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1. 发明申请

US20020146777A1 Canine parathyroid hormone 1 receptor 审中-公开
标题翻译：犬甲状旁腺激素1受体
公开(公告)号：US20020146777A1
公开(公告)日：2002-10-10
申请号：US09943446
申请日：2001-08-30
发明人： Tessa A. Castleberry , Bihong Lu , Thomas A. Owen , Steven L. Smock
IPC分类号： C07K014/635 , C07H021/04 , C12N001/18 , C12P021/02 , C12N005/06
CPC分类号： C07K14/72
摘要： The present invention provides isolated canine PTH1 protein, DNA molecules encoding said protein, vectors and cells carrying said DNA molecules, specific bind partners for the protein, and methods of discovering ligands for canine PTH1.
摘要翻译：本发明提供分离的犬PTH1蛋白，编码所述蛋白质的DNA分子，携带所述DNA分子的载体和细胞，用于蛋白质的特异性结合伙伴，以及发现犬PTH1配体的方法。

2. 发明申请

US20040077528A1 Purification and stabilization of peptide and protein pharmaceutical agents 有权
标题翻译：肽和蛋白质药剂的纯化和稳定
公开(公告)号：US20040077528A1
公开(公告)日：2004-04-22
申请号：US10719734
申请日：2003-11-21
申请人： MannKind Corporation
发明人： Solomon S. Steiner , Rodney J. Woods , Joseph W. Sulner
IPC分类号： A61K038/23 , A61K038/28 , C07K014/61 , C07K014/585 , C07K014/635
CPC分类号： A61K47/22 , A61K9/0019 , A61K9/0073 , A61K9/0075 , A61K9/14 , A61K9/145 , A61K9/1617 , A61K9/1676 , A61K38/28 , A61K47/6949 , B82Y5/00 , C07D241/08 , C07K1/30 , C07K1/32 , C07K14/605 , C07K14/62 , Y10S514/866
摘要： Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal one or more impurities, i.e. undesirable components, from the peptide or protein. In a preferred embodiment, a peptide, such as insulin, containing one or more impurities, e.g., zinc ions, is entrapped in diketopiperazine to form a precipitate of peptide/diketopiperazine/impurity, which is then washed with a solvent for the impurity to be removed, which is a nonsolvent for the diketopiperazine and a nonsolvent for the peptide. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and/or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In a preferred embodiment, insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. The charge on the insulin molecule is masked by hydrogen bonding it to the diketopiperazine, thereby enabling the insulin to pass through the target membrane. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.
摘要翻译：提供了通过将肽或蛋白质掺入二酮哌嗪或竞争性络合剂来促进从肽或蛋白质中去除一种或多种杂质（即不合需要的组分）来纯化肽和蛋白质的方法。在优选的实施方案中，将包含一种或多种杂质（例如锌离子）的肽例如包被在二酮哌嗪中以形成肽/二酮哌嗪/杂质的沉淀物，然后用溶剂洗涤以使杂质为去除，这是二酮哌嗪的非溶剂和肽的非溶剂。提供制剂和方法用于改善活性剂在生物膜上的转运，导致例如血药剂浓度的快速增加。制剂包括由（i）可以带电或中性的活性剂形成的微粒，和（ii）掩蔽试剂的电荷和/或与靶生物膜形成氢键的运输增强剂，以便于运输。在优选的实施方案中，胰岛素经由包含富马酰二酮哌嗪和胰岛素的微粒的肺部递送以其生物活性形式施用。胰岛素分子上的电荷被氢键键合到二酮哌嗪上，从而使胰岛素能够通过靶膜。这种递送胰岛素的方法导致血浆胰岛素浓度的快速增加，其与由静脉内递送产生的增加相当。

3. 发明申请

US20030235889A1 Materials and methods involving conditional retention domains 审中-公开
标题翻译：涉及条件性保留域的材料和方法
公开(公告)号：US20030235889A1
公开(公告)日：2003-12-25
申请号：US10440799
申请日：2003-05-19
申请人： ARIAD Gene Therapeutics, Inc.
发明人： Victor Rivera , Timothy P. Clackson , James E. Rothman
IPC分类号： C12P021/04 , C12N005/06 , C07K014/675 , C07K014/62 , C07K014/635 , C07K016/18
CPC分类号： C07K14/62 , A01K2217/05 , C07K14/47 , C07K14/4702 , C07K14/811 , C07K2319/00 , C07K2319/03 , C07K2319/04 , C07K2319/09 , C07K2319/32 , C07K2319/50 , C07K2319/60 , C07K2319/71 , C07K2319/715 , C07K2319/75 , C07K2319/81 , C12N15/625 , C12N2799/022
摘要： Materials and methods involving conditional retention domains (CRDs) are disclosed. Also disclosed are fusion proteins containing CRDs and cells expressing such fusion proteins. In addition, the invention provides novel methods for producing target proteins in vivo using fusion proteins containing conditional retention domains and methods for identifying novel CRDs.
摘要翻译：公开了涉及条件保留域（CRDs）的材料和方法。还公开了含有CRD和表达这种融合蛋白的细胞的融合蛋白。此外，本发明提供了使用含有条件保留结构域的融合蛋白体内产生靶蛋白质的新方法和鉴定新型CRD的方法。

4. 发明申请

US20040241165A1 Novel rfrp-3 and dna thereof 失效
标题翻译：新的rfrp-3和dna
公开(公告)号：US20040241165A1
公开(公告)日：2004-12-02
申请号：US10487634
申请日：2004-02-24
发明人： Shuji Hinuma , Hiromi Yoshida , Yugo Habata , Masaki Hosoya , Chieko Kitada
IPC分类号： A61K039/395 , A61K038/24 , C07K014/635
CPC分类号： C07K14/47 , A61K38/00
摘要： The RFRP-3 peptide of the present invention which is an agent for promoting prolactin secretion is useful as a prophylactic and/or therapeutic agent for various diseases associated with prolactin secretion, such as hypoovarianism, seminal vesicle hypoplasia, menopausal syndrome and hypothyroidism.
摘要翻译：作为促进催乳素分泌的药剂的本发明的RFRP-3肽可用作与催乳素分泌相关的各种疾病的预防和/或治疗剂，例如低血浆病，精囊发育不全，绝经期综合征和甲状腺机能减退。

5. 发明申请

US20040005668A1 Production of human parathyroid hormone from microorganisms 审中-公开
标题翻译：从微生物生产人甲状旁腺激素
公开(公告)号：US20040005668A1
公开(公告)日：2004-01-08
申请号：US10359091
申请日：2003-02-06
申请人： NPS Allelix Corp.
发明人： Kaare M. Gautvik , Peter Alestrom , Tordis Beate Oyen , Odd Stokke Gabrielsen
IPC分类号： C12P021/02 , C12N001/18 , C07K014/635 , C07H021/04 , C12N015/74
CPC分类号： C07K14/635 , A61K38/00 , C07K2319/02 , C12N15/64 , C12N15/66 , C12N15/67 , C12N15/70 , C12N15/81
摘要： The invention provides recombinant plasmids containing in DNA sequences coding for human preproparathyroid hormone. The invention further provides microorganisms, for example E. coli, transformed by these plasmids. The invention also provides a plasmid for insertion into yeast and a transformed yeast in which the plasmid contains DNA coding for parathyroid hormone. Parathyroid hormone is then secreted by the transformed yeast. Further the invention provides alternate polypeptides having parathyroid hormone activity, including PTH analogs, fragments and extensions, and provides alternate leader sequences and secretion signal sequences which can be used in the present invention. Finally, there are provided methods for purification of the secreted PTH hormone and/or derivatives.
摘要翻译：本发明提供含有编码人前甲状腺激素的DNA序列的重组质粒。本发明还提供了由这些质粒转化的微生物，例如大肠杆菌。本发明还提供了用于插入酵母的质粒和其中质粒含有编码甲状旁腺激素的DNA的转化酵母。甲状旁腺激素然后被转化的酵母分泌。此外，本发明提供了具有甲状旁腺激素活性的替代多肽，包括PTH类似物，片段和延伸，并提供可用于本发明的替代前导序列和分泌信号序列。最后，提供了分泌的PTH激素和/或衍生物的纯化方法。

6. 发明申请

US20030165930A1 Polynucleotides encoding for polymorphic isoforms of the pthrp protein, the encoded proteins and their therapeutic applications thereof 审中-公开
标题翻译：编码pthrp蛋白多态异构体的多核苷酸，编码蛋白及其治疗应用
公开(公告)号：US20030165930A1
公开(公告)日：2003-09-04
申请号：US10276231
申请日：2003-03-03
发明人： Tommaso A Dragani , Giacomo Manenti
IPC分类号： C12Q001/68 , G01N033/574 , A01K067/00 , C07H021/04 , C12P021/02 , C12N005/06 , C07K014/635
CPC分类号： C07K14/635 , A01K2217/05 , A61K39/00 , A61K48/00
摘要： Described herein is the identification of two polymorphic isoforms of the gene encoding the PTHrP protein, of the allelic proteins, of a first polynucleotide comprising the polymorphic domain corresponding to SEQ ID NO: 2 and comprising a first polymorphic position, of a second polynucleotide comprising a second polymorphic domain and corresponding to SEQ ID NO: 7 which encode for two variants of the PTHrP protein; also described is the use of these genes, alleles or polynucleotides to determine the risk of tumor in animals and humans and genetically modified cells and non-human animals.
摘要翻译：本文描述了鉴定编码PTHrP蛋白的等位基因蛋白的PTHrP蛋白的两个多态异构体，所述第一多核苷酸包含对应于SEQ ID NO：2的多态性结构域并且包含第一多态位置，第二多核苷酸包含第二多态性结构域并对应于编码PTHrP蛋白的两个变体的SEQ ID NO：7; 还描述了这些基因，等位基因或多核苷酸用于确定动物和人类以及遗传修饰的细胞和非人动物中肿瘤风险的用途。

7. 发明申请

US20030228665A1 Production of human parathyroid hormone from microorganisms 审中-公开
标题翻译：从微生物生产人甲状旁腺激素
公开(公告)号：US20030228665A1
公开(公告)日：2003-12-11
申请号：US10437038
申请日：2003-05-14
申请人： Allelix BioPharmaceuticals, Inc.
发明人： Kaare M. Gautvik , Peter Alestrom , Tordis Beate Oyen , Odd Stokke Gabrielsen
IPC分类号： C07K014/635 , C07H021/04 , C12N001/18 , C12P021/02
CPC分类号： C07K14/635 , A61K38/00 , C07K2319/02 , C12N15/64 , C12N15/66 , C12N15/67 , C12N15/70 , C12N15/81
摘要： The invention provides recombinant plasmids containing in DNA sequences coding for human preproparathyroid hormone. The invention further provides microorganisms, for example E. coli, transformed by these plasmids. The invention also provides a plasmid for insertion into yeast and a transformed yeast in which the plasmid contains DNA coding for parathyroid hormone. Parathyroid hormone is then secreted by the transformed yeast. Further the invention provides alternate polypeptides having parathyroid hormone activity, including PTH analogs, fragments and extensions, and provides alternate leader sequences and secretion signal sequences which can be used in the present invention. Finally, there are provided methods for purification of the secreted PTH hormone and/or derivatives.
摘要翻译：本发明提供含有编码人前甲状腺激素的DNA序列的重组质粒。本发明还提供了由这些质粒转化的微生物，例如大肠杆菌。本发明还提供了用于插入酵母的质粒和其中质粒含有编码甲状旁腺激素的DNA的转化酵母。甲状旁腺激素然后被转化的酵母分泌。此外，本发明提供了具有甲状旁腺激素活性的替代多肽，包括PTH类似物，片段和延伸，并提供可用于本发明的替代前导序列和分泌信号序列。最后，提供了分泌的PTH激素和/或衍生物的纯化方法。

8. 发明申请

US20030198596A1 Isolation of a gene encoding human thyrotropin beta subunit 审中-公开
公开(公告)号：US20030198596A1
公开(公告)日：2003-10-23
申请号：US10091706
申请日：2002-03-05
申请人： SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH
发明人： Ione A. Kourides , Graham Kerr Whitfield
IPC分类号： A61K049/00 , C07H021/04 , C12P021/02 , C12N005/06 , C07K014/635
CPC分类号： C07K14/59 , C12N2799/021
摘要： The gene expressing the beta subunit of human thyroid stimulating hormone has been isolated. The gene has been incorporated into plasmid pBR322. Vectors can be used to transform cells which in turn produce pure beta subunits. The beta subunits can then be combined with the alpha subunit of human glycoprotein hormones to produce pure thyroid stimulating hormone.

9. 发明申请

US20030187232A1 Growth factor modified protein matrices for tissue engineering 有权
公开(公告)号：US20030187232A1
公开(公告)日：2003-10-02
申请号：US10323046
申请日：2002-12-17
申请人： Eidgenossische Technische Hochschule Zurich Universitat Zurich
发明人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama-Elbert , Anna Jen
IPC分类号： C07K014/635 , C07K014/755 , C07K014/61 , A61K038/24 , A61K038/27 , C12P021/06
CPC分类号： C07K14/475
摘要： Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and/or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.

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