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1. 发明申请

US20050208497A1 Promoter motifs in Candida tropicalis 有权
标题翻译：热带假丝酵母的启动子图案
公开(公告)号：US20050208497A1
公开(公告)日：2005-09-22
申请号：US10640962
申请日：2003-08-14
申请人： C. Wilson , David Craft , Yeyan Zhang , Jeffrey Stavenhagen
发明人： C. Wilson , David Craft , Yeyan Zhang , Jeffrey Stavenhagen
IPC分类号： C12N9/02 , C12Q1/68 , C07H21/04 , C12N1/18 , C12N15/74
CPC分类号： C12N9/0042
摘要： The present invention provides modified promoters from Candida troplicalis CYP and POX4 genes. The modified promoters have various sequence motifs added, deleted, or altered in order to modulate expression of a coding sequence operably linked thereto. The sequence motifs comprise repressors of gene induction (URS sequences) and activators of gene induction (UAS sequences) as well as oleic acid response elements (ORE sequences). Yeast host cells comprising such modified promoters are also provided. Methods of altering expression of a protein of the beta or omega oxidation pathways using a subject modified promoter are also provided.
摘要翻译：本发明提供了来自假丝酵母CYP和POX4基因的修饰的启动子。修饰的启动子具有添加，缺失或改变的各种序列基序，以便调节与其可操作地连接的编码序列的表达。序列基序包括基因诱导阻遏物（URS序列）和基因诱导活化剂（UAS序列）以及油酸反应元件（ORE序列）。还提供了包含这种修饰的启动子的酵母宿主细胞。还提供了使用受试者修饰的启动子改变β或ω-氧化途径的蛋白质表达的方法。

2. 发明授权

US07960512B2 Identification and engineering of antibodies with variant Fc regions and methods of using same 有权
标题翻译：具有变体Fc区的抗体的鉴定和工程及其使用方法
公开(公告)号：US07960512B2
公开(公告)日：2011-06-14
申请号：US10902588
申请日：2004-07-28
申请人： Jeffrey Stavenhagen , Sujata Vijh , Christopher Rankin , Sergey Gorlatov , Ling Huang
发明人： Jeffrey Stavenhagen , Sujata Vijh , Christopher Rankin , Sergey Gorlatov , Ling Huang
IPC分类号： C12P21/08 , C07K16/00 , C07K17/00
CPC分类号： A61K39/39558 , A61K2039/505 , C07K16/00 , C07K16/005 , C07K2317/52 , C07K2317/732 , C07K2317/734
摘要： The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which 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 are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.
摘要翻译：本发明涉及包括变体Fc区的分子，特别是多肽，更特别是免疫球蛋白（例如，抗体），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，所述变体Fc区相对于包含野生型Fc区的可比分子，以更高的亲和力结合FcγRIIIA和/或FcγRIIA。本发明的分子特别可用于预防，治疗或改善与疾病，病症或感染相关的一种或多种症状。本发明的分子特别可用于治疗或预防需要由FcγR介导的效应细胞功能增强的功效（例如ADCC）的疾病或病症，例如癌症，感染性疾病和增强治疗功效的治疗性抗体，其作用由ADCC介导。

3. 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。

4. 发明申请

US20080131435A1 Identification and Engineering of Antibodies With Variant Fc Regions and Methods of Using Same 有权
标题翻译：具有变异Fc区的抗体的鉴定和工程及其使用方法
公开(公告)号：US20080131435A1
公开(公告)日：2008-06-05
申请号：US12022772
申请日：2008-01-30
申请人： Jeffrey Stavenhagen , Sujata Vijh , Christopher Rankin , Sergey Gorlatov , Ling Huang
发明人： Jeffrey Stavenhagen , Sujata Vijh , Christopher Rankin , Sergey Gorlatov , Ling Huang
IPC分类号： A61K39/395 , C07K16/00 , C12N15/00 , C07H21/04 , C12N5/00 , C12P21/04
CPC分类号： C07K14/70535 , C07K14/36 , C07K14/405 , C07K16/005 , C07K16/283 , C07K16/2887 , C07K16/32 , C07K16/44 , C07K2317/24 , C07K2317/52 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/76 , C07K2317/92 , C07K2319/70 , G01N33/6857 , G01N2333/70535
摘要： The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which 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 are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.
摘要翻译：本发明涉及包括变体Fc区的分子，特别是多肽，更特别是免疫球蛋白（例如，抗体），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，所述变体Fc区相对于包含野生型Fc区的可比较分子，以更大的亲和力结合FcγRIIIA和/或FcγRIIA。本发明的分子特别可用于预防，治疗或改善与疾病，病症或感染相关的一种或多种症状。本发明的分子特别可用于治疗或预防需要通过FcγAMR介导的效应细胞功能增强的功效（例如ADCC）的疾病或病症，例如癌症，感染性疾病和增强治疗功效的治疗性抗体，其作用由ADCC介导。

5. 发明授权

US07355008B2 Identification and engineering of antibodies with variant Fc regions and methods of using same 有权
标题翻译：具有变体Fc区的抗体的鉴定和工程及其使用方法
公开(公告)号：US07355008B2
公开(公告)日：2008-04-08
申请号：US10754922
申请日：2004-01-09
申请人： Jeffrey Stavenhagen , Sujata Vijh , Christopher Rankin , Sergey Gorlatov , Ling Huang
发明人： Jeffrey Stavenhagen , Sujata Vijh , Christopher Rankin , Sergey Gorlatov , Ling Huang
IPC分类号： C07K16/00 , C12P21/08 , C07K1/00
CPC分类号： C07K14/70535 , C07K14/36 , C07K14/405 , C07K16/005 , C07K16/283 , C07K16/2887 , C07K16/32 , C07K16/44 , C07K2317/24 , C07K2317/52 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/76 , C07K2317/92 , C07K2319/70 , G01N33/6857 , G01N2333/70535
摘要： The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds FcγRIIA and/or FcγRIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.
摘要翻译：本发明涉及包括变体Fc区的分子，特别是多肽，更特别是免疫球蛋白（例如，抗体），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，所述变体Fc区相对于包含野生型Fc区的可比分子，以更高的亲和力结合FcγRIIA和/或FcγRIIA。本发明的分子特别可用于预防，治疗或改善与疾病，病症或感染相关的一种或多种症状。本发明的分子特别可用于治疗或预防需要通过FcγAMR介导的效应细胞功能增强的功效（例如ADCC）的疾病或病症，例如癌症，感染性疾病和增强治疗功效的治疗性抗体，其作用由ADCC介导。

6. 发明授权

US09028815B2 Identification and engineering of antibodies with variant FC regions and methods of using same 有权
标题翻译：用变体FC区鉴定和设计抗体及其使用方法
公开(公告)号：US09028815B2
公开(公告)日：2015-05-12
申请号：US13182209
申请日：2011-07-13
申请人： Jeffrey Stavenhagen , Sujata Vijh , Christopher Rankin , Sergey Gorlatov , Ling Huang
发明人： Jeffrey Stavenhagen , Sujata Vijh , Christopher Rankin , Sergey Gorlatov , Ling Huang
IPC分类号： A61K39/395 , A61K39/40 , C07K16/28 , C07K16/32 , C07K16/44 , C07K16/00
CPC分类号： C07K14/70535 , C07K14/36 , C07K14/405 , C07K16/005 , C07K16/283 , C07K16/2887 , C07K16/32 , C07K16/44 , C07K2317/24 , C07K2317/52 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/76 , C07K2317/92 , C07K2319/70 , G01N33/6857 , G01N2333/70535
摘要： The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which 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 are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.
摘要翻译：本发明涉及包括变体Fc区的分子，特别是多肽，更特别是免疫球蛋白（例如，抗体），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，所述变体Fc区相对于包含野生型Fc区的可比分子，以更高的亲和力结合FcγRIIIA和/或FcγRIIA。本发明的分子特别可用于预防，治疗或改善与疾病，病症或感染相关的一种或多种症状。本发明的分子特别可用于治疗或预防需要由FcγR介导的效应细胞功能增强的功效（例如ADCC）的疾病或病症，例如癌症，感染性疾病和增强治疗功效的治疗性抗体，其作用由ADCC介导。

7. 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。

8. 发明申请

US20080138344A1 Identification and Engineering of Antibodies with Variant Fc Regions and Methods of Using Same 有权
标题翻译：具有变异Fc区的抗体的鉴定和工程及其使用方法
公开(公告)号：US20080138344A1
公开(公告)日：2008-06-12
申请号：US12022762
申请日：2008-01-30
申请人： Jeffrey Stavenhagen , Sujata Vijh , Christopher Rankin , Sergey Gorlatov , Ling Huang
发明人： Jeffrey Stavenhagen , Sujata Vijh , Christopher Rankin , Sergey Gorlatov , Ling Huang
IPC分类号： A61K39/395 , C07K16/00 , C07H21/04 , C12N15/00 , C12N5/00 , C12P21/04
CPC分类号： C07K14/70535 , C07K14/36 , C07K14/405 , C07K16/005 , C07K16/283 , C07K16/2887 , C07K16/32 , C07K16/44 , C07K2317/24 , C07K2317/52 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/76 , C07K2317/92 , C07K2319/70 , G01N33/6857 , G01N2333/70535
摘要： The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which 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 are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.
摘要翻译：本发明涉及包括变体Fc区的分子，特别是多肽，更特别是免疫球蛋白（例如，抗体），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，所述变体Fc区相对于包含野生型Fc区的可比较分子，以更大的亲和力结合FcγRIIIA和/或FcγRIIA。本发明的分子特别可用于预防，治疗或改善与疾病，病症或感染相关的一种或多种症状。本发明的分子特别可用于治疗或预防需要通过FcγAMR介导的效应细胞功能增强的功效（例如ADCC）的疾病或病症，例如癌症，感染性疾病和增强治疗功效的治疗性抗体，其作用由ADCC介导。

9. 发明授权

US08217147B2 Identification and engineering of antibodies with variant Fc regions and methods of using same 有权
公开(公告)号：US08217147B2
公开(公告)日：2012-07-10
申请号：US11502820
申请日：2006-08-10
申请人： Jeffrey Stavenhagen , Sergey Gorlatov , Christopher Rankin , Nadine Tuaillon
发明人： Jeffrey Stavenhagen , Sergey Gorlatov , Christopher Rankin , Nadine Tuaillon
IPC分类号： C07K16/00 , C12P21/08 , C07H21/04 , C12Q1/68 , C12N15/00 , C12N5/16 , C07K17/00
CPC分类号： G01N33/574 , A61K2039/505 , C07K16/283 , C07K16/2887 , C07K16/32 , C07K16/44 , C07K2317/24 , C07K2317/52 , C07K2317/72 , C07K2317/732 , C07K2317/734 , C07K2317/76 , C07K2317/92 , C07K2319/30
摘要： The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which 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 are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

10. 发明申请

US20050037000A1 Identification and engineering of antibodies with variant Fc regions and methods of using same 有权
标题翻译：具有变体Fc区的抗体的鉴定和工程及其使用方法
公开(公告)号：US20050037000A1
公开(公告)日：2005-02-17
申请号：US10754922
申请日：2004-01-09
申请人： Jeffrey Stavenhagen , Sujata Vijh , Christopher Rankin , Sergey Gorlatov , Ling Huang
发明人： Jeffrey Stavenhagen , Sujata Vijh , Christopher Rankin , Sergey Gorlatov , Ling Huang
IPC分类号： C07K16/00 , A61K39/395 , C07K16/44
CPC分类号： C07K14/70535 , C07K14/36 , C07K14/405 , C07K16/005 , C07K16/283 , C07K16/2887 , C07K16/32 , C07K16/44 , C07K2317/24 , C07K2317/52 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/76 , C07K2317/92 , C07K2319/70 , G01N33/6857 , G01N2333/70535
摘要： The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds FcγRIIA and/or FcγRIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.
摘要翻译：本发明涉及包括变体Fc区的分子，特别是多肽，更特别是免疫球蛋白（例如，抗体），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，所述变体Fc区相对于包含野生型Fc区的可比分子，以更高的亲和力结合FcγRIIA和/或FcγRIIA。本发明的分子特别可用于预防，治疗或改善与疾病，病症或感染相关的一种或多种症状。本发明的分子特别可用于治疗或预防需要通过FcγAMR介导的效应细胞功能增强的功效（例如ADCC）的疾病或病症，例如癌症，感染性疾病和增强治疗功效的治疗性抗体，其作用由ADCC介导。

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