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1. 发明申请

WO2014089113A1 ENHANCING ANTI-CANCER ACTIVITY OF IMMUNOMODULATORY FC FUSION PROTEINS 审中-公开
标题翻译：增强免疫球蛋白融合蛋白的抗癌活性
公开(公告)号：WO2014089113A1
公开(公告)日：2014-06-12
申请号：PCT/US2013/072918
申请日：2013-12-03
申请人： BRISTOL-MYERS SQUIBB COMPANY
发明人： ENGELHARDT, John, J. , KORMAN, Alan, J. , QUIGLEY, Michael , SELBY, Mark, J. , WANG, Changyu
IPC分类号： A61K39/00 , A61P35/00 , C07K16/28
CPC分类号： C07K14/435 , A61K2039/505 , C07K16/2818 , C07K16/2875 , C07K16/2878 , C07K2317/41 , C07K2317/52 , C07K2317/71 , C07K2317/72 , C07K2317/73 , C07K2317/75 , C07K2317/76 , C07K2319/30
摘要： The present disclosure provides a method for enhancing the anti-tumor efficacy of an Fc fusion protein which binds specifically to a target, e.g. , a co-inhibitory or co-stimulatory receptor of ligand, on a T cell in a subject afflicted with a cancer or a disease caused by an infectious agent and alters the activity of the immunomodulatory target, thereby potentiating an endogenous immune response against cells of the cancer or the infectious agent, wherein the method comprises selecting, designing or modifying the Fc region of the Fc fusion protein so as to enhance the binding of said Fc region to an activating Fc receptor (FcR). The disclosure also provides an Fc fusion protein produced by said method which has an enhanced ability to potentiate an endogenous immune response against cells of a cancer or an infectious agent in a subject. The disclosure further provides a method for treating a subject which comprises administering to the subject a therapeutically effective amount of an Fc fusion protein, wherein the Fc region of the Fc fusion protein has been selected, designed or modified so as to increase the binding of said Fc region to an activating FcR.
摘要翻译：本公开提供了一种增强Fc融合蛋白的抗肿瘤功效的方法，其特异性结合靶基因，例如配体的共抑制或共刺激受体，在患有癌症的受试者的T细胞上或由感染因子引起的疾病并改变免疫调节靶的活性，从而增强针对癌细胞或感染因子的内源性免疫应答，其中所述方法包括选择，设计或修饰Fc融合蛋白的Fc区以增强所述Fc区与活化Fc受体（FcR）的结合。本公开还提供了通过所述方法产生的Fc融合蛋白，其具有增强受试者中癌症或感染因子的细胞的内源性免疫应答的增强能力。本公开进一步提供了治疗受试者的方法，其包括向受试者施用治疗有效量的Fc融合蛋白，其中已经选择，设计或修饰了Fc融合蛋白的Fc区，以增加所述Fc融合蛋白的结合 Fc区到激活的FcR。

2. 发明申请

WO2017087678A2 ANTIBODIES AGAINST GLUCOCORTICOID-INDUCED TUMOR NECROSIS FACTOR RECEPTOR (GITR) AND USES THEREOF 审中-公开
标题翻译：针对糖皮质激素诱导的肿瘤坏死因子受体（GITR）的抗体及其用途
公开(公告)号：WO2017087678A2
公开(公告)日：2017-05-26
申请号：PCT/US2016/062540
申请日：2016-11-17
申请人： BRISTOL-MYERS SQUIBB COMPANY
发明人： WANG, Changyu , LONBERG, Nils , KORMAN, Alan, J. , SELBY, Mark, J. , SRINIVASAN, Mohan , HENNING, Karla, A. , HAN, Michelle, Minhua , CHEN, Guodong , HUANG, Richard , CHAKRABORTY, Indrani , HUANG, Haichun , WONG, Susan, Chien-Szu , LI, Huiming , BARNHART, Bryan, C. , YAMNIUK, Aaron, P. , LEI, Ming , SCHWEIZER, Liang , HATCHER, Sandra, V. , RAJPAL, Arvind
IPC分类号： C07K16/28
CPC分类号： C07K16/2878 , A61K2039/507 , C07K16/2818 , C07K2317/21 , C07K2317/34 , C07K2317/732 , C07K2317/75 , C07K2317/77 , C07K2317/92
摘要： Provided herein are antibodies, or antigen binding portions thereof, that bind to glucocorticoid-inducible TNF receptor (GITR). Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.
摘要翻译：本文提供结合糖皮质激素诱导型TNF受体（GITR）的抗体或其抗原结合部分。还提供了这些蛋白质在治疗应用中的用途，例如用于治疗癌症。进一步提供了产生抗体的细胞，编码抗体重链和/或轻链可变区的多核苷酸，以及包含编码抗体重链和/或轻链可变区的多核苷酸的载体。

3. 发明申请

WO2016196228A1 ANTIBODIES AGAINST OX40 AND USES THEREOF 审中-公开
标题翻译：反对OX40的抗体及其用途
公开(公告)号：WO2016196228A1
公开(公告)日：2016-12-08
申请号：PCT/US2016/034470
申请日：2016-05-26
申请人： BRISTOL-MYERS SQUIBB COMPANY
发明人： CAI, Zhehong , CHAKRABORTY, Indrani , GARCIA, Marie-Michelle, Navarro , KEMPE, Thomas, D. , KORMAN, Alan, J. , KOZHICH, Alexander, T. , LEMAR, Hadia , MAURER, Mark , MILBURN, Christina, Maria , QUIGLEY, Michael , RODRIGUEZ, Maria , SHAO, Xiang , SRINIVASAN, Mohan , STEVENS, Brenda, L. , THUDIUM, Kent , WONG, Susan, Chien-Szu , GOKEMEIJER, Jochem , WANG, Xi-Tao , CHANG, Han , HUANG, Christine , JURE-KUNKEL, Maria , YANG, Zheng , FENG, Yan , GUIRNALDA, Patrick , LONBERG, Nils , BARNHART, Bryan C. , YAMNIUK, Aaron P. , HENNING, Karla A. , HAN, Michelle Minhua , LEI, Ming , SCHWEIZER, Liang , HATCHER, Sandra V. , RAJPAL, Arvind , AANUR, Praveen , SELBY, Mark J.
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00
CPC分类号： C07K16/2878 , A61K2039/505 , A61K2039/507 , C07K16/2818 , C07K16/30 , C07K16/3023 , C07K16/3038 , C07K16/3069 , C07K2317/21 , C07K2317/31 , C07K2317/33 , C07K2317/34 , C07K2317/565 , C07K2317/567 , C07K2317/73 , C07K2317/74 , C07K2317/75 , C07K2317/76 , C07K2317/92 , C07K2317/94
摘要： Provided herein are antibodies, or antigen binding portions thereof, that bind to OX40. Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.
摘要翻译：本文提供了结合OX40的抗体或其抗原结合部分。还提供了这些蛋白质在治疗应用中的用途，例如在癌症的治疗中。还提供了产生抗体的细胞，编码抗体的重链和/或轻链可变区的多核苷酸，以及包含编码抗体的重链和/或轻链可变区的多核苷酸的载体。

4. 发明申请

WO2016081746A2 ANTIBODIES COMPRISING MODIFIED HEAVY CONSTANT REGIONS 审中-公开
标题翻译：包含改造的重型区域的抗体
公开(公告)号：WO2016081746A2
公开(公告)日：2016-05-26
申请号：PCT/US2015/061632
申请日：2015-11-19
申请人： BRISTOL-MYERS SQUIBB COMPANY
发明人： LONBERG, Nils , KORMAN, Alan, J. , SELBY, Mark, J. , BARNHART, Bryan , YAMNIUK, Aaron, P. , SRINIVASAN, Mohan , HENNING, Karla , HAN, Michalle, Minhua , LEI, Ming , SCHWEIZER, Liang , HATCHER, Sandra, V. , RAJPAL, Arvind
IPC分类号： C07K16/00
CPC分类号： C07K16/00 , C07K16/2878 , C07K16/2896 , C07K2317/522 , C07K2317/524 , C07K2317/53 , C07K2317/71 , C07K2317/72 , C07K2317/75 , C07K2317/77 , C07K2317/92
摘要： Provided herein are heavy chain constant regions (referred to as "modified heavy chain constant regions"), or functionally equivalent fragments thereof, that enhance biological properties of antibodies relative to the same antibodies in unmodified form. An exemplary modified heavy chain constant region includes an IgG2 hinge and three constant domains ( i.e ., CH1, CH2, and CH3 domains), wherein one or more of the constant region domains are of a non-IgG2 isotype ( e.g ., IgG1, IgG3 or IgG4). The heavy chain constant region may comprise wildtype human IgG domain sequences, or variants of these sequences. Also provided herein are methods for enhancing certain biological properties of antibodies that comprise a non-IgG2 hinge, such as internalization, agonism and antagonism, wherein the method comprises replacing the non-IgG2 hinge of the antibody with an IgG2 hinge.
摘要翻译：本文提供了增强抗体相对于未修饰形式的相同抗体的生物学性质的重链恒定区（称为“修饰的重链恒定区”）或其功能上相当的片段。示例性的修饰的重链恒定区包括IgG2铰链和三个恒定结构域（即CH1，CH2和CH3结构域），其中一个或多个恒定区结构域是非IgG2同种型（例如，IgG1，IgG3或 IgG4的）。重链恒定区可以包含野生型人IgG结构域序列或这些序列的变体。本文还提供了增强包含非IgG2铰链的抗体的某些生物学特性的方法，例如内化，激动和拮抗作用，其中所述方法包括用IgG2铰链替代抗体的非IgG2铰链。

5. 发明申请

WO2018218056A8 ANTIBODIES COMPRISING MODIFIED HEAVY CONSTANT REGIONS 审中-公开
公开(公告)号：WO2018218056A8
公开(公告)日：2018-11-29
申请号：PCT/US2018/034446
申请日：2018-05-24
申请人： BRISTOL-MYERS SQUIBB COMPANY
发明人： YAMNIUK, Aaron, P. , KORMAN, Alan, J. , SELBY, Mark, J. , BARNHART, Bryan, C. , LONBERG, Nils , SRINIVASAN, Mohan , HENNING, Karla, A. , HAN, Michelle, Minhua , LEI, Ming , SCHWEIZER, Liang , HATCHER, Sandra, V. , RAJPAL, Arvind
IPC分类号： C07K16/28
摘要： Provided herein are heavy chain constant regions (referred to as "modified heavy chain constant regions"), or functionally equivalent fragments thereof, that enhance biological properties of antibodies relative to the same antibodies in unmodified form. An exemplary modified heavy chain constant region includes an IgG2 hinge and three constant domains (i.e., CH1, CH2, and CH3 domains), wherein one or more of the constant region domains are of a non-IgG2 isotype (e.g., IgG1, IgG3 or IgG4). The heavy chain constant region may comprise wildtype human IgG domain sequences, or variants of these sequences. Also provided herein are methods for enhancing certain biological properties of antibodies that comprise a non-IgG2 hinge, such as internalization, agonism and antagonism, wherein the method comprises replacing the non-IgG2 hinge of the antibody with an IgG2 hinge.

6. 发明申请

WO2018187613A2 ANTI-ICOS AGONIST ANTIBODIES AND USES THEREOF 审中-公开
公开(公告)号：WO2018187613A2
公开(公告)日：2018-10-11
申请号：PCT/US2018/026318
申请日：2018-04-05
申请人： BRISTOL-MYERS SQUIBB COMPANY
发明人： ENGELHARDT, John, J. , SELBY, Mark, J. , KORMAN, Alan, J. , FEINGERSH, Mary, Diane , STEVENS, Brenda, L.
IPC分类号： C07K16/28
摘要： The present invention provides isolated monoclonal antibodies (e.g., humanized and human monoclonal antibodies) that bind to human Inducible T Cell COStimulator (ICOS) and exhibit therapeutically desirable functional properties, e.g., the ability to stimulate human ICOS activity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells, and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules, and pharmaceutical compositions comprising the antibodies of the invention are also provided. The antibodies of the invention can be used, for example, as an agonist to stimulate or enhance an immune response in a subject, e.g., antigen- specific T cell responses against a tumor or viral antigen. The antibodies of the invention can also be used in combination with other antibodies (e.g., PD-1, PD-L1, and/or CTLA-4 antibodies) to treat, for example, cancer. Accordingly, the antibodies can be used in therapeutic applications and methods to detect ICOS protein.

7. 发明申请

WO2017152085A8 COMBINATION THERAPY WITH ANTI-CD73 ANTIBODIES 审中-公开
公开(公告)号：WO2017152085A8
公开(公告)日：2017-09-08
申请号：PCT/US2017/020714
申请日：2017-03-03
申请人： BRISTOL-MYERS SQUIBB COMPANY
发明人： BARNHART, Bryan, C. , KORMAN, Alan, J. , LONBERG, Nils , YAMNIUK, Aaron, P. , SRINIVASAN, Mohan , HENNING, Karla, A. , LEI, Ming , SEGA, Emanuela , GOODENOUGH, Angela , JURE-KUNKEL, Maria , CHEN, Guodong , SACK, John, S. , HUANG, Richard, Y. , CORBETT, Martin, J. , MYERS, Joseph, E. Jr. , SCHWEIZER, Liang , HATCHER, Sandra, V. , ALTURA, Rachel , HUANG, Haichun , ZHANG, Pingping , HILT, Edward, J. , HEDRICK, Michael, Nathan
IPC分类号： C07K16/28 , A61K39/00
摘要： Provided are methods for clinical treatment of tumors (e.g., advanced solid tumors) using an anti-CD73 antibody in combination with an immuno-oncology agent, such as an anti-PD- 1 antibody.

8. 发明申请

WO2017087678A3 ANTIBODIES AGAINST GLUCOCORTICOID-INDUCED TUMOR NECROSIS FACTOR RECEPTOR (GITR) AND USES THEREOF 审中-公开
公开(公告)号：WO2017087678A3
公开(公告)日：2017-05-26
申请号：PCT/US2016/062540
申请日：2016-11-17
申请人： BRISTOL-MYERS SQUIBB COMPANY
发明人： WANG, Changyu , LONBERG, Nils , KORMAN, Alan, J. , SELBY, Mark, J. , SRINIVASAN, Mohan , HENNING, Karla, A. , HAN, Michelle, Minhua , CHEN, Guodong , HUANG, Richard , CHAKRABORTY, Indrani , HUANG, Haichun , WONG, Susan, Chien-Szu , LI, Huiming , BARNHART, Bryan, C. , YAMNIUK, Aaron, P. , LEI, Ming , SCHWEIZER, Liang , HATCHER, Sandra, V. , RAJPAL, Arvind
IPC分类号： C07K16/28 , A61K39/00
摘要： Provided herein are antibodies, or antigen binding portions thereof, that bind to glucocorticoid-inducible TNF receptor (GITR). Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.

9. 发明申请

WO2016196792A1 ANTI-GITR ANTIBODIES FOR CANCER DIAGNOSTICS 审中-公开
标题翻译：用于癌症诊断的抗GITR抗体
公开(公告)号：WO2016196792A1
公开(公告)日：2016-12-08
申请号：PCT/US2016/035514
申请日：2016-06-02
申请人： BRISTOL-MYERS SQUIBB COMPANY
发明人： WANG, Xi-tao , ADELAKUN, Olufemi, A. , LEWIN, Anne, C. , KORMAN, Alan, J. , SELBY, Mark, J. , WANG, Changyu , HUANG, Haichun , HENNING, Karla, A. , LONBERG, Nils , SRINIVASAN, Mohan , HAN, Michelle, Minhua , CHEN, Guodong , HUANG, Richard , CHAKRABORTY, Indrani , WONG, Susan, Chien-Szu , LI, Huiming
IPC分类号： G01N33/566 , C07K16/28
CPC分类号： G01N33/57492 , C07K16/2866 , C07K16/2878 , C07K2317/21 , C07K2317/24 , C07K2317/56 , C07K2317/92 , G01N33/566 , G01N2333/4703 , G01N2333/7051 , G01N2333/70578 , G01N2333/7151 , G01N2800/52 , G01N2800/7028
摘要： Provided herein are diagnostic antibodies that bind to glucocorticoid-induced tumor necrosis factor receptor (GITR). Such antibodies are useful for methods of detecting the expression of GITR in biological samples, for example, tumor tissue, and identifying a cancer patient likely to respond to anti-GITR immunotherapy or predicting whether a cancer patient will respond to anti-GITR immunotherapy.
摘要翻译：本文提供了结合糖皮质激素诱导的肿瘤坏死因子受体（GITR）的诊断抗体。这样的抗体可用于检测生物样品（例如肿瘤组织）中GITR表达的方法，并鉴定可能对抗GITR免疫治疗作出反应的癌症患者或预测癌症患者是否将对抗GITR免疫治疗作出反应。

10. 发明申请

WO2015042246A1 COMBINATION OF ANTI-LAG-3 ANTIBODIES AND ANTI-PD-1 ANTIBODIES TO TREAT TUMORS 审中-公开
标题翻译：抗LAG-3抗体与抗PD-1抗体组合治疗肿瘤
公开(公告)号：WO2015042246A1
公开(公告)日：2015-03-26
申请号：PCT/US2014/056277
申请日：2014-09-18
申请人： BRISTOL-MYERS SQUIBB COMPANY
发明人： KORMAN, Alan, J. , LONBERG, Nils , FONTANA, David, J. , GUTIERREZ, Andres, A. , SELBY, Mark, J. , LEWIS, Katherine, E.
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00
CPC分类号： C07K16/2818 , A61K2039/505 , A61K2039/507 , A61K2039/54 , A61K2039/545 , C07K16/2803 , C07K2317/21 , C07K2317/24 , C07K2317/53 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/94
摘要： Provided are methods for clinical treatment of tumors (e.g., advanced solid tumors) using an anti-LAG-3 antibody in combination with an anti-PD-1 antibody.
摘要翻译：提供了使用抗LAG-3抗体与抗PD-1抗体组合的临床治疗肿瘤（例如，晚期实体瘤）的方法。

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