CN1339319A - Medicine for treating AIDS and its preparing method - Google Patents
Medicine for treating AIDS and its preparing method Download PDFInfo
- Publication number
- CN1339319A CN1339319A CN00123486A CN00123486A CN1339319A CN 1339319 A CN1339319 A CN 1339319A CN 00123486 A CN00123486 A CN 00123486A CN 00123486 A CN00123486 A CN 00123486A CN 1339319 A CN1339319 A CN 1339319A
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- China
- Prior art keywords
- epitope
- medicine
- aids
- immune deficiency
- deficiency syndrome
- 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.)
- Pending
Links
- 208000030507 AIDS Diseases 0.000 title claims abstract description 52
- 239000003814 drug Substances 0.000 title claims abstract description 35
- 238000000034 method Methods 0.000 title claims description 12
- 229940079593 drug Drugs 0.000 title description 5
- 229920001184 polypeptide Polymers 0.000 claims abstract description 18
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 18
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 18
- 230000003472 neutralizing effect Effects 0.000 claims abstract description 17
- 230000008878 coupling Effects 0.000 claims abstract description 13
- 238000010168 coupling process Methods 0.000 claims abstract description 13
- 238000005859 coupling reaction Methods 0.000 claims abstract description 13
- 239000002671 adjuvant Substances 0.000 claims abstract description 11
- 239000000427 antigen Substances 0.000 claims abstract description 5
- 102000036639 antigens Human genes 0.000 claims abstract description 5
- 108091007433 antigens Proteins 0.000 claims abstract description 5
- 102000014914 Carrier Proteins Human genes 0.000 claims abstract description 4
- 108010078791 Carrier Proteins Proteins 0.000 claims abstract description 4
- 241001465754 Metazoa Species 0.000 claims abstract description 3
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 29
- 208000011580 syndromic disease Diseases 0.000 claims description 24
- 230000036039 immunity Effects 0.000 claims description 10
- 210000004408 hybridoma Anatomy 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- 230000007910 cell fusion Effects 0.000 claims description 4
- 238000011091 antibody purification Methods 0.000 claims description 2
- 241000700605 Viruses Species 0.000 abstract description 5
- 230000007812 deficiency Effects 0.000 abstract description 3
- 230000003053 immunization Effects 0.000 abstract description 2
- 108010052285 Membrane Proteins Proteins 0.000 abstract 2
- 102000018697 Membrane Proteins Human genes 0.000 abstract 2
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 238000013329 compounding Methods 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 229940124321 AIDS medicine Drugs 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- LLXVXPPXELIDGQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)benzoate Chemical compound C=1C=CC(N2C(C=CC2=O)=O)=CC=1C(=O)ON1C(=O)CCC1=O LLXVXPPXELIDGQ-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101710181478 Envelope glycoprotein GP350 Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000000680 avirulence Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000001814 protein method Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
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
- 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
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- 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
Abstract
The AIDS treating medicine of the present invention includes at least a kind of monoclonal antibody, the antigen of which is GPGRAFY neutralizing epitope and its variation epitopes GPGQTFY or GPGQAWY of human immune deficiency virus membrane protein gp120. It is prepared through the steps of: artificial synthesis of at least one polypeptide containing GPGRAFY neutralizing epitope and/or its variation epitopes of human immune deficiency virus membrane protein gp120; coupling the said polypeptide to carrier protein or carrier polypeptide; immunizing animal with the said conjugate; preparing hybrid tumor; and compounding the obtained antibody with medicinal adjuvant to obtain the medicine.
Description
The present invention relates to medicine with the treatment acquired immune deficiency syndrome (AIDS) of biotechnology preparation and preparation method thereof, particularly relate to medicine with the treatment acquired immune deficiency syndrome (AIDS) of the Monoclonal Antibody of HIV (human immunodeficiency virus) (Human Immunodeficiency Virus) memebrane protein and preparation method thereof.
Acquired immune deficiency syndrome (AIDS) claims acquired immune deficiency syndrome (AIDS) again, is a kind of immune disease that is caused by HIV (human immunodeficiency virus) (HIV).Because it is propagated rapidly, case fatality rate is high, and does not still have the specific treatment method at present, does not more have vaccine and can prevent, thereby the title of " century plague " is arranged.
Existingly be used for only deferrable period of disease and prolong patient's life of clinical anti-AIDS drug, and cost an arm and a leg, toxicity is big.Recently external anti-AIDS drug clinical research result proves, the mucosa that can suppress HIV-1 virus at neutralizing antibody (monoclonal antibody) being used in combination in passive immunotherapy of the several specific neutralizing epitopes on the HIV-1 memebrane protein gp120 infects and mother-to-baby transmission, and can remove HIV-1 virus (Nature Medicine 1999,5:204 in the blood; Nature Medicine 2000,6:200; Nature Medicine 1999,5:211); Main neutralizing epitope GPGRAFY on the HIV-1 gp120 and discern the antibody of this epi-position can vitro inhibition HIV-1 target cell infection, and (Nature 1990,345:622 to prevent HIV-1 to infect chimpanzee; Science 1992,256:1687; Nature 1992,355:728-730; J.Biol.Chem.1995,271:8236).
The medicine that the purpose of this invention is to provide a kind of effective treatment acquired immune deficiency syndrome (AIDS), this medicine can tackle the variation of HIV (human immunodeficiency virus) (Human Immunodeficiency Virus).
Another object of the present invention provides a kind of method for preparing the medicine of above-mentioned treatment acquired immune deficiency syndrome (AIDS).
For achieving the above object, the present invention takes following design: a kind of medicine for the treatment of acquired immune deficiency syndrome (AIDS), it consists essentially of at least a monoclonal antibody, and the antigen of described antibody is neutralizing epitope GPGRAFY epi-position and the variant epitope thereof on human immunodeficiency virus's memebrane protein gp120.
Described variant epitope is GPGQTFY or GPGQAWY.
It is preferably composed of the following components that the present invention treats the medicine of acquired immune deficiency syndrome (AIDS):
The monoclonal antibody of GPGRAFY-epitope specificity
The monoclonal antibody of GPGQTFY-epitope specificity
The monoclonal antibody of GPGQAWY-epitope specificity
A kind of method for preparing the medicine of above-mentioned treatment acquired immune deficiency syndrome (AIDS) consists essentially of following steps:
(1), synthetic at least one contains the epitope polypeptide of the neutralizing epitope on human immunodeficiency virus's memebrane protein gp120 respectively, described neutralizing epitope be selected from the GPGRAFY epi-position or/and its variant epitope or at least once multiple GPGRAFY epi-position or/and its variant epitope;
(2), aforementioned polypeptides is coupled to respectively on carrier protein or the carrier polypeptide forms coupling matter;
(3), be equipped with acceptable adjuvant immunity animal respectively with above-mentioned coupling matter;
(4), adopt conventional cell-fusion techniques to prepare hybridoma respectively;
(5), the antibody purification that will obtain from above-mentioned different hybridoma cell lines, be mixed and made into the medicine of treatment acquired immune deficiency syndrome (AIDS).
Wherein, at least one polypeptide of described synthetic is preferably at least once multiple GPGRAFY epi-position or its variant epitope that contain respectively on human immunodeficiency virus's memebrane protein gp120.The variant epitope of described GPGRAFY epi-position is GPGQTFY or GPGQAWY.
Studies show that, in treating AIDS, can reduce the carrying capacity of virus, delay the carrying out of disease at the antibody of neutralizing epitope on the HIV-1 virus membrane antigen.The medicine that the present invention treats acquired immune deficiency syndrome (AIDS) is to contain GPGRAFY epi-position on the anti human immune deficiency virus memebrane protein gp120 and variant epitope thereof (as GPGQTFY, the medicine of multiple antibody GPGQAWY), even produce in HIV (human immunodeficiency virus) (Human Immunodeficiency Virus) under the situation of variation, injected in the human body of this medicine and also had the virus that corresponding antibody is killed variation.
Medicine of the present invention is avirulence not only, and in the immunization therapy effect that improves acquired immune deficiency syndrome (AIDS), also can reduce the treating AIDS cost.
The present invention adopts the method for synthetic epitope polypeptide to induce, prepare the monoclonal antibody of predetermined epitope specificity, overcome and need utilize native protein or recombiant protein immunity, a large amount of then screenings and evaluation just can obtain many complex work of the monoclonal antibody of predetermined epitope specificity.
According to the present invention, can produce the medicine of its respective type very soon according to the variation situation of HIV (human immunodeficiency virus) (Human Immunodeficiency Virus), need not test for a long time, reduce production costs.This technology will produce significant impact to world's preventive medicine research, and will bring huge economic benefit and social benefit.
The invention will be further described below in conjunction with non-limiting specific embodiment.
Embodiment one: by the antibody of the neutralizing epitope GPGRAFY on the anti-HIV-1 gp120 is the medicine of the treatment acquired immune deficiency syndrome (AIDS) made of main active, by following steps production:
(1), one of synthetic contains the epitope polypeptide C-(GPGRAFY) 4 of 4 multiple GPGRAFY neutralizing epitopes on human immunodeficiency virus's memebrane protein gp120;
(2), utilize MBS (m-maleimidobenzoyl-N-hydroxy succinimide ester) with above-mentioned epitope polypeptide and carrier protein BSA coupling connection;
(3), above-mentioned coupling matter is mixed with freund adjuvant that (ratio of weight and number of two kinds of materials is coupling matter: immune Balb/c mice freund adjuvant=1: 1).Use for the first time complete freund adjuvant, later per two all immunity once, the full freund adjuvant that toos many or too much for use, the antigen dose of each immunity is: contain the coupling matter of 10 microgram epitope polypeptides/time/only, immune 3 times altogether;
(4), adopt conventional cell-fusion techniques to merge the mouse boosting cell after the immunity and mouse myeloma cell line, and the preparation hybridoma;
(5), filter out the clone that can produce the monoclonal antibody of predefined epitope specificity, the antibody of purifying is made the medicine of treatment acquired immune deficiency syndrome (AIDS) from above-mentioned hybridoma cell line.
This medicine using dosage is in actual applications determined according to patient's the state of an illness.
Embodiment two: by the antibody of the neutralizing epitope GPGRAFY on the anti-HIV-1 gp120 and variant epitope GPGQTFY, GPGQAWY is the medicine of the treatment acquired immune deficiency syndrome (AIDS) made of main active, by following steps production:
(1), 4 of synthetic contain neutralizing epitope GPGRAFY on human immunodeficiency virus's memebrane protein gp120 and the epitope polypeptide of variant epitope GPGQTFY, GPGQAWY thereof respectively:
CGPGRAFYGPGRAFYGPGRAFYGPGRAFY
CGPGQTFYGPGQTFYGPGQTFYGPGQTFY
CGPGQAWYGPGQAWYGPGQAWYGPGQAWY
(2), utilize glutaraldehyde or MBS that aforementioned polypeptides is coupled to respectively on the carrier protein bovine serum albumin and form coupling matter;
(3), above-mentioned coupling matter is mixed with freund adjuvant that (volume ratio of two kinds of materials is coupling matter: immune Balb/c mice freund adjuvant=1: 1).Use for the first time complete freund adjuvant, later per two all immunity once, full freund adjuvant toos many or too much for use.The antigen dose of each immunity is: contain the coupling matter of 10 microgram epitope polypeptides/time/only, immunity is 3 times altogether;
(4), adopt conventional cell-fusion techniques to merge the mouse boosting cell after the immunity and mouse myeloma cell line, and the preparation hybridoma;
(5), filter out the clone that can produce the monoclonal antibody of predefined epitope specificity from above-mentioned hybridoma cell line.
(6), obtain neutralizing epitope GPGRAFY on the anti-HIV-1 gp120 and 3 kinds of antibody of variant epitope GPGQTFY, GPGQAWY thereof respectively from above-mentioned hybridoma cell line, above-mentioned antibody is made the medicine of treatment acquired immune deficiency syndrome (AIDS), wherein, the probability of occurrence of the various epi-positions that drawn by the statistical procedures that is suitable for the crowd of the addition of various antibody is adjusted.
Use medicine of the present invention, can obviously resist the variation of HIV (human immunodeficiency virus) (Human Immunodeficiency Virus), reduce the carrying capacity of HIV (human immunodeficiency virus) (Human Immunodeficiency Virus), delay the carrying out of disease, reach the purpose of healing at last.
Claims (6)
1, a kind of medicine for the treatment of acquired immune deficiency syndrome (AIDS), it consists essentially of at least a monoclonal antibody, and the antigen of described antibody is neutralizing epitope GPGRAFY epi-position and the variant epitope thereof on human immunodeficiency virus's memebrane protein gp120.
2, a kind of medicine for the treatment of acquired immune deficiency syndrome (AIDS) according to claim 1, it is characterized in that: described variant epitope is GPGQTFY or GPGQAWY.
3, a kind of medicine for the treatment of acquired immune deficiency syndrome (AIDS) according to claim 1 and 2, it is characterized in that: it is composed of the following components: the monoclonal antibody of GPGRAFY-epitope specificity
The monoclonal antibody of GPGQTFY-epitope specificity
The monoclonal antibody of GPGQAWY-epitope specificity
4, a kind of method for preparing the medicine of the described treatment acquired immune deficiency syndrome (AIDS) of claim 1-3 consists essentially of following steps:
(1), synthetic at least one contains the epitope polypeptide of the neutralizing epitope on human immunodeficiency virus's memebrane protein gp120 respectively, described neutralizing epitope be selected from the GPGRAFY epi-position or/and its variant epitope or at least once multiple GPGRAFY epi-position or/and its variant epitope;
(2), aforementioned polypeptides is coupled to respectively on carrier protein or the carrier polypeptide forms coupling matter;
(3), be equipped with acceptable adjuvant immunity animal respectively with above-mentioned coupling matter;
(4), adopt conventional cell-fusion techniques to prepare hybridoma respectively;
(5), the antibody purification that will obtain from above-mentioned different hybridoma cell lines, be mixed and made into the medicine of treatment acquired immune deficiency syndrome (AIDS).
5, the method for the medicine of preparation treatment acquired immune deficiency syndrome (AIDS) according to claim 4, it is characterized in that: at least one polypeptide of described synthetic, contain at least once multiple GPGRAFY epi-position or its variant epitope on human immunodeficiency virus's memebrane protein gp120 respectively.
6, according to the method for the medicine of claim 4 or 5 described preparations treatment acquired immune deficiency syndrome (AIDS), it is characterized in that: the variant epitope of described GPGRAF epi-position is GPGQTF or GPGQAWF.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN00123486A CN1339319A (en) | 2000-08-18 | 2000-08-18 | Medicine for treating AIDS and its preparing method |
| PCT/CN2001/001191 WO2002026259A1 (en) | 2000-08-18 | 2001-07-20 | A pharmaceutical composition for treating acids and its preparation |
| AU2002212074A AU2002212074A1 (en) | 2000-08-18 | 2001-07-20 | A pharmaceutical composition for treating acids and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN00123486A CN1339319A (en) | 2000-08-18 | 2000-08-18 | Medicine for treating AIDS and its preparing method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1339319A true CN1339319A (en) | 2002-03-13 |
Family
ID=4589906
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN00123486A Pending CN1339319A (en) | 2000-08-18 | 2000-08-18 | Medicine for treating AIDS and its preparing method |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN1339319A (en) |
| AU (1) | AU2002212074A1 (en) |
| WO (1) | WO2002026259A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103459410A (en) * | 2011-02-25 | 2013-12-18 | 埃斯特韦实验室有限公司 | Rapid selection method for HIV gp-120 variants |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5266478A (en) * | 1987-05-29 | 1993-11-30 | Tanox Biosystems, Inc. | Antibodies which target a neutralization site within the second variable region of human immunodeficiency virus type 1 gp120 |
| JPH0292298A (en) * | 1988-09-30 | 1990-04-03 | Olympus Optical Co Ltd | Monoclonal antibody against hiv-constructing protein |
| RU2128222C1 (en) * | 1991-08-22 | 1999-03-27 | Ниссин Сокухин Кабусики Кайся | Murine monoclonal antibody nmo1, hybridoma cellular line, fragment of murine monoclonal antibody (variants) |
| US5618922A (en) * | 1994-07-25 | 1997-04-08 | Nissin Shokuhin Kabushiki Kaisha | NM03 antibody materials and methods |
| DE69527089T2 (en) * | 1995-04-19 | 2003-01-02 | Polymun Scient Immunbio Forsch | MONOCLONAL ANTIBODIES AGAINST HIV-1 AND Vaccines Manufactured From It |
| JP2001502315A (en) * | 1996-10-10 | 2001-02-20 | プローブ・インターナショナル | Compositions and methods for treating viral infection |
-
2000
- 2000-08-18 CN CN00123486A patent/CN1339319A/en active Pending
-
2001
- 2001-07-20 WO PCT/CN2001/001191 patent/WO2002026259A1/en active Application Filing
- 2001-07-20 AU AU2002212074A patent/AU2002212074A1/en not_active Abandoned
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103459410A (en) * | 2011-02-25 | 2013-12-18 | 埃斯特韦实验室有限公司 | Rapid selection method for HIV gp-120 variants |
| CN103459410B (en) * | 2011-02-25 | 2016-05-25 | 埃斯特韦实验室有限公司 | The fast selecting method of HIV gp-120 variant |
| US9605030B2 (en) | 2011-02-25 | 2017-03-28 | Laboratorios Del Dr. Esteve, S.A. | Rapid selection method for HIV gp-120 variants |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2002212074A1 (en) | 2002-04-08 |
| WO2002026259A1 (en) | 2002-04-04 |
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