GB2319252A - Polypeptides involved in the interaction of HIV gp120 with the fusin, and the CC-CKR-5 co-receptors thereof - Google Patents
Polypeptides involved in the interaction of HIV gp120 with the fusin, and the CC-CKR-5 co-receptors thereof Download PDFInfo
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- GB2319252A GB2319252A GB9623340A GB9623340A GB2319252A GB 2319252 A GB2319252 A GB 2319252A GB 9623340 A GB9623340 A GB 9623340A GB 9623340 A GB9623340 A GB 9623340A GB 2319252 A GB2319252 A GB 2319252A
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- Prior art keywords
- hiv
- receptor
- peptide
- ckr
- fusin
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 47
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 26
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 title claims abstract description 25
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 title claims abstract description 25
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 title claims abstract description 25
- 108010061299 CXCR4 Receptors Proteins 0.000 title claims abstract description 25
- 229920001184 polypeptide Polymers 0.000 title abstract 5
- 230000003993 interaction Effects 0.000 title description 25
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims abstract description 49
- 208000030507 AIDS Diseases 0.000 claims abstract description 7
- 239000000203 mixture Substances 0.000 claims abstract description 6
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 6
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 6
- 101710121417 Envelope glycoprotein Proteins 0.000 claims abstract description 4
- 239000013603 viral vector Substances 0.000 claims abstract description 4
- 241000700618 Vaccinia virus Species 0.000 claims abstract description 3
- 239000007787 solid Substances 0.000 claims abstract description 3
- 102100021696 Syncytin-1 Human genes 0.000 claims abstract 2
- 230000000890 antigenic effect Effects 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 239000000427 antigen Substances 0.000 claims 1
- 102000036639 antigens Human genes 0.000 claims 1
- 108091007433 antigens Proteins 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 238000001228 spectrum Methods 0.000 abstract description 14
- 208000031886 HIV Infections Diseases 0.000 abstract description 2
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 abstract 1
- 238000004458 analytical method Methods 0.000 description 17
- 210000001744 T-lymphocyte Anatomy 0.000 description 14
- 108010041397 CD4 Antigens Proteins 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- 102000002110 C2 domains Human genes 0.000 description 2
- 108050009459 C2 domains Proteins 0.000 description 2
- 102100027723 Endogenous retrovirus group K member 6 Rec protein Human genes 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 102000001326 Chemokine CCL4 Human genes 0.000 description 1
- 108010055165 Chemokine CCL4 Proteins 0.000 description 1
- 102000001327 Chemokine CCL5 Human genes 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 101710141347 Major envelope glycoprotein Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 101150098024 ple4 gene Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000008478 viral entry into host cell Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
-
- 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
- C07K14/575—Hormones
- C07K14/57563—Vasoactive intestinal peptide [VIP]; Related peptides
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing 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
-
- 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
A polypeptide (I), from the second conserved domain of the human immunodeficiency virus Type-1 (HIV-1) envelope glycoprotein (gp120), presents, in the informational spectrum (IS), as a dominant, the frequency components F1 in the region 0.030-0.040 and/or F2 in the region 0.180-0.220, which polypeptide is preferably related to the primary structure: VVRSANFTDN AKTIIVQLNE SVEINCTRP. A polypeptide (II), from the fusin receptor, is related to the primary structure: GIVGNGLVIL VMGYQKKLRS MTAKYRLHLS. A polypeptide (III), from the CC-CKR-5 receptor, is related to the primary structure: DFGNTMCQLL TGLYFIGFFS GIFFIILLTI. A composition comprises at least one of (I) to (III), either conjugated to a protein or keyhole limpet haemocyanin, or expressed on the surface of a viral vector(preferably vaccinia virus). A pharmaceutical, for use in the treatment of AIDS, comprises at least one, and preferably at least two, of (I) to (III). A test kit comprises at least one of (I) to (III), immobilised on a porous surface of a solid carrier, preferably the wells of a microtitre plate.
Description
PRPTIDRS FOR PRRVINTION OF THR INTERACTION BREN RIV-1 AND ITS MAJOR FUSIN AND CC-CKR-5 CO-RSCBPTORS This invention relates to peptide sequences derived from the second conserved domain of HIV-1 envelope glycoprotein 120, from fusin receptor or from CC-CKR-5.
Backaround of the invention
The first step in infection with human immunodeficiency virus type 1 (HIV-l) involves the binding of its major envelope glycoprotein gp 120 to the
CD4 receptor. The CD4 receptor alone is, however, not sufficient for viral penetration of target cells.
Recently, two major coreceptors for primary isolates of
HIV-1 were identified. For the "macrophage-tropic" isolates of HIV-1 the CC-CKR-5 molecule, representing a receptor for the ss-chemokines RANTES, MIP-la and MIP-1ss, was identified as major co-receptor [Deng et al., Nature it1, 661 (1996); Dragic et al., ibid, 667). As the major co-receptor for the fusin, a seven-transmembrane, G protein-coupled receptor, was identified Fenf et al.,
Science 222, 872 (1996)).
This finding leads to the question of which domain of HIV-1 gp 120 participates in the interaction with the
CC-CKR-5 and fusin co-receptors. The answer to this question is crucial for the development of new a strategy in the prevention and therapy of AIDS.
Summary of the invention It is the object of the present invention to provide peptides for use in vaccines raising antibodies that protect cells from the HIV-1 infection through the blocking of its interaction with the major fusin and
CC-CKR-5 co-receptors.
It is also an object of the present invention to provide peptides that compete with HIV-1 for its interaction with the major co-receptors, for use in the
AIDS therapy.
It is a further object of the present invention to provide peptides that may be used as an immunogen to elicit monoclonal antibodies which may be used as a therapeutic agent that prevents the development of AIDS or slows down its progression by blocking HIV-1 interaction with its major co-receptors.
It is also an object of this invention to identify the domain of fusin and CC-CKR-5 co-receptors that participate in the interaction with HIV-1 gp 120. These domains represent the potential target for the blocking of interaction with HIV-1 by the antibodies or the mimetic peptides.
Detailed descrlptlon of the invention
In order to identify the information responsible for the interaction between the HIV-1 gp 120 and the
CC-CKR-5 and fusin co-receptors, their primary structures were subjected to the "informational spectrum analysis. In this analysis, we used the gp 120 of "T-cell line tropic" (IIIB, LAV, SF2, and RF), and "macrophage-tropic" (HXB2, Ba-l, SF 162 and JR-FL) HIV-1 isolates. According to this analysis, the IS frequency component F(0.035) is characteristic for the interaction between the "T-cell line tropic" HIV-1 isolates and the fusin molecule. According to the same analysis, interaction between the CC-CKR-5 receptor and "macrophage-tropic" HIV-1 isolates is characterized by the IS frequency component F(0.207).
The important task represents identification oi region(s) of the HIV1 gp 120 participating in its interaction with the CC-CKR-5 and fusin coreceptors. Ir order to identify this region, we have scanned primary structures of gp 120 molecules from different HIV-1 isolates looking for the region which dominantly contributes to the IS frequency components F(0.035) and
F(0.207). This analysis revealed the C-terminus of the second conserved domain (C2) as the most important part of gp 120 for its interaction with the co-receptor for both group of HIV-1 isolates, "T-cell line tropic" and "macrophage-tropic1' isolates. The consensus peptide VVRSANFTDNARTIIVQLNESVEINCTRP within C2 domain of gp 12C was identified as the most responsible domain for interaction between coreceptor and gp 120 for "T-cell line tropic" and "macrophage-tropic" HIV-1 isolates.
The invention refers therefore, according to a first embodiment, to peptides derived from the second conserved domain of HIV envelope glycoprotein gp 12C having in the IS as a dominant the frequency components F1 in the region 0.030-0.040 and/or F2 in the region 0.180-0.220. These peptides have preferably from 15 tc 35 aminoacids, more preferably from 20 to 30 aminoacids.
The ISM analysis of information encoded in the primary structure of gp 120 from different HIV-1 isolates revealed that (i) frequency component F(0.035) corresponds to interaction between "T-cell line tropic"
HIV-1 isolates and fusin co-receptor, and (ii) frequency
F(0.207) is responsible for the interaction of the "macrophage-tropic" HIV1 isolates and CC-CKR-5 receptor.
It was also shown that in communications with the CD4 receptor "T-cell line tropic" and "macrophage-tropic"
HIV-1 isolates use the IS frequency components F(0.035) and F(0.207), respectively.
The invention also provides the peptide GIVGNGLVILVMGYQKKLRSMTAXYRLHLS from the fusin molecule and the peptide DFGNTMCQLLTGLYFIGFFSGIFFIILLTI from the
CC-CKR-5 receptor that are responsible for interaction with HIV-1 gp 120.
The peptides of the invention are useful as a mimetic for the prevention of interaction between HIV-1 gp 120 and fusin and CC-CKR-5 co-receptors.
The peptides of the invention may also be used for the preparation of vaccines to provide protection against the development of AIDS or slowing down its progression in HIV-1 infected patients. The vaccine will contain an effective immunogenic amount of peptides, e.g. 1 pg 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.
Adjuvants may be employed, such as aluminium hydroxide gel. Administration may be by injection, e.g.
intramuscularly, intraperitoneally, subcutaneously or intravenously. Administration may take place once or at a plurality of times, e.g. at 1 - 4 week interval.
The peptides may also be expressed on the surface of a suitably engineered viral vector, e.g. vaccinia virus. Preferably, the compositions according to the invention comprise at least two peptides as defined above.
Antigenic sequences from crab as well as proteins from other invertebrates can also be added to the peptides of invention to promote antigenicity.
The peptides according to the invention may be used as immunogens to elicit monoclonal antibodies, using conventional techniques, for use in the therapy of AIDS.
The peptides, suitable bound to the porous surface of solid substrates, such as wells of a microtiter plate, may be used for the preparation of test kits.
DescrlDtlon of the drawinas
Figure 1 shows (a) the consensus IS of gp 120 from the "T-cell line tropic" HIV-1 isolates (IIIB, LAV, SF2 and RF), (b) the cross-spectra of the consensus IS of gp 120 from the "T-cell line tropic" HIV-1 isolates and the
IS of CD4 receptor, (c) the cross-spectra of the consensus IS of gp 120 from the "T-cell line tropic"
HIV-1 isolates and the fusin receptor, (d) the crossspectra of the consensus IS of gp 120 from the "T-cell line tropic" HIV-1 isolates and the CC-CKR-5 receptor.
Figure 2 shows (a) the consensus IS of gp 120 from the "macrophage-tropic" HIV-1 isolates (HXB2, Ba-l,
SF162 and JR-FL), (b) the cross-spectra of the consensus
IS of gp 120 from the macrophage-tropic" HIV-1 isolates and the IS of CD4 receptor, (c) the cross-spectra of the consensus IS of gp 120 from the "macrophage-tropic" HIV-1 isolates and the CC-CKR-5 receptor, (d) the cross-spectra of the consensus IS of gp 120 from the "macrophage-tropic" HIV-1 isolates and the fusin receptor.
Figure 3 shows the positions of the. peptides with
S/N ratio > 1 at the IS frequency F(0.207) in the primary structures of gp 120 from HXB2, Ba-1 and SF162
HIV-1 isolates.
Figure 4 shows (a) positions of the peptides with
S/N ratio > 1 at the IS frequency F(0.035) in the primary structure of the fusin, and (b) IS spectrum of the peptide 52 - 81 from the fusin with the maximal value of the amplitude at the frequency F(0.035).
Figure 5 shows (a) positions of the peptides with
S/N ratio > 1 at the IS frequency F(0.207) in the primary structure of the CC-CKR-5 receptor, and (b) IS spectrum of the peptide 94 - 123 from the CC-CKR-5 receptor with the maximal value of the amplitude at the frequency F(0.207).
Exaiclel In order to determine which of the characteristic frequencies from IS of the gp 120 from the "T-cell line tropic" HIV-1 isolates are responsible for their interaction with the CD4 receptor and the fusin co-receptor, the ISM analysis of these proteins has been performed.
These analysis revealed that the consensus IS (CIS) of gp 120 from the IIIB, LAV, SF2 and RF HIV-1 isolates (Fig. la), cross-spectra between this CIS and IS of the
CD4 receptor (Fig. Ib), as well as cross-spectra between this CIS and IS of the fusin molecule (Fig. lc) contain only one characteristic peak corresponding to the frequency component F(0.035). Contrary, cross-spectra between CIS of gp 120 from analyzed "T-cell tropic"
HIV-1 isolates and IS of the CC-CKR-5 molecule, representing the co-receptor of the "macrophage-tropic" isolates, do not contain any characteristic peak above the noise (Fig. ld).
According to these analysis it can be concluded that the IS frequency component F(0.035) is characteristic for the interaction between gp 120 from "T-cell tropic" HIV-1 isolates and the CD4 receptor and the fusin coreceptor.
Hxale2 In order to determine which of the characteristic frequencies from IS of the gpl20 from the "macrophage-tropic" HIV-1 isolates are responsible for their interaction with the CD4 receptor and the CC-CKR-5 co-receptor, the ISM analysis of these proteins has been performed. These analysis revealed that the consensus IS (CIS) of gp 120 from the HXB2, Ba-l, SF 162 and JR-FL
HIV-1 isolates (Fig. 2a), cross-spectra between this CIS and IS of the CD4 receptor (Fig. 2b), as well as cross-spectra between this CIS and IS of the CC-CKR-5 molecule (Fig. 2c) contain only one characteristic peak corresponding to the frequency component F(0.207).
Contrary, the cross-spectra between CIS of gp 120 from analyzed "macrophage-tropic" HIV-1 isolates and IS of the fusin molecule, representing co-receptor of the "T-cell tropic" isolates, does not contain any characteristic peak above the noise (Fig. 2d).
According to these analysis it can be concluded that the IS frequency component F(0.207) is characteristic for the interaction between gp 120 from "macrophage-tropic" HIV-1 isolates and the CD4 receptor and the CC-CKR-5 co-receptor.
Rxamle3 In order to identify the domain of gp 120 from the "macrophage-tropic" HIV-1 isolates with the maximal amplitude at the IS frequency F(0.207), their primary structures were scanned with peptides of different lengths (from 20 to 30 a.a.). Results of this analysis for HXB2, Bal and SF160 isolates are given in Fig. 3.
These analysis reveald that the consensus peptide WRSANFTDNAXTIIVQLNBSVEINCTRP from the C-terminus of the
C2 domain of gp 120 from the "macrophage-tropic" HIV1 isolates represents the region with the highest amplitude corresponding to the frequency component
F(0.207). It means that this region of the "macrophage-tropic" HIV-1 isolates is most important for their interaction with the CC-CK1R-5 co-receptor.
Exa=ple4 In order to identify the domain of the fusin molecule with the maximal amplitude at the IS frequency
F(0.035), its primary structure was scanned with peptides of different lengths (from 20 to 30 a.a.). The results of this analysis are given in Fig.4a. These analysis revealed that the peptide GIVGNGLVILVNGYQKKLRSMTAKYRLHLS represents the region of these molecules with highest amplitude corresponding to the frequency component F(0.035). It means that this domain of the fusin molecule is the most important for its interaction with HIV-1 gp 120. The IS of this peptide is given in Fig. 4b.
Example 5
In order to identify the domain of the CC-CKR-5 molecule with the maximal amplitude at the IS frequency
F(0.207), its primary structure was scanned with peptides of different lengths (from 20 to 30 a.a.). The results of this analysis are given in Fig. 5a. These analysis revealed that the peptide DFGNTMCQLLTGLYFIGFFSGIFFIILLTI represents the region of this molecule with the highest amplitude corresponding to the frequency component F(0.207). It means that this domain of the CC-CKR-5 receptor is the most important for its interaction with HIV-1 gp 120. The IS of this peptide is given in Fig. Sb.
Claims (12)
1. A peptide derived from the second conserved domain of HIV-1 envelope glycoprotein gp 120 presenting in the
IS as a dominant the frequency component F 1 in the region 0.030-0.040 and/or F2 in the region 0.180-0.220.
2. A peptide according to claim 1 with the primary structure VVRSANFTDNAKTIIVQLNESVEINCTRP.
3. A peptide derived from the fusin receptor with the primary structure GIVGNGLVILVMGYQKKLRSMTAKYRLHLS.
4. A peptide derived from the CC-CKR-5 with the primary structure DPGNTMCQLLTGLYFIGFFSGIFFIILLTI.
5. A test kit containing at least one antigenic peptide according to any of claims 1 to 4, bound to a porous surface of solid substrate.
6. A test kit to claim 5, wherein the antigen peptide is bound to wells of a microtitre plate.
7. A pharmaceutical composition containing as an active ingredient at least one peptide as claimed in any one of claims 1 to 4.
8. A composition of matter comprising at least one peptide according to any of claims 1 to 4 conjugated to a protein or KLH.
9. A composition of matter comprising at least one peptide according to any of claims 1 to 4 expressed on the surface of the viral vector.
10. A composition according to claim 9 where the viral vector is vaccinia virus.
11. Use of at least one peptide according to claims 1 to 4, in the manufactures of a medicament for preventing
AIDS or slowing down its progression.
12. A composition of matter containing as active ingredients at lest two peptides according to any of claims 1 to 4.
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9623340A GB2319252A (en) | 1996-11-08 | 1996-11-08 | Polypeptides involved in the interaction of HIV gp120 with the fusin, and the CC-CKR-5 co-receptors thereof |
DE0808846T DE808846T1 (en) | 1996-05-22 | 1997-05-16 | Peptides that react with antibodies that mark the progress of HIV disease |
EP97107975A EP0808846A3 (en) | 1996-05-22 | 1997-05-16 | Peptides which react with antiboby representing the prognostic marker for HIV disease progression |
ES97107975T ES2113333T1 (en) | 1996-05-22 | 1997-05-16 | PEPTIDES THAT REACT WITH ANTIBODIES THAT REPRESENT THE FORECAST MARKER OF THE PROGRESSION OF THE AIDS DISEASE. |
JP9130879A JPH10237100A (en) | 1996-05-22 | 1997-05-21 | Peptides which react with antibody representing the prognostic marker for hiv disease progression |
US08/859,699 US20010007017A1 (en) | 1996-05-22 | 1997-05-21 | Peptides which react with antibody representing the prognostic marker for hiv disease progression |
CA002205077A CA2205077A1 (en) | 1996-05-22 | 1997-05-21 | Peptides which react with antibody representing the prognostic marker for hiv disease progression |
GR980300031T GR980300031T1 (en) | 1996-05-22 | 1998-05-29 | Peptides which react with antiboby representing the prognostic marker for HIV disease progression |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9623340A GB2319252A (en) | 1996-11-08 | 1996-11-08 | Polypeptides involved in the interaction of HIV gp120 with the fusin, and the CC-CKR-5 co-receptors thereof |
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GB2319252A true GB2319252A (en) | 1998-05-20 |
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GB9623340A Withdrawn GB2319252A (en) | 1996-05-22 | 1996-11-08 | Polypeptides involved in the interaction of HIV gp120 with the fusin, and the CC-CKR-5 co-receptors thereof |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7067117B1 (en) | 1997-09-11 | 2006-06-27 | Cambridge University Technical Services, Ltd. | Compounds and methods to inhibit or augment an inflammatory response |
US7238711B1 (en) | 1999-03-17 | 2007-07-03 | Cambridge University Technical Services Ltd. | Compounds and methods to inhibit or augment an inflammatory response |
US7700087B2 (en) | 1997-09-11 | 2010-04-20 | Cambridge Enterprise Limited | Compounds and methods to inhibit or augment an inflammatory response |
-
1996
- 1996-11-08 GB GB9623340A patent/GB2319252A/en not_active Withdrawn
Non-Patent Citations (8)
Title |
---|
Biochemical and Biophysical Research Communications 1992,189(2),705-710 * |
Biochemistry 1996,35(11),3362-3367 * |
Cancer Biochem.Biophys. 1988,10,91-106 * |
J.Biological Chemistry 1996,271(29),17161-17166 * |
J.Leukocyte Biology 1996,60,147-152 * |
Nature 1996,381,661-666 * |
Nature 1996,381,667-673 * |
Science 1996,272,872-877 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7067117B1 (en) | 1997-09-11 | 2006-06-27 | Cambridge University Technical Services, Ltd. | Compounds and methods to inhibit or augment an inflammatory response |
US7700087B2 (en) | 1997-09-11 | 2010-04-20 | Cambridge Enterprise Limited | Compounds and methods to inhibit or augment an inflammatory response |
US7238711B1 (en) | 1999-03-17 | 2007-07-03 | Cambridge University Technical Services Ltd. | Compounds and methods to inhibit or augment an inflammatory response |
US7989466B2 (en) | 1999-03-17 | 2011-08-02 | Cambridge Enterprise Limited | Methods to inhibit or augment an inflammatory response |
US8481558B2 (en) | 1999-03-17 | 2013-07-09 | Cambridge Enterprise Limited | Compounds to inhibit or augment an inflammatory response |
Also Published As
Publication number | Publication date |
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GB9623340D0 (en) | 1997-01-08 |
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