Antiviral Agents Bulletin, Oct. 1995, U.S. Patents


Highlights of U.S. Patents

Highlights of recently issued U.S. patents for which abstracts/claims are presented below include:

Antiviral Agents
- Indolocarbazole inhibitors of protein kinases useful for treatment of viral infections patented by Godecke AG (5,438,050).
- Pyrimidine intermediates for production of antiviral agents patented by Medivir AB (5,440,040).
- Vaginal barrier film-forming foams containing cholic acid and salts of cholic acid as active ingredients for prevention of sexually transmitted diseases patented by Safe Sex Products Licensing Societe Anonyme (5,439,685).
- Iodine-based solutions for sterilization of tissue and medical device implants patented by Carbomedics, Inc. (5,437,287).
- Nontoxic germicide/disinfectant formulations patented by Rost, Inc. (5,441,723).
- 1-beta-D-Arabinofuranosyl-(E)-5-(2-halogenovinyl)uracil derivatives patented by Yamasa Shoyu K.K. (5,446,031).
Anti-HIV and Antiretroviral Agents
- HIV protease inhibitors based on peptide mimics having a constrained peptide backbone conformation patented by SmithKline Beecham Corp. (5,438,118).
- Cosalane and related compounds with activity against HIV patented by the Purdue Research Foundation and U.S. Public Health Service/NIH (5,439,899).
- Synthetic HIV-1-based polypeptides for topical inhibition of HIV-infection patented by the New York Blood Center (5,444,044).
- Compounds which inhibit HIV and its activation patented by Warner-Lambert Co. (5,444,085).
- Water soluble hydroxy-substituted texaphyrins for photoinactivation of HIV and HIV-infected cells patented by the University of Texas System (5,439,570).
- Dextrin sulfate derivatives for treatment of HIV and retroviral infections patented by ML Labs. (5,439,892).
- 2',3'-Dideoxy-3'-fluoronucleosides with antiretroviral activity patented by Medivir AB (5,446,029).
Anti-Herpesvirus Agents
- Cytomegalovirus (CMV) antisense oligonucleotides including ISIS 2922 patented by Isis Pharmaceuticals, Inc. (5,442,049). [See article above reporting efficacy for treatment of CMV retinitis in AIDS patients].
- Peptides for treatment or prevention of herpes simplex virus (HSV) infections patented by Houghten Pharmaceuticals Inc. (5,441,936).
- Calix(n)arene derivatives for prevention of herpes simplex virus (HSV) infections patented by Genelabs Technologies, Inc. (5,441,983).
Anti-Hepatitis Agents
- 2',3'-Dideoxy-3'-fluoronucleosides useful for treatment of hepatitis B virus (HBV) infections patented by Medivir AB (5,446,029).
- beta-D-Dioxolane nucleoside enantiomers useful for treatment of hepatitis B virus (HBV) infections patented by Emory University (5,444,063).
HIV Vaccines
- Non-infectious recombinant HIV particles for vaccine use patented by Connaught Labs. Ltd., a subsidiary of Rhone-Poulenc Rorer (5,439,809).
- Recombinant HIV gag-env fusion proteins for vaccines and diagnostics patented by Korea Green Cross Corp. (5,443,828).
- Human HIV gp120 monoclonal antibodies patented by the Univ. of Arizona and Teijin Limited (5,445,960).
Other Viral Vaccines and Vectors
- The entire rubella virus gene sequence and clones useful for vaccines patented by Georgia State Research Foundation, Inc. (5,439,814).
- A method for direct molecular cloning of poxviruses patented by Immuno AG (5,445,953).
- Hepatitis delta virus polypeptides for vaccines and immunodiagnostics patented by the U.S. Public Health Service/CDC (5,445,932).
- Recombinant papillomavirus capsid proteins that self-assemble into empty viral capsid structures useful for human papillomavirus (HPV) vaccines patented by the U.S. Public Health Service/NIH (5,437,951). [Discussed in the July 1993 Bulletin, p. 203].
- A cDNA clone, 20E, and polypeptides from a new non-A, non-B, non-C hepatitis virus patented by Dade International Inc. (5,437,974).
- Poxvirus vectors patented by Duke Univ. (5,443,964).
- Recombinant infectious laryngotracheitis virus glycoprotein B and its incorporation into avipoxvirus vectors for poultry vaccines patented by the University of Delaware (5,443,831).
- A method for packaging RNA in recombinant plant pseudovirus particles patented by Rutgers University (5,443,969).
- A chicken hepatocyte-derived cell line for culture of infectious laryngotracheitis virus (ILTV) patented by Solvay Animal Health, Inc. (5,443,982).
Vaccine Adjuvants and Carriers
- Modified saponins derived from Quillaja saponaria patented by Cambridge Biotech Corp. (5,443,829). [This includes coverage for QS-21 Stimulon adjuvant licensed to numerous companies for vaccine adjuvant use. See the November 1992 Bulletin (p. 333) and other articles about QS-21 Stimulon adjuvant].
- A method for mucosal immunization by mixing antigens with particulate hydroxylated calcium phosphate capable of absorption across mucous membranes patented by Institut Swisse de Recherches Experimentales sur le Cancer (5,443,832).
Immune Stimulants and Modulators
- Fused cycloalkylimidazopyridines that induce interferon-alpha for treatment of viral infections patented by Minnesota Mining & Mfg. Co./3M Co. (5,444,065).
- Aloe-derived acemannan with immune stimulating activity patented by Carrington Labs., Inc. (5,441,943). [Currently in clinical trials for treatment of HIV and other viral infections. See October 1992 Bulletin (p. 291)].
- Crystalline metal-interferon alpha-2 complexes useful for subcutaneous injection patented by Schering Corp. (5,441,734).
- 2',3'-Dideoxy-2',3'-didehydro-7,8-disubstituted guanosines with immune stimulating activity patented by The Scripps Research Institute (5,441,942).
- Cystine derivatives with immune stimulating activity patented by Astra AB (5,441,976).
Antisense Oligonucleotides, Nucleosides and Nucleotides
- Cytomegalovirus antisense oligonucleotides including ISIS 2922 (discussed in a news story above) patented by Isis Pharmaceuticals, Inc. (5,442,049).
- 3-Nitropyrrole nucleoside and its incorporation into oligonucleotides patented by individuals (5,438,131).
- Production of 2-amino-6-halogenopurines useful as intermediates for production of antiviral agents patented by Sumika Fine Chemicals Co., Ltd. (5,440,037).
- beta-D-Dioxolane nucleoside enantiomers useful for treatment of hepatitis B virus (HBV) infections patented by Emory University (5,444,063).
- 1-beta-D-Arabinofuranosyl-(E)-5-(2-halogenovinyl)uracil derivatives patented by Yamasa Shoyu K.K. (5,446,031).
Viral Diagnostics
- Recombinant hepatitis C virus (HCV) peptide antigens patented by Genelabs Technologies, Inc. (5,443,965).
- Immunogenic peptides useful for detection of retroviruses patented by Genetic Systems Corp. (5,439,792).

U.S. Patents

Each month the Antiviral Agents Bulletin presents abstracts of recently issued antiviral and virus-related U.S. patents. Patents are listed in numerical order. The abstract and major claim are generally presented as officially issued by the Patent and Trademark Office. Abstracts, claims, graphics and gene sequences may be deleted or edited for clarity.

Full copies of U.S. patents may be requested through your in-house library, local research libraries, commercial document delivery services, or from the Patent Office itself. Nearly every state in the U.S. has one or more patent depository libraries with copies of all U.S. patents, patent databases, and search assistance available.

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Sterilization of Tissue Implants Using Iodine

Assignee: Carbomedics, Inc.

Patent No.: 5,437,287
Inventors: Phillips, R.E.; Moore, M.A.; Russell, R.L.; Cheung, D.

Abstract:
The present invention provides an iodine-based solution, and a method of using that solution, which sterilizes tissue implants without denaturing the proteins in the implant and without inducing calcification of the implant in vivo. Preferably, the tissue implants sterilized using the present invention are fixed without using glutaraldehyde. Most preferably, the tissue implants are fixed by photooxidation.
Claim:
A method for sterilizing a medical device intended for implantation inside the body of a mammal comprising the steps of: providing an implant comprised at least in part of excised proteinaceous tissue; and incubating said implant in a germicidal solution comprising elemental iodine at a concentration, a temperature, and for a time effective to sterilize said implant without damaging said implant, said germicidal solution having a pH between about 5.0-6.8.
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Self-Assembling Recombinant Papillomavirus Capsid Proteins

Assignee: U.S. Public Health Service (NIH)

Patent No.: 5,437,951
Inventors: Lowy, D.R.; Schiller, J.T.; Kirnbauer, R.

Abstract:
Recombinant papillomavirus capsid proteins that are capable of self-assembly into capsomer structures and viral capsids that comprise conformational antigenic epitopes are provided. The capsomer structures and viral capsids, consisting of the capsid proteins that are expression products of a bovine, monkey or human papillomavirus L1 conformational coding sequence proteins, can be prepared as vaccines to induce a high-titer neutralizing antibody response in vertebrate animals. The self-assembling capsid proteins can also be used as elements of diagnostic immunoassay procedures for papillomavirus infection.
Claim:
A genetic construct comprising a papillomavirus L1 gene wherein said construct directs recombinant expression in a transformed eukaryotic host cell of at least one papillomavirus L1 epitope by self-assembly of papillomavirus capsids comprising a L1 polypeptide, wherein said L1 polypeptide is characterized as having the amino acid sequence encoded by the nucleotide sequence of Seq. ID no. 2 [not shown].
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DNA Sequence and Encoded Polypeptide Useful in the Diagnosis of Hepatitis Disease

Assignee: Dade International Inc.

Patent No.: 5,437,974
Inventors: Ryan, T.E.; Saeed, B.; Kieselburg, M.K.; Byrne, R.E.; Stevens, P.W.; Arima, T.; Todd, J.

Abstract:
A novel cDNA clone, 20E, has been isolated and characterized as encoding a previously unknown polypeptide antigen recognized by antibodies in the serum of certain patients with non-A non-B hepatitis (NANBH). The nucleic acid sequence is not represented in the genome of the hepatitis C virus (HCV). Neither is the nucleic acid sequence represented in the human genome. The data suggest that the RNA sequence corresponding to clone 20E is contained within the genome of an external infective agent other than HCV, and therefore may represent an additional etiologic agent or contributing factor to the development of NANBH in human patients. The 20E nucleic acid and corresponding polypeptide and respective variants thereof will be useful in a variety of procedures directed at prevention and diagnosis of NANBH.
Claim:
A polypeptide as defined in the Sequence Listing by Seq. ID No. 7 [not shown].
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Indolocarbazole Derivatives, Processes for Their Preparation and Compositions Containing Them

Assignee: Godecke AG

Patent No.: 5,438,050
Inventors: Kleinschroth, J.; Hartenstein, J.; Barth, H.; Schachtele, C.; Rudolph, C.; Weinheimer, G.; Osswald, H.

Abstract:
New indolocarbazoles of formula [see claim] or a pharmaceutically acceptable salt thereof, processes for their preparation, compositions containing, and methods for using the composition for the inhibition of protein kinases, such as protein kinase C, for the prevention and/or treatment of heart and blood vessel diseases such as thromboses, arterioscleroses, hypertension, or for inflammatory processes, allergies, cancers, viral diseases, and certain degenerative damages of the central nervous system are disclosed.
Claim:
A compound:







or a pharmaceutically acceptable salt thereof wherein R1 and R2 taken together are alkylene of from 2-4 carbon atoms unsubstituted or substituted by hydroxyl, alkoxy of 1-4 carbon atoms or amino which is unsubstituted or is mono- or di-substituted by benzyl or by alkyl of from 1-4 carbon atoms; X and Y are each hydrogen or one is hydrogen and the other is hydroxyl or alkoxy of from 1-4 carbon atoms; R3, R4, R5, R6, and R10 are each independently hydrogen, bromine, chlorine, methyl, ethyl, hydroxyl methoxy, 2-aminoethoxy, 3-aminopropoxy, 1-amino-2-propoxy, 2-dimethylaminoethoxy, 3-dimethylamino-1-propoxy, 3-dimethylamino-2-propoxy, or 2-diethylaminoethoxy; R6 and R7 are hydrogen with the proviso that at least one and as many as four of R3 to R4 are not hydrogen.
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HIV Protease Inhibitors

Assignee: SmithKline Beecham Corp.

Patent No.: 5,438,118
Inventors: Callahan, J.F.; Huffman, W.F.; Moore, M.L.; Newlander, K.A.

Abstract:
Peptide mimics, having a constrained peptide backbone conformation, are HIV protease inhibitors. A compound of this invention is, for example, 3-benzyl-5(alaninyl-1-aminoethyl)-2,3,6,7-tetrahydro-N-azepinyl-2-propionyl-valinyl-valinyl methyl ester.
Claim:
A compound of the formula:





in which D is A' or X is:



V and W are each independently N or C; one of Ñ indicated bonds is a double bond and the other is a single bond or, when W is N, Ñ both are single bonds; R is hydrogen or OH, or when W is N, R is =O; R1 is C1-6 alkyl, (CH2)n Ar, (CH2)n Het, (CH2)n CONHR', (CH2)n OR' or (CH2)n SR'; R2 is: a) 2H, when V is N; b) OH, OR', =CHR' or NHR', when c) =O, when W and V are both N; A' is hydrogen, C1-6 alkyl, benzyl, halobenzyl, dihalobenzyl or tosyl; A is hydrogen or an amino protecting group; B is a D or L amino acid or is a covalent bond; Q is a D or L amino acid selected for Ser, Thr, Asp, His, Cys, Arg and Ala; G is Gly, Asn, Ala, beta-Ala, Arg, Gly, Ile, Leu, Lys, Ser, Thr, Val, Met or His; Y and E are each independently a D or L amino acid; a, b, c and d are each independently 0 or 1; Z is hydrogen (CH2)n OR', (CH2)n NHR', C1-6 alkyl, (CH2)n SR', O(CH2)p OR', NH(CH2)p OR', O(CH2)p SR' or NH(CH2)p SR'; R3 and R4 are each independently hydrogen, C1-6 alkyl, (CH2)n Het, (CH2)n Ar, (CH2)n CONHR', (CH2)n OR', (CH2)n SR', (CH2)n NHR', CH(OH)CH3 or (CH2)3 NHC(=NH)NH2; R' is hydrogen, C1-4 alkyl or benzyl; n is 0 to 3; p is 1 to 3; Het is indolyl or imidazolyl, or pyridyl or thienyl optionally substituted by one or two C1-4 alkyl, OR' or SR'; and Ar is phenyl optionally substituted by one or two C1-4 alkyl, OR', NO2, NH2, halogen, CF3 or SR'; or a pharmaceutically acceptable salt thereof.
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3-Nitropyrrole Nucleoside

Assignee: Unassigned or Assigned to Individuals

Patent No.: 5,438,131
Inventors: Bergstrom, D.E.; Andrews, P.C.; Nichols, R.; Zhang, P.

Abstract:
Oligonucleotides having at least ten nucleosides, at least two of which are selected from the group consisting of A, T, C and G, and at least one nucleoside being a universal nucleoside of the formula [not shown] wherein: each Rn is H, OH, F or OCH3; Z is a member of the group consisting of O, S and CH2; and B is a five-membered, heterocyclic base having at least two double bonds, and further having an electron withdrawing group bonded thereto, said base with electron withdrawing group being represented by the formula [not shown] wherein: said base with electron withdrawing group is bonded at X4 to the sugar portion of the nucleoside; X1, X3 and X5 are each members of the group consisting of N, O, C, S and Se; X2 and X4 are each members of the group consisting of N and C; and W is a member of the group consisting of F, Cl, Br, I, O, S, OH, SH, NH2, NO2, C(O)H, C(O)NHOH, C(S)NHOH, NO, C(NOCH3)NH2, OCH3, SCH3, SeCH3, ONH2, NHOCH3, N3, CN, C(O)NH2, C(NOH)NH2, CSNH2 and CO2H.
Claim:
A nucleoside of the formula:






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Water Soluble Texaphyrin Metal Complexes for Singlet Oxygen Production

Assignee: University of Texas System

Patent No.: 5,439,570
Inventors: Sessler, J.L.; Hemmi, G.W.; Mody, T.D.

Abstract:
The present invention involves water soluble hydroxy-substituted texaphyrins retaining lipophilicity, the synthesis of such compounds and their uses. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Various metal (e.g., transition, main group, and lanthanide) complexes of the hydroxy-substituted texaphyrin derivatives of the present invention have unusual water solubility and stability. They absorb light strongly in a physiologically important region (i.e., 690-880 nm). They have enhanced relaxivity and therefore are useful in magnetic resonance imaging. They form long-lived triplet states in high yield and act as photosensitizers for the generation of singlet oxygen. Thus, they are useful for inactivation or destruction of human immunodeficiency virus (HIV-1), mononuclear or other cells infected with such virus as well as tumor cells. They are water soluble, yet they retain sufficient lipophilicity so as to have greater affinity for lipid rich areas such as atheroma and tumors. They may be used for magnetic resonance imaging followed by photodynamic tumor therapy in the treatment of atheroma and tumors. These properties, coupled with their high chemical stability and appreciable solubility in water, add to their usefulness.
Claim:
A method of light induced singlet oxygen production comprising: administering to a host a water soluble hydroxy-substituted aromatic pentadentate expanded porphyrin analog metal complex retaining lipophilicity and having intrinsic biolocalization selectivity; and exposing the host to light in the presence of oxygen to produce singlet oxygen.
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Pharmaceutical Composition for the Prevention of Sexually Transmitted Diseases

Assignee: Safe Sex Products Licensing Societe Anonyme

Patent No.: 5,439,685
Inventor: Augros, J.J.

Abstract:
A pharmaceutical composition for the prevention of sexually transmitted diseases, intended to be contacted with a mucosa. The composition contains, on the one hand, at least one constituent active against the viruses and bacteria responsible for the said sexually transmitted diseases and, on the other hand, a product inhibiting the penetration of the active constituent across a mucosa, in combination with a pharmaceutically acceptable vehicle adapted to the topical administration of this composition. Advantageously, the product inhibiting penetration is a film-former capable of forming a film with which the active constituent or constituents are associated.
Claim:
A pharmaceutical composition for preventing the transmission of sexually transmitted diseases, comprising in combination, a vaginal tampon containing an active agent being selected from the group consisting of cholic acid and salts of cholic acid; and dimethylpolysiloxane in the form of an emulsion and being present in an amount effective to form a substantially uniform film coating on the vaginal mucosa and to inhibit penetration of said active agent across the vaginal mucosa; wherein said vaginal tampon comprises an open cell foam.
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Cysteine Thiol-Protected Peptides for Use in Immunoassays

Assignee: Genetic Systems Corp.

Patent No.: 5,439,792
Inventors: Patrick, F.; Monji, N.; Montana, J.P.

Abstract:
Peptides immunoreactive with antibodies to native proteins, and which have at least two cysteine residues that contribute to mimicking an epitope of the protein, are prepared with the cysteine thiol groups protected. When deprotected, the peptides have enhanced immunoreactivity. The peptides are particularly useful for detecting antibodies or antigens associated with retroviruses, including the clinically important lymphotropic retroviruses HIV-1, HIV-2, HTLV-I, and HTLV-II.
Claim:
A method for preparing a peptide coated solid phase for immunological detection and/or quantitation of antibody to a cyclic viral protein epitope, comprising: (a) synthesizing the peptide which comprises an amino acid sequence of 10 to 50 amino acids and having two Cys residues which are separated from each other by at least about three but fewer than twenty non-Cys amino acid residues; (b) protecting thiol groups of the cysteine encoded within the peptide sequence by chemically reversible means resistant to highly acidic cleavage to form a protected peptide composition; (c) immobilizing the protected peptide composition on a solid phase; (d) removing the chemically reversible protection means from the immobilized peptide composition; and (e) incubating the immobilized peptide composition under conditions conducive to the formation of disulfide bonds between the Cys residues.
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Non-Infectious HIV Particles Lacking Long Terminal Repeats

Assignee: Connaught Labs. Ltd.

Patent No.: 5,439,809
Inventors: Haynes, J.; Klein, M.H.; Rovinski, B.; Cao, S.X.

Abstract:
An immunogenic HIV retrovirus-like particle which is non-infectious and non-replicating and which is useful as a candidate vaccine component against HIV infection, is produced by genetic engineering. A DNA molecule comprising the HIV genome devoid of long terminal repeats is incorporated into an expression vector, which is introduced into mammalian cells for expression of the HIV retrovirus-like particle.
Claim:
A genetically-engineered, non-infectious, non-replicating and immunogenic HIV retrovirus-like particle, produced by: incorporating into an expression vector a DNA molecule comprising the HIV genome devoid of long terminal repeats, introducing the expression vector into mammalian cells, and expressing said DNA molecule in said mammalian cells to produce said HIV retrovirus-like particle.
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DNA Encoding Infectious Rubella Virus

Assignee: Georgia State Research Foundation, Inc.

Patent No.: 5,439,814
Inventors: Frey, T.K.; Dominguez, G.; Wang, C.-Y.

Abstract:
The entire rubella virus genomic RNA has been sequenced. An infectious cDNA clone has been constructed. Mutants of this clone that are rendered non-pathogenic are used as vaccines to vaccinate humans, including pregnant or older women, with decreased risk of causing fetal infection, autoimmune disease or neurological symptoms.
Claim:
An isolated DNA molecule comprising a nucleotide sequence encoding an infectious rubella virus.
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Dextrin Sulphates as Anti HIV-1 Agents and Composition

Assignee: ML Laboratories

Patent No.: 5,439,892
Inventor: Davies, D.S.

Abstract:
The invention provides an agent against HIV-1 and related viruses, the agent being or including dextrin sulphate containing at most two sulphate groups per glucose unit. The invention also provides a composition containing such an agent, and the use of the agent or composition against HIV-1 and related viruses. By restricting the degree of substitution of the dextrin sulphate to a maximum of 2, the invention makes it possible to produce a dextrin sulphate having adequate anti-HIV activity while maintaining toxicity within acceptable limits.
Claim:
An agent against HIV-1 and related viruses, the agent being or including dextrin sulphate containing at most two sulphate groups per glucose unit, and wherein the weight average molecular weight of the dextrin sulphate varies from 15,000 to 25,000.
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Cosalane and Related Compounds Having Activity Against AIDS and AIDS-Related Infections

Assignee: Purdue Research Foundation; U.S. Public Health Service (NIH)

Patent No.: 5,439,899
Inventors: Cushman, M.; Haugwitz, R.D.; Golebiewski, W.M.

Abstract:
Novel compounds having anti-HIV activity are disclosed along with formulations and methods for treating human immunodeficiency viral infections employing these compounds.
Claim:
A compound having the following structure:










wherein R1 and R5 independently are H; a halogen; hydroxy; amino; lower alkoxy; benzoyloxy; lower acyloxy; COOH or a salt thereof; SO3 H or a salt thereof; PO3 H2 or a salt thereof; C8 H17 or a longer chain alkyl; aryl group; COOR where R is aryl or lower alkyl; SO3 R where R is aryl or lower alkyl; PO3 (R)2 where R is aryl or lower alkyl; CONR'R'' where R' and R'' are each independently H, lower alkyl, aryl, or OH; SO2 NR'R'' where R' and R'' are each independently H, lower alkyl, or aryl; SR where R is lower alkyl or aryl; SCH2 Ph; SCOR where R is lower alkyl or aryl; or NR'R'' where R' and R'' are each independently H, lower alkyl, or aryl; and X is an alkane or alkene radical having up to seven carbon atoms.
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Method for Production of 2-Amino-6-Halogenopurine Derivatives

Assignee: Sumika Fine Chemicals Co., Ltd.

Patent No.: 5,440,037
Inventors: Igi, M.; Hayashi, T.

Abstract:
The present invention is directed to a method for production of a 2-amino-6-halogenopurine, a novel synthesis intermediate therefor and a method for production of said synthesis intermediate. The desired 2-amino-6-halogenopurine is an intermediate for the production of the compounds useful as antiviral agents, and by using the compound of the present invention as a starting material, the 2-amino-6-halogenopurine can be produced in high yield.

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Pyrimidine Intermediates

Assignee: Medivir AB

Patent No.: 5,440,040
Inventors: Gronowitz, S.

Abstract:
The present invention is directed to compounds of formula I [not shown], wherein R1 is OH, NH2; R2 is a heteroaromatic or aromatic substituent; R3 is H, OH, F, OCH3; R4 is H, F, OH or an ether or ester residue thereof, OCH3, CN, C=CH, N3; R5 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:





wherein R1 and R2 are as defined above, as intermediates.
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Non-Toxic Hypocompatible Biodegradable Germicide

Assignee: Rost, Inc.

Patent No.: 5,441,723
Inventor: Simmons, P.L.

Abstract:
A non-toxic hypocompatible biodegradable germicide effective against a wide range of pathogenic organisms comprising a composition including a monohydric alcohol from the group consisting of isopropyl, methyl, ethyl, n-propyl, n-butyl, tert-butyl or allyl or mixtures thereof and a polyhydric alcohol from the group consisting of propylene glycol; 1,3-propanediol; 1,2-butanediol, PEG 400; glycerol or 1,4-butanediol or mixtures thereof in proportion by weight such that the polyhydric alcohol reduces the surface glaze formed by the monohydric alcohol and surface tension formed by water or water-based body fluids enabling the disinfectant/antiseptic to kill the pathogenic organisms and act equally effective on a patient or inanimate surface without deleterious effect to either.
Claim:
A non-toxic, hypocompatible, biodegradable germicide effective for contact and killing of a challenge of pathogenic organisms comprising Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella choleraesuis, HIV-1, HIV-2, tuberculosis, polio, herpes simplex type 2, Trichophyton mentagrophytes or mold, said germicide comprising: (i) a disinfecting amount of at least about 65% to about 75% by weight of at least one monohydric alcohol selected from the group consisting of isopropyl, methyl, ethyl, n-propyl, n-butyl, tert-butyl, allyl alcohols and mixtures thereof; (ii) a surface glaze reducing amount of from about 4% to about 16% by weight of at least one polyhydric alcohol, selected from the group consisting of isopropyl, methyl, ethyl, n-propyl, n-butyl, tert-butyl, allyl alcohols, and mixtures thereof; (iii) from at least about 9% to about 20% by weight water in an organic azeotropic combination with the monohydric alcohol; and wherein components (i), (ii) and (iii) are mixed homogeneously with a pH of from about 5 to about 7 and in proportions effective to interact in a manner to reduce surface glaze formed on pathogenic organisms to be disinfected and reduce the surface tension of water or water-based body fluids containing the pathogenic organisms found on a surface to be disinfected, such that the pathogenic organisms of said challenge can be contacted and killed before evaporation of said monohydric alcohol.
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Metal-Interferon-alpha Crystals

Assignee: Schering Corporation

Patent No.: 5,441,734
Inventors: Reichert, P.; McNemar, C.; Nagabhushan, N.; Nagabhushan, T.L.; Tindall, S.; Hruza, A.

Abstract:
The present invention provides for crystalline zinc-interferon alpha-2 (IFN alpha-2) having a monoclinic morphology. The present invention further provides for crystalline cobalt-IFN alpha-2, crystalline calcium-IFN alpha-2, and crystalline IFN alpha-2 having a serum half-life of at least about 12 hours when injected into a primate. The present invention further provides for a method for producing a crystalline IFN alpha-2 comprising forming a soluble metal-IFN alpha-2 complex, and equilibrating the soluble metal-IFN alpha-2 complex in solution with an acetate salt of the metal under conditions that will cause the metal-IFN alpha-2 solution to become supersaturated and form crystalline metal-IFN alpha-2. The present invention also includes crystalline metal-alpha interferon having monoclinic, plate and needle morphologies.
Claim:
A method for administering interferon alpha-2 (IFN alpha-2) to an individual comprising injecting a crystalline zinc-IFN alpha-2 to the individual wherein the crystalline zinc-IFN alpha-2 has a monclinic morphology and wherein the crystalline zinc-IFN alpha-2 diffracts x-rays to about 2.7 Angstroms upon x-ray diffraction analysis and wherein the zinc-IFN alpha-2 has a serum half-life of at least about 12 hours when injected subcutaneously in a primate.
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Antiviral Peptides

Assignee: Houghten Pharmaceuticals Inc.

Patent No.: 5,441,936
Inventors: Houghten, R.A.; Weber, P.A.

Abstract:
The present invention provides antiviral peptides having the general structure, Arg-Arg-Trp-Trp-Cys-Arg-X, where X is an amino acid or an amino acid analog, the stereochemistry of the amino acids or amino acid analogs can be (D)- or (L)-amino acids and the amino and carboxy termini of the peptide can be modified. The invention also provides a pharmaceutical composition comprising an antiviral peptide and methods of using an antiviral peptide in vitro or in vivo to reduce or inhibit a herpes simplex virus infection.
Claim:
An antiviral peptide, comprising:



wherein X is:



wherein R1 is H, COCH2, CH2Ph, CH2CH2Ph, COPh, COO-t-butyl, COOCH2Ph or a linear or branched alkyl having 2 to 6 carbons; R2 is H, C2H5 or CH2Ph; R3 is H, CH3, CH2-Ph, CH2-pyridyl, CH2-imidazole, CH2-indole, CH2Ñ(CH2)2COOH, CH2Ñ(CH2)2CONHR5, CH2Ñ(CH2)nNHR5, CH2Ñ(CH2)nSR5, CH2Ñ(CH2)nNC(NH)NH2; or CH2Ñ(CH2)nOH; R4 is OH, NH2, SH, NHCH3, N(CH3)2, NHCH2Ph, or OR5; and R5 is H, CH3, or a linear or branched alkyl having 2 to 6 carbons; and wherein Ph is C6 H5, Y is O or Ha, n is 0, 1, 2 or 3 and Ò*Ó denotes a chiral center, which can be R or S.
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2',3'-Dideoxy-2',3'-Didehydro-7,8-Disubstituted Guanosines and Their Immunostimulative Effect

Assignee: The Scripps Research Institute

Patent No.: 5,441,942
Inventors: Goodman, M.G.; Chen, R.; Reitz, A.

Abstract:
Immunostimulating 7,8-disubstituted guanine derivatives that also contain a beta-9,1'-linked-2',3'-dideoxy-2',3'-didehydroribosyl substituent are disclosed whose structures are represented by formula I:







wherein X is O or S; R1 is a hydrocarbyl or substituted hydrocarbyl moiety having a length of about one to about seven carbon atoms; R2 is hydrogen or C1-C8 acyl; and the pharmaceutically acceptable base addition salts thereof. Also disclosed are compositions containing an immunostimulating guanine derivative and processes for using the same.
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Uses of Aloe Products

Assignee: Carrington Laboratories, Inc.

Patent No.: 5,441,943
Inventors: McAnalley, B.H.; Carpenter, R.H.; McDaniel, H.R.

Abstract:
Acemannan has been shown to be effective in treating a number of conditions where the principal mechanism of resolution or cure requires intervention by the patientÕs immune system. Acemannan has direct stimulatory effects on the immune system. Methods for treating cancer, viral diseases, respiratory and immune regulatory diseases, inflammations, infections and infestations by administering an acetylated mannan derivative, such as acemannan derived from aloe, are described. The method finds use in tissue cultures, animals and plants.
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Pharmacological Use of Certain Cystine Derivatives

Assignee: Astra AB

Patent No.: 5,441,976
Inventors: Andersson, C.-M.;Bergstrand, H.S.; Hallberg, A.R.; Sarnstrand, B.O.; Tunek, A.P.

Abstract:
A pharmaceutical preparation and method for the treatment of diseases due to defects in the immune system using cystine derivatives.
Claim:
A pharmaceutical preparation for the treatment of diseases wherein an immunostimulating substance is effective, comprising as active ingredient a compound selected from the group consisting of racemic N,N'-dibutyrylcystine, N,N'-diisovalerylcystine, N,N'-dicaprylylcystine, N,N'-diacetylcystine dimethyl ester, N,N'-diacetylcystine diethyl ester, the D and L optical isomers thereof and physiologically acceptable salts thereof in a pharmaceutically acceptable carrier.
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Treatment of Infection by Enveloped Virus with Calix- (N)arene Compounds

Assignee: Genelabs Technologies, Inc.

Patent No.: 5,441,983
Inventors: Hwang, K.M.; Qi, Y.M.; Liu, S.-Y.; Choy, W.; Chen, J.

Abstract:
A method for inhibiting cell infection by an enveloped virus, by administering to an infection site, a therapeutically effective amount of a calix(n)arene compound derivatized, at its ring positions meta to the bridge attachments to the ring, with polar substituent having a terminal carboxylate, phosphate, or sulfonate groups, including esters and amides which are cleavable in vivo. The compound may be administered orally, or topically, e.g., for treatment of herpes virus.
Claim:
A method of inhibiting infection of a mammalian cell by herpes simplex virus HSV-1 or HSV-2 comprising administering to the site of infection a therapeutically effective dose of a calix(n)arene compound which is derivatized, at its ring positions meta to the bridge attachments to the ring, with polar substituents having a terminal carboxylate, phosphonate, or sulfonate group.
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Oligonucleotides for Modulating the Effects of Cytomegalovirus Infections

Assignee: Isis Pharmaceuticals, Inc.

Patent No.: 5,442,049
Inventors: Anderson, K.; Draper, K.; Baker, B.

Abstract:
Compositions and methods for modulating the effects of cytomegalovirus (CMV) infections are disclosed, comprising contacting CMV mRNA with an oligonucleotide which can bind with at least portions of the CMV RNA. In accordance with the preferred embodiments, oligonucleotides such as ISIS 2922 are designed to bind with portions of the CMV mRNAs which code for the IE1, IE2 or DNA polymerase proteins. In accordance with a preferred embodiment, methods of treatment of human cytomegalovirus are disclosed.
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Chimeric HIV-2 Gag Particles

Assignee: Korea Green Cross Corp.

Patent No.: 5,443,828
Inventors: Kang, C.-Y.; Luo, L.

Abstract:
The chimeric proteins, and a potential vaccine and diagnostic reagent comprising gag-env chimeric protein particles are disclosed. The preparation comprises linking gag of HIV-2 to env to form the chimeric gene, inserting the obtained chimeric gene into the DNA of a baculovirus, infecting insect cells or insect host with the resulting recombinant virus, culturing it and purifying the obtained chimeric protein. The gag chimeric protein of HIV according to the present invention retains both antigenic and immunogenic properties.
Claim:
A recombinant gag-env chimeric polypeptide particle of human immunodeficiency virus, comprising: an HIV-2 gag polypeptide selected from the group consisting of HIV-2 gag polypeptides which extend from the N-terminal amino acid of Gag to a minimum of amino acid 376 and a maximum of amino acid 425 and wherein said gag polypeptides have a proline at amino acid 373, 375 or 377; and an env polypeptide from HIV comprising the V3 loop domain of gp120; the env polypeptide linked to the C-terminus of the gag polypeptide.
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Modified Saponins Isolated from Quillaja saponaria

Assignee: Cambridge Biotech Corp.

Patent No.: 5,443,829
Inventors: Kensil, C.A.; Soltysik, S.; Marciani, D.J.

Abstract:
Disclosed herein are modified saponins or fractions thereof obtainable by modification of a crude Quillaja saponaria extract or by modification of purified saponins obtainable from a crude Quillaja saponaria extract useful in pharmaceutical compositions for enhancing the transport of pharmacologically active substances across mucous membranes of an animal. Also disclosed are modified saponins having reduced irritability wherein the aldehyde group is reduced and the fatty acid moiety may be removed by hydrolysis. Also disclosed are pharmaceutical compositions comprising the modified saponins of the invention.
Claim:
A composition comprising a chemically modified saponin or a fraction thereof obtainable from a crude Quillaja saponaria extract, wherein the chemically modified saponin or fraction thereof comprises at least one of QA-17, QA-18, QA-21, QA-21-V1 or QA-21-V2, and wherein the chemical modification of the saponin or fraction thereof consists of (1) the reduction of the triterpene aldehyde group of QA-17, QA-18, QA-21, QA-21-V1 and QA-21-V2 to a methylenealcohol or a methyleneamino group; alone or in combination with (2) the hydrolysis of the fatty acid arabinose moiety or fatty acid arabinose-rhamnose moiety of QA-17, QA-18, QA-21, QA-21-V1 and QA-21-V2 to give the corresponding glycoside fragment.
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Gene Encoding Glycoprotein B of Infectious Laryngotracheitis Virus

Assignee: University of Delaware

Patent No.: 5,443,831
Inventors: Keeler, C.L.; Poulsen, D.J.

Abstract:
An isolated nucleic acid molecule encoding the gB glycoprotein of infectious laryngotracheitis virus is disclosed. Also disclosed is incorporation of the gB gene into recombinant avipox virus for a vaccine used to immunize fowl.
Claim:
A method of immunizing a fowl against infectious laryngotracheitis virus, comprising administering to the fowl an amount of the recombinant avipox virus of claim 4 effective to protect the fowl against symptoms of infectious laryngotracheitis virus disease.
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Hydroxyapatite-Antigen Conjugates and Methods for Generating a Poly-Ig Immune Response

Assignee: Institut Swisse de Recherches Experimentales sur le Cancer

Patent No.: 5,443,832
Inventors: Amerongen, H.M.; Neutra, M.R.; Kraehenbuhl, J.-P.

Abstract:
A method for generating antigen-sensitized IgA-producing lymphoblasts in a mammal, using an immunogen comprising an antigen or antigen mixture in association with hydroxylated calcium phosphate (hydroxyapatite) is administered to a mucosal surface of the mammal.
Claim:
A method for vaccinating a mammal to cause an immunogenic response comprising IgA antibodies, said method comprising the step of administering to a mucosal surface of the mammal an immunogen comprising an antigen or antigen mixture in association with particulate hydroxylated calcium phosphate of a size suitable for transport across epithelium.
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Poxvirus Insertion/Expression Vector

Assignee: Duke University

Patent No.: 5,443,964
Inventors: Pickup, D.J.; Patel, D.D.

Abstract:
The invention comprises a plasmid vector, utilizing genetic material that causes high levels of expression of poxvirus genes, and the method of using this genetic material. One preferred embodiment comprises an upstream cis-acting element of a poxvirus gene encoding the major protein component of the poxvirus A-type inclusion. A second preferred embodiment of the invention comprises a downstream cis-acting element of a poxvirus gene encoding the major protein component of the poxvirus A-type inclusion. These elements are inserted upstream and downstream respectively, of selected cloned genes in the plasmid vector to obtain very high levels of expression of the cloned gene.
Claim:
A recombinant vector comprising: i) a vaccinia virus, ii) a 3' cis-acting element II (CAE-II) of a gene encoding the major component of a cowpox virus A-type inclusion body, and iii) a gene encoding a protein other than the major component of a cowpox virus A-type inclusion body; wherein said gene (iii) is present in said vaccinia virus (i) operably linked to and upstream of said CAE-II.
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Hepatitis C Virus Epitopes

Assignee: Genelabs Technologies, Inc.

Patent No.: 5,443,965
Inventors: Reyes, G.R.; Kim, J.P.; Moeckli, R.

Abstract:
Peptide antigens which are immunoreactive with sera from individuals infected with hepatitis C virus (HCV) are disclosed. Several of the antigens are immunologically reactive with antibodies present in individuals identified as having chronic and acute HCV infection. The antigens are useful in diagnostic methods for detecting HCV infection in humans. Also disclosed are corresponding genomic-fragment clones containing polynucleotides encoding the open reading frame sequences for the antigenic peptides.
Claim:
A method of producing a polypeptide which is immunoreactive with sera from humans infected with hepatitis C virus (HCV), comprising introducing into a suitable non-human host, a recombinant expression system containing an open reading frame (ORF) having a polynucleotide sequence which encodes a polypeptide immunoreactive with sera from humans infected with hepatitis C virus (HCV), where (i) the polypeptide has the sequence presented as Seq. ID No. 2 [not shown], (ii) the polynucleotide has the sequence presented in Seq. ID No. 1 [not shown], and (iii) the vector is designed to express the ORF in said host, and culturing said host under conditions resulting in the expression of the ORF sequence.
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RNA Packaging System

Assignee: Rutgers University

Patent No.: 5,443,969
Inventors: Wilson, T.M.; Hwang-Lee, D.-J.

Abstract:
The present invention relates to an in vivo system for expression and packaging of recombinant RNA into pseudovirus particles. The invention is based on the discovery that plant viral coat proteins (CPs) may be efficiently expressed in E. coli, and that these recombinant coat proteins will function to assemble in vivo and package recombinant chimeric RNA, containing an operatively linked origin-of-assembly (OAS) sequence, to form mature viral particles containing a foreign RNA. The invention provides for packaging of RNA into a ribonuclease-resistant form that is easily purified and stored, and which overcomes the prior art problems with degradation of RNA by ribonucleases. Significantly, the method of the invention is RNA sequence- and length-independent. The components of the invention include a source in the bacterial host of viral coat proteins, and a source in the bacterial host to direct the transcription of a DNA molecule comprising an OAS-encoding DNA and a foreign DNA, which DNA molecule can be transcribed in the host cell to produce an RNA molecule comprising an OAS operatively linked to an RNA of interest. The CPs and OAS are from a plant virus having a rod-shaped helical particle and a single-stranded RNA genome, most preferably tobacco mosaic virus.
Claim:
A method of producing and encapsidating a recombinant RNA molecule in a plant pseudovirus particle comprising culturing a bacterium containing (a) a first recombinant nucleic acid encoding a tobacco mosaic virus coat protein, and (b) a second recombinant nucleic acid that can be transcribed to produce RNA molecule comprising a tobacco mosaic virus origin-of-assembly sequence operatively linker to an RNA sequence of interest, with the proviso that the RNA sequence of interest is not a tobacco mosaic virus RNA; whereby the tobacco mosaic virus coat protein is expressed and the second recombinant nucleic acid is transcribed in the bacterium, and the coat protein assembles into a particle encapsidating the RNA molecule.
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Methods for the Cultivation of Infectious Laryngotracheitis Virus

Assignee: Solvay Animal Health, Inc.

Patent No.: 5,443,982
Inventors: Welniak, E.; Petersen, G.R.

Abstract:
This invention involves a chemically transformed chicken hepatocyte derived cell line which is capable of efficiently supporting replication of infectious laryngotracheitis virus (ILTV) and methods for cultivating ILTV using this hepatocellular carcinoma cell line. The virus harvested from these continuous cell culture methods can be used as a vaccine against ILTV infection.
Claim:
A method for obtaining infectious laryngotracheitis virus comprising (i) infecting a continuous avian hepatocellular cell line, wherein said cell line is CH-SAH, with infectious laryngotracheitis virus, (ii) culturing said virus, and (iii) recovering virus produced thereby.
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Synthetic Polypeptides as Inhibitors of HIV-1

Assignee: New York Blood Center

Patent No.: 5,444,044
Inventors: Jiang, S.; Lin, K.; Neurath, A.R.

Abstract:
A synthetic HIV-1-based polypeptide as well as methods for topically inhibiting HIV-1 infectivity or replication. The polypeptide of the present invention has an amino acid sequence substantially corresponding to a specified region of the HIV-1IIIB virus. The polypeptide of the present invention may be administered in effective amounts for topically inhibiting HIV-1 infectivity or replication. The polypeptide is useful for inhibiting the replication of the HIV-1 virus as well as HIV-1-mediated cytopathogenesis and cell fusion at levels which are within acceptable ranges of cytotoxicity.
Claim:
A prophylactic method of topically inhibiting HIV-1 infectivity or replication, comprising: topically administering to a subject an effective amount of a prophylactic antiviral substance, wherein said prophylactic antiviral substance includes: an HIV-1-based polypeptide having an amino acid sequence of the envelope glycoprotein of HIV-1IIIB or a natural variant thereof from amino acid 600 to amino acid 862, or a portion thereof containing the sequence from amino acid residue 637 to amino acid residue 666.
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Enantiomerically Pure beta-D-Dioxolane Nucleosides with Selective Anti-Hepatitis B Virus Activity

Assignee: Emory University

Patent No.: 5,444,063
Inventor: Schinazi, R.F.

Abstract:
A method and composition for the treatment of humans infected with HBV that includes the administration of an HBV treatment amount of a beta-dioxolanyl purine nucleoside of the formula [see claim] wherein R is OH, Cl, NH2, or H, or a pharmaceutically acceptable salt or derivative of the compound, optionally in a pharmaceutically acceptable carrier or diluent.
Claim:
A method for the treatment of HBV infection in a human or other host animal, comprising administering an HBV treatment amount of an enantiomerically pure beta-D-dioxolanyl nucleoside of the structure:









wherein R is OH, and X is selected from the group consisting of hydrogen, alkyl, acyl, monophosphate, diphosphate, and triphosphate, or its pharmaceutically acceptable salt, and wherein the compound is at least 95% free of the corresponding beta-L enantiomer.
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Fused Cycloalkylimidazopyridines as Inducer of Interferon Alpha Biosynthesis

Assignee: Minnesota Mining & Mfg. Co. (3M Co.)

Patent No.: 5,444,065
Inventors: Nikolaides, N.; Gerster, J.F.

Abstract:
6,7-propylene-, butylene-, or pentylene-bridged imidazopyridin-4-amines that induce interferon (alpha) biosynthesis in human cells. Also disclosed are pharmaceutical compositions containing such compounds and methods of inducing interferon (alpha) biosynthesis and treating viral infections involving the use of such compounds.
Claim:
A method of inducing interferon alpha biosynthesis in an animal, comprising the step of administering to said animal in an amount effective to induce said interferon alpha biosynthesis a compound of the formula:






wherein n is 1, 2, or 3, and R1 is selected from...[truncated].
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Methods of Inhibiting HIV and Inhibiting the Activation of HIV

Assignee: Warner-Lambert Co.

Patent No.: 5,444,085
Inventors: Connor, D.T.; Gracheck, S.J.; Post, L.

Abstract:
The present invention discloses compounds which substantially inhibit HIV or the activation of HIV in HIV-infected individuals. The compounds, their derivatives, and pharmacologic salts may be formulated into a pharmacologic agent to treat HIV infections. These pharmacologic agents may be used to treat immunosuppression, and other diseases of the immune system. The present invention also provides methods for preparing the compounds and formulating the compounds into pharmacologic agents.
Claim:
A method for substantially inhibiting HIV or the activation of HIV in an HIV-infected individual which comprises administering a therapeutically effective amount of a compound of the following formula I:





wherein R1 is lower alkyl, phenyl, or benzyl; R2 is hydrogen, lower alkyl, phenyl, benzyl, thiophene, (CH2)m Q, or phenyl, benzyl, or thiophene substituted with (CH2)m Q; n is an integer from 0 to 2; m is an integer from 0 to 6; Q is CO2 R7 where R7 is hydrogen or lower alkyl; and R3, R4, R5, R6 are independently hydrogen, halo, hydroxy, nitro, amino, lower alkyl, and lower alkoxy as well as of the pharmaceutically acceptable salts of compounds of formula I.
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Method for Detection of a New Marker Associated with Hepatitis Delta Virus Infection

Assignee: U.S. Public Health Service (CDC)

Patent No.: 5,445,932
Inventors: Fields, H.A.; Khudyakov, Y.; Favorov, M.

Abstract:
Reagents and methods for the detection of a marker which is associated with severe forms of hepatitis delta virus infection are described. A vaccine comprising immunogenically active HDAg' polypeptides is also described.
Claim:
A method of predicting the clinical outcome of hepatitis delta virus (HDV) hepatitis, comprising detecting the presence of anti-HDAg' antibodies in a biological sample from a patient having HDV infection, wherein the presence of anti-HDAg' antibodies predicts a shortened lifespan in said patient.
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Direct Molecular Cloning of a Modified Poxvirus Genome

Assignee: Immuno AG

Patent No.: 5,445,953
Inventors: Dorner F.; Falkner F.G.; Scheiflinger, F.

Abstract:
A method is disclosed for producing a modified eukaryotic cytoplasmic DNA virus by direct molecular cloning of a modified DNA molecule comprising a modified cytoplasmic DNA virus genome. The inventive method comprises the steps of (I) modifying under extracellular conditions a DNA molecule comprising a first cytoplasmic DNA virus genome to produce a modified DNA molecule comprising the modified cytoplasmic DNA virus genome; (II) introducing the modified DNA molecule into a first host cell which packages the modified DNA molecule into infectious virions; and (III) recovering from the host cell virions comprised of the modified viral genome. The host cell is infected with a helper virus which is expressed to package the modified viral genome into infectious virions. Examples of packaging a modified poxvirus genome by a helper poxvirus of the same or different genus are described. Also disclosed are novel poxvirus vectors for direct molecular cloning of open reading frames into a restriction enzyme cleavage site that is unique in the vector. In one model poxvirus vector, the open reading frame is transcribed by a promoter located in the vector DNA upstream of a multiple cloning site comprised of several unique cleavage sites.
Claim:
A method for producing a modified chordopoxvirus by direct molecular cloning of a modified chordopox viral genome, wherein said method comprises the steps of (I) modifying under extracellular conditions a purified DNA molecule comprising a first genome of a first chordopoxvirus to produce a modified DNA molecule comprising said modified viral genome; (II) infecting a first host cell with a second chordopoxvirus that is not from the same genus as said first chordopoxvirus, said second chordopoxvirus comprising a second viral genome which is expressed to package said modified first viral genome into infectious virions; (III) introducing said modified DNA molecule into said first host cell, which packages said modified viral genome into infectious virions; and (IV) recovering from said first host cell infectious virions comprised of said modified viral genome.
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Monoclonal Antibodies Specific for HIV and Hybridomas for Their Production

Assignee: Univ. of Arizona; Teijin Limited

Patent No.: 5,445,960
Inventors: Masuho, Y.; Sugano, T.; Matsumoto, Y.-I.; Hersh, E.M.; Petersen, E.A.; Lake, D.; Kawamura, T.

Abstract:
Human IgG1 monoclonal antibodies are produced by hybridoma ATCC HB10074 and bind to gp120 of HIV.
Claim:
A hybridoma having all of the identifying characteristics of ATCC accession no. HB10074.
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Anti-Retroviral Activity of 2',3'-Dideoxy-3'-Fluoronucleosides

Assignee: Medivir AB

Patent No.: 5,446,029
Inventors: Eriksson, B.F.; Johansson, K.N.; Stening, G.B.; Oberg, B.F.

Claim:
A method for therapeutic treatment of hepatitis B virus (HBV) infections in man, comprising administering to a patient in need thereof, an effective anti-hepatitis B viral amount of a compound of the formula:



wherein Base is selected from the group consisting of thymine, cytosine, adenine and guanine, or a physiologically acceptable salt thereof.
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1-beta-D-Arabinofuranosyl-(E)-5-(2-Halogenovinyl)Uracil Derivatives

Assignee: Yamasa Shoyu K.K.

Patent No.: 5,446,031
Inventors: Sakata, S.; Machida, H.; Ijichi, K.; Kano, F.

Abstract:
The present invention relates to a novel 1-beta-D-arabinofuranosyl-(E)-5-(2-halogenovinyl)uracil derivative represented by the following formula (I), whose concentration in blood as XVAU can be kept high for many hours when it is administered orally. The present invention also relates to an antiviral agent comprising as an active ingredient the compound of the present invention. Further, the present invention relates to a method for treating viral diseases which comprises administering to a patient with a viral disease a safe and effective amount of the compound of the present invention [see claim] wherein X represents a halogen; and R1, R2, and R3, which may be the same or different, each represent a hydrogen atom, a lower alkyl group or an aralkyl group, provided that R1, R2 and R3 are not hydrogen at the same time.
Claims:
1. A 1-beta-D-arabinofuranosyl-(E)-5-(2-halogenovinyl)uracil compound represented by the following formula (I):









wherein X represents a halogen; and wherein R1 and R2 are hydrogen and R3 is alkyl having 1 to 10 carbon atoms.
3. A pharmaceutical composition consisting essentially of, as an active ingredient, the compound of claim 1 with a pharmaceutically acceptable carrier, which is in the form of a preparation suitable for oral administration.
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