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1. 发明授权

US4754018A Antibiotic prepared from lysobacter sp. SC 14,067 and analogs thereof 失效
标题翻译：溶解细菌制备的抗生素 SC 14,067及其类似物
公开(公告)号：US4754018A
公开(公告)日：1988-06-28
申请号：US23425
申请日：1987-03-09
申请人： Adrienne A. Tymiak , Donald R. Kirsch , Joseph O'Sullivan , John E. McCullough
发明人： Adrienne A. Tymiak , Donald R. Kirsch , Joseph O'Sullivan , John E. McCullough
IPC分类号： C07G11/00 , A61K35/74 , A61P31/04 , C12P1/04 , C12R1/01 , C07K5/12
CPC分类号： C12P1/04 , Y10S930/19
摘要： A novel antibiotic substance EM5587 is prepared by cultivation of a strain of the microorganism Lysobacter sp. SC 14,067, A.T.C.C. No. 53042. Chemical analogs of EM5587 are prepared by chemical synthesis.
摘要翻译：通过培养微生物溶菌杆菌属菌株制备新型抗生素物质EM5587。 SC 14,067，A.T.C.C. 号53042.通过化学合成制备EM5587的化学类似物。

2. 发明授权

US5024839A Dactylocycline A and dactylocycline B 失效
标题翻译： Dactylocycline A和Dactylocycline B
公开(公告)号：US5024839A
公开(公告)日：1991-06-18
申请号：US137635
申请日：1987-12-24
申请人： Carol A. Aklonis , Helen A. Ax , Donald R. Kirsch , Joseph O'Sullivan , Adrienne Tymiak , J. Scott Wells
发明人： Carol A. Aklonis , Helen A. Ax , Donald R. Kirsch , Joseph O'Sullivan , Adrienne Tymiak , J. Scott Wells
IPC分类号： A61K35/74 , C12P1/06 , C12P29/00 , C12R1/01
CPC分类号： C12P29/00 , C12P1/06
摘要： Cultivation of a strain of the microorganism Dactylosporangium sp. A.T.C.C. No. 53693, yields the antibiotic substance EM5586 which contains the novel useful components dactylocycline A and dactylocycline B.

3. 发明授权

US5294725A Scopularin 失效
公开(公告)号：US5294725A
公开(公告)日：1994-03-15
申请号：US305338
申请日：1989-01-31
申请人： Donald R. Kirsch , Joseph O'Sullivan , Douglas W. Phillipson
发明人： Donald R. Kirsch , Joseph O'Sullivan , Douglas W. Phillipson
IPC分类号： C07D309/10 , C07D405/04 , C07H15/12 , C07H15/26
CPC分类号： C07D405/04 , C07D309/10 , C07H15/12 , C07H15/26
摘要： A novel antibiotic substance, Scopularin, is prepared by cultivation of a strain of the microorganism, Scopulariopsis, A.T.C.C. No. 20,914. This compound and its alcohol derivative have also been found to have cytochrome P450 inhibition activity.
摘要翻译：通过培养微生物菌株Scopulariopsis，A.T.C.C.制备新型抗生素物质Scopularin。第20,914号。该化合物及其醇衍生物也被发现具有细胞色素P450抑制活性。

4. 发明申请

US20120035203A1 BUTACLAMOL FOR THE TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS 审中-公开
标题翻译： BUTACLAMOL用于治疗左心室狭窄症
公开(公告)号：US20120035203A1
公开(公告)日：2012-02-09
申请号：US13265008
申请日：2010-04-27
申请人： Donald R. Kirsch , Radhia Benmohamed
发明人： Donald R. Kirsch , Radhia Benmohamed
IPC分类号： A61K31/4375 , A61P25/00
CPC分类号： A61K31/4375
摘要： The present invention relates to the use of butaclamol and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases.
摘要翻译：本发明涉及丁酰胺及其药物组合物用于治疗肌萎缩性侧索硬化（ALS）和其它神经变性疾病的受试者的用途。

5. 发明授权

US5525496A DNA sequence encoding sterol .DELTA.14 reductase 失效
公开(公告)号：US5525496A
公开(公告)日：1996-06-11
申请号：US440674
申请日：1995-05-15
申请人： Margaret Hsien-fen Kuh Lai , Donald R. Kirsch , Martin Bard
发明人： Margaret Hsien-fen Kuh Lai , Donald R. Kirsch , Martin Bard
IPC分类号： C12N9/02 , C12N15/53 , A61K38/44 , C12N15/81
CPC分类号： C12N9/001
摘要： A gene encoding Saccharomyces cerevisiae sterol .DELTA.14 reductase of the ergosterol biosynthetic pathway is isolated and cloned by selecting strains carrying sequences on a 2.mu. based vector for resistance to a morpholine fungicide such as fenpropimorph. Four distinct plasmid inserts which produce morpholine resistance are obtained, and one of these is characterized and sequenced. The purified and isolated DNA sequence encoding sterol .DELTA.14 reductase encodes a polypeptide exhibiting homology to the S. cerevisiae sterol C-24(28) reductase enzyme in the ergosterol biosynthetic pathway.

6. 发明授权

US5418144A Spindle pole body screen for fungicides 失效
标题翻译：主轴杆体屏幕为杀菌剂
公开(公告)号：US5418144A
公开(公告)日：1995-05-23
申请号：US66764
申请日：1993-05-25
申请人： Donald R. Kirsch , Margaret H. K. Lai
发明人： Donald R. Kirsch , Margaret H. K. Lai
IPC分类号： C12Q1/18 , C12N1/00
CPC分类号： C12Q1/18 , Y10S435/942
摘要： A method for the identification of agents which inhibit spindle pole body formation or function, thus exhibiting selective fungicidal activity, involves the incubation of test samples in cultures of a Saccharomyces cerevisiae strain that produces excess numbers of spindle pole bodies. Cultures containing samples that inhibit spindle pole bodies exhibit enhanced growth because the growing yeast is rescued from the adverse effects of excess spindle bodies. In the preferred practice of the invention, the test sample is added to a S. cerevisiae culture or culture area containing a strain that has a conditional mutation producing excess spindle pole bodies, such as diploid esp1-1 strains. The culture or culture area is preincubated under permissive conditions wherein the strain can grow to some extent, and then conditions are shifted to restrictive conditions so that the mutant strain either cannot grow or grows poorly. The extent of growth in the culture or culture area containing test sample is then compared with the extent of growth in the absence of test sample, and the presence of spindle pole body inhibition is determined by observation of whether culture growth in the presence of test sample exceeds growth in its absence. Preferred embodiments employ test samples on disks or in wells in solidified cultures, facilitating easy visual inspection of growth. A presumptive spindle pole body inhibitor, identified in random screening, is used as a positive control which can be compared to the test sample.
摘要翻译：用于鉴定抑制纺锤体体形成或功能，从而显示出选择性杀真菌活性的试剂的方法涉及在产生过量纺锤体的酿酒酵母菌株的培养物中孵育测试样品。含有抑制锭子极体的样品的培养物表现出增强的生长，因为生长的酵母被从多余的纺锤体的不利影响中拯救出来。在本发明的优选实践中，将测试样品加入到含有产生过量纺锤体的条件突变的菌株的酿酒酵母培养物或培养物区域中，例如二倍体esp1-1菌株。培养或培养区域在允许条件下进行预培养，其中菌株可以在一定程度上生长，然后将条件转移到限制条件，使得突变菌株不能生长或生长差。然后将含有测试样品的培养或培养区域的生长程度与不存在测试样品的生长程度进行比较，并通过观察测试样品存在培养生长来确定主轴极体抑制的存在超过其缺席时的增长。优选实施例在盘或在固化培养物中的孔中采用测试样品，便于生长的容易的视觉检查。使用随机筛选鉴定的推定的主轴极体抑制剂作为阳性对照，可与测试样品进行比较。

7. 发明授权

US10167263B2 Treatment of amyotrophic lateral sclerosis 有权
公开(公告)号：US10167263B2
公开(公告)日：2019-01-01
申请号：US13129854
申请日：2009-11-20
申请人： Donald R. Kirsch , Radhia Benmohamed , Anthony C. Arvanites , Richard I. Morimoto , Tian Chen , Richard B. Silverman
发明人： Donald R. Kirsch , Radhia Benmohamed , Anthony C. Arvanites , Richard I. Morimoto , Tian Chen , Richard B. Silverman
IPC分类号： C07D231/20 , C07D401/12 , C07D403/12 , C07D231/22 , A61B5/00 , C07D403/04 , C07D405/06 , C07D409/04 , C07D417/04 , C07D417/12 , C07D417/14
摘要： The present invention relates to the identification of compounds and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided compounds.

8. 发明授权

US6110698A Screen for ultraspiracle inhibitors 失效
标题翻译：超滤阻垢剂屏幕
公开(公告)号：US6110698A
公开(公告)日：2000-08-29
申请号：US865960
申请日：1997-05-30
申请人： Julia N. Heinrich , Fernando Dela E. Cruz , Donald R. Kirsch
发明人： Julia N. Heinrich , Fernando Dela E. Cruz , Donald R. Kirsch
IPC分类号： C12Q1/02 , C12N15/00 , C12N15/63 , C12N15/81
CPC分类号： C12Q1/02
摘要： This invention discloses methods for identifying compounds, variant nuclear proteins and other auxiliary proteins that interfere with the Drosophila ultraspiracle protein ("Usp") and homologs thereof. The methods disclosed involve transformed yeast cells which contain a Usp binding partner, Usp or a homolog thereof which can bind with the Usp binding partner, and a reporter gene which requires a functional Usp--Usp binder partner complex for expression. The transformed yeast cells are incubated in the presence of a test compound to form a test culture and in the absence of a test compound to form a control culture. The expression of the reporter gene is monitored in one example by exposing the test and control cultures to canavanine under conditions in which control cultures exhibit reduced growth and detecting test cultures in which growth is increased relative to growth of control cultures.
摘要翻译：本发明公开了鉴定化合物，变体核蛋白和干扰果蝇超尖锐蛋白（“Usp”）及其同系物的其它辅助蛋白质的方法。所公开的方法涉及含有可与Usp结合配偶体结合的Usp结合配偶体，Usp或其同系物的转化酵母细胞，以及需要功能性的Usp-Usp结合物配合物复合物进行表达的报告基因。将转化的酵母细胞在测试化合物存在下孵育以形成测试培养物，并且在没有测试化合物的情况下形成对照培养物。在一个实例中，通过将测试和对照培养物暴露于刀豆氨酸，在对照培养物显示减少的生长并检测其中生长相对于对照培养物的生长增加的测试培养物的条件下，监测报道基因的表达。

9. 发明授权

US5527687A Enzyme induction screen for ergosterol biosynthesis inhibitors 失效
标题翻译：麦角甾醇生物合成抑制剂的酶诱导筛选
公开(公告)号：US5527687A
公开(公告)日：1996-06-18
申请号：US68986
申请日：1993-05-25
申请人： Donald R. Kirsch , Margaret H. K. Lai
发明人： Donald R. Kirsch , Margaret H. K. Lai
IPC分类号： C12Q1/18 , C12Q1/26 , C12Q1/34 , C12Q1/54 , C12Q1/48
CPC分类号： C12Q1/34 , C12Q1/18 , C12Q1/26 , C12Q2334/52 , G01N2333/395 , G01N2333/924 , Y10S435/942
摘要： A method for screening for sterol biosynthesis inhibitors of potential use as fungicides or antihypercholesterolemic agents identifies agents by the induction of lanosterol 14-.alpha.-demethylase, an enzyme in the biosynthetic pathway of ergosterol and cholesterol, in cultures containing the agents. In one screening test, test samples are incubated in a culture of a Saccharomyces cerevisiae strain sensitive to ergosterol biosynthesis and containing a gene fusion of a lanosterol 14-.alpha.-demethylase clone with a gene for bacterial .beta.-galactosidase. After incubation of the culture, an increase in lancsterol 14-.alpha.-demethylase activity is determined indirectly by measuring .beta.-galactosidase activity. The culture media contains a chromogenic substrate of .beta.-galactosidase such as orthonitrophenyl-.beta.-D-galactoside or 5-bromo-4-chloro-3-indoyl-.beta.-D-galactoside, so that active samples are identified by the production of colored product. For comparison purposes, screening tests may employ a lanosterol 14-.alpha.-demethylase inhibitor such as dinaconazole as a positive control.
摘要翻译：用于筛选潜在用作杀真菌剂或抗高胆固醇血症药的甾醇生物合成抑制剂的方法通过诱导羊毛甾醇14-α-甲基化酶（在麦角甾醇和胆固醇的生物合成途径中的酶）在含有该试剂的培养物中鉴定药剂。在一次筛选试验中，将测试样品在对麦角甾醇生物合成敏感的酿酒酵母菌株的培养物中培养，并含有羊毛甾醇14-α-甲基化酶克隆与细菌β-半乳糖苷酶基因的基因融合物。培养物培养后，通过测量β-半乳糖苷酶活性间接测定兰曲星14-α-甲基化酶活性的增加。培养基含有β-半乳糖苷酶如邻硝基苯基-β-D-半乳糖苷或5-溴-4-氯-3-吲哚基-β-D-半乳糖苷的显色底物，使活性样品通过生产有色产品。为了比较目的，筛选试验可以使用羊毛甾醇14-α-甲基化酶抑制剂如依替康唑作为阳性对照。

10. 发明授权

US5512472A DNA sequence encoding sterol .DELTA.14 reductase 失效
标题翻译：编码固醇DELTA14还原酶的DNA序列
公开(公告)号：US5512472A
公开(公告)日：1996-04-30
申请号：US439131
申请日：1995-05-11
申请人： Margaret H. K. Lai , Donald R. Kirsch , Martin Bard
发明人： Margaret H. K. Lai , Donald R. Kirsch , Martin Bard
IPC分类号： C12N9/02 , C12N15/53 , C12N15/09 , C12N15/81
CPC分类号： C12N9/001
摘要： A gene encoding Saccharomyces cerevisiae sterol .DELTA.14 reductase of the ergosterol biosynthetic pathway is isolated and cloned by selecting strains carrying sequences on a 2.mu. based vector for resistance to a morpholine fungicide such as fenpropimorph. Four distinct plasmid inserts which produce morpholine resistance are obtained, and one of these is characterized and sequenced. The purified and isolated DNA sequence encoding sterol .DELTA.14 reductase encodes a polypeptide exhibiting homology to the S. cerevisiae sterol C-24(28) reductase enzyme in the ergosterol biosynthetic pathway.
摘要翻译：通过选择在2基于载体上携带序列的菌株来分离和克隆麦角甾醇生物合成途径的酿酒酵母甾醇DELTA 14还原酶的基因，以抵抗吗啉杀真菌剂例如茴香霉素。获得产生吗啉抗性的四种不同的质粒插入片段，其中之一被表征和测序。编码固醇DELTA14还原酶的纯化和分离的DNA序列编码与麦角甾醇生物合成途径中的酿酒酵母甾醇C-24（28）还原酶具有同源性的多肽。

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