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WO1988008429A1 - Procedes et compositions immunotherapeutiques - Google Patents

Procedes et compositions immunotherapeutiques Download PDF

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Publication number
WO1988008429A1
WO1988008429A1 PCT/US1988/001213 US8801213W WO8808429A1 WO 1988008429 A1 WO1988008429 A1 WO 1988008429A1 US 8801213 W US8801213 W US 8801213W WO 8808429 A1 WO8808429 A1 WO 8808429A1
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WO
WIPO (PCT)
Prior art keywords
composition according
infection
patient
hiv
amino acid
Prior art date
Application number
PCT/US1988/001213
Other languages
English (en)
Inventor
Richard A. Fisher
Walter Gilbert
Vicki L. Sato
Kuzhalmannam L. Ramachandran
Original Assignee
Biogen N.V.
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 Biogen N.V. filed Critical Biogen N.V.
Publication of WO1988008429A1 publication Critical patent/WO1988008429A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
    • C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Definitions

  • This invention relates to immunotherapeutic methods and compositions. More particularly, this invention relates to methods for eliciting specific antibody responses in immunodeficient patients using immunogens comprising antigen/T-cell independent carrier conjugates. According to a preferred embodiment, this invention relates to immunogens comprising peptides from the env region of the HIV genome coupled to T-cell independent carriers, which are useful in preventing or treating acquired immune deficiency syndrome and AIDS related complex.
  • T-4 lymphocytes also known as helper or inducer cells, interact with other specialized cell types of the immune system to confer immunity to or defense against infection. More specifically, T-4 lymphocytes stimulate production of growth factors which are critical to the functioning of the immune system. For example, they activate macrophages ("killer cells”) to attack infected or otherwise abnormal host cells, and induce monocytes (“scavenger cells”) to encompass and destroy invading microbes. They also induce maturation of B lymphocytes into cells which produce defensive antibodies to specific antigens.
  • killer cells macrophages
  • scavenger cells monocytes
  • T-dependent antigens require interaction with both T lymphocytes and B lymphocytes, with the T lymphocytes somehow regulating the proliferation and differentiation of B lymphocytes into antibody secreting cells by mechanisms not yet fully understood.
  • B lymphocyte differentiation and antibody formation may occur, however, without T lymphocyte induction, in response to T-independent antigens or, possibly, supplies of exogenous growth factors.
  • This complex immune defense system may be partially or totally disrupted as a result of a given therapeutic regimen.
  • chemotherapy and radiation therapies used to treat malignant diseases, or immunosuppressants administered to prevent rejection of transplanted organs often cause selective destruction of circulating T-4 lymphocytes or contribute to other T lymphocyte abnormalities in the patient undergoing treatment.
  • Such side effects of these treatments may lead to complete immunosuppression and attendant susceptibility of the patient to a wide range of opportunistic infections. Even when immunosuppression is not complete, in those patients having depleted T lymphocyte populations, exposure to a given antigen alone may not be sufficient to elicit the formation of antibodies.
  • HIV human immunodeficiency virus
  • ARCS AIDS related complex
  • T-4 lymphocytes Upon infection of a host, the primary targets of the HIV virus, T-4 lymphocytes, are rendered non-functional. In addition to T-4 lymphocytes, the HIV virus are also been shown to infect central nervous system cells, macrophages and B lymphocytes [J. M. Ismach, "AIDS: Can The National Cope", Medical World News (March 25, 1985)].
  • the present invention solves the problems referred to above by providing immunotherapeutic methods and compositions for use in the treatment of immunodeficient patients.
  • the methods and compositions of this invention are characterized by immunogens which comprise antigens specific for a target infection coupled to T-cell independent carriers.
  • human immunodeficiency virus HIV
  • HTLV-III human T-cell lymphotropic virus type III
  • LAV lymphadenopathy-associated virus
  • ARV AIDS-associated retrovirus
  • immunogens comprising peptides from the env region of the HIV genome coupled to T-cell independent carriers may be used to elicit antibodies reactive with the native env protein of the HIV virus.
  • Such immunogens are useful in preventing or treating acquired immune deficiency syndrome and AIDS related complex.
  • Figure 1 depicts the amino acid sequences of each of peptides 1-2, 4-6, 31, 64 and 78 used in one embodiment of the antigen/T-cell independent carrier conjugates of this invention, as well as that of the region between amino acid 600 and amino acid 750 of the HIV env gene.
  • the amino acids are represented by single letter codes as follows:
  • antigens specific for a target infection are coupled to one or more T-cell independent carriers, for example carriers such as Ficoll, lipopolysaccharide ("LPS"), dextran sulfate or Staphylococcus aureus Cowan strain, before use.
  • T-cell independent carriers for example carriers such as Ficoll, lipopolysaccharide ("LPS"), dextran sulfate or Staphylococcus aureus Cowan strain
  • LPS lipopolysaccharide
  • dextran sulfate or Staphylococcus aureus Cowan strain
  • the antigens may also be coupled to any other conventional polymeric T-independent carrier to which peptides may be conjugated.
  • These antigens are coupled to the carrier according to a procedure such as that set forth in Example 2 of this application.
  • the antigens may be coupled to the carrier in various conventional ways using, for example, methods using glutaraldehyde [M.
  • Antigens which may be coupled to T-independent carriers to form immunogenic conjugates according to this invention include peptides involved in the pathogenesis of the HIV virus.
  • Such peptides include peptides from the env region of the HIV genome, for example, peptides characterized by an amino acid sequence derived substantially from the region between about amino acid 600 and amino acid 750 of the HIV env gene or the D-retro forms of those peptides -- those produced by synthesis with D amino acids in the opposite orientation, beginning with the carboxy terminal amino acid of the L form.
  • antigens which may be coupled to T-independent carriers to form the immunogenic conjugates of this invention include those which are specific for opportunistic infections afflicting immunosuppressed or immunocompromised patients.
  • antigens include, for example, antigens directed against bacterial pneumonia, pneumosistis pneumonia, hepatitis, varicella virus, cytomegalovirus and Epstein-Barr virus. These antigens may be prepared according to any conventional method including, for example, chemical synthesis or recombinant DNA technology.
  • the antigen/ T-cell independent carrier conjugate is employed in the methods and compositions of this invention in a conventional manner.
  • the coupled antigen alone or in combination with other coupled antigens of this invention, may be mixed with one or a combination of well-recognized adjuvants and additives, preferably by first dissolving the coupled antigen, for example, in PBS with 0.1% SDS.
  • coupled antigens may be linked to hydrophobic groups to build the adjuvant into the composition.
  • the coupled antigen may be administered to a patient in combination with lymphokines, such as B cell growth factors, which are known to stimulate the activity of B lymphocytes.
  • compositions may be employed using the antigen/T-cell independent carrier conjugates of this invention.
  • the above-prepared compositions are then employed in a conventional manner for the treatment of opportunistic infections in immunodeficient patients.
  • Such methods of treatment and their dosage levels and requirements are well-recognized in the art and may be chosen by those of skill in the art from available methods and techniques.
  • the conjugates of this invention may be combined with a pharmaceutically acceptable adjuvant for administration to patient in a pharmaceutically acceptable manner and in an amount effective to elicit antibodies specific for the target infection and to lessen the severity of that infection.
  • the dosage and treatment regimens will depend upon factors such as the patient's health status, the severity and course of infection and the judgment of the treating physician.
  • the antigen/T-cell independent carrier conjugates of this invention are useful in vaccines and methods for protecting immunodeficient humans against opportunistic infections for at least some period of time.
  • the conjugates may be employed in these vaccines and methods either alone or together with other conjugates of this invention in a manner consistent with the conventional utilization of antigens in vaccines.
  • the antigen/T-cell independent carrier conjugates of this invention may be combined with pharmaceutically acceptable adjuvants conventionally employed in vaccines and administered in immunologically effective amounts to protect immunodeficient patients for some time against opportunistic infections.
  • the immunogenic conjugates may be combined with B lymphocyte-stimulating factors for administration as a vaccine.
  • compositions and vaccines of this invention may be administered to patients via conventional modes of administration.
  • the frequency of administration will depend upon factors such as the particular composition or vaccine employed and the condition of the patient.
  • the need for subsequent treatments with these compositions or boosters of these vaccines will depend upon the results of the initial treatment or vaccination.
  • the compositions, vaccines and methods of this invention may be used to treat human as well as other mammalian patients.
  • conjugates of this invention we coupled peptides involved in the pathogenesis of HIV infection to T-cell independent carriers to form the conjugates of this invention and tested the conjugates in several conventional assays to demonstrate their ability to elicit anti-HIV antibody responses in immunodeficient hosts. It should be understood that the present invention also relates to conjugates comprising the D-retro form of each of these illustrative peptides.
  • Example 2 Coupling Of An HIV-Peptide To A Carboxymethyl Ficoll Carrier
  • carboxymethyl Ficoll according to the procedure described in J. K. Inman, "Thymus- Independent Antigens: The Preparation Of Covalent, Hapten-Ficoll Conjugates", J. Immunol., 114, pp. 704-09 (1975).
  • Example 4 - ELISA With Anti-Peptide/T-Cell Independent Carrier Conjugate Sera against HIV env Peptide Coated Plates we determined that antiserum raised in an animal by each of the peptide/T-cell independent carrier conjugates of this invention binds to its respective peptide. Accordingly, the coupled peptides of this invention are immunogenic and elicit a response in test animals.
  • FCS/PBS fetal calf serum in PBS solution
  • test serum comprised pooled samples of antisera raised against the peptide 4/Ficoll conjugate of this invention at dilutions of 1:10 or 1:25.
  • PBS saline-PO 4
  • PBS saline-PO 4
  • PBS-Tween-20 0.05%
  • each plate had a series of "background" control wells containing no test serum and to which one of the following had been added: -- saline-PO 4 (EBS) containing 20% normal goat serum -- PBS-Tween-20 (0.05%) containing 1% normal goat serum and goat - anti-mouse-IgM HRP at a dilution of 1:4000
  • test plate also had a negative and positive control serum.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Virology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne des compositions et des procédés immunothérapeutiques et plus particulièrement des procédés pour tirer et obtenir des réponses d'anticorps spécifiques chez des patients immunodéficients utilisant des immunogènes comprenant des conjugués porteurs indépendants de cellules T/antigènes. Selon un mode préférentiel de réalisation, cette invention concerne des immunogènes comprenant des peptides de la région env du génome HIV couplé à des porteurs indépendants de cellules T, qui sont utiles pour la prévention ou le traitement du syndrome de déficience immunitaire acquise et du complexe apparenté au SIDA.
PCT/US1988/001213 1987-04-24 1988-04-20 Procedes et compositions immunotherapeutiques WO1988008429A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US4217887A 1987-04-24 1987-04-24
US042,178 1987-04-24

Publications (1)

Publication Number Publication Date
WO1988008429A1 true WO1988008429A1 (fr) 1988-11-03

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PCT/US1988/001213 WO1988008429A1 (fr) 1987-04-24 1988-04-20 Procedes et compositions immunotherapeutiques

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EP (1) EP0311675A4 (fr)
AU (1) AU1711888A (fr)
WO (1) WO1988008429A1 (fr)

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0473721A1 (fr) * 1989-05-25 1992-03-11 Sloan-Kettering Institute For Cancer Research Anticorps anti-idiotypique induisant une reaction immunitaire contre un glycosphingolipide, et son utilisation
US5274122A (en) * 1992-10-15 1993-12-28 Merck & Co., Inc. Acidic derivatives of homocysteine thiolactone
EP0625910A1 (fr) * 1992-02-11 1994-11-30 Henry M. Jackson Foundation For The Advancement Of Military Medicine Structure immunogene a double vecteur
US5464933A (en) * 1993-06-07 1995-11-07 Duke University Synthetic peptide inhibitors of HIV transmission
US5606030A (en) * 1990-07-19 1997-02-25 Merck & Co., Inc. Coconjugates of OMPC, HIV related peptides and anionic moieties
US6017536A (en) * 1993-06-07 2000-01-25 Trimeris, Inc. Simian immunodeficiency virus peptides with antifusogenic and antiviral activities
US6093794A (en) * 1993-06-07 2000-07-25 Trimeris, Inc. Isolated peptides derived from the Epstein-Barr virus containing fusion inhibitory domains
US6432402B1 (en) 1989-05-25 2002-08-13 Sloan-Kettering Institute For Cancer Research Anti-idiotypic antibody which induces an immune response against a glycosphingolipid and use thereof
US6518013B1 (en) 1993-06-07 2003-02-11 Trimeris, Inc. Methods for the inhibition of epstein-barr virus transmission employing anti-viral peptides capable of abrogating viral fusion and transmission
US6605427B2 (en) 2000-02-10 2003-08-12 Panacos Pharmaceuticals, Inc. Assay for detection of viral fusion inhibitors
US6805862B1 (en) 1989-05-25 2004-10-19 Sloan-Kattering Institute For Cancer Research Anti-idiotypic antibody which induces an immune response against a glycosphingolipid and use thereof
EP1692265A2 (fr) * 2003-11-04 2006-08-23 The Administrators Of The Tulane Educational Fund Methode de prevention des infections virales: fusion cellulaire par inhibition de la region de depart de fusion dans des virus a arn avec proteines d'enveloppe fusiogenes a membrane de classe i
EP1714153A2 (fr) * 2004-02-06 2006-10-25 I.N.S.E.R.M. Institut National de la Sante et de la Recherche Medicale Polypeptide derive de gp41, composition de vaccin comprenant ce polypeptide et utilisations de celle-ci pour traiter une personne infectee par un virus vih
US7713937B2 (en) 2006-11-10 2010-05-11 Cara Therapeutics, Inc. Synthetic peptide amides and dimeric forms thereof
US7727963B2 (en) 2006-11-10 2010-06-01 Cara Therapeutics, Inc. Synthetic peptide amides
US7803524B2 (en) 1994-02-23 2010-09-28 Siemens Healthcare Diagnostics Products Gmbh Antigenic HIV gp41 chimeric polypeptides comprising the MVP5180/91 epitope SKGKLIS
US7842662B2 (en) 2006-11-10 2010-11-30 Cara Therapeutics, Inc. Synthetic peptide amide dimers
US8222204B2 (en) 2006-05-03 2012-07-17 The Administrators of the Tulane Educational Fund and Autoimmune Technologies, LLC Influenza inhibiting compositions and methods
US8236766B2 (en) 2006-11-10 2012-08-07 Cara Therapeutics, Inc. Uses of synthetic peptide amides
US8604165B2 (en) 2007-06-25 2013-12-10 The Administrators Of The Tulane Educational Fund Influenza inhibiting compositions and methods
US8906859B2 (en) 2006-11-10 2014-12-09 Cera Therapeutics, Inc. Uses of kappa opioid synthetic peptide amides

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* Cited by examiner, † Cited by third party
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DE3854550T2 (de) * 1987-11-24 1996-04-25 Abbott Lab HIV-Peptide und Methoden für den Nachweis von HIV.

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US4629783A (en) * 1985-04-29 1986-12-16 Genetic Systems Corporation Synthetic antigen for the detection of AIDS-related disease

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US4185090A (en) * 1972-02-02 1980-01-22 Abbott Laboratories Chemically modified endotoxin immunizing agent
WO1986002383A1 (fr) * 1984-10-18 1986-04-24 Institut Pasteur Antigenes d'enveloppe du virus des lymphadenopathies et leurs applications
US4629783A (en) * 1985-04-29 1986-12-16 Genetic Systems Corporation Synthetic antigen for the detection of AIDS-related disease

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Bio/Technology (New York, USA) Volume 3, issued October 1985, (CHANG et al) Y-Cell Lymphotropic Virus-III (HTLV-III) with an Immunoassay Employing a Recombinant Escherichia Coli-Derived Viral Antigenic Peptide", pages 905-909. see fig. 1 in particular. *
Science, (Washington, D.C., USA) Volume 231, issued March 1986. (KENNEDY et al.), "Antiserum to a Synthetic Peptide Recognizes the HTLV-III Envelope Glycoprotein". pages 1556-1559. see page 1556 in particular. *
See also references of EP0311675A4 *

Cited By (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6432402B1 (en) 1989-05-25 2002-08-13 Sloan-Kettering Institute For Cancer Research Anti-idiotypic antibody which induces an immune response against a glycosphingolipid and use thereof
EP0473721A4 (fr) * 1989-05-25 1994-03-23 Sloan Kettering Institute For Cancer Research
EP1334984A1 (fr) * 1989-05-25 2003-08-13 Sloan-Kettering Institute For Cancer Research Anticorps anti-idiotypiques induisant une réaction immunitaire contre un glycosphingolipide, et son utilisation
EP0884329A1 (fr) * 1989-05-25 1998-12-16 Sloan-Kettering Institute For Cancer Research Anticorps anti-idiotypiques induisant une réaction immunitaire contre un glycosphingolipide, et son utilisation
US6805862B1 (en) 1989-05-25 2004-10-19 Sloan-Kattering Institute For Cancer Research Anti-idiotypic antibody which induces an immune response against a glycosphingolipid and use thereof
EP0473721A1 (fr) * 1989-05-25 1992-03-11 Sloan-Kettering Institute For Cancer Research Anticorps anti-idiotypique induisant une reaction immunitaire contre un glycosphingolipide, et son utilisation
US5606030A (en) * 1990-07-19 1997-02-25 Merck & Co., Inc. Coconjugates of OMPC, HIV related peptides and anionic moieties
EP0625910A1 (fr) * 1992-02-11 1994-11-30 Henry M. Jackson Foundation For The Advancement Of Military Medicine Structure immunogene a double vecteur
US5585100A (en) * 1992-02-11 1996-12-17 Henry Jackson Foundation Dual carrier immunogenic construct
EP0625910A4 (en) * 1992-02-11 1996-03-06 Us Gov Sec Army Dual carrier immunogenic construct.
EP1958646A1 (fr) * 1992-02-11 2008-08-20 Henry M. Jackson Foundation For The Advancement Of Military Medicine Conception immunogène à deux porteuses
US5955079A (en) * 1992-02-11 1999-09-21 Henry Jackson Foundation For The Advancement Of Military Medicine Dual carrier immunogenic construct
EP0911036A3 (fr) * 1992-02-11 2001-05-09 Henry M. Jackson Foundation For The Advancement Of Military Medicine Structure immunogene à double vecteur
US5274122A (en) * 1992-10-15 1993-12-28 Merck & Co., Inc. Acidic derivatives of homocysteine thiolactone
EP1595890A3 (fr) * 1993-06-07 2007-03-21 Duke University Peptides de synthèse inhibiteurs de la transmission du VIH
US7122190B2 (en) 1993-06-07 2006-10-17 Duke University Fusion proteins comprising DP-178 and other viral fusion inhibitor peptides useful for treating aids
US6133418A (en) * 1993-06-07 2000-10-17 Duke University Synthetic peptide inhibitors of HIV transmission
US6333395B1 (en) 1993-06-07 2001-12-25 Shawn Barney Compositions for inhibition of membrane fusion-associated events, including human parainfluenza virus transmission
US6093794A (en) * 1993-06-07 2000-07-25 Trimeris, Inc. Isolated peptides derived from the Epstein-Barr virus containing fusion inhibitory domains
US6518013B1 (en) 1993-06-07 2003-02-11 Trimeris, Inc. Methods for the inhibition of epstein-barr virus transmission employing anti-viral peptides capable of abrogating viral fusion and transmission
US7988974B2 (en) 1993-06-07 2011-08-02 Duke University Antifusogenic proteins comprising human immunodeficiency virus type 1 (HIV-1) gp41 DP-178 polypeptide variants and a macromolecular carrier
US6017536A (en) * 1993-06-07 2000-01-25 Trimeris, Inc. Simian immunodeficiency virus peptides with antifusogenic and antiviral activities
EP0774971A4 (fr) * 1993-06-07 1998-06-10 Univ Duke Peptides de synthese inhibiteurs de la transmission du vih
US6824783B1 (en) 1993-06-07 2004-11-30 Duke University Methods for inhibition of membrane fusion-associated events, including HIV transmission
US6951717B1 (en) 1993-06-07 2005-10-04 Trimeris, Inc. Methods and compositions for inhibition of membrane fusion-associated events, including HIV transmission
EP1595890A2 (fr) * 1993-06-07 2005-11-16 Duke University Peptides de synthèse inhibiteurs de la transmission du VIH
US7794725B1 (en) 1993-06-07 2010-09-14 Trimeris, Inc. Isolated peptides derived from human immunodeficiency virus types 1 and 2 containing fusion inhibitory domains
US6228983B1 (en) 1993-06-07 2001-05-08 Trimeris, Inc. Human respiratory syncytial virus peptides with antifusogenic and antiviral activities
US5464933A (en) * 1993-06-07 1995-11-07 Duke University Synthetic peptide inhibitors of HIV transmission
EP0774971A1 (fr) * 1993-06-07 1997-05-28 Duke University Peptides de synthese inhibiteurs de la transmission du vih
US7273614B2 (en) 1993-06-07 2007-09-25 Duke University Nucleic acids encoding DP-178 and other viral fusion inhibitor peptides useful for treating aids
US7803524B2 (en) 1994-02-23 2010-09-28 Siemens Healthcare Diagnostics Products Gmbh Antigenic HIV gp41 chimeric polypeptides comprising the MVP5180/91 epitope SKGKLIS
US6605427B2 (en) 2000-02-10 2003-08-12 Panacos Pharmaceuticals, Inc. Assay for detection of viral fusion inhibitors
EP1692265A4 (fr) * 2003-11-04 2007-08-29 Univ Tulane Methode de prevention des infections virales: fusion cellulaire par inhibition de la region de depart de fusion dans des virus a arn avec proteines d'enveloppe fusiogenes a membrane de classe i
US7491793B2 (en) 2003-11-04 2009-02-17 The Administrators Of The Tulane Educational Fund Influenza virus inhibiting peptides
US9725487B2 (en) 2003-11-04 2017-08-08 The Administrators Of The Tulane Educational Fund Compositions and methods for measles virus inhibition
EP1692265A2 (fr) * 2003-11-04 2006-08-23 The Administrators Of The Tulane Educational Fund Methode de prevention des infections virales: fusion cellulaire par inhibition de la region de depart de fusion dans des virus a arn avec proteines d'enveloppe fusiogenes a membrane de classe i
US8598116B2 (en) 2003-11-04 2013-12-03 The Administrators Of The Tulane Treatment of influenza virus infection
EP2261376A3 (fr) * 2003-11-04 2011-02-23 The Administrators of the Tulane Educational Fund Procédé de prévention de la fusion virus-cellule en inhibant la fonction de la région d'initiation dans des virus à ARN dotés de protéines d'enveloppe fusiogène de membrane de classe I
EP1714153A2 (fr) * 2004-02-06 2006-10-25 I.N.S.E.R.M. Institut National de la Sante et de la Recherche Medicale Polypeptide derive de gp41, composition de vaccin comprenant ce polypeptide et utilisations de celle-ci pour traiter une personne infectee par un virus vih
US8222204B2 (en) 2006-05-03 2012-07-17 The Administrators of the Tulane Educational Fund and Autoimmune Technologies, LLC Influenza inhibiting compositions and methods
US7727963B2 (en) 2006-11-10 2010-06-01 Cara Therapeutics, Inc. Synthetic peptide amides
US8906859B2 (en) 2006-11-10 2014-12-09 Cera Therapeutics, Inc. Uses of kappa opioid synthetic peptide amides
US8236766B2 (en) 2006-11-10 2012-08-07 Cara Therapeutics, Inc. Uses of synthetic peptide amides
US8486894B2 (en) 2006-11-10 2013-07-16 Cara Therapeutics, Inc. Synthetic peptide amides and dimeric forms thereof
US8536131B2 (en) 2006-11-10 2013-09-17 Cara Therapeutics, Inc. Synthetic peptide amides and dimers thereof
US7842662B2 (en) 2006-11-10 2010-11-30 Cara Therapeutics, Inc. Synthetic peptide amide dimers
US10913769B2 (en) 2006-11-10 2021-02-09 Cara Therapeutics, Inc. Synthetic peptide amides and dimers thereof
US8217007B1 (en) 2006-11-10 2012-07-10 Cara Therapeutics, Inc. Synthetic peptide amides
US8951970B2 (en) 2006-11-10 2015-02-10 Cara Therapeutics, Inc. Synthetic peptide amides for pain
US9321810B2 (en) 2006-11-10 2016-04-26 Cara Therapeutics, Inc. Uses of kappa opioid synthetic peptide amides
US9334305B2 (en) 2006-11-10 2016-05-10 Cara Therapeutics, Inc. Synthetic peptide amides and dimers thereof
US7713937B2 (en) 2006-11-10 2010-05-11 Cara Therapeutics, Inc. Synthetic peptide amides and dimeric forms thereof
US9359399B2 (en) 2006-11-10 2016-06-07 Cara Therapeutics, Inc. Synthetic peptide amides
US9353157B2 (en) 2007-06-25 2016-05-31 The Administrators Of The Tulane Educational Fund Influenza inhibiting compositions and methods
US8604165B2 (en) 2007-06-25 2013-12-10 The Administrators Of The Tulane Educational Fund Influenza inhibiting compositions and methods

Also Published As

Publication number Publication date
AU1711888A (en) 1988-12-02
EP0311675A4 (fr) 1989-10-04
EP0311675A1 (fr) 1989-04-19

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