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1. 发明申请

WO2012170072A1 ENGINEERED ANTIBODY-TNFSF MEMBER LIGAND FUSION MOLECULES 审中-公开
标题翻译：工程抗体 - TNFSF成员配体融合分子
公开(公告)号：WO2012170072A1
公开(公告)日：2012-12-13
申请号：PCT/US2012/000275
申请日：2012-06-06
申请人： IMMUNGENE, INC.
发明人： GREWAL, Iqbal , KHARE, Sanjay, D. , GRESSER, Michael , SYED, Rashid
IPC分类号： C12P21/08 , A61K38/19 , A61P35/00 , A61K39/00
CPC分类号： C07K16/2887 , A61K38/00 , A61K38/191 , A61K38/212 , A61K39/39558 , A61K45/06 , C07K14/525 , C07K2319/00
摘要： The field of the present invention relates to genetically engineered fusion molecules, methods of making said fusion molecules, and uses thereof in anti-tumor immunotherapies. More specifically, the present invention relates to engineered fusion molecules comprising an antibody (Ab) which can target tumor cells (e.g., RITUXIN®), fused to one or more biologic moieties capable of inducing apoptosis in tumor cells, e.g., tumor necrosis factor super family (TNFSF) member ligands such as TNF-α, CD40L, CD95L (also "FasL/Apo-lL") and TRAIL/ Apo-2L. Importantly, the engineered fusion molecules of the present invention retain the death-inducing properties of the biologic moiety at optimum concentrations and with reduced systemic toxicities, thus improving the therapeutic index of the engineered fusion molecules.
摘要翻译：本发明的领域涉及基因工程融合分子，制备所述融合分子的方法及其在抗肿瘤免疫治疗中的用途。更具体地，本发明涉及包含能够靶向肿瘤细胞的抗体（Ab）的工程化融合分子，所述抗体（例如RITUXIN？）与一个或多个能诱导肿瘤细胞凋亡的生物部分融合，例如肿瘤坏死因子超级家族（TNFSF）成员配体如TNF-α，CD40L，CD95L（也称为“FasL / Apo-L1”）和TRAIL / Apo-2L。重要的是，本发明的工程化融合分子将生物部分的死亡诱导性质保持在最佳浓度并具有降低的全身毒性，从而改善了工程化融合分子的治疗指数。

2. 发明申请

WO2014028502A1 ENGINEERED ANTIBODY-INTERFERON FUSION MOLECULES FOR TREATMENT OF AUTOIMMUNE DISEASES 审中-公开
标题翻译：用于治疗自身免疫疾病的工程抗体 - 干扰素融合分子
公开(公告)号：WO2014028502A1
公开(公告)日：2014-02-20
申请号：PCT/US2013/054747
申请日：2013-08-13
申请人： IMMUNGENE INC.
发明人： GREWAL, Iqbal , GRESSER, Michael , KHARE, Sanjay
IPC分类号： A61K39/00 , C12P21/04 , C07K1/00 , C07K14/00 , C07K17/00 , C07K16/00
CPC分类号： C07K14/57 , C07K14/555 , C07K14/56 , C07K16/28 , C07K16/2803 , C07K16/2818 , C07K16/2833 , C07K16/2866 , C07K16/2875 , C07K16/2878 , C07K16/2881 , C07K16/2896 , C07K16/40 , C07K2317/24 , C07K2317/54 , C07K2317/55 , C07K2317/622 , C07K2317/624 , C07K2317/626 , C07K2319/00 , C07K2319/33
摘要： The field of the present invention relates to genetically engineered fusion molecules, methods of making said fusion molecules, and uses thereof for treatment of autoimmune diseases. More specifically, the present invention provides novel genetically engineered fusion molecules comprising an interferon (IFN) molecule attached to an antibody (Ab) which targets an antigen which is differentially expressed or up-regulated on activated T cells as compared to resting T cells, wherein the fusion molecule when contacted to an activated T cell results in induced apoptosis and programmed cell death or impairment of functions of said activated T cell.
摘要翻译：本发明的领域涉及基因工程融合分子，制备所述融合分子的方法及其用于治疗自身免疫性疾病的用途。更具体地，本发明提供了新颖的遗传工程融合分子，其包含连接于抗体（Ab）的干扰素（IFN）分子，抗体（Ab）靶向与活化的T细胞差异表达或上调的抗原，与静息T细胞相比，其中当与活化的T细胞接触时，融合分子导致诱导的细胞凋亡和程序性细胞死亡或所述活化的T细胞功能的损伤。

3. 发明申请

WO2017087843A1 METHODS OF TREATING PROLIFERATIVE DISEASES USING ENGINEERED ANTIBODY-INTERFERON FUSION MOLECULES 审中-公开
标题翻译：使用工程抗体 - 干扰素融合分子治疗增殖性疾病的方法
公开(公告)号：WO2017087843A1
公开(公告)日：2017-05-26
申请号：PCT/US2016/062845
申请日：2016-11-18
申请人： IMMUNGENE, INC
发明人： GRESSER, Michael , STEWARD, Kristopher , KHARE, Sanjay
IPC分类号： A61K39/395 , C07K14/56 , C07K16/28 , C07K19/00
CPC分类号： C07K14/56 , A61K2039/505 , A61K2039/54 , A61K2039/545 , C07K16/2887 , C07K2319/00
摘要： The present invention relates to methods of treating a proliferative disease (such as cancer), comprising administering to a patient an effective amount (either as monotherapy or combination therapy) of a tumor-associated antigen antibody ("TAA Ab")-interferon (IFN) fusion molecule. In particular, the present invention relates to methods of treating recurrent, resistant or refractory proliferative diseases, using very low doses.
摘要翻译：本发明涉及治疗增殖性疾病（例如癌症）的方法，所述方法包括向患者施用有效量（作为单一疗法或联合疗法）的肿瘤相关抗原抗体（“ ; TAA Ab“） - 干扰素（IFN）融合分子。特别地，本发明涉及使用非常低的剂量治疗复发性，耐药性或难治性增殖性疾病的方法。

4. 发明申请

WO2017091611A1 ENHANCED CANCER IMMUNOTHERAPY USING ANTIBODY-INTERFERON FUSION MOLECULES 审中-公开
标题翻译：利用抗体 - 干扰素融合分子增强癌症免疫治疗
公开(公告)号：WO2017091611A1
公开(公告)日：2017-06-01
申请号：PCT/US2016/063403
申请日：2016-11-22
申请人： IMMUNGENE, INC
发明人： GRESSER, Michael , STEWARD, Kristopher , KHARE, Sanjay , GREWAL, Iqbal
IPC分类号： A61K38/21 , A61K39/395 , A61P35/00
CPC分类号： A61K38/21 , A61K39/395 , C07K2319/01 , A61K2300/00
摘要： The present invention relates to fusion molecules designed to improve the efficacy of cancer immunotherapy, comprising one or more IFN molecules attached to an antibody which specifically binds to an immune-checkpoint protein antigen. The fusion molecules of the present invention may be administered alone, or in combination with other non- fused immune-checkpoint protein antigen inhibitors or targeted immunotherapies to treat patients that initially failed to respond to previous anti-cancer therapy.
摘要翻译：本发明涉及设计用于改善癌症免疫治疗功效的融合分子，其包含一个或多个IFN分子附着于特异性结合免疫检查点蛋白质抗原的抗体。本发明的融合分子可以单独施用，或者与其他非融合免疫检查点蛋白抗原抑制剂或靶向免疫疗法组合施用以治疗最初对先前的抗癌疗法无响应的患者。

5. 发明申请

WO2016201337A1 ENGINEERED ANTIBODY-INTERFERON FUSION MOLECULES FOR THE TREATMENT OF GLUCOSE-REGULATED PROTEIN 94 (GRP94) EXPRESSING CANCERS 审中-公开
标题翻译：用于治疗葡萄糖调节蛋白94（GRP94）表达癌症的工程抗体 - 干扰素融合分子
公开(公告)号：WO2016201337A1
公开(公告)日：2016-12-15
申请号：PCT/US2016/037038
申请日：2016-06-10
申请人： IMMUNGENE, INC.
发明人： STEWARD, Kristopher , GRESSER, Michael , KHARE, Sanjay
IPC分类号： C07K14/56 , C07K14/565
CPC分类号： C07K14/555 , A61K2039/505 , C07K16/18 , C07K16/30 , C07K16/3061 , C07K2319/00
摘要： The present invention relates to methods of treating a cancer that expresses or overexpresses GRP94 in an individual, comprising administering to the individual a therapeutically effective amount of an isolated non-naturally occurring fusion molecule comprising an antibody or antigen-binding fragment that binds GRP94 ("GRP94 Ab") attached to an interferon (IFN) molecule (hereinafter "GRP94 Ab-IFN fusion molecule"), as monotherapy at therapeutically effective low doses, or in combination with immunotherapy, wherein the combination therapy provides increased effector cell killing. The methods of the present invention are particularly effective treating recurrent, resistant, or refractory GRP94 expressing cancers.
摘要翻译：本发明涉及治疗个体中表达或过表达GRP94的癌症的方法，其包括向个体施用治疗有效量的分离的非天然存在的融合分子，其包含结合GRP94的抗体或抗原结合片段（“ 连接到干扰素（IFN）分子（以下称为“GRP94Ab-IFN融合分子”）作为治疗有效低剂量的单一疗法，或与免疫治疗组合，其中联合疗法提供增加的效应细胞杀伤。本发明的方法特别有效地治疗复发性，耐药性或难治性GRP94表达癌症。

6. 发明申请

WO2009114110A1 ENGINEERED FUSION MOLECULES IMMUNOTHERAPY IN CANCER AND INFLAMMATORY DISEASES 审中-公开
标题翻译：工程化融合分子在癌症和炎症疾病中的免疫治疗
公开(公告)号：WO2009114110A1
公开(公告)日：2009-09-17
申请号：PCT/US2009/001465
申请日：2009-03-07
申请人： IMMUNGENE, INC.
发明人： KHARE, Sanjay, D.
IPC分类号： A61K39/395 , C07K16/30 , A61P35/00
CPC分类号： C07K16/32 , A61K47/6813 , A61K47/6855 , C07K14/521 , C07K14/523 , C07K2319/33 , C07K2319/74 , C07K2319/75
摘要： The field of the present invention relates to genetically engineered fusion molecules, methods of making said fusion molecules, and uses thereof in anti-tumor immunotherapies. More specifically, the present invention relates to engineered fusion molecules consisting of a tumor targeting moiety fused with one or more costimulatory molecules/chemokines/cytokines.
摘要翻译：本发明的领域涉及基因工程融合分子，制备所述融合分子的方法及其在抗肿瘤免疫治疗中的用途。更具体地，本发明涉及由与一种或多种共刺激分子/趋化因子/细胞因子融合的肿瘤靶向部分组成的工程化融合分子。

7. 发明申请

WO2017180764A1 FOCUSED INTERFERON IMMUNOTHERAPY 审中-公开
标题翻译：聚焦干扰素免疫治疗
公开(公告)号：WO2017180764A1
公开(公告)日：2017-10-19
申请号：PCT/US2017/027242
申请日：2017-04-12
申请人： IMMUNGENE, INC.
发明人： GRESSER, Michael , KHARE, Sanjay , STEWARD, Kristopher
IPC分类号： C07K16/00 , C07K14/555
摘要： The present invention relates to methods of treating a proliferative disease (such as cancer) in an individual, comprising administering to the individual a non-naturally occurring fusion molecule comprising an antibody against one or more tumor-associated antigen ("TAA Ab") attached to an interferon (IFN) molecule (hereinafter "TAA Ab-IFN fusion molecule"), as monotherapy at therapeutically effective low doses, or in combination with immunotherapy, wherein the combination therapy provides increased effector cell killing. The methods of the present invention are particularly effective treating recurrent, resistant, or refractory proliferative diseases.
摘要翻译：本发明涉及治疗个体中增殖性疾病（例如癌症）的方法，其包括向个体施用包含针对一种或多种肿瘤相关的抗体的非天然存在的融合分子作为治疗有效低剂量的单一疗法或与免疫疗法组合的抗原（“TAA Ab”）（下文称为“TAA Ab-IFN融合分子”），其中所述组合疗法提供增加的效应物细胞杀伤。本发明的方法特别有效地治疗复发性，耐药性或难治性增殖性疾病。

8. 发明申请

WO2016201350A1 COMBINATION THERAPY FOR TREATMENT OF CANCER 审中-公开
标题翻译：用于治疗癌症的组合治疗
公开(公告)号：WO2016201350A1
公开(公告)日：2016-12-15
申请号：PCT/US2016/037054
申请日：2016-06-10
申请人： IMMUNGENE, INC.
发明人： GRESSER, Michael , KHARE, Sanjay , STEWARD, Kristopher
IPC分类号： C07K16/24 , C07K16/46 , C07K14/555 , C07K14/715 , A61K38/21 , C12N15/19 , C12N15/20 , C12N15/21
CPC分类号： A61K38/21 , A61K31/145 , A61K31/222 , A61K31/336 , A61K31/4045 , A61K31/407 , A61K31/427 , A61K31/5377 , A61K31/69 , A61K39/39558 , C07K14/56 , C07K14/565 , C07K16/18 , C07K2319/00 , C07K2319/75 , A61K2300/00
摘要： Combinations of agents that have a synergistic effect for the treatment of cancer are disclosed herein. The present disclosure is directed to combination therapy methods designed to prevent, treat or manage a cancer that expresses a selective tumor-associated antigen (TAA) in an individual. Specifically, the disclosure provides combination therapies comprising use of a TAA antibody-IFN fusion molecule and a proteasome inhibitor, so as to prevent, treat or manage the cancer.
摘要翻译：本文公开了对治疗癌症具有协同作用的药剂的组合。本公开涉及旨在预防，治疗或管理在个体中表达选择性肿瘤相关抗原（TAA）的癌症的组合治疗方法。具体地，本公开提供了包括使用TAA抗体-IFF融合分子和蛋白酶体抑制剂的组合疗法，以便预防，治疗或治疗癌症。

9. 发明申请

WO2016201251A1 FOCUSED INTERFERON IMMUNOTHERAPY FOR TREATMENT OF CANCER 审中-公开
标题翻译：聚焦干扰素治疗癌症免疫治疗
公开(公告)号：WO2016201251A1
公开(公告)日：2016-12-15
申请号：PCT/US2016/036925
申请日：2016-06-10
申请人： IMMUNGENE, INC.
发明人： GRESSER, Michael , KHARE, Sanjay , STEWARD, Kristopher
IPC分类号： A61K38/21 , C07K14/56 , C07K14/565 , C07K16/30 , C07K19/00
CPC分类号： A61K38/21 , C07K14/56 , C07K14/565 , C07K16/30 , C07K2319/00 , A61K2300/00
摘要： The present invention relates to methods of treating a proliferative disease (such as cancer) in an individual, comprising administering to the individual a non-naturally occurring fusion molecule comprising an antibody against one or more tumor-associated antigen ("TAA Ab") attached to an interferon (IFN) molecule (hereinafter "TAA Ab-IFN fusion molecule"), as monotherapy at therapeutically effective low doses, or in combination with immunotherapy, wherein the combination therapy provides increased effector cell killing. The methods of the present invention are particularly effective treating recurrent, resistant, or refractory proliferative diseases.
摘要翻译：本发明涉及治疗个体中增殖性疾病（例如癌症）的方法，包括向个体施用包含针对一种或多种与肿瘤相关的抗原（“TAA Ab”）的抗体的非天然存在的融合分子涉及干扰素（IFN）分子（以下称为“TAA Ab-IFN融合分子”），作为治疗有效低剂量的单一疗法，或与免疫治疗组合，其中联合疗法提供增加的效应细胞杀伤。本发明的方法特别有效地治疗复发性，抗性或难治性增殖性疾病。

10. 发明申请

WO2013134138A1 ENGINEERED ANTIBODY-INTERFERON MUTANT FUSION MOLECULES 审中-公开
标题翻译：工程抗体干扰突变融合分子
公开(公告)号：WO2013134138A1
公开(公告)日：2013-09-12
申请号：PCT/US2013/028899
申请日：2013-03-04
申请人： IMMUNGENE, INC. , GREWAL, Iqbal , KHARE, Sanjay, D. , GRESSER, Michael , SYED, Rashid
发明人： GREWAL, Iqbal , KHARE, Sanjay, D. , GRESSER, Michael , SYED, Rashid
IPC分类号： A61K38/21 , A61K39/395 , A61P35/00 , C07K14/56 , C07K16/30
CPC分类号： C07K14/56 , A61K38/00 , A61K38/212 , A61K39/39558 , A61K45/06 , A61K2039/505 , C07K16/18 , C07K16/2803 , C07K16/2827 , C07K16/2851 , C07K16/2863 , C07K16/2887 , C07K16/2896 , C07K16/30 , C07K16/32 , C07K2317/73 , C07K2317/76 , C07K2317/90 , C07K2319/00 , C07K2319/30 , C07K2319/33
摘要： The field of the present invention relates to genetically engineered fusion molecules, methods of making said fusion molecules, and uses thereof in anti-tumor immunotherapies. More specifically, the present invention relates to fusion molecule constructs wherein a tumor associated antigen (TAA) antibody (Ab) serves as a targeting moiety to selectively deliver a cytokine to a tumor cell for purposes of killing or inhibiting the growth or proliferation of said tumor cell. In various embodiments, the engineered fusion molecules comprise a TAA Ab fused to an interferon-alpha (IFN-α) mutant molecule. The engineered Ab-IFN-α mutant fusion molecules of the present invention demonstrate improved therapeutic index and preserved or increased efficacy as compared to Ab-wildtype IFN-α fusion molecules, and/or demonstrate improved PK properties as compared to Ab-wildtype IFN-α fusion molecules.
摘要翻译：本发明的领域涉及基因工程融合分子，制备所述融合分子的方法及其在抗肿瘤免疫治疗中的用途。更具体地，本发明涉及融合分子构建体，其中肿瘤相关抗原（TAA）抗体（Ab）用作靶向部分以选择性地将细胞因子递送至肿瘤细胞，以用于杀死或抑制所述肿瘤的生长或增殖细胞。在各种实施方案中，工程改造的融合分子包含与干扰素-α（IFN-α）突变分子融合的TAA Ab。与Ab-野生型IFN-α融合分子相比，本发明的工程改造的Ab-IFN-α突变融合分子表现出改善的治疗指数和保存或增加的功效，和/或与Ab-野生型IFN- α融合分子。

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