US20030099663A1 - Pharmaceutical composition comprising an antigen - Google Patents

Pharmaceutical composition comprising an antigen Download PDF

Info

Publication number
US20030099663A1
US20030099663A1 US10/114,823 US11482302A US2003099663A1 US 20030099663 A1 US20030099663 A1 US 20030099663A1 US 11482302 A US11482302 A US 11482302A US 2003099663 A1 US2003099663 A1 US 2003099663A1
Authority
US
United States
Prior art keywords
antigen
composition according
vaccine
compounds
core
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.)
Abandoned
Application number
US10/114,823
Other languages
English (en)
Inventor
Julia-Kristina Fleitmann
Frank Mattner
Michael Buschle
Jack Melling
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.)
CISTEM Biotechnologies GmbH
Original Assignee
CISTEM Biotechnologies GmbH
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 CISTEM Biotechnologies GmbH filed Critical CISTEM Biotechnologies GmbH
Assigned to CISTEM BIOTECHNOLOGIES GMBH reassignment CISTEM BIOTECHNOLOGIES GMBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MELLING, JACK, FLEITMANN, JULIA-KRISTINA, BUSCHLE, MICHAEL, MATTNER, FRANK
Publication of US20030099663A1 publication Critical patent/US20030099663A1/en
Priority to US11/082,595 priority Critical patent/US20050163797A1/en
Priority to US12/248,397 priority patent/US20090104217A1/en
Priority to US12/248,744 priority patent/US20090130135A1/en
Priority to US13/110,454 priority patent/US8277815B2/en
Abandoned legal-status Critical Current

Links

Images

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
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/29—Hepatitis virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55516—Proteins; Peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55522—Cytokines; Lymphokines; Interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55583—Polysaccharides
    • 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
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16211—Lymphocryptovirus, e.g. human herpesvirus 4, Epstein-Barr Virus
    • C12N2710/16234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • 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
    • C12N2740/16034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/24011—Flaviviridae
    • C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
    • C12N2770/24222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/24011—Flaviviridae
    • C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
    • C12N2770/24234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • the invention relates to a pharmaceutical composition especially to be used as a vaccine.
  • Vaccines are a very successful, yet cost saving medical intervention.
  • Several catastrophic illnesses including small pox and poliomyelitis have been, due to intense vaccination programmes, eliminated from the face of this earth or are on the brink of extinction (Nossal, Nat Med 4, (1998), 475-476).
  • vaccines can save more lives (and money) than any other medical intervention.
  • this notion is valid for a whole panel of diseases including tuberculosis, diphteria, pertussis, measles and tetanus, there are no effective vaccines for numerous ailments including most viral infections, such as AIDS, and other illnesses including malaria, or even cancer.
  • T cells which recognize molecules expressed on pathogen infected cells.
  • vaccines are designed that induce both T cells distinguishing diseased, and/or infected cells from normal cells and, simultaneously, antibodies secreted by B cells recognizing pathogens in extracellular compartments.
  • vaccines are administered as a combination of pathogen-derived antigens together with compounds that induce or enhance immune responses against these antigens (these compounds are usually termed adjuvants).
  • antigens are whole organisms such as inactivated or attenuated viruses or bacteria, fungi, protozoa or even cancer cells.
  • Antigens may also consist of sub-fractions of theses organism/tissues, proteins or, in their most simple form, peptides.
  • Antigens can also be recognized by the immune system in form of glycosylated proteins or peptides and may also be or contain polysaccharides or lipids.
  • Short peptides can be used since for example cytotoxic T cells recognize antigens in form of short usually 8-11 amino acids long peptides in conjunction with major histocompatibility complex (MHC) (Rammensee et al., Immunogenetics 41, (1995), 178-228). B cells recognize longer peptides starting at around 15 amino acids (Harlow et al, Cold Spring Harbor: Cold Spring Harbor Laboratory, (1988)). By contrast to T cell epitopes the three dimensional structure of B cell antigens may also be important for recognition by antibodies. In order to obtain sustained, antigen-specific immune responses, adjuvants need to trigger immune cascades that involve all cells of the immune system necessary.
  • MHC major histocompatibility complex
  • said adjuvants are acting, but are not restricted in their mode of action, on so-called antigen presenting cells (APCs). These cells usually first encounter the antigen(s) followed by presentation of processed or unmodified antigen to immune effector-cells. Intermediate cell types may also be invovled. Only effector cells with the appropriate specificity are activated in a productive immune response.
  • the adjuvant may also locally retain antigens and co-injected other factors.
  • the adjuvant may act as a chemoattractant for other immune cells or may act locally and/or systemically as a stimulating agent for the immune system.
  • HGH Human growth hormone
  • HGH greatly enhances the efficacy of a viral vaccine preparation
  • Stephenson and Melling who showed that HGH greatly enhances the efficacy of a viral vaccine preparation, first demonstrated the usefulness of HGH in a vaccine context (Stephenson et al., J Infect Dis 164, (1991), 188-191). They co-injected HGH with a vaccine for tick-born encephalitis (TBE) virus, an endemic virus transmitted by ticks.
  • TBE tick-born encephalitis
  • HGH potentiated vaccine efficacy and led to the protection of animals after only one injection of the vaccine.
  • the mechanism of how HGH enhanced vaccine efficacy is unclear, but it was speculated that cell mediated immunity played a significant role.
  • HGH human immuno deficiency virus
  • Mellado et al. demonstrated that if an antigen derived from human immuno deficiency virus (HIV) is applied to mice, they develop a so called Th1 type T helper cell response indicative of a cellular immune response (Mellado et al., Vaccine 16, (1998), 1111-1115).
  • HGH which is viewed as exemplary for a whole class of primarily neuroactive compounds (see e.g. Levite, PNAS 95 (1998), 12544-12549, Scholzen et al, Exp. Dermetal. 7 (1998), 81-96), may have a positive effect on the immune system, but the mechanisms remain unclear.
  • Polycationic polymers for example the polycationic amino acid polymers poly-L-arginine and poly-L-lysine, have been shown to allow very efficient charging of antigen presenting cells (APCs) with antigens in vitro and in vivo (Buschle et al., Gene Ther Mol Biol 1, (1998), 309-321; Buschle et al., Proc Natl Acad Sci USA 94, (1997), 3256-3261; Schmidt et al., Proc Natl Acad Sci USA 94, (1997), 3262-3267). This is thought to be the key event for triggering immune cascades eventually leading to the induction of antigen specific immune effector cells that are able to destroy or neutralize targets.
  • APCs antigen presenting cells
  • GB 1 290 141 discloses a vaccine containing antigenic material with a base-rich peptide as an adjuvant.
  • the vaccine may consist (as antigenic material) of live or killed organisms, whole or disrupted, or of preparations of natural toxins or products of the organsim, or of preparations of extracts of the organisms, alone or in combination with one another.
  • the base-rich peptide used as an adjuvant must contain at least 50% residues which have a free amino group, such as polylysine, polyornithine, polyarginine and polydiaminobutyric acids.
  • U.S. Pat. No. 3,725,545 describes that it is possible to potentiate the antibody production ability of nucleic acids containing preparations by adding cationically charged polymers in combination with single-stranded or multi-stranded nucleic acid polymers.
  • polycationic polymers are polyornithine, lysozyme, DEAE-Dextran, histone, hexadimethrine bromide and polylysine.
  • WO 91/04052 also relates to DEAE-Dextran as a polycationic adjuvant in a vaccine composition.
  • This polycationic adjuvant is incorporated into a vaccine which further comprises the antigenic substance (the antigen) and saponin as a further adjuvant.
  • the antigenic substance the antigen
  • saponin the antigen
  • neither polycationic compounds nor saponin as combined adjuvants may be regarded as an immunostimulating substance within the course of the present invention.
  • an immunostimulating substance selected from neuroactive compounds, hormones, compounds having a growth hormone activity and mixtures thereof, and
  • HGH human growth hormone
  • the immunostimulating effect is especially given as these substances e.g. induce T cells, B cells, NK cells or APCs or alter the cytokine secretion of T cells, B cells, NK cells or APCs.
  • the present invention is based on the careful selection of immunostimulating substances to be used in connection with the polycationic polymer.
  • the polycationic polymer serves as adjuvant in the present invention. It is therefore clear that other adjuvants described in the prior art may not be regarded as immunostimulating substances in the course of the present invention. Although such additional adjuvants may be also added to the present vaccine, they cannot substitute the immunostimulating substance selected according to the present invention.
  • HGH is specifically preferred for the present invention as immunostimulating substance.
  • isoforms are known for this protein, recombinant forms of such isoforms being specifically preferred for the present invention.
  • HGH is administered in a stabilized composition according to the present invention, especially with stabilizers such as glycine, tensides, mannitol or polyoxyethylene-polyoxypropylene block copolymers, and buffers, such as sodium phosphate or citrate (WO 89/09614, EP 0 211 601 A, EP 0 587 958 A).
  • the antigens to be used in the present compositions are not critical.
  • proteins or peptides derived from a viral or a bacterial pathogen or from fungi or parasites are used as such antigens (including derivatized antigens like glycosylated, lipidated, glycolipidated or hydroxylated antigens.
  • carbohydrates, lipids or glycolipids may be used as antigens themselves.
  • Preferred pathogens are selected from HIV, HBV, HCV, Influenza virus, Rotavirus, Staphylococcus aureus, Chlamydia pneumoniae, Mycobacterium tuberculosis, Streptococcus pneumoniae, Bacillus anthracis, Vibrio cholerae , Plasmodium sp. ( Pl. falciparum, Pl. vivax , etc.), Aspergillus sp. or Candida albicans .
  • the derivation process may include the purification of a specific protein from the pathogen, the inactivation of the pathogen as well as the proteolytic or chemical derivatization or stabilization of such a protein.
  • tumor antigens cancer vaccines
  • autoimmune antigens may be used in the pharmaceutical composition according to the present invention. With such compositions a tumor vaccination or a treatment for autoimmume diseases may be performed.
  • antigens are used which induce an antigen-spcific type-1 like tumoral and cell mediated immune response in vivo.
  • CD4- and CD8-epitopes are preferred, especially in connection with vaccines against pathogens and tumors.
  • Preferred immunostimulating substances include pituitary growth hormones or derivatives thereof, especially proteolytically or recombinantly produced derivatives which exhibit the functional properties of the growth hormone (described e.g. in the U.S. Pat. Nos. 5,854,026 or 5,849,535, 5,424,199 or 5,580,723). It has been shown that such substances are also able to alter the cytokine secretion of T cells, Bcells or NK cells, but they may also exert effects on APCs or B cells or NK cells. Their immunostimulating effect was connected in the literature with sepcific receptors on T cells (s. Levite (1998)).
  • Other preferred neuroactive compounds are selected from but are not restricted to growth hormones, especially human growth hormone, neurokinin A, vasoactive intestinal peptide, neuropeptide Y, substance P, Thyrotrophin (TSH), Insulin-like growth factor I (IGF-1), prolactin, lactogen, luteinizing hormone, follicle stimulating hormone, dehydroepiandosterone (DHEA), Thymosin, Thymulin, Kentsin, melatonin, semaphorins (s. Levite (19913); Scholzen et al (1998); Aronin et al, Ann. Rev. Physiol. 48 (1986), 537-549; Berczi, Acta Paediatr Suppl.
  • growth hormones especially human growth hormone, neurokinin A, vasoactive intestinal peptide, neuropeptide Y, substance P, Thyrotrophin (TSH), Insulin-like growth factor I (IGF-1), prolactin, lactogen, lute
  • the polycationic compound to be used according to the present invention may be any polycationic compound which shows the characteristic effect according to the WO 97/30721.
  • Preferred polycationic compounds are selected from basic polypeptides, organic polycations, basic polyaminoacids or mixtures thereof. These polyaminoacids should have a chain length of at least 4 amino acid residues (see: Tuftsin as described in Goldman et al (1983)).
  • polycationic compounds may be produced chemically or recombinantly or may be derived from natural sources.
  • Preferred polycationic compounds derived from natural sources include HIV-REV or HIV-TAT derived cationic peptides, antennapedia peptides, chitosan (or other derivatives of chitin) and other peptides derived from these peptides or proteins by biochemical or recombinant production.
  • the present invention also relates to vaccines which comprise a composition according to the present invention.
  • the present invention is also drawn to the use of the composition according to the present invention for manufacturing a vaccine.
  • the present compositions may be applied to a patient, e.g. a vaccination candidate, in effient amounts e.g. by weekly, bi-weekly or mounthly intervals. Patients to be treated with the present compositions may also be vaccinated repeatedly or only once.
  • a preferred use of the present invention is the active immunisation, especially of humans or aninmals without protection against the specific antigen.
  • the route of application for the present composition is not critical, e.g. subcutaneous, intramuscular, intradermal or transdermal injection is suitable as well as oral uptake.
  • the present composition is also possible to apply the present composition separatedly e.g. by injecting the immunostimulating substance separatedly from the antigen/polycation composition.
  • the present invention is therefore also directed to a kit comprising a composition containing the antigen and the polycationic polymer as one component and a composition containing the immunostimulating or chemotactic substance as a second component.
  • the components may be applied at the same site or time, however, an application at different sites or at a different time or for a different time period is also possible. It is also possible to vary the systemic or local applications of the composition or the components, respectively.
  • the present application relates to a vaccine against HCV infections comprising a polycationic polymer, an immunostimulating substance and an HCV antigen being selected from the group consisting of Core 23-44 (KFPGGGQIVGGVYLLPRRGPRL), CORE 131-150 (ADLMGYIPLVGAPLGGAARA), CORE 132-140 (DLMGYIPAV), NS3 1073-1081 (CINGVCWTV), NS3 1207-1226 (SPVFTDNSSPPAVPQSFQVA), NS3 1248-1261 (GYKVLVLNPSVAAT), NS3 1585-1604 (YLVAYQATVCARAQAPPPSW), NS4 1655-1675 (VVTSTWVLVGGVLAALAAYCL), NS4 1765-1784 (MWNFISGIQYLAGLSTLPGN), NS4 1909-1929 (GEGAVQWMNRLIAFASRGNHV), NS4 1785-1804 (PAIASLMAFTAAVTSPLTT
  • the CD8 epitopes are especially selected from Core 31-40, Core 35-44, Core 132-140, NS3 1585-1593, NS3 1585-1594, NS4 1666-1675, NS4 1769-1777, NS4 1773-1783, NS4 1787-1795, NS4 1789-1797, NS4 1789-1798, NS4 1807-1816, NS4 1809-1817 und NS4 1811-1820.
  • HCV epitopes have been shown to be surprisingly effective in vaccines containing polycationic peptides, especially polyarginine.
  • the present invention also relates to a vaccine comprising the selected HCV antigens together with the polyamino acid adjuvants, especially polyarginine, and optionally the immunogenic compounds according to the present invention.
  • FIG. 1 shows the synergistic action of poly-L-arginine and human growth hormone in the induction of antigen specific T cells.
  • FIG. 2 shows the synergistic action of poly-L-arginine and substance P in the induction of antigen specific T cells.
  • Peptides were synthesized by standard solid phase F-moc synthesis, HPLC purified and analysed by mass spectroscopy for purity.
  • mice On day 0 mice were injected subcutaneously with a total volume of 100 ⁇ l containing the above mentioned compounds. Animals were sacrificed 10 days after injection of the vaccine and mesenteric and inguinal lymph nodes harvested. Results are illustrated in FIG. 1.
  • Lymphocytes were prepared from lymph nodes as follows: cells were passed through a 70 ⁇ m sieve and washed twice with DMEM medium (GIBCO BRL) containing 2,5% fetal calf serum (FCS; SIGMA chemicals). Cells were adjusted to 10 7 cells/ml in complete medium (DMEM +10% FCS). IFN- ⁇ -ELISPOT assays were carried out in triplicate as described (Miyahira et al., 1995). This method is a widely used procedure allowing the quantification of antigen-specific T cells. Lymphocytes were restimulated with TRP-2 peptide or with an ovalbumin-derived peptide (SIINFEKL) with the same MHC restriction serving as negative control.
  • DMEM medium containing 2,5% fetal calf serum (FCS; SIGMA chemicals). Cells were adjusted to 10 7 cells/ml in complete medium (DMEM +10% FCS). IFN- ⁇ -ELISPOT assays were carried out in triplicate as described
  • HCV antigens according to table 1 and the antigens disclosed in Lamonaca et al., Hepatology 30(4) (1999), 1088-1098.
  • HIV antigens according to table 2 TABLE 2 Peptide Sequence Gag 77-85 SLYNTVATL Envelope 77-85 DPNPQEVVL POL 476-484 ILKEPVHGV
  • Epstein-Barr virus the antigens according to table 1 of Rickinson et al Ann. Rev. Immunol. 15 (1997), 405-431.
  • Substance P was tested as a further example for a neuroactive peptide (Marx, Science 205 (1979), 886).
  • Substance P (RPKPQQFFGLM-NH 2 ; SP) was synthesized and purified according to standard procedures. Experiments were conducted as in Example 1 with the exception that spleens instead of lymph nodes were used.
  • Splenocytes prepared from spleens as follows: cells were passed through a 70 ⁇ m sieve and washed once with DMEM medium (GIBCO BRL). Red blood cells were lysed with “red blood cells lysis buffer” (Sigma) for 1 minute and washed twice with DMEM medium (GIBCO BRL). Cells were adjusted to 3*10 6 cells/ml in complete medium (DEMEM+5% FCS). IFN- ⁇ -ELISPOT was carried out as described (Miyahira et al., 1995).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Virology (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)
US10/114,823 1999-10-01 2002-04-01 Pharmaceutical composition comprising an antigen Abandoned US20030099663A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US11/082,595 US20050163797A1 (en) 1999-10-01 2005-03-17 Pharmaceutical composition comprising an antigen
US12/248,397 US20090104217A1 (en) 1999-10-01 2008-10-09 Pharmaceutical Composition Comprising An Antigen
US12/248,744 US20090130135A1 (en) 1999-10-01 2008-10-09 Hcv vaccines
US13/110,454 US8277815B2 (en) 1999-10-01 2011-05-18 Pharmaceutical composition comprising an antigen

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
AT0168099A AT408721B (de) 1999-10-01 1999-10-01 Pharmazeutische zusammensetzung enthaltend ein antigen
AT1680/99 1999-10-01
EPPCT/EP00/09657 2000-10-02
PCT/EP2000/009657 WO2001024822A2 (fr) 1999-10-01 2000-10-02 Composition pharmaceutique comprenant un antigene

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/009657 Continuation WO2001024822A2 (fr) 1999-10-01 2000-10-02 Composition pharmaceutique comprenant un antigene

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/082,595 Continuation US20050163797A1 (en) 1999-10-01 2005-03-17 Pharmaceutical composition comprising an antigen

Publications (1)

Publication Number Publication Date
US20030099663A1 true US20030099663A1 (en) 2003-05-29

Family

ID=3518675

Family Applications (4)

Application Number Title Priority Date Filing Date
US10/114,823 Abandoned US20030099663A1 (en) 1999-10-01 2002-04-01 Pharmaceutical composition comprising an antigen
US11/082,595 Abandoned US20050163797A1 (en) 1999-10-01 2005-03-17 Pharmaceutical composition comprising an antigen
US12/248,397 Abandoned US20090104217A1 (en) 1999-10-01 2008-10-09 Pharmaceutical Composition Comprising An Antigen
US13/110,454 Expired - Fee Related US8277815B2 (en) 1999-10-01 2011-05-18 Pharmaceutical composition comprising an antigen

Family Applications After (3)

Application Number Title Priority Date Filing Date
US11/082,595 Abandoned US20050163797A1 (en) 1999-10-01 2005-03-17 Pharmaceutical composition comprising an antigen
US12/248,397 Abandoned US20090104217A1 (en) 1999-10-01 2008-10-09 Pharmaceutical Composition Comprising An Antigen
US13/110,454 Expired - Fee Related US8277815B2 (en) 1999-10-01 2011-05-18 Pharmaceutical composition comprising an antigen

Country Status (8)

Country Link
US (4) US20030099663A1 (fr)
EP (6) EP1218031B1 (fr)
AR (1) AR025937A1 (fr)
AT (2) AT408721B (fr)
AU (1) AU7912100A (fr)
DE (1) DE60029115T2 (fr)
PE (1) PE20010704A1 (fr)
WO (1) WO2001024822A2 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040209804A1 (en) * 2002-12-31 2004-10-21 Chandrika Govardhan Human growth hormone crystals and methods for preparing them
US20050158336A1 (en) * 2003-12-12 2005-07-21 City Of Hope Synthetic conjugate of CpG single-stranded DNA and T-help/CTL fusion peptide
US20050208482A1 (en) * 2004-03-16 2005-09-22 Cohen David I Tat-based immunomodulatory compositions and methods for their discovery and use
US20050226890A1 (en) * 1999-08-12 2005-10-13 Cohen David I Tat-based vaccine compositions and methods of making and using same
US20050244434A1 (en) * 1999-08-12 2005-11-03 Cohen David I Tat-based tolerogen compositions and methods of making and using same
US20080145383A1 (en) * 2004-03-12 2008-06-19 Intercell Ag Method for Solubilizing Peptide Mixtures
US20090023629A1 (en) * 2005-12-23 2009-01-22 Altus Pharmaceuticals Inc. Compositions comprising polycation-complexed protein crystals and methods of treatment using them
US20090155294A1 (en) * 2003-07-11 2009-06-18 Michael Buschle Hcv vaccines
US20110150924A1 (en) * 2009-12-22 2011-06-23 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Device, Method, and system for neural modulation as vaccine adjuvant in a vertebrate subject
US8277815B2 (en) 1999-10-01 2012-10-02 Intercell Ag Pharmaceutical composition comprising an antigen
US9206239B2 (en) 2009-03-23 2015-12-08 Pin Pharma, Inc. Treatment of cancers with immunostimulatory HIV Tat derivative polypeptides
US9663556B2 (en) 2013-10-04 2017-05-30 Pin Pharma, Inc. Treatment of cancers with immunostimulatory HIV tat derivative polypeptides

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004517609A (ja) * 2000-09-01 2004-06-17 エピミューン インコーポレイテッド Ｈｌａ−ａ２．１結合ペプチドおよびそれらの用途
EP1195381A1 (fr) * 2000-09-28 2002-04-10 Immusystems GmbH Epitopes du virus de l'hépatite C spécifiques à des lymphocytes T de type CD4+
WO2002053184A2 (fr) * 2001-01-05 2002-07-11 Intercell Ag Utilisations de composes polycationiques
CA2433967A1 (fr) * 2001-01-05 2002-07-11 Intercell Ag Utilisations de composes polycationiques
US7244438B2 (en) 2001-01-05 2007-07-17 Intercell Ag Uses for polycationic compounds
AT410798B (de) 2001-01-26 2003-07-25 Cistem Biotechnologies Gmbh Verfahren zur identifizierung, isolierung und herstellung von antigenen gegen ein spezifisches pathogen
EP1390495B1 (fr) * 2001-05-21 2007-07-04 Intercell AG Molécules oligodésoxynucléiques immunostimulatrices
JP2005533855A (ja) 2002-07-24 2005-11-10 インターツェル・アクチェンゲゼルシャフト 病原性ウイルスからの別のリーディングフレームによりコードされる抗原
CA2484339A1 (fr) 2002-09-13 2004-03-25 Intercell Ag Procede pour isoler des peptides du virus de l'hepatite c
JP5116971B2 (ja) 2002-10-15 2013-01-09 インターセル アーゲー Ｂ群連鎖球菌の接着因子をコードする核酸、ｂ群連鎖球菌の接着因子、およびその使用
EP2287314A1 (fr) 2003-03-04 2011-02-23 Intercell AG Antigènes pyogènes streptococcus
WO2004084938A1 (fr) 2003-03-24 2004-10-07 Intercell Ag Vaccins ameliores
EP1608756B1 (fr) 2003-03-31 2009-11-18 Intercell AG Antigénes staphylococcus epidermidis
EP2333114A1 (fr) 2003-04-15 2011-06-15 Intercell AG S. pneumoniae antigènes
CA2522986A1 (fr) 2003-05-07 2004-11-18 Intercell Ag Antigenes i + ii contre s. agalactiae
EP2327720A1 (fr) 2003-05-30 2011-06-01 Intercell AG Antigènes d'entérocoque
US9573979B2 (en) 2004-09-24 2017-02-21 Susanne Modrow Modified VP1-capsid protein of parvovirus B19
DE602005015605D1 (de) * 2004-10-29 2009-09-03 Intercell Ag Hcv impfstoff für chronische hcv patienten
AU2006342608A1 (en) * 2006-04-25 2007-11-01 Intercell Ag HCV vaccinations
EP2287189A1 (fr) 2006-07-07 2011-02-23 Intercell AG Petits antigènes de Streptococcus pyogenes et leur utilisation
AU2007295927A1 (en) 2006-09-15 2008-03-20 Intercell Ag Borrelia antigens
EP1923069A1 (fr) 2006-11-20 2008-05-21 Intercell AG Peptides protecteurs contre S. pneumoniae et compositions, méthodes et utilisations associés
CA2675379A1 (fr) 2007-01-12 2008-07-17 Intercell Ag Proteines protectrices de s. agalactia, leurs combinaisons et leurs procedes d'utilisation
EP2152731A2 (fr) 2007-05-02 2010-02-17 Intercell AG Antigènes de la klebsiella
CN101883782A (zh) 2007-06-18 2010-11-10 英特塞尔股份公司 衣原体抗原
WO2009046872A2 (fr) * 2007-09-11 2009-04-16 Mondobiotech Laboratories Ag Utilisation d'un peptide en tant qu'agent thérapeutique
CN101977927A (zh) 2008-03-17 2011-02-16 英特塞尔股份公司 针对肺炎链球菌保护的肽以及与其有关的组合物、方法和用途
WO2009129498A2 (fr) * 2008-04-17 2009-10-22 Immuneregen Biosciences, Inc. Substance p et ses analogues en tant qu’adjuvant d’une composition immunogène pour le cancer
WO2010089340A2 (fr) 2009-02-05 2010-08-12 Intercell Ag Peptides protecteurs contre e. faecalis, procédés et utilisations liés à ceux-ci
WO2010092176A2 (fr) 2009-02-13 2010-08-19 Intercell Ag Antigènes haemophilus influenzae non typables
LT2753352T (lt) 2010-09-03 2017-05-25 Valneva Austria Gmbh Išskirtas toksino a ir toksino b baltymų polipeptidas iš c. difficile ir jo panaudojimas
EP2446898A1 (fr) * 2010-09-30 2012-05-02 Laboratorios Del. Dr. Esteve, S.A. Utilisation de l'hormone de croissance pour améliorer la réponse immunitaire chez des patients immunodéprimés
BR112013029417B1 (pt) * 2011-05-18 2022-10-25 Matrivax, Inc Composições de vacina de matriz proteica incluindo policátions e método de preparo das mesmas
WO2015106003A1 (fr) 2014-01-08 2015-07-16 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Voies de ras en tant que marqueurs de protection contre le vih et méthode d'amélioration d'efficacité de vaccin
WO2015153969A1 (fr) 2014-04-04 2015-10-08 The Board Of Trustees Of The Leland Stanford Junior University Découverte de ligands pour les récepteurs de cellule t
JP2022533318A (ja) 2019-05-20 2022-07-22 ヴァルネヴァ エスイー 気道感染の治療または予防のためのサブユニットワクチン
WO2020240268A1 (fr) 2019-05-31 2020-12-03 Universidad De Chile Formulation immunogène qui induit une protection contre escherichia coli produisant la toxine shiga (stec)
CA3210412A1 (fr) 2021-04-09 2022-10-13 Urban Lundberg Vaccin contre le metapneumovirus humain
WO2023232901A1 (fr) 2022-06-01 2023-12-07 Valneva Austria Gmbh Vaccin contre clostridium difficile

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3725545A (en) * 1971-02-03 1973-04-03 R Maes Enhancement of antibody production by nucleic acid-polycation complexes
US5562910A (en) * 1989-09-25 1996-10-08 University Of Utah Research Foundation Vaccine compositions and method for enhancing an immune response
US5980911A (en) * 1994-05-04 1999-11-09 Commonwealth Scientific And Industrial Research Organisation Adjuvant
US6558670B1 (en) * 1999-04-19 2003-05-06 Smithkline Beechman Biologicals S.A. Vaccine adjuvants
US6572866B1 (en) * 1997-05-01 2003-06-03 Protechtion Unlimited, Inc. Nerve growth factor as a vaccine adjuvant
US20030152580A1 (en) * 1994-07-21 2003-08-14 Alessandro Sette Hla binding peptides and their uses

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1290141A (fr) * 1968-05-31 1972-09-20
US4342832A (en) 1979-07-05 1982-08-03 Genentech, Inc. Method of constructing a replicable cloning vehicle having quasi-synthetic genes
US4777245A (en) * 1984-01-06 1988-10-11 Genelabs Incorporated Non-human primate monoclonal antibodies and methods
EP0211601A3 (fr) 1985-07-30 1988-01-13 International Minerals And Chemical Corporation Stabilisation d'hormones de croissance
US4837202A (en) 1987-09-14 1989-06-06 Pitman-Moore, Inc. Method for stimulating the immune system
US5096885A (en) 1988-04-15 1992-03-17 Genentech, Inc. Human growth hormone formulation
GB8821656D0 (en) 1988-09-15 1988-10-12 Health Lab Service Board Pharmaceutical compositions for eliciting immunostimulant effect
DE3834729A1 (de) * 1988-10-12 1990-04-19 Behringwerke Ag Verwendung von zink-oder eisenhydroxid zur adjuvierung von antigenloesungen und auf diese weise adjuvierte antigenloesungen
DE68929151T2 (de) 1988-10-28 2000-07-20 Genentech, Inc. Verfahren zum nachweis von aktiven domänen und aminosäureresten in polypeptiden und hormonvarianten
US5534617A (en) 1988-10-28 1996-07-09 Genentech, Inc. Human growth hormone variants having greater affinity for human growth hormone receptor at site 1
GB8921470D0 (en) * 1989-09-22 1989-11-08 Peptide Technology Ltd Vaccines
FR2658895B1 (fr) 1990-02-27 1992-07-03 Hydraulique Meca Ste Nle Gle Robinet-vanne.
GB9010058D0 (en) * 1990-05-04 1990-06-27 Health Lab Service Board Method and composition for the treatment of cancer
US6172189B1 (en) * 1990-08-24 2001-01-09 Abbott Laboratories Hepatitis C assay utilizing recombinant antigens
US5574132A (en) * 1991-04-05 1996-11-12 Biochem Immunosystems Inc. Peptides and mixtures thereof for detecting antibodies to hepatitis C virus (HCV)
US5202119A (en) 1991-06-28 1993-04-13 Genentech, Inc. Method of stimulating immune response
JPH06199894A (ja) * 1992-08-27 1994-07-19 Asahi Chem Ind Co Ltd Ｃ型肝炎ウイルスのコア蛋白質領域に存在するｔ細胞エピトープ
EP0587958A1 (fr) 1992-09-14 1994-03-23 Fabriques De Tabac Reunies S.A. Procédé et dispositif de régulation de la vitesse d'un produit transporté dans une conduite, et machine à cigarettes équipée d'un tel dispositif
WO1994015634A1 (fr) * 1992-12-30 1994-07-21 Matthias Rath Oligopeptide tat et rev utilises pour le traitement du vih
FR2708855B1 (fr) * 1993-08-13 1995-10-13 Dolisos Lab Compositions pharmaceutiques immunoadjuvantes ou immunostimulantes.
US5830877A (en) 1993-08-26 1998-11-03 The Regents Of The University Of California Method, compositions and devices for administration of naked polynucleotides which encode antigens and immunostimulatory
EP0992581B2 (fr) * 1993-11-04 2011-05-25 Innogenetics N.V. Epitopes immunodominants de lymphocytes T humains du virus de l'hépatite C
JPH10503473A (ja) * 1994-04-08 1998-03-31 アメリカ合衆国 細胞傷害性ｔリンパ球刺激およびｈｃｖ曝露診断用ｃ型肝炎ウイルスコアペプチド
US5831068A (en) * 1995-08-21 1998-11-03 Duke University Method to increase the density of antigen on antigen presenting cells
ES2190388T3 (es) 1995-09-21 2006-04-01 Genentech, Inc. Variantes de la hormona de crecimiento humana.
AUPN801296A0 (en) * 1996-02-12 1996-03-07 Csl Limited Stabilised growth hormone formulation and method of preparation thereof
CO4600681A1 (es) 1996-02-24 1998-05-08 Boehringer Ingelheim Pharma Composicion farmaceutica para la modulacion inmunitaria
US6231859B1 (en) * 1996-12-02 2001-05-15 Aquila Biopharmaceuticals, Inc. Saponin adjuvant compositions
US6413517B1 (en) * 1997-01-23 2002-07-02 Epimmune, Inc. Identification of broadly reactive DR restricted epitopes
EP0855184A1 (fr) * 1997-01-23 1998-07-29 Grayson B. Dr. Lipford Composition pharmaceutique comprenant un polynucléotide et un antigène notamment pour la vaccination
DE69834494T2 (de) * 1997-07-10 2007-03-01 Mannkind Corp., Valencia Vorrichtung zur induktion einer ctl-antwort
AUPP060097A0 (en) 1997-11-28 1998-01-08 Commonwealth Scientific And Industrial Research Organisation Adjuvant system for enhanced response
US6072889A (en) 1997-12-03 2000-06-06 The Raytheon Company Method and system for imaging target detection
WO2000011186A1 (fr) * 1998-08-21 2000-03-02 The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Vaccins contenant un peptide modifie du vhc
CA2377525A1 (fr) * 1999-07-19 2001-03-29 Epimmune, Inc. Induction de reponses immunitaires cellulaires au virus de l'hepatite c mettant en oeuvre des compositions de peptides et d'acide nucleique
AT408721B (de) 1999-10-01 2002-02-25 Cistem Biotechnologies Gmbh Pharmazeutische zusammensetzung enthaltend ein antigen
EP1195381A1 (fr) * 2000-09-28 2002-04-10 Immusystems GmbH Epitopes du virus de l'hépatite C spécifiques à des lymphocytes T de type CD4+
TWI358301B (en) 2003-07-11 2012-02-21 Intercell Ag Hcv vaccines
DE602005015605D1 (de) * 2004-10-29 2009-09-03 Intercell Ag Hcv impfstoff für chronische hcv patienten

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3725545A (en) * 1971-02-03 1973-04-03 R Maes Enhancement of antibody production by nucleic acid-polycation complexes
US5562910A (en) * 1989-09-25 1996-10-08 University Of Utah Research Foundation Vaccine compositions and method for enhancing an immune response
US5980911A (en) * 1994-05-04 1999-11-09 Commonwealth Scientific And Industrial Research Organisation Adjuvant
US20030152580A1 (en) * 1994-07-21 2003-08-14 Alessandro Sette Hla binding peptides and their uses
US6572866B1 (en) * 1997-05-01 2003-06-03 Protechtion Unlimited, Inc. Nerve growth factor as a vaccine adjuvant
US6558670B1 (en) * 1999-04-19 2003-05-06 Smithkline Beechman Biologicals S.A. Vaccine adjuvants

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050226890A1 (en) * 1999-08-12 2005-10-13 Cohen David I Tat-based vaccine compositions and methods of making and using same
US20050244434A1 (en) * 1999-08-12 2005-11-03 Cohen David I Tat-based tolerogen compositions and methods of making and using same
US8277815B2 (en) 1999-10-01 2012-10-02 Intercell Ag Pharmaceutical composition comprising an antigen
US9376479B2 (en) 2002-12-31 2016-06-28 Anjinomoto Althea, Inc. Human growth hormone crystals and methods for preparing them
US20040209804A1 (en) * 2002-12-31 2004-10-21 Chandrika Govardhan Human growth hormone crystals and methods for preparing them
US20090155294A1 (en) * 2003-07-11 2009-06-18 Michael Buschle Hcv vaccines
US20110300170A1 (en) * 2003-07-11 2011-12-08 Michael Buschle Hcv vaccines
US9090673B2 (en) * 2003-12-12 2015-07-28 City Of Hope Synthetic conjugate of CpG DNA and T-help/CTL peptide
US10987420B2 (en) 2003-12-12 2021-04-27 City Of Hope Synthetic conjugate of CpG DNA and T-help/CTL peptide
US10596254B2 (en) 2003-12-12 2020-03-24 City Of Hope Synthetic conjugate of CpG DNA and T-help/CTL peptide
US9974854B2 (en) 2003-12-12 2018-05-22 City Of Hope Synthetic conjugate of CpG DNA and T-help/CTL peptide
US20050158336A1 (en) * 2003-12-12 2005-07-21 City Of Hope Synthetic conjugate of CpG single-stranded DNA and T-help/CTL fusion peptide
US20080145383A1 (en) * 2004-03-12 2008-06-19 Intercell Ag Method for Solubilizing Peptide Mixtures
US20080155703A1 (en) * 2004-03-16 2008-06-26 Cohen David I Tat-Based Immunomodulatory Compositions and Methods of Their Discovery and Use
US20050208482A1 (en) * 2004-03-16 2005-09-22 Cohen David I Tat-based immunomodulatory compositions and methods for their discovery and use
US20110195078A1 (en) * 2004-03-16 2011-08-11 Nanirx, Inc. Tat-based immunomodulatory compositions and methods for their discovery and use
US7927580B2 (en) 2004-03-16 2011-04-19 Nanirx, Inc. Tat-based immunomodulatory compositions and methods of their discovery and use
US20090023629A1 (en) * 2005-12-23 2009-01-22 Altus Pharmaceuticals Inc. Compositions comprising polycation-complexed protein crystals and methods of treatment using them
US9206239B2 (en) 2009-03-23 2015-12-08 Pin Pharma, Inc. Treatment of cancers with immunostimulatory HIV Tat derivative polypeptides
US8321012B2 (en) 2009-12-22 2012-11-27 The Invention Science Fund I, Llc Device, method, and system for neural modulation as vaccine adjuvant in a vertebrate subject
US8364258B2 (en) 2009-12-22 2013-01-29 The Invention Science Fund I, Llc Device, method, and system for neural modulation as vaccine adjuvant in a vertebrate subject
US8725251B2 (en) 2009-12-22 2014-05-13 The Invention Science Fund I, Llc Device, method, and system for neural modulation as vaccine adjuvant in a vertebrate subject
US8788037B2 (en) 2009-12-22 2014-07-22 The Invention Science Fund I, Llc Device, method, and system for neural modulation as vaccine adjuvant in a vertebrate subject
US20110150924A1 (en) * 2009-12-22 2011-06-23 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Device, Method, and system for neural modulation as vaccine adjuvant in a vertebrate subject
US9663556B2 (en) 2013-10-04 2017-05-30 Pin Pharma, Inc. Treatment of cancers with immunostimulatory HIV tat derivative polypeptides
US10159707B2 (en) 2013-10-04 2018-12-25 Pin Pharma, Inc. Treatment of cancers with immunostimulatory HIV Tat derivative polypeptides

Also Published As

Publication number Publication date
EP1745798A2 (fr) 2007-01-24
AT408721B (de) 2002-02-25
US20110300169A1 (en) 2011-12-08
AU7912100A (en) 2001-05-10
AR025937A1 (es) 2002-12-18
EP2269640A3 (fr) 2011-05-04
PE20010704A1 (es) 2001-07-11
EP2269641A3 (fr) 2011-05-04
EP2269642A2 (fr) 2011-01-05
DE60029115D1 (de) 2006-08-10
US8277815B2 (en) 2012-10-02
ATA168099A (de) 2001-07-15
EP1218031A2 (fr) 2002-07-03
EP2269643A2 (fr) 2011-01-05
EP2269643A3 (fr) 2011-05-04
EP2269640A2 (fr) 2011-01-05
EP2269642A3 (fr) 2011-05-04
US20090104217A1 (en) 2009-04-23
EP2269641A2 (fr) 2011-01-05
WO2001024822A3 (fr) 2001-12-20
WO2001024822A2 (fr) 2001-04-12
ATE331529T1 (de) 2006-07-15
EP1218031B1 (fr) 2006-06-28
US20050163797A1 (en) 2005-07-28
EP1745798A3 (fr) 2007-03-07
DE60029115T2 (de) 2007-06-14

Similar Documents

Publication Publication Date Title
US8277815B2 (en) Pharmaceutical composition comprising an antigen
US7528223B2 (en) Antigens encoded by alternative reading frames from pathogenic viruses
RU2118164C1 (ru) Вакцинная композиция, обладающая свойством вызывать цитолитический т-клеточный ответ у млекопитающих, способ получения цитолитического т-клеточного ответа in vivo, способ получения вакцины
US8784837B2 (en) Vaccines comprising an immunostimulatory peptide and an immunostimulatory oligodeoxynucleic acid molecule
RU2121849C1 (ru) Вакцинная композиция против гепатита, способ профилактики гепатита
AU3166501A (en) Pharmaceutical composition for immunomodulation and preparation of vaccines comprising an antigen and an immunogenic oligodeoxynucleotide and a polycationic polymer as adjuvants
US20100047271A1 (en) Vaccine compositions
JP2006521321A (ja) 免疫応答を促進するためのミョウバンおよびＴｈ１免疫応答誘起アジュバントの使用
US8691234B2 (en) Vaccine formulation potentiated by the combination of DNA and an antigen
KR20040022423A (ko) 아쥬반트로서 제１형 ｉｆｎ을 포함하는 백신 및 이와관련된 방법
EP1448223B1 (fr) Augmentation de la thymosine assurant une immunisation genetique
US20030060413A1 (en) Derivatives of pseudo-peptides, their preparation and their biological uses
Guillén et al. Development of a technological framework for using virus-like particles as adjuvants in prophylactic and therapeutic vaccines: demonstration of effect in animal models and humans

Legal Events

Date Code Title Description
AS Assignment

Owner name: CISTEM BIOTECHNOLOGIES GMBH, AUSTRIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:FLEITMANN, JULIA-KRISTINA;MATTNER, FRANK;BUSCHLE, MICHAEL;AND OTHERS;REEL/FRAME:013155/0018;SIGNING DATES FROM 20020311 TO 20020327

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION