公开(公告)号：US06750334B1

公开(公告)日：2004-06-15

申请号：US08595590

申请日：1996-02-02

申请人： Gary S. Gray ,  Jerry Carson ,  Kashi Javaherian ,  Cindy L. Jellis ,  Paul D. Rennert ,  Sandra Silver

发明人： Gary S. Gray ,  Jerry Carson ,  Kashi Javaherian ,  Cindy L. Jellis ,  Paul D. Rennert ,  Sandra Silver

IPC分类号： C07H2104

CPC分类号： C07K14/70503 ,  A61K38/00 ,  A61K2039/5154 ,  C07K2319/00

摘要： CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g., CD28 and/or CTLA4) on the surface of T cells to thereby suppress an immune response in the subject, for example to inhibit transplantation rejection, graft versus host disease or autoimmune responses.

摘要翻译： 描述了具有修饰的免疫球蛋白恒定区介导的效应子功能的CTLA4-免疫球蛋白融合蛋白，以及编码融合蛋白的核酸。 CTLA4免疫球蛋白融合蛋白包含两个组分：具有CTLA4活性的第一肽和包含免疫球蛋白恒定区的第二个肽，其被修饰以相对于CTLA4-IgG1融合蛋白减少至少一个恒定区介导的生物效应子功能。 本发明的核酸可以整合到各种表达载体中，这又可以指导各种宿主，特别是真核细胞中相应的蛋白质的合成。 本文所述的CTLA4-免疫球蛋白融合蛋白可以施用于受试者以抑制抗原呈递细胞上的CTLA4配体（例如B7-1和/或B7-2）与CTLA4配体的受体（例如， CD28和/或CTLA4），从而抑制受试者的免疫应答，例如抑制移植排斥反应，移植物抗宿主病或自身免疫应答。

公开(公告)号：US06444792B1

公开(公告)日：2002-09-03

申请号：US09227595

申请日：1999-01-08

申请人： Gary S. Gray ,  Jerry Carson ,  Kashi Javaherian ,  Paul D. Rennert ,  Sandra Silver

发明人： Gary S. Gray ,  Jerry Carson ,  Kashi Javaherian ,  Paul D. Rennert ,  Sandra Silver

IPC分类号： A61K39395

CPC分类号： C07K14/70503 ,  A61K38/00 ,  A61K2039/5154 ,  C07K2319/00

摘要： CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g., CD28 and/or CTLA4) on the surface of T cells to thereby suppress an immune response in the subject, for example to inhibit transplantation rejection, graft versus host disease or autoimmune responses.

摘要翻译： 描述了具有修饰的免疫球蛋白恒定区介导的效应子功能的CTLA4-免疫球蛋白融合蛋白，以及编码融合蛋白的核酸。 CTLA4免疫球蛋白融合蛋白包含两个组分：具有CTLA4活性的第一肽和包含免疫球蛋白恒定区的第二个肽，其被修饰以相对于CTLA4-IgG1融合蛋白减少至少一个恒定区介导的生物效应子功能。 本发明的核酸可以整合到各种表达载体中，这又可以指导各种宿主，特别是真核细胞中相应的蛋白质的合成。 本文所述的CTLA4-免疫球蛋白融合蛋白可以施用于受试者以抑制抗原呈递细胞上的CTLA4配体（例如B7-1和/或B7-2）与CTLA4配体的受体（例如， CD28和/或CTLA4），从而抑制受试者的免疫应答，例如抑制移植排斥反应，移植物抗宿主病或自身免疫应答。

公开(公告)号：US20050196402A1

公开(公告)日：2005-09-08

申请号：US10985832

申请日：2004-11-08

申请人： Gary Gray ,  Jerry Carson ,  Kashi Javaherian ,  Paul Rennert ,  Sandra Silver

发明人： Gary Gray ,  Jerry Carson ,  Kashi Javaherian ,  Paul Rennert ,  Sandra Silver

IPC分类号： A61K38/00 ,  C07K14/705 ,  C12N1/21 ,  A61K39/395 ,  C07K16/46

CPC分类号： C07K14/70503 ,  A61K38/00 ,  A61K2039/5154 ,  C07K2319/00

摘要： CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g., CD28 and/or CTLA4) on the surface of T cells to thereby suppress an immune response in the subject, for example to inhibit transplantation rejection, graft versus host disease or autoimmune responses.

摘要翻译： 描述了具有修饰的免疫球蛋白恒定区介导的效应子功能的CTLA4-免疫球蛋白融合蛋白，以及编码融合蛋白的核酸。 CTLA4免疫球蛋白融合蛋白包含两个组分：具有CTLA4活性的第一肽和包含免疫球蛋白恒定区的第二个肽，其被修饰以相对于CTLA4-IgG1融合蛋白减少至少一个恒定区介导的生物效应子功能。 本发明的核酸可以整合到各种表达载体中，这又可以指导各种宿主，特别是真核细胞中相应的蛋白质的合成。 本文所述的CTLA4-免疫球蛋白融合蛋白可以施用于受试者以抑制抗原呈递细胞上的CTLA4配体（例如B7-1和/或B7-2）与CTLA4配体的受体（例如， CD28和/或CTLA4），从而抑制受试者的免疫应答，例如抑制移植排斥反应，移植物抗宿主病或自身免疫应答。