公开(公告)号：US07276341B2

公开(公告)日：2007-10-02

申请号：US10376121

申请日：2003-02-27

申请人： John B. Harley ,  Judith A. James

发明人： John B. Harley ,  Judith A. James

IPC分类号： G01N33/53 ,  G01N33/00 ,  A61K38/04 ,  C07K5/00 ,  C07K7/00 ,  C07K16/00 ,  C07K17/00

CPC分类号： C07K14/005 ,  A01K2267/0325 ,  A61K38/00 ,  A61K39/00 ,  C07K14/4713 ,  C12N2760/20222 ,  G01N33/564 ,  G01N33/56983 ,  G01N33/6878 ,  G01N2800/104 ,  G01N2800/24 ,  Y02A50/403

摘要： A number of octapeptides were generated from the sequences encoding the 60 kDa Ro/SSA peptide, the La/SSB autoantigen, the 70 kD nuclear ribonucleoprotein (nRNP), and the Sm B/B′ polypeptide, which represent linear epitopes for autoantibodies present in the sera of SLE and SS patients. These peptides are useful in solid phase assays for patients characterized by the presence of these autoantibodies, and can be used to categorize patients as to the likelihood of developing certain conditions associated with SLE. The peptides are also potentially useful in treatment of these patients using immobilized peptide to remove autoantibody and to block binding of the autoantibodies with patient molecules reactive with the autoantibodies.

摘要翻译： 从编码60kDa Ro / SSA肽，La / SSB自身抗原，70kD核核糖核蛋白（nRNP）和Sm B / B'多肽的序列产生许多八肽，其代表存在于自身抗体中的自身抗体的线性表位 SLE和SS患者的血清。 这些肽可用于以这些自身抗体存在为特征的患者的固相测定，并且可用于将患者分类为与SLE相关的某些病症发展的可能性。 这些肽也可用于治疗这些患者，使用固定肽去除自身抗体并阻断自身抗体与与自身抗体反应的患者分子的结合。

公开(公告)号：US06897287B1

公开(公告)日：2005-05-24

申请号：US07867819

申请日：1992-04-13

申请人： John B. Harley

发明人： John B. Harley

IPC分类号： A61K38/00 ,  A61K39/00 ,  C07K14/145 ,  C07K14/47 ,  G01N33/564 ,  G01N33/569 ,  G01N33/68 ,  A61K38/04

CPC分类号： C07K14/005 ,  A01K2267/0325 ,  A61K38/00 ,  A61K39/00 ,  C07K14/4713 ,  C12N2760/20222 ,  G01N33/564 ,  G01N33/56983 ,  G01N33/6878 ,  G01N2800/104 ,  G01N2800/24 ,  Y02A50/403

摘要： A number of octapeptides were generated from the sequences encoding the 60 kDa Ro/SSA peptide, the La/SSB autoantigen, the 70 kD nuclear ribonucleoprotein (nRNP), and the Sm B/B′ polypeptide, which represent linear epitopes for autoantibodies present in the sera of SLE and SS patients. These peptides are useful in solid phase assays for patients characterized by the presence of these autoantibodies, and can be used to categorize patients as to the likelihood of developing certain conditions associated with SLE. The peptides are also potentially useful in treatment of these patients using immobilized peptide to remove autoantibody and to block binding of the autoantibodies with patient molecules reactive with the autoantibodies.

摘要翻译： 从编码60kDa Ro / SSA肽，La / SSB自身抗原，70kD核核糖核蛋白（nRNP）和Sm B / B'多肽的序列产生许多八肽，其代表存在于自身抗体中的自身抗体的线性表位 SLE和SS患者的血清。 这些肽可用于以这些自身抗体存在为特征的患者的固相测定，并且可用于将患者分类为与SLE相关的某些病症发展的可能性。 这些肽也可用于治疗这些患者，使用固定肽去除自身抗体并阻断自身抗体与与自身抗体反应的患者分子的结合。

公开(公告)号：US06642008B1

公开(公告)日：2003-11-04

申请号：US09718693

申请日：2000-11-22

申请人： John B. Harley ,  Judith Ann James ,  Kenneth M. Kaufman

发明人： John B. Harley ,  Judith Ann James ,  Kenneth M. Kaufman

IPC分类号： G01N3353

CPC分类号： C07K14/005 ,  A61K39/00 ,  A61K39/12 ,  A61K39/245 ,  A61K2039/545 ,  A61K2039/55566 ,  C07K16/085 ,  C12N2710/16222 ,  C12N2710/16234 ,  Y02A50/386 ,  Y02A50/414

摘要： Compositions that bind specific viral proteins expressed during the latent stage of the viral life cycle are disclosed. These compositions bind the latent viral proteins while the viral proteins are expressed in their cellular host, and provide a means for targeting cells that harbor latent virus. In a preferred embodiment the compositions are antibodies which bind the extracellular region of the latent viral protein, most preferably LMP-2A, an EBV latent protein, conjugated to a diagnostic or cytotoxic agent or immobilized to a solid support for infected cell removal. These antibodies can distinguish cells expressing EBV DNA from cells which do not. Compositions that can be used to elicit production of these antibodies, or as a vaccine, are also disclosed. Methods for generating diagnostic or cytotoxic reagents and vaccines based on the viral epitopes that identify cells harboring latent virus are also discloset. The antibody conjugates can be used in diagnostic assays to identify cells expressing latent viral protein and people harboring latent viral particles. The antibody conjugates can also be used to remove infected cells or kill the infected cells. Alternatively, or in addition, the viral proteins or portions thereof can be used as a vaccine to induce an immune reaction by the host to kill the infected cells. These methods can be used to detect or treat patients harboring latent viruses like EBV and who risk developing autoimmune diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).

摘要翻译： 公开了在病毒生命周期潜伏期期间结合特异性病毒蛋白质的组合物。 这些组合物结合潜在的病毒蛋白质，同时病毒蛋白质在其细胞宿主中表达，并提供靶向隐藏潜伏病毒的细胞的手段。 在优选的实施方案中，组合物是结合潜在病毒蛋白的细胞外区域，最优选LMP-2A，与诊断或细胞毒性剂缀合或固定在固体支持物上用于感染细胞去除的EBV潜伏蛋白的抗体。 这些抗体可以区分表达EBV DNA的细胞与不具有细胞的细胞。 还可以公开可用于引发这些抗体或疫苗生产的组合物。 还公开了用于产生诊断或细胞毒性试剂和基于鉴定潜在病毒的细胞的病毒表位的疫苗的方法。 抗体缀合物可用于诊断测定以鉴定表达潜伏性病毒蛋白的细胞和携带潜伏病毒颗粒的人群。 抗体缀合物也可用于去除感染的细胞或杀死被感染的细胞。 或者或另外，病毒蛋白质或其部分可以用作疫苗以诱导宿主杀死受感染细胞的免疫反应。 这些方法可用于检测或治疗患有潜伏病毒如EBV的患者，以及患有发展自身免疫性疾病如系统性红斑狼疮（SLE）或类风湿性关节炎（RA）的患者。

公开(公告)号：US06232522B1

公开(公告)日：2001-05-15

申请号：US08160604

申请日：1993-11-30

申请人： John B. Harley ,  Judith A. James ,  R. Hal Scofield

发明人： John B. Harley ,  Judith A. James ,  R. Hal Scofield

IPC分类号： C07K500

CPC分类号： C07K14/4713 ,  A01K2267/0325 ,  A61K38/00 ,  A61K39/00 ,  C07K14/005 ,  C12N2760/20222 ,  G01N33/564 ,  G01N33/56983 ,  G01N33/6878 ,  G01N2800/104 ,  G01N2800/24 ,  Y02A50/403

摘要： A specific method has been developed to produce an autoimmune response and resulting clinical symptoms for a particular disease process. Peptides or other structures derived from an autoantigen and which are bound by auto antibody or T cell receptors are identified and used to induce an immune response. This immune response evolves into an autoimmune response directed against the other portions of the protein from which the peptide was derived. Subsequently, clinical manifestations may appear that are also found in the clinical illness. selected from the group including viruses, bacteria, fungi, parasites, rickettsia, plasmids, and insects which contains a structure or a peptide sequence that is similar to a structure or peptide sequence that has been identified by the method of claim 1 to the extent that it is bound by one of the group selected from antigen specific B cell surface receptors, and antigen specific T cell receptors.

摘要翻译： 已经开发了一种特定的方法来产生针对特定疾病过程的自身免疫反应和产生的临床症状。 鉴定出衍生自自身抗原并且被自身抗体或T细胞受体结合的肽或其它结构并用于诱导免疫应答。 这种免疫应答演变成针对来自肽的蛋白质的其它部分的自身免疫应答。 随后，临床表现也可能出现在临床疾病中。 选自包含病毒，细菌，真菌，寄生虫，立克次体，质粒和昆虫的组，其包含与通过权利要求1的方法鉴定的结构或肽序列类似的结构或肽序列， 它被选自抗原特异性B细胞表面受体和抗原特异性T细胞受体中的一个组结合。

公开(公告)号：US5264351A

公开(公告)日：1993-11-23

申请号：US269983

申请日：1988-11-09

申请人： John B. Harley

发明人： John B. Harley

IPC分类号： G01N33/564 ,  G01N33/68 ,  C07K15/28

CPC分类号： G01N33/564 ,  G01N33/6875 ,  G01N2800/24 ,  Y10S530/868

摘要： Monoclonal antibodies against autoimmune RNA proteins such as La/SSB, Ro/SSA, nNP and Sm. These monoclonal antibodies, which are produced by a continuous hybridoma cell line, may be used in methods for detecting the presence of selected autoimmune RNA proteins and antibodies against such proteins in biological samples, and may be incorporated into diagnostic test kits for this purpose. The monoclonal antibodies may be applied in methods for screening subjects for systemic lupus erythematosus, subacute cutaneous erythematosus, neonatal lupus, Siogren's syndrome, complete congential heart block, and other disorders which involve the presence of antibodies against autoimmune RNA proteins.

摘要翻译： 针对自身免疫性RNA蛋白如La / SSB，Ro / SSA，nNP和Sm的单克隆抗体。 这些由连续杂交瘤细胞系产生的单克隆抗体可用于检测生物样品中选择的自身免疫RNA蛋白和针对这种蛋白质的抗体的存在的方法中，并且可以将其并入用于此目的的诊断测试试剂盒中。 单克隆抗体可以用于筛选系统性红斑狼疮，亚急性皮肤红斑狼疮，新生儿狼疮，西格伦氏综合征，完全先天性心脏阻塞的受试者和涉及针对自身免疫RNA蛋白的抗体存在的其它病症的方法。