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1. WO1999009162 - DELAYED PROGRESSION TO AIDS BY A MISSENSE ALLELE OF THE CCR2 GENE

Publication Number WO/1999/009162
Publication Date 25.02.1999
International Application No. PCT/US1998/016523
International Filing Date 10.08.1998
Chapter 2 Demand Filed 06.03.1999
IPC
A61K 38/00 2006.1
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Applicants
  • THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES [US]/[US] (AL, AM, AT, AU, AZ, BA, BB, BE, BF, BG, BJ, BR, BY, CA, CF, CG, CH, CI, CM, CN, CU, CY, CZ, DE, DK, EE, ES, FI, FR, GA, GB, GE, GH, GM, GN, GR, GW, HR, HU, ID, IE, IL, IS, IT, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MC, MD, MG, MK, ML, MN, MR, MW, MX, NE, NL, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, SN, SZ, TD, TG, TJ, TM, TR, TT, UA, UG, UZ, VN, YU, ZW)
  • DEAN, Michael [US]/[US] (UsOnly)
  • O'BRIEN, Stephen, J. [US]/[US] (UsOnly)
  • SMITH, Michael [US]/[US] (UsOnly)
  • CARRINGTON, Mary [US]/[US] (UsOnly)
Inventors
  • DEAN, Michael
  • O'BRIEN, Stephen, J.
  • SMITH, Michael
  • CARRINGTON, Mary
Agents
  • SPRATT, Gwendolyn, D.
Priority Data
60/055,65914.08.1997US
Publication Language English (en)
Filing Language English (EN)
Designated States
Title
(EN) DELAYED PROGRESSION TO AIDS BY A MISSENSE ALLELE OF THE CCR2 GENE
(FR) EVOLUTION RETARDEE EN SIDA GRACE A UN ALLELE FAUX-SENS DU GENE CCR2
Abstract
(EN) The present invention relates to a CCR2 mutant, designated 'CCR2-64I'. 'CCR2-64I' is a CCR2 gene sequence which has a nucleotide substitution (a G to A substitution) at position 190 (counting from the ATG start codon) such that the valine found position 64 in the wild-type CCR2 amino acid sequence is replaced by an isoleucine. CCR2 is a C-C chemokine receptor and has been implicated as a co-receptor for HIV-1. It has been discovered that the presence of the CCR2-64I allele correlates with a postponement of AIDS outcomes, and that infected individuals who have the CCR2-64I allele are at reduced risk for progression from HIV-1 infection to the development of clinical AIDS and death. Isolated nucleic acid molecule encoding CCR2-64I and the establishment of cell lines that express CCR2-64I provides valuable tools for continuing research on HIV infection. Diagnostic methods for analysis of the allelic frequency of CCR2 wild-type and 64I genes are provided. In addition, antibodies which bind to CCR2-64I, CCR2-64I variants, and CCR2 binding agents represent potential anti-HIV agents.
(FR) Cette invention se rapporte à un mutant CCR2, appelé 'CCR2-64I'. 'CCR2-64I' est une séquence de gènes CCR2 qui possède une substitution nucléotidique (substitution G à A) à la position 190 (en comptant à partir du codon de départ ATG), de sorte que la valine située à la position 64 dans la séquence d'acides aminés de type sauvage est remplacée par une isolencine. Le CCR2 est un récepteur de chémokine C-C, impliqué comme co-récepteur pour le VIH-1. On a découvert que la présence de l'allèle CCR2-64I est à mettre en corrélation avec un report de l'évolution en SIDA, et que les sujets infectés ayant l'allèle CCR2-64I présentent moins de risque de voir leur infection à VIH-1 évoluer en SIDA clinique et en mort. Une mollécule d'acide nucléique isolée codant le CCR2-64I et l'établissement de lignées cellulaires qui expriment le CCR2-64I fournissent des outils valables permettant la poursuite des recherches sur les infections à VIH. Des procédés diagnostiques pour l'analyse de la fréquence allélique des gènes 64-I et de type sauvage du CCR2 sont présentés. En outre des anticorps qui se lient au CCR2-64I, des variants de CCR2-64I et des agents de liaison de CCR2 représentent des agents anti-VIH potentiels.
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