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1. 发明授权

US08216574B2 Engineering Fc antibody regions to confer effector function 有权
标题翻译：工程化Fc抗体区域以产生效应子功能
公开(公告)号：US08216574B2
公开(公告)日：2012-07-10
申请号：US12565911
申请日：2009-09-24
申请人： Jeffrey Stavenhagen , Scott Koenig
发明人： Jeffrey Stavenhagen , Scott Koenig
IPC分类号： A61K39/395 , C07K16/00
CPC分类号： C07K16/30 , C07K16/00 , C07K16/283 , C07K16/2887 , C07K16/2896 , C07K16/32 , C07K2317/41 , C07K2317/52 , C07K2317/72 , C07K2317/732 , C07K2317/734 , C07K2319/30 , G01N33/574
摘要： The present invention relates to molecules having a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region. These modified molecules confer an effector function to a molecule, where the parent molecule does not detectably exhibit this effector function. In particular, the molecules of the invention have an increased effector cell function mediated by a FcγR, such as, but not limited to, ADCC. In one embodiment, the variant Fc region binds FcγRIIIA and/or FcγRIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention have particular utility in treatment, prevention or management of a disease or disorder, such as cancer, in a sub-population of patients, wherein the target antigen is expressed at low levels in the target cell population, in particular, in patients refractory to treatment with an existing therapeutic antibody due to the low level of target antigen expression on the cancer or associated cells.
摘要翻译：本发明涉及具有变体Fc区的分子，其中所述变体Fc区相对于野生型Fc区包含至少一个氨基酸修饰。这些修饰的分子赋予分子的效应子功能，其中母体分子不可检测地显示出该效应子功能。特别地，本发明的分子具有由FcγR介导的增加的效应细胞功能，例如但不限于ADCC。在一个实施方案中，相对于包含野生型Fc区的可比分子，变体Fc区以更高的亲和力结合FcγRIIIA和/或FcγRIIA。本发明的分子在患者的亚群中治疗，预防或治疗疾病或病症（例如癌症）具有特别的用途，其中目标抗原在靶细胞群体中以低水平表达，特别是，在由于癌细胞或相关细胞上的靶抗原表达水平低的现有治疗性抗体治疗难治的患者中。

2. 发明申请

US20050260213A1 Fcgamma-RIIB-specific antibodies and methods of use thereof 审中-公开
标题翻译： FcγRIIB特异性抗体及其使用方法
公开(公告)号：US20050260213A1
公开(公告)日：2005-11-24
申请号：US11108135
申请日：2005-04-15
申请人： Scott Koenig , Maria Veri , Nadine Tuaillon , Ezio Bonvini , Jeffrey Stavenhagen , Christopher Rankin
发明人： Scott Koenig , Maria Veri , Nadine Tuaillon , Ezio Bonvini , Jeffrey Stavenhagen , Christopher Rankin
IPC分类号： A61K39/395 , C07K16/28 , C07K16/46
CPC分类号： C07K16/283 , A61K2039/505 , C07K2317/24 , C07K2317/34 , C07K2317/41 , C07K2317/71 , C07K2317/732 , C07K2317/76 , C07K2317/92
摘要： The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA. The present invention also provides the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.
摘要翻译：本发明涉及以比所述抗体或其片段更大的亲和力结合FcγRIIA，特别是人FcγRIIA的FcγRIIB特别是人FcγRIIB特异性结合的抗体或其片段。本发明还提供抗FcγRIIB抗体或其抗原结合片段作为单一药物治疗用于治疗，预防，治疗或改善癌症，优选B细胞恶性肿瘤，特别是B细胞细胞性慢性淋巴细胞白血病或非霍奇金淋巴瘤，自身免疫性疾病，炎症性疾病，IgE介导的过敏性疾病或其一种或多种症状。本发明提供了通过施用本发明的抗体来增强治疗性抗体的效应功能来增强治疗性抗体的治疗效果的方法。本发明还提供了通过施用本发明的抗体来增强疫苗组合物的功效的方法。

3. 发明申请

US20100196362A1 Engineering Fc Antibody Regions to Confer Effector Function 有权
标题翻译：工程Fc抗体区域，以实现效应功能
公开(公告)号：US20100196362A1
公开(公告)日：2010-08-05
申请号：US12565911
申请日：2009-09-24
申请人： Jeffrey Stavenhagen , Scott Koenig
发明人： Jeffrey Stavenhagen , Scott Koenig
IPC分类号： A61K39/395 , C07K16/00
CPC分类号： C07K16/30 , C07K16/00 , C07K16/283 , C07K16/2887 , C07K16/2896 , C07K16/32 , C07K2317/41 , C07K2317/52 , C07K2317/72 , C07K2317/732 , C07K2317/734 , C07K2319/30 , G01N33/574
摘要： The present invention relates to molecules having a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region. These modified molecules confer an effector function to a molecule, where the parent molecule does not detectably exhibit this effector function. In particular, the molecules of the invention have an increased effector cell function mediated by a FcγR, such as, but not limited to, ADCC. In one embodiment, the variant Fc region binds FcγRIIIA and/or FcγRIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention have particular utility in treatment, prevention or management of a disease or disorder, such as cancer, in a sub-population of patients, wherein the target antigen is expressed at low levels in the target cell population, in particular, in patients refractory to treatment with an existing therapeutic antibody due to the low level of target antigen expression on the cancer or associated cells.
摘要翻译：本发明涉及具有变体Fc区的分子，其中所述变体Fc区相对于野生型Fc区包含至少一个氨基酸修饰。这些修饰的分子赋予分子的效应子功能，其中母体分子不可检测地显示出该效应子功能。特别地，本发明的分子具有由FcγR介导的增加的效应细胞功能，例如但不限于ADCC。在一个实施方案中，相对于包含野生型Fc区的可比分子，变体Fc区以更高的亲和力结合FcγRIIIA和/或FcγRIIA。本发明的分子在患者的亚群中治疗，预防或治疗疾病或病症（例如癌症）具有特别的用途，其中目标抗原在靶细胞群体中以低水平表达，特别是，在由于癌细胞或相关细胞上的靶抗原表达水平低的现有治疗性抗体治疗难治的患者中。

4. 发明授权

US08663634B2 Methods for the treatment of autoimmune disorders using immunosuppressive monoclonal antibodies with reduced toxicity 有权
标题翻译：使用免疫抑制性单克隆抗体治疗自身免疫性疾病的方法，毒性降低
公开(公告)号：US08663634B2
公开(公告)日：2014-03-04
申请号：US11485557
申请日：2006-07-11
申请人： Scott Koenig , Ronald Wilder , Ezio Bonvini , Leslie S. Johnson
发明人： Scott Koenig , Ronald Wilder , Ezio Bonvini , Leslie S. Johnson
IPC分类号： A61K39/395 , A61K39/40 , C07K16/00
CPC分类号： C07K16/2809 , A61K38/28 , A61K2039/505 , C07K2317/24 , C07K2317/524 , C07K2317/53 , C07K2317/71 , A61K2300/00
摘要： The present invention provides methods of treating, preventing or ameliorating the symptoms of T cell-mediated immunological diseases, particularly autoimmune diseases, through the use of anti-CD3 antibodies. In particular, the methods of the invention provide for administration of antibodies that specifically bind the epsilon subunit within the human CD3 complex. Such antibodies modulate the T cell receptor/alloantigen interaction and, thus, regulate the T cell mediated cytotoxicity associated with autoimmune disorders. Additionally, the invention provides for modification of the anti-CD3 antibodies such that they exhibit reduced or eliminated effector function and T cell activation as compared to non-modified anti-CD3 antibodies.
摘要翻译：本发明提供了通过使用抗CD3抗体来治疗，预防或改善T细胞介导的免疫疾病，特别是自身免疫性疾病的症状的方法。特别地，本发明的方法提供了特异性结合人CD3复合物内的ε亚基的抗体的施用。这种抗体调节T细胞受体/同种异体抗原相互作用，因此调节与自身免疫疾病相关的T细胞介导的细胞毒性。另外，本发明提供抗CD3抗体的修饰，使得与未修饰的抗CD3抗体相比，它们表现出降低或消除的效应子功能和T细胞活化。

5. 发明授权

US08187593B2 FcγRIIB specific antibodies and methods of use thereof 有权
标题翻译： FcγRIIB特异性抗体及其使用方法
公开(公告)号：US08187593B2
公开(公告)日：2012-05-29
申请号：US12167760
申请日：2008-07-03
申请人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
发明人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
IPC分类号： A61K39/395 , A61K39/40 , A61K39/00 , C07K16/00
CPC分类号： C07K16/283 , A01K2267/0331 , A61K2039/505 , C07K16/2896 , C07K16/32 , C07K2317/24 , C07K2317/34 , C07K2317/732 , C07K2317/92
摘要： The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies. The present invention provides pharmaceutical compositions comprising an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in amounts effective to prevent, treat, manage, or ameliorate a cancer, such as a B-cell malignancy, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The invention further provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention with a vaccine composition.
摘要翻译：本发明涉及以比所述抗体或其片段更大的亲和力结合FcγRIIA，特别是人FcγRIIA的FcγRIIB特别是人FcγRIIB特异性结合的抗体或其片段。本发明还包括使用抗FcγRIIB抗体或其抗原结合片段作为治疗，预防，治疗或改善癌症，优选B细胞恶性肿瘤，特别是B细胞恶性肿瘤的单一药物治疗细胞性慢性淋巴细胞白血病或非霍奇金淋巴瘤，自身免疫性疾病，炎症性疾病，IgE介导的过敏性疾病或其一种或多种症状。本发明还包括与其他癌症疗法组合的抗FcγRIIB抗体或其抗原结合片段的用途。本发明提供了包含抗FcγRIIB抗体或其抗原结合片段的药物组合物，其量有效地预防，治疗，治疗或改善诸如B细胞恶性肿瘤，自身免疫病症，炎症性疾病，IgE介导的过敏性疾病或其一种或多种症状。本发明还提供了通过施用本发明的抗体来增强治疗性抗体的效应子功能来增强治疗性抗体的治疗效果的方法。本发明还提供了通过用疫苗组合物施用本发明的抗体来增强疫苗组合物的功效的方法。

6. 发明申请

US20120009186A1 FcGammaRIIB Specific Antibodies and Methods of Use Thereof 审中-公开
标题翻译： FcGammaRIIB特异性抗体及其使用方法
公开(公告)号：US20120009186A1
公开(公告)日：2012-01-12
申请号：US13238942
申请日：2011-09-21
申请人： Scott Koenig , Maria Concetta Veri
发明人： Scott Koenig , Maria Concetta Veri
IPC分类号： A61K39/395 , A61P35/00 , C07K16/28
CPC分类号： C07K16/283 , A61K2039/505 , C07K16/2896 , C07K16/32 , C07K2317/24 , C07K2317/732
摘要： The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.
摘要翻译：本发明涉及以比所述抗体或其片段更大的亲和力结合FcγRIIA，特别是人FcγRIIA的FcγRIIB特别是人FcγRIIB特异性结合的抗体或其片段。本发明提供了通过施用本发明的抗体来增强治疗性抗体的效应功能来增强治疗性抗体的治疗效果的方法。本发明还提供了通过施用本发明的抗体来增强疫苗组合物的功效的方法。

7. 发明授权

US08044180B2 FcγRIIB specific antibodies and methods of use thereof 有权
标题翻译： FcγRIIB特异性抗体及其使用方法
公开(公告)号：US08044180B2
公开(公告)日：2011-10-25
申请号：US12167792
申请日：2008-07-03
申请人： Scott Koenig , Maria Concetta Veri
发明人： Scott Koenig , Maria Concetta Veri
IPC分类号： C07K16/00 , C12P21/08 , A61K39/395 , A61K39/00 , A61K39/42 , C12N5/00 , C07K17/00
CPC分类号： C07K16/283 , A61K2039/505 , C07K16/2896 , C07K16/32 , C07K2317/24 , C07K2317/732
摘要： The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.
摘要翻译：本发明涉及以比所述抗体或其片段更大的亲和力结合FcγRIIA，特别是人FcγRIIA的FcγRIIB特别是人FcγRIIB特异性结合的抗体或其片段。本发明提供了通过施用本发明的抗体来增强治疗性抗体的效应功能来增强治疗性抗体的治疗效果的方法。本发明还提供了通过施用本发明的抗体来增强疫苗组合物的功效的方法。

8. 发明申请

US20090076251A1 FcGammaRIIB Specific Antibodies and Methods of Use Thereof 有权
公开(公告)号：US20090076251A1
公开(公告)日：2009-03-19
申请号：US12186058
申请日：2008-08-05
申请人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
发明人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
IPC分类号： C07K16/28
CPC分类号： C07K16/283 , A61K2039/505 , C07K16/2896 , C07K16/32 , C07K2317/24 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/72 , C07K2317/732
摘要： The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, more particularly the extracellular domain of FcγRIIB with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA, and block the Fc binding site of FcγRIIB. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies. The present invention provides pharmaceutical compositions comprising an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in amounts effective to prevent, treat, manage, or ameliorate a cancer, such as a B-cell malignancy, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The invention further provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention with a vaccine composition. The invention further provides methods of treating cancer and/or regulating immune complex-mediated cell activation by administering the antibodies of the invention to enhance an immune response. The invention also provides methods of breaking tolerance to an antigen by administering an antigen-antibody complex and an antibody of the invention.

9. 发明申请

US20090074771A1 FcGammaRIIB Specific Antibodies and Methods of Use Thereof 有权
公开(公告)号：US20090074771A1
公开(公告)日：2009-03-19
申请号：US12186065
申请日：2008-08-05
申请人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
发明人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
IPC分类号： A61K39/395 , G01N33/53 , A61P37/02
CPC分类号： C07K16/283 , A61K2039/505 , C07K16/32 , C07K2317/34 , C07K2317/41 , C07K2317/71 , C07K2317/732 , C07K2317/76
摘要： The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, more particularly the extracellular domain of FcγRIIB with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA, and block the Fc binding site of FcγRIIB. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies. The present invention provides pharmaceutical compositions comprising an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in amounts effective to prevent, treat, manage, or ameliorate a cancer, such as a B-cell malignancy, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The invention further provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention with a vaccine composition. The invention further provides methods of treating cancer and/or regulating immune complex-mediated cell activation by administering the antibodies of the invention to enhance an immune response. The invention also provides methods of breaking tolerance to an antigen by administering an antigen-antibody complex and an antibody of the invention.

10. 发明申请

US20080063649A1 Methods of priming the immunogenic activity of vaccines useful for eliciting a protective immune response 失效
标题翻译：引发用于引发保护性免疫应答的疫苗的免疫原性活性的方法
公开(公告)号：US20080063649A1
公开(公告)日：2008-03-13
申请号：US11935188
申请日：2007-11-05
申请人： Scott Koenig
发明人： Scott Koenig
IPC分类号： A61K39/395 , A61P31/04 , A61P43/00
CPC分类号： C07K16/1027 , A61K39/00 , A61K39/395 , A61K39/40 , A61K39/42 , A61K2039/505 , A61K2039/545 , Y02A50/464 , Y02A50/466 , Y02A50/474
摘要： Disclosed are methods for vaccine priming, using co-treatment, at a temporally similar or at a previous time, with a priming antibody capable of priming, or enhancing, or potentiating the effects of a vaccine, or vaccine composition. Also disclosed are methods of using this process to prevent or treat disease.
摘要翻译：公开了疫苗引发的方法，其使用能够在时间上相似或以前的时间使用能够引发或增强或增强疫苗或疫苗组合物的作用的引发抗体进行共同治疗。还公开了使用该方法预防或治疗疾病的方法。

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