公开(公告)号：EP4448566A1

公开(公告)日：2024-10-23

申请号：EP22854336.9

申请日：2022-12-16

申请人： The United States of America, as represented by the Secretary, Department of Health and Human Services

发明人： PASTAN, Ira H. ,  ONDA, Masanori ,  HO, Mitchell ,  LIU, Xiu-fen ,  BERA, Tapan ,  CHAKRABORTY, Anirban

IPC分类号： C07K16/18 ,  C07K16/30 ,  C07K14/825 ,  A61P35/00

公开(公告)号：EP3494135A1

公开(公告)日：2019-06-12

申请号：EP17746316.3

申请日：2017-07-20

申请人： The United States of America, as represented by The Secretary, Department of Health and Human Services

发明人： HO, Mitchell ,  LI, Nan ,  DIMITROV, Dimiter, S.

IPC分类号： C07K16/18 ,  C07K16/30 ,  C12N15/113 ,  A61K47/68 ,  A61P35/00 ,  A61K39/00

公开(公告)号：EP2998320B1

公开(公告)日：2018-07-18

申请号：EP15188264.4

申请日：2012-04-19

申请人： The United States of America, as represented by the Secretary, Department of Health and Human Services

发明人： HO, Mitchell ,  FENG, Mingqian ,  GAO, Wei ,  KIM, Heungnam ,  DIMITROV, Dimiter S.,

IPC分类号： C07K16/30 ,  A61K39/395 ,  C07K16/28 ,  G01N33/574 ,  G01N33/68 ,  A61K39/00 ,  C07K14/21 ,  A61K47/68 ,  A61P35/00

CPC分类号： C07K16/3076 ,  A61K39/39558 ,  A61K47/6803 ,  A61K47/6813 ,  A61K47/6829 ,  A61K47/6849 ,  A61K47/6851 ,  A61K2039/505 ,  C07K14/21 ,  C07K16/28 ,  C07K16/303 ,  C07K16/3092 ,  C07K2317/21 ,  C07K2317/31 ,  C07K2317/33 ,  C07K2317/41 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/33 ,  C07K2319/55 ,  G01N33/57438 ,  G01N33/57492 ,  G01N33/6893 ,  G01N2333/705 ,  G01N2400/40

摘要： Described herein is the identification of human monoclonal antibodies that bind GPC3 or heparan sulfate (HS) chains on GPC3 with high affinity. The antibodies described herein are capable of inhibiting HCC cell growth and migration. Provided are human monoclonal antibodies specific for GPC3 or HS chains on GPC3, including immunoglobulin molecules, such as IgG antibodies, as well as antibody fragments, such as single-domain VH antibodies or single chain variable fragments (scFv). Further provided are compositions including the antibodies that bind GPC3 or HS chains on GPC3, nucleic acid molecules encoding these antibodies, expression vectors comprising the nucleic acids, and isolated host cells that express the nucleic acids. Methods of treating cancer and/or inhibiting tumor growth or metastasis are also provided. Further provided are methods of detecting cancer in a subject and confirming a diagnosis of cancer in a subject.

公开(公告)号：EP3070104B1

公开(公告)日：2017-12-27

申请号：EP16166924.7

申请日：2012-04-19

申请人： The United States of America, as represented by The Secretary, Department of Health and Human Services

发明人： HO, Mitchell ,  FENG, Mingqian ,  DIMITROV, Dimiter S.

IPC分类号： C07K16/30 ,  A61K39/395 ,  C07K16/28 ,  G01N33/574 ,  G01N33/68 ,  A61K39/00 ,  C07K14/21

CPC分类号： C07K16/3076 ,  A61K39/39558 ,  A61K47/6803 ,  A61K47/6813 ,  A61K47/6829 ,  A61K47/6849 ,  A61K47/6851 ,  A61K2039/505 ,  C07K14/21 ,  C07K16/28 ,  C07K16/303 ,  C07K16/3092 ,  C07K2317/21 ,  C07K2317/31 ,  C07K2317/33 ,  C07K2317/41 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/33 ,  C07K2319/55 ,  G01N33/57438 ,  G01N33/57492 ,  G01N33/6893 ,  G01N2333/705 ,  G01N2400/40

摘要： Described herein is the identification of human monoclonal antibodies that bind GPC3 or heparan sulfate (HS) chains on GPC3 with high affinity. The antibodies described herein are capable of inhibiting HCC cell growth and migration. Provided are human monoclonal antibodies specific for GPC3 or HS chains on GPC3, including immunoglobulin molecules, such as IgG antibodies, as well as antibody fragments, such as single-domain VH antibodies or single chain variable fragments (scFv). Further provided are compositions including the antibodies that bind GPC3 or HS chains on GPC3, nucleic acid molecules encoding these antibodies, expression vectors comprising the nucleic acids, and isolated host cells that express the nucleic acids. Methods of treating cancer and/or inhibiting tumor growth or metastasis are also provided. Further provided are methods of detecting cancer in a subject and confirming a diagnosis of cancer in a subject.

公开(公告)号：EP4196504A1

公开(公告)日：2023-06-21

申请号：EP21762956.7

申请日：2021-08-10

申请人： The United States of America, as represented by the Secretary, Department of Health and Human Services

发明人： HO, Mitchell ,  LI, Nan ,  HONG, Jessica, Diana

IPC分类号： C07K16/30 ,  C07K16/28 ,  C07K14/725 ,  A61P35/00 ,  A61K39/00

公开(公告)号：EP3883608A1

公开(公告)日：2021-09-29

申请号：EP20703568.4

申请日：2020-01-02

申请人： The United States of America, as represented by the Secretary, Department of Health and Human Services

发明人： HO, Mitchell ,  PASTAN, Ira H. ,  HONG, Jessica D. ,  LI, Nan

IPC分类号： A61K39/395 ,  C07K16/30

公开(公告)号：EP3833684A1

公开(公告)日：2021-06-16

申请号：EP19759784.2

申请日：2019-08-06

申请人： The United States of America, as represented by the Secretary, Department of Health and Human Services

发明人： HO, Mitchell ,  FLEMING, Bryan D. ,  LI, Nan

IPC分类号： C07K16/18 ,  C07K16/30 ,  A61K39/00 ,  A61K47/68 ,  C07K14/725

公开(公告)号：EP2900695B1

公开(公告)日：2018-01-17

申请号：EP13766859.6

申请日：2013-09-16

申请人： The United States Of America, As Represented By The Secretary, Department Of Health And Human Services

发明人： HO, Mitchell ,  PASTAN, Ira, H. ,  DIMITROV, Dimiter, S. ,  TANG, Zhewei ,  FENG, Mingqian ,  GAO, Wei

IPC分类号： C07K16/30 ,  A61K39/395 ,  A61P35/00 ,  G01N33/574 ,  A61K39/00

CPC分类号： C07K16/30 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/30 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/569 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/00 ,  G01N33/57492 ,  G01N2333/705

摘要： Described herein is the use of phage display antibody engineering technology and synthetic peptide screening to identify SD1 and SD2, human single-domain antibodies to mesothelin. SD1 recognizes a conformational epitope at the C-terminal end (residues 539-588) of human mesothelin close to the cell surface. SD2 binds full-length mesothelin. To investigate SD1 as a potential therapeutic agent, a recombinant human Fc (SD1-hFc) fusion protein was generated. The SD1-hFc protein exhibits strong complement-dependent cytotoxicity (CDC), in addition to antibody-dependent cellular cytotoxicity (ADCC), against mesothelin-expressing tumor cells. Furthermore, the SD1-hFc protein causes significant tumor growth inhibition of tumor xenografts in nude mice. SD1 and SD2 are the first human single-domain antibodies targeting mesothelin-expressing tumors.

公开(公告)号：EP3070104A1

公开(公告)日：2016-09-21

申请号：EP16166924.7

申请日：2012-04-19

申请人： The United States of America, as represented by The Secretary, Department of Health and Human Services

发明人： HO, Mitchell ,  FENG, Mingqian ,  DIMITROV, Dimiter S.

IPC分类号： C07K16/30 ,  A61K39/395 ,  A61K47/48 ,  C07K16/28 ,  G01N33/574 ,  G01N33/68 ,  A61K39/00

CPC分类号： C07K16/3076 ,  A61K39/39558 ,  A61K47/6803 ,  A61K47/6813 ,  A61K47/6829 ,  A61K47/6849 ,  A61K47/6851 ,  A61K2039/505 ,  C07K14/21 ,  C07K16/28 ,  C07K16/303 ,  C07K16/3092 ,  C07K2317/21 ,  C07K2317/31 ,  C07K2317/33 ,  C07K2317/41 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/33 ,  C07K2319/55 ,  G01N33/57438 ,  G01N33/57492 ,  G01N33/6893 ,  G01N2333/705 ,  G01N2400/40

摘要： Described herein is the identification of human monoclonal antibodies that bind GPC3 or heparan sulfate (HS) chains on GPC3 with high affinity. The antibodies described herein are capable of inhibiting HCC cell growth and migration. Provided are human monoclonal antibodies specific for GPC3 or HS chains on GPC3, including immunoglobulin molecules, such as IgG antibodies, as well as antibody fragments, such as single-domain VH antibodies or single chain variable fragments (scFv). Further provided are compositions including the antibodies that bind GPC3 or HS chains on GPC3, nucleic acid molecules encoding these antibodies, expression vectors comprising the nucleic acids, and isolated host cells that express the nucleic acids. Methods of treating cancer and/or inhibiting tumor growth or metastasis are also provided. Further provided are methods of detecting cancer in a subject and confirming a diagnosis of cancer in a subject.

摘要翻译： 本文描述了以高亲和力在GPC3上结合GPC3或硫酸乙酰肝素（HS）链的人单克隆抗体的鉴定。 本文所述的抗体能够抑制HCC细胞生长和迁移。 提供对GPC3上的GPC3或HS链特异性的人单克隆抗体，包括免疫球蛋白分子，例如IgG抗体，以及抗体片段，例如单域VH抗体或单链可变片段（scFv）。 进一步提供的是包含结合GPC3上的GPC3或HS链的抗体，编码这些抗体的核酸分子，包含核酸的表达载体和表达核酸的分离的宿主细胞的组合物。 还提供了治疗癌症和/或抑制肿瘤生长或转移的方法。 还提供了检测受试者中的癌症并确认受试者中癌症诊断的方法。

公开(公告)号：EP1689783A2

公开(公告)日：2006-08-16

申请号：EP04812188.3

申请日：2004-11-24

申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

发明人： PASTAN, Ira H. ,  HO, Mitchell ,  BANG, Sook-Hee

IPC分类号： C07K16/28 ,  C07K19/00 ,  C12N15/13 ,  C12N15/62 ,  A61K39/395 ,  C07K14/21 ,  A61K47/48

CPC分类号： C07K16/2803 ,  A61K47/6829 ,  A61K47/6849 ,  C07K14/70503 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/624 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/30

摘要： Recombinant immunotoxins are fusion proteins composed of the Fv domains of antibodies fused to bacterial or plant toxins. RFB4 (Fv)-PE38 is an immunotoxin that targets CD22 expressed on B cells and B cell malignancies. The present invention provides antibodies and antibody fragments that have improved ability to bind the CD22 antigen compared to RFB4. Immunotoxins made with the antibodies and antibody fragments of the invention have improved cytotoxicity to CD22-expressing cancer cells. Compositions that incorporate these antibodies into chimeric immunotoxin molecules that can be used in medicaments and methods for inhibiting the growth and proliferation of such cancers. Additionally, the invention provides a method of increasing the cytotoxicity of forms of Pseudomonas exotoxin A ('PE') with the mutation of a single amino acid, as well as compositions of such mutated PEs, nucleic acids encoding them, and methods for using the mutated PEs.