Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
1995-06-02
2004-01-27
Smith, Lynette R. F. (Department: 1645)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C530S387100, C530S387900, C530S388230, C424S130100, C424S139100, C424S158100
Reexamination Certificate
active
06682896
ABSTRACT:
BACKGROUND OF THE INVENTION
Human interferons (IFN's) are members of a biologically potent family of cytokines. Known activities of these proteins include those which are antiviral, antiproliferative and immunomodulatory. Three antigenically distinct types of interferons are known: &agr;(leukocyte), &bgr;(fibroblast) and &ggr;(immune). They all bind to high affinity cell surface receptors; IFN&agr; and IFN-&bgr; share a receptor that is distinct from the one bound by IFN&ggr;. The events responsible for biological activity beyond receptor binding are poorly understood. Recent studies, however, showing IFN's efficacy in treating certain viral diseases and cancer have been encouraging. These clinical observations have stimulated interest in further understanding the molecular basis of activity. To this end, study of genetically engineered IFN's has provided insight to structure-function relationships. An altered form of fibroblast interferon, rIFN-&bgr;
ser
, is one such protein. It is a recombinant molecule the sequence of which is based on human fibroblast interferon. In this protein, a cysteine residue at position
17
was replaced with serine by site-directed mutagenesis. The resulting molecule is fully active having the same biologic activities as natural IFN-&bgr; and it is now a clinically useful protein therapeutic. In this disclosure IFN-&bgr; will be used to denote both natural and recombinant forms of IFN-&bgr; but rIFN-&bgr; is sometimes used to indicate the recombinant form of IFN-&bgr; when that more clearly describes the work presented. In clinical usage it has been found that some patients produce antibodies to IFN-&bgr; which neutralize its biologic activity. In other words these antibodies have the ability to inhibit all or some of the beneficial activities of IFN-&bgr;. The present invention is concerned with the discovery of peptides that represent the sites to which neutralizing antibodies bind to IFN-&bgr;. These peptides may be the same epitopes responsible for the biologic activity of IFN-&bgr;. The peptides of this invention may be useful in inhibiting the neutralizing effect of neutralizing antibodies to IFN-&bgr;. They also have diagnostic applications for the detection of neutralizing antibodies. Antibodies raised to or having specific binding affinity for the peptides mentioned above are also a part of this invention as they can be used to detect and monitor levels of IFN-&bgr; in patients during the course of treatment.
SUMMARY OF INVENTION
The present invention discloses synthetic peptides which represent epitopic sites on both natural and recombinant Human IFN-&bgr; (HuIFN-&bgr;) one aspect of the invention, the epitopic peptides represent the site(s) where neutralizing antibodies bind to IFN-&bgr; thereby reducing or eliminating its activity. Another aspect of this invention provides a diagnostic or prognostic assay whereby a patient receiving IFN-&bgr; therapy can be assessed for production of IFN-&bgr; neutralizing antibodies. A third aspect of this invention provides a method for treating a patient to reduce or eliminate the effect of neutralizing antibodies during IFN-&bgr; therapy. A fourth aspect of this invention provides a method for detecting IFN-&bgr; levels in a sample. The peptides of this invention may also represent the epitopes responsible for IFN-&bgr;'s biological activity.
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Portner Ginny Allen
Schering Aktiengesellschaft
Smith Lynette R. F.
Washtien Wendy L.
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