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    • 1. 发明申请
    • Methods for identifying small molecules that modulate premature translation termination and nonsense mediated mrna decay
    • 用于鉴定调节过早翻译终止和废话介导的mrna衰变的小分子的方法
    • US20060257866A1
    • 2006-11-16
    • US10521775
    • 2003-07-24
    • Ellen WelchNeil AlmsteadRobert RandoMathew Pellegrini
    • Ellen WelchNeil AlmsteadRobert RandoMathew Pellegrini
    • C40B30/06C12Q1/68
    • B82Y30/00G01N33/5308G01N2500/04
    • The present invention relates to a method for screening and identifying compounds that modulate premature translation termination and/or nonsense-mediated messenger ribonucleic acid (“mRNA”) by interacting with a preselected target ribonucleic acid (“RNA”). In particular, the present invention relates to identifying compounds that bind to regions of the 28S ribosomal RNA (“rRNA”) and analogs thereof. Direct, noncompetitive binding assays are advantageously used to screen libraries of compounds for those that selectively bind to a preselected target RNA. Binding of target RNA molecules to a particular compound is detected using any physical method that measures the altered physical property of the target RNA bound to a compound. The structure of the compound attached to the labeled RNA is also determined. The methods used will depend, in part, on the nature of the library screened. The methods of the present invention provide a simple, sensitive assay for high-throughput screening of libraries of compounds to identify pharmaceutical leads.
    • 本发明涉及通过与预选的靶核糖核酸(“RNA”)相互作用来筛选和鉴定调节过早翻译终止和/或无义介导的信使核糖核酸(“mRNA”)的化合物的方法。 特别地,本发明涉及鉴定结合28S核糖体RNA(“rRNA”)的区域的化合物及其类似物。 直接的非竞争性结合测定法有利地用于筛选选择性结合预选靶RNA的化合物文库。 使用测量与化合物结合的靶RNA的改变的物理性质的任何物理方法检测靶RNA分子与特定化合物的结合。 还测定了附着于标记的RNA的化合物的结构。 所使用的方法部分取决于所筛选图书馆的性质。 本发明的方法提供了用于识别药物引线的化合物文库的高通量筛选的简单,灵敏的测定。
    • 2. 发明申请
    • Methods for identifying small molecules that bind specific RNA structural motifs
    • 鉴定结合特异性RNA结构基序的小分子的方法
    • US20060228730A1
    • 2006-10-12
    • US11347748
    • 2006-02-03
    • Robert RandoEllen Welch
    • Robert RandoEllen Welch
    • C40B40/08
    • G01N33/5308G01N33/58
    • The present invention relates to a method for screening and identifying test compounds that bind to a preselected target ribonucleic acid (“RNA”). Direct, non-competitive binding assays are advantageously used to screen libraries of compounds for those that selectively bind to a preselected target RNA. Binding of target RNA molecules to a particular test compound is detected using any physical method that measures the altered physical property of the target RNA bound to a test compound. The structure of the test compound attached to the labeled RNA is also determined. The methods used will depend, in part, on the nature of the library screened. The methods of the present invention provide a simple, sensitive assay for high-throughput screening of libraries of compounds to identify pharmaceutical leads.
    • 本发明涉及筛选和鉴定结合预选靶核糖核酸(“RNA”)的测试化合物的方法。 直接的非竞争性结合测定法有利地用于筛选选择性结合预选靶RNA的化合物文库。 使用测量与测试化合物结合的靶RNA的改变的物理性质的任何物理方法检测靶RNA分子与特定测试化合物的结合。 还测定了附着于标记的RNA的测试化合物的结构。 所使用的方法部分取决于所筛选图书馆的性质。 本发明的方法提供了用于识别药物引线的化合物文库的高通量筛选的简单,灵敏的测定。
    • 6. 发明授权
    • Oligonucleotide inhibitors of bcl-xL
    • bcl-xL的寡核苷酸抑制剂
    • US07074769B2
    • 2006-07-11
    • US09753169
    • 2001-01-02
    • Cy A. SteinPaul CossumRobert RandoJoshua Ojwang
    • Cy A. SteinPaul CossumRobert RandoJoshua Ojwang
    • A01N43/04A61K31/70C07H21/00C07H21/04
    • C07H21/00C07H19/06C07H19/12C07H19/16
    • This invention provides an antisense oligonucleotide or analog thereof comprising 10 or more contiguous bases or base analogs from the sequence of bases of sequence A, B, C, D, E, F, G, H, I, J, K, L, or M of FIG. 1. This invention also provides the above-described antisense oligonucleotides, wherein the nucleotide sequence comprises nucleotide sequence A, A′, B, C, C′, D, E, E, E′, F, G, G′, H, H′, I, I′, J, K, K′, L, L′, M, or M′ of FIGS. 2A and 2B. This invention also provides the above-described antisense oligonucleotides, wherein the oligonucleotide is encapsulated in a liposome or nanoparticle. This invention also provides the above-described antisense oligonucleotides, wherein the phosphate backbone comprises phosphorothioate bonds. In addition, this invention provides a method of treating cancer, comprising introducing into a tumor cell an effective amount of the the above-described antisense oligonucleotide, thereby reducing the levels of bcl-xL protein produced and treating cancer. This invention also provides the above-described methods, wherein the introducing comprises using porphyrin or lipofectin as a delivery agent. This invention also provides the above-described pharmaceutical compositions, wherein the oligonucleotide is encapsulated in a liposome or nanoparticle. This invention further provides the above-described pharmaceutical compositions, wherein the pharmaceutical composition comprises tetra meso-(4-methylpyridyl)porphine or tetra meso-(anilinium)porphine or a combination thereof.
    • 本发明提供了包含来自序列A,B,C,D,E,F,G,H,I,J,K,L的碱基的10个或更多个连续碱基或碱基类似物的反义寡核苷酸或其类似物, M。 本发明还提供了上述反义寡核苷酸,其中核苷酸序列包含核苷酸序列A,A',B,C,C',D,E,E,E',F,G,G' H',I,I',J,K,K',L,L',M或M' 2A和2B。本发明还提供了上述反义寡核苷酸,其中寡核苷酸被包封在脂质体或纳米颗粒中。 本发明还提供了上述反义寡核苷酸,其中磷酸骨架包含硫代磷酸酯键。 此外,本发明提供了一种治疗癌症的方法,包括向肿瘤细胞中引入有效量的上述反义寡核苷酸,从而降低产生的bcl-xL蛋白的水平和治疗癌症。 本发明还提供了上述方法,其中引入包括使用卟啉或脂质体作为递送剂。 本发明还提供了上述药物组合物,其中寡核苷酸被包封在脂质体或纳米颗粒中。 本发明还提供了上述药物组合物,其中所述药物组合物包含四内消旋 - (4-甲基吡啶基)卟吩或四中 - (苯胺)卟吩或其组合。
    • 7. 发明申请
    • Methods, compositions, formulations, and uses of cellulose and acrylic-based polymers
    • US20050244365A1
    • 2005-11-03
    • US10837153
    • 2004-05-03
    • Mohamed LabibRobert Rando
    • Mohamed LabibRobert Rando
    • A61K31/74C08B3/16C08B11/20C08B13/00C08F216/18C08F222/06C08G63/48
    • C08B11/20A61K8/731A61K31/74A61Q17/005C08B3/16C08B13/00C08F216/18C08F222/06
    • Compositions, formulations, and methods for the treatment or prevention, or decreasing the frequency of transmission of a virus (such as human immunodeficiency virus type 1 (HIV-1), Herpes Simplex virus type 1 (HSV1), or Herpes Simplex Virus Type 2 (HSV2), or other virus), or a bacterial infection (such as Trichomonas vaginalis, Neisseris gonorrhoeae Haemopholus ducreyl, or Chlamydia trachomatis, or other bacterial species), or a fungal infection, using an anionic cellulose- or acrylic-based oligomer, polymer, or copolymer. The present invention also includes administering a therapeutically effective amount of said oligomer, polymer, or copolymer, or a pharmaceutically acceptable salt thereof, or with a pharmaceutically acceptable carrier or diluent, thereof. The invention relies on the unique biochemical substitution of the cellulose or acrylic backbone such that the resultant molecule can remain molecularly dispersed in solution (or gel or other formulation) and mostly dissociated over a wide range of physiological microenvironments, such as the low pH found within the vaginal lumen, preferably from a pH of 14 to below 3.5. These specific substitutions also impart on the resultant molecule potent antiviral, anti-bacterial, and anti-fungal properties. In addition, these compositions can be used as general disinfectants for human use such as in contact lens solutions, mouthwashes, toothpastes, suppositories, or as more generalized disinfectants found in soaps, household cleaning products, paints, water treatments modalities, or can be incorporated into cosmetic, and can be used as vehicles for drug delivery, an adjuvant in a therapeutic formulation, or as a preservative. These compounds can be delivered in a liquid or solid dosage form and can be incorporated into barrier devices such as condoms, diaphragms, or cervical caps, to help prevent the transmission of STDs. The compounds of this invention can also be used in combination therapies with other classes of antiviral, antibacterial, or antifungal agent having similar or differing mechanisms of action including, but not limited to, anionic or cationic polymers, copolymers, or oligomers, surfactants, protease inhibitors, DNA or RNA polymerase inhibitors (including reverse transcriptase inhibitors), fusion inhibitors, cell wall biosynthesis inhibitors, integrase inhibitors, or virus or bacterial attachment inhibitors.
    • 8. 发明申请
    • Cellulose and acrylic based polymers and the use thereof for the treatment of infectious diseases
    • 纤维素和丙烯酸类聚合物及其用于治疗感染性疾病的用途
    • US20070148124A1
    • 2007-06-28
    • US11592479
    • 2006-11-03
    • Mohamed LabibRobert Rando
    • Mohamed LabibRobert Rando
    • A61K31/74C08G63/91
    • C08B11/20A61K8/731A61K31/74A61Q17/005C08B3/16C08B13/00C08F216/18C08F222/06
    • The present invention provides methods for the treatment or prevention of a viral, bacterial, or fungal infection using an anionic cellulose- or acrylic-based polymer, a prodrug thereof, or a pharmaceutically acceptable salt of said anionic cellulose based polymer or acrylic based polymer or prodrug of either. The present invention also provides pharmaceutical compositions comprising an anionic cellulose or acrylic based polymer, a prodrug thereof, or a pharmaceutically acceptable salt of said anionic cellulose-based polymer or prodrug. The present invention further provides combination therapies for the treatment or prevention of a viral, bacterial, or fungal infection using an anionic cellulose or acrylic-based polymer, a prodrug thereof, or a pharmaceutically acceptable salt of said anionic cellulose based or acrylic based polymer or prodrug of either and one or more anti-infective agents.
    • 本发明提供使用阴离子纤维素或丙烯酸类聚合物,其前药或所述阴离子纤维素基聚合物或丙烯酸类聚合物的药学上可接受的盐来治疗或预防病毒,细菌或真菌感染的方法,或 二者的前药。 本发明还提供包含阴离子纤维素或丙烯酸类聚合物,其前药或所述阴离子纤维素基聚合物或前药的药学上可接受的盐的药物组合物。 本发明还提供了使用阴离子纤维素或丙烯酸类聚合物,其前药或所述阴离子纤维素基或丙烯酸类聚合物的药学上可接受的盐治疗或预防病毒,细菌或真菌感染的组合疗法,或 任一种和一种或多种抗感染剂的前药。