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1. 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。

2. 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。

3. 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。

4. 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。

5. 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。

6. 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。

7. 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。

8. 发明申请

WO2008020968A3 RECOMBINANT INTERFERON-BETA WITH ENHANCED BIOLOGICAL ACTIVITY 审中-公开
标题翻译：重组干扰素β具有增强的生物活性
公开(公告)号：WO2008020968A3
公开(公告)日：2008-05-29
申请号：PCT/US2007016722
申请日：2007-07-24
申请人： NOVARTIS VACCINES & DIAGNOSTIC , JOHNSON-JACKSON DEBORAH , FURUYA KENJI , ZAROR ISABEL , LARSON DOUGLAS
发明人： JOHNSON-JACKSON DEBORAH , FURUYA KENJI , ZAROR ISABEL , LARSON DOUGLAS
IPC分类号： C07K14/565
CPC分类号： C07K14/565
摘要： Human interferon-ß protein analogs in which the asparagine at position 25, numbered in accordance with native human interferon-ß, is recombinantly replaced with an aspartate residue exhibit a biological activity of human interferon-ß (e.g. IFN-ß 1b) at an increased level relative to IFN-ß 1b. These analogs are obtained by introducing a gene coding for Asp25 IFN-ß into a cell and expressing the recombinant protein. The resulting IFN-ß protein analog is suitable for large scale manufacturing for incorporation in HA-containing or HA-free therapeutics for treatment of diseases including multiple sclerosis. A reduced Lys endoproteinase-C peptide map technique that produces a fingerprint profile for proteins using an enzymatic digest followed by RP-HPLC is also useful in quality control as an ID test for the IFN-ß protein analog products.
摘要翻译：人类干扰素-β蛋白类似物，其中根据天然人干扰素-β编号的25位天冬酰胺被天冬氨酸残基重组取代，表现出人类干扰素-β（例如IFN-β1b）的生物学活性增加水平相对于IFN-β1b。这些类似物通过将编码Asp25IFN-β的基因导入细胞并表达重组蛋白来获得。所得到的IFN-β蛋白类似物适合于大规模生产以掺入含有HA或HA的治疗剂中，用于治疗包括多发性硬化症的疾病。利用酶促消化产生指纹图谱，然后进行RP-HPLC的还原Lys内切蛋白酶-C肽图谱技术在质量控制中也可用作IFN-β蛋白类似物产品的ID测试。

9. 发明申请

WO2008020968A8 RECOMBINANT INTERFERON-BETA WITH ENHANCED BIOLOGICAL ACTIVITY 审中-公开
标题翻译：重组干扰素与增强的生物活性
公开(公告)号：WO2008020968A8
公开(公告)日：2009-08-06
申请号：PCT/US2007016722
申请日：2007-07-24
申请人： NOVARTIS AG , JOHNSON-JACKSON DEBORAH , FURUYA KENJI , ZAROR ISABEL , LARSON DOUGLAS
发明人： JOHNSON-JACKSON DEBORAH , FURUYA KENJI , ZAROR ISABEL , LARSON DOUGLAS
IPC分类号： C07K14/565
CPC分类号： C07K14/565
摘要： Human interferon-ß protein analogs in which the asparagine at position 25, numbered in accordance with native human interferon-ß, is recombinantly replaced with an aspartate residue exhibit a biological activity of human interferon-ß (e.g. IFN-ß 1b) at an increased level relative to IFN-ß 1b. These analogs are obtained by introducing a gene coding for Asp25 IFN-ß into a cell and expressing the recombinant protein. The resulting IFN-ß protein analog is suitable for large scale manufacturing for incorporation in HA-containing or HA-free therapeutics for treatment of diseases including multiple sclerosis. A reduced Lys endoproteinase-C peptide map technique that produces a fingerprint profile for proteins using an enzymatic digest followed by RP-HPLC is also useful in quality control as an ID test for the IFN-ß protein analog products.
摘要翻译：人类干扰素-β蛋白类似物，其中根据天然人类干扰素β编号的位置25的天冬酰胺用天冬氨酸残基重组替代，表现出人干扰素β（例如IFN-β1b）在增加的生物活性水平相对于IFN-β1b。这些类似物通过将编码Asp25 IFN-β的基因导入细胞并表达重组蛋白而获得。所得到的IFN-β蛋白类似物适用于大规模制造，用于掺入含HA或不含HA的治疗剂中用于治疗包括多发性硬化的疾病。使用酶促消化产生RP-HPLC产生蛋白质指纹图谱的降低的Lys内蛋白酶-C肽图技术在用于IFN-β蛋白模拟产物的ID测试的质量控制中也是有用的。

10. 发明申请

WO9634965A3 CHIMERIC MCP AND DAF PROTEINS WITH CELL SURFACE LOCHIMERIC MCP AND DAF PROTEINS WITH CELL SURFACE LOCALIZING DOMAIN CALIZING DOMAIN 审中-公开
标题翻译：具有细胞表面LOCHIMERIC MCP和DAF蛋白的CHIMERIC MCP和DAF蛋白与细胞表面定位域修饰域
公开(公告)号：WO9634965A3
公开(公告)日：1997-01-03
申请号：PCT/US9606301
申请日：1996-05-03
申请人： CHIRON CORP
发明人： INNIS MICHAEL A , ZAROR ISABEL , CREASEY ABLA A
IPC分类号： C12N15/09 , A61K38/00 , C07K14/705 , C07K19/00 , C12N15/62 , C12N1/80 , C12N5/00
CPC分类号： C07K14/705 , A61K38/00 , C07K2319/00
摘要： Chimeric proteins containing sequences from MCP and DAF and further containing peptide sequences capable of binding glycosaminoglycans. Nucleotide sequences encoding the chimeric proteins, expression vectors containing the nucleotide sequences, as well as transformed host cells capable of producing the chimeric proteins are claimed.

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