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    Recombinant anti-HIV antibody and process for preparing the same
    2.
    发明授权
    Recombinant anti-HIV antibody and process for preparing the same 失效
    重组抗HIV抗体及其制备方法

    公开(公告)号：US5773247A

    公开(公告)日：1998-06-30

    申请号：US491845

    申请日：1995-07-14

    申请人： Hiroaki Maeda ,  Kazuhiko Kimachi ,  Yasuyuki Eda ,  Kouichi Shiosaki ,  Kiyoshi Osatomi ,  Sachio Tokiyoshi

    发明人： Hiroaki Maeda ,  Kazuhiko Kimachi ,  Yasuyuki Eda ,  Kouichi Shiosaki ,  Kiyoshi Osatomi ,  Sachio Tokiyoshi

    IPC分类号： A61K38/00 ,  A61K39/395 ,  C07K16/10 ,  C12N15/13 ,  C12P21/08 ,  C12P21/06 ,  C07H21/04 ,  C12N5/00

    CPC分类号： C07K16/1063 ,  A61K38/00 ,  C07K2319/00

    摘要： The present invention relates to a gene fragment coding for a variable region of an antibody having a neutralizing activity against human immunodeficiency virus (HIV) and a process for preparing the same. A mouse-human chimeric antibody and a mouse-human reshaped antibody having a neutralizing activity against HIV can be prepared by obtaining a specific nucleotide sequence of a gene fragment coding for a variable region of H chain and L chain of an antibody having a neutralizing activity against HIV, and then artificially fusing DNAs synthesized based on these nucleotide sequences with a gene coding for a human immunoglobulin. The novel recombinant anti-HIV antibody of the present invention is useful for treatment and prevention of AIDS.

    摘要翻译： PCT No.PCT / JP93 / 00039 Sec。 371 1995年7月14日第 102（e）日期1995年7月14日PCT提交1993年1月14日PCT公布。 第WO94 / 15969号公报 日期：1994年7月12日本发明涉及编码对人免疫缺陷病毒（HIV）具有中和活性的抗体的可变区的基因片段及其制备方法。 可以通过获得编码具有中和活性的抗体的H链和L链的可变区的基因片段的特异性碱基序列来制备具有针对HIV的中和活性的小鼠 - 人嵌合抗体和小鼠 - 人重整抗体 然后人造地将基于这些核苷酸序列合成的DNA与编码人免疫球蛋白的基因融合。 本发明的新型重组抗HIV抗体可用于治疗和预防艾滋病。

    Anti-HIV monoclonal antibody
    3.
    发明授权
    Anti-HIV monoclonal antibody 失效
    抗HIV单克隆抗体

    公开(公告)号：US6114143A

    公开(公告)日：2000-09-05

    申请号：US513968

    申请日：1995-09-11

    申请人： Yasuyuki Eda ,  Hiroaki Maeda ,  Keiichi Makizumi ,  Kouichi Shiosaki ,  Kiyoshi Osatomi ,  Kazuhiko Kimachi ,  Hirofumi Higuchi ,  Sachio Tokiyoshi

    发明人： Yasuyuki Eda ,  Hiroaki Maeda ,  Keiichi Makizumi ,  Kouichi Shiosaki ,  Kiyoshi Osatomi ,  Kazuhiko Kimachi ,  Hirofumi Higuchi ,  Sachio Tokiyoshi

    IPC分类号： A61K38/00 ,  C07K16/10 ,  C12P21/04 ,  C12P21/08 ,  C12N15/09 ,  A61K39/395 ,  C12P11/00

    CPC分类号： C07K16/1063 ,  A61K38/00 ,  C07K2317/24

    摘要： A monoclonal antibody useful for clinical application which recognizes the conserved region of V3-PND region of glycoprotein antigen having a molecular weight of about 1.2.times.10.sup.5 daltons (gp120) on a coating membrane of human immunodeficiency virus (HIV) and which has an ability to neutralize a broad range of various HIV variants, or a fragment thereof, and the chimeric and humanized antibodies derived therefrom are provided. By using as an immunogen a plurality of peptides having PND-Tip region containing the highly conserved GPGR sequence within PND of HIV gp120, a monoclonal antibody having a neutralizing activity to many HIV variants can be prepared. By transplanting the gene fragment coding for the variable region of said monoclonal antibody or complementarity determining region (CDR) of said region to a human antibody gene, a chimeric antibody or a reshaped antibody having an anti-HIV neutralizing activity which are effective for clinical application can be obtained.

    摘要翻译： PCT No.PCT / JP94 / 00371 Sec。 371 1995年9月11日第 102（e）1995年9月11日PCT PCT 1994年3月9日PCT公布。 公开号WO94 / 20632 日期1994年9月15日一种可用于临床应用的单克隆抗体，其识别在人免疫缺陷病毒（HIV）的包被膜上具有约1.2×10 5道尔顿（gp120）分子量的糖蛋白抗原的V3-PND区的保守区， 具有中和各种各样的HIV变体或其片段的能力，并且提供了由其衍生的嵌合和人源化抗体。 通过使用多种具有含有HIV gp120的PND内的高度保守的GPGR序列的PND-Tip区的肽，可以制备对许多HIV变体具有中和活性的单克隆抗体。 通过将编码所述区域的所述单克隆抗体或互补决定区（CDR）的可变区的基因片段移植到人抗体基因，嵌合抗体或具有抗HIV中和活性的重构抗体，其对临床应用有效 可以获得。

    Cat-mouse heterohybridoma and gene fragment coding for constant region of feline immunoglobulin
    4.
    发明授权
    Cat-mouse heterohybridoma and gene fragment coding for constant region of feline immunoglobulin 失效
    猫鼠异种杂交瘤和编码猫免疫球蛋白恒定区的基因片段

    公开(公告)号：US5880274A

    公开(公告)日：1999-03-09

    申请号：US559947

    申请日：1995-11-17

    申请人： Hiroaki Maeda ,  Yasuyuki Eda ,  Kazuhiko Kimachi ,  Yoichi Ono ,  Sachio Tokiyoshi

    发明人： Hiroaki Maeda ,  Yasuyuki Eda ,  Kazuhiko Kimachi ,  Yoichi Ono ,  Sachio Tokiyoshi

    IPC分类号： C07K16/00 ,  C07K16/08 ,  C07K16/46 ,  C12N5/20 ,  C12N5/26 ,  C12N15/13 ,  C12P21/08 ,  C07H21/04 ,  C12N5/00 ,  C12N15/00

    CPC分类号： C12N5/166 ,  C07K16/00 ,  C07K16/081 ,  C07K16/462 ,  C07K2317/24 ,  C07K2319/00

    摘要： A Gene fragment which comprises a DNA sequence coding for an amino acid sequence of a constant region of feline immunoglobulin .lambda. chain; a gene fragment which comprises a DNA sequence coding for an amino acid sequence of a constant region of feline immunoglobulin .kappa. chain; a gene fragment which comprises a DNA sequence coding for the constant region of feline immunoglobulin .gamma. chain; a recombinant DNA molecule coding for an amino acid sequence of a mouse-cat chimeric antibody which comprises a gene fragment coding for an amino acid sequence of a variable region of a mouse immunoglobulin and a gene fragment coding for an amino acid sequence of a constant region of a feline immunoglobulin wherein the latter gene fragment is linked to the 3' site of the former gene fragment; a polypeptide of a mouse-cat chimeric antibody which is expressed from a cell transformed with an expression vector for cells wherein said recombinant DNA molecule coding for an amino acid sequence of the mouse-cat chimeric antibody is incorporated; a cat-mouse heterohybridoma which produces feline immunoglobulin; and a process for preparing a feline immunoglobulin gene.

    摘要翻译： 一种基因片段，其包含编码猫免疫球蛋白λ链的恒定区的氨基酸序列的DNA序列; 一种基因片段，其包含编码猫免疫球蛋白κ链的恒定区的氨基酸序列的DNA序列; 包含编码猫免疫球蛋白γ链恒定区的DNA序列的基因片段; 编码小鼠-cat嵌合抗体的氨基酸序列的重组DNA分子，其包含编码小鼠免疫球蛋白的可变区的氨基酸序列的基因片段和编码恒定区的氨基酸序列的基因片段 的猫免疫球蛋白，其中后一个基因片段连接到前一个基因片段的3'位点; 将从编码小鼠-cat嵌合抗体的氨基酸序列的所述重组DNA分子并入的细胞的表达载体转化的细胞中表达的小鼠-cat嵌合抗体的多肽; 产生猫免疫球蛋白的猫 - 鼠异种杂交瘤; 以及制备猫免疫球蛋白基因的方法。

    Dog-mouse heterohybridoma and gene fragment coding for constant region of canine immunoglobulins
    5.
    发明授权
    Dog-mouse heterohybridoma and gene fragment coding for constant region of canine immunoglobulins 失效
    犬小鼠异源杂交瘤和编码犬免疫球蛋白恒定区的基因片段

    公开(公告)号：US5852183A

    公开(公告)日：1998-12-22

    申请号：US646981

    申请日：1996-05-08

    申请人： Hiroaki Maeda ,  Yasuyuki Eda ,  Kazuhiko Kimachi ,  Yoichi Ono ,  Sachio Tokiyoshi

    发明人： Hiroaki Maeda ,  Yasuyuki Eda ,  Kazuhiko Kimachi ,  Yoichi Ono ,  Sachio Tokiyoshi

    IPC分类号： A61K39/00 ,  C07K16/46 ,  C12N5/26 ,  C12N15/13 ,  C07H2/04 ,  C07H21/02

    CPC分类号： C07K16/462 ,  A61K39/00 ,  C07K2317/24

    摘要： A gene fragment which comprises a DNA sequence coding for an amino acid sequence of a constant region of canine immunoglobulin lambda chain; a gene fragment which comprises a DNA sequence coding for an amino acid sequence of a constant region of canine immunoglobulin kappa chain; a gene fragment which comprises a DNA sequence coding for the constant region of canine immunoglobulin gamma chain; a recombinant DNA molecule coding for an amino acid sequence of a mouse-dog chimeric antibody which comprises a gene fragment coding for an amino acid sequence of a variable region of a mouse immunoglobulin and a gene fragment coding for an amino acid sequence of a constant region of a canine immunoglobulin wherein the latter gene fragment; a polypeptide of a mouse-dog chimeric antibody which is expressed from a cell transformed with an expression vector for cells wherein said recombinant DNA molecule cording for an amino acid sequence of the mouse-dog chimeric antibody is incorporated; a dog-mouse heterohybridoma which produces canine immunoglobulin; and a process for preparing a canine immunoglobulin gene.

    摘要翻译： 一种基因片段，其包含编码犬免疫球蛋白λ链的恒定区的氨基酸序列的DNA序列; 基因片段，其包含编码犬免疫球蛋白κ链恒定区的氨基酸序列的DNA序列; 包含编码犬免疫球蛋白γ链的恒定区的DNA序列的基因片段; 编码小鼠 - 狗嵌合抗体的氨基酸序列的重组DNA分子，其包含编码小鼠免疫球蛋白的可变区的氨基酸序列的基因片段和编码恒定区的氨基酸序列的基因片段 的犬免疫球蛋白，其中后者基因片段; 从用细胞表达载体转化的细胞中表达小鼠 - 狗嵌合抗体的多肽，其中并入所述针对小鼠 - 狗嵌合抗体的氨基酸序列的重组DNA分子; 产生犬免疫球蛋白的狗 - 小鼠异源杂交瘤; 以及制备犬免疫球蛋白基因的方法。

    Dog-mouse heterohybridoma and gene fragment coding for constant region of canine immunoglobulins
    7.
    发明授权
    Dog-mouse heterohybridoma and gene fragment coding for constant region of canine immunoglobulins 失效
    犬小鼠异源杂交瘤和编码犬免疫球蛋白恒定区的基因片段

    公开(公告)号：US5593861A

    公开(公告)日：1997-01-14

    申请号：US306520

    申请日：1994-09-15

    申请人： Hiroaki Maeda ,  Yasuyuki Eda ,  Kazuhiko Kimachi ,  Yoichi Ono ,  Sachio Tokiyoshi

    发明人： Hiroaki Maeda ,  Yasuyuki Eda ,  Kazuhiko Kimachi ,  Yoichi Ono ,  Sachio Tokiyoshi

    IPC分类号： A61K39/00 ,  C07K16/46 ,  C12N5/26 ,  C12N15/13 ,  C12N15/00 ,  C07H21/04 ,  C12P21/04 ,  C12P21/06

    CPC分类号： C07K16/462 ,  A61K39/00 ,  C07K2317/24

    摘要： A gene fragment which comprises a DNA sequence coding for an amino acid sequence of a constant region of canine immunoglobulin lambda chain; a gene fragment which comprises a DNA sequence coding for an amino acid sequence of a constant region of canine immunoglobulin kappa chain; a gene fragment which comprises a DNA sequence coding for the constant region of canine immunoglobulin gamma chain; a recombinant DNA molecule coding for an amino acid sequence of a mouse-dog chimeric antibody which comprises a gene fragment coding for an amino acid sequence of a variable region of a mouse immunoglobulin and a gene fragment coding for an amino acid sequence of a constant region of a canine immunoglobulin; a polypeptide of a mouse-dog chimeric antibody which is expressed from a cell transformed with an expression vector for cells wherein said recombinant DNA molecule cording for an amino acid sequence of the mouse-dog chimeric antibody is incorporated; a dog-mouse heterohybridoma which produces canine immunoglobulin; and a process for preparing a canine immunoglobulin gene.

    摘要翻译： 一种基因片段，其包含编码犬免疫球蛋白λ链的恒定区的氨基酸序列的DNA序列; 基因片段，其包含编码犬免疫球蛋白κ链恒定区的氨基酸序列的DNA序列; 包含编码犬免疫球蛋白γ链的恒定区的DNA序列的基因片段; 编码小鼠 - 狗嵌合抗体的氨基酸序列的重组DNA分子，其包含编码小鼠免疫球蛋白的可变区的氨基酸序列的基因片段和编码恒定区的氨基酸序列的基因片段 的犬免疫球蛋白; 从用细胞表达载体转化的细胞中表达小鼠 - 狗嵌合抗体的多肽，其中并入所述针对小鼠 - 狗嵌合抗体的氨基酸序列的重组DNA分子; 产生犬免疫球蛋白的狗 - 小鼠异源杂交瘤; 以及制备犬免疫球蛋白基因的方法。

    Humanized immunoglobulin reacting specifically with Fas ligand or active fragments thereof and region inducing apoptosis originating in Fas ligand
    8.
    发明授权
    Humanized immunoglobulin reacting specifically with Fas ligand or active fragments thereof and region inducing apoptosis originating in Fas ligand 有权
    与Fas配体或其活性片段特异性反应的人源化免疫球蛋白和诱导Fas配体凋亡的区域

    公开(公告)号：US06777540B1

    公开(公告)日：2004-08-17

    申请号：US09254180

    申请日：1999-04-15

    申请人： Ko Okumura ,  Motomi Nakata ,  Hirofumi Higuchi ,  Yoshitaka Ushio ,  Hiroaki Maeda ,  Yasuyuki Eda

    发明人： Ko Okumura ,  Motomi Nakata ,  Hirofumi Higuchi ,  Yoshitaka Ushio ,  Hiroaki Maeda ,  Yasuyuki Eda

    IPC分类号： C07K1600

    CPC分类号： C07K16/2875 ,  C07K14/70575 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2319/00

    摘要： Novel humanized immunoglobulins and active fragments thereof which are specifically reactive to Fas ligand are provided, and a site on Fas ligand which is important to inhibit apoptosis induced by the Fas-Fas ligand interaction against Fas-expressing cells is demonstrated. The novel humanized immunoglobulins and active fragments thereof which are specifically reactive to Fas ligand are prepared from hybridomas which produce monoclonal antibodies specifically reactive to Fas ligand, via recombinant DNA techniques. The humanized immunoglobulins can inhibit the physiological reactions between Fas ligand and Fas such as apoptosis. Further, identification of the site which is on Fas ligand and responsible for apoptosis induction allows creation of recombinant proteins or peptides which are specifically reactive to the amino acids within the site so as to inhibit apoptosis, and to find new therapeutic or diagnostic agents.

    摘要翻译： 提供了与Fas配体特异性反应的新型人源化免疫球蛋白及其活性片段，证明了Fas配体上对Fas-Fas配体与Fas表达细胞相互作用诱导的细胞凋亡重要的位点。 通过重组DNA技术从与Fas配体特异性反应的单克隆抗体的杂交瘤制备与Fas配体特异性反应的新型人源化免疫球蛋白及其活性片段。 人源化免疫球蛋白可以抑制Fas配体和Fas之间的生理反应，如细胞凋亡。 此外，鉴定在Fas配体上并负责细胞凋亡诱导的位点允许产生对位点内的氨基酸具有特异性反应性的重组蛋白质或肽，以便抑制细胞凋亡，并找到新的治疗剂或诊断剂。