Patents Examined by J. Oliver Wilson
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Patent number: 5457191Abstract: This invention relates to compounds based on the 3-deazapurines ring system and to methods for making such compounds. The invention also generally relates to the field of "antisense" agents, agents that are capable of specific hybridization with a nucleotide sequence of an RNA. The 3-deazapurine-containing compounds of this invention can be useful for modulating the activity of RNA when incorporated into oligonucleotides. Oligonucleotides and their analogs are used for a variety of therapeutic and diagnostic purposes, such as treating diseases, regulating gene expression in experimental systems, assaying for RNA and for RNA products through the employment of antisense interactions with such RNA, diagnosing diseases, modulating the production of proteins and cleaving RNA in site specific fashions.Type: GrantFiled: March 5, 1993Date of Patent: October 10, 1995Assignee: ISIS Pharmaceuticals, Inc.Inventors: P. Dan Cook, Oscar L. Acevedo, Robert S. Andrews
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Patent number: 5440040Abstract: The present invention is directed to compounds of formula (I), ##STR1## wherein R.sup.1 is OH, NH.sub.2 ; R.sup.2 is a heteroaromatic or aromatic substituent; R.sup.3 is H, OH, F, OCH.sub.3 ; R.sup.4 is H, F, OH or an ether or ester residue thereof, OCH.sub.3, CN, C.dbd.CH, N.sub.3 ; R.sup.5 is OH or an ether or ester residue thereof including mono, di- and triphosphate esters (.alpha.), wherein n is 0 or 1 and M is hydrogen or a pharmaceutically acceptable counterion such as sodium, potassium, ammonium or alkylammonium; and pharmaceutically acceptable salts thereof; and pharmaceutical compositions comprising said compounds can be used for therapeutic treatment of virus infections. The present invention is also directed to compounds of formula (I'), ##STR2## wherein R.sup.1 and R.sup.2 are as defined above, as intermediates.Type: GrantFiled: January 18, 1991Date of Patent: August 8, 1995Assignee: Medivir ABInventor: Salo Gronowitz
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Patent number: 5426183Abstract: A catalytic stereoselective glycosylation process for preparing beta- and alpha-anomer enriched 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides involving reacting an alpha- or beta- anomer enriched 2-deoxy-2,2-difluorocarbohydrate or 2-deoxy-2-fluorocarbohydrate with at least a molar equivalent of a nucleobase derivative in an inert solvent and in the presence of a catalyst.Type: GrantFiled: April 7, 1993Date of Patent: June 20, 1995Assignee: Eli Lilly and CompanyInventor: Douglas P. Kjell
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Patent number: 5420117Abstract: This invention provides a 5-substituted uridine derivative of the formula ##STR1## wherein X is F or CF.sub.3, R.sub.1 and R.sub.2 each represent a group --OSi--(R.sub.4)(R.sub.5)(R.sub.6) (wherein R.sub.4, R.sub.5 and R.sub.6 represent C.sub.1 -C.sub.10 alkyl or the like), OH, aminoacyloxy group wherein the amino group may be substituted with lower alkyl group or carboxylalkylcarbonyloxy group, R.sub.3 is a group --OSi(R.sub.4)(R.sub.5)(R.sub.6), H, OH, aminoacyloxy group wherein the amino group may be substituted with lower alkyl group, or carboxylalkylcarbonyloxy group, and at least one of R.sub.1, R.sub.2 and R.sub.3 is a group --OSi--(R.sub.4)(R.sub.5)(R.sub.6), with the proviso that when X is fluorine atom, R.sub.3 is not hydrogen, and an intermediate for the preparation thereof, preparation processes of the derivative and anti-tumor agent containing the derivative as an active ingredient.Type: GrantFiled: October 19, 1992Date of Patent: May 30, 1995Assignee: Taiho Pharmaceutical Co., Ltd.Inventors: Tadafumi Terada, Katsuhiko Fujimoto, Junichi Yamashita, Mitsugi Yasumoto, Setsuo Takeda, Junji Uchida, Konstanty Wierzba, Yuji Yamada
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Patent number: 5416203Abstract: An oligonucleotide conjugated to a steroid the oligonucleotide comprising: ##STR1## wherein A is selected from the group consisting of an aliphatic alkyl, branched aliphatic alkyl and an alkyl (branched) chain of 2 to 18 carbon atoms, R is selected from the group consisting of H and lower alkyl up to 12 carbon atoms; B is a naturally occurring base, the steroid is bound to the oligonucleotide utilizing the naturally occurring bases through an (-oxycarbonyl-amino)-decylamine-moiety, and NUC is an oligonucleotide.Type: GrantFiled: July 26, 1993Date of Patent: May 16, 1995Assignee: Northwestern UniversityInventor: Robert L. Letsinger
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Patent number: 5410068Abstract: The invention pertains to compounds and methods for the reversible modification of natural products, biopolymers or synthons for natural products or biopolymers, such as nucleosides, nucleotides, and oligonucleosides. The modification enables one to perform a variety of chemistries on these compounds, yet can be removed to regenerate functional groups on the natural products, biopolymer or synthon of interest.Type: GrantFiled: October 23, 1989Date of Patent: April 25, 1995Assignee: PerSeptive Biosystems, Inc.Inventors: James M. Coull, Brian Gildea, Hubert Koester
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Patent number: 5393744Abstract: A compound having the following formula I: ##STR1## in which: R' represents a hydrogen atom or an azido group,alc represents an alkyl group of 1 to 4 carbon atoms, an alkoxy group of 1 to 4 carbon atoms or an amino group.Type: GrantFiled: January 29, 1990Date of Patent: February 28, 1995Assignee: Institut PasteurInventors: Tam Huynh Dinh, Catherine Gouyette, Bernadette Dupraz, Jean Igolen, Nathalie Savatier, Jean-Francois Nicolas, Francoise Barre-Sinoussi
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Patent number: 5344823Abstract: A new antitumor antibiotic designated BMY-41219 is produced by fermentation of Saccharothrix aerocolonigenes ATCC 39243. The BMY-41219 antibiotic exhibits antitumor activity.Type: GrantFiled: February 6, 1992Date of Patent: September 6, 1994Assignee: Bristol-Myers Squibb CompanyInventors: Kin S. Lam, Leonard A. McDonald, Jacqueline Mattei, Salvatore Forenza, James A. Matson
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Patent number: 5321131Abstract: Disclosed are compounds consisting of a plurality of nucleosides which are covalently linked by at least one aminoalkylphosphoramidate linkage of the formula ##STR1## wherein n=2 to 6 and Nu.sub.1 and Nu.sub.2 represent nucleoside phosphates.Type: GrantFiled: March 8, 1990Date of Patent: June 14, 1994Assignee: Hybridon, Inc.Inventors: Sudhir Agrawal, Jinyan Tang
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Patent number: 5302707Abstract: Compositions and methods for producing the activating moiety of a site-directed catalytic antibody are provided. The activating moiety serves to enhance the rate of chemical reactions involving the conversion of the prodrug to one or more active substrates or drugs. The activating moiety typically comprises a catalytic antibody. Compositions and methods for producing the catalytic antibodies, as well as the haptens which are used to generate the catalytic antibodies, are provided. Compositions and methods for producing the prodrugs are also provided.Type: GrantFiled: March 26, 1992Date of Patent: April 12, 1994Assignee: Affymax Technologies N.V.Inventors: David A. Campbell, Mark A. Gallop
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Patent number: 5284834Abstract: This invention comprises a series of N.sup.6 -substituted adenosine analogues bearing functionalized chains for the covalent attachment to probes or solid supports. In these compounds coronary vasodilation in the open thorax dog model, typical of A.sub.2 -adenosine receptor agonists, is shown. The potency is modulated by distal structural changes in the chain, with the highest A.sub.2 -potency observed for two methylamides, a primary amine congener, and a biotin conjugate. These compounds have antihypertensive activity and certain components are charged and are excluded from crossing the blood-brain barrier.Type: GrantFiled: August 6, 1992Date of Patent: February 8, 1994Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Kenneth A. Jacobson, Kenneth L. Kirk, John W. Daly
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Patent number: 5283353Abstract: The invention resides in oligosaccharide derivatives which are obtained by the enzynmatic cleavage of carbohydrates linked to proteins through asparagine groups. The oligosaccharide moieties of the instant invention are 1-amino-1-deoxyoligosaccharide compounds which are cleaved from a glycoprotein with an aminohydrolase enzyme, wherein the amino group of the oligosaccharide is subsequently substituted with a fluorescent reporter compound. The compounds of the instant invention are characterized by the glycosylamine bonds exhibiting less than 10% hydrolysis at 25.degree. C. in aqueous solution over a two days at pH values between 4-10.Type: GrantFiled: June 5, 1990Date of Patent: February 1, 1994Assignees: Genzyme Corporation, Purdue Research FoundationInventors: James R. Rasmussen, John M. Risley, Robert L. Van Etten
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Patent number: 5264561Abstract: The instant invention is drawn to a method for manufacturing 2',3'-dideoxy-2',3'-didehydronucleoside compounds by reacting a ribonucleoside derivative wherein the hydroxyl in the 5'-position of the furanose ring of said ribonucleoside is protected by a silyl protective group, with an acid anhydride such as acetic anhydride in the presence of a catalyst such as hydrous zirconium oxide, and then subjecting the reaction product to decarboxylation. The decarboxylation can be effected by heating the reaction product. This method can be performed in a single step, and requires no reagents which are expensive or chemicals which should be handled with care. Hence, it serves to manufacture 2',3'-dideoxy-2',3'-didehydronucleosides easily at low cost.Type: GrantFiled: March 20, 1992Date of Patent: November 23, 1993Assignees: Japan Tobacco Inc., Yuki Gosei Kogyo Co, Ltd.Inventors: Takashi Ebata, Hajime Matsushita, Nobuhiro Mizutani, Junji Ohki, Junko Tanaka, Hiromi Kaibara, Kazuo Itoh
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Patent number: 5264562Abstract: Oligonucleotide analogs wherein one or more phosphodiester linkages between adjacent nucleotides are replaced by an formacetal/ketal type linkage are resistant to nucleases and do not need to exhibit the diastereomerism characteristic of many other oligonucleotide analogs, and thus are capable of strong hybridization to target RNA or DNA. These oligonucleotide analogs are useful in therapies which modulate gene expression using "antisense" or other specifically binding oligomers.Type: GrantFiled: April 24, 1991Date of Patent: November 23, 1993Assignee: Gilead Sciences, Inc.Inventor: Mark Matteucci
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Patent number: 5264564Abstract: Oligonucleotide analogs wherein one or more phosphodiester linkages between adjacent nucleotides are replaced by an formacetal/ketal type linkage are resistant to nucleases and do not need to exhibit the diastereomerism characteristic of many other oligonucleotide analogs, and thus are capable of strong hybridization to target RNA or DNA. These oligonucleotide analogs are useful in therapies which modulate gene expression using "antisense" or other specifically binding oligomers.Type: GrantFiled: July 30, 1990Date of Patent: November 23, 1993Assignee: Gilead SciencesInventor: Mark Matteucci
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Patent number: 5250673Abstract: Novel 2'-deoxy-5-substituted uridine derivative represented by the general formula, ##STR1## wherein R.sub.1 is a hydrogen atom, a benzoyl group or a tetrahydrofuranyl group; R.sub.2 is a fluorine atom or a trifluoromethyl group; and any one of R.sub.3 and R.sub.4 is a hydrogen atom and the other one is an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, a benzyl group having as the substituents selected from the group consisting of a halogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms and a nitro group, or an alkyl group having 1 to 3 carbon atoms having one or two phenyl groups as the substituents.The novel 2'-deoxy-5-substituteduridine derivative possesses excellent antitumor activity with less toxicity, thus it is useful as antitumor agent.Type: GrantFiled: October 17, 1989Date of Patent: October 5, 1993Assignee: Taiho Pharmaceutical Company, Ltd.Inventors: Setsuro Fujii, Jun-ichi Yamashita, Hiroshi Matsumoto, Setsuo Takeda, Tadafumi Terada, Mitsugi Yasumoto, Norio Unemi
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Patent number: 5243042Abstract: The invention relates to antibacterially active 5-amino-3-(.beta.-D-ribofuranosyl)imidazo[4,5-d][1,3]thiazin-7(3H)-one, also referred to as 1-thiaguanosine, a composition and method comprising the same and processes and intermediates for the preparation of 1-thiaguanosine and 5-amino-3-(.beta.-D-ribofuranosyl)imidazo[4,5-d][1,3]oxazin-7(3H)-one, also referred to as oxanosine, a known compound.Type: GrantFiled: August 2, 1990Date of Patent: September 7, 1993Assignee: Hoffmann-La Roche Inc.Inventors: Kin-Chun Luk, Dennis D. Keith
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Patent number: 5233031Abstract: The present invention provides a series of cytotoxic phosphoramidate analogs of 5-fluoro-2'-deoxyuridine of the general formula (I): ##STR1## wherein R.sup.1 is H, F or (C.sub.1 -C.sub.4)alkyl; R.sup.2 is CH.sub.2 CH.sub.2 X wherein X is Cl, Br, I or p-toluenesulfonyl; R.sup.3 is (C.sub.1 -C.sub.4)alkyl or CH.sub.2 CH.sub.2 X wherein X is Cl, Br, I or p-toluenesulfonyl; or wherein R.sup.2 and R.sup.3, taken together with the N atom, can be a 5- or 6-membered heterocyclic ring which is aliphatic or aliphatic interrupted by a ring oxygen or a second ring nitrogen; R.sup.4 is H, one equivalent of a pharmaceutically-acceptable cation or (4,4,6-trimethyltetrahydro-1,3-oxazin-2-yl)ethyl, and the pharmaceutically-acceptable salts thereof.Type: GrantFiled: September 23, 1991Date of Patent: August 3, 1993Assignee: University of RochesterInventors: Richard F. Borch, Kristin M. Fries
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Patent number: 5231191Abstract: The invention provides a novel cleavage reagent for hydrolysing base-labile linking groups between a solid phase support and oligonucleotides. The cleavage reagent comprises a lower alkyl alcohol, water, and a non-nuccleophilic hindered alkylamine containing from 3 to 6 carbon atoms in a ratio of about 1:1:1 to about 1:3:1, respectively. An important property of the cleavage reagent is that it preserves the fluorescent characteristics of rhodamine dyes during cleavage, thereby making it possible to completely synthesize rhodamine-labeled oligonucleotides by solid phase methods. Rhodamine phosphoramidites are provided to further enhance the efficiency of synthesizing rhodamine-labeled oligonucleotides by such methods.Type: GrantFiled: October 22, 1990Date of Patent: July 27, 1993Assignee: Applied Biosystems, Inc.Inventors: Sam L. Woo, Steven M. Menchen, Steven Fung
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Patent number: 5231175Abstract: A process for the preparation of 2' and 3'-(halo-substituted)-2',3'-dideoxy nucleosides by reacting a protected anhydrothymidine compound with a halogenating composition containing a transition metal or lanthanide compound.Type: GrantFiled: February 10, 1992Date of Patent: July 27, 1993Assignee: American Cyanamid CompanyInventors: Kenneth E. Green, David M. Blum, Michael P. Trova