公开(公告)号：US20110259744A1

公开(公告)日：2011-10-27

申请号：US12800574

申请日：2010-05-18

申请人： William R. Moyle

发明人： William R. Moyle

IPC分类号： G01N27/447 ,  G01N33/559

CPC分类号： G01N27/44726

摘要： A sensor device is provided for detecting an analyte in a sample in which an analyte is bound to a detection reagent to form a bound complex. The device comprises (a) a sample (5) comprising an ionic analyte and a detection reagent in a conductive fluid, wherein the detection reagent has a net charge different from the analyte; (b) a first permeable polymeric hydrogel plate (3) and a first spacer plate (8), which plates provide a compartment for the sample; (c) an anode (1) juxtaposed to the outside of the first hydrogel plate and not in contact with the sample; (d) a cathode (9) juxtaposed to the outside of the first spacer plate and not in contact with the sample; (e) a voltage generator (10) to apply an electric potential to the anode and cathode; and (f) a detector (11). The bound complex formed from the analyte and detection reagent is detected by the detector because the bound complex has a charge that causes it to migrate in a direction opposite from that of the unbound analyte when the electric potential is applied. The present invention further methods for new rapid clinical uses such as for pap smears, diagnosis of sexually transmitted diseases, diagnoses of skin cancers, diagnosis of oral cancers and monitoring lymphocytes.

摘要翻译： 提供了一种用于检测样品中分析物与检测试剂结合以形成结合复合物的分析物的传感器装置。 该装置包括（a）包含导电流体中的离子分析物和检测试剂的样品（5），其中检测试剂具有不同于分析物的净电荷; （b）第一可渗透聚合物水凝胶板（3）和第一间隔板（8），所述板提供样品的隔室; （c）与第一水凝胶板的外部并置并不与样品接触的阳极（1）; （d）与第一间隔板的外部并置并且不与样品接触的阴极（9）; （e）向阳极和阴极施加电位的电压发生器（10）; 和（f）检测器（11）。 由分析物和检测试剂形成的结合络合物由检测器检测，因为结合的复合物具有使电荷在施加电位时沿与未结合的分析物相反的方向迁移的电荷。 本发明还涉及新的快速临床应用的方法，例如宫颈涂片，性传播疾病的诊断，皮肤癌的诊断，口腔癌的诊断和监测淋巴细胞。

公开(公告)号：US08530190B1

公开(公告)日：2013-09-10

申请号：US09104400

申请日：1998-06-25

申请人： William R. Moyle

发明人： William R. Moyle

IPC分类号： A61K38/24 ,  A61P5/06 ,  C07K14/59 ,  C07K1/00 ,  C07K14/00 ,  C07K16/00 ,  C07K17/00 ,  C07H21/04 ,  C12N15/09 ,  C12N5/07 ,  C12N5/10 ,  C12N5/00 ,  C12N5/02 ,  C12N15/00

CPC分类号： C07K14/59 ,  A61K38/00

摘要： The invention relates to analogs of glycoprotein hormones with an intersubunit disulfide crosslink and their preparation and use. Corresponding DNA sequences and host cells, as well as pharmaceutical compositions are also disclosed.

摘要翻译： 本发明涉及具有亚氨基二硫键交联的糖蛋白激素的类似物及其制备和用途。 还公开了相应的DNA序列和宿主细胞，以及药物组合物。

公开(公告)号：US07384781B2

公开(公告)日：2008-06-10

申请号：US11231654

申请日：2005-09-21

申请人： William R. Moyle ,  Russell C. Scaduto, Jr.

发明人： William R. Moyle ,  Russell C. Scaduto, Jr.

IPC分类号： C12M1/34 ,  C12M3/00

CPC分类号： C12Q1/6841 ,  B01L3/50851 ,  B01L2300/0822 ,  B01L2300/1827 ,  B01L2400/0421 ,  G01N21/6428 ,  G01N21/6458 ,  G01N21/648 ,  G01N33/54373 ,  G01N33/5438 ,  C12Q2565/607

摘要： A sensor device is provided for detecting an analyte in a sample in which an analyte is bound to a detection reagent to form a bound complex. The device comprises (a) a sample (5) comprising an ionic analyte and a detection reagent in a conductive fluid, wherein the detection reagent has a net charge different from the analyte; (b) a first permeable polymeric hydrogel plate (3) and a first spacer plate (8), which plates provide a compartment for the sample; (c) an anode (1) juxtaposed to the outside of the first hydrogel plate and not in contact with the sample; (d) a cathode (9) juxtaposed to the outside of the first spacer plate and not in contact with the sample; (e) a voltage generator (10) to apply an electric potential to the anode and cathode; and (f) a detector (11). The bound complex formed from the analyte and detection reagent is detected by the detector because the bound complex has a charge that causes it to migrate in a direction opposite from that of the unbound analyte when the electric potential is applied.

摘要翻译： 提供了一种用于检测样品中分析物与检测试剂结合以形成结合复合物的分析物的传感器装置。 该装置包括（a）包含导电流体中的离子分析物和检测试剂的样品（5），其中检测试剂具有不同于分析物的净电荷; （b）第一可渗透聚合物水凝胶板（3）和第一间隔板（8），所述板提供样品的隔室; （c）与第一水凝胶板的外部并置并不与样品接触的阳极（1）; （d）与第一间隔板的外部并置并且不与样品接触的阴极（9）; （e）向阳极和阴极施加电位的电压发生器（10）; 和（f）检测器（11）。 由分析物和检测试剂形成的结合络合物由检测器检测，因为结合的复合物具有使电荷在施加电位时沿与未结合的分析物相反的方向迁移的电荷。

公开(公告)号：US07001597B1

公开(公告)日：2006-02-21

申请号：US08867587

申请日：1997-06-02

申请人： William R. Moyle

发明人： William R. Moyle

IPC分类号： A61K39/395

CPC分类号： C07K14/59 ,  A61K38/00 ,  A61K39/00 ,  A61K2039/505 ,  C07K16/26 ,  C07K2317/76 ,  C07K2319/00

摘要： The present invention relates to methods for enhancing fertility by reducing the activities and/or levels of circulating glycoprotein hormones having lutropin (LH) activity. The molecules of the invention are antibodies or other binding agents that reduce the biological activities of LH. The present invention also relates to novel methods for devising and/or selecting antibodies to specific portions of proteins including LH and human chorionic gonadotropin (hCG) to permit their biological activities to be reduced to desired degrees. The present invention also relates to the preparation of single subunit gonadotropins and gonadotropin antagonists for use in stimulating and inhibiting fertility and for controlling ovarian hyperstimulation. In a preferred embodiment, the present invention pertains to a method for stimulating fertility in mammals by reducing the activity of glycoprotein hormones having luteinizing hormone activity in circulation and thereby stimulating the production of follicle stimulating hormone which comprises administering to the mammal a therapeutically effective amount of a binding agent that binds luteinizing hormone.

摘要翻译： 本发明涉及通过降低具有劳拉（LH）活性的循环糖蛋白激素的活性和/或水平来提高生育力的方法。 本发明的分子是降低LH生物活性的抗体或其它结合剂。 本发明还涉及用于设计和/或选择包括LH和人绒毛膜促性腺激素（hCG）的蛋白质的特定部分的抗体的新方法，以使其生物活性降低至所需程度。 本发明还涉及用于刺激和抑制生育力和用于控制卵巢过度刺激的单亚基促性腺激素和促性腺激素拮抗剂的制备。 在一个优选的实施方案中，本发明涉及一种通过降低在循环中具有黄体生成激素活性的糖蛋白激素的活性来刺激哺乳动物的生育力的方法，从而刺激促卵泡激素的产生，其包括向哺乳动物施用治疗有效量的 结合促黄体激素的结合剂。

公开(公告)号：US06242580B1

公开(公告)日：2001-06-05

申请号：US09282357

申请日：1999-03-31

申请人： Irving Boime ,  William R. Moyle

发明人： Irving Boime ,  William R. Moyle

IPC分类号： C07K1459

CPC分类号： C07K14/59 ,  A61K38/00 ,  A61K39/00 ,  C07K14/575 ,  C07K16/26 ,  C07K2319/00

摘要： Single-chain forms of the glycoprotein hormone quartet, at least some members of which are found in most vertebrates, are disclosed. The &agr; and &bgr; subunits of the wild-type heterodimers or their variants or their fragments are covalently linked, optionally through a linker moiety. Some of the single-chain forms are agonists and others antagonists of the glycoprotein hormone activity.

摘要翻译： 公开了在大多数脊椎动物中发现的至少一些成员的糖链蛋白激素四重奏的单链形式。 野生型异二聚体或其变体或其片段的α和β亚基任选地通过连接体部分共价连接。 一些单链形式是激动剂和糖蛋白激素活性的其它拮抗剂。

公开(公告)号：US5284778A

公开(公告)日：1994-02-08

申请号：US759645

申请日：1991-09-12

申请人： Robert E. Canfield ,  E. Glenn Armstrong ,  William R. Moyle ,  Gordon J. MacDonald ,  Donna M. Anderson

发明人： Robert E. Canfield ,  E. Glenn Armstrong ,  William R. Moyle ,  Gordon J. MacDonald ,  Donna M. Anderson

IPC分类号： G01N33/76 ,  G01N33/536

CPC分类号： G01N33/76

摘要： This invention provides a quantitative assay for determining the amount of a biologically active ligand selected from the group consisting of human chorionic gonadotropin and luetinizing hormone present in a sample comprising contacting the sample with both the receptor to which the ligand naturally binds in order to effect its biologicaly activity and a monoclonal antibody directed to the ligand or to a complex of the ligand and the receptor so as to form a complex of the ligand bound to both the receptor, at the site to which the ligand naturally binds to the receptor, and the monoclonal antibody. In the complex so formed, either the receptor or the monoclonal antibody is labeled with a detectable marker and a determination is made of the amount of labeled receptor or of labeled monoclonal antibody bound to the ligand or the amount of labeled receptor or of labeled monoclonal antibody not bound to the ligand, or both such amounts.This invention further provides a quantitative assay for determining the amount present in a sample of a receptor to which a biologically acitve ligand selected from the group consisting of human chorionic gonadotropin and luetinizing hormone naturally binds in order to effect its biological activity. Finally, this invention provides kits for quantitatively assaying for the amount present in a sample of a biologically active ligand or for a receptor to which the ligand naturally binds in order to effect its biological activity.

摘要翻译： 本发明提供了用于确定选自样品中存在的人绒毛膜促性腺激素和呼吸系数激素的生物活性配体的量的定量测定法，其包括将样品与配体天然结合的受体相接触以实现其 生物活性和针对配体或配体和受体的复合物的单克隆抗体，以便在配体天然与受体结合的位点处形成与受体结合的配体的复合物，以及 单克隆抗体。 在如此形成的复合物中，受体或单克隆抗体用可检测的标记物标记，并且确定与配体结合的标记受体或标记的单克隆抗体的量或标记的受体或标记的单克隆抗体的量 不与配体结合，或两者都相同。 本发明进一步提供了一种定量测定法，用于确定存在于受体的样品中的量，其中选自人绒毛膜促性腺激素和呼吸系数激素的生物活性配体天然结合以实现其生物学活性。 最后，本发明提供了用于定量测定生物活性配体样品中存在的量或配体天然结合的受体以实现其生物学活性的试剂盒。

公开(公告)号：US20090209453A1

公开(公告)日：2009-08-20

申请号：US11911571

申请日：2006-04-13

申请人： William R. Moyle

发明人： William R. Moyle

IPC分类号： A61K38/16 ,  C07K14/00 ,  C07K17/00 ,  C07H21/04 ,  C12N15/63 ,  C12N5/00

CPC分类号： C07K14/59 ,  A61K38/00 ,  A61K47/62

摘要： This invention relates to the field of glycoprotein hormone analogs and their uses as agonists, antagonists, targeting vectors, and immunogens. In particular, this invention describes a method for stabilizing a heterodimer that permits the preparation of functional glycoprotein hormone analogs. The analogs of present invention comprise at least one alpha subunit polypeptide and at least one beta subunit polypeptide, wherein the seatbelt region of the beta subunit is linked to the alpha subunit. The invention also provides for a beta subunit polypeptide wherein the C-terminal amino acid is from residue 10 to residue 20 of the seatbelt region.

摘要翻译： 本发明涉及糖蛋白激素类似物领域及其作为激动剂，拮抗剂，靶向载体和免疫原的用途。 特别地，本发明描述了一种稳定异二聚体的方法，其允许制备功能性糖蛋白激素类似物。 本发明的类似物包含至少一个α亚基多肽和至少一个β亚基多肽，其中β亚基的安全带区域连接到α亚基。 本发明还提供β-亚基多肽，其中C-末端氨基酸来自安全带区域的残基10至残基20。

公开(公告)号：US5508261A

公开(公告)日：1996-04-16

申请号：US425673

申请日：1995-04-18

申请人： William R. Moyle ,  Robert K. Campbell ,  Gordon J. Macdonald ,  Yi Han ,  Yanhong Wang

发明人： William R. Moyle ,  Robert K. Campbell ,  Gordon J. Macdonald ,  Yi Han ,  Yanhong Wang

IPC分类号： C07K14/59 ,  A61K38/24 ,  A61K38/22 ,  C07K14/575

CPC分类号： C07K14/59

摘要： The present invention pertains to an alpha, beta-heterodimeric polypeptide having binding affinity to vertebrate luteinizing hormone (LH) receptors and vertebrate follicle stimulating hormone (FSH) receptors comprising a glycoprotein hormone alpha-subunit polypeptide and a non-naturally occurring beta-subunit polypeptide, wherein the beta-subunit polypeptide is a chain of amino acids comprising the following four joined subsequences:(a) a first subsequence homologous to the amino acid sequence of residues 1-93 of the beta-subunit selected from the group consisting of human chorionic gonadotrophin (hCG), vertebrate luteinizing hormone (LH), vertebrate follicle stimulating hormone (FSH), and vertebrate thyroid stimulating hormone (TSH);(b) a second subsequence homo logous to the amino acid sequence of residues 94-97 of the beta-subunit selected from the group consisting of human chorionic gonadotrophin (hCG) and vertebrate luteinizing hormone (LH);(c) a third subsequence homologous to the amino acid sequence of residues 98-100 of the beta-subunit selected from the group consisting of human chorionic gonadotrophin (hCG), vertebrate luteinizing hormone (LH), vertebrate follicle stimulating hormone (FSH), and vertebrate thyroid stimulating hormone (TSH); and(d) a fourth subsequence homologous to the amino acid sequence of residues 101-110 of the beta-subunit of vertebrate follicle stimulating hormone.

摘要翻译： 本发明涉及对脊椎动物黄体生成激素（LH）受体和包含糖蛋白激素α-亚基多肽和非天然存在的β-亚基多肽的脊椎动物刺激素（FSH）受体具有结合亲和力的α，β-异二聚体多肽 ，其中所述β-亚基多肽是包含以下四个连接的亚序列的氨基酸链：（a）与β-亚基的残基1-93的氨基酸序列同源的第一亚序列，所述第一亚序列选自人绒毛膜 促性腺激素（hCG），脊椎动物黄体激素（LH），脊椎动物刺激素（FSH）和脊椎动物促甲状腺激素（TSH）; （b）与选自人绒毛膜促性腺激素（hCG）和脊椎动物黄体生成素（LH）的β-亚基的残基94-97的氨基酸序列同源的第二个亚序列; （c）与选自人绒毛膜促性腺激素（hCG），脊椎动物黄体生成激素（LH），脊椎动物刺激素（FSH）的β-亚单位的残基98-100的氨基酸序列同源的第三子序列， 和脊椎动物刺激激素（TSH）; 和（d）与脊椎动物促卵泡激素的β-亚基的残基101-110的氨基酸序列同源的第四个亚序列。

公开(公告)号：US4792528A

公开(公告)日：1988-12-20

申请号：US16213

申请日：1987-02-19

申请人： Robert E. Canfield ,  Paul H. Ehrlich ,  William R. Moyle

发明人： Robert E. Canfield ,  Paul H. Ehrlich ,  William R. Moyle

IPC分类号： G01N33/53 ,  G01N33/543 ,  G01N33/577 ,  G01N33/74 ,  G01N33/76 ,  G01N33/537 ,  G01N33/561

CPC分类号： G01N33/5306 ,  G01N33/54393 ,  G01N33/577 ,  G01N33/74 ,  G01N33/76

摘要： Mixtures of monoclonal antibodies which contain effective assaying amounts of each of at least two monoclonal antibodies that bind to different antigenic sites on the antigen and are capable under appropriate conditions of binding simultaneously to an antigen are useful in enhanced sensitivity assays for the antigen. By utilizing such mixtures in diagnostic assays for important antigens such as the polypeptide human chorionic gonadotropin enhanced sensitivity can be achieved as compared with assays employing individual monoclonal antibodies.

摘要翻译： 含有有效测定量的至少两种单克隆抗体结合抗原上的不同抗原位点并且能够在与抗原同时结合的适当条件下的有效测定量的单克隆抗体的混合物可用于抗原的增强的灵敏度测定。 通过在用于重要抗原（例如多肽）的诊断测定中利用这些混合物，与使用单独单克隆抗体的测定相比，可以实现人绒毛膜促性腺激素增强的灵敏度。

公开(公告)号：US20090023148A1

公开(公告)日：2009-01-22

申请号：US12148243

申请日：2008-04-17

申请人： William R. Moyle ,  Russell C. Scaduto, JR.

发明人： William R. Moyle ,  Russell C. Scaduto, JR.

IPC分类号： C12Q1/68 ,  G01N33/53

CPC分类号： B01L3/50851 ,  B01L2300/0822 ,  B01L2300/1827 ,  B01L2400/0421 ,  C12Q1/6841 ,  G01N21/6428 ,  G01N21/6458 ,  G01N21/648 ,  G01N33/54373 ,  G01N33/5438 ,  C12Q2565/607

摘要： A sensor device is provided for detecting an analyte in a sample in which an analyte is bound to a detection reagent to form a bound complex. The device comprises (a) a sample (5) comprising an ionic analyte and a detection reagent in a conductive fluid, wherein the detection reagent has a net charge different from the analyte; (b) a first permeable polymeric hydrogel plate (3) and a first spacer plate (8), which plates provide a compartment for the sample; (c) an anode (1) juxtaposed to the outside of the first hydrogel plate and not in contact with the sample; (d) a cathode (9) juxtaposed to the outside of the first spacer plate and not in contact with the sample; (e) a voltage generator (10) to apply an electric potential to the anode and cathode; and (f) a detector (11). The bound complex formed from the analyte and detection reagent is detected by the detector because the bound complex has a charge that causes it to migrate in a direction opposite from that of the unbound analyte when the electric potential is applied.

摘要翻译： 提供了一种用于检测样品中分析物与检测试剂结合以形成结合复合物的分析物的传感器装置。 该装置包括（a）包含导电流体中的离子分析物和检测试剂的样品（5），其中检测试剂具有不同于分析物的净电荷; （b）第一可渗透聚合物水凝胶板（3）和第一间隔板（8），所述板提供样品的隔室; （c）与第一水凝胶板的外部并置并不与样品接触的阳极（1）; （d）与第一间隔板的外部并置并且不与样品接触的阴极（9）; （e）向阳极和阴极施加电位的电压发生器（10）; 和（f）检测器（11）。 由分析物和检测试剂形成的结合络合物由检测器检测，因为结合的复合物具有使电荷在施加电位时沿与未结合的分析物相反的方向迁移的电荷。