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公开(公告)号：US20020072588A1
公开(公告)日：2002-06-13
申请号：US09899896
申请日：2001-07-05
IPC分类号： A61K039/395 , C07K014/62
CPC分类号： C07K16/18 , A61K2039/505 , C07K2317/55
摘要： The invention provides methods and compositions for inhibiting autoantibody binding in demyelinating disease such as multiple sclerosis. The compositions comprise immunoglobulin CDR3 sequences derived from combinatorial phage display libraries selected for high-affinity binding to myelin oligodendrocyte glycoprotein.
摘要翻译： 本发明提供了用于抑制脱髓鞘疾病如多发性硬化中自身抗体结合的方法和组合物。 组合物包含衍生自选择用于与髓鞘少突胶质细胞糖蛋白高亲和力结合的组合噬菌体展示文库的免疫球蛋白CDR3序列。
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2.发明申请Glucose dependent release of insulin from glucose sensing insulin derivatives 有权从葡萄糖感测胰岛素衍生物中葡萄糖依赖性释放胰岛素公开(公告)号：US20020028767A1
公开(公告)日：2002-03-07
申请号：US09870884
申请日：2001-05-31
发明人： Thomas Hoeg Jensen , Svend Havelund , Jan Markussen , Soren Ostergaard , Signe Ridderberg , Per Balschmidt , Lauge Schaffer , Ib Jonassen
IPC分类号： A61K038/28 , C07K014/62
CPC分类号： C07K14/62
摘要： Insulin derivatives having a built-in glucose sensor, capable of delivering insulin from a depot as a function of the glucose concentration in the surrounding medium (e.g. tissue), such that the rate of insulin release from the depot increases with an increased glucose concentration and decreases with a decreased glucose concentration.
摘要翻译： 具有内置葡萄糖传感器的胰岛素衍生物，其能够将来自贮库的胰岛素作为周围介质（例如组织）中的葡萄糖浓度的函数，使得从贮库中释放的胰岛素的速率随着葡萄糖浓度的增加而增加，并且 葡萄糖浓度降低。
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3.发明申请Adipocyte Insulin adpinsl with Insulin A and B chains and an effective method of treating type 2 diabetes in a subject using adipocyte insulin 失效胰岛素A和B链的脂肪细胞胰岛素Adpinsl和使用脂肪细胞胰岛素治疗受试者的2型糖尿病的有效方法公开(公告)号：US20040053816A1
公开(公告)日：2004-03-18
申请号：US10396551
申请日：2003-03-26
IPC分类号： A61K038/28 , C07H021/04 , C07K014/62
CPC分类号： C07K14/461 , A61K38/00
摘要： The present invention relates to an adipocyte Insulin adplnsl with Insulin A and B chains of SEQ ID Nos. 1 and 2, a effective method of treating type 2 diabetes in a subject using adipocyte insulin, said method comprising steps of administering the insulin to a diabetic intraperitoneally, an Insulin gene of SEQ ID No. 3, a process of isolating protein Insulin from the adipocytes of the Carp, said method comprising steps of reverse transcripting RNA of adipocytes to obtain cDNA, using oligonucleotide primers of SEQ ID Nos. 5 and 5 to identify AdpInsl gene from cDNA, and deducing amino acid sequence from cDNA to obtain protein Insulin, and an adipocyte of Catla Catla useful for producing the said Insulin.
摘要翻译： 本发明涉及具有SEQ ID NO.1和2的胰岛素A和B链的脂肪细胞胰岛素adplns1，这是使用脂肪细胞胰岛素治疗受试者的2型糖尿病的有效方法，所述方法包括将胰岛素给予糖尿病 腹膜内地是SEQ ID No.3的胰岛素基因，从鲤鱼的脂肪细胞分离蛋白质胰岛素的方法，所述方法包括使用SEQ ID No.5和5的寡核苷酸引物的脂肪细胞的逆转录RNA以获得cDNA的步骤 从cDNA中鉴定AdpInsl基因，并从cDNA中推导氨基酸序列以获得蛋白质胰岛素，以及可用于产生所述胰岛素的Catla Catla的脂肪细胞。
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公开(公告)号：US20030229010A1
公开(公告)日：2003-12-11
申请号：US10448535
申请日：2003-06-02
IPC分类号： A61K038/28 , C07K014/62
CPC分类号： C12N9/96 , A61K9/1075 , A61K9/4858 , A61K38/00 , A61K47/56 , A61K47/60 , C07K1/1077 , C07K14/62
摘要： A therapeutic formulation comprising a microemulsion of a therapeutic agent in free and/or conjugatively coupled form, wherein the microemulsion comprises a water-in-oil (w/o) microemulsion including a lipophilic phase and a hydrophilic phase, and has a hydrophilic and lipophilic balance (HLB) value between 3 and 7, wherein the therapeutic agent may for example be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, papain, Ara-A (Arabinofuranosyladenine), Acylguanosine, Nordeoxyguanosine, Azidothymidine, Didesoxyadenosine, Dideoxycytidine, Dideoxyinosine Floxuridine, 6-Mercaptopurine, Doxorubicin, Daunorubicin, or I-darubicin, Erythromycin, Vancomycin, oleandomycin, Ampicillin; Quinidine and Heparin. In a particular aspect, the invention comprises an insulin composition suitable for parenteral as well as non-parenteral administration, preferably oral or parenteral administration, comprising insulin covalently coupled with a polymer including (i) a linear polyalkylene glycol moiety and (ii) a lipophilic moiety, wherein the insulin, the linear polyalkylene glycol moiety and the lipophilic moiety are conformationally arranged in relation to one another such that the insulin in the composition has an enhanced in vivo resistance to enzymatic degradation, relative to insulin alone. The microemulsion compositions of the invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic, applications.
摘要翻译： 一种包含游离和/或共轭偶联形式的治疗剂的微乳液的治疗剂型，其中所述微乳液包括包含亲油相和亲水相的油包水（w / o）微乳液，并具有亲水和亲脂性 平衡（HLB）值在3和7之间，其中治疗剂可以例如选自胰岛素，降钙素，ACTH，胰高血糖素，生长抑素，生长激素，生长因子，甲状旁腺激素，促红细胞生成素，下丘脑释放因子，催乳素，甲状腺 刺激激素，内啡肽，脑啡肽，加压素，非天然存在的阿片样物质，超氧化物歧化酶，干扰素，天冬酰胺酶，精氨酸酶，精氨酸脱胺酶，腺苷脱氨酶，核糖核酸酶，胰蛋白酶，糜蛋白酶，木瓜蛋白酶，Ara-A（阿拉伯呋喃糖基腺嘌呤），酰基鸟苷，脱氧鸟苷，叠氮胸苷 ，Didesoxyadenosine，Dideoxycytidine，Dideoxyinosine Flouxuridine，6-Mercapupurine，Doxorubicin，Daororubicin， 或I-dorubicin，红霉素，万古霉素，夹竹桃霉素，氨苄青霉素; 奎尼丁和肝素。 在一个特定方面，本发明包括适于肠胃外和非肠胃外给药的胰岛素组合物，优选口服或非肠道给药，其包含与聚合物共价偶联的胰岛素，所述聚合物包括（i）线性聚亚烷基二醇部分和（ii）亲脂性 部分，其中胰岛素，线性聚亚烷基二醇部分和亲脂性部分相对于彼此构象地排列，使得组合物中的胰岛素相对于单独的胰岛素具有增强的体内抗酶降解性。 本发明的微乳液组合物可用于治疗以及非治疗性，例如诊断性应用。
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公开(公告)号：US20030186846A1
公开(公告)日：2003-10-02
申请号：US10307678
申请日：2002-12-02
IPC分类号： A61K038/28 , C07K014/62
CPC分类号： A61K38/28
摘要： The present invention relates to insulin derivatives having a built-in glucose sensor and a polyol moiety, capable to deliver insulin from an injected depot of an insulin derivative according to the invention as a function of the glucose concentration in the surrounding tissue.
摘要翻译： 本发明涉及具有内置葡萄糖传感器和多元醇部分的胰岛素衍生物，其能够根据本发明的胰岛素衍生物的注射贮库递送胰岛素作为周围组织中葡萄糖浓度的函数。
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公开(公告)号：US20020198140A1
公开(公告)日：2002-12-26
申请号：US10152535
申请日：2002-05-20
发明人： Svend Havelund
IPC分类号： A61K038/28 , C07K014/62
CPC分类号： A61K9/0075 , A61K9/145 , A61K38/28 , C07K14/62
摘要： The present invention provides methods and compositions for treating diabetes by administering acylated insulin or an acylated insulin analog via a pulmonary route. The insulin or insulin analog may be in the form of a dry powder or a solution.
摘要翻译： 本发明提供了通过经由肺途径施用酰化胰岛素或酰化胰岛素类似物来治疗糖尿病的方法和组合物。 胰岛素或胰岛素类似物可以是干粉或溶液的形式。
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公开(公告)号：US20030229009A1
公开(公告)日：2003-12-11
申请号：US10382022
申请日：2003-03-05
IPC分类号： A61K038/28 , C07K014/62
摘要： Methods for synthesizing proinsulin polypeptides are described that include contacting a proinsulin polypeptide including an insulin polypeptide coupled to one or more peptides by peptide bond(s) capable of being cleaved to yield the insulin polypeptide with an oligomer under conditions sufficient to couple the oligomer to the insulin polypeptide portion of the proinsulin polypeptide and provide a proinsulin polypeptide-oligomer conjugate, and cleaving the one or more peptides from the proinsulin polypeptide-oligomer conjugate to provide the insulin polypeptide-oligomer conjugate. Methods of synthesizing proinsulin polypeptide-oligomer conjugates are also provided as are proinsulin polypeptide-oligomer conjugates. Methods of synthesizing C-peptide polypeptide-oligomer conjugates and other pro-polypeptide-oligomer conjugates are also provided.
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公开(公告)号：US20020160938A1
公开(公告)日：2002-10-31
申请号：US09934766
申请日：2001-08-23
IPC分类号： A61K038/28 , C07K014/62
CPC分类号： C07K14/62 , A61K38/28 , Y10S435/81 , Y10S514/866
摘要： The invention provides an analogue of a pharmaceutical active whose molecular weight is less than 25,000 Daltons, the analogue comprising a pharmaceutical active whose molecular weight is less than 25,000 Daltons covalently linked to a pendant molecular group wherein as a result of the administration of the composition to the human or animal body an active complex having a molecular weight of 25,000 Daltons or greater is present in the human or animal circulatory system. The analogue is hepatoselective when administered to the circulatory system. Preferably the analogue is an insulin analogue comprising an insulin or functional equivalent thereof covalently linked to the pendant molecular group wherein the active complex is an insulin complex. Such an insulin analogue may be used in a method of insulin replacement therapy.
摘要翻译： 本发明提供了分子量小于25,000道尔顿的药物活性物质的类似物，该类似物包含与侧链分子基团共价连接的分子量小于25,000道尔顿的药物活性物质，其中作为将组合物施用于 人体或动物体内分子量为25,000道尔顿或更高的活性配合物存在于人或动物循环系统中。 当给予循环系统时，类似物是肝选择性的。 优选地，类似物是包含与侧分子基团共价连接的胰岛素或其功能等同物的胰岛素类似物，其中活性复合物是胰岛素复合物。 这种胰岛素类似物可以用于胰岛素替代疗法的方法中。
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公开(公告)号：US20020155994A1
公开(公告)日：2002-10-24
申请号：US10083058
申请日：2002-02-25
IPC分类号： A61K038/28 , C07K014/62
CPC分类号： A61K9/0019 , A61K9/1688 , A61K38/28
摘要： The present invention relates to protracted acting, water-soluble aggregates of derivatives of human insulin, derivatives of human insulin capable of forming such aggregates, pharmaceutical compositions containing them, and to the use of such aggregates in the treatment of diabetes.
摘要翻译： 本发明涉及人胰岛素衍生物的延长作用的水溶性聚集体，能够形成这种聚集体的人胰岛素的衍生物，含有它们的药物组合物，以及这些聚集体在治疗糖尿病中的用途。
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10.发明申请Method for making insulin precursors and insulin precursor analogues having improved fermentation yield in yeast 审中-公开制备酵母中发酵产量提高的胰岛素前体和胰岛素前体类似物的方法公开(公告)号：US20010041787A1
公开(公告)日：2001-11-15
申请号：US09740359
申请日：2000-12-19
IPC分类号： C07K014/62 , C07H021/04 , C12N001/15 , C12P021/02
CPC分类号： C07K14/62
摘要： Novel insulin precursors and insulin precursor analogs comprising a connecting peptide (mini C-peptide) of preferably up to 15 amino acid residues and comprising at least one Gly are provided. The precursors can be converted into human insulin or a human insulin analog. The precursors will typically have a distance between B27 (atom CG2) and A1 (atom CA) of less than 5 null.
摘要翻译： 提供了包含优选至多15个氨基酸残基并且包含至少一个Gly的连接肽（小C肽）的新型胰岛素前体和胰岛素前体类似物。 前体可转化为人胰岛素或人胰岛素类似物。 前体通常具有小于5埃的B27（原子CG2）和A1（原子CA）之间的距离。
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