• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    ANTIBODY ANTIGEN ANTIBODIES AND METHODS OF USE. The present invention relates to antibodies that bind to tumor-associated CD44 antigen or tumor-associated EphA2 antigen are disclosed herein, as well as related compositions and methods of use. Methods of use include methods of cancer therapies, diagnosis and screening.
    公开号:BR112013001640A2
    申请号:R112013001640-0
    申请日:2011-07-22
    公开日:2020-08-04
    发明作者:Yu Zhou；James D. Marks
    申请人:The Regents Of The University Of California；
    IPC主号:
    专利说明:

    Invention Patent Descriptive Report for "MONOCLONAL ANTIBODY THAT CONNECTS TO THE EPYPES OF EphA2 AND CD44, ITS
    USE IN CANCER TREATMENT AND CANCER CELL DETECTION, AS WELL AS COMPOSITION, KIT, NUCLEIC ACID AND 5 EXPRESSION VECTOR ". Cross Reference This application claims the benefit of Provisional Patent Application US 61 / 366,823, filed on 22 December July 2010, whose request is hereby incorporated by reference in its entirety. Declaration Regarding Research Sponsored by the Federal Government This invention was carried out with government support under concession No. CA058207 granted by the National In stitutes of Health. The government has certain rights Introduction Extensive studies of cancer transcription patterns have led to the verification of molecular targets to distinguish malignant from benign cancers and more aggressive cancers from those that are less aggressive. Cancers often overexpress a certain number of proteins, including certain cell surface antigens, for example, cell surface receptors. bind to such overexpressed cell surface antigens can facilitate the detection and treatment of such cancers. Several approaches have been used to generate antibodies to cancer cell surface receptors that can be used as potential therapeutic agents. The identification of overexpressed cell surface receptors and antibodies that bind to them provides a pathway for the development of cancer therapies, especially for cancer subtypes with poor prognosis and resistance to conventional therapies. CD44 and EphA2 are two overexpressed cell surface receptors, and are known from protein transcription and analysis profiles to be overexpressed in basal breast cancers. Antibodies specific for cell surface receptors The following sheet 1a / 105 follows
    1a / 105 home-expressed over a number of cancers have been used for the development of immunotherapeutic targets.
    For example, HER2, CD20, and EGFR are overexpressed in a number of tumors and the antibodies that
    Following sheet 2/105
    权利要求:
    Claims (17)
    [1]
    1. Isolated monoclonal antibody, characterized by the fact that (a) it specifically binds to an EphA2 epitope, whose top epitope is specifically bound by, or whose isolated monoclonal antibody competes for binding to EphA2 with, the D2-1A7 antibody , 2D6, D2-1A9, D2-1B1, A3H9, A3G3, A3D10, A3D1, A3C8, 1A3, 1A5, 1A8, 1A12, 1B2, 1C2, 1C7, 1D8, or 15H11; (b) specifically binds to an epitope of CD44, whose epitope is specifically bound by, or whose isolated monoclonal antibody competes for binding to CD44 with, the antibody F2-1A6, F2-1H9, E8H11, E8H7, E8G12, E8F11 , E8C9, D6G9, D6D3, D1C5, D1D1, HB8, HC2, HC4, HE3, HF1, or HH3, or that competes with the antibody F2-1A6, F2-1H9, E8H11, E8H7, E8G12, E8F11, E8C9, D6G9, D6D3, D1C5, D1D1, HB8, HC2, HC4, HE3, HF1, or HH3, by binding to CD44.
    [2]
    A monoclonal antibody according to claim 1, characterized by the fact that said antibody specifically binds to an EphA2 epitope, the epitope of which is specifically bound by an D2-1A7, 2D6, D2-1A9 antibody, D2-1B1, A3H9, A3G3, A3D10, A3D1, A3C8, 1A3, 1A5, 1A8, 1A12, 1B2, 1C2, 1C7, 1D8, or 15H11.
    [3]
    A monoclonal antibody according to claim 1, step (a) or claim 2, characterized in that, when bound to EphA2 on the surface of a living mammal cell, it is internalized within the cell.
    [4]
    Monoclonal antibody according to any one of claims 1 to 3, characterized in that said antibody comprises: a) a heavy chain (VH) polypeptide comprising: a VH CDR1, a VH CDR2 and a VH CDR3 of D2 -1A7; a VH CDR1, a VH CDR2 and a VH CDR3 of 2D6; a VH CDR1, a VH CDR2 and a VH CDR3 from D2-1A9; a VH CDR1, a VH CDR2 and a VH CDR3 from D2-1B1;
    a VH CDR1, a VH CDR2 and a VH CDR3 of D2-A3H9; a VH CDR1, a VH CDR2 and a VH CDR3 from D2-A3G3; a VH CDR1, a VH CDR2 and a VH CDR3 from D2-A3D10; a VH CDR1, a VH CDR2 and a VH CDR3 of D2-A3D1; 5 a VH CDR1, a VH CDR2 and a VH CDR3 of D2-A3C8; a VH CDR1, a VH CDR2 and a VH CDR3 of 1A3; a VH CDR1, a VH CDR2 and a VH CDR3 of 1A5; a VH CDR1, a VH CDR2 and a VH CDR3 of 1A8; a VH CDR1, a VH CDR2 and a VH CDR3 of 1A12; a VH CDR1, a VH CDR2 and a VH CDR3 of 1B2; a VH CDR1, a VH CDR2 and a VH CDR3 of 1C2; a VH CDR1, a VH CDR2 and a VH CDR3 of 1C7; a VH CDR1, a VH CDR2 and a VH CDR3 of 1D8; or a VH CDR1, a VH CDR2 and a VH CDR3 of 15H11; b) a light chain polypeptide (VL) comprising: a VL CDR1, a VL CDR2 and a VL CDR3 of D2-1A7; a VL CDR1, a VL CDR2 and a VL CDR3 of 2D6; a CDR1 VL, a CDR2 VL and a D2-1A9 VR CDR3; a VL CDR1, a VL CDR2 and a VL CDR3 of D2-1B1; a VL CDR1, a VL CDR2 and a VL CDR3 of D2-A3H9; a CDR1 VL, a CDR2 VL and a D2-A3G3 CDR3 VL; a VL CDR1, a VL CDR2 and a VL CDR3 of D2-A3D10; a CDR1 VL, a CDR2 VL and a D2-A3D1 VL CDR3; a CDR1 VL, a CDR2 VL and a D2-A3C8 VL CDR3; a VL CDR1, a VL CDR2 and a VL CDR3 of 1A3; a VL CDR1, a VL CDR2 and a VL CDR3 of 1A5; a VL CDR1, a VL CDR2 and a VL CDR3 of 1A8; a VL CDR1, a VL CDR2 and a VL CDR3 of 1A12; a VL CDR1, a VL CDR2 and a VL CDR3 of 1B2; a VL CDR1, a VL CDR2 and a VL CDR3 of 1C2; a VL CDR1, a VL CDR2 and a VL CDR3 of 1C7; a VL CDR1, a VL CDR2 and a VL CDR3 of 1D8; or a VL CDR1, a VL CDR2 and a VL CDR3 of 15H11; or c) a VH polypeptide according to a) and a VL polypeptide according to b).
    [5]
    5. Monoclonal antibody according to any of claims 1 to 4, characterized by the fact that said antibody is a single chain Fv (scFv), IgG, Fab, (Fab ') 2 or (scFv') 2.
    [6]
    6. Monoclonal antibody according to any of claims 1 to 5, characterized by the fact that said antibody is conjugated to a second molecule.
    [7]
    7. Composition, characterized by the fact that it comprises: a pharmaceutically acceptable vehicle; and a monoclonal antibody, as defined in any one of claims 1 to 6.
    [8]
    8. Kit, characterized by the fact that it comprises a composition, as defined in claim 7 in a container.
    [9]
    9. Use of a monoclonal antibody, as defined in any one of claims 1 to 6, or of a composition, as defined in claim 7, characterized by the fact that it is for the manufacture of a drug for the treatment of cancer in an individual.
    [10]
    10. Use of a monoclonal antibody, as defined in any of claims 1 to 6, characterized by the fact that it is for the manufacture of a kit to detect a cancer cell in an individual.
    [11]
    11. Isolated nucleic acid, characterized by the fact that it comprises a nucleotide sequence encoding an amino acid sequence of: a) a variable heavy chain (VH) polypeptide comprising a VH CDR1, a VH CDR2 and a VH CDR3 of an antibody, as defined in any one of claims 1 to 4; or b) a variable light chain (VL) polypeptide comprising a VL CDR1, a VL CDR2 and a VL CDR3 of an antibody, as defined in any one of claims 1 to 4; or c) a VH polypeptide comprising a VH CDR1, a VH
    CDR2 and a VH CDR3; and a VL polypeptide comprising a VL CDR1, a VL CDR2 and a VL CDR3 of an antibody, as defined in any one of claims 1 to 4.
    [12]
    12. Expression vector, characterized by the fact that it comprises one or more nucleic acid (s), as defined in claim 11.
    [13]
    13. Recombinant host cell, characterized by the fact that it comprises the expression vector, as defined in claim 12.
    [14]
    14. Recombinant host cell according to claim 13, characterized in that the cell expresses an antibody comprising the VH polypeptide and the VL polypeptide from step c).
    [15]
    15. Recombinant host cell according to claim 13, characterized in that it comprises: i) an expression vector comprising a nucleotide sequence that encodes an amino acid sequence of a variable heavy chain (VH) polypeptide comprising a VH CDR1 comprising the amino acid sequence SYAMH (SEQ ID NO: 29), a VH CDR2 comprising the amino acid sequence VISYDGSNKYYADSVKG (SEQ ID NO: 45), and a VH CDR3 comprising the amino acid sequence ASVGATGPFDI ( SEQ ID NO: 42); and ii) an expression vector comprising a nucleotide sequence that encodes an amino acid sequence of a variable light chain (VL) polypeptide comprising a VL CDR1 comprising the QGDSLRSYYAS amino acid sequence (SEQ ID NO: 17), a VL CDR2 comprising the amino acid sequence GENNRPS (SEQ ID NO: 71), and a VL CDR3 comprising the amino acid sequence NSRDSSGTHLTV (SEQ ID NO: 60).
    [16]
    16. Recombinant host cell according to claim 15, characterized in that it expresses an antibody comprising a variable heavy chain (VH) polypeptide comprising CDR1, CDR2 and CDR3 of i) and, a chain polypeptide mild variable (VL) comprising CDR1, CDR2 and CDR3 of ii).
    [17]
    17. Invention, characterized by any forms of its con-
    accreditations or any applicable category of claim, for example, product or process or use encompassed by the material initially described, revealed or illustrated in the patent application.
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    法律状态:
    2020-08-18| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2020-09-01| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |
    2020-10-20| B08F| Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette]|Free format text: REFERENTE A 9A ANUIDADE. |
    2021-02-09| B08K| Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette]|Free format text: EM VIRTUDE DO ARQUIVAMENTO PUBLICADO NA RPI 2598 DE 20-10-2020 E CONSIDERANDO AUSENCIA DE MANIFESTACAO DENTRO DOS PRAZOS LEGAIS, INFORMO QUE CABE SER MANTIDO O ARQUIVAMENTO DO PEDIDO DE PATENTE, CONFORME O DISPOSTO NO ARTIGO 12, DA RESOLUCAO 113/2013. |
    2021-11-03| B350| Update of information on the portal [chapter 15.35 patent gazette]|
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