公开(公告)号：US20060194952A1

公开(公告)日：2006-08-31

申请号：US11430745

申请日：2006-05-09

申请人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan ,  John Wesolowski

发明人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan ,  John Wesolowski

IPC分类号： C07H21/04 ,  C07K16/46 ,  C07K14/54

CPC分类号： C07K16/30 ,  C07K2317/52 ,  C07K2319/00 ,  C07K2319/30

摘要： Disclosed are methods for the genetic construction and expression of antibody-based fusion proteins with enhanced circulating half-lives. The fusion proteins of the present invention lack the ability to bind to immunoglobulin Fc receptors, either as a consequence of the antibody isotype used for fusion protein construction, or through directed mutagenesis of antibody isotypes that normally bind Fc receptors. The fusion proteins of the present invention may also contain a functional domain capable of binding an immunoglobulin protection receptor.

摘要翻译： 公开了用于具有增强的循环半衰期的基于抗体的融合蛋白的遗传构建和表达的方法。 作为用于融合蛋白构建的抗体同种型或通过定向诱变通常结合Fc受体的抗体同种型，本发明的融合蛋白缺乏结合免疫球蛋白Fc受体的能力。 本发明的融合蛋白还可以含有能够结合免疫球蛋白保护受体的功能结构域。

公开(公告)号：US20050137384A1

公开(公告)日：2005-06-23

申请号：US10935532

申请日：2004-09-07

申请人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan

发明人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K47/48 ,  A61P37/04 ,  C07K14/54 ,  C07K16/30 ,  C07K19/00 ,  C12P21/00 ,  C07K16/46

CPC分类号： C07K14/5434 ,  A61K38/00 ,  A61K2039/57 ,  C07K14/54 ,  C07K16/30 ,  C07K2319/00 ,  C07K2319/30

摘要： Disclosed are methods for producing fusion proteins with the heterodimeric cytokine, interleukin-12. In order to insure that the proper ratio of fused and non-fused subunits are obtained in the fusion protein, a specific stepwise approach to genetic engineering is used. This consists of first expressing the non-fused p40 IL-12 subunit in a production cell line, followed by or simultaneously expressing in the same cell, a second recombinant fusion protein consisting of the fused polypeptide linked by a peptide bond to the p35 subunit of IL-12. Molecules containing the p35 fusion protein cannot be secreted from the transfected mammalian cell without first complexing in a one to one ratio with the p40 subunit, thus ensuring the production of active heterodimeric fusion proteins.

摘要翻译： 公开了用异二聚体细胞因子白细胞介素-12产生融合蛋白的方法。 为了确保在融合蛋白中获得融合和非融合亚基的适当比例，使用了基因工程的具体逐步方法。 这包括首先在生产细胞系中表达非融合的p40IL-12亚基，随后或在同一细胞中同时表达第二重组融合蛋白，其由通过肽键连接到p35亚基的p35亚基组成的融合多肽 IL-12。 含有p35融合蛋白的分子不能从转染的哺乳动物细胞中分泌，而与p40亚单位一对一比例没有首先复合，从而确保活性异二聚体融合蛋白的产生。

公开(公告)号：US08420087B2

公开(公告)日：2013-04-16

申请号：US10596997

申请日：2005-01-05

申请人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan ,  Rakesh Verma

发明人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan ,  Rakesh Verma

IPC分类号： A61K39/00 ,  A61K39/395 ,  C12P21/08 ,  C07K16/00

CPC分类号： C07K14/5434 ,  A61K47/6813 ,  A61K47/6851 ,  C07K16/244 ,  C07K16/30 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2319/00 ,  C07K2319/30

摘要： The invention provides a compound comprising a target specific portion and an effector portion wherein the target specific portion comprises or consists of a monoclonal antibody having specificity for oncofoetal fibronectin, or a fragment or variant thereof which retains the antigen binding specificity of the parent monoclonal antibody and the effector portion comprises or consists of interleukin-12, or a functional fragment or variant thereof, characterized in the monoclonal antibody having specificity for oncofoetal fibronectin binds to a region of oncofoetal fibronectin other than the ED-B region. The invention further provides nucleic acids encoding the compounds of the invention, and the use of such compounds in medicine, e.g. in the treatment of cancer.

摘要翻译： 本发明提供了包含目标特异性部分和效应部分的化合物，其中靶特异性部分包含具有对母体纤连蛋白特异性的单克隆抗体或其保留亲本单克隆抗体的抗原结合特异性的片段或变体， 效应部分包含白细胞介素-12或其功能片段或变体，其特征在于具有结合纤维连接蛋白不同于ED-B区域的纤维结合蛋白的特异性的单克隆抗体。 本发明还提供了编码本发明化合物的核酸，以及这些化合物在医学中的用途，例如， 在治疗癌症。

公开(公告)号：US20070202103A1

公开(公告)日：2007-08-30

申请号：US10596997

申请日：2005-01-05

申请人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan ,  Rakesh Verma

发明人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan ,  Rakesh Verma

IPC分类号： A61K39/395 ,  C07H21/04 ,  C12P21/06 ,  C12N5/06 ,  C07K16/30

CPC分类号： C07K14/5434 ,  A61K47/6813 ,  A61K47/6851 ,  C07K16/244 ,  C07K16/30 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2319/00 ,  C07K2319/30

摘要： The invention provides a compound comprising a target specific portion and an effector portion wherein the target specific portion comprises or consists of a monoclonal antibody having specificity for oncofoetal fibronectin, or a fragment or variant thereof which retains the antigen binding specificity of the parent monoclonal antibody and the effector portion comprises or consists of interleukin-12, or a functional fragment or variant thereof, characterised in the monoclonal antibody having specificity for oncofoetal fibronectin binds to a region of oncofoetal fibronectin other than the ED-B region. The invention further provides nucleic acids encoding the compounds of the invention, and the use of such compounds in medicine, e.g. in the treatment of cancer.

摘要翻译： 本发明提供了包含目标特异性部分和效应部分的化合物，其中靶特异性部分包含具有对母体纤连蛋白特异性的单克隆抗体或其保留亲本单克隆抗体的抗原结合特异性的片段或变体， 效应部分包含白细胞介素-12或其功能片段或变体，其特征在于单克隆抗体对于除ED-B区域之外的结合纤维结合蛋白的区域具有特异性。 本发明还提供了编码本发明化合物的核酸，以及这些化合物在医学中的用途，例如， 在治疗癌症。

公开(公告)号：US20090088561A1

公开(公告)日：2009-04-02

申请号：US12244520

申请日：2008-10-02

申请人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan ,  John Wesolowski

发明人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan ,  John Wesolowski

IPC分类号： C07H21/00

CPC分类号： C07K16/30 ,  C07K2317/52 ,  C07K2319/00 ,  C07K2319/30

摘要： Disclosed are methods for the genetic construction and expression of antibody-based fusion proteins with enhanced circulating half-lives. The fusion proteins of the present invention lack the ability to bind to immunoglobulin Fc receptors, either as a consequence of the antibody isotype used for fusion protein construction, or through directed mutagenesis of antibody isotypes that normally bind Fc receptors. The fusion proteins of the present invention may also contain a functional domain capable of binding an immunoglobulin protection receptor.

摘要翻译： 公开了用于具有增强的循环半衰期的基于抗体的融合蛋白的遗传构建和表达的方法。 作为用于融合蛋白构建的抗体同种型或通过定向诱变通常结合Fc受体的抗体同种型，本发明的融合蛋白缺乏结合免疫球蛋白Fc受体的能力。 本发明的融合蛋白还可以含有能够结合免疫球蛋白保护受体的功能结构域。

公开(公告)号：US20080025947A1

公开(公告)日：2008-01-31

申请号：US11825220

申请日：2007-07-05

申请人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan

发明人： Stephen Gillies ,  Kin-Ming Lo ,  Yan Lan

IPC分类号： A61K38/20 ,  A61P37/04 ,  C07K14/55

CPC分类号： C07K16/2866 ,  A61K2039/55533 ,  C07K14/55 ,  C07K16/2812 ,  C07K16/30

摘要： Methods directed to enhancing the effectiveness of IL-2 in stimulating the immune system is disclosed. According to one method, an antagonist directed against the CD25 subunit of the high-affinity IL-2 receptor complex is administered in conjunction with IL-2. The CD25 antagonist may be an anti-CD25 antibody. According to another method, an anti-IL-2 antibody is administered in conjunction with IL-2. In another method, a mutant IL-2 with diminished ability to bind the CD25 subunit of the high-affinity IL-2 receptor complex is administered. In another method, an CD4 antagonist is administered in conjunction with IL-2 in order to stimulate the immune system.

摘要翻译： 公开了旨在增强IL-2在刺激免疫系统中的有效性的方法。 根据一种方法，与IL-2结合施用针对高亲和力IL-2受体复合物的CD25亚基的拮抗剂。 CD25拮抗剂可以是抗CD25抗体。 根据另一种方法，抗IL-2抗体与IL-2联合施用。 在另一种方法中，施用了与高亲和力IL-2受体复合物的CD25亚基结合能力降低的突变体IL-2。 在另一种方法中，CD4拮抗剂与IL-2联合施用以刺激免疫系统。

公开(公告)号：US20130017168A1

公开(公告)日：2013-01-17

申请号：US13434354

申请日：2012-03-29

申请人： Stephen D. Gillies ,  Kin-Ming Lo ,  Yan Lan

发明人： Stephen D. Gillies ,  Kin-Ming Lo ,  Yan Lan

IPC分类号： A61K38/20 ,  A61P35/00 ,  A61P37/04

CPC分类号： C07K16/2866 ,  A61K2039/55533 ,  C07K14/55 ,  C07K16/2812 ,  C07K16/30

摘要： Methods directed to enhancing the effectiveness of IL-2 in stimulating the immune system is disclosed. According to one method, an antagonist directed against the CD25 subunit of the high-affinity IL-2 receptor complex is administered in conjunction with IL-2. The CD25 antagonist may be an anti-CD25 antibody. According to another method, an anti-IL-2 antibody is administered in conjunction with IL-2. In another method, a mutant IL-2 with diminished ability to bind the CD25 subunit of the high-affinity IL-2 receptor complex is administered. In another method, an CD4 antagonist is administered in conjunction with IL-2 in order to stimulate the immune system.

摘要翻译： 公开了旨在增强IL-2在刺激免疫系统中的有效性的方法。 根据一种方法，与IL-2结合施用针对高亲和力IL-2受体复合物的CD25亚基的拮抗剂。 CD25拮抗剂可以是抗-CD25抗体。 根据另一种方法，抗IL-2抗体与IL-2联合施用。 在另一种方法中，施用了与高亲和力IL-2受体复合物的CD25亚基结合能力降低的突变体IL-2。 在另一种方法中，CD4拮抗剂与IL-2联合施用以刺激免疫系统。

公开(公告)号：US07576193B2

公开(公告)日：2009-08-18

申请号：US11804895

申请日：2007-05-21

申请人： Stephen D. Gillies ,  Kin-Ming Lo ,  Yan Lan

发明人： Stephen D. Gillies ,  Kin-Ming Lo ,  Yan Lan

IPC分类号： C12N5/10 ,  C12N15/24 ,  C12N15/62 ,  C12N15/63

CPC分类号： C07K14/5434 ,  A61K38/00 ,  A61K2039/57 ,  C07K14/54 ,  C07K16/30 ,  C07K2319/00 ,  C07K2319/30

摘要： Disclosed are methods for producing fusion proteins with the heterodimeric cytokine, interleukin-12. In order to insure that the proper ratio of fused and non-fused subunits are obtained in the fusion protein, a specific stepwise approach to genetic engineering is used. This consists of first expressing the non-fused p40 IL-12 subunit in a production cell line, followed by or simultaneously expressing in the same cell, a second recombinant fusion protein consisting of the fused polypeptide linked by a peptide bond to the p35 subunit of IL-12. Molecules containing the p35 fusion protein cannot be secreted from the transfected mammalian cell without first complexing in a one to one ratio with the p40 subunit, thus ensuring the production of active heterodimeric fusion proteins.

公开(公告)号：US20100015089A1

公开(公告)日：2010-01-21

申请号：US12498491

申请日：2009-07-07

申请人： Stephen D. Gillies ,  Kin-Ming Lo ,  Yan Lan

发明人： Stephen D. Gillies ,  Kin-Ming Lo ,  Yan Lan

IPC分类号： A61K38/20

CPC分类号： C07K14/5434 ,  A61K38/00 ,  A61K2039/57 ,  C07K14/54 ,  C07K16/30 ,  C07K2319/00 ,  C07K2319/30

摘要： Disclosed are methods for producing fusion proteins with the heterodimeric cytokine, interleukin-12. In order to insure that the proper ratio of fused and non-fused subunits are obtained in the fusion protein, a specific stepwise approach to genetic engineering is used. This consists of first expressing the non-fused p40 IL-12 subunit in a production cell line, followed by or simultaneously expressing in the same cell, a second recombinant fusion protein consisting of the fused polypeptide linked by a peptide bond to the p35 subunit of IL-12. Molecules containing the p35 fusion protein cannot be secreted from the transfected mammalian cell without first complexing in a one to one ratio with the p40 subunit, thus ensuring the production of active heterodimeric fusion proteins.

摘要翻译： 公开了用异二聚体细胞因子白细胞介素-12产生融合蛋白的方法。 为了确保在融合蛋白中获得融合和非融合亚基的适当比例，使用了基因工程的具体逐步方法。 这包括首先在生产细胞系中表达非融合的p40IL-12亚基，随后或在同一细胞中同时表达第二重组融合蛋白，其由通过肽键连接到p35亚基的p35亚基组成的融合多肽 IL-12。 含有p35融合蛋白的分子不能从转染的哺乳动物细胞中分泌，而与p40亚单位一对一比例没有首先复合，从而确保活性异二聚体融合蛋白的产生。

公开(公告)号：US20080311655A1

公开(公告)日：2008-12-18

申请号：US11804895

申请日：2007-05-21

申请人： Stephen D. Gillies ,  Kin-Ming Lo ,  Yan Lan

发明人： Stephen D. Gillies ,  Kin-Ming Lo ,  Yan Lan

IPC分类号： C12N5/06 ,  C12N15/11

CPC分类号： C07K14/5434 ,  A61K38/00 ,  A61K2039/57 ,  C07K14/54 ,  C07K16/30 ,  C07K2319/00 ,  C07K2319/30

摘要： Disclosed are methods for producing fusion proteins with the heterodimeric cytokine, interleukin-12. In order to insure that the proper ratio of fused and non-fused subunits are obtained in the fusion protein, a specific stepwise approach to genetic engineering is used. This consists of first expressing the non-fused p40 IL-12 subunit in a production cell line, followed by or simultaneously expressing in the same cell, a second recombinant fusion protein consisting of the fused polypeptide linked by a peptide bond to the p35 subunit of IL-12. Molecules containing the p35 fusion protein cannot be secreted from the transfected mammalian cell without first complexing in a one to one ratio with the p40 subunit, thus ensuring the production of active heterodimeric fusion proteins.

摘要翻译： 公开了用异二聚体细胞因子白细胞介素-12产生融合蛋白的方法。 为了确保在融合蛋白中获得融合和非融合亚基的适当比例，使用了基因工程的具体逐步方法。 这包括首先在生产细胞系中表达非融合的p40IL-12亚基，随后或在同一细胞中同时表达第二重组融合蛋白，其由通过肽键连接到p35亚基的p35亚基组成的融合多肽 IL-12。 含有p35融合蛋白的分子不能从转染的哺乳动物细胞中分泌，而与p40亚单位一对一比例没有首先复合，从而确保活性异二聚体融合蛋白的产生。