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1. 发明申请

WO2009011892A2 USE OF SUIF PROTEINS AND HEPARAN SULFATE IN GDNF-DEPENDENT NEURAL INNERVATION AND PROTECTION 审中-公开
标题翻译：在GDNF依赖性神经保护和保护中使用SUIF蛋白和HEPARAN硫酸盐
公开(公告)号：WO2009011892A2
公开(公告)日：2009-01-22
申请号：PCT/US2008/008754
申请日：2008-07-17
申请人： BOSTON BIOMEDICAL RESEARCH INSTITUTE , EMERSON, Charles , AI, Xingbin
发明人： EMERSON, Charles , AI, Xingbin
IPC分类号： C07K1/00
CPC分类号： A61K38/465 , A61K31/727 , A61K38/185 , C12Y301/06 , A61K2300/00
摘要： The present invention is based on the discovery that Sulf protein deficiencies lead to direct defects in GDNF-dependent neural innervation and formation of neural crestderived enteric glial cells. Sulfs regulate cellular Heparan Sulfate (HS) 6-O-sulfation, and thus reduce GDNF binding to HS, thereby enhancing GDNF signaling to induce neurite outgrowth for muscle innervation. These findings reveal cooperative functions of MSulfs in controlling HS transmission and reception of GDNF from target muscle to innervating neurons, and establish Sulfs as new regulators of tissue interactions during neural development. Methods are described for using SuIf proteins to regulate GDNF signaling and treat pathologies characterized by neuronal innervation defects, including Parkinson's Disease, brain injury, and esophageal disorders. Included are methods wherein the increase in GDNF signaling is assayed by monitoring phosphorylation of downstream kinases and formation of glial cells.
摘要翻译：本发明基于以下发现：Sulf蛋白缺乏导致GDNF依赖性神经支配和神经嵴部肠神经胶质细胞形成的直接缺陷。 Sulfs调节细胞硫酸氢埃（HS）6-O-硫酸化，从而减少GDNF与HS的结合，从而增强GDNF信号传导以诱导神经突向肌肉神经支配的生长。这些发现揭示了MSulfs在控制GDNF从目标肌肉到神经元神经元的HS传播和接收过程中的协同作用，并建立了Sulfs作为神经发育过程中组织相互作用的新调节剂。描述了使用SuIf蛋白来调节GDNF信号并且治疗以神经元神经支配缺陷为特征的病理学的方法，包括帕金森病，脑损伤和食管障碍。包括其中通过监测下游激酶的磷酸化和胶质细胞的形成来测定GDNF信号传导的增加的方法。

2. 发明申请

WO2007067514A2 METHODS FOR IDENTIFYING MODULATORS OF HEDGEHOG AUTOPROCESSING 审中-公开
标题翻译：识别HEDGEHOG自动调节器的方法
公开(公告)号：WO2007067514A2
公开(公告)日：2007-06-14
申请号：PCT/US2006/046345
申请日：2006-12-05
申请人： BOSTON BIOMEDICAL RESEARCH INSTITUTE
发明人： HENRY, Paulus , XINGBIN, Ai , CHARLES, Emerson
IPC分类号： C12Q1/66 , C12N5/06
CPC分类号： G01N33/542 , C12Q1/37 , C12Q1/66 , G01N33/5008 , G01N33/5011 , G01N33/582 , G01N33/6872 , G01N2500/00
摘要： The present invention relates to methods of screening for modulators of Hedgehog peptide autoprocessing with methods that are useful in both in vivo and high-throughput in vitro systems. The present invention also relates to reagents identified by the methods of the present invention for use in the modulation of Hh autoprocessing, especially as they relate to the treatment of illnesses and diseases that are caused, at least in part, by the misregulation of Hh autoprocessing.
摘要翻译：本发明涉及使用可用于体内和高通量的方法筛选Hedgehog肽自动加工的方法

3. 发明申请

WO2005099772A2 METHODS FOR PREVENTING OR REDUCING ISCHEMIA/REPERFUSION INDUCED MYOCARDIAL CELL DEATH 审中-公开
标题翻译：预防或减少ISCHEMIA / REPERFUSION诱导的心肌细胞死亡的方法
公开(公告)号：WO2005099772A2
公开(公告)日：2005-10-27
申请号：PCT/US2005/012021
申请日：2005-04-12
申请人： BOSTON BIOMEDICAL RESEARCH INSTITUTE
发明人： ERHARDT, Peter , TOTH, Ambrus
IPC分类号： A61K48/00
CPC分类号： A61K48/005 , A01K2267/0375 , C07K14/4747 , G01N33/74 , G01N2500/02 , G01N2500/10 , G01N2510/00
摘要： Provided herein are methods relating to inhibition of PUMA function for preventing or reducing myocardial cell death. A method for preventing or reducing ischemia/reperfusion induced myocardial cell death in a human is provided as are methods for identifying pharmaceuticals which interfere with PUMA function. Also herein provided is a method for reducing stem cell death in stem cell explants wherein the explants are intended to restore cardiac efficiency following cell death in response to coronary infarct.
摘要翻译：本文提供了与抑制PUMA功能以预防或减少心肌细胞死亡有关的方法。提供了一种用于预防或减少人类中缺血/再灌注诱导的心肌细胞死亡的方法，用于鉴定干扰PUMA功能的药物的方法。本文还提供了一种用于减少干细胞移植物中的干细胞死亡的方法，其中外植体旨在在响应于冠状动脉梗塞的细胞死亡后恢复心脏效率。

4. 发明申请

WO2008079324A1 IMMUNOLOGICAL MODULATION OF INSULIN-LIKE GROWTH FACTOR 1 FOR CANCER PREVENTION/TREATMENT AND PROLONGING LONGEVITY 审中-公开
标题翻译：胰岛素样生长因子1的免疫调节用于癌症预防/治疗和延长长期
公开(公告)号：WO2008079324A1
公开(公告)日：2008-07-03
申请号：PCT/US2007/026140
申请日：2007-12-20
申请人： BOSTON BIOMEDICAL RESEARCH INSTITUTE
发明人： RASO, Victor
IPC分类号： C07K1/00
CPC分类号： A61K39/00 , A61K38/00 , A61K2039/6018 , A61K2039/605 , A61K2039/6075 , A61K2039/6081 , C07K14/65
摘要： Provided is a simple and safe immunization procedure to reduce cancer incidence and increase longevity by modulating IGF-1 levels in the body. Described are cancer preventive vaccines and methods that elicit circulating antibodies specific to insulin- like growth factor 1 (IGF-1 ) in the body. Many cancers will be less likely to occur and spread in the absence or reduced levels of the stimulatory signals provided by IGF-1. Longevity also can be extended by immunologically lowering the level of bioavailable IGF-1 in adult animals. This prolongation of lifespan resulting from lower IGF-1 levels is produced independently of the inhibitory effects on carcinogenesis. However, the two IGF-1 -mediated processes are linked mechanistically. Methods of active and passive immunization to suppress IGF-1 activity are included. Also described are methods for increasing longevity or reducing one or more symptoms of aging in a warm-blooded animal comprising administering anti-IGF-1 antibodies such that IGF-1 is inactivated or suppressed or administering IGF-1 antigen such that the animal produces endogenous antibodies to IGF-11.
摘要翻译：提供了一种简单和安全的免疫程序，通过调节人体IGF-1水平来减少癌症发生率并延长寿命。描述了在体内引发对胰岛素样生长因子1（IGF-1）特异性的循环抗体的癌症预防疫苗和方法。在IGF-1提供的刺激信号的不存在或降低的水平下，许多癌症将不太可能发生和扩散。通过免疫降低成年动物中生物可利用的IGF-1的水平，可以延长寿命。 IGF-1水平降低导致的寿命延长与癌变发生的抑制作用无关。然而，两个IGF-1介导的过程在机械上相互联系。包括主动和被动免疫抑制IGF-1活性的方法。还描述了在温血动物中增加寿命或减少一种或多种老化症状的方法，包括施用抗IGF-1抗体，使得IGF-1被灭活或抑制或施用IGF-1抗原，使得动物产生内源性 IGF-11抗体。

5. 发明申请

WO1985004811A1 BISPECIFIC ANTIBODY DETERMINANTS 审中-公开
标题翻译：双重抗体决定因子
公开(公告)号：WO1985004811A1
公开(公告)日：1985-11-07
申请号：PCT/US1985000737
申请日：1985-04-22
申请人： BOSTON BIOMEDICAL RESEARCH INSTITUTE, INC.
发明人： BOSTON BIOMEDICAL RESEARCH INSTITUTE, INC. , PAULUS, Henry, P.
IPC分类号： A61K39/395
CPC分类号： G01N33/531 , C07K16/468 , G01N33/533
摘要： A method of preparing a bispecific monoclonal antibody determinant comprising the steps of providing two different monoclonal antibody determinants, each determinant comprising two identical L-H half-molecules linked by one or more disulfide bond, subjecting the two different antibody determinants to conditions sufficient to break the disulfide bonds linking the L-H half-molecules, whereby each determinant is split into a pair of identical half-molecules, derivatizing one pair of identical half-molecules with a thiol activating agent, and combining the half-molecules to form the bispecific antibody determinants by the formation of one or more disulfide bonds.
摘要翻译：一种制备双特异性单克隆抗体决定簇的方法，包括以下步骤：提供两种不同的单克隆抗体决定簇，每个决定簇包含由一个或多个二硫键连接的两个相同的LH半分子，使两个不同的抗体决定簇具有足以破坏二硫键的条件连接LH半分子的键，其中每个决定簇被分成一对相同的半分子，用硫醇活化剂衍生一对相同的半分子，并将半分子组合以形成双特异性抗体决定簇形成一个或多个二硫键。

6. 发明申请

WO2012174365A2 METHODS FOR PRODUCING PANCREATIC PRECURSOR CELLS AND USES THEREOF 审中-公开
标题翻译：生产胰腺前体细胞的方法及其用途
公开(公告)号：WO2012174365A2
公开(公告)日：2012-12-20
申请号：PCT/US2012/042644
申请日：2012-06-15
申请人： BOSTON BIOMEDICAL RESEARCH INSTITUTE, INC. , SHERLEY, James, L. , PARE, Jean-Francois
发明人： SHERLEY, James, L. , PARE, Jean-Francois
IPC分类号： A61K38/26 , A61K38/28 , A61K48/00 , A61P3/10 , A61P3/00
CPC分类号： C12N5/0678 , A61K35/39 , C12N2500/40 , C12N2509/00
摘要： The present invention is directed to methods for readily propagating somatic pancreatic precursor cells. The methods comprise isolating cells from intact pancreatic samples and enhancing guanine nucleotide (GNP) biosynthesis in cultures comprising these cells, thereby expanding guanine nucleotide pools. This in turn conditionally suppresses asymmetric cell kinetics in the cells, thereby generating pancreatic precursor cells.
摘要翻译：本发明涉及容易繁殖体细胞胰腺前体细胞的方法。该方法包括从完整的胰腺样品中分离细胞并增强包含这些细胞的培养物中的鸟嘌呤核苷酸（GNP）生物合成，从而扩大鸟嘌呤核苷酸库。这又有条件地抑制细胞中的不对称细胞动力学，从而产生胰腺前体细胞。

7. 发明申请

WO2012129228A2 NOVEL RETRO-INVERSO LEPTIN PEPTIDE ANTAGONISTS 审中-公开
公开(公告)号：WO2012129228A2
公开(公告)日：2012-09-27
申请号：PCT/US2012/029805
申请日：2012-03-20
申请人： BOSTON BIOMEDICAL RESEARCH INSTITUTE, INC. , LEAVIS, Paul, C.
发明人： LEAVIS, Paul, C.
IPC分类号： A61K38/17 , A61P43/00
CPC分类号： A61K38/2271
摘要： Disclosed herein are peptides comprising a leptin sequence and methods for their use in preventing ObR signaling in a leptin-responsive cell. A leptin peptide of the present invention binds to but does not activate ObR signaling in a leptin-responsive cell, thereby inhibiting the up-regulatory effects of leptin on ObR signaling in the leptin-responsive cell. Administration of the peptide effectively prevents embryo implantation in a mammal to which the peptide has been administered. Also disclosed herein is a method for identifying a peptide antagonist of ObR, wherein the peptide comprises a leptin sequence. Further disclosed are truncations, modifications and retro-inversions of the peptides of the present invention.
摘要翻译：本文公开了包含瘦蛋白序列的肽和其用于预防瘦素应答细胞中的ObR信号传导的方法。本发明的瘦蛋白肽在瘦素应答细胞中结合但不激活ObR信号传导，从而抑制瘦素对瘦素反应细胞中ObR信号传导的上调作用。肽的施用有效地防止已经给予肽的哺乳动物中的胚胎植入。本文还公开了用于鉴定ObR的肽拮抗剂的方法，其中所述肽包含瘦蛋白序列。进一步公开的是本发明的肽的截短，修饰和逆转。

8. 发明申请

WO2006079057A2 METHODS AND COMPOSITIONS FOR SPECIFIC INHIBITION OF PROTEIN SPLICING BY SMALL MOLECULES 审中-公开
标题翻译：通过小分子特异性抑制蛋白质分离的方法和组合物
公开(公告)号：WO2006079057A2
公开(公告)日：2006-07-27
申请号：PCT/US2006/002409
申请日：2006-01-24
申请人： BOSTON BIOMEDICAL RESEARCH INSTITUTE
发明人： HENRY, Paulus
IPC分类号： A61K31/095
CPC分类号： A61K31/095 , A61K31/275 , A61K31/34 , A61K31/36 , A61K31/381 , A61K31/401 , A61K31/433 , A61K31/53
摘要： The present invention relates to compositions ( i.e ., various organic small molecules as exemplified herein) and methods for the inhibition of protein splicing and especially relates to the inhibition of protein autosplicing of intein- containing proteins. Additionally, the present invention relates to the use of the inhibitors of protein splicing of the invention for the treatment of various diseases including but not limited to tuberculosis. Furthermore, the invention provides the first instance of small molecule inhibitors of protein splicing with drug-like characteristics.
摘要翻译：本发明涉及组合物（即本文举例说明的各种有机小分子）以及抑制蛋白质剪接的方法，特别涉及抑制含内蛋白蛋白质的蛋白质自动切片。此外，本发明涉及本发明的蛋白质剪接抑制剂用于治疗各种疾病（包括但不限于结核病）的用途。此外，本发明提供了具有药物样特征的蛋白质剪接的小分子抑制剂的第一例。

9. 发明申请

WO2005110461A2 LEPTIN PEPTIDE ANTAGONISTS 审中-公开
公开(公告)号：WO2005110461A2
公开(公告)日：2005-11-24
申请号：PCT/US2005/015198
申请日：2005-05-03
申请人： BOSTON BIOMEDICAL RESEARCH INSTITUTE
发明人： GONZALEZ, Ruben, Rene , LEAVIS, Paul, C.
IPC分类号： A61K38/17
CPC分类号： C07K14/5759 , A61K38/2264 , G01N33/5041 , G01N33/74
摘要： Disclosed herein are peptides comprising a leptin sequence and methods for their use in preventing ObR signaling in a leptin-responsive cell. A leptin peptide of the present invention binds to but does not activate ObR signaling in a leptin-responsive cell, thereby inhibiting the up-regulatory effects of leptin on ObR signaling in the leptin-responsive cell. Administration of the peptide effectively prevents embryo implantation in a mammal to which the peptide has been administered. Also disclosed herein is a method for identifying a peptide antagonist of ObR, wherein the peptide comprises a leptin sequence.
摘要翻译：本文公开了包含瘦蛋白序列的肽以及它们用于预防瘦素应答细胞中的ObR信号传导的方法。本发明的瘦蛋白肽在瘦素反应性细胞中结合但不激活ObR信号传导，从而抑制瘦素对瘦素反应性细胞中ObR信号传递的上调作用。肽的施用有效地防止已经给予肽的哺乳动物中的胚胎植入。本文还公开了用于鉴定ObR的肽拮抗剂的方法，其中所述肽包含瘦蛋白序列。

10. 发明申请

WO1998008090A1 ANTI-IDIOTYPIC ANTIBODIES TO AN EPIGLYCANIN 审中-公开
标题翻译：抗巨细胞抗原抗体
公开(公告)号：WO1998008090A1
公开(公告)日：1998-02-26
申请号：PCT/US1996013231
申请日：1996-08-16
申请人： BOSTON BIOMEDICAL RESEARCH INSTITUTE , CODINGTON, John, F.
发明人： BOSTON BIOMEDICAL RESEARCH INSTITUTE
IPC分类号： G01N33/53
CPC分类号： A61K51/1078 , A61K39/00 , A61K39/0011 , A61K48/00 , A61K2039/51 , A61K2123/00 , C07K16/30 , C07K16/4266 , G01N33/57484 , G01N33/686
摘要： Methods of assaying for the presence of Human Carcinoma Antigen (HCA). Also disclosed are methods of in vivo imaging of a tumor and methods for treating and/or preventing a carcinoma. Further disclosed are anti-idiotypic antibodies which bind to an antibody which binds HCA; anti-anti-idiotypic antibodies which bind to a member of the group consisting of epiglycanin, HCA and an anti-idiotypic antibody which binds to an antibody which binds to HCA; and kits for detecting human carcinoma antigen.
摘要翻译：测定人癌抗原（HCA）存在的方法。还公开了肿瘤的体内成像的方法和用于治疗和/或预防癌症的方法。进一步公开的是与结合HCA的抗体结合的抗独特型抗体; 结合至结构于HCA的抗体的表鬼臼乙烯，HCA和抗独特型抗体的成员的抗 - 抗独特型抗体; 和用于检测人癌抗原的试剂盒。

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