公开(公告)号：US20050191655A1

公开(公告)日：2005-09-01

申请号：US10985655

申请日：2004-11-09

申请人： Roderic Dale

发明人： Roderic Dale

IPC分类号： C12Q1/68 ,  C12M1/34

CPC分类号： C12Q1/6837

摘要： The present invention provides methods for producing arrays having associated modified nucleic acid structures, e.g. acid stable and/or end-blocked nucleic acids such as 2′-O—R oligonucleotides. In one embodiment, arrays produced using the methods of the invention exhibit an increased binding affinity with complementary nucleic acids, and in particular with complementary RNA. In another embodiment, the associated nucleic acids of the array produced using the methods of the invention exhibit substantial acid resistance, allowing the arrays to be treated with low pH solutions. In another embodiment, the modified associated nucleic acids of the array produced using the methods of the invention exhibit substantial resistance to nuclease degradation.

摘要翻译： 本发明提供了制备具有相关联的修饰的核酸结构的阵列的方法，例如 酸稳定的和/或端封闭的核酸如2'-O-R寡核苷酸。 在一个实施方案中，使用本发明的方法产生的阵列表现出与互补核酸，特别是与互补RNA的增加的结合亲和力。 在另一个实施方案中，使用本发明的方法制备的阵列的相关核酸表现出显着的耐酸性，允许阵列用低pH值溶液处理。 在另一个实施方案中，使用本发明的方法制备的阵列的修饰的相关核酸表现出对核酸酶降解的显着抗性。

公开(公告)号：US20050118618A1

公开(公告)日：2005-06-02

申请号：US10937112

申请日：2004-09-08

申请人： Roderic Dale

发明人： Roderic Dale

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6837 ,  C12Q2525/113

摘要： A method for detecting nucleic acid sequences in two or more collections of nucleic acid molecules, the method comprising: (a) providing an array of modified polynucleotides bound to a solid surface, each said modified polynucleotide comprising a determinable nucleic acid; (b) contacting the array of modified polynucleotides with: (i) a first collection of labeled nucleic acid comprising a sequence substantially complementary to a nucleic acid of said array, and (ii) at least a second collection of labeled nucleic acid comprising a sequence substantially complementary to a modified polynucleotide of said array; wherein the first and second labels are distinguishable from each other; and (c) detecting hybridization of the first and second labeled complementary nucleic acids to nucleic acids of said arrays; wherein the modified oligonucleotides are characterized by a characteristic selected from the group consisting of (a) a binding affinity of at least about 1.25 times that of a corresponding, non-modified oligonucleotide, (b) a pH stability of at least one hour at 37 C at a pH in a range of about 0.5 to 10; and (c) a nuclease resistance of at least twice that of a naturally occurring oligonucleotide having the same sequence and number of bases.

摘要翻译： 一种用于检测两个或更多个核酸分子集合中的核酸序列的方法，所述方法包括：（a）提供与固体表面结合的修饰多核苷酸阵列，每个所述修饰的多核苷酸包含可测定的核酸; （b）将经修饰的多核苷酸阵列与以下物质接触：（i）包含与所述阵列的核酸基本上互补的序列的标记核酸的第一次收集，和（ii）至少第二次标记的核酸集合，其包含序列 基本上与所述阵列的修饰的多核苷酸互补; 其中所述第一和第二标签彼此可区分; 和（c）检测第一和第二标记的互补核酸与所述阵列的核酸的杂交; 其中修饰的寡核苷酸的特征在于选自（a）至少约1.25倍相应未修饰寡核苷酸的结合亲和力的特征，（b）在37℃下至少1小时的pH稳定性 pH在约0.5至10的范围内; 和（c）具有相同序列和碱基数的天然存在的寡核苷酸的至少两倍的核酸酶抗性。

公开(公告)号：US20050107344A1

公开(公告)日：2005-05-19

申请号：US10937094

申请日：2004-09-08

申请人： Roderic Dale ,  Steven Gatton ,  Amy Arrow ,  Terry Thompson

发明人： Roderic Dale ,  Steven Gatton ,  Amy Arrow ,  Terry Thompson

IPC分类号： C07H19/10 ,  A01N57/12 ,  A01N57/16 ,  A61K9/70 ,  A61K31/66 ,  A61K31/6615 ,  A61K31/675 ,  A61K31/683 ,  A61K31/70 ,  A61K31/7024 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  A61K48/00 ,  A61L2/16 ,  A61P17/00 ,  A61P17/02 ,  A61P31/04 ,  A61P31/10

CPC分类号： A61K31/66 ,  A01N57/12 ,  A01N57/16 ,  A61K9/0014 ,  A61K31/70

摘要： The present invention provides protonated compounds having antimicrobial activity. The invention also provides antimicrobial compositions comprising protonated compounds of the invention. The protonated compounds of the invention provide efficacious antimicrobial activity against resistant strains of bacteria and opportunistic fungi.

摘要翻译： 本发明提供具有抗微生物活性的质子化化合物。 本发明还提供包含本发明的质子化化合物的抗微生物组合物。 本发明的质子化化合物为细菌和机会真菌的抗性菌株提供有效的抗微生物活性。

公开(公告)号：US20060223083A1

公开(公告)日：2006-10-05

申请号：US11277750

申请日：2006-03-28

申请人： Roderic Dale

发明人： Roderic Dale

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6837 ,  C12Q2525/113

摘要： A method for detecting nucleic acid sequences in two or more collections of nucleic acid molecules, the method comprising: (a) providing an array of modified polynucleotides bound to a solid surface, each said modified polynucleotide comprising a determinable nucleic acid; (b) contacting the array of modified polynucleotides with: (i) a first collection of labeled nucleic acid comprising a sequence substantially complementary to a nucleic acid of said array, and (ii) at least a second collection of labeled nucleic acid comprising a sequence substantially complementary to a modified polynucleotide of said array; wherein the first and second labels are distinguishable from each other; and (c) detecting hybridization of the first and second labeled complementary nucleic acids to nucleic acids of said arrays; wherein the modified oligonucleotides are characterized by a characteristic selected from the group consisting of (a) a binding affinity of at least about 1.25 times that of a corresponding, non-modified oligonucleotide, (b) a pH stability of at least one hour at 37 C at a pH in a range of about 0.5 to 10; and (c) a nuclease resistance of at least twice that of a naturally occurring oligonucleotide having the same sequence and number of bases.

摘要翻译： 一种用于检测两个或更多个核酸分子集合中的核酸序列的方法，所述方法包括：（a）提供与固体表面结合的修饰多核苷酸阵列，每个所述修饰的多核苷酸包含可测定的核酸; （b）将经修饰的多核苷酸阵列与以下物质接触：（i）包含与所述阵列的核酸基本上互补的序列的标记核酸的第一次收集，和（ii）至少第二次标记的核酸集合，其包含序列 基本上与所述阵列的修饰的多核苷酸互补; 其中所述第一和第二标签彼此可区分; 和（c）检测第一和第二标记的互补核酸与所述阵列的核酸的杂交; 其中修饰的寡核苷酸的特征在于选自（a）至少约1.25倍相应未修饰寡核苷酸的结合亲和力的特征，（b）在37℃下至少1小时的pH稳定性 pH在约0.5至10的范围内; 和（c）具有相同序列和碱基数的天然存在的寡核苷酸的至少两倍的核酸酶抗性。

公开(公告)号：US20050025815A1

公开(公告)日：2005-02-03

申请号：US10644969

申请日：2003-08-21

申请人： Roderic Dale ,  Steven Gatton ,  Amy Arrow

发明人： Roderic Dale ,  Steven Gatton ,  Amy Arrow

IPC分类号： C12N15/09 ,  A01N43/04 ,  A01N57/16 ,  A61B17/04 ,  A61F13/00 ,  A61K8/00 ,  A61K8/60 ,  A61K9/08 ,  A61K9/14 ,  A61K9/70 ,  A61K31/675 ,  A61K31/70 ,  A61K31/7024 ,  A61K31/7068 ,  A61K31/7076 ,  A61K31/7125 ,  A61K47/12 ,  A61K48/00 ,  A61K51/00 ,  A61L15/16 ,  A61P31/02 ,  A61P31/04 ,  A61Q19/00 ,  C07H19/00 ,  C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  C12Q1/02 ,  C12Q1/68

CPC分类号： A01N57/16 ,  A61B17/06166 ,  A61B2017/00893 ,  A61K8/606 ,  A61K31/70 ,  A61L15/46 ,  A61L17/005 ,  A61L17/04 ,  A61L17/105 ,  A61L24/0015 ,  A61L24/106 ,  A61L27/54 ,  A61L27/60 ,  A61L2300/258 ,  A61L2300/404 ,  A61Q19/00

摘要： The present invention provides devices and compositions for the management of infection of topical lesions, each of the devices and compositions containing protonated/acidified nucleic acids either on its surface, or integrated into the device. These modified nucleic acids are effective as bactericidal and/or bacteriostatic agents without regard to the class of bacteria, so are especially useful when diagnosis is difficult or when multiple infectious organisms are present. The antibiotic activity of nucleic acids of the invention is not dependent on either the specific sequence of the nucleic acid or the length of the nucleic acid molecule. The nucleic acids used in the invention are protonated/acidified to give a pH when dissolved in water of less than pH 7 to about 1, more preferably less than pH 4.5 to about 1, and even more preferably less than pH 2 to about 1.

摘要翻译： 本发明提供了用于管理局部损伤感染的装置和组合物，每个装置和组合物在其表面上含有质子化/酸化的核酸或整合到装置中。 这些修饰的核酸在不考虑细菌类的情况下作为杀菌剂和/或抑菌剂是有效的，因此当诊断困难时或当存在多种感染性生物时特别有用。 本发明的核酸的抗生素活性不依赖于核酸的特定序列或核酸分子的长度。 本发明中使用的核酸被质子化/酸化，当溶解在低于pH7至约1，更优选小于pH 4.5至约1，甚至更优选小于pH 2至约1的水中时产生pH。

公开(公告)号：US20070053971A1

公开(公告)日：2007-03-08

申请号：US11552951

申请日：2006-10-25

申请人： Roderic Dale

发明人： Roderic Dale

IPC分类号： A61K31/7076 ,  A61K31/7072 ,  A61K9/127

CPC分类号： A61K9/0014 ,  A61K9/1271 ,  A61K31/7072 ,  A61K31/7076 ,  C07H11/04 ,  C07H19/10 ,  Y02A50/473 ,  Y02A50/475 ,  Y02A50/481

摘要： The present invention provides protonated compounds having antiviral and antimicrobial activity. The invention also provides antimicrobial compositions comprising protonated compounds of the invention. The protonated compounds of the invention provide efficacious antimicrobial activity against resistant strains of bacteria and opportunistic fungi. The invention also provides antiviral compositions comprising compounds of the invention. Viruses that may be treated by compositions of the invention include, but are not limited to, HIV, HSV, CMV, HBV, HCV and influenza virus.

摘要翻译： 本发明提供具有抗病毒和抗微生物活性的质子化化合物。 本发明还提供包含本发明的质子化化合物的抗微生物组合物。 本发明的质子化化合物为细菌和机会真菌的抗性菌株提供有效的抗微生物活性。 本发明还提供包含本发明化合物的抗病毒组合物。 可以通过本发明的组合物治疗的病毒包括但不限于HIV，HSV，CMV，HBV，HCV和流感病毒。

公开(公告)号：US20060018826A1

公开(公告)日：2006-01-26

申请号：US10958999

申请日：2004-10-05

申请人： Gretchen Unger ,  Roderic Dale ,  Thomas Thompson

发明人： Gretchen Unger ,  Roderic Dale ,  Thomas Thompson

IPC分类号： A61K51/00 ,  A61K48/00 ,  A61K31/675 ,  C07H21/04

CPC分类号： A61K9/5138 ,  A61K9/0019 ,  A61K9/5094 ,  A61K39/0011 ,  A61K47/62 ,  A61K47/645 ,  A61K47/6935 ,  A61K48/0008 ,  A61K48/0041 ,  A61K49/0065 ,  A61K49/0067 ,  A61K2039/55555 ,  A61L31/10 ,  A61L31/16 ,  B82Y5/00 ,  C12N15/111 ,  C12N15/87 ,  C12N2320/32

摘要： Certain aspects of the invention relate to the use of small particles in biological systems, including the delivery of biologically active agents to cells or tissues using nanoparticles of less than about 200 nm in approximate diameter. Embodiments include collection of particles having a bioactive component, a surfactant molecule, a biocompatible polymer, and a cell recognition component, wherein the cell recognition component has a binding affinity for a cell recognition target. Compositions and methods of use are also set forth, including the use of antisense directed against Protein Kinase CK2, CK2alpha, CK2 alpha′, and CK2 beta.

摘要翻译： 本发明的某些方面涉及在生物系统中使用小颗粒，包括使用近似直径小于约200nm的纳米粒子将生物活性剂递送至细胞或组织。 实施方案包括收集具有生物活性成分的颗粒，表面活性剂分子，生物相容性聚合物和细胞识别组分，其中细胞识别组分对细胞识别目标具有结合亲和性。 还阐述了组合物和使用方法，包括使用针对蛋白激酶CK2，CK2alpha，CK2α'和CK2β的反义。

公开(公告)号：US20050202541A1

公开(公告)日：2005-09-15

申请号：US11035693

申请日：2005-01-14

申请人： Amy Arrow ,  Roderic Dale ,  Tod Woolf

发明人： Amy Arrow ,  Roderic Dale ,  Tod Woolf

IPC分类号： C12N15/113 ,  A61K48/00 ,  C07H21/02 ,  C12P19/34

CPC分类号： C12N15/113 ,  C12N2310/311 ,  C12N2310/315 ,  C12N2310/317 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/346 ,  C12N2310/3521 ,  C12N2310/3523 ,  C12N2310/3527

摘要： This invention relates to antisense oligonucleotides that target mRNAs in cells as substrates for the cellular enzyme RNase H and thereby cause specific degradation of the targeted mRNA. The oligonucleotides have three components: an RNase H activating region, a complementary region and 3′ and 5′ ends. The invention optimizes each of the components to resist intracellular nucleases, to increase hybridization to target mRNA, to specifically inactivate target mRNA in cells, and to decrease cytotoxicity.

公开(公告)号：US20050136458A1

公开(公告)日：2005-06-23

申请号：US10984030

申请日：2004-09-14

申请人： Roderic Dale ,  Steven Gatton

发明人： Roderic Dale ,  Steven Gatton

IPC分类号： C07H21/04 ,  C12N15/10 ,  C12Q1/68

CPC分类号： C12N15/101 ,  C07H21/04 ,  C12Q1/6806

摘要： Concentration of oligonucleotides in salt solutions is accomplished by loading a solution of the oligonucleotide dissolved in aqueous sodium chloride or other salt solution onto a reverse-phase poly(styrene-divinylbene) liquid chromatography (LC) column. The column bearing oligonucleotide is then washed with water to low conductivity and eluted with an organic eluent such as ethanol, thus effecting a combination desalting concentration procedure in one step, thus this procedure has utility in the desalting and concentration of oligonucleotides that have been purified and/or treated by anion exchange chromatography. In situ cationic exchange of the associated cation of the oligonucleotide can also be incorporated into the procedure of the new invention.

摘要翻译： 盐溶液中寡核苷酸的浓度通过将溶解在氯化钠水溶液或其它盐溶液中的寡核苷酸溶液加载到反相聚（苯乙烯 - 二乙烯基苯）液相色谱（LC）柱上来完成。 然后将带有柱的寡核苷酸用水洗涤至低电导率，并用有机洗脱液如乙醇洗脱，从而在一步中实现脱盐浓缩程序的组合，因此该方法可用于脱盐和浓缩已经纯化的寡核苷酸， /或通过阴离子交换色谱法处理。 寡核苷酸的相关阳离子的原位阳离子交换也可以并入新发明的方法中。