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1. 发明授权

US06800607B2 Modified BDNF 失效
标题翻译：改性BDNF
公开(公告)号：US06800607B2
公开(公告)日：2004-10-05
申请号：US10220315
申请日：2002-08-29
申请人： Rie Igarashi , Yutaka Mizushima , Mutsuo Taiji , Chikao Nakayama , Hiroshi Noguchi
发明人： Rie Igarashi , Yutaka Mizushima , Mutsuo Taiji , Chikao Nakayama , Hiroshi Noguchi
IPC分类号： A61K3816
CPC分类号： C07K14/475 , A61K38/00
摘要： Modified BDNF having improved pharmacological activities, pharmacokinetics and physical properties can be obtained by modifying BDNF with a 1-acyl-glycerol derivative. This BDNF being modified with a 1-acyl-glycerol derivative of the present invention has more efficacious and more excellent pharmacokinetic properties with retaining the useful effects being characteristic to BDNF which are useful as remedies for neurodegenerative diseases and diabetes mellitus, and hence, it is particularly useful as a therapeutic agent for treatment of type 2 diabetes mellitus.
摘要翻译：通过用1-酰基 - 甘油衍生物改性BDNF可以获得具有改善的药理活性，药代动力学和物理性能的改性BDNF。用本发明的1-酰基 - 甘油衍生物修饰的BDNF具有更有效和更优异的药代动力学性质，保留了BDNF特有的有效作用，可作为神经变性疾病和糖尿病的治疗方法，因此，特别可用作治疗2型糖尿病的治疗剂。

2. 发明授权

US06797691B1 Methods and compositions for inhibiting angiogenesis 失效
标题翻译：抑制血管生成的方法和组合物
公开(公告)号：US06797691B1
公开(公告)日：2004-09-28
申请号：US09603478
申请日：2000-06-23
申请人： Noël P. Bouck , David W. Dawson , Paul R. Gillis , Olga Volpert , Susan E. Crawford , Veronica M. Stellmach
发明人： Noël P. Bouck , David W. Dawson , Paul R. Gillis , Olga Volpert , Susan E. Crawford , Veronica M. Stellmach
IPC分类号： A61K3816
CPC分类号： C07K14/811 , A61K38/57 , A61K48/00 , G01N33/57484 , G01N33/6881
摘要： The present invention provides a method of inhibiting angiogenesis within a tissue by providing exogenous PEDF to cells associated with the tissue. The presence of exogenous PEDF inhibits angiogenesis within the tissue, in part by interfering with the ability of vascular endothelia to expand within the tissue. The invention also provides a method for determining the severity of a tumor by assaying for the presence of PEDF within the tumor. The invention further provides a method of inhibiting endothelial cell migration, a method of stimulating the growth of hair in a mammal, a method for inhibiting the growth of a tumor, a method of inducing differentiation of a neuroblastoma cell, a method of slowing the growth of a neuroblastoma cell, and method of treating ischemic retinopathy in a mammal. To facilitate the inventive methods, the present invention provides pharmaceutical compositions including sources of PEDF.
摘要翻译：本发明提供了通过向与组织相关的细胞提供外源PEDF来抑制组织内的血管生成的方法。外源PEDF的存在抑制组织内的血管发生，部分原因是干扰血管内皮在组织内扩张的能力。本发明还提供了通过测定肿瘤内PEDF的存在来确定肿瘤严重程度的方法。本发明还提供抑制内皮细胞迁移的方法，刺激哺乳动物毛发生长的方法，抑制肿瘤生长的方法，诱导成神经细胞瘤细胞分化的方法，减慢生长的方法的神经母细胞瘤细胞，以及治疗哺乳动物缺血性视网膜病变的方法。为了促进本发明的方法，本发明提供了包含PEDF来源的药物组合物。

3. 发明授权

US06797690B1 Carrot antifreeze polypeptides 失效
标题翻译：胡萝卜防冻多肽
公开(公告)号：US06797690B1
公开(公告)日：2004-09-28
申请号：US09308140
申请日：1999-12-30
申请人： Louise Jane Byass , Charlotte Juliette Doucet , Richard Anthony Fenn , Andrew John McArthur , Christopher Michael Sidebottom , Margaret Felicia Smallwood
发明人： Louise Jane Byass , Charlotte Juliette Doucet , Richard Anthony Fenn , Andrew John McArthur , Christopher Michael Sidebottom , Margaret Felicia Smallwood
IPC分类号： A61K3816
CPC分类号： A23G9/38 , A23G9/42 , C07K14/415 , C12N15/8273
摘要： Novel antifreeze polypeptides which can be easily obtained from an abundant natural source. Antifreeze polypeptides obtained from carrots show markedly better properties as compared to polypeptides obtained from other vegetables. The antifreeze polypeptides of the invention are capable of providing good recrystallization inhibition properties without significantly changing the crystal shape of the ice-crystals, therewith possibly leading to more favorable properties, e.g., soft ice-cream.
摘要翻译：可以从丰富的天然来源容易地获得的新型防冻多肽。与从其他蔬菜获得的多肽相比，从胡萝卜获得的抗冻多肽显示出更好的性质。本发明的防冻多肽能够提供良好的重结晶抑制性能，而不会显着改变冰晶的晶体形状，从而可能导致更有利的性质，例如软冰淇淋。

4. 发明授权

US06790831B2 Systemic carnitine deficiency gene and use thereof 失效
标题翻译：全身肉碱缺乏基因及其用途
公开(公告)号：US06790831B2
公开(公告)日：2004-09-14
申请号：US09798743
申请日：2001-03-02
申请人： Jun-Ichi Nezu , Asuka Ose
发明人： Jun-Ichi Nezu , Asuka Ose
IPC分类号： A61K3816
CPC分类号： C07K14/705 , A61K38/00 , A61K48/00 , C07K14/47 , Y10T436/143333
摘要： The gene responsible for systemic carnitine deficiency was found to be the OCTN2 gene involved in the transportation of organic cations. This invention enables tests for this disease by detecting whether or not the OCTN2 gene has a mutation. Furthermore, systemic carnitine deficiency can be treated using the normal OCTN2 gene and its protein.
摘要翻译：发现引起全身肉碱缺乏的基因是涉及有机阳离子运输的OCTN2基因。本发明能够通过检测OCTN2基因是否具有突变来测试该疾病。此外，可以使用正常的OCTN2基因及其蛋白质治疗系统性肉碱缺乏症。

5. 发明授权

US06774106B2 Methods and compositions of matter concerning APRIL/G70, BCMA, BLYS/AGP-3 and TACI 失效
标题翻译：关于APRIL / G70，BCMA，BLYS / AGP-3和TACI的物质的方法和组成
公开(公告)号：US06774106B2
公开(公告)日：2004-08-10
申请号：US09854864
申请日：2001-05-14
申请人： Lars Eyde Theill , Gang Yu
发明人： Lars Eyde Theill , Gang Yu
IPC分类号： A61K3816
CPC分类号： C07K14/70575 , A61K38/00 , C07K2319/00
摘要： This invention concerns interactions among APRIL/G70, AGP-3/BLYS, BCMA, and TACI and related methods of use and compositions of matter. It has been found that (1) sAPRIL/G70 binds to the cell-surface receptors BCMA and TACI on T and B lymphoma cells, resulting in stimulation of proliferation of primary human and mouse B and T cells both in vitro and in vivo; (2) APRIL competes with AGP3's binding to TACI and BCMA; (3) sBCMA inhibits APRIL and AGP3 binding to its receptors; (4) sBCMA ameliorates T cell dependent and T cell independent humoral immune responses in vivo; (5) sTACI inhibits APRIL and AGP3 binding to its receptors and ameliorates T cell dependent and T cell independent humoral immune responses in vivo; and (6) BCMA exhibits similarity with TACI within a single cysteine rich domain located N-terminal to a potential transmembrane domain. These discoveries provides a strategy for development of therapeutics for treatment of autoimmune diseases, and cancer, for prevention of transplant rejection. Disease states and disease parameters associated with APRIL and AGP-3 may be affected by modulation of BCMA or TACI; disease states and parameters associated with TACI can be affected by modulation of APRIL; disease states and parameters can be affected by modulation of any of TACI, BCMA, APRIL and AGP-3 by a single therapeutic agent or two or more therapeutic agents together.
摘要翻译：本发明涉及APRIL / G70，AGP-3 / BLYS，BCMA和TACI之间的相互作用以及相关使用方法和物质组成。已经发现（1）sAPRIL / G70结合T细胞和B淋巴瘤细胞上的细胞表面受体BCMA和TACI，导致在体外和体内刺激原代人和小鼠B和T细胞的增殖; （2）APRIL与AGP3与TACI和BCMA的绑定相竞争; （3）sBCMA抑制APRIL和AGP3与其受体的结合; （4）sBCMA体内改善T细胞依赖性和T细胞独立体液免疫应答; （5）sTACI抑制APRIL和AGP3与其受体的结合，并改善体内T细胞依赖性和T细胞独立的体液免疫应答; 和（6）BCMA在位于潜在跨膜结构域N末端的单个富含半胱氨酸的结构域中显示与TACI的相似性。这些发现提供了治疗自身免疫性疾病和癌症治疗用于预防移植排斥反应的策略。与APRIL和AGP-3相关的疾病状态和疾病参数可能受到BCMA或TACI调节的影响; 与TACI相关的疾病状态和参数可能受APRIL调节的影响; 疾病状态和参数可以通过单个治疗剂或两种或更多种治疗剂一起调节TACI，BCMA，APRIL和AGP-3中的任何一种来影响。

6. 发明授权

US06737402B2 Method of preparing fetuin to induce apoptosis 失效
标题翻译：制备胎球蛋白以诱导凋亡的方法
公开(公告)号：US06737402B2
公开(公告)日：2004-05-18
申请号：US09902208
申请日：2001-07-09
申请人： David Tsai
发明人： David Tsai
IPC分类号： A61K3816
CPC分类号： A61K38/1741 , A61K33/30 , C07K14/4747 , C07K14/71 , A61K2300/00
摘要： The present invention provides for an improved method of preparing fetuin by using a chelating agent to remove inorganic ions, such as zinc, calcium, and barium, from fetuin. Then, reloading the “naked” fetuin with Zinc Acetate to form a product that is mainly Fetuin-Zinc. This improved method of preparing Fetuin-Zinc or supercharged zinc fetuin increases the effectiveness of inducing apoptosis in cancer cells by three to four times.
摘要翻译：本发明提供了一种通过使用螯合剂从胎球蛋白中除去诸如锌，钙和钡的无机离子来制备胎球蛋白的改进方法。然后，用“醋酸锌”重新装载“赤裸”的胎球蛋白，形成主要为蛋白锌的产品。这种改进的制备Fetuin锌或增强的胎儿胎球蛋白的方法增加了将癌细胞凋亡诱导3至4次的有效性。

7. 发明授权

US06734165B2 Method for re-sensitizing vancomycin resistant bacteria which selectively cleave a cell wall depsipeptide 失效
标题翻译：对万古霉素抗性细菌进行再敏化的方法，其选择性地切割细胞壁depipipeptide
公开(公告)号：US06734165B2
公开(公告)日：2004-05-11
申请号：US09938746
申请日：2001-08-23
申请人： Gabriela Chiosis , Ivo G. Boneca , W. Clark Still
发明人： Gabriela Chiosis , Ivo G. Boneca , W. Clark Still
IPC分类号： A61K3816
CPC分类号： A61K31/40 , A61K38/14 , A61K2300/00
摘要： The present invention relates a method for re-sensitizing vancomycin resistant Gram-positive bacteria in which resistance results from the conversion of an amide bond to an ester bond in the cell wall peptide precursors of the bacteria which comprises using an antibacterial amount of vancomycin or a homolog of vancomycin and an amount of an agent effective to selectively cleave the ester bond so as to thereby re-sensitize vancomycin resistant bacteria.
摘要翻译：本发明涉及一种对万古霉素抗性的革兰氏阳性菌进行再敏化的方法，其中抗细菌量为万古霉素或细菌的细菌壁肽前体中的酰胺键转变为酯键，万古霉素的同系物和一定量的有效选择性地切割酯键的试剂，从而使万古霉素抗性细菌再敏化。

8. 发明授权

US06689748B1 Method of treating mast cell activation-induced diseases with a proteoglycan 失效
标题翻译：用蛋白多糖治疗肥大细胞活化诱导的疾病的方法
公开(公告)号：US06689748B1
公开(公告)日：2004-02-10
申请号：US09056707
申请日：1998-04-08
申请人： Theoharis C. Theoharides
发明人： Theoharis C. Theoharides
IPC分类号： A61K3816
CPC分类号： A61K45/06 , A61K31/13 , A61K31/202 , A61K31/353 , A61K31/522 , A61K31/7008 , A61K31/7048 , A61K31/728 , A61K31/737 , Y10S514/826 , A61K2300/00
摘要： The invention provides a method for preventing and treating the harmful biological effects of biochemicals secreted from activated mast cells in the organism of warm blooded animals and more especially human beings, said effects being associated with allergy (including but not limited to allergic conjunctivitis, allergic rhinitis, allergic otitis, asthma, allergic uticaria, food allergy and atopic dermatitis), hyperproliferative diseases such as leukemia and systemic mastocytosis, interstitial cystitis, inflammatory bowel disease, irritable bowel syndrome, osteoporosis and scleroderma. The method consists in administering to said animals and especially to human beings an effective amount of a proteoglycan such as chondroitin sulfate with mast cell secretion inhibitory activity, alone or in combination with one or more synergistic adjuvants such those belonging to the class of flavonoids or compounds with histamine-1 receptor antagonist activity.
摘要翻译：本发明提供了一种预防和治疗由活化肥大细胞分泌的生物化学物质在温血动物生物中，特别是人类的有害生物学效应的方法，所述效果与过敏有关（包括但不限于过敏性结膜炎，过敏性鼻炎过敏性耳炎，哮喘，过敏性反应和特应性皮炎），过度增生性疾病如白血病和全身肥大细胞增多症，间质性膀胱炎，炎性肠病，肠易激综合征，骨质疏松症和硬皮病。该方法包括向所述动物特别是人类施用有效量的蛋白多糖如硫酸软骨素，其具有肥大细胞分泌抑制活性，单独或与一种或多种协同佐剂组合，例如属于类黄酮或化合物具有组胺-1受体拮抗剂活性。

9. 发明授权

US06656906B1 Hybrid polypeptides with enhanced pharmacokinetic properties 失效
公开(公告)号：US06656906B1
公开(公告)日：2003-12-02
申请号：US09350641
申请日：1999-07-09
申请人： Shawn Barney , Kelly I. Guthrie , Gene Merutka , Mohmed K. Anwer , Dennis M. Lambert
发明人： Shawn Barney , Kelly I. Guthrie , Gene Merutka , Mohmed K. Anwer , Dennis M. Lambert
IPC分类号： A61K3816
CPC分类号： C07K14/005 , A61K38/00 , A61K47/62 , C07K5/1021 , C07K5/1024 , C07K14/59 , C07K2319/00 , C12N2740/16122 , C12N2760/18522 , Y02A50/465
摘要： The present invention relates to enhancer peptide sequences originally derived from various retroviral envelope (gp41) protein sequences that enhance the pharmacokinetic properties of any core polypeptide to which they are linked. The invention is based on the discovery that hybrid polypeptides comprising the enhancer peptide sequences linked to a core polypeptide possess enhanced pharmacokinetic properties such as increased half life. The invention further relates to methods for enhancing the pharmacokinetic properties of any core polypeptide through linkage of the enhancer peptide sequences to the core polypeptide. The core polypeptides to be used in the practice of the invention can include any pharmacologically useful peptide that can be used, for example, as a therapeutic or prophylactic reagent.

10. 发明授权

US06649591B2 Polydithicarbamate-containing non-targeting marcomolecules and the use thereof for therapeutic and diagnostic applications 失效
标题翻译：含二硫代氨基甲酸盐的非靶向大分子及其用于治疗和诊断应用的用途
公开(公告)号：US06649591B2
公开(公告)日：2003-11-18
申请号：US09409645
申请日：1999-10-01
申请人： Ching-San Lai
发明人： Ching-San Lai
IPC分类号： A61K3816
CPC分类号： C07C333/20
摘要： In accordance with the present invention, there is provided a new class of drugs for therapeutic treatment of such indications as cerebral stroke and other ischemia/reperfusion injury. Thus, in accordance with the present invention, dithiocarbamates are linked to the surface of a non-immunogenic, non-targeting macromolecule other than an antibody (e.g., albumin protein) either by using cross-linking reagents or by nonspecific binding to produce polydithiocarbamate-macromolecule-containing compositions, which represent a new class of drugs for therapeutic treatment of such indications as cerebral stroke and other ischemia/reperfusion injury. In accordance with another aspect of the present invention, combinational therapeutic methods have been developed for the in vivo inactivation or inhibition of formation (either directly or indirectly) of species which induce the expression of inducible nitric oxide synthase, as well as reducing nitric oxide levels produced as a result of .NO synthase expression. In accordance with yet another aspect of the present invention, magnetic resonance imaging methods have been developed for the measurement of cerebral and cardiac blood flow and infarct volume in ischemic stroke or heart attack situations. Such methods employ iron-containing complexes of a composition comprising a dithiocarbamate and a non-immunogenic, non-targeting macromolecule other than an antibody as contrast agents.
摘要翻译：根据本发明，提供了一类用于治疗性治疗诸如脑中风和其他缺血/再灌注损伤的适应症的药物。因此，根据本发明，二硫代氨基甲酸酯通过使用交联试剂或通过非特异性结合与除抗体（例如白蛋白蛋白）之外的非免疫原性非靶向大分子的表面连接以产生聚二硫代氨基甲酸盐 - 其代表用于治疗性治疗诸如脑卒中和其他缺血/再灌注损伤的新一类药物的大分子组合物。根据本发明的另一方面，已经开发出组合治疗方法用于体内失活或抑制诱导一氧化氮合酶表达的物种的形成（直接或间接），以及还原一氧化氮水平作为.NO合酶表达的结果产生。根据本发明的另一方面，已经开发了用于测量缺血性卒中或心脏病发作情况下的脑和心脏血流量和梗死体积的磁共振成像方法。这样的方法使用包含二硫代氨基甲酸盐和除抗体之外的非免疫原性非靶向大分子作为造影剂的组合物的含铁络合物。

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