WO1999053063A1 - PEPTIDE LIGAND HAVING SPECIFIC AFFINITY FOR THE HIV1 RETROVIRUS p24 PROTEIN - Google Patents
PEPTIDE LIGAND HAVING SPECIFIC AFFINITY FOR THE HIV1 RETROVIRUS p24 PROTEIN Download PDFInfo
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- WO1999053063A1 WO1999053063A1 PCT/FR1999/000831 FR9900831W WO9953063A1 WO 1999053063 A1 WO1999053063 A1 WO 1999053063A1 FR 9900831 W FR9900831 W FR 9900831W WO 9953063 A1 WO9953063 A1 WO 9953063A1
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Classifications
-
- 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
- C07K16/1054—Lentiviridae, e.g. HIV, FIV, SIV gag-pol, e.g. p17, p24
-
- 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
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
Definitions
- the present invention relates to a peptide ligand having a specific affinity for the p24 protein of the acquired immunodeficiency virus type 1 (HIV-1).
- the invention also relates to a murine, or chimeric human-murine type antibody, having a specific affinity with respect to the p24 protein of HIV-1, the DNA molecule corresponding to the peptide ligand, the cassettes and vectors comprising this DNA molecule, a method of in vitro detection of HIV-1 infection from a biological sample, as well as the use of chimeric antibodies for use as a medicament.
- AIDS Acquired Immunodeficiency Syndrome
- AIDS is a slow-growing disease and people with HIV are infectious when they have had no symptoms of the disease for years. It is therefore necessary to be able to diagnose infection with the virus as soon as possible.
- HIV genome has been sequenced, and the functions of the various genes have been elucidated.
- Viral reverse transcriptase and integrase are produced by cleavage of a large gag-pol fusion protein, while viral capsid proteins are produced by cleavage of the gag protein.
- a gag p55 precursor protein is cut by a protease encoded by the pol gene, which produces the main protein p24 (sometimes called p25) and the proteins p1 8 and p1 3.
- Each antibody consists of two “light” chains and two “heavy” chains.
- the antigen binding region or binding site region determining complementarity
- the two chains fold into a series of unstructured clusters, distributed in a discreet manner, which are called domains.
- a single domain antibody (Dabs) comprises only one of the domains of a given antibody.
- variable regions which include hypervariable regions which differ from one antibody to another, the rest of these variable regions being made up of relatively constant amino acids. forming a framework with the specific structure of the antibody.
- the other domains of the antibody, particularly those in the C-terminal position, are said to be constant, that is to say that they are identical for all the antibodies of the same class.
- the first object of the present invention relates mainly to a peptide ligand and / or peptide equivalent having a specific affinity with respect to the p24 protein of the HIV-1 retrovirus, comprising at least one peptide strand corresponding to the N— part.
- the light chain comprising a series of amino acids determining three so-called hypervariable regions L1, L2 and L3, respectively positioned from 70 to 99, from 145 to 165, from 262 to 285, according to the sequence of amino acids described by the sequence SEQ ID No 1, and the heavy chain comprising a sequence of amino acids determining three regions called hypervariable H1, H2 and H3, respectively positioned from 76 to 105, of 155 to 195, from 295 to 327, according to the sequence of amino acids described by the sequence SEQ ID No 2.
- "equivalent" for a peptide means that the chemical structure is similar and that the function of the peptide is identical.
- a peptide equivalent may therefore have different amino acids but will have identical functionality, in this case vis-à-vis the p24 protein. Therefore, an amino acid is said to be equivalent to another amino acid, when their chemical characteristics, such as polarity, hydrophobicity, and / or basicity, and / or acidity, and / or neutrality, are substantially the same.
- a leucine is equivalent to an isoleucine, within the meaning of the preceding definition.
- the peptide ligands according to the invention can be such as in the native state, when it is a monoclonal antibody for example, or chemically modified.
- chemical modification is meant any chemical alteration of at least one functional group of the peptide sequence, substantially preserving, or even increasing, the biological properties of said peptide sequence with respect to the p24 antigen of HIV-1.
- Part of the chemical modifications considered above are the replacement of an amino acid of the L series with an amino acid of the D series, a modification of the side chains of the amino acids, such as acetylation of the amino functions, carboxymethylation of the thiol functions, an esterification of peptide bonds such as carba, retro-inverso, reduced and methylene-oxy bonds.
- the peptide ligand comprises a peptide strand comprising the light chain and the heavy chain of an antibody corresponding respectively to the sequence SEQ ID No 1 and SEQ ID No 2.
- the ligand comprises a peptide strand which consists of the light chain and / or the heavy chain of an antibody corresponding respectively to the sequence SEQ ID No 1 and SEQ ID No 2.
- the ligand is an antibody.
- the ligand is a monoclonal antibody of murine origin, named in the present invention "13B5".
- the ligand is an antibody of chimeric type, consisting of regions called constant of human origin and regions called hypervariable of murine origin.
- Such antibodies can also be called recombinant antibodies.
- the inserts of recombinant DNA coding for the variable regions are fused, with a DNA coding for constant regions of the heavy and light chains, then they are transferred into appropriate host cells, for example after incorporation into hybrid vectors.
- Fab fragment of the antibody 13B5 Since the sequence of the Fab fragment of the antibody 13B5 is disclosed in the present invention, those skilled in the art can manufacture, using recombinant DNA technology with host cells such as yeasts or bacteria, various antibody fragments comprising the hypervariable regions mentioned above, and which retain their specificity towards p24.
- the ligand comprises a marker.
- a marker is called conjugate.
- Said conjugate can be made from a fragment of said antibody, insofar as the latter retains its specificity towards p24.
- the label can be, for example, an enzyme, a fluorescent type label, a chemiluminescent type label, an avidin, a biotin, or a radioactively labeled antibody.
- the enzymes used for the antibody conjugates of the invention are, for example, Raiford peroxidase, alkaline phosphatase, beta-D-galactosidase, glucose oxidase, glucoamylase, carbonic anhydrase, acetylcholinesterase, lysosyme, malate dehydrogenase or glucose-6-phosphatase dehydrogenase.
- the markers used for the fluorescent type conjugates according to the invention can be fluorescein, fluorochrome, rhodamine.
- the chemiluminescent type markers are for example the acridium esters of luminol.
- the antibodies or antibody fragments are linked to the conjugation partner directly or by a spacer group or chelating agent.
- chelating agents As an example of chelating agents, mention may be made of ethylene diaminetetraacetic acid (EDTA), diethylenetriamine-pentaacetic acid (DPTA), 1, 4,8, 1 1 -tetra azatetradecane, acid 1, 4, 8, 1 1 - tetraazatetradecane-1, 4.8, 1 1 -tetraacetic, acid 1 -oxa-4.7, 1 2, 1 5- tetraaza heptadecane-4.7, 1 2, 1 5-tetraacetic, or the like.
- EDTA ethylene diaminetetraacetic acid
- DPTA diethylenetriamine-pentaacetic acid
- 1, 4,8, 1 1 -tetra azatetradecane acid 1, 4, 8, 1 1 - tetraazatetradecane-1
- 4.8 1 1 -tetraacetic, acid 1 -oxa-4.7, 1 2, 1 5- tetraaza heptadecane-4.7, 1
- the radioactively labeled antibodies according to the present invention contain, for example, radioactive iodine (I 1 23 , I 125 'I 131 ), tritium (H 3 ), carbon (C 14 ), sulfur (S 35 ) , yttrium (Y 90 ), technetium (TC 99m ), or the like.
- the peptide ligands according to the present invention are obtained from the ligants according to the present invention by iodization known per se, for example with radioactive potassium or sodium iodide and a reagent chemically oxidizing, such as sodium hypochlorite, chloramine T or the like, or an enzymatically oxidizing reagent, such as lactoperoxidase and glucose oxidase.
- the ligands according to the present invention can also be coupled to yttrium, for example by chelation with DPTA.
- the binding of the enzyme with the antibody according to the present invention can be carried out by reacting an antibody according to the present invention with a coupling reagent, for example, glutaraldehyde, periodate, N, N'-O-phenylenedimaleimide , N- (m-maleimidobenzoyl oxy) -succinimide, N- (3- [2'-pyridyldithio] -propionoxy) -succinimide, N- ethyl-N '- (3-dimethylamino-propyl) -carbodiimide.
- a coupling reagent for example, glutaraldehyde, periodate, N, N'-O-phenylenedimaleimide , N- (m-maleimidobenzoyl oxy) -succinimide, N- (3- [2'-pyridyldithio] -propionoxy) -succinimide, N-
- the conjugates with biotin are prepared for example by reacting the antibody according to the present invention with an activated ester of biotin such as the ester of biotin N-hydroxysuccinimide.
- the conjugates with a fluorescent or chemiluminescent label are prepared in the presence of a coupling reagent, for example those mentioned above, or by a reaction with isothiocyanate, preferably fluorescein isothyocyanate.
- the ligand is recognized by an antibody-marker conjugate.
- the ligand according to the present invention will therefore comprise a useful part for the recognition of this second labeled antibody.
- the constant heavy chains of the murine or human type will be used in the case where the ligand is an antibody.
- the antibodies of the present invention can be digested by proteases. Several fragments, Fab, Fab 'and Fc, are thus obtained.
- antibody fragments are that they can be made quite easily by bacteria or yeast.
- single domain antibody (Dabs) technology offers the ability to clone antibody-like molecules into bacteria and screen millions of antibodies much more simply than monoclonal antibodies. .
- a second object according to the invention is a method for detecting p24 of HIV-1 in a biological sample comprising bringing said sample into contact with at least one ligand according to the invention, and the measurement of the Iigand-p24 complex formed.
- a third object according to the invention is a diagnostic kit for detecting an infection with HIV-1 comprising at least one ligand according to the invention.
- a fourth object according to the invention is the use of antibodies of the human-murine chimeric type according to the invention for the preparation of a medicament intended for treating patients suffering from an infection with HIV-1.
- a fifth object according to the invention is the DNA molecule coding for a peptide ligand according to claim 1.
- a peptide ligand according to claim 1 mention may be made of the nucleic acid sequences of the sequences SEQ ID Nos. 1 and 2.
- FIGS. 1 and 2 respectively represent the amino acid sequence of the light and heavy chains of the Fab fragment of the antibody 13B5 with the hypervariable regions framed, coded by the sequences SEQ ID Nos. 1 and 2.
- FIG. 3 represents the results of an indirect ELISA test according to Example 3. On the abscissa is shown the antibody concentration (/ g / ml), and on the ordinate the measurement of OD (optical density) at 405 nm.
- the sequences SEQ ID No 1 and SEQ ID No 2 respectively represent the nucleotide and amino acid sequences of the light chain and of the heavy chain of the Fab fragment of the antibody 1 3B5.
- a sixth object according to the invention is the functional expression cassettes in a cell originating from a prokaryotic or eukaryotic organism, allowing the expression of DNA coding for a peptide ligand according to the invention, the vectors comprising the cassettes of expression described above, and cells from a eukaryotic or prokaryotic organism comprising an expression cassette or a vector according to the invention.
- mice of the BALB / C species and of the BALB / C BYJICO strain (supplied by IFFA Credo), and the myeloma line SP2 / 0-AG14 were used as antigen.
- b) Immunization protocol The mice were immunized 1 5 days apart using
- IP intraperitoneal
- ACF complete Freund's adjuvant
- AIF incomplete Freund's adjuvant
- Iscove's Modified Dulbecco Medium supplemented with sodium bicarbonate (3024 mg / l), 10% fetal calf serum (SVF), pH 6.7 to 7.3, and at 25 ° C.
- Additional reagents were: insulin 4 mg / l, 2-mercaptoethanol (10 ⁇ M), ethanolamine (20 // M), penicillin (100 U / ml), streptomycin (50 // g / ml ).
- the heterolploid cells obtained were subcultured every two or three days. e) Freezing of cells
- composition medium was used: IMDM supplemented with 10% fetal calf serum (SVF) and 10% dimethyl sulfoxide (DMSO-Sigma).
- the cell concentration was 3.6 x 10 6 cells per ampoule (2 x 10 6 cells / ml).
- the cells were slowly frozen at -80 ° C in 10% IMDM-SVF-10% DMSO medium for 24 to 72 hours, then the cells were stored in liquid nitrogen at -180 ° C.
- mice 4 to 6 weeks old, of the BALB / C species, of the BALB / C BYJICO strain (IFFA Credo) are used.
- a cell suspension of clone 13B5 was prepared which was centrifuged at 200 G for 10 minutes at 25 ° C. The cells were then resuspended in 9% NaCl at 10 6 cells / ml.
- the ascites fluid was then harvested after 10 days +/- 2 days.
- mice conjugated 100 ⁇ l of anti-Ig (H + L) immunoglobulins from mice conjugated to alkaline phosphatase (Jackson Laboratories).
- reaction was then blocked with 100 ⁇ l of 1N NaOH.
- the ELISA shows that the 13B5 antibody specifically recognizes the p24 of HIV-1.
- the 13B5 antibody is of the lgG1, k isotype.
- the membrane was then taken up and then incubated in a solution of PBS-Rministerlait 3% Tween 0.05% containing the antibody 3B5 diluted to 10 / g / ml, at room temperature, for 1 hour 30 minutes. The membrane was then taken up, washed 3 times in 0.05% PBS-Tween, then incubated 10
- conjugates are revealed by a solution of beta-naphthyl acid phosphate 0.5 mg / ml and O-Dianisidine 0.5 mg / ml in tetraborate buffer 12.07 g / l, MgSO4 1.2 g / l, pH 9. A single band is observed with an expected molecular weight, approximately 27,000, compatible with the theoretical molecular weight of p24, 26,707.
- the antibody 13B5 specifically recognizes p24 in western blotting.
- P24 diluted in PBS 0.5 ⁇ g / ml, 350 ⁇ l per Vidas cone was adsorbed. Washed with 600 ⁇ l 0.1% PBS-Tween 20 buffer.
- the antibody 1 3B5 was diluted a first time 1000 times to approximately 10 / g / ml, then 10 to 10, in a 100 mM Tris buffer, 300 mM NaCl, 5% Tween 20, 2% BSA, Regulated 0 , 2%, pH 7. The antibody 3B5 is then added and incubated at 37 ° C.
- RNA from hybridoma cells was extracted using a technique derived from the method of Chomczynski (1987) using the kit
- the cDNA solution contained a mixture of all single stranded cDNAs from reverse transcription of all mRNAs produced by hybridoma cells. It was therefore necessary to select and amplify the DNA with previously selected DNA primers. - choice of DNA primers: The N-terminal sequencing of the light and heavy chains was carried out automatically by Edman degradation. Only the first 10 amino acids of the light chain could be determined:
- PCR tests were carried out at different hybridization temperatures, with different concentrations of cDNA and DNA primers. To evaluate the stringency of the reactions, controls were carried out under the same conditions with a single DNA primer per reaction medium in order to eliminate the non-specific amplification conditions.
- PCR reactions were carried out in a reaction mixture of 50 ⁇ ⁇ varying according to the chain to be amplified (cf. Table I).
- the reaction medium contained a mixture of two DNA polymerases: TAQ and PWO (Expand Long Template System by Boerhinger Mannheim). Table I below presents the PCR reaction mixtures of the light and heavy chains of the Fab fragment of the antibody 13B5.
- the amplification started with a denaturation of 2 minutes at 94 ° C and then continued with 30 identical cycles comprising a denaturation phase of 30 seconds at 94 ° C, a hybridization phase 13
- Qiagen plasmid midi This technique is based on a modified alkaline lysis followed by purification on an anion exchange column. About 100 ⁇ g of plasmid DNA could be extracted from each 50 ml culture (LB-ampicillin). The plasmid DNA of a clone for each chain was manually sequenced on the direct strand and reverses using oligonucleotides internal to the gene sequences. In order to avoid possible errors of interpretation of the sequences due to the fact of the errors of the polymerase during the amplification, 5 other clones containing the gene coding for the light chain and 5 other clones containing the gene coding for the heavy chain have been sequenced entirely in both directions.
- Example 2 Description of a process for producing a recombinant antibody from the Fab13B5 sequence.
- the purpose of the process described is to produce a recombinant antibody or ScFv (Single chain Fv) from the clones coding respectively for the heavy and light chains of the Fab.
- the Pharmacia kit "Recombinant Phage antibody System” will be used to carry out this process (reference 27 9401-01, 27902-01, 279043-01).
- VH and VL hypervariable regions of the heavy and light chains
- the genes coding for the hypervariable regions of the heavy (VH) and light (VL) chains will be amplified by PCR, from the plasmids isolated during example 1, paragraph 7 , cloning, using primers chosen from the “framework” regions of the variable regions of immunoglobulins. Pharmacia kits will be used below.
- the resulting PCR products will then be assembled, using a linker, into a single gene (750 bp) coding for a Scfv.
- the Scfv fragment consisting of the VH and VL regions separated by the peptide sequence (GGGGS) 3 will be obtained.
- the Scfv gene will then be amplified with primers specific for the 5 'ends of the VH and 3' of the VL and containing the Sfil and NotI restriction sites respectively.
- the resulting amplification product will then be digested with restriction enzymes Sfil and NotI, then ligated with the phagemid pCANTAB ⁇ E previously opened with the restriction enzymes Sfil and
- Colonies containing the phage will be infected with a phage helper M1 3K07 to produce recombinant phages which contain the gene coding for ScfV. These recombinant phages also express on their surface one or more copies of Scfv in the form of the Scfv-g3p fusion protein.
- the p24 protein is adsorbed on a NUNC (polystyrene) Maxisorb type ELISA plate in PBS at 25 ng per well for 2 hours at 37 ° C.
- NUNC polystyrene
- the plate was then saturated with 200 ml of 0.05% PBS-Tween 20 buffer 3% BSA for 2 hours at 37 ° C.
- the antibody 13B5 coupled to biotin is then diluted to 1 ⁇ g / ml, then 4 in 4 in PBS-Tween 20 buffer at 0.05% 1% BSA. We then put 200 ⁇ ⁇ per well of each dilution to incubate with p24 for 2 hours at 37 ° C.
- pNPP p-nitrophenyl phosphate
- the plate is washed 3 times with 0.05% PBS-Tween 20 buffer.
- the antibody 13B5 recognizes p24 in indirect ELISA. It gives a detection signal higher than those obtained for the other antibodies and the maximum detection signal is reached for an antibody concentration of approximately 0.2 ⁇ g / ml.
- the polyclonal antibodies and the monoclonal antibodies 15F8 and 23A5 give a maximum detection signal for a significantly higher antibody concentration, of approximately 1 // g / ml for 1 5F8 and the polyclonal, and greater than 1 // g / ml for 23A5.
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- Virology (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- AIDS & HIV (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99913376A EP1068319A1 (en) | 1998-04-10 | 1999-04-09 | PEPTIDE LIGAND HAVING SPECIFIC AFFINITY FOR THE HIV1 RETROVIRUS p24 PROTEIN |
AU31519/99A AU3151999A (en) | 1998-04-10 | 1999-04-09 | Peptide ligand having specific affinity for the hiv1 retrovirus p24 protein |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9804876A FR2777285B1 (en) | 1998-04-10 | 1998-04-10 | PEPTIDE LIGAND WITH SPECIFIC AFFINITY TO HIV-1 RETROVIRUS P24 PROTEIN |
FR98/04876 | 1998-04-10 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1999053063A1 true WO1999053063A1 (en) | 1999-10-21 |
Family
ID=9525401
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FR1999/000831 WO1999053063A1 (en) | 1998-04-10 | 1999-04-09 | PEPTIDE LIGAND HAVING SPECIFIC AFFINITY FOR THE HIV1 RETROVIRUS p24 PROTEIN |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1068319A1 (en) |
AU (1) | AU3151999A (en) |
FR (1) | FR2777285B1 (en) |
WO (1) | WO1999053063A1 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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ZA200902419B (en) | 2006-10-19 | 2010-07-28 | Genentech Inc | Anti-notch3 agonist antibodies and their use in the treatment of notch3-related diseases |
KR20150023953A (en) | 2006-10-19 | 2015-03-05 | 제넨테크, 인크. | Anti-Notch3 agonist antibodies and their use in the treatment of Notch3-related diseases |
KR20150004933A (en) | 2006-12-18 | 2015-01-13 | 제넨테크, 인크. | Antagonist anti-notch3 antibodies and their use in the prevention and treatment of notch3-related diseases |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4843011A (en) * | 1985-08-01 | 1989-06-27 | Akzo N.V. | Monoclonal antibodies for binding HTLV-III proteins, and cell lines for their production |
EP0345461A2 (en) * | 1988-06-10 | 1989-12-13 | Abbott Laboratories | Mouse monoclonal antibodies to HIV-1P24 and their use in diagnostic tests |
WO1990009805A1 (en) * | 1989-02-28 | 1990-09-07 | New York University | Human monoclonal antibodies to human immunodeficiency virus |
WO1990014358A1 (en) * | 1989-05-15 | 1990-11-29 | Akzo N.V. | T-lymphotropic retrovirus monoclonal antibodies |
WO1991007493A1 (en) * | 1989-11-13 | 1991-05-30 | Xoma Corporation | Chimeric mouse human antibodies with specificity to hiv antigens |
EP0519866A1 (en) * | 1991-06-18 | 1992-12-23 | Ciba-Geigy Ag | Novel anti-HIV antibodies |
-
1998
- 1998-04-10 FR FR9804876A patent/FR2777285B1/en not_active Expired - Fee Related
-
1999
- 1999-04-09 EP EP99913376A patent/EP1068319A1/en not_active Withdrawn
- 1999-04-09 WO PCT/FR1999/000831 patent/WO1999053063A1/en not_active Application Discontinuation
- 1999-04-09 AU AU31519/99A patent/AU3151999A/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4843011A (en) * | 1985-08-01 | 1989-06-27 | Akzo N.V. | Monoclonal antibodies for binding HTLV-III proteins, and cell lines for their production |
EP0345461A2 (en) * | 1988-06-10 | 1989-12-13 | Abbott Laboratories | Mouse monoclonal antibodies to HIV-1P24 and their use in diagnostic tests |
WO1990009805A1 (en) * | 1989-02-28 | 1990-09-07 | New York University | Human monoclonal antibodies to human immunodeficiency virus |
WO1990014358A1 (en) * | 1989-05-15 | 1990-11-29 | Akzo N.V. | T-lymphotropic retrovirus monoclonal antibodies |
WO1991007493A1 (en) * | 1989-11-13 | 1991-05-30 | Xoma Corporation | Chimeric mouse human antibodies with specificity to hiv antigens |
EP0519866A1 (en) * | 1991-06-18 | 1992-12-23 | Ciba-Geigy Ag | Novel anti-HIV antibodies |
Non-Patent Citations (1)
Title |
---|
R. GRUNOW ET AL.: "Monoclonal antibodies to p24-core protein of HIV-1 mediate ADCC and inhibit virus spread in vitro.", CLINICAL AND DIAGNOSTIC VIROLOGY, vol. 3, no. 3, 1995, Amsterdam, Pays-Bas, pages 221 - 231, XP002085007 * |
Also Published As
Publication number | Publication date |
---|---|
AU3151999A (en) | 1999-11-01 |
FR2777285B1 (en) | 2000-05-19 |
FR2777285A1 (en) | 1999-10-15 |
EP1068319A1 (en) | 2001-01-17 |
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