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    Monoclonal Antibodies to Progastrin
    22.
    发明申请
    Monoclonal Antibodies to Progastrin 有权
    促胃泌素的单克隆抗体

    公开(公告)号：US20070248608A1

    公开(公告)日：2007-10-25

    申请号：US11663126

    申请日：2005-09-21

    申请人： Stephen Grimes

    发明人： Stephen Grimes

    IPC分类号： A61K38/00 ,  A01N37/18 ,  A61K39/00 ,  A61K39/395 ,  A61P1/02 ,  C07K16/00 ,  C12N15/00 ,  C12P21/08 ,  G01N33/00 ,  G01N33/53

    CPC分类号： G01N33/6893 ,  A61K2039/505 ,  C07K16/26 ,  C07K2317/34 ,  G01N33/74 ,  G01N2333/595 ,  G01N2800/06

    摘要： The present invention provides progastrin-binding molecules specific for progastrin that do not bind gastrin-17(G17), gastrin-34(G34), glycine-extended gastrin-17(G17-Gly), or glycine-extended gastrin-34(G34-Gly). Further, the invention provides monoclonal antibodies (MAbs) selective for sequences at the N-terminus and the C-terminus of the gastrin precursor molecule, progastrin and the hybridomas that produce these MAbs. Also provided are panels of MAbs useful for the detection and quantitation of progastrin and gastrin hormone species in immuno-detection and quantitation assays. These assays are useful for diagnosing and monitoring a gastrin-promoted disease or condition, or for monitoring the progress of a course of therapy. The invention further provides solid phase assays including immunohistochemical (IHC) and immunofluorescence (IF) assays suitable for detection and visualization of gastrin species in solid samples, such as biopsy samples or tissue slices. The progastrin-binding molecules are useful therapeutically for passive immunization against progastrin in progastrin-promoted diseases or conditions. Also provided are surrogate reference standard (SRS) molecules that are peptide chains of from about 10 to about 35 amino acids, wherein the SRS molecule comprises at least two epitopes found in a protein of interest of greater than about 50 amino acids. Such SRS molecules are useful as standards in place of authentic proteins of interest.

    摘要翻译： 本发明提供了不结合胃泌素-17（G17），胃泌素-34（G34），甘氨酸延长胃泌素-17（G17-Gly）或甘氨酸延长胃泌素-34（G34）的泌乳素特异性的前胃泌素结合分子 -Gly）。 此外，本发明提供对胃泌素前体分子的N-末端和C末端的序列选择性的单克隆抗体（MAb），前导肽和产生这些MAb的杂交瘤。 还提供了用于在免疫检测和定量测定中检测和定量前胃泌素和胃泌素激素物质的MAb的小组。 这些测定法可用于诊断和监测胃泌素促进的疾病或病症，或用于监测治疗过程的进展。 本发明进一步提供固相测定法，包括免疫组织化学（IHC）和免疫荧光（IF）测定法，其适于检测和可视化固体样品例如活检样本或组织切片中的胃泌素种类。 促胃泌素结合分子可用于治疗前列腺素促进的疾病或病症中针对前胃泌素的被动免疫。 还提供了作为约10至约35个氨基酸的肽链的替代参考标准（SRS）分子，其中SRS分子包含在大于约50个氨基酸的目的蛋白中发现的至少两个表位。 这样的SRS分子可用作代替感兴趣的真实蛋白质的标准物。

    Chimeric peptide immunogens
    23.
    发明申请
    Chimeric peptide immunogens 审中-公开
    嵌合肽免疫原

    公开(公告)号：US20050106137A1

    公开(公告)日：2005-05-19

    申请号：US10931566

    申请日：2004-08-31

    申请人： Stephen Grimes

    发明人： Stephen Grimes

    IPC分类号： A61K39/00 ,  C07K7/23 ,  A61K39/395 ,  C07K16/44

    CPC分类号： A61K39/0006 ,  A61K39/00 ,  A61K2039/6031 ,  A61K2039/6037 ,  A61K2039/6068 ,  C07K7/23 ,  C07K2319/00 ,  Y02A50/412

    摘要： Chimeric peptide epitopes can serve as effective immunogens against hormones and other small peptides or proteins. Immunogenic peptides are selected from promiscuous helper T-lymphocyte epitopes and synthesized together with self antigenic peptide sequences optionally fused through a spacer moiety. Examples of the chimeric peptide immunogens of the invention include peptide sequences which may be from any antigen, such as a gonadotropin releasing hormone (GnRH), linked with an immunogenic peptide sequence such as a promiscuous helper T-lymphocyte epitope of measles virus protein F, tetanus toxoid, or malaria protein CSP. Compositions of the chimeric immunogen are found effective in eliciting high and specific anti-GnRH antibody titers. This invention also relates to compositions and methods for synergistically enhancing or suppressing an immune response to a target antigen.

    摘要翻译： 嵌合肽表位可以作为针对激素和其他小肽或蛋白质的有效免疫原。 免疫原性肽选自混杂辅助性T淋巴细胞表位，并与通过间隔基部分任选融合的自身抗原肽序列一起合成。 本发明的嵌合肽免疫原的实例包括与免疫原性肽序列如麻疹病毒蛋白F的混杂辅助T淋巴细胞表位连接的任何抗原例如促性腺激素释放激素（GnRH）的肽序列， 破伤风类毒素或疟疾蛋白质CSP。 发现嵌合免疫原的组合物在引发高和特异性抗GnRH抗体滴度方面是有效的。 本发明还涉及用于协同增强或抑制对靶抗原的免疫应答的组合物和方法。

    Chimeric peptide immunogens
    24.
    发明授权
    Chimeric peptide immunogens 失效
    嵌合肽免疫原

    公开(公告)号：US06783761B2

    公开(公告)日：2004-08-31

    申请号：US09848834

    申请日：2001-05-04

    申请人： Stephen Grimes ,  Dov Michaeli ,  Vernon C. Stevens

    发明人： Stephen Grimes ,  Dov Michaeli ,  Vernon C. Stevens

    IPC分类号： A61K3900

    CPC分类号： A61K39/0006 ,  A61K39/00 ,  A61K2039/6031 ,  A61K2039/6037 ,  A61K2039/6068 ,  C07K7/23 ,  C07K2319/00 ,  Y02A50/412

    摘要： Chimeric peptide epitopes can serve as effective immunogens against hormones and other small peptides or proteins. Thus, immunogenic peptides are selected from promiscuous Th epitopes and synthesized together with self antigenic peptide sequences fused with or without end to end spacer peptide interconnections. A peptide sequence which may be of the gonadotropin releasing hormone is linked with an immunogenic peptide sequence selected from a promiscuous Th-epitope of measles virus protein F, tetanus toxoid, or malaria protein CSP. Compositions of the chimeric immunogen are found effective in eliciting high and specific anti-GnRH antibody titers.

    摘要翻译： 嵌合肽表位可以作为针对激素和其他小肽或蛋白质的有效免疫原。 因此，免疫原性肽选自混杂的Th表位，并与与或不具有端对端间隔肽互连融合的自身抗原肽序列一起合成。 可以是促性腺激素释放激素的肽序列与选自麻疹病毒蛋白F，破伤风类毒素或疟疾蛋白CSP的混杂Th-表位的免疫原性肽序列连接。 发现嵌合免疫原的组合物在引发高和特异性抗GnRH抗体滴度方面是有效的。

    Immunogenic compositions to the CCK-B/gastrin receptor and methods for the treatment of tumors
    25.
    发明授权
    Immunogenic compositions to the CCK-B/gastrin receptor and methods for the treatment of tumors 失效
    CCK-B /胃泌素受体的免疫原性组合物和治疗肿瘤的方法

    公开(公告)号：US06548066B1

    公开(公告)日：2003-04-15

    申请号：US09076372

    申请日：1998-05-12

    申请人： Dov Michaeli ,  Martyn Caplin ,  Susan A. Watson ,  Stephen Grimes

    发明人： Dov Michaeli ,  Martyn Caplin ,  Susan A. Watson ,  Stephen Grimes

    IPC分类号： A61K39385

    CPC分类号： C07K14/72 ,  A61K38/00 ,  A61K39/0005 ,  A61K39/0011 ,  A61K2039/505 ,  A61K2039/6037 ,  C07K16/2869 ,  C07K16/30 ,  C07K2317/34 ,  C07K2317/77 ,  G01N33/57488

    摘要： The invention concerns immunogens, immunogenic compositions and method for the treatment of gastrin-dependent tumors. The immunogens comprise a peptide from the CCK-B/gastrin-receptor conjugated to a spacer and to an immunogenic carrier. The immunogens are capable of inducing antibodies in vivo which bind to the CCK-B/gastrin-receptor in tumor cells, thereby preventing growth stimulating peptide hormones from binding to the receptors, and inhibiting tumor cell growth. The immunogens also comprise antibodies against the CCK-B/gastrin-receptor for passive immunization. The invention also concerns diagnostic methods for detecting gastrin-dependent tumors in vivo or from a tissue biopsy using the antibodies of the invention.

    摘要翻译： 本发明涉及用于治疗胃泌素依赖性肿瘤的免疫原，免疫原性组合物和方法。 免疫原包含与间隔基缀合的CCK-B /胃泌素受体的肽和免疫原性载体。 免疫原能够在体内诱导结合肿瘤细胞中的CCK-B /胃泌素受体的抗体，从而防止生长刺激肽激素与受体结合并抑制肿瘤细胞生长。 免疫原还包括针对被动免疫的CCK-B /胃泌素受体的抗体。 本发明还涉及使用本发明的抗体在体内或组织活组织检查中检测胃泌素依赖性肿瘤的诊断方法。

    IMMUNOTHERAPEUTIC COMPOSITIONS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
    28.
    发明申请
    IMMUNOTHERAPEUTIC COMPOSITIONS FOR THE TREATMENT OF ALZHEIMER'S DISEASE 有权
    用于治疗阿尔茨海默病的免疫组织化学

    公开(公告)号：US20110206742A1

    公开(公告)日：2011-08-25

    申请号：US13057952

    申请日：2009-08-06

    申请人： Peter Blackburn ,  Stephen Grimes

    发明人： Peter Blackburn ,  Stephen Grimes

    IPC分类号： A61K9/107 ,  A61P25/28 ,  A61K39/00 ,  A61K39/385

    CPC分类号： A61K39/0007 ,  A61K2039/55566 ,  A61K2039/6037 ,  A61K2039/6081 ,  Y02A50/466

    摘要： A safe and effective vaccine to prevent, slow, halt or reverse progression of Alzheimer's disease in human patients is disclosed. The vaccine includes Aβ1-42 or an beta amyloid self epitope (e.g. Aβ1-15, or other 7-mer or 15-mer peptide epitopes derived from Aβ1-42) conjugated to an immunogenic carrier (e.g. DT) formulated in a water-in-oil Th2-biased adjuvant/delivery system.

    摘要翻译： 公开了一种安全有效的预防，缓慢，停止或逆转老年痴呆症进展的疫苗。 该疫苗包括与免疫原性载体（例如DT）缀合的Aβ1-42或β淀粉样蛋白自身表位（例如A＆bgr; 1-15或衍生自A＆bgr; 1-42的其它7-聚体或15聚体肽表位） 配制在含油Th2偏置的佐剂/输送系统中。

    Gastrin hormone immunoassays
    29.
    发明授权
    Gastrin hormone immunoassays 有权
    胃泌素激素免疫测定

    公开(公告)号：US07964371B2

    公开(公告)日：2011-06-21

    申请号：US11800889

    申请日：2007-05-07

    申请人： Stephen Grimes ,  John Little ,  Lorraine McLoughlin

    发明人： Stephen Grimes ,  John Little ,  Lorraine McLoughlin

    IPC分类号： G01N33/53 ,  G01N33/537 ,  G01N33/543

    CPC分类号： G01N33/6893 ,  G01N33/74 ,  G01N2333/595

    摘要： The invention provides assay methods for the detection and quantitation of gastrin hormones, including total and free gastrin hormone in a sample. ELISA-type heterogeneous phase assays suitable for use with biological fluid samples such as blood, plasma or other bodily fluids of a mammal, particularly a human subject are provided. The method provides a precise assay for the amounts of free and total G17 and G34 in biological fluid samples, as well as the amounts of free and total Gly-extended G17, and Gly-extended G34. Also provided are methods of determining suitable treatment for patient suffering from a gastrin hormone-mediated disease or condition employing gastrin hormone immunoassays.

    摘要翻译： 本发明提供了用于检测和定量胃泌素激素的测定方法，包括样品中的总的和游离的胃泌素激素。 提供了适用于哺乳动物，特别是人类受试者的生物流体样品如血液，血浆或其它体液的ELISA型异相测定。 该方法提供了生物流体样品中游离和总G17和G34的量的精确测定，以及游离和总Gly扩展的G17和Gly延伸的G34的量。 还提供了确定患有胃泌素激素介导的疾病或使用胃泌素激素免疫测定的病症的患者的适合治疗的方法。

    TREATMENT AND PREVENTION OF CANCEROUS AND PRE-CANCEROUS CONDITIONS OF THE LIVER, LUNG AND ESOPHAGUS
    30.
    发明申请
    TREATMENT AND PREVENTION OF CANCEROUS AND PRE-CANCEROUS CONDITIONS OF THE LIVER, LUNG AND ESOPHAGUS 审中-公开
    治疗和预防肝癌，肺癌和ESOPHAGUS癌症和癌前病变

    公开(公告)号：US20110117108A1

    公开(公告)日：2011-05-19

    申请号：US13012433

    申请日：2011-01-24

    申请人： Philip C. Gevas ,  Dov Michaeli ,  Stephen Grimes

    发明人： Philip C. Gevas ,  Dov Michaeli ,  Stephen Grimes

    IPC分类号： A61K39/395 ,  A61K39/00 ,  A61P35/00

    CPC分类号： C07K14/72 ,  A61K2039/505

    摘要： The invention relates to the treatment and/or prevention of cancerous and/or, precancerous conditions of the liver, lung and esophagus by actively and/or passively immunizing a patient against the peptide hormone gastrin and/or a gastrin receptor, e.g., the CCK-B/gastrin receptor. The immunizations of the invention may be employed as a monotherapy, an adjunctive therapy, or as part of a combination therapy.

    摘要翻译： 本发明涉及通过主动地和/或被动地免疫患者对肽激素胃泌素和/或胃泌素受体（例如CCK）来治疗和/或预防肝，肺和食道的癌性和/或癌前病症 -B /胃泌素受体。 本发明的免疫可用作单一疗法，辅助治疗或组合疗法的一部分。