公开(公告)号：US20070259373A1

公开(公告)日：2007-11-08

申请号：US11809905

申请日：2007-05-31

申请人： Gena Whitney ,  Gregory Opiteck ,  Leah Garulacan ,  Chandra Ramanathan ,  Murray McKinnon ,  Kelly Bennett ,  Lauren Barber ,  Angela Cacace ,  Zenta Tsuchihashi ,  John Feder

发明人： Gena Whitney ,  Gregory Opiteck ,  Leah Garulacan ,  Chandra Ramanathan ,  Murray McKinnon ,  Kelly Bennett ,  Lauren Barber ,  Angela Cacace ,  Zenta Tsuchihashi ,  John Feder

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C07K14/705 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/5008 ,  G01N33/5011 ,  G01N33/5017 ,  G01N33/5023 ,  G01N33/5041 ,  G01N33/5044 ,  G01N33/5091 ,  G01N33/566 ,  G01N33/574 ,  G01N33/6884 ,  G01N33/74 ,  G01N2333/726 ,  G01N2500/00 ,  G01N2800/122

摘要： The present invention describes a G-protein coupled receptor (GPCR) family member newly identified as being modified, e.g., phosphorylated, and associated with tyrosine phosphorylated activation complexes, following exposure of cells to smoke from tobacco burning substances, namely, cigarette smoke. This GPCR protein is RAI-3, which was first found to be phosphorylated in cells treated with cigarette smoke and to be associated with other proteins activated in cigarette smoke treated cells by virtue of the present invention. Because cigarette smoke is considered to be a major causative factor of chronic obstructive pulmonary disease (COPD) and disorders and conditions related thereto, the RAI-3 protein is newly provided as a cellular drug target for screening, discovering, and identifying modulators for the treatment and/or prevention of COPD and its related disorders and conditions, such as emphysema and chronic bronchitis. In accordance with the present invention RAI-3 modulators, e.g., agonists and antagonists, can be used as therapeutics in the treatment of COPD and numerous other diseases and disorders that are associated with regulation of NF-κB and/or its associated or interacting signaling molecules. This invention further provides SNPs of RAI-3, e.g., for determining COPD association in individuals.

摘要翻译： 本发明描述了在将烟草暴露于烟草燃烧物质（即香烟烟雾）之后，新鉴定为被修饰，例如磷酸化并与酪氨酸磷酸化活化复合物相关的G-蛋白偶联受体（GPCR）家族成员。 该GPCR蛋白是RAI-3，其首先被发现在用香烟烟雾处理的细胞中被磷酸化并且与通过本发明在香烟烟雾处理的细胞中活化的其它蛋白质相关联。 由于香烟烟雾被认为是慢性阻塞性肺疾病（COPD）的主要致病因素及与之相关的病症和病症，所以RAI-3蛋白质作为筛选，发现和鉴定调节剂治疗的细胞药物靶点被新提供 和/或预防COPD及其相关疾病和病症如肺气肿和慢性支气管炎。 根据本发明，RAI-3调节剂（例如激动剂和拮抗剂）可用作治疗COPD和许多与调节NF-κB和/或其相关或相互作用的信号相关的其它疾病和病症 分子。 本发明还提供RAI-3的SNP，例如用于确定个体中的COPD关联。

公开(公告)号：US07517652B2

公开(公告)日：2009-04-14

申请号：US11809905

申请日：2007-05-31

申请人： Gena S. Whitney ,  Gregory Opiteck ,  Leah Ann Garulacan ,  Chandra S. Ramanathan ,  Murray McKinnon ,  John N. Feder

发明人： Gena S. Whitney ,  Gregory Opiteck ,  Leah Ann Garulacan ,  Chandra S. Ramanathan ,  Murray McKinnon ,  John N. Feder

IPC分类号： C12Q1/68 ,  C07H21/04

CPC分类号： C12Q1/6886 ,  C07K14/705 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/5008 ,  G01N33/5011 ,  G01N33/5017 ,  G01N33/5023 ,  G01N33/5041 ,  G01N33/5044 ,  G01N33/5091 ,  G01N33/566 ,  G01N33/574 ,  G01N33/6884 ,  G01N33/74 ,  G01N2333/726 ,  G01N2500/00 ,  G01N2800/122

摘要： The present invention describes a G-protein coupled receptor (GPCR) family member newly identified as being modified, e.g., phosphorylated, and associated with tyrosine phosphorylated activation complexes, following exposure of cells to smoke from tobacco burning substances, namely, cigarette smoke. This GPCR protein is RAI-3, which was first found to be phosphorylated in cells treated with cigarette smoke and to be associated with other proteins activated in cigarette smoke treated cells by virtue of the present invention. Because cigarette smoke is considered to be a major causative factor of chronic obstructive pulmonary disease (COPD) and disorders and conditions related thereto, the RAI-3 protein is newly provided as a cellular drug target for screening, discovering, and identifying modulators for the treatment and/or prevention of COPD and its related disorders and conditions, such as emphysema and chronic bronchitis. In accordance with the present invention RAI-3 modulators, e.g., agonists and antagonists, can be used as therapeutics in the treatment of COPD and numerous other diseases and disorders that are associated with regulation of NF-κB and/or its associated or interacting signaling molecules. This invention further provides SNPs of RAI-3, e.g., for determining COPD association in individuals.

摘要翻译： 本发明描述了在将烟草暴露于烟草燃烧物质（即香烟烟雾）之后，新鉴定为被修饰，例如磷酸化并与酪氨酸磷酸化活化复合物相关的G-蛋白偶联受体（GPCR）家族成员。 该GPCR蛋白是RAI-3，其首先被发现在用香烟烟雾处理的细胞中被磷酸化并且与通过本发明在香烟烟雾处理的细胞中活化的其它蛋白质相关联。 由于香烟烟雾被认为是慢性阻塞性肺疾病（COPD）的主要致病因素及与之相关的病症和病症，所以RAI-3蛋白质作为筛选，发现和鉴定调节剂治疗的细胞药物靶点被新提供 和/或预防COPD及其相关疾病和病症如肺气肿和慢性支气管炎。 根据本发明，RAI-3调节剂（例如激动剂和拮抗剂）可用作治疗COPD和许多与调节NF-κB和/或其相关或相互作用的信号相关的其它疾病和病症 分子。 本发明还提供RAI-3的SNP，例如用于确定个体中的COPD关联。

公开(公告)号：US08168759B2

公开(公告)日：2012-05-01

申请号：US12505166

申请日：2009-07-17

申请人： Murray McKinnon ,  Steven G. Nadler ,  Suzanne J. Suchard ,  Brendan Classon ,  Steve Holmes ,  Olga Ignatovich ,  Christopher Plummer ,  Steve Grant

发明人： Murray McKinnon ,  Steven G. Nadler ,  Suzanne J. Suchard ,  Brendan Classon ,  Steve Holmes ,  Olga Ignatovich ,  Christopher Plummer ,  Steve Grant

IPC分类号： C07K16/00 ,  A61K39/395

CPC分类号： C07K16/2818 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/2896 ,  C07K2317/31 ,  C07K2317/569 ,  C07K2317/73

摘要： Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

摘要翻译： 公开了单价结合CD28的结构域抗体。 对CD28结合而言是单价的域抗体可抑制CD28活性。 在一个方面，结构域抗体由一个方面组成或包含单个免疫球蛋白可变区，其特异性结合并拮抗CD28的活性，一方面，没有实质上激动的CD28活性。 另一方面，结构域抗体是人结构域抗体。 本公开还包括在个体中拮抗CD80和/或CD86相互作用的方法以及涉及与CD28相互作用的CD80和/或CD86相互作用的疾病或病症的方法，所述方法涉及对个体施用结构域抗体。

公开(公告)号：US20120201814A1

公开(公告)日：2012-08-09

申请号：US13416033

申请日：2012-03-09

申请人： Murray McKinnon ,  Steven G. Nadler ,  Suzanne J. Suchard ,  Brendan Classon ,  Steve Holmes ,  Olga Ignatovich ,  Christopher Plummer ,  Steve Grant

发明人： Murray McKinnon ,  Steven G. Nadler ,  Suzanne J. Suchard ,  Brendan Classon ,  Steve Holmes ,  Olga Ignatovich ,  Christopher Plummer ,  Steve Grant

IPC分类号： A61K39/395 ,  A61P29/00 ,  A61P37/02 ,  A61P37/00 ,  A61P37/06

CPC分类号： C07K16/2818 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/2896 ,  C07K2317/31 ,  C07K2317/569 ,  C07K2317/73

摘要： Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

摘要翻译： 公开了单价结合CD28的结构域抗体。 对CD28结合而言是单价的域抗体可抑制CD28活性。 在一个方面，结构域抗体由一个方面组成或包含单个免疫球蛋白可变区，其特异性结合并拮抗CD28的活性，一方面，没有实质上激动的CD28活性。 另一方面，结构域抗体是人结构域抗体。 本公开还包括在个体中拮抗CD80和/或CD86相互作用的方法以及涉及与CD28相互作用的CD80和/或CD86相互作用的疾病或病症的方法，所述方法涉及对个体施用结构域抗体。

公开(公告)号：US09085629B2

公开(公告)日：2015-07-21

申请号：US13415914

申请日：2012-03-09

申请人： Murray McKinnon ,  Steven G. Nadler ,  Suzanne J. Suchard ,  Brendan Classon ,  Steve Holmes ,  Olga Ignatovich ,  Christopher Plummer ,  Steve Grant

发明人： Murray McKinnon ,  Steven G. Nadler ,  Suzanne J. Suchard ,  Brendan Classon ,  Steve Holmes ,  Olga Ignatovich ,  Christopher Plummer ,  Steve Grant

IPC分类号： C07K16/28

CPC分类号： C07K16/2818 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/2896 ,  C07K2317/31 ,  C07K2317/569 ,  C07K2317/73

摘要： Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

摘要翻译： 公开了单价结合CD28的结构域抗体。 对CD28结合而言是单价的域抗体可抑制CD28活性。 在一个方面，结构域抗体由一个方面组成或包含单个免疫球蛋白可变区，其特异性结合并拮抗CD28的活性，一方面，没有实质上激动的CD28活性。 另一方面，结构域抗体是人结构域抗体。 本公开还包括在个体中拮抗CD80和/或CD86相互作用的方法以及涉及与CD28相互作用的CD80和/或CD86相互作用的疾病或病症的方法，所述方法涉及对个体施用结构域抗体。

公开(公告)号：US08454959B2

公开(公告)日：2013-06-04

申请号：US13416033

申请日：2012-03-09

申请人： Murray McKinnon ,  Steven G. Nadler ,  Suzanne J. Suchard ,  Brendan Classon ,  Steve Holmes ,  Olga Ignatovich ,  Christopher Plummer ,  Steve Grant

发明人： Murray McKinnon ,  Steven G. Nadler ,  Suzanne J. Suchard ,  Brendan Classon ,  Steve Holmes ,  Olga Ignatovich ,  Christopher Plummer ,  Steve Grant

IPC分类号： A61K39/395

CPC分类号： C07K16/2818 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/2896 ,  C07K2317/31 ,  C07K2317/569 ,  C07K2317/73

摘要： Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

公开(公告)号：US20130109846A1

公开(公告)日：2013-05-02

申请号：US13415914

申请日：2012-03-09

申请人： Murray McKinnon ,  Steven G. Nadler ,  Suzanne J. Suchard ,  Brendan Classon ,  Steve Holmes ,  Olga Ignatovich ,  Christopher Plummer ,  Steve Grant

发明人： Murray McKinnon ,  Steven G. Nadler ,  Suzanne J. Suchard ,  Brendan Classon ,  Steve Holmes ,  Olga Ignatovich ,  Christopher Plummer ,  Steve Grant

IPC分类号： C07K16/28

CPC分类号： C07K16/2818 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/2896 ,  C07K2317/31 ,  C07K2317/569 ,  C07K2317/73

摘要： Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

公开(公告)号：US20100028354A1

公开(公告)日：2010-02-04

申请号：US12505166

申请日：2009-07-17

申请人： Murray McKinnon ,  Steven G. Nadler ,  Suzanne J. Suchard ,  Brendan Classon ,  Steve Holmes ,  Olga Ignatovich ,  Christopher Plummer ,  Steve Grant

发明人： Murray McKinnon ,  Steven G. Nadler ,  Suzanne J. Suchard ,  Brendan Classon ,  Steve Holmes ,  Olga Ignatovich ,  Christopher Plummer ,  Steve Grant

IPC分类号： A61K39/395 ,  C07K16/00 ,  A61P37/00

CPC分类号： C07K16/2818 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/2896 ,  C07K2317/31 ,  C07K2317/569 ,  C07K2317/73

摘要： Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

摘要翻译： 公开了单价结合CD28的结构域抗体。 对CD28结合而言是单价的域抗体可抑制CD28活性。 在一个方面，结构域抗体由一个方面组成或包含单个免疫球蛋白可变区，其特异性结合并拮抗CD28的活性，一方面，没有实质上激动的CD28活性。 另一方面，结构域抗体是人结构域抗体。 本公开还包括在个体中拮抗CD80和/或CD86相互作用的方法以及涉及与CD28相互作用的CD80和/或CD86相互作用的疾病或病症的方法，所述方法涉及对个体施用结构域抗体。