FUSION PROTEINS OF NATURAL HUMAN PROTEIN FRAGMENTS TO CREATE ORDERLY MULTIMERIZED IMMUNOGLOBULIN Fc COMPOSITIONS

Abstract

The current invention involves a series of fully recombinant multimerized forms of immunoglobulin Fc which thereby present polyvalent immunoglobulin Fc to immune cell receptors. The fusion proteins exist as both homodimeric and highly ordered multimeric fractions, termed stradomers. In comparison to the homodimeric fraction, purified multimeric stradomers have higher affinity and avidity for Fc Rs with slower dissociation and are useful in the treatment and prevention of disease. The current invention demonstrates that directly linking IgG1 Fc regions to multimerization domains leads to enhanced multimerization and biological activity.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 61 / 368,465, filed Jul. 28, 2011, the contents of which are incorporated by reference herein in its entirety.DESCRIPTION OF THE TEXT FILE SUBMITTED ELECTRONICALLY[0002]The contents of the text file submitted electronically herewith are incorporated herein by reference in their entirety: A computer readable format copy of the Sequence Listing (filename: GLIK—006—01US_SeqList_ST25.txt, date recorded: Jul. 26, 2011 file size 61 kilobytes).FIELD OF THE INVENTION[0003]This invention relates generally to the fields of immunology, autoimmunity, inflammation, and tumor immunology. More specifically, the present invention relates to biologically active biomimetic molecules comprising naturally linked immunoglobulin Fc domains, compositions comprising such biomimetics, and methods of making and using such biomimetics.[0004]The invention also relates to the treatment and prophylaxis...

AI Technical Summary

Benefits of technology

[0012]There is a need for an alternative to IVIG that solves the problems of high protein load, inconvenient patient dosing, infectious risk, IgA anaphylaxis, and limited availability while maintaining and enhancing the efficacy of the aggregate fraction of IVIG. The present invention relates to biologically active fusion protein biomimetic molecules comprising human immunoglobulin Fc and a single naturally occurring multimerization domain, compositions comprising the same, and methods of using the same. These biomimetics have broad application for treating immunological and inflammatory disorders including but not limited to autoimmune diseases, just like hIVIG after which these biomimetics were modeled. Further, certain of these biomimetics also have utility as laboratory reagents, such as for use in immunological assays for testing immune cell function, in the diagnosis of disease and in blocking non-specific binding of Fc in antibody-based immunoassays. Moreover, the biomimetics and compositions of the present invention have the advantage of overcoming the above-listed limitations of hIVIG as well as the multimerization limitations of the precursor biomimetic stradomers.

Problems solved by technology

While hIVIG has been an effective clinical treatment, there are several shortcomings to hIVIG treatments, including the potential for inadequate sterility, the presence of impurities or infectious agents including viruses and prions, lack of availability of this pooled human blood product, lot-to-lot variation, high expense, large protein load affecting renal function, and long administration time, generally over many hours and sometimes two consecutive days monthly.

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