Identification of novel broadly cross-reactive neutralizing human monoclonal antibodies using sequential antigen panning of phage display libraries

    公开(公告)号:AU2009200792B2

    公开(公告)日:2011-11-10

    申请号:AU2009200792

    申请日:2009-02-27

    Abstract: The present invention provides a method of identifying novel broadly crossreactive neutralizing monoclonal anti-bodies using sequential antigen panning of phage display libraries, antibodies obtained in accordance with such a method, as well as fusion proteins and conjugates comprising same, and related isolated or purified nucleic acid molecules, vectors, host cells, compositions, and methods of use to inhibit an infection, reduce the severity of an infection, treat an infection, treat an infection, and inhibit cancer. Flow chart of sequential antigen panning (m12 and m14) pComb3H phage Preabsorption on pre-washed M-280 streptavidin beads Depletion with sCD4 1" round of panning (rp) against 50 nM biotinylated gpl40sg. 6-sCD4 1" round panned library Preabsorption on pre-washed M-280 streptavidin beads Depletion with sCD4 2 nd rp against 10 nM biotinylated gpl4089.6-sCD4 complexes 2 "d round panned library Preabsorption on pre-washed M-280 streptavidin beads 3 rd rp against 2 nM biotinylated gpl40sg.6-sCD4 complexes 3rd round panned library 4, rp against 2 nM biotinylated gpl40WHXB2-SCD4 complexes 4h round panned library screen individual clones from 4*, 5* and 6"1 round panned libraries by phage ELISA using gpl20/l4089.6/HBx2 and gpl20 Ma and their complexes with sCD4 as antigens selection of clones with highest binding activity to all antigens

    Identification of a domain in the tumor necrosis factor receptor family that mediates pre-ligand receptor assembly and function

    公开(公告)号:AU2006203490B9

    公开(公告)日:2011-01-20

    申请号:AU2006203490

    申请日:2006-08-11

    Abstract: The present invention provides a polypeptide comprising the isolated amino acid sequence of a pre-ligand assembly domain (PLAD) of a TNF-like receptor. Also provided by this invention is a polypeptide comprising the isolated amino acid sequence of a pre-ligand assembly domain (PLAD), wherein the PLAD is selected from the group consisting of: the PLAD of a TNF-R, the PLAD of p60, the PLAD of p80, the PLAD of Fas (CD95/APO-1), the PLAD of TRAIL receptors, the PLAD of LT&bgr;R, the PLAD of CD40, the PLAD of CD30, the PLAD of CD27, the PLAD of HVEM, the PLAD of OX40 and the PLAD of DR4. TNF-R, p60, p80, Fas, TRAIL receptor, LT&bgr;R, CD40, CD30, CD27, HVEM, OX40, DR4, TROY, EDAR, XEDAR, DCR3, AITR, 4-1BB, DR3, RANK, TACI, BCMA, DR6, DPG, DR5, DCR1 AND DCR2 are all members of the TNF receptor superfamily or the TNF-like receptor family. The invention also provides the PLAD for other members of the TNF receptor superfamily. The polypeptides of the present invention can be utilized to inhibit oligomerization of members of the TNF receptor superfamily. These polypeptides can also be utilized to inhibit ligand binding to members of the TNF receptor superfamily. The present invention also provides a composition comprising an inhibitor of TNF receptor oligomerization. Further provided by this invention are members of the TNF receptor superfamily that are lacking a PLAD.

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