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1. 发明授权

US06610520B1 Gene encoding human manganese superoxide dismutase and recombinant polypeptide encoded thereby 失效
标题翻译：编码人类锰超氧化物歧化酶的基因和由此编码的重组多肽
公开(公告)号：US06610520B1
公开(公告)日：2003-08-26
申请号：US08299047
申请日：1994-08-31
申请人： Jacob R. Hartman , Yaffa Beck
发明人： Jacob R. Hartman , Yaffa Beck
IPC分类号： C12N902
CPC分类号： A61K38/446 , C12N9/0089 , Y02A50/473
摘要： A double-stranded cDNA molecule which includes DNA encoding human manganese superoxide dismutase has been created. The sequence of one strand of a double-stranded DNA molecule which encodes human manganese superoxide dismutase has been discovered. Such molecules may be introduced in procaryotic, e.g., bacterial, or eukaryotic, e.g., yeast or mammalian, cells and the resulting cells cultured or grown under suitable conditions so as to produce human manganese superoxide dismutase or analogs thereof which may then be recovered. By this invention, human MnSOD gene fragments from various plasmids may be ligated to yield a complete genomic human MnSOD gene fragment. Human MnSOD or analogs thereof may be used to catalyze the reduction of superoxide radicals, reduce reperfusion injury, prolong the survival time of isolated organs, or treat inflammations. The invention also concerns a method of producing enzymatically active human manganese superoxide dismutase or an analog thereof in a bacterial cell which contains and is capable of expressing a DNA sequence encoding the superoxide dismutase by maintaining the bacterial cell under suitable conditions and in a suitable production medium. The production medium is supplemented with an amount of Mn++ so that the concentration of Mn++ in the medium is greater than about 2 ppm. Genomic MnSOD DNA should also be capable of expression in eucaryotic cells under suitable conditions. This invention also concerns a method of recovering purified enzymatically active manganese superoxide dismutase from bacterial cells. It should also be possible to recover manganese SOD from genomic MnSOD DNA expressed in eucaryotic cells using similar methods.
摘要翻译：已经产生了包含编码人锰超氧化物歧化酶的DNA的双链cDNA分子。已经发现编码人锰超氧化物歧化酶的双链DNA分子的一条链的序列。这样的分子可以在原核细胞中，例如细菌的，或真核的，例如酵母或哺乳动物细胞中引入，所得细胞在合适的条件下培养或生长，以产生可以被回收的人锰超氧化物歧化酶或其类似物。通过本发明，可以连接各种质粒的人类MnSOD基因片段以产生完整的基因组人类MnSOD基因片段。人类MnSOD或其类似物可用于催化超氧自由基的还原，减少再灌注损伤，延长分离的器官的存活时间或治疗炎症。本发明还涉及生产酶活性人锰超氧化物歧化酶或其类似物的方法在细菌细胞中，其含有并且能够通过将细菌细胞维持在合适的条件下并在合适的生产培养基中表达编码超氧化物歧化酶的DNA序列。生产培养基补充一定量的Mn ++，使得培养基中Mn ++的浓度大于约2ppm。基因组MnSOD DNA也应该能够在合适条件下在真核细胞中表达。本发明还涉及从细菌细胞中回收纯化的酶活性锰超氧化物歧化酶的方法。也可以使用类似的方法从真核细胞中表达的基因组MnSOD DNA中回收锰SOD。

2. 发明授权

US06361772B1 Human manganese superoxide dismutase DNA, its expression and method of recovering human manganese superoxide dismutase 失效
标题翻译：人锰超氧化物歧化酶DNA，其表达及回收人锰超氧化物歧化酶的方法
公开(公告)号：US06361772B1
公开(公告)日：2002-03-26
申请号：US08686466
申请日：1996-07-25
申请人： Jacob R. Hartman , Yaffa Beck
发明人： Jacob R. Hartman , Yaffa Beck
IPC分类号： A61K3844
CPC分类号： A61K38/446 , C12N9/0089 , Y02A50/473
摘要： A double-stranded cDNA molecule which includes DNA encoding human manganese superoxide dismutase has been created. The sequence of one strand of a double-stranded DNA molecule which encodes human manganese superoxide dismutase has been discovered. Such molecules may be introduced in procaryotic, e.g., bacterial, or eukaryotic, e.g., yeast or mammalian, cells and the resulting cells cultured or grown under suitable conditions so as to produce human manganese superoxide dismutase or analogs thereof which may then be recovered. By this invention, human MnSOD gene fragments from various plasmids may be ligated to yield a complete genomic human MnSOD gene fragment. Human MnSOD or analogs thereof may be used to catalyze the reduction of superoxide radicals, reduce reperfusion injury, prolong the survival time of isolated organs, or treat inflammations. The invention also concerns a method of producing enzymatically active human manganese superoxide dismutase or an analog thereof in a bacterial cell which contains and is capable of expressing a DNA sequence encoding the superoxide dismutase by maintaining the bacterial cell under suitable conditions and in a suitable production medium. The production medium is supplemented with an amount of Mn++ so that the concentration of Mn++ in the medium is greater than about 2 ppm. Genomic MnSOD DNA should also be capable of expression in eucaryotic cells under suitable conditions. This invention also concerns a method of recovering purified enzymatically active manganese superoxide dismutase from bacterial cells. It should also be possible to recover manganese SOD from genomic MnSOD DNA expressed in eucaryotic cells using similar methods.
摘要翻译：已经产生了包含编码人锰超氧化物歧化酶的DNA的双链cDNA分子。已经发现编码人锰超氧化物歧化酶的双链DNA分子的一条链的序列。这样的分子可以在原核细胞中，例如细菌的，或真核的，例如酵母或哺乳动物细胞中引入，所得细胞在合适的条件下培养或生长，以产生可以被回收的人锰超氧化物歧化酶或其类似物。通过本发明，可以连接各种质粒的人类MnSOD基因片段以产生完整的基因组人类MnSOD基因片段。人类MnSOD或其类似物可用于催化超氧自由基的还原，减少再灌注损伤，延长分离的器官的存活时间或治疗炎症。本发明还涉及生产酶活性人锰超氧化物歧化酶或其类似物的方法在细菌细胞中，其含有并且能够通过将细菌细胞维持在合适的条件下并在合适的生产培养基中表达编码超氧化物歧化酶的DNA序列。生产培养基补充一定量的Mn ++，使得培养基中Mn ++的浓度大于约2ppm。基因组MnSOD DNA也应该能够在合适条件下在真核细胞中表达。本发明还涉及从细菌细胞中回收纯化的酶活性锰超氧化物歧化酶的方法。也可以使用类似的方法从真核细胞中表达的基因组MnSOD DNA中回收锰SOD。

3. 发明授权

US5270195A Plasmids for expression and method of producing a human manganese superoxide dimutase analog 失效
标题翻译：用于表达的质粒和生产人锰超氧化物二脱水酶类似物的方法
公开(公告)号：US5270195A
公开(公告)日：1993-12-14
申请号：US912213
申请日：1992-07-10
申请人： Jacob R. Hartman , Yaffa Beck
发明人： Jacob R. Hartman , Yaffa Beck
IPC分类号： C12N1/21 , C12N9/02 , C12N15/53
CPC分类号： C12N9/0089
摘要： An expression plasmid has been constructed which includes DNA encoding human manganese superoxide dismutase. Such plasmids may be introduced into host cells and the resulting cells cultured or grown under suitable conditions so as to produce enzymatically active human manganese superoxide dismutase or analogs thereof which may then be recovered. A method of producing an enzymatically active analog of human manganese superoxide dismutase by supplementing the culture media with Mn.sup.++ has been developed.
摘要翻译：已经构建了包含编码人锰超氧化物歧化酶的DNA的表达质粒。可以将这样的质粒引入宿主细胞，并将所得细胞在合适的条件下培养或生长，以便产生酶活性的人锰超氧化物歧化酶或其类似物，然后可以回收它们。已经开发了通过用Mn ++补充培养基来生产人锰超氧化物歧化酶的酶活性类似物的方法。

4. 发明授权

US5540911A Methods of use of human manganese superoxide dismutase 失效
标题翻译：人锰超氧化物歧化酶的使用方法
公开(公告)号：US5540911A
公开(公告)日：1996-07-30
申请号：US370461
申请日：1995-01-09
申请人： Jacob R. Hartman , Yaffa Beck
发明人： Jacob R. Hartman , Yaffa Beck
IPC分类号： A61K38/00 , A61K38/44 , C12N9/02 , C12N15/53 , A61K37/50
CPC分类号： A61K38/446 , C12N9/0089
摘要： This invention provides plasmids for expression of human superoxide dismutase of analogs thereof. The invention further provides a method of producing enzymatically active human MnSOD or an analog thereof by introducing plasmids for expression of human MnSOD into procaryotic or eucaryotic cells and growing the resulting cells under suitable conditions, including conditions wherein the production medium is supplemented with Mn.sup.++. The invention additionally provides a method of recovering purified enzymatically active MnSOD from procaryotic and eucaryotic cells. Human MnSOD or analogs thereof may be used to reduce reperfusion injury, prolong the survival time of isolated organs or treat inflammations or bronchial pulmonary dysplasia.
摘要翻译：本发明提供了用于表达其类似物的人超氧化物歧化酶的质粒。本发明还提供了通过将质粒用于表达人类MnSOD的原料或真核细胞，并在合适的条件下生长所得细胞，包括其中生产培养基中补充有Mn ++的条件，生产酶活性人类MnSOD或其类似物的方法。本发明另外提供从原核和真核细胞中回收纯化的酶活性MnSOD的方法。人类MnSOD或其类似物可用于减少再灌注损伤，延长分离的器官的存活时间或治疗炎症或支气管肺发育不良。

5. 发明授权

US5246847A Polypeptide analogs of human manganese superoxide dismutase and compositions and complexes thereof 失效
标题翻译：人锰超氧化物歧化酶的多肽类似物及其组合物及其复合物
公开(公告)号：US5246847A
公开(公告)日：1993-09-21
申请号：US842740
申请日：1992-02-27
申请人： Jacob R. Hartman , Yaffa Beck
发明人： Jacob R. Hartman , Yaffa Beck
IPC分类号： A61K38/44 , C12N9/02
CPC分类号： C12N9/0089 , A61K38/446
摘要： A double-stranded cDNA molecule which includes DNA encoding human manganese superoxide dismutase has been created. The sequence of one strand of a double-stranded DNA molecule which encodes human maganese superoxide dismutase has been discovered. Such molecules may be introduced in procaryotic, e.g., bacterial, or eukaryotic, e.g., yeast or mammalian, cells and the resulting cells cultured or grown under suitable conditions so as to produce human manganese superoxide dismutase or analogs thereof which may then be recovered. Human MnSOD or analogs thereof may be used to catalyze the reduction of superoxide radicals, reduce reperfusion injury, prolong the survival time of isolated organs, or treat inflammations.The invention also concerns a method of producing enzymatically active human manganese superoxide dismutase or an analog thereof in a bacterial cell which contains and is capable of expressing a DNA sequence encoding the superoxide dismutase by maintaining the bacterial cell under suitable conditions and in a suitable production medium. The production medium is supplemented with an amount of Mn.sup.++ so that the concentration of Mn.sup.++ in the medium is greater than about 2 ppm.This invention also concerns a method of recovering purified enzymatically active manganese superoxide dismutase from bacterial cells.
摘要翻译：已经产生了包含编码人锰超氧化物歧化酶的DNA的双链cDNA分子。已经发现了编码人类超氧化物歧化酶的双链DNA分子的一条链的序列。这样的分子可以在原核细胞中，例如细菌的，或真核的，例如酵母或哺乳动物细胞中引入，所得细胞在合适的条件下培养或生长，以产生可以被回收的人锰超氧化物歧化酶或其类似物。人类MnSOD或其类似物可用于催化超氧自由基的还原，减少再灌注损伤，延长分离的器官的存活时间或治疗炎症。本发明还涉及在细菌细胞中生产酶促活性人锰超氧化物歧化酶或其类似物的方法，其含有并且能够通过将细菌细胞维持在合适的条件下并在合适的生产培养基中表达编码超氧化物歧化酶的DNA序列。生产培养基补充一定量的Mn ++，使得培养基中Mn ++的浓度大于约2ppm。本发明还涉及从细菌细胞中回收纯化的酶活性锰超氧化物歧化酶的方法。

6. 发明申请

US20100204205A1 TOLERABILITY OF MIRTAZAPINE AND A SECOND ACTIVE AGENT BY USING THEM IN COMBINATION 审中-公开
标题翻译：通过使用它们在组合中，咪达嗪和第二活性剂的耐受性
公开(公告)号：US20100204205A1
公开(公告)日：2010-08-12
申请号：US12610419
申请日：2009-11-02
申请人： Nir Barak , Yaffa Beck , Srinivas Rao , Jay D. Kranzler , Jeffery J. Anderson
发明人： Nir Barak , Yaffa Beck , Srinivas Rao , Jay D. Kranzler , Jeffery J. Anderson
IPC分类号： A61K31/55 , A61P25/18 , A61P25/24 , A61P25/22 , A61P25/06 , A61P25/02 , A61P11/00 , A61P1/00
CPC分类号： A61K31/4402 , A61K31/55 , A61K45/06 , A61K2300/00
摘要： A reduction in the side effects of treating with an agent having combined 5HT2/5HT3 and alpha-2 antagonistic activity is obtained by administering an agent having histamine H1 receptor agonist activity. A combined dosage form comprising an agent having 5HT2/5HT3 and alpha-2 antagonistic activity and an agent having histamine H1 receptor agonist activity is presented. Some embodiments of the combined dosage form comprise an immediate release component comprising an agent having 5HT2/5HT3 and alpha-2 antagonistic activity and a delayed release component comprising an agent having histamine H1 receptor agonist activity. Some embodiments of the combined dosage form comprise a delayed release component comprising an agent having 5HT2/5HT3 and alpha-2 antagonistic activity and an immediate release component comprising an agent having histamine H1 receptor agonist activity. Methods of treatment and kits for administration are also provided.
摘要翻译：通过施用具有组胺H1受体激动剂活性的试剂，可以减少用具有组合的5HT 2 / 5HT 3和α-2拮抗活性的药物进行治疗的副作用。提供了包含具有5HT2 / 5HT3和α-2拮抗活性的药剂和具有组胺H1受体激动剂活性的药剂的组合剂型。组合剂型的一些实施方案包括立即释放组分，其包含具有5HT 2 / 5HT 3和α-2拮抗活性的试剂和包含具有组胺H1受体激动剂活性的试剂的延迟释放组分。组合剂型的一些实施方案包括包含具有5HT2 / 5HT3和α-2拮抗活性的试剂的延迟释放组分和包含具有组胺H1受体激动剂活性的试剂的速释组分。还提供了治疗方法和用于给药的试剂盒。

7. 发明授权

US4780414A Method of producing high molecular weight sodium hyallronate by fermentation of streptococcus 失效
标题翻译：通过链球菌发酵生产高分子量的羟龙胆酸钠的方法
公开(公告)号：US4780414A
公开(公告)日：1988-10-25
申请号：US815957
申请日：1986-01-09
申请人： Abraham Nimrod , Benjamin Greenman , Dov Kanner , Moshe Landsberg , Yaffa Beck
发明人： Abraham Nimrod , Benjamin Greenman , Dov Kanner , Moshe Landsberg , Yaffa Beck
IPC分类号： C12N15/00 , A61K8/72 , A61K8/73 , A61K8/99 , A61K31/715 , A61P27/02 , A61P29/00 , A61Q19/00 , C08B37/00 , C08B37/08 , C12N1/20 , C12N15/01 , C12P19/04 , C12P19/26 , C12Q1/14 , C12R1/46
CPC分类号： A61K31/715 , A61K8/735 , A61Q19/00 , C08B37/0072 , C12P19/26 , C12R1/46 , A61K2800/75 , Y10S435/803 , Y10S435/818 , Y10S435/885
摘要： A novel mutant microorganism Streptococcus zooepidemicus HA-116 ATCC 39920, has been produced. The microorganism produces large amounts of high molecular weight hyaluronic acid. The invention provides a method of obtaining such microorganisms.The invention also concerns a method of obtaining sodium hyaluronate which comprises growing with vigorous agitation a microorganism of the genus Streptococcus under appropriate conditions in a suitable nutrient medium containing a sugar component as a carbon source. The sugar component is present in a substantially constant concentration between 0.2 and 10 grams per liter. The medium has a substantially constant pH between about 6.0 and 7.5 and includes a substantially constant magnesium ion concentration above 0.05 grams per liter. The sodium hyaluronate excreted into the medium by the organism is purified using methods involving precipation, redissolving and reprecipating the hyaluronate. Composition of sodium hyaluronate which are characterized by an absence of pyrogenicity and skin irritation are obtained.
摘要翻译：已经生产了一种新型突变体微生物链球菌动物疫苗HA-116 ATCC 39920。微生物产生大量的高分子量透明质酸。本发明提供了获得这种微生物的方法。本发明还涉及一种获得透明质酸钠的方法，其包括在合适的条件下，在含有糖组分作为碳源的合适的营养培养基中，剧烈搅拌生长链球菌属的微生物。糖组分以0.2至10克/升之间的基本恒定的浓度存在。介质具有在约6.0和7.5之间的基本上恒定的pH，并且包括大于0.05克/升的基本上恒定的镁离子浓度。使用涉及沉淀，再溶解和再沉淀透明质酸的方法纯化由生物体排出到培养基中的透明质酸钠。获得特征在于没有致热原性和皮肤刺激性的透明质酸钠的组成。

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