Abstract: The present invention relates to the treatment of IgE-mediated disease. The inventors hypothesized that formation of immune complexes between Omalizumab and IgE might be responsible for some of the adverse reactions observed in highly atopic patients (i.e. patients with a history of anaphylaxis and/or high IgE titers). Immune complexes can induce inflammation through activation of Fc gamma receptors (Fc?Rs) and/or the complement cascade. They identified that Omalizumab:hIgE immune complexes activate human Fc?Rs in vitro. Moreover, similarly to some of the reported side effects observed in human, Omalizumab:hIgE immune complexes can induce anaphylaxis when injected in mice expressing human Fc?Rs. Using publicly available omalizumab VH and VL sequences, they cloned and produced two mutant versions of omalizumab in which residues in the Fc portion of the Ab were mutated.

Abstract: In a hermetic integrated-circuit package, the peripheral wall that bounds the cavity 2 containing the integrated circuit has, all the length of the peripheral wall, a surface containing a relief, which is defined by a raised planar zone z1, on the side inside the package of the cavity, and a recessed zone z2, on the exterior of the raised planar zone. The planar zone makes direct contact with the closing plate 6 of the package, without interposition of adhesive, over the entire length of the peripheral wall, except where planarity defects prevent the contact. The recessed zone does not make direct contact with the closing plate, and contains an adhesive bead that joins the closing plate and the upper portion of the peripheral wall over all the peripheral length of the latter. The adhesive bead 9 has a surface Se in open air between the closing plate and the recessed zone, on the exterior side of the package.

Abstract: In a hermetic integrated-circuit package, the peripheral wall that bounds the cavity 2 containing the integrated circuit has, all the length of the peripheral wall, a surface containing a relief, which is defined by a raised planar zone z1, on the side inside the package of the cavity, and a recessed zone z2, on the exterior of the raised planar zone. The planar zone makes direct contact with the closing plate 6 of the package, without interposition of adhesive, over the entire length of the peripheral wall, except where planarity defects prevent the contact. The recessed zone does not make direct contact with the closing plate, and contains an adhesive bead that joins the closing plate and the upper portion of the peripheral wall over all the peripheral length of the latter. The adhesive bead 9 has a surface Se in open air between the closing plate and the recessed zone, on the exterior side of the package.