
公开(公告)日：2005-05-19
申请号：PCT/US2004036954
申请日：2004-11-04
申请人： CHIRON CORP , LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL , AUKERMAN LEA
发明人： LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL , AUKERMAN LEA
IPC分类号： C07K16/28 , A61K39/395
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-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 chronic lymphocytic leukemia cells.
摘要翻译：提供了用于治疗慢性淋巴细胞白血病受试者的治疗方法。该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抗原时表现出拮抗剂活性。抗CD40抗体或其抗原结合片段的拮抗剂活性有益地抑制表达人CD40的慢性淋巴细胞白血病细胞的增殖和/或分化。

3. 发明申请

WO2005044307A3 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：WO2005044307A3
公开(公告)日：2005-08-25
申请号：PCT/US2004037159
申请日：2004-11-04
申请人： CHIRON CORP , LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL
发明人： LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL
IPC分类号： A61K39/395 , C07K16/28 , A61P35/02
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。

4. 发明申请

WO2005044305A3 METHODS OF THERAPY FOR SOLID TUMORS EXPRESSING THE CD40 CELL-SURFACE ANTIGEN 审中-公开
标题翻译：表达CD40细胞表面抗原的固体肿瘤的治疗方法
公开(公告)号：WO2005044305A3
公开(公告)日：2005-08-11
申请号：PCT/US2004036955
申请日：2004-11-04
申请人： CHIRON CORP , LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL
发明人： LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00
CPC分类号： C07K16/2878 , A61K2039/505 , C07K16/2887 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/92
摘要： Methods of therapy are provided for treating a subject for a solid tumor that comprises carcinoma cells expressing the CD40 cell-surface antigen. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a subject 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. Binding of the anti-CD40 antibody or suitable antigen-binding fragment thereof beneficially inhibits growth of solid tumors via ADCC-dependent killing of the CD40-expressing carcinoma cells.
摘要翻译：提供治疗方法用于治疗受试者的包含表达CD40细胞表面抗原的癌细胞的实体瘤。该方法包括向有需要的受试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抗原时表现出拮抗剂活性。抗-CD40抗体或其合适的抗原结合片段的结合通过ADCC依赖性杀死表达CD40的癌细胞有益地抑制实体瘤的生长。

5. 发明申请

WO2005044855A3 USE OF ANTAGONIST ANTI-CD40 MONOCLONAL ANTIBODIES FOR TREATMENT OF MULTIPLE MYELOMA 审中-公开
标题翻译：拮抗剂抗CD40单克隆抗体用于治疗多发性骨髓瘤
公开(公告)号：WO2005044855A3
公开(公告)日：2005-09-15
申请号：PCT/US2004037281
申请日：2004-11-04
申请人： CHIRON CORP , LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL
发明人： LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL
IPC分类号： C07K16/28 , A61K39/395 , A61P35/02
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 CD40expressing multiple myeloma cells.
摘要翻译：提供了治疗患有多发性骨髓瘤的受试者的治疗方法。该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抗原时表现出拮抗剂活性。抗体或其抗原结合片段的拮抗剂活性有益地抑制表达人CD40的多发性骨髓瘤细胞的增殖和/或分化。

6. 发明申请

WO2006073443A2 ANTAGONIST ANTI-CD40 MONOCLONAL ANTIBODIES AND METHODS FOR THEIR USE 审中-公开
标题翻译：拮抗性抗CD40单克隆抗体及其使用方法
公开(公告)号：WO2006073443A2
公开(公告)日：2006-07-13
申请号：PCT/US2005014359
申请日：2005-04-27
申请人： CHIRON CORP , LUQMAN MOHAMMAD
发明人： LUQMAN MOHAMMAD
IPC分类号： A61P35/02 , A61K39/395
CPC分类号： C07K16/2878 , A61K2039/505 , C07K2317/21 , C07K2317/73 , C07K2317/92
摘要： Compositions and methods for inhibiting CD40-directed activities that are mediated via the binding of C4BP to CD40 are provided. The compositions of the invention include anti-CD40 antibodies, or antigen-binding fragments thereof, that have the following characteristics: 1) are free of significant CD40 agonist activity when bound to CD40 antigen; and 2) are capable of specifically binding to CD40 antigen expressed on the surface of cells, wherein this binding to CD40 antigen blocks C4BP-mediated CD40 signaling, thereby inhibiting one or more CD40-directed activities. These antagonist anti-CD40 antibodies can effectively be used to treat CD40-associated diseases that are mediated by C4BP stimulation of CD40 signaling, including cancers, such as B cell-related cancers and solid tumors, and diseases or disorders that have an autoimmune and/or inflammatory component, including organ and tissue transplant rejection.
摘要翻译：提供了用于抑制通过C4BP与CD40结合介导的CD40引导的活性的组合物和方法。本发明的组合物包括具有以下特征的抗CD40抗体或其抗原结合片段：1）当与CD40抗原结合时没有显着的CD40激动剂活性; 和2）能够与细胞表面上表达的CD40抗原特异性结合，其中这种与CD40抗原的结合阻断C4BP介导的CD40信号传导，从而抑制一种或多种CD40定向活性。这些拮抗性抗CD40抗体可以有效地用于治疗由C4BP刺激CD40信号传导介导的CD40相关疾病，包括癌症如B细胞相关癌症和实体瘤，以及具有自身免疫性和/ 或炎症成分，包括器官和组织移植排斥。

7. 发明申请

WO2005044854A3 ANTAGONIST ANTI-CD40 MONOCLONAL ANTIBODIES AND METHODS FOR THEIR USE 审中-公开
标题翻译：拮抗性抗CD40单克隆抗体及其使用方法
公开(公告)号：WO2005044854A3
公开(公告)日：2005-08-11
申请号：PCT/US2004037152
申请日：2004-11-04
申请人： CHIRON CORP , LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL , CHEN BAO-LU , LU XIAOFENG , LEE SANG HOON , HURST DEBORAH
发明人： LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL , CHEN BAO-LU , LU XIAOFENG , LEE SANG HOON , HURST DEBORAH
IPC分类号： A61K38/20 , A61K39/395 , C07K16/28 , A61P33/06 , A61P35/02 , C12N5/20
CPC分类号： C07K16/2878 , A61K38/2013 , A61K39/39558 , A61K2039/505 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/92 , A61K2300/00
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 CD40expressing cells, such as B cells.
摘要翻译：提供了用于治疗由表达CD40的细胞上的CD40信号传导介导的疾病的治疗方法。该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抗原时表现出拮抗剂活性。抗CD40抗体或其抗原结合片段的拮抗剂活性有益地抑制人CD40表达细胞如B细胞的增殖和/或分化。

8. 发明申请

WO2005044306A2 USE OF ANTAGONIST ANTI-CD40 ANTIBODIES FOR TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES AND ORGAN TRANSPLANT REJECTION 审中-公开
标题翻译：用于治疗自身免疫性和炎症性疾病和有机移植物排斥反应的ANTAG-AN抗CD40抗体的应用
公开(公告)号：WO2005044306A2
公开(公告)日：2005-05-19
申请号：PCT/US2004036957
申请日：2004-11-04
申请人： CHIRON CORP , LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL
发明人： LONG LI , LUQMAN MOHAMMAD , YABANNAVAR ASHA , ZAROR ISABEL
IPC分类号： A61K38/20 , A61K39/395 , C07K16/28
CPC分类号： C07K16/2878 , A61K38/2013 , A61K39/39558 , A61K2039/505 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/92 , A61K2300/00
摘要： Methods of therapy for treating a subject for an autoimmune disease and/or inflammatory disease 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 CD40L-mediated stimulation of CD40-expressing cells, and thus inhibits survival and signaling pathways of human CD40-expressing cells that are mediated by CD40L.
摘要翻译：提供了用于治疗受试者自身免疫疾病和/或炎性疾病的治疗方法。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明显的激动剂活性，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活性有利地抑制CD40L介导的表达CD40的细胞的刺激，从而抑制由CD40L介导的人CD40表达细胞的存活和信号传导途径。

9. 发明申请

WO2006125143A3 METHODS FOR DIAGNOSIS AND TREATMENT OF PROLIFERATIVE DISORDERS MEDIATED BY CD40 SIGNALING 审中-公开
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：WO2006125143A3
公开(公告)日：2007-03-22
申请号：PCT/US2006019414
申请日：2006-05-18
申请人： NOVARTIS AG , XOMA TECHNOLOGY , AUKERMAN SHARON LEA , JALLAL BAHIJA , LUQMAN MOHAMMAD
发明人： AUKERMAN SHARON LEA , JALLAL BAHIJA , LUQMAN MOHAMMAD
IPC分类号： G01N33/574 , A61K39/395
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. 发明申请

WO9506728A3 T CELL EPITOPES OF RYEGRASS POLLEN ALLERGEN 审中-公开
标题翻译： RYEGRASS POLLEN ALLERGEN的T细胞抗原
公开(公告)号：WO9506728A3
公开(公告)日：1995-05-04
申请号：PCT/US9409024
申请日：1994-08-05
申请人： IMMULOGIC PHARMA CORP , GRIFFITH IRWIN J , KUO MEI CHANG , LUQMAN MOHAMMAD
发明人： GRIFFITH IRWIN J , KUO MEI-CHANG , LUQMAN MOHAMMAD
IPC分类号： G01N33/53 , A61K38/00 , A61K39/36 , A61K39/395 , A61P37/08 , C07K14/415 , C07K16/16 , C12N1/21 , C12N15/02 , C12N15/09 , C12N15/29 , C12P21/02 , C12P21/08 , C12R1/19 , G01N33/577
CPC分类号： C07K16/16 , A61K38/00 , C07K14/415
摘要： The present invention provides isolated peptides of Lol pV, a major protein allergen of the species Lolium perenne. Therapeutic peptides within the scope of the invention comprise at least one T cell epitope, or preferably at least two T cell epitopes of a protein allergen of Lol pV. Diagnostic peptides within the scope of the invention bind IgE. The invention also provides modified peptides having similar or enhanced therapeutic properties or other desirable properties as the corresponding, naturally-occurring allergen or portion thereof. The invention further provides nucleic acid sequences coding for peptides of the invention. Use of the therapeutic compositions comprising one or more peptides of the invention in the manufacture of medicaments for treating sensitivity to Lol pV or an allergen immunologically related to Lol pV, or for general ryegrass sensitivity in an individual, is also provided. The invention also provides nucleic acid sequence coding for Dac gV protein allergen as well as the amino acid sequence of Dac gV protein allergen.

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