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1. 发明申请

WO2019185035A1 ANTI-PD-L1 ANTIBODIES AND USE THEREOF 审中-公开
公开(公告)号：WO2019185035A1
公开(公告)日：2019-10-03
申请号：PCT/CN2019/080496
申请日：2019-03-29
申请人： ADAGENE INC. , LUO, Peizhi , GUILIN SANJIN PHARMACEUTICAL CO., LTD.
发明人： LUO, Peizhi , DU, Fangyong , LIU, Guizhong , LI, Yan
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00 , G01N33/577 , G01N33/68
摘要： The present disclosure provides antibodies that bind to the T-cell co-inhibitor ligand programmed death-ligandl (PD-L1) protein, and methods of use. In various embodiments of the disclosure, the antibodies are fully human antibodies that bind to PD-L1. In certain embodiments, the present disclosure provides multi-specific antigen-binding molecules comprising a first binding specificity that binds to PD-L1 and a second binding specificity that binds to a tumor cell antigen, an infected cell-specific antigen, or a T-cell co-inhibitor. In some embodiments, the antibodies of the disclosure are useful for inhibiting or neutralizing PD-L1 activity, thus providing a means of treating a disease or disorder such as cancer or viral infection.

2. 发明申请

WO2012058137A2 METHODS FOR DIVERSIFYING ANTIBODIES, ANTIBODIES DERIVED THEREFROM AND USES THEREOF 审中-公开
标题翻译：用于分化抗体的方法，其衍生的抗体及其用途
公开(公告)号：WO2012058137A2
公开(公告)日：2012-05-03
申请号：PCT/US2011/057426
申请日：2011-10-24
申请人： MERCK SHARP & DOHME CORP. , WANG, Kevin Caili , LI, Yan , HSIEH, Mark , WANG, Xinwei , DONG, Feng , LUO, Peizhi (Peter) , ZHONG, Pingyu
发明人： WANG, Kevin Caili , LI, Yan , HSIEH, Mark , WANG, Xinwei , DONG, Feng , LUO, Peizhi (Peter) , ZHONG, Pingyu
IPC分类号： C40B30/04
CPC分类号： C12N15/1055 , C07K16/00 , C07K16/005 , C07K16/087 , C07K16/2863 , C07K16/2866 , C07K16/32 , C07K2317/21 , C07K2317/55 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , G01N33/6845
摘要： The invention provides methods of introducing diversity into antibody molecules comprising introducing or substituting at least one amino acid sequence in the CDR of the target antibody together with at least one amino acid in the FW region spanning the 3 amino acid adjoining the CRD on each side. The resulting diverse antibodies with variant CDRs and FW region sequences comprising diverse amino acid sequences are also described. These polypeptides regions, herein referred to as 3+CDR3+, that form the gist of the invention contribution described herein provide a flexible and simple source of sequence diversity that can be used as a source for expressing and identifying diverse antibodies or antigen binding polypeptides. Libraries comprising a plurality of these polypeptides are also provided. In addition, methods of and compositions for generating and using these polypeptides and libraries are provided. A method of producing diverse antibodies comprising amino acid substitutions in one of the CDR region and the FW region comprising 3 contiguous FW sequence amino acids adjacent to each CDR on either side is described herein. The substitutions are relative to database or germline sequences. Not all substitution are preserved in conservative regions.
摘要翻译：本发明提供了将多样性引入抗体分子的方法，包括在靶抗体的CDR中引入或取代至少一个氨基酸序列以及跨越与CRD相邻的3个氨基酸的FW区域中的至少一个氨基酸。还描述了所得到的具有包含不同氨基酸序列的变体CDR和FW区序列的多种抗体。形成本文所述发明要点的这些多肽区域（本文称为3 + CDR3 +）提供了可用作表达和鉴定多种抗体或抗原结合多肽的来源的灵活和简单的序列多样性来源。还提供了包含多个这些多肽的文库。此外，提供了用于产生和使用这些多肽和文库的方法和组合物。本文描述了在包含与任一侧上的每个CDR相邻的3个连续的FW序列氨基酸的CDR区域和FW区域之一中产生包含氨基酸取代的多种抗体的方法。替代是相对于数据库或种系序列。并非所有替代都保留在保守区域。

3. 发明申请

WO2003099999A3 GENERATION AND SELECTION OF PROTEIN LIBRARY IN SILICO 审中-公开
公开(公告)号：WO2003099999A3
公开(公告)日：2003-12-04
申请号：PCT/US2003/016037
申请日：2003-05-20
申请人： ABMAXIS, INC. , LUO, Peizhi , HSIEH, Mark , ZHONG, Pingyu , WANG, Caili , CAO, Yicheng , LIU, Shengjiang
发明人： LUO, Peizhi , HSIEH, Mark , ZHONG, Pingyu , WANG, Caili , CAO, Yicheng , LIU, Shengjiang
IPC分类号： G06F19/00
摘要： The present invention provides a methodology for efficiently generating and screening protein libraries for optimized proteins with desirable biological functions, such as improved binding affinity towards biologically and/or therapeutically important target molecules. The process is carried out computationally in a high throughput manner by mining the ever-expanding databases of protein sequences of all organisms, especially human. In one embodiment, a method for constructing a library of designed proteins, comprising the steps of: providing an amino acid sequence derived from a lead protein, the amino acid sequence being designated as a lead sequence; comparing the lead sequence with a plurality of tester protein sequences; and selecting from the plurality of tester protein sequences at least two peptide segments that have at least 15% sequence identity with the lead sequence, the selected peptide segments forming a hit library; and forming a library of designed proteins by substituting the lead sequence with the hit library. The library of designed proteins can be expressed in vitro or in vivo to produce a library of recombinant proteins that can be screened for novel or improved function(s) over the lead protein, such as an antibody against therapeutically important target.

4. 发明申请

WO2003012069A2 COMPOSITIONS AND METHODS FOR GENERATING CHIMERIC HETEROMULTIMERS 审中-公开
标题翻译：组合物和方法用于生成CHIMERIC HETERMULTIMERS
公开(公告)号：WO2003012069A2
公开(公告)日：2003-02-13
申请号：PCT/US2002/024582
申请日：2002-07-31
申请人： ABMAXIS, INC. , WANG, Caili , ZHONG, Pingyu , LIU, Shengjiang , LUO, Peizhi , LI, Shengfeng , WANG, Xinwei
发明人： WANG, Caili , ZHONG, Pingyu , LIU, Shengjiang , LUO, Peizhi , LI, Shengfeng , WANG, Xinwei
IPC分类号： C12N
CPC分类号： C07K16/00 , C07K2317/56 , C07K2319/00
摘要： The present invention provides a technique for specific assembly of monomericpolypeptides to form a heteromultimer. This technique is particularly useful for generatinga genetically diverse repertoire of heteromultimers such as antigen-binding units. Theinvention also provides both non-single-chain and single-chain antigen-binding units thatare assembled by the technique described herein. The present invention also provides recombinant polynucleotides, vectors, host cells, and kits for producing the subjectantigen-binding units. Further provided by the invention are methods of using thesubject antigen-binding units.
摘要翻译：本发明提供了用于特异性组装单体多肽以形成异源多聚体的技术。这种技术对于产生异源多聚体如抗原结合单位的遗传多样性谱特别有用。本发明还提供通过本文所述技术组装的非单链和单链抗原结合单元。本发明还提供重组多核苷酸，载体，宿主细胞和用于产生主要抗原结合单元的试剂盒。本发明进一步提供的是使用主题抗原结合单元的方法。

5. 发明申请

WO2012058137A3 METHODS FOR DIVERSIFYING ANTIBODIES, ANTIBODIES DERIVED THEREFROM AND USES THEREOF 审中-公开
标题翻译：用于分化抗体的方法，其衍生的抗体及其用途
公开(公告)号：WO2012058137A3
公开(公告)日：2014-04-10
申请号：PCT/US2011057426
申请日：2011-10-24
申请人： MERCK SHARP & DOHME , WANG KEVIN CAILI , LI YAN , HSIEH MARK , WANG XINWEI , DONG FENG , LUO PEIZHI PETER , ZHONG PINGYU
发明人： WANG KEVIN CAILI , LI YAN , HSIEH MARK , WANG XINWEI , DONG FENG , LUO PEIZHI PETER , ZHONG PINGYU
IPC分类号： C12P21/02
CPC分类号： C12N15/1055 , C07K16/00 , C07K16/005 , C07K16/087 , C07K16/2863 , C07K16/2866 , C07K16/32 , C07K2317/21 , C07K2317/55 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , G01N33/6845
摘要： Disclosed are methods of introducing diversity into antibody molecules substitutions of at least one amino acid sequence in the CDR of the target antibody together with at least one amino acid in the FW region spanning the 3 amino acid adjoining the CRD on each side. The resulting diverse antibodies with variant CDRs and flanking region sequences comprising diverse amino acid sequences Libraries comprising a plurality of these polypeptides are also provided as well as methods of and compositions for generating and using these polypeptides and libraries.
摘要翻译：公开了将多样性引入到靶抗体的CDR中的至少一个氨基酸序列的取代的多样性的方法以及跨越与每个CRD相邻的3个氨基酸的FW区域中的至少一个氨基酸。所得到的具有不同CDR的多态抗体和包含不同氨基酸序列的侧翼区序列也提供了包含多个这些多肽的文库以及生成和使用这些多肽和文库的方法和组合物。

6. 发明申请

WO2007014169A3 ANTI-CD26 ANTIBODIES AND METHODS OF USE THEREOF 审中-公开
标题翻译：抗CD26抗体及其使用方法
公开(公告)号：WO2007014169A3
公开(公告)日：2007-05-10
申请号：PCT/US2006028702
申请日：2006-07-24
申请人： Y S THERAPEUTICS INC , AOYAGI TEIKICHI , LUO PEIZHI , ZHONG PINGYU , HSIEH MARK , LI YAN , WANG CAILI C , MORIMOTO CHIKAO
发明人： AOYAGI TEIKICHI , LUO PEIZHI , ZHONG PINGYU , HSIEH MARK , LI YAN , WANG CAILI C , MORIMOTO CHIKAO
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00 , A61P37/00 , C07K16/40 , C12N15/13
CPC分类号： C07K16/2896 , A61K38/00 , A61K2039/505 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/73 , C07K2317/92 , G01N33/574 , G01N2333/70596 , G01N2500/00
摘要： The present invention provides novel anti-CD26 antibodies and other, related polypeptides, as well as novel polynucleotides encoding the antibodies and polypeptides. The invention also provides methods of making the antibodies and polypeptides. Compositions and cells comprising the antibodies or polypeptides are further provided. Methods of using the antibodies and/or polypeptides, such as to inhibit cell proliferation and in the treatment of conditions associated with CD26, are also provided.
摘要翻译：本发明提供了新的抗CD26抗体和其他相关多肽，以及编码该抗体和多肽的新型多核苷酸。本发明还提供了制备抗体和多肽的方法。还提供了包含抗体或多肽的组合物和细胞。还提供了使用抗体和/或多肽的方法，例如抑制细胞增殖和治疗与CD26相关的病症。

7. 发明申请

WO2007014169A2 ANTI-CD26 ANTIBODIES AND METHODS OF USE THEREOF 审中-公开
标题翻译：抗CD26抗体及其使用方法
公开(公告)号：WO2007014169A2
公开(公告)日：2007-02-01
申请号：PCT/US2006/028702
申请日：2006-07-24
申请人： Y'S THERAPEUTICS, INC. , AOYAGI, Teikichi , LUO, Peizhi , ZHONG, Pingyu , HSIEH, Mark , LI, Yan , WANG, Caili, C. , MORIMOTO, Chikao
发明人： AOYAGI, Teikichi , LUO, Peizhi , ZHONG, Pingyu , HSIEH, Mark , LI, Yan , WANG, Caili, C. , MORIMOTO, Chikao
IPC分类号： C07K16/00
CPC分类号： C07K16/2896 , A61K38/00 , A61K2039/505 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/73 , C07K2317/92 , G01N33/574 , G01N2333/70596 , G01N2500/00 , Y02A50/473
摘要： The present invention provides novel anti-CD26 antibodies and other, related polypeptides, as well as novel polynucleotides encoding the antibodies and polypeptides. The invention also provides methods of making the antibodies and polypeptides. Compositions and cells comprising the antibodies or polypeptides are further provided. Methods of using the antibodies and/or polypeptides, such as to inhibit cell proliferation and in the treatment of conditions associated with CD26, are also provided.
摘要翻译：本发明提供新的抗CD26抗体和其它相关多肽，以及编码抗体和多肽的新型多核苷酸。本发明还提供了制备抗体和多肽的方法。进一步提供包含抗体或多肽的组合物和细胞。还提供了使用抗体和/或多肽的方法，例如抑制细胞增殖和治疗与CD26相关的病症。

8. 发明申请

WO2005054273A2 HUMANIZED ANTIBODIES AGAINST VASCULAR ENDOTHELIAL GROWTH FACTOR 审中-公开
标题翻译：人类抗血管内皮生长因子的抗体
公开(公告)号：WO2005054273A2
公开(公告)日：2005-06-16
申请号：PCT/US2004039501
申请日：2004-11-22
申请人： ABMAXIS INC , ZHONG PINGYU , LUO PEIZHI , WANG KEVIN C , HSIEH MARK , LI YAN
发明人： ZHONG PINGYU , LUO PEIZHI , WANG KEVIN C , HSIEH MARK , LI YAN
IPC分类号： C07K16/00 , C07K16/22 , C40B40/10 , C07K
CPC分类号： C07K16/00 , B01J2219/00689 , B01J2219/00695 , B01J2219/007 , B01J2219/00725 , C07K16/22 , C07K2299/00 , C07K2317/21 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/73 , C07K2317/92 , C07K2319/00 , C40B40/10 , Y02A90/26
摘要： Methods are provided for designing and selecting antibodies against human antigens with high affinity and specificity in silico and in vitro. In some particular embodiments, methods are provided for designing and selecting humanized or fully human antibodies against vascular endothelial growth factor (VEGF) with high affinity and specificity. In another aspect of the invention, monoclonal antibodies against VEGF are provided. In particular, humanized or human anti-VEGF monoclonal antibodies are provided with ability to bind to human VEGF with high affinity, inhibit VEGF-induced proliferation of endothelial cells in vitro and inhibit VEGF-induced angiogenesis in vivo. These antibodies and their derivative can be used in a wide variety of applications such as diagnosis, prevention, and treatment of diseases such as cancer, AMD, diabetic retinopathy, and other diseases derived from pathological angiogenesis.
摘要翻译：提供了用于在计算机和体外以高亲和力和特异性设计和选择针对人抗原的抗体的方法。在一些具体实施方案中，提供了用于以高亲和力和特异性设计和选择针对血管内皮生长因子（VEGF）的人源化或完全人抗体的方法。在本发明的另一方面，提供了针对VEGF的单克隆抗体。特别地，人源化或人抗VEGF单克隆抗体具有以高亲和力结合人VEGF的能力，在体外抑制VEGF诱导的内皮细胞增殖并抑制体内VEGF诱导的血管生成。这些抗体及其衍生物可用于广泛的应用，例如诊断，预防和治疗诸如癌症，AMD，糖尿病性视网膜病和其它源于病理血管发生的疾病。

9. 发明申请

WO2003099999A2 GENERATION AND SELECTION OF PROTEIN LIBRARY IN SILICO 审中-公开
标题翻译：生成和选择硅胶中的蛋白质图书馆
公开(公告)号：WO2003099999A2
公开(公告)日：2003-12-04
申请号：PCT/US2003/016037
申请日：2003-05-20
申请人： ABMAXIS, INC. , LUO, Peizhi , HSIEH, Mark , ZHONG, Pingyu , WANG, Caili , CAO, Yicheng , LIU, Shengjiang
发明人： LUO, Peizhi , HSIEH, Mark , ZHONG, Pingyu , WANG, Caili , CAO, Yicheng , LIU, Shengjiang
IPC分类号： C12N
CPC分类号： C40B50/02 , C07K16/00 , C07K16/22 , C07K2317/24 , C07K2317/622 , C07K2319/00 , G06F19/18 , G06F19/22
摘要： The present invention provides a methodology for efficiently generating and screening protein libraries for optimized proteins with desirable biological functions, such as improved binding affinity towards biologically and/or therapeutically important target molecules. The process is carried out computationally in a high throughput manner by mining the ever-expanding databases of protein sequences of all organisms, especially human. In one embodiment, a method for constructing a library of designed proteins, comprising the steps of: providing an amino acid sequence derived from a lead protein, the amino acid sequence being designated as a lead sequence; comparing the lead sequence with a plurality of tester protein sequences; and selecting from the plurality of tester protein sequences at least two peptide segments that have at least 15% sequence identity with the lead sequence, the selected peptide segments forming a hit library; and forming a library of designed proteins by substituting the lead sequence with the hit library. The library of designed proteins can be expressed in vitro or in vivo to produce a library of recombinant proteins that can be screened for novel or improved function(s) over the lead protein, such as an antibody against therapeutically important target.
摘要翻译：本发明提供了一种用于有效地产生和筛选具有所需生物学功能的优化蛋白质的蛋白质文库的方法，例如改善对生物和/或治疗重要的靶分子的结合亲和力。该过程以高通量方式通过开发不断扩大的所有生物体，特别是人的蛋白质序列数据库进行。在一个实施方案中，构建设计蛋白质文库的方法，包括以下步骤：提供衍生自铅蛋白的氨基酸序列，所述氨基酸序列指定为引导序列; 将引导序列与多个测试蛋白序列进行比较; 以及从所述多个测试蛋白序列中选择与所述引物序列具有至少15％序列同一性的至少两个肽片段，所选择的肽片段形成命中文库; 并通过用命中库替换引导序列形成设计蛋白质的文库。设计的蛋白质文库可以在体外或体内表达，以产生重组蛋白文库，该文库可以筛选出超过铅蛋白质的新的或改进的功能，例如针对治疗重要靶标的抗体。

10. 发明申请

WO2003012069A3 COMPOSITIONS AND METHODS FOR GENERATING CHIMERIC HETEROMULTIMERS 审中-公开
公开(公告)号：WO2003012069A3
公开(公告)日：2003-02-13
申请号：PCT/US2002/024582
申请日：2002-07-31
申请人： ABMAXIS, INC. , WANG, Caili , ZHONG, Pingyu , LIU, Shengjiang , LUO, Peizhi , LI, Shengfeng , WANG, Xinwei
发明人： WANG, Caili , ZHONG, Pingyu , LIU, Shengjiang , LUO, Peizhi , LI, Shengfeng , WANG, Xinwei
IPC分类号： C07K16/00
摘要： The present invention provides a technique for specific assembly of monomericpolypeptides to form a heteromultimer. This technique is particularly useful for generating a genetically diverse repertoire of heteromultimers such as antigen-binding units. The invention also provides both non-single-chain and single-chain antigen-binding units that are assembled by the technique described herein. The present invention also provides recombinant polynucleotides, vectors, host cells, and kits for producing the subjectantigen-binding units. Further provided by the invention are methods of using the subject antigen-binding units.

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