Based on a variety of different observations, interferon alpha (IFN-α) is a cytokine believed to be involved in a number of autoimmune diseases. Although systemic lupus erythomatosus (SLE) patients often do not have measurable serum levels of IFN-α, they appear to have a clear IFN-α gene signature. In addition, induction of dendritic cell (DC) maturation by treatment of DCs with SLE patient serum can be inhibited by an anti-IFN-α antibody. It has also been shown that knockout of the IFN-α/β receptor in New Zeeland Black (NZB) mice having an SLE phenotype results in a near normal phenotype (Santiago-Raber et al., J Exp Med. 2003; 197(6):777-88).
Antibodies against IFN-α have therefore been suggested as tools to neutralize the activity of this cytokine for the treatment of such autoimmune diseases, alone or in combination. Specific murine antibodies (ACO-1 to ACO-6) that recognize a wide range of different IFN-α subtypes were generated and characterized as described in the international patent application published as WO20060086586. However, murine antibodies are not suitable for use in humans because of their immunogenicity, and it is therefore desirable to generate humanized antibodies where the murine CDRs are grafted onto a human scaffold antibody. However humanized antibodies often suffer from functional deficiencies as compared to the murine parent, such as, e.g., a lower affinity and/or stability and/or undesirable immunogenicity. Such deficiencies in humanized antibodies can in some cases be compensated for by making one or a few back point mutations. It is usually desirable to perform no or only a very few back point mutations since the presence of too many back mutations tend to result in undesirable low stability and/or an undesirable degree of immunogenicity. The provision of a safe and stable humanized anti-IFN-α antibody having desirable biological properties such as e.g. retaining affinity and potency of the humanized anti-IFN-α antibody to a large number of IFN-α subtypes is thus desirable.
There is thus a need in the art for humanized anti-IFN-α antibodies having desirable features with respect to features such e.g. stability, specificity, safety, immunogenicity, etc. Furthermore, there is a need in the art for efficient methods for producing such antibodies.
USPTO Backgrounds
USPTO Backgrounds