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1. 发明授权

US06300089B1 Methods and compositions for early detection and treatment of insulin dependent diabetes mellitus 失效
标题翻译：早期检测和治疗胰岛素依赖性糖尿病的方法和组合物
公开(公告)号：US06300089B1
公开(公告)日：2001-10-09
申请号：US08468583
申请日：1995-06-06
申请人： Mark A. Atkinson , Noel K. Maclaren
发明人： Mark A. Atkinson , Noel K. Maclaren
IPC分类号： G01N3353
CPC分类号： G01N33/74 , A61K38/00 , A61K39/00 , A61K47/62 , A61K47/6871 , C07K14/72 , C07K16/40 , C07K19/00 , C12N9/88 , C12N15/88 , G01N33/564 , G01N33/573 , G01N33/6893 , G01N2800/042 , Y10S435/811 , Y10S436/811
摘要： The subject invention concerns a novel process for the early detection of insulin dependent diabetes (IDD). The novel process described here enables the detection of the onset of IDD before clinical symptoms appear. The novel process involves the detection, in a sample of biological fluid, of an autoantibody which is highly specific to individuals who will later develop the clinical manifestations of IDD. Novel treatments for the prevention of IDD are also described.
摘要翻译：本发明涉及早期检测胰岛素依赖性糖尿病（IDD）的新方法。这里描述的新颖方法使得能够在出现临床症状之前检测IDD的发作。该新方法涉及在生物流体样品中检测对随后发展IDD的临床表现的个体高度特异性的自身抗体。还描述了防治IDD的新型治疗方法。

2. 发明授权

US5762937A Methods and compositions for the early detection and treatment of insulin dependent diabetes mellitus 失效
标题翻译：用于早期检测和治疗胰岛素依赖性糖尿病的方法和组合物
公开(公告)号：US5762937A
公开(公告)日：1998-06-09
申请号：US219816
申请日：1994-03-28
申请人： Mark A. Atkinson , Noel K. Maclaren
发明人： Mark A. Atkinson , Noel K. Maclaren
IPC分类号： A61K38/00 , C07K14/47 , C12N9/88 , A61K35/39 , A61K39/00
CPC分类号： C07K14/4713 , C12N9/88 , A61K38/00 , G01N2800/042
摘要： The invention pertains to the discovery of antigenic cross reactivity between a pancreatic 64K autoantigen and glutamic acid decarboxylase (GAD). Autoantibodies toward GAD were found to be associated with insulin dependent diabetes (IDD). More specifically, the invention pertains to the use of GAD for the diagnosis, prevention and treatment of insulin dependent diabetes (IDD).
摘要翻译：本发明涉及胰腺64K自身抗原与谷氨酸脱羧酶（GAD）之间的抗原交叉反应性的发现。发现GAD的自身抗体与胰岛素依赖性糖尿病（IDD）有关。更具体地，本发明涉及GAD用于诊断，预防和治疗胰岛素依赖性糖尿病（IDD）的用途。

3. 发明授权

US6001360A Method and compositions for early detection and treatment of insulin dependent diabetes mellitus 失效
标题翻译：早期发现和治疗胰岛素依赖性糖尿病的方法和组合物
公开(公告)号：US6001360A
公开(公告)日：1999-12-14
申请号：US474598
申请日：1995-06-07
申请人： Mark A. Atkinson , Noel K. Maclaren
发明人： Mark A. Atkinson , Noel K. Maclaren
IPC分类号： A61K35/39 , A61K39/00 , C12N9/88
CPC分类号： C12N9/88 , G01N2800/042 , Y10S530/868
摘要： Compositions and methods for the treatment or prevention of insulin dependent diabetes (IDD) are provided. Specifically, glutamic acid decarboxylase (GAD) proteins, and fragments. thereof, can be administered to an animal in order to the reduce the severity of IDD.
摘要翻译：提供了治疗或预防胰岛素依赖性糖尿病（IDD）的组合物和方法。具体来说，谷氨酸脱羧酶（GAD）蛋白质和片段。可以给予动物以降低IDD的严重性。

4. 发明授权

US5645998A Methods and compositions for the early detection and treatment of insulin dependent diabetes mellitus 失效
标题翻译：用于早期检测和治疗胰岛素依赖性糖尿病的方法和组合物
公开(公告)号：US5645998A
公开(公告)日：1997-07-08
申请号：US242689
申请日：1994-05-13
申请人： Mark A. Atkinson , Noel K. Maclaren
发明人： Mark A. Atkinson , Noel K. Maclaren
IPC分类号： A61K38/00 , A61K39/00 , A61K47/48 , C07K14/72 , C07K16/40 , C07K19/00 , C12N9/88 , C12N15/88 , G01N33/564 , G01N33/573 , G01N33/68 , G01N33/74
CPC分类号： A61K47/48238 , A61K47/48646 , C07K14/72 , C07K16/40 , C07K19/00 , C12N15/88 , C12N9/88 , G01N33/564 , G01N33/573 , G01N33/6893 , G01N33/74 , A61K38/00 , A61K39/00 , G01N2800/042 , Y10S435/811 , Y10S436/811
摘要： The subject invention concerns a process for the early detection of insulin dependent diabetes (IDD). The process described here enables the detection of the onset of IDD before clinical symptoms appear. The process involves the detection, in a sample of biological fluid, of an autoantibody which is highly specific to individuals who will later develop the clinical manifestations of IDD. Novel treatments for the prevention of IDD are also described.
摘要翻译：本发明涉及早期检测胰岛素依赖型糖尿病（IDD）的方法。这里描述的过程能够在出现临床症状之前检测IDD的发作。该过程涉及在生物流体样品中检测对随后发展IDD的临床表现的个体高度特异性的自身抗体。还描述了防治IDD的新型治疗方法。

5. 发明授权

US5376533A Methods and compositions for the detection of Addison's disease 失效
标题翻译：用于检测艾迪生病的方法和组合物
公开(公告)号：US5376533A
公开(公告)日：1994-12-27
申请号：US066281
申请日：1993-05-24
申请人： Noel K. Maclaren , Yao H. Song
发明人： Noel K. Maclaren , Yao H. Song
IPC分类号： G01N33/564 , G01N33/573
CPC分类号： G01N33/564 , G01N33/573 , Y10S436/811
摘要： An epitope of 21-hydroxylase has been identified which specifically reacts with autoantibodies to 21-hydroxylase. This epitope immunoreacts with anti-adrenocortical autoantibodies characteristically present in patients having autoimmune Addison's disease. The peptide can be used in a specific, sensitive immunoassay for the detection of these autoantibodies in the diagnosis of Addison's disease. The immunoassay permits the diagnosis of autoimmune Addison's disease and has considerable value in the screening of persons at risk. Persons in the early phases or at clinical onset of any kind of adrenocortical disease can also be screened to exclude Addison's disease as a cause.
摘要翻译：已经鉴定了21-羟化酶的表位，其与21-羟化酶的自身抗体特异性反应。与具有自身免疫性艾迪生氏病的患者相比，该表位与抗肾上腺皮质自身抗体具有特异性的免疫反应。该肽可用于特异性，敏感的免疫测定中，用于检测这些自身抗体以诊断艾迪生病。免疫测定允许诊断自身免疫性艾迪生病，并且在筛查处于危险中的人中具有相当的价值。任何类型的肾上腺皮质疾病的早期阶段或临床发作的人员也可以筛选出排除艾迪生病的原因。

6. 发明授权

US5891435A Methods and compositions for delaying or preventing the onset of autoimmune disease 失效
标题翻译：用于延缓或预防自身免疫性疾病发作的方法和组合物
公开(公告)号：US5891435A
公开(公告)日：1999-04-06
申请号：US48979
申请日：1993-04-16
申请人： Andrew Muir , Noel K. Maclaren
发明人： Andrew Muir , Noel K. Maclaren
IPC分类号： A61K38/00 , A61K38/26 , A61K38/28 , A61K38/51 , A61P3/08 , A61P3/10 , A61P17/00 , A61P43/00
CPC分类号： A61K38/51 , A61K38/26 , A61K38/28
摘要： The subject invention concerns compositions and methods useful for the prevention or amelioration of autoimmune diseases. Specifically exemplified are compositions and methods useful in immunizing to prevent insulin dependent diabetes. In a preferred embodiment, diabetes is prevented by the parenteral administration of a composition comprising specific antigenic peptides of insulin and further comprising incomplete Fruend's adjuvant.
摘要翻译：本发明涉及可用于预防或改善自身免疫疾病的组合物和方法。具体举例说明了用于免疫预防胰岛素依赖性糖尿病的组合物和方法。在优选的实施方案中，通过肠胃外施用包含胰岛素的特异性抗原肽的组合物进一步包含不完全的Fruend佐剂来防止糖尿病。

7. 发明授权

US06391651B1 Materials and methods for detection of insulin dependent diabetes 失效
标题翻译：用于检测胰岛素依赖性糖尿病的材料和方法
公开(公告)号：US06391651B1
公开(公告)日：2002-05-21
申请号：US08514213
申请日：1995-08-11
申请人： Noel K. Maclaren , Abner L. Notkins , Michael S. Lan
发明人： Noel K. Maclaren , Abner L. Notkins , Michael S. Lan
IPC分类号： G01N33564
CPC分类号： C07K14/4713 , A61K38/00 , A61K39/00 , C07K14/705 , C12N9/16 , Y10S530/845
摘要： The method and compositions of this invention provide an effective and reliable substitute for the currently employed ICA assay for diabetes. By providing a method for detecting autoantibodies to both GAD65 and IA-2 auto-antigens, the method provides a chemical assay which has improved reliability. In addition, these antigens may be employed in therapeutic regimens aimed at achieving immune tolerance and therefore amelioration of the clinical condition.
摘要翻译：本发明的方法和组合物为目前使用的糖尿病ICA测定提供了有效和可靠的替代物。通过提供用于检测GAD65和IA-2自身抗原的自身抗体的方法，该方法提供了具有改善的可靠性的化学测定。此外，这些抗原可以用于旨在实现免疫耐受并因此改善临床状况的治疗方案中。

8. 发明授权

US6066475A Parathyroid cytosolic autoantigens recognized by autoantibodies from patients with acquired hypoparathyroidism 失效
标题翻译：甲状旁腺胞质自身抗原由获得性甲状旁腺功能减退症患者自身抗体识别
公开(公告)号：US6066475A
公开(公告)日：2000-05-23
申请号：US991922
申请日：1997-12-16
申请人： Noel K. Maclaren , Yao-Huo Song
发明人： Noel K. Maclaren , Yao-Huo Song
IPC分类号： G01N33/53 , A61K31/00 , A61K38/00 , A61K38/22 , A61K39/00 , A61K39/395 , A61P5/00 , A61P5/18 , C07K14/47 , C07K14/705 , C07K16/18 , C12N5/00 , C12N5/10 , C12N15/09 , C12P21/02 , C12R1/91 , G01N33/564 , C12P21/00 , C12N1/14 , C12N1/20
CPC分类号： C07K14/4713 , C07K16/18 , A61K38/00
摘要： Disclosed are novel autoantigens and methods useful in the detection of autoantibodies in persons that have developed, or are at risk of developing, autoimmune hypoparathyroidism. The novel autoantigens of the subject invention may be used to achieve early diagnosis and treatmcnt of autoimmune hypoparathyroidism, and possibly other autoimmune diseases which arc frequently associated with autoimmune hypoparathyroidism.
摘要翻译：公开了可用于检测自身免疫性甲状旁腺功能减退症或发展为自身免疫性甲状旁腺功能减退症的人的自身抗体的新型自身抗原和方法。本发明的新型自身抗原可用于实现自身免疫性甲状旁腺功能减退的早期诊断和治疗，以及可能与自身免疫性甲状旁腺功能减退相关的其它自身免疫性疾病。

9. 发明授权

US5989551A Materials and methods for detection and treatment of insulin-dependent diabetes 失效
标题翻译：用于胰岛素依赖性糖尿病检测和治疗的材料和方法
公开(公告)号：US5989551A
公开(公告)日：1999-11-23
申请号：US548159
申请日：1995-10-25
申请人： Noel K. Maclaren , Abner L. Notkins , Michael S. Lan , Qing Li
发明人： Noel K. Maclaren , Abner L. Notkins , Michael S. Lan , Qing Li
IPC分类号： A61K38/00 , A61K39/00 , A61P3/10 , A61P37/02 , C07K14/47 , C07K14/705 , C12N9/16
CPC分类号： C07K14/4713 , C07K14/705 , C12N9/16 , A61K38/00 , A61K39/00
摘要： The method and compositions of this invention provide an effective and reliable substitute for the currently employed ICA assay for diabetes. By providing a method for detecting autoantibodies to GAD.sub.65, IA-2 and a previously unidentified antigen termed IA-2.beta. herein, the method provides a chemical assay which has improved reliability. In addition, these antigens may be employed in therapeutic regimens aimed at achieving amelioration of the clinical condition.
摘要翻译：本发明的方法和组合物为目前使用的糖尿病ICA测定提供了有效和可靠的替代物。通过提供一种用于检测GAD65，IA-2和本来称为IA-2β的先前未鉴定的抗原的自身抗体的方法，该方法提供了具有改善的可靠性的化学测定。此外，这些抗原可以用于旨在改善临床状况的治疗方案中。

10. 发明授权

US5723343A Autoantibodies in patients with acquired hypoparathyroidism and assay method therefor 失效
公开(公告)号：US5723343A
公开(公告)日：1998-03-03
申请号：US519905
申请日：1995-08-28
申请人： Noel K. Maclaren , Yao-Huo Song
发明人： Noel K. Maclaren , Yao-Huo Song
IPC分类号： G01N33/53 , A61K31/00 , A61K38/00 , A61K38/22 , A61K39/00 , A61K39/395 , A61P5/00 , A61P5/18 , C07K14/47 , C07K14/705 , C07K16/18 , C12N5/00 , C12N5/10 , C12N15/09 , C12P21/02 , C12R1/91 , G01N33/564 , G01N33/531 , G01N33/567
CPC分类号： C07K14/4713 , C07K16/18 , A61K38/00
摘要： Acquired hypoparathyroidism (AH) occurs frequently as a component of type I autoimmune polyglandular disease (APS-I) or as a sporadic isolated disease in adults. Whereas autoantibodies to the parathyroid glands have been reported in AH, their very existence remains controversial. We report here the detection of autoantibodies as identified through immunoblotting using sera from AH patients. The antibodies were specific to parathyroid autoantigens obtained through differential centrifugation of fresh human hypercellular parathyroid glands, obtained shortly after their surgical removal for tertiary hyperparathyroidism in patients with renal failure. Autoantibodies were detected against several parathyroid specific proteins in the 17 AH sera tested. Twelve (70%) reacted to a protein of 70 kDa, while 16 (94%) reacted to a protein of 80 kDa, and 3 (18%) reacted to a protein of 120-140 kDa, respectively. The 70 and 80 kDa proteins were localized to the cytosolic fraction of the parathyroid extract, and the 120-140 kDa protein to the membrane fraction. The autoantibodies were also detectable using a dog parathyroid gland as an antigen source. However, they could not be identified using cultured human melanocytes or in rat pituitary cells as antigen sources. Sera from 50 patients with various other autoimmune diseases as well as 22 normal controls were also tested, and none reacted with any of the above specific parathyroid proteins. It is concluded that autoantibodies to 3 major autoantigens in the human parathyroid gland extract have been detected in AH patients. Furthermore, our data indicates that the 120-140 kDa autoantigen is the calcium sensing receptor and that the reactive epitope largely resides in its extracellular domain. These data confirm the autoimmune nature of AH, and the invention provides a method for detecting AH or propensity for AH as well as a method for treating AH.

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