WO1987007613A1 - Small peptides which inhibit binding to t-4 receptors and act as immunogens - Google Patents
Small peptides which inhibit binding to t-4 receptors and act as immunogens Download PDFInfo
- Publication number
- WO1987007613A1 WO1987007613A1 PCT/US1987/001270 US8701270W WO8707613A1 WO 1987007613 A1 WO1987007613 A1 WO 1987007613A1 US 8701270 W US8701270 W US 8701270W WO 8707613 A1 WO8707613 A1 WO 8707613A1
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- WIPO (PCT)
- Prior art keywords
- thr
- ser
- peptide
- tyr
- asn
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70514—CD4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1036—Retroviridae, e.g. leukemia viruses
- C07K16/1045—Lentiviridae, e.g. HIV, FIV, SIV
- C07K16/1063—Lentiviridae, e.g. HIV, FIV, SIV env, e.g. gp41, gp110/120, gp160, V3, PND, CD4 binding site
-
- 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 synthetically produced short peptide sequences which inhibit HTLV-III/LAV (here- inafter referred to as HIV) binding to human cells by blocking receptor sites on the cell surface, and thus preventing viral infectivity of human T cell.
- HIV HTLV-III/LAV
- these peptides also have use as vaccines to pre- ven-t development of Acquired Immune Disease Syndrome (AIDS).
- Monoclonal antibodies to the ' peptides could also be used as • diagnostic agents to identify the HIV virus.
- peptides and antibodies to the peptides would have use in preparing test kits for identification of HIV carriers or persons suffering from AIDS.
- HIV HIV
- the complete nucleotide sequence of the AIDS (HIV) virus has been reported by several -investigators. (See Lee Ratner, et al., Nature 313, p. 277, January 1985; Muesing, et al., Nature 313, p. 450, February 1985; and Wain-Habson, et al.. Cell 40, pp. 9-17, January 1985.)
- the envelope gene has been associated particu- larly with antigenicity and infectivity. However, the envelope portion is also known to have regions which are highly divergent.
- the HIV virus envelope glycopro- tein has been shown to affix covalently to the brain membranes of humans, rats, and monkeys and to cells of the immune system.
- viruses may exert cell and tissue tropism by attachment at highly specific sites on cell membrane receptors has encouraged investigators to seek agents which would bind at the viral receptor sites of cell membranes and thus prevent binding of a specific virus to these cells.
- a demonstration of specific receptor-mediated vaccinia virus infectivity being blocked by synthetic peptides has been previously demonstrated (Epstein, et al.. Nature 318, pp. 663-667).
- the HIV virus has been shown to bind to a surface molecule known as the CD4 or T4 region, which is present on various cells susceptable to HIV infection, including T lymphocytes and macrophages. (See Shaw, et al.. Science 226, pp.
- PURPOSE It was the object of the present invention to provide peptides that would act to alleviate symptoms of AIDS by preventing binding of HIV (AIDS virus) to receptor sites of cells of brain membranes and the immune system. It was also an object of the present invention to provide peptides for use as vaccines to be used to give rise to antibodies that would protect against deve- lopment of AIDS in persons who might become exposed to the HIV (AIDS virus). It was a further object of the present invention to provide diagnostic means of identifying presence of antibodies to HIV or HIV envelope protein.”
- a peptide of formula (I) - R a -Ser-Thr-Thr-Thr-Asn-Tyr-R b (I) where R a represents an amino terminal residue Ala- or D-Ala and R b represents a carboxy terminal residue -Thr or -Thr amide or a derivative thereof with an addi- tional Cys- residue at one or both of the amino and carboxy terminals, or a peptide of formula (II): - R 1 -R 2 -R -R 4 -R 5 (II) where R 1 is an amino terminal residue Thr-, Ser-, Asn-, Glu-, Arg-, lie- or Leu-, R 2 is Thr, Ser or Asp, R 3 is Thr, Ser, Asn, Arg, Gin, Lys or Trp, R 4 is Tyr, and R 5 is preferably a carboxy terminal residue -Thr, -Arg or
- the active compounds of the invention may exist as physiologically acceptable salts of the peptides. This class of peptides has been found to bind to the T4 viral receptors.
- M ost preferred peptides are the following octapeptides of formula (I ) : D-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr and D-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-amide and the following pentapeptides of formula (II): - Thr-Asp-Asn-Tyr-Thr Thr-Thr-Ser-Tyr-Thr Thr-Thr-Asn-Tyr-Thr and their analogues with D-Thr as the amino terminal residue and/or an amide derivate at the carboxy terminal.
- the compounds of the invention may be beneficially modified by the methods known to enhance passage of molecules across the blood-brain barrier. Acetylation has proven to be especially useful for enhancing binding activity of the peptide.
- the terminal amino and carboxy sites are particularly preferred sites for modification.
- the peptides of this may also be modified in a constraining conformation to provide improved stability and oral availability.
- peptide T (contained in the ARV isolate) to be the relevant moiety, as addi- tional viral sequences became available, it became clear that the relevant, bioactive sequence, might be a shorter pentapeptide comprising, nominally, peptide T [4-8] , or the sequence TTNYT.
- Table 1 substantial homologies were discerned only in this, shorter, region. The majority of changes are the interconversions of serine (S) and threonine (T), two closely related amino acids. The tyrosine of posi- tion 7 of peptide T is an invariant feature of all these constructs indicating that it may be obligatory for bioactivity.
- Substitutions occurring at position 5 include T, G, R or S.
- Position 4 and 6 were first re- stricted (with one exception) to S, T and N, all amino acids containing uncharged polar groups with closely similar steric properties.
- An assessment of general sequence concordance among 5 various AIDS viral isolates (9, 10) reveals that the region around and including the peptide T sequence is a highly variable area. Such variability may indicate specialization through strong selective diversification of the function(s) which may be defined at this locus.
- these peptide T analogs seem to exist in multiple forms, reminiscent of met and leu enkephalin.
- These pentapep- tide sequences represented in these various AIDS virus isolates are biologically active and capable of interac- ting as agonists of the CD4 receptor - previously known largely as a surface "marker" of T helper cells.
- lumbers refer to relative positions of amino acids within the ARV env sequence (9) .
- the seven amino acid peptide CYS-THR-THR-ASN-TYR- THR-CYS is also active. Addition of cysteines to a core does not adversely affect activity.
- the pepties were custom synethesized by Peninsula Laboratories under a confidentiality agreement between the inventors and the manufacturer. The Merrifield method of solid phase peptide synethesis was used. (See U.S. Patent No.3,531,258 which " is incorporated herein by reference.)
- the synethesized peptides are especially preferred. While peptide T and the pentapep- tide which is a portion thereof could be ioslated from the virus, the peptides prepared in accord with Merri- field are free of viral and cellular debris.
- the peptides of the invention may be produced by conventional methods of peptide synthesis. Both solid phase and liquid phase methods may be used. We have found the solid phase of Merrifield to be particu- larly convenient. In this process, the peptide is synthe- sized in a stepwise manner while the carboxy end of the chain is covalently attached to the insoluble support. During the intermediate synthetic stages, the peptide remains in the solid phase and therefore can be conven- iently manipulated.
- the solid support is a chloro- methylated styrene-divinylbenzene copolymer.
- N-protected form of the carboxy terminal amino acid e.g., a t-bu-toxycarbonyl protected (Boc-) amino acid
- a t-bu-toxycarbonyl protected (Boc-) amino acid is reacted with the chloromethyl residue of the chloromethylated styrene divinlybenzene copolymer resin to produce a protected amino acyl derivative of the resin, where the amino acid is coupled to the resin a benzyl ester.
- This is deprotected and reacted with a protected form of the next required amino acid thus producing a protected dipeptide attached to the resin.
- the amino acid will generally be used in activated form, e.g., by use of a carbodiimide or active ester.
- the compounds of the invention were found to effec- tively block receptor sites of cells and to prevent cell infectivity with HIV (AIDS virus) in monkey, rat and human brain membranes and cells of the immune system.
- a pharmaceutical composition comprising a peptide compound of the invention in association with a pharma- ceutically acceptable carrier or excipient, adapted for use in human or veterinary medicine.
- Such composi- tions may be presented for use in conventional manner in admixture with one or more physiologically accpetable carriers of excipients.
- the compositions may optionally further contain one or more other therapeutic agents which may, if desired, be a different antiviral agent.
- the peptides according to the invention may be formulated for oral, buccal, parenteral, topical or rectal administration.
- the peptides according to the inven- tion may be formulated for injection or infusion and may be presented in unit dose form in ampoules or in multidose containers with an added preservative.
- the compositions may take such forms as suspensions, solu- tions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stab- ilizing and/or dispersing agents.
- the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use.
- compositions according to the invention may also contain other active ingredients such as antimicrobial agents or preservatives.
- the compositions may contain from 0.001-99% of the active material.
- the invention further provides a process for pre- paring a pharmaceutical composition which comprises bringing a peptide of the invention into association with a pharmaceutically acceptable excipient or carrier.
- the daily dosage as employed for treatment of an adult human of approximately 70 kg body weight will range from 0.2 mg to 10 mg, preferably 0.5 to 5 mg, which may be admin- istered in 1 to 4 doses, for example, depending on the route of administration and the condition of the patient. It was postulated that the affinity constants are similar to those of morphine.
- a further aspect of this invention relates to vaccine preparations containing a peptide according to the invention, to provide protection against infection by AIDS virus.
- the vaccine will contain an effective immunogenic amount of peptide, e.g., 1 ⁇ g to 20 mg/kg of host, optionally conjugated to a protein such as human serum albumin, in a suitable vehicle, e.g., sterile water, saline or buffered saline.
- a suitable vehicle e.g., sterile water, saline or buffered saline.
- Adjuvants may be employed, such as aluminum hydroxide gel.
- Administra- tion may be by injection, e.g., intramuscularly, inter- peritoneally, subcutaneously, or intravenously.
- Admini- stration may take place once or at a plurality of times, e.g., at 1-4 week intervals.
- a yet further aspect of this invention relates to test kits for the detection of the AIDS virus and antibodies to the AIDS virus containing a peptide accord- ing to the invention as source of antigen, or a mono- clonal antibody elicited by a peptide according to the invention.
- a peptide according to the invention may be used in a test kit to detect AIDS infec- tion and to diagnose AIDS and pre-AIDS conditions by using it as the test reagent in an enzyme-linked immuno- sorbent assay (ELISA) or an enzyme immunodot assay.
- ELISA enzyme-linked immuno- sorbent assay
- test kits may include an insoluble porous surface or solid substrate to which the antigenic peptide or monoclonal antibody has been preabsorbed or covalently bound, such surface or substrate preferably in the form of icrotiter plates or wells; test sera; heteroantisera which specifically bind to and saturate the antigen or antibody absorbed to the surface or support; various diluents and buffers; labelled conjugates for the detec- tion of specifically bound antibodies and other signal- generating reagents such as enzyme substrates, cofactors and chromogens.
- the peptide according to the invention may be used as an immunogen to elicit monoclonal antibodies which specifically bind to the relevant portion of the envelope sequence of the AIDS virus, using conventional techniques; such monoclonal antibodies form a further feature of the invention.
- HTLV-IIIb of HIV was propaged in H9 cells, and the gp 120 was isolated by immunoaffinity chromatography and preparative NaDodS0 4 /PAGE. Purified gp 120 was labelled with 125 I by the chloramine-T method. Fresh human, monkey and rat hippocamus were quickly homogenized (Polytron, Brinkmann Instruments) in 100 vol of ice-cold 50 mM Hepes (pH 7.4).
- the membranes collected by centrifugation (15,000 x g) were washed in the original buffer volume and were used fresh or stored at -70°C. Before use, brain membranes and highly purified T cells (ref. 16; gift of Larry, Wahl) were preincubated for 15-30 min in phosphate-buffered saline (PBS).
- PBS phosphate-buffered saline
- Membranes derived from 20 mg (initial wet weight) of brain were incubated with 28,000 cpm of 1 5 I-gp 120 for 1 hr at 37 °C in 200 1 (final volumne) of 50 mM Hepes containing 0.1% bovine serum albumin and the peptidase inhibitors bacitracin (0.005%), aprotinin (0.005%), leupeptin (0.001%), and chymostatin (0.001%). Incubations were rapidly vacuum-filtered and counted to determine the receptor-bound material. Immunoprecipitation.
- Immunoprecipitates were prepared by incubation (overnight at 4°C) of 0.5% Triton X-100/PBS solubilized, lactoperoxidase/glucose oxidase/ I-iodinated brain membranes or intact T cells with indicated mAbs at 10 ⁇ g per reaction.
- a solid-phase immunoabsorbant (immunobeads , Bio-Rad) was used to pre- cipitate immune complexes prior to their resolution by NaDodSO 4 /PAGE.
- Control incubations contained no primary mAb or a subclass control mAb (OKT8). Chemical Neuoranatomy and Computer-Assisted Densi- tometry.
- Figure 1A shows a cross-linking of 1 5I-gp 120
- brain membranes contain a T4 antigen of about 60
- T lymphocytes (Fig. 1C) which is absent in brain mem-
- Example 3 Chemical Neuroanatomy, Computer-Assis- ted Densitometry. Cryostat-cut 25 micron sections of fresh-frozen human, monkey, and rat brain were thaw- mounted and dried onto gel-coated slides and receptors visualized as described by Herkenham and Pert, J. Neuro- sci. , 2_, pp. 1129-1149 (1982). Incubations, with or without antibodies (10 ⁇ g/ml) against T4, T4A, T8 and Til, were conducted overnight at 0° C in RPMI, cross- linked onto their antigens and visualized with 125 I-goat anti-mouse antibody.
- T4 antigen on a rostral to caudal series or coronal sections of squirrel monkey brain.
- These experiments show that there are detectable levels of T4 monoclonal antibody binding to cytoarchitec- tionally meaningful areas of the brain stem (e.g., the substantia nigra), but the striking pattern of cortical enrichment is apparent at every level of the neuoraxis.
- OKT8 a T-lymphocyte directed monoclonal antibody from the same subclass as OKT4, exhibits no observable pat- tern.
- the more superficial layers within the cerebral cortex contain the densest concentrations of the T4 antigen; the frontal and perilimbic cortex overlying the amydala are particularly receptor-rich throughout the deep layers.
- the hippocampal formation has the desest concentration of receptors in the monkey, rat and human brain.
- Dark field microscopy of squirrel monkey sections dipped in photographic emulsion revealed that the band of densest receptor labelling is located within the molecular layers of the dentate gyrus and hippocampus proper (which contain very few neurons).
- receptors appear to be rightly distributed over the neuropil (the neuronal extensions of dendrites and axons) or may be localized to a specific subset of un- stained astroglial cells.
- mice Mabs directed against other human cell surface antigens including OKT8 and OKTll gave no detectable pattern on rat brain when visualized by 12 I-goat anti-mouse IgG secondary antibody just as there was no reproducible, detectable antigen/receptor with secondary antibody alone.
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
HU873289A HUT48907A (en) | 1986-06-03 | 1987-05-27 | Process for production of small peptides linked to 1,4 receptors with immunogene effect and medical preparatives containing these substances |
KR1019880700115A KR930008448B1 (ko) | 1986-06-03 | 1987-05-27 | T-4수용체에 대한 결합을 억제하며, 면역원으로서 작용하는 소형 펩티드 |
DK198800532A DK173667B1 (da) | 1986-06-03 | 1988-02-02 | Små peptider, der hæmmer binding til T-4 receptorer og virker som immunogener, farmaceutisk produkt som omfatter mindst 1 af peptiderne samt prøveudstyr til påvisning af antistoffer |
NO880479A NO176022C (no) | 1986-06-03 | 1988-02-03 | Analogifremgangsmåte til fremstilling av små peptider som hindrer binding til T4-reseptorer og virker som immunorganer |
FI885630A FI94352C (fi) | 1986-06-03 | 1988-12-02 | Menetelmä peptidien valmistamiseksi, jotka estävät sitoutumista T-4-reseptoreihin ja toimivat immunogeeneinä |
FI943795A FI99115C (fi) | 1986-06-03 | 1994-08-18 | T-4 reseptoreihin sitoutuvaa antigeeniä kohtaan suunnattujen vasta-aineiden kanssa reagoivia peptidejä ja niiden diagnostinen käyttö |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US86991986A | 1986-06-03 | 1986-06-03 | |
US869,919 | 1986-06-03 | ||
US87858686A | 1986-06-26 | 1986-06-26 | |
US878,586 | 1986-06-26 | ||
US4814887A | 1987-05-11 | 1987-05-11 | |
US048,148 | 1987-05-11 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1987007613A1 true WO1987007613A1 (en) | 1987-12-17 |
Family
ID=27367286
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1987/001270 WO1987007613A1 (en) | 1986-06-03 | 1987-05-27 | Small peptides which inhibit binding to t-4 receptors and act as immunogens |
Country Status (16)
Country | Link |
---|---|
JP (1) | JP2680011B2 (ko) |
KR (1) | KR930008448B1 (ko) |
AU (1) | AU604719B2 (ko) |
CA (1) | CA1341066C (ko) |
DE (1) | DE3787927T2 (ko) |
DK (1) | DK173667B1 (ko) |
ES (1) | ES2061497T3 (ko) |
FI (1) | FI94352C (ko) |
HU (1) | HUT48907A (ko) |
IE (1) | IE61725B1 (ko) |
IL (1) | IL82719A (ko) |
MX (1) | MX172337B (ko) |
NO (1) | NO176022C (ko) |
NZ (1) | NZ220485A (ko) |
PT (1) | PT84992B (ko) |
WO (1) | WO1987007613A1 (ko) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1893233A2 (en) * | 2005-06-23 | 2008-03-05 | Candace Pert | Therapeutic peptides and vaccines |
US8603965B2 (en) | 2006-06-12 | 2013-12-10 | Fusogen Pharmaceuticals, Inc. | Pharmaceutical composition for the prophylaxis and treatment of HIV infection and its use |
-
1987
- 1987-05-27 AU AU75408/87A patent/AU604719B2/en not_active Ceased
- 1987-05-27 KR KR1019880700115A patent/KR930008448B1/ko not_active IP Right Cessation
- 1987-05-27 HU HU873289A patent/HUT48907A/hu unknown
- 1987-05-27 CA CA000538202A patent/CA1341066C/en not_active Expired - Fee Related
- 1987-05-27 JP JP62503520A patent/JP2680011B2/ja not_active Expired - Fee Related
- 1987-05-27 WO PCT/US1987/001270 patent/WO1987007613A1/en active IP Right Grant
- 1987-05-28 NZ NZ220485A patent/NZ220485A/xx unknown
- 1987-05-28 IE IE138887A patent/IE61725B1/en not_active IP Right Cessation
- 1987-05-29 IL IL82719A patent/IL82719A/xx not_active IP Right Cessation
- 1987-06-02 PT PT84992A patent/PT84992B/pt unknown
- 1987-06-03 MX MX006751A patent/MX172337B/es unknown
- 1987-06-03 ES ES87304939T patent/ES2061497T3/es not_active Expired - Lifetime
- 1987-06-03 DE DE87304939T patent/DE3787927T2/de not_active Expired - Fee Related
-
1988
- 1988-02-02 DK DK198800532A patent/DK173667B1/da active IP Right Grant
- 1988-02-03 NO NO880479A patent/NO176022C/no unknown
- 1988-12-02 FI FI885630A patent/FI94352C/fi not_active IP Right Cessation
Non-Patent Citations (8)
Title |
---|
CELL, Volume 40, issued January 1985, WAIN-HOBSON et al., "Nucleotide Sequence of the Aids Virus, Lav", pages 9-17. * |
CELL, Volume 45, issued 06 June 1986, STARCICH et al., "Identification and Characterization of Conserved and Variable Regions in the Envelope Gene of HTLV-III/LAV, the Retrovirus of Aids", pages 637-648. * |
NATURE, (London, England), Volume 312, issued December 1984, DALGLEISH et al., "The CD4 (T4) Antigen is an Essential Component of the Receptor for the Aids Retrovirus", pages 763-767. * |
NATURE, (London, England), Volume 312, issued December 1984, KLATZMANN et al., "T-Lymphocyte T4 Molecule Behaves as the Receptor for Human Retrovirus Lav", pages 767-768. * |
NATURE, (London, England), Volume 313, issued January 1985, RATNER et al., "Complete Nucleotide Sequence of the Aids Virus, HTLV-III", pages 277-284. * |
NATURE, (London, England), Volume 320, issued 10 April 1986, CHAKRABARTI et al., "Expression of the HTLV-III Envelope Gene by a Recombinant Vaccinia Virus", pages 535-537. * |
PROC. NATL. ACAD. SCI. U.S.A., Volume 83, issued December 1986, PERT et al., "Octapeptides Deduced from the Neuropeptide Receptor-Like Pattern of Antigen T4 in Brain Potently Inhibit Human Immunodeficiency Virus Receptor Binding and T-Cell Infectivity", pages 9254-9258. * |
SCIENCE, (Washington, D.C., U.S.A.), Volume 227, issued February 1985, SANCHEZ-PESCADOR et al., "Nucleotide Sequence and Expression of an Aids - Associated Retrovirus (ARV-Z)", pages 484-492. * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1893233A2 (en) * | 2005-06-23 | 2008-03-05 | Candace Pert | Therapeutic peptides and vaccines |
EP1893233A4 (en) * | 2005-06-23 | 2010-03-31 | Rapid Pharmaceuticals Ag | PEPTIDES AND THERAPEUTIC VACCINES |
AU2006261133B2 (en) * | 2005-06-23 | 2012-04-05 | Rapid Pharmaceuticals Ag | Therapeutic peptides and vaccines |
US8603965B2 (en) | 2006-06-12 | 2013-12-10 | Fusogen Pharmaceuticals, Inc. | Pharmaceutical composition for the prophylaxis and treatment of HIV infection and its use |
Also Published As
Publication number | Publication date |
---|---|
ES2061497T3 (es) | 1994-12-16 |
NO880479L (no) | 1988-02-03 |
CA1341066C (en) | 2000-08-01 |
FI94352B (fi) | 1995-05-15 |
NO176022B (no) | 1994-10-10 |
JPH01502659A (ja) | 1989-09-14 |
PT84992B (pt) | 1990-03-08 |
DE3787927D1 (de) | 1993-12-02 |
DK173667B1 (da) | 2001-05-28 |
HUT48907A (en) | 1989-07-28 |
NZ220485A (en) | 1989-08-29 |
IL82719A (en) | 1992-11-15 |
DE3787927T2 (de) | 1994-03-03 |
NO880479D0 (no) | 1988-02-03 |
FI885630A (fi) | 1988-12-02 |
FI94352C (fi) | 1995-08-25 |
IE871388L (en) | 1987-12-03 |
JP2680011B2 (ja) | 1997-11-19 |
AU604719B2 (en) | 1991-01-03 |
IL82719A0 (en) | 1987-11-30 |
DK53288A (da) | 1988-02-02 |
KR880701247A (ko) | 1988-07-26 |
FI885630A0 (fi) | 1988-12-02 |
AU7540887A (en) | 1988-01-11 |
PT84992A (en) | 1987-07-01 |
IE61725B1 (en) | 1994-11-30 |
KR930008448B1 (ko) | 1993-09-04 |
NO176022C (no) | 1995-01-18 |
DK53288D0 (da) | 1988-02-02 |
MX172337B (es) | 1993-12-14 |
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