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公开(公告)号:WO2011053699A1
公开(公告)日:2011-05-05
申请号:PCT/US2010/054475
申请日:2010-10-28
Applicant: ABBOTT LABORATORIES , CARSON, Gerald R. , GION, Wendy R. , KUNES, Yune Z. , LEISE III, Walter F. , DAVIS-TABER, Rachel A. , FUNG, Emma
Inventor: CARSON, Gerald R. , GION, Wendy R. , KUNES, Yune Z. , LEISE III, Walter F. , DAVIS-TABER, Rachel A. , FUNG, Emma
CPC classification number: C07K16/00 , C07K16/241 , C07K16/244 , C07K2317/14 , C07K2317/21 , C07K2317/76 , C07K2319/50 , C07K2319/92
Abstract: Embodiments of the invention relate to vector constructs and methods for expression of polypeptides including multimeric products such as therapeutic antibodies. Particular constructs allow for the generation of expression products from a single open reading frame (sORF). An embodiment provides an isolated or purified expression vector for generating one or more recombinant protein products comprising a single open reading frame insert; said insert comprising a signal peptide nucleic acid sequence encoding a signal peptide; a first nucleic acid sequence encoding a first polypeptide; a first intervening nucleic acid sequence encoding a first protein cleavage site, wherein said first protein cleavage site is provided by an intein segment of a Ion protease gene of Pyrococcus or a klbA gene of Pyrococcus or Methanococcus , or a modified intein segment derived therefrom; and a second nucleic acid sequence encoding a second polypeptide. Certain embodiments of constructs and methods employ an intein segment of a Ion protease gene of Pyrococcus abyssi , Pyrococcus furiosus , or Pyrococcus horikoshii OT3; or an intein segment of a klbA gene of Pyrococcus abyssi , Pyrococcus furiosus , or Methanococcus jannaschii ; or other intein segment.
Abstract translation: 本发明的实施方案涉及用于表达多肽的载体构建体和方法,包括多聚体产物,例如治疗性抗体。 特定结构允许从单个开放阅读框(sORF)生成表达产物。 一个实施方案提供了用于产生一种或多种包含单个开放阅读框插入物的重组蛋白产物的分离或纯化的表达载体; 所述插入片段包含编码信号肽的信号肽核酸序列; 编码第一多肽的第一核酸序列; 编码第一蛋白切割位点的第一插入核酸序列,其中所述第一蛋白切割位点由Pyrococcus的离子蛋白酶基因的内含肽片段或Pyrococcus或Methanococcus的klbA基因或由其衍生的修饰的内含肽片段提供; 和编码第二多肽的第二核酸序列。 构建体和方法的某些实施方案采用激烈的球孢球菌,激烈火球菌或火球菌OT3的离子蛋白酶基因的内含肽片段; 或激烈球菌(Crrococcus abyssi),激烈火球菌(Pyrococcus furiosus)或季戊糖(Methanococcus jannaschii)的klbA基因的内含肽片段; 或其他内含肽片段。
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2.
公开(公告)号:WO2009029123A1
公开(公告)日:2009-03-05
申请号:PCT/US2007/087514
申请日:2007-12-14
Applicant: ABBOTT LABORATORIES , REILLY, Edward, B. , LACY, Susan, E. , FUNG, Emma , BELK, Jonathan, P. , ROGUSKA, Michael , STOLL, Vincent, S. , JAKOB, Clarissa
Inventor: REILLY, Edward, B. , LACY, Susan, E. , FUNG, Emma , BELK, Jonathan, P. , ROGUSKA, Michael , STOLL, Vincent, S. , JAKOB, Clarissa
IPC: C07K16/28
CPC classification number: C07K16/2863 , C07K2317/21 , C07K2317/34 , C07K2317/565 , C07K2317/622 , C07K2317/74 , C07K2317/92
Abstract: The present invention relates to antibodies and antigen-binding portions thereof that bind to and activate an erythropoietin receptor. The invention also relates to nucleic acid sequences encoding such antibodies and antigen-binding portions. The present invention further relates to methods of activating the endogenous activity of an erythropoietin receptor in a mammal using said antibodies and antigen-binding portions, methods of treatment, as well as pharmaceutical compositions comprising said antibodies and antigen-binding portions. The invention further provides compositions and crystals of an erythropoietin receptor in complex with an anti-erythropoietin receptor antibody. Specifically, the high-resolution structure provides binding sites defined by the structure coordinated determined herein.
Abstract translation: 本发明涉及结合并激活促红细胞生成素受体的抗体及其抗原结合部分。 本发明还涉及编码这种抗体和抗原结合部分的核酸序列。 本发明还涉及使用所述抗体和抗原结合部分,治疗方法以及包含所述抗体和抗原结合部分的药物组合物来激活哺乳动物中促红细胞生成素受体的内源性活性的方法。 本发明还提供与抗促红细胞生成素受体抗体复合的促红细胞生成素受体的组合物和晶体。 具体地,高分辨率结构提供由本文确定的结构所定义的结合位点。
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公开(公告)号:WO2007005608A3
公开(公告)日:2008-10-09
申请号:PCT/US2006025584
申请日:2006-06-29
Applicant: ABBOTT LAB , LACY SUSAN E , FUNG EMMA , BELK JONATHAN P , DIXON RICHARD W , ROGUSKA MICHAEL , HINTON PAUL R , KUMAR SHANKAR
Inventor: LACY SUSAN E , FUNG EMMA , BELK JONATHAN P , DIXON RICHARD W , ROGUSKA MICHAEL , HINTON PAUL R , KUMAR SHANKAR
IPC: C07K16/00
CPC classification number: C07K16/244 , A61K39/3955 , A61K45/06 , C07K2317/24 , C07K2317/567 , C07K2317/76 , C07K2317/92 , G01N33/6869
Abstract: The present invention encompasses IL-12p40 binding proteins, particularly antibodies that bind human interleukin-12 (hIL-12) and/or human IL-23 (hIL-23). Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-12 and/or hIL-23 and neutralize h IL-12 and/or hIL-23 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and/or hIL-23 and for inhibiting hIL-12 and/or hIL-23 activity, e.g., in a human subject suffering from a disorder in which hIL-12 and/or hIL-23 activity is detrimental.
Abstract translation: 本发明包括IL-12p40结合蛋白,特别是结合人白细胞介素-12(hIL-12)和/或人IL-23(hIL-23)的抗体。 具体地,本发明涉及作为嵌合,CDR移植和人源化抗体的抗体。 优选的抗体对hIL-12和/或hIL-23具有高亲和力,并在体外和体内中和h IL-12和/或hIL-23活性。 本发明的抗体可以是全长抗体或其抗原结合部分。 还提供了制备方法和使用本发明抗体的方法。 本发明的抗体或抗体部分可用于检测hIL-12和/或hIL-23和用于抑制hIL-12和/或hIL-23活性,例如在患有hIL -12和/或hIL-23活性是有害的。
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公开(公告)号:WO2007005608A2
公开(公告)日:2007-01-11
申请号:PCT/US2006/025584
申请日:2006-06-29
Applicant: ABBOTT LABORATORIES , LACY, Susan E. , FUNG, Emma , BELK, Jonathan P. , DIXON, Richard W. , ROGUSKA, Michael , HINTON, Paul R. , KUMAR, Shankar
Inventor: LACY, Susan E. , FUNG, Emma , BELK, Jonathan P. , DIXON, Richard W. , ROGUSKA, Michael , HINTON, Paul R. , KUMAR, Shankar
IPC: C07K14/715
CPC classification number: C07K16/244 , A61K39/3955 , A61K45/06 , C07K2317/24 , C07K2317/567 , C07K2317/76 , C07K2317/92 , G01N33/6869
Abstract: The present invention encompasses IL-12p40 binding proteins, particularly antibodies that bind human interleukin-12 (hIL-12) and/or human IL-23 (hIL-23). Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-12 and/or hIL-23 and neutralize h IL-12 and/or hIL-23 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and/or hIL-23 and for inhibiting hIL-12 and/or hIL-23 activity, e.g., in a human subject suffering from a disorder in which hIL-12 and/or hIL-23 activity is detrimental.
Abstract translation: 本发明包括IL-12p40结合蛋白,特别是结合人白细胞介素-12(hIL-12)和/或人IL-23(hIL-23)的抗体。 具体地,本发明涉及作为嵌合,CDR移植和人源化抗体的抗体。 优选的抗体对hIL-12和/或hIL-23具有高亲和力,并在体外和体内中和h IL-12和/或hIL-23活性。 本发明的抗体可以是全长抗体或其抗原结合部分。 还提供了制备方法和使用本发明抗体的方法。 本发明的抗体或抗体部分可用于检测hIL-12和/或hIL-23和用于抑制hIL-12和/或hIL-23活性,例如在患有hIL -12和/或hIL-23活性是有害的。
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5.
公开(公告)号:WO2005100403A3
公开(公告)日:2006-07-13
申请号:PCT/US2005011956
申请日:2005-04-08
Applicant: ABBOTT LAB , REILLY EDWARD B , LACY SUSAN E , FUNG EMMA , BELK JONATHAN P , ROGUSKA MICHAEL
Inventor: REILLY EDWARD B , LACY SUSAN E , FUNG EMMA , BELK JONATHAN P , ROGUSKA MICHAEL
CPC classification number: C07K16/2863 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/74 , C07K2317/92
Abstract: The present invention relates to antibodies and antigen-binding portions thereof that bind to and activate an erythropoietin receptor. The invention also relates to nucleic acid sequences encoding such antibodies and antigen-binding portions. The present invention further relates to methods of activating the endogenous activity of an erythropoietin receptor in a mammal using said antibodies and antigen-binding portions, methods of treatment, as well as pharmaceutical compositions comprising said antibodies and antigen-binding portions.
Abstract translation: 本发明涉及结合并激活促红细胞生成素受体的抗体及其抗原结合部分。 本发明还涉及编码这种抗体和抗原结合部分的核酸序列。 本发明还涉及使用所述抗体和抗原结合部分,治疗方法以及包含所述抗体和抗原结合部分的药物组合物来激活哺乳动物中促红细胞生成素受体的内源性活性的方法。
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公开(公告)号:WO2012024650A3
公开(公告)日:2012-05-31
申请号:PCT/US2011048518
申请日:2011-08-19
Applicant: ABBOTT LAB , LACY SUSAN E , BARBON JEFFREY A , CHHAYA MEHA , FUNG EMMA , HUTCHINS CHARLES W , LANG DIANE M , BARLOW EVE H , LEDDY MARY , CHARI RAVI
Inventor: LACY SUSAN E , BARBON JEFFREY A , CHHAYA MEHA , FUNG EMMA , HUTCHINS CHARLES W , LANG DIANE M , BARLOW EVE H , LEDDY MARY , CHARI RAVI
IPC: C07K16/22
CPC classification number: C07K16/22 , A61K2039/505 , C07K2317/24 , C07K2317/31 , C07K2317/50 , C07K2317/51 , C07K2317/515 , C07K2317/54 , C07K2317/55 , C07K2317/565 , C07K2317/569 , C07K2317/60 , C07K2317/622 , C07K2317/624 , C07K2317/626 , C07K2317/64 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C07K2317/94 , G01N33/566
Abstract: The present disclosure encompasses NGF binding proteins, specifically to antibodies that are chimeric, CDR grafted and caninized antibodies, and methods of making and uses thereof. The antibodies, or antibody portions, of the disclosure are useful for detecting NGF and for inhibiting NGF activity, e.g., in a mammal subject suffering from a disorder in which NGF activity is detrimental.
Abstract translation: 本公开内容涵盖NGF结合蛋白,特别是嵌合抗体,CDR移植和可插入抗体的抗体及其制备及其用途的方法。 本公开的抗体或抗体部分可用于检测NGF和抑制NGF活性,例如在患有NGF活性有害的病症的哺乳动物受试者中。
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公开(公告)号:WO2012024650A2
公开(公告)日:2012-02-23
申请号:PCT/US2011/048518
申请日:2011-08-19
Applicant: ABBOTT LABORATORIES , LACEY, Susan E. , BARBON, Jeffrey A. , CHHAYA, Meha , FUNG, Emma , HUTCHINS, Charles W. , LANG, Diane M. , BARLOW, Eve H. , LEDDY, Mary , CHARI, Ravi
Inventor: LACEY, Susan E. , BARBON, Jeffrey A. , CHHAYA, Meha , FUNG, Emma , HUTCHINS, Charles W. , LANG, Diane M. , BARLOW, Eve H. , LEDDY, Mary , CHARI, Ravi
IPC: C07K16/22
CPC classification number: C07K16/22 , A61K39/3955 , A61K2039/505 , C07K2317/24 , C07K2317/31 , C07K2317/50 , C07K2317/51 , C07K2317/515 , C07K2317/54 , C07K2317/55 , C07K2317/565 , C07K2317/569 , C07K2317/60 , C07K2317/622 , C07K2317/624 , C07K2317/626 , C07K2317/64 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C07K2317/94 , G01N33/566
Abstract: The present disclosure encompasses NGF binding proteins, specifically to antibodies that are chimeric, CDR grafted and caninized antibodies, and methods of making and uses thereof. The antibodies, or antibody portions, of the disclosure are useful for detecting NGF and for inhibiting NGF activity, e.g., in a mammal subject suffering from a disorder in which NGF activity is detrimental.
Abstract translation: 本公开内容包括NGF结合蛋白,具体涉及嵌合,CDR移植和犬源化抗体的抗体,以及其制备和使用方法。 本公开内容的抗体或抗体部分可用于检测NGF和抑制NGF活性,例如在患有NGF活性是有害的病症的哺乳动物受试者中。
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8.
公开(公告)号:WO2005100403A2
公开(公告)日:2005-10-27
申请号:PCT/US2005/011956
申请日:2005-04-08
Applicant: ABBOTT LABORATORIES , REILLY, Edward, B. , LACY, Susan, E. , FUNG, Emma , BELK, Jonathan, P. , ROGUSKA, Michael
Inventor: REILLY, Edward, B. , LACY, Susan, E. , FUNG, Emma , BELK, Jonathan, P. , ROGUSKA, Michael
IPC: C07K16/28
CPC classification number: C07K16/2863 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/74 , C07K2317/92
Abstract: The present invention relates to antibodies and antigen-binding portions thereof that bind to and activate an erythropoietin receptor. The invention also relates to nucleic acid sequences encoding such antibodies and antigen-binding portions. The present invention further relates to methods of activating the endogenous activity of an erythropoietin receptor in a mammal using said antibodies and antigen-binding portions, methods of treatment, as well as pharmaceutical compositions comprising said antibodies and antigen-binding portions.
Abstract translation: 本发明涉及结合并激活促红细胞生成素受体的抗体及其抗原结合部分。 本发明还涉及编码这种抗体和抗原结合部分的核酸序列。 本发明还涉及使用所述抗体和抗原结合部分,治疗方法以及包含所述抗体和抗原结合部分的药物组合物来激活哺乳动物中促红细胞生成素受体的内源性活性的方法。
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