FR2766715A1 - Product containing synergistic mixture of double-stranded RNA and antiviral agent - Google Patents

Product containing synergistic mixture of double-stranded RNA and antiviral agent Download PDF

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Publication number
FR2766715A1
FR2766715A1 FR9709975A FR9709975A FR2766715A1 FR 2766715 A1 FR2766715 A1 FR 2766715A1 FR 9709975 A FR9709975 A FR 9709975A FR 9709975 A FR9709975 A FR 9709975A FR 2766715 A1 FR2766715 A1 FR 2766715A1
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FR
France
Prior art keywords
viral
product according
hepatitis
dsrna
double
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
FR9709975A
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French (fr)
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FR2766715B1 (en
Inventor
De Paillette Evelyne Deschamps
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ipsen Pharma SAS
Original Assignee
Societe de Conseils de Recherches et dApplications Scientifiques SCRAS SAS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Societe de Conseils de Recherches et dApplications Scientifiques SCRAS SAS filed Critical Societe de Conseils de Recherches et dApplications Scientifiques SCRAS SAS
Priority to FR9709975A priority Critical patent/FR2766715B1/en
Priority to ARP980103723A priority patent/AR013269A1/en
Priority to TW087112434A priority patent/TW589189B/en
Priority to ZA986903A priority patent/ZA986903B/en
Priority to CA002299554A priority patent/CA2299554A1/en
Priority to BR9811121-3A priority patent/BR9811121A/en
Priority to AU89872/98A priority patent/AU750026B2/en
Priority to IL13427598A priority patent/IL134275A0/en
Priority to DE69803391T priority patent/DE69803391T2/en
Priority to PCT/FR1998/001727 priority patent/WO1999007409A1/en
Priority to CN98808902A priority patent/CN1269725A/en
Priority to KR1020007001163A priority patent/KR20010022572A/en
Priority to PL98338377A priority patent/PL338377A1/en
Priority to AT98941527T priority patent/ATE211393T1/en
Priority to PT98941527T priority patent/PT1001801E/en
Priority to EP98941527A priority patent/EP1001801B1/en
Priority to HU0003384A priority patent/HUP0003384A3/en
Priority to DK98941527T priority patent/DK1001801T3/en
Priority to US09/485,086 priority patent/US6509154B1/en
Priority to JP2000506998A priority patent/JP2001513514A/en
Priority to ES98941527T priority patent/ES2171039T3/en
Priority to MYPI98003552A priority patent/MY132954A/en
Publication of FR2766715A1 publication Critical patent/FR2766715A1/en
Priority to NO20000555A priority patent/NO20000555L/en
Application granted granted Critical
Publication of FR2766715B1 publication Critical patent/FR2766715B1/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A61K38/212—IFN-alpha

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Product comprises at least one double-stranded RNA (I) and at least one antiviral agent (II), for use simultaneously, separately or staged in time for treating viral diseases.

Description

Produit comprenant au moins un ARN double brin en
association avec au moins un agent anti-viral pour une
utilisation thérapeutique simultanée séparée ou étalée dans le
temps dans le traitement d'une maladie virale
La présente invention concerne un produit comprenant au moins un ARN double brin (ARNdb) en association avec au moins un agent anti-viral pour une utilisation thérapeutique simultanée, séparée ou étalée dans le temps, dans le traitement d'une maladie virale. Un tel produit peut notamment être utilisé dans le traitement d'une hépatite virale.Product comprising at least one double-stranded RNA in
combination with at least one anti-viral agent for a
separate or spread simultaneous therapeutic use in the
time in treating a viral disease
The present invention relates to a product comprising at least one double-stranded RNA (dsRNA) in combination with at least one anti-viral agent for simultaneous, separate or spread over time therapeutic use in the treatment of a viral disease. Such a product can in particular be used in the treatment of viral hepatitis.

La demanderesse a trouvé que l'association d'ARNdb avec un agent anti-viral, et notamment l'interféron, procure un effet synergique inattendu dans le traitement des maladies virales, notamment le traitement d'une hépatite virale.The Applicant has found that the combination of dsRNA with an anti-viral agent, and in particular interferon, provides an unexpected synergistic effect in the treatment of viral diseases, in particular the treatment of viral hepatitis.

L'invention a donc pour objet un produit comprenant au moins un ARNdb en association avec au moins un agent anti-viral pour une utilisation thérapeutique simultanée, séparée ou étalée dans le temps, dans le traitement d'une maladie virale.The subject of the invention is therefore a product comprising at least one dsRNA in association with at least one anti-viral agent for simultaneous therapeutic use, separated or spread over time, in the treatment of a viral disease.

Selon un aspect préféré de l'invention, 1'ARNdb est l'acide polyadénylique complexé avec l'acide polyuridylique, aussi appelé poly(A)-poly(U). D'autres ARNdb peuvent être utilisés pour l'invention, notamment un complexe de l'acide polyinosinique avec l'acide polycytidylique, également connu sous le nom de poly(I)-poly(C), ainsi que ces mêmes complexes modifiés par introduction d'acide uridylique dans la chaîne de l'acide polycytidylique (pour une description de ces produits, se référer notamment à la demande de brevet européen EP () 3()() 68()). L'ARNdb utilisé peut être par exemple un mélange d'ARNdb tels que défini ci-dessus. De préférence, les ARNdb sont préparés selon le procédé décrit dans le brevet français No. 2 622 586.According to a preferred aspect of the invention, dsRNA is polyadenylic acid complexed with polyuridylic acid, also called poly (A) -poly (U). Other dsRNAs can be used for the invention, in particular a complex of polyinosinic acid with polycytidylic acid, also known as poly (I) -poly (C), as well as these same complexes modified by introduction of uridylic acid in the polycytidylic acid chain (for a description of these products, refer in particular to European patent application EP () 3 () () 68 ()). The dsRNA used can for example be a mixture of dsRNA as defined above. Preferably, the dsRNAs are prepared according to the method described in French patent No. 2,622,586.

Les agents anti-viraux associés à I'ARNdb pourront par exemple être choisis parmi l'interféron, le ganciclovir, la coumermycine Al et la didéoxyinosine (DDI).The anti-viral agents associated with dsRNA may for example be chosen from interferon, ganciclovir, coumermycin A1 and dideoxyinosine (DDI).

De préférence, la maladie virale traitée par le produit selon l'invention est une hépatite virale, notamment l'hépatite C. Preferably, the viral disease treated with the product according to the invention is viral hepatitis, in particular hepatitis C.

L'invention a également pour objet des compositions pharmaceutiques comprenant, à titre de principe actif, un produit selon l'invention, c'est-à-dire un produit comprenant au moins un ARNdb en association avec au moins un agent anti-viral, en association avec des excipients ou supports appropriés, pour une utilisation thérapeutique simultanée, séparée ou étalée dans le temps, dans le traitement des maladies virales.A subject of the invention is also pharmaceutical compositions comprising, as active principle, a product according to the invention, that is to say a product comprising at least one dsRNA in association with at least one anti-viral agent, in combination with suitable excipients or carriers, for simultaneous, separate or spread over time therapeutic use in the treatment of viral diseases.

De préférence, la maladie virale traitée par les compositions pharmaceutiques selon l'invention sera une hépatite virale, tout particulièrement l'hépatite C.Preferably, the viral disease treated by the pharmaceutical compositions according to the invention will be viral hepatitis, very particularly hepatitis C.

Enfin, l'invention concerne l'utilisation d'un produit selon l'invention, c'est-à-dire un produit comprenant au moins un ARNdb et au moins un agent anti-viral, pour fabriquer un médicament destiné à traiter des maladies virales, en particulier l'hépatite virale. De préférence, la maladie virale traitée par le produit selon l'invention sera l'hépatite C.Finally, the invention relates to the use of a product according to the invention, that is to say a product comprising at least one dsRNA and at least one anti-viral agent, for manufacturing a medicament intended to treat diseases viral, especially viral hepatitis. Preferably, the viral disease treated by the product according to the invention will be hepatitis C.

Les compositions phalmaccutiques comprenant un produit selon l'invention peuvent être sous forme d'un solide, par exemple des poudres, des granules, des comprimés, des gélules, des liposomes ou des suppositoires. Les supports solides appropriés peuvent être, par exemple, le phosphate de calcium, le stéarate de magnésium, le talc, les sucres, le lactose, la dextrine, l'amidon, la gélatine, la cellulose, la cellulose de méthyle, la cellulose carboxymêthyle de sodium, la polyvinylpyrrolidine et la cire.The phalmaccutic compositions comprising a product according to the invention can be in the form of a solid, for example powders, granules, tablets, capsules, liposomes or suppositories. Suitable solid supports can be, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, carboxymethyl cellulose sodium, polyvinylpyrrolidine and wax.

Les compositions pharmaceutiques contenant un produit selon l'invention peuvent aussi se présenter sous forme liquide, par exemple, des solutions, des émulsions, des suspensions ou des sirops. Les supports liquides appropriés peuvent titre, par exemple, l'eau, les solvants organiques tels que le glycérol ou les glycols, de même que leurs mélanges, dans des proporlions variées, dans l'eau.The pharmaceutical compositions containing a product according to the invention can also be presented in liquid form, for example, solutions, emulsions, suspensions or syrups. Suitable liquid carriers may, for example, water, organic solvents such as glycerol or glycols, as well as their mixtures, in various proportions, in water.

Le mode d'administration d'un produit selon l'invention est choisi parmi les modes d'administration classiques. Ainsi, l'administration d'ARNdb peut par exemple se faire par voie topique, orale, parentérale, par injeCtion intramusculaire ou intraveineuse. De même, l'administration des agents anti-viraux peut se faire selon les mêmes voies. Pour chacun de ces composés, I'homme du mélier choisira la méthode d'administration la plus appropriée.The mode of administration of a product according to the invention is chosen from conventional modes of administration. Thus, the administration of dsRNA can for example be done topically, orally, parenterally, by intramuscular or intravenous injection. Similarly, the administration of anti-viral agents can be done according to the same routes. For each of these compounds, the man in the mix will choose the most appropriate method of administration.

La dose d'administration envisagée pour médicament selon l'invention est comprise entre 0,1 mg à 10 g suivant le type de composé actif utilisé. The administration dose envisaged for a medicament according to the invention is between 0.1 mg to 10 g depending on the type of active compound used.

A moins qu'ils ne soient définis d'une autre manière, tous les termes techniques et scientifiques utilisés ici ont la même signification que celle couramment comprise par un spécialiste ordinaire du domaine auquel appartient cette invention. De même, toutes les publications, demandes de brevets, tous les brevets et toutes autres références mentionnées ici sont incorporées par référence.Unless otherwise defined, all technical and scientific terms used herein have the same meaning as that commonly understood by an ordinary specialist in the field to which this invention belongs. Likewise, all publications, patent applications, all patents and all other references mentioned herein are incorporated by reference.

Propriétés cliniques des produits de l'invention
Un groupe de 10 malades atteints d'hépatite C a été traité successivement par du poly(A)poly(U), puis par de l'interféron.Clinical properties of the products of the invention
A group of 10 patients with hepatitis C was treated successively with poly (A) poly (U), then with interferon.

Le traitement s'est déroulé de la façon suivante - dans un premier temps, les malades ont reçu deux fois par semaine durant 24 semaines une dose de 15() mg de poly(A)-poly(U) administrée par voie intraveineuse; - à l'issue de ce premier traitement, les malades ont reçu 3 fois par semaine durant 24 semaines une dose de 3 millions d'unités d'interféron administrée par voie intraveineuse.The treatment proceeded as follows - initially, the patients received twice a week for 24 weeks a dose of 15 () mg of poly (A) -poly (U) administered intravenously; - At the end of this first treatment, the patients received a dose of 3 million units of interferon administered intravenously 3 times a week for 24 weeks.

A l'issue de ce double traitement, on a observé une rémission de la maladie chez 6 patients, une rémission suivie d'une rechute chez un septième patient, tandis que le traitement n'a pas eu d'effet pour 3 patients seulement.At the end of this double treatment, a remission of the disease was observed in 6 patients, a remission followed by a relapse in a seventh patient, while the treatment had no effect for only 3 patients.

A titre de comparaison, un traitement effectué uniquement avec de l'interféron offre une rémission dans seulement 2O à 3O % des cas (cf. La revue du praticien, 45, p. 25192522 (1995)). By way of comparison, treatment carried out only with interferon offers remission in only 2O to 30% of cases (see The practitioner's review, 45, p. 25192522 (1995)).

Claims (10)

Revendications:Claims: 1. Produit caractérisé en ce qu'il comprend au moins un ARNdb en association avec au moins un agent anti-viral pour une utilisation thérapeutique simultanée, séparée ou étalée dans le temps, dans le traitement d'une maladie virale.1. Product characterized in that it comprises at least one dsRNA in association with at least one anti-viral agent for simultaneous therapeutic use, separate or spread over time, in the treatment of a viral disease. 2. Produit selon la revendication 1, caractérisé en ce que l'ARNdb est l'acide polyadénylique complexé avec l'acide polyuridylique.2. Product according to claim 1, characterized in that the dsRNA is polyadenylic acid complexed with polyuridylic acid. 3. Produit selon la revendication l, caractérisé en ce que l'ARNdb un complexe de l'acide polyinosinique avec l'acide polycytidylique.3. Product according to claim l, characterized in that the dsRNA a complex of polyinosinic acid with polycytidylic acid. 4. Produit selon l'une des revendications l à 3, caractérisé en ce que l'agent anti-viral est choisi parmi l'interféron, le ganciclovir, la coumermycine Al et la didéoxyinosine (DDI).4. Product according to one of claims l to 3, characterized in that the anti-viral agent is chosen from interferon, ganciclovir, coumermycin Al and dideoxyinosine (DDI). 5. Produit selon la revendication 4, caractérisé en ce que l'agent anti-viral est l'interféron.5. Product according to claim 4, characterized in that the anti-viral agent is interferon. 6. Produit selon l'une des revendications 1 à 5, caractérisé en ce que la maladie virale est une hépatite virale.6. Product according to one of claims 1 to 5, characterized in that the viral disease is viral hepatitis. 7. Produit selon la revendication 6, caractérisé en ce que l'hépatite virale est l'hépatite C.7. Product according to claim 6, characterized in that the viral hepatitis is hepatitis C. 8. Composition pharmaceutique comprenant, à titre de principe actif, un produit selon l'une quelconque des revendications 1 à 7, en association avec des excipients ou supports appropriés.8. Pharmaceutical composition comprising, as active principle, a product according to any one of claims 1 to 7, in association with suitable excipients or carriers. 9. Utilisation d'un produit selon l'une des revendications 1 à 8 pour fabriquer un médicament destiné à traiter des maladies virales, en particulier l'hépatite virale.9. Use of a product according to one of claims 1 to 8 for manufacturing a medicament intended to treat viral diseases, in particular viral hepatitis. 10. Utilisation selon la revendication 9, caractérisée en ce que la maladie virale est l'hépatite C. 10. Use according to claim 9, characterized in that the viral disease is hepatitis C.
FR9709975A 1997-08-04 1997-08-04 PRODUCT INCLUDING AT LEAST DOUBLE-STRANDED RNA IN ASSOCIATION WITH AT LEAST ONE ANTI-VIRAL AGENT FOR SIMULTANEOUS THERAPEUTIC USE, SEPARATE OR OVER TIME, IN THE TREATMENT OF A VIRAL DISEASE Expired - Fee Related FR2766715B1 (en)

Priority Applications (23)

Application Number Priority Date Filing Date Title
FR9709975A FR2766715B1 (en) 1997-08-04 1997-08-04 PRODUCT INCLUDING AT LEAST DOUBLE-STRANDED RNA IN ASSOCIATION WITH AT LEAST ONE ANTI-VIRAL AGENT FOR SIMULTANEOUS THERAPEUTIC USE, SEPARATE OR OVER TIME, IN THE TREATMENT OF A VIRAL DISEASE
ARP980103723A AR013269A1 (en) 1997-08-04 1998-07-29 PRODUCT CONTAINING AT LEAST A DOUBLE FILAMENT RNA COMBINED WITH AT LEAST AN ANTI-VIRAL AGENT, FOR THERAPEUTIC USE IN THE TREATMENT OF A VIRAL DISEASE, ESPECIALLY OF VIRAL HEPATITIS
TW087112434A TW589189B (en) 1997-08-04 1998-07-29 Kit containing at least one double-stranded RNA combined with at least one anti-viral agent for therapeutic use in the treatment of a viral disease, notably of viral hepatitis
ZA986903A ZA986903B (en) 1997-08-04 1998-07-31 Product containing at least one double-stranded RNA combined with at least one anti-viral agent for therapeutic use in the treatment of a viral disease notably of viral hepatitis
EP98941527A EP1001801B1 (en) 1997-08-04 1998-08-03 Product comprising at least a double stranded rna combined with at least an interferon for the treatment of viral hepatitis
AU89872/98A AU750026B2 (en) 1997-08-04 1998-08-03 Product comprising at least a double stranded RNA combined with at least an antiviral agent
IL13427598A IL134275A0 (en) 1997-08-04 1998-08-03 Product comprising at least a double standed rna combined with at least an antiviral agent
DE69803391T DE69803391T2 (en) 1997-08-04 1998-08-03 COMPOSITION CONTAINING AT LEAST ONE DOUBLE STRANDED RNA AND AT LEAST ONE INTERFERON FOR THE TREATMENT OF VIRAL HEPATITIS
PCT/FR1998/001727 WO1999007409A1 (en) 1997-08-04 1998-08-03 Product comprising at least a double stranded rna combined with at least an antiviral agent
CN98808902A CN1269725A (en) 1997-08-04 1998-08-03 Product comprising at least double stranded RNA combined with at least an antiviral agent
KR1020007001163A KR20010022572A (en) 1997-08-04 1998-08-03 Product Comprising at Least a Double Stranded RNA Combined with at Least an Antiviral Agent
PL98338377A PL338377A1 (en) 1997-08-04 1998-08-03 Product containing at least one double-string rna (ds rna) in combination with at least one antiviral agent
CA002299554A CA2299554A1 (en) 1997-08-04 1998-08-03 Product comprising at least a double stranded rna combined with at least an antiviral agent
PT98941527T PT1001801E (en) 1997-08-04 1998-08-03 A PRODUCT UNDERTAKING AT LEAST A DOUBLE SPIRAL RNA IN ASSOCIATION WITH AT LEAST AN INTERFERENCE FOR THE TREATMENT OF VIRAL HEPATITIS
BR9811121-3A BR9811121A (en) 1997-08-04 1998-08-03 Product, pharmaceutical composition, and use of a product
HU0003384A HUP0003384A3 (en) 1997-08-04 1998-08-03 Product comprising at least a double stranded rna combined with at least an antiviral agent
DK98941527T DK1001801T3 (en) 1997-08-04 1998-08-03 Product comprising at least one double-chain RNA combined with at least one interferon for the treatment of viral hepatitis
US09/485,086 US6509154B1 (en) 1997-08-04 1998-08-03 Product comprising at least a double stranded RNA combined with at least an antiviral agent
JP2000506998A JP2001513514A (en) 1997-08-04 1998-08-03 Product containing at least one double-stranded RNA (dsRNA) in combination with at least one antiviral agent
ES98941527T ES2171039T3 (en) 1997-08-04 1998-08-03 PRODUCT THAT INCLUDES AT LEAST A double-stranded RNA IN ASSOCIATION WITH AT LEAST ONE INTERFER FOR THE TREATMENT OF VIRAL HEPATITIS.
AT98941527T ATE211393T1 (en) 1997-08-04 1998-08-03 COMPOSITION CONTAINING AT LEAST ONE DOUBLE STRAND RNA AND AT LEAST ONE INTERFERON FOR THE TREATMENT OF VIRAL HEPATITIS
MYPI98003552A MY132954A (en) 1997-08-04 1998-08-04 Product containing at least one double-stranded rna combined with at least one anti-viral agent for therapeutic use in the treatment of a viral disease, notably of viral hepatitis
NO20000555A NO20000555L (en) 1997-08-04 2000-02-03 Product containing at least one double stranded RNA combined with at least one antiviral agent

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR9709975A FR2766715B1 (en) 1997-08-04 1997-08-04 PRODUCT INCLUDING AT LEAST DOUBLE-STRANDED RNA IN ASSOCIATION WITH AT LEAST ONE ANTI-VIRAL AGENT FOR SIMULTANEOUS THERAPEUTIC USE, SEPARATE OR OVER TIME, IN THE TREATMENT OF A VIRAL DISEASE

Publications (2)

Publication Number Publication Date
FR2766715A1 true FR2766715A1 (en) 1999-02-05
FR2766715B1 FR2766715B1 (en) 2001-02-16

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FR9709975A Expired - Fee Related FR2766715B1 (en) 1997-08-04 1997-08-04 PRODUCT INCLUDING AT LEAST DOUBLE-STRANDED RNA IN ASSOCIATION WITH AT LEAST ONE ANTI-VIRAL AGENT FOR SIMULTANEOUS THERAPEUTIC USE, SEPARATE OR OVER TIME, IN THE TREATMENT OF A VIRAL DISEASE

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ZA (1) ZA986903B (en)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0213921A2 (en) * 1985-08-26 1987-03-11 Hem Research, Inc. Modulation of virus-related events by double-stranded RNAs
EP0281380A2 (en) * 1987-03-03 1988-09-07 Hem Pharmaceuticals Corp. Synergistic interplay of interleukin-2 and dsRNAs
EP0286224A2 (en) * 1987-03-23 1988-10-12 Hem Pharmaceuticals Corp. Treatment of human viral infection by dsRNA combined with viral inhibitors
EP0300680A2 (en) * 1987-07-17 1989-01-25 Hem Pharmaceuticals Corp. Doublestranded RNA correction of abnormalities in circulating immune complexes and monocyte function
EP0306347A2 (en) * 1987-09-04 1989-03-08 Hem Pharmaceuticals Corp. Diagnosis of double-stranded RNA deficiency states
WO1991018611A1 (en) * 1990-05-25 1991-12-12 Hem Research, Inc. Diagnosis and treatment of viral hepatitis

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0213921A2 (en) * 1985-08-26 1987-03-11 Hem Research, Inc. Modulation of virus-related events by double-stranded RNAs
EP0281380A2 (en) * 1987-03-03 1988-09-07 Hem Pharmaceuticals Corp. Synergistic interplay of interleukin-2 and dsRNAs
EP0286224A2 (en) * 1987-03-23 1988-10-12 Hem Pharmaceuticals Corp. Treatment of human viral infection by dsRNA combined with viral inhibitors
EP0300680A2 (en) * 1987-07-17 1989-01-25 Hem Pharmaceuticals Corp. Doublestranded RNA correction of abnormalities in circulating immune complexes and monocyte function
EP0306347A2 (en) * 1987-09-04 1989-03-08 Hem Pharmaceuticals Corp. Diagnosis of double-stranded RNA deficiency states
WO1991018611A1 (en) * 1990-05-25 1991-12-12 Hem Research, Inc. Diagnosis and treatment of viral hepatitis

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE AIDSLINE US NATIONAL LIBRARY OF MEDICINE (NLM),BETHESDA, MD, US; DE CLERCQ E ET AL: "Retrogen increases the anti-HIV activity of AZT, DDI and DDC.", XP002064031 *
INT CONF AIDS, JUL 19-24 1992, 8 (3) P25 (ABSTRACT NO. PUA 6087) *

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FR2766715B1 (en) 2001-02-16
ZA986903B (en) 1999-01-28

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