Gliknik Inc.

University System of Maryland

Henrik Olsen

David S Block

Scott E Strome

Dan H Schulze

Emmanuel Y Mérigeon

The present invention provides methods for the identification of patients with an inflammatory or autoimmune disease that demonstrate an inadequate response to treatment with a multi-Fc therapeutic, and the determination of an optimal dose of a multi-Fc therapeutic for said patient based on the patient's circulating levels of inactivated C3b (iC3b) and/or additional complement components that may be employed as a surrogate for iC3b based on an analogous response to multi-Fc therapeutics. The present invention further provides for improvements in the use of such multi-Fc therapeutics in the treatment of autoimmune and inflammatory diseases.

Methods of treating inflammatory disorders with multivalent Fc compounds

The present disclosure involves optimized methods for production of biologically active proteins termed optimally manufactured stradomers. The present disclosure further provides compositions and methods useful in the treatment of diseases and conditions including autoimmune diseases, inflammatory diseases, or infectious diseases.

Manufacturing optimization of GL-2045, a multimerizing stradomer

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. The invention involves stradomers that increase multimerization and bind preferentially to complement and that are useful in the treatment and prevention of disease.

Fusion proteins of human protein fragments to create orderly multimerized immunoglobulin Fc compositions with enhanced complement binding

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 FcγRs 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.

Fusion proteins of natural human protein fragments to create orderly multimerized immunoglobulin Fc compositions

The present disclosure involves optimized methods for production of hiologically active proteins termed optimally manufactured stradomers. The present disclosure further provides compositions and methods useful in the treatment of diseases and conditions including autoimmune diseases, inflammatory diseases, or infectious diseases.

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&#x3b3;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.

The present disclosure involves biologically active proteins termed cysteine-optimized multimerizing stradomers. Thus, the present disclosure provides compositions and methods providing anti-autoimmune and anti-inflammatory activities, useful in the treatment of diseases and conditions including autoimmune diseases, inflammatory diseases, or infectious diseases.

Cysteine-optimized stradomers

IVIG replacement compounds are derived from recombinant and/or biochemical creation of immunologically active biomimetic(s). These replacement compounds are then screened in vitro to assess each replacement compound's efficiency at modulating immune function. Particular replacement compounds are selected for further in vivo validation and dosage/administration optimization. Finally, the replacement compounds are used to treat a wide range of diseases, including inflammatory and autoimmune diseases.

Immunoglobulin constant region Fc receptor binding agents

IVIG replacement compounds are derived from recombinant and/or biochemical creation of immunologically active biomimetic(s). These replacement compounds are then screened in vitro to assess each replacements compound's efficiency at modulating immune function. Particular replacement compounds are selected for further in vivo validation and dosage/administration optimization. Finally, the replacement compounds are used to treat a wide range of diseases, including inflammatory and autoimmune diseases.

The current invention involves biologically active proteins termed stradobodies. The stradobodies have two or more domains that create stradobody multimers. The stradobodies have both antigen-binding capacity and the ability to bind Fc receptors (FcR), and are useful in the treatment and prevention of disease.

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Baltimore, MD, United States of America

Henrik Olsen