Antibodies against a complex of cd4 and a chemokine receptor...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 5/16 (2006.01) A01K 67/027 (2006.01) A61K 39/395 (2006.01) C07K 14/155 (2006.01) C07K 14/715 (2006.01) C07K 14/73 (2006.01) C07K 16/10 (2006.01) C07K 16/28 (2006.01) C07K 16/46 (2006.01) G01N 33/566 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2256306

This invention is directed to monoclonal antibodies produced by using CD4- expressing T lymphocytes, such as peripheral blood mononuclear T cells, thymocytes, splenocytes and leukemia or lymphoma derived T cell line cells such as HPB-ALL or SUP-T as the immunogen in accordance with the protocols and screening procedures described. The monoclonal antibodies of the present invention are characterized by their ability to neutralize in vitro and in vivo primary isolates of Human Immunodeficiency Virus (HIV) and related immunodeficiency viruses. The antibodies are directed against a host cell antigen complex comprising CD4 protein in association with domains from chemokine receptors and have broad neutralizing activities against primary isolates from all clades of HIV type 1 (HIV-1) and primary isolates of HIV type 2 (HIV-2) and Simian Immunodeficiency Virus (SIV). The present invention is also directed to a method of selecting and producing such antibodies, hybridomas which secrete such antibodies, pharmaceutical compositions comprising such antibodies and methods for pre- and post-exposure prevention of immunodeficiency virus infection in primates, including humans, by such antibodies whose primary targets are CD4-expressing lymphocytes.

La présente invention concerne des anticorps monoclonaux que l'on produit en utilisant comme immunogène, selon les protocoles et les procédures de dépistage décrits, des lymphocytes T exprimant les CD4, tels que les cellules T mononucléaires circulantes, les thymocytes, les sphénocytes et des cellules T de lignées cellulaires dérivées d'une leucémie ou d'un lymphome telles que HPB-ALL ou SUP-T. Les anticorps monoclonaux de la présente invention sont caractérisés par leur capacité à neutraliser in vitro et in vivo les isolats primaires du virus de l'immunodéficience humaine (VIH) et des virus d'immunodéficience associés. Ces anticorps sont dirigés contre un complexe antigénique de cellule hôte comprenant une protéine CD4 associée à des domaines de récepteurs des chémokines et ils présentent une large activité de neutralisation des isolats primaires de tous les clades de VIH type 1 (VIH-1), et des isolats primaires du VIH type 2 (VIH-2) et du virus d'immunodéficience simienne (VIS). La présente invention concerne également un procédé de sélection et de production de ces anticorps, d'hybridomes sécrétant ces anticorps, de compositions pharmaceutiques comprenant ces anticorps, ainsi que des procédés faisant appel à ces anticorps dont les cibles primaires sont les lymphocytes exprimant les CD4, et permettant de prévenir l'infection par le virus d'immunodéficience avant et après l'exposition au virus chez les primates, y compris l'être humain.

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