The molecular basis of many autoimmune diseases remains unknown. Due in part to this lack of a molecular-level understanding, the state of the art in the development of diagnostic agents and effective therapies for autoimmune diseases is far from optimal. For example, there is no highly reliable serum protein marker for diagnosis of most autoimmune diseases. Almost without exception, drugs employed to treat these conditions either inhibit an event downstream of the autoimmune response itself, such as inflammation, or attempt to modulate or suppress the entire immune system non-selectively (Hemmer & Hartung, 2007), with significant undesirable side effects. For both diagnostic and therapeutic applications, one would ideally like to have molecules that target autoreactive B cells (and the antibodies they produce) and T cells directly, but ignore B and T cells that recognize foreign antigens. The present applicant has filed a patent application covering certain such molecules and methods, U.S. Ser. No. 12/789,711 and which is hereby incorporated by reference. Such molecules could be employed as diagnostic agents and research tools for the detection and enrichment of autoimmune antibodies, B cells and T cells. In addition, these molecules could serve as the foundation for a novel drug development program aimed at eradicating these autoreactive cells without affecting the proper function of the immune system. It is also known that certain libraries of random ligands on microarrays can screen for various disease associated biomarkers. U.S. patent application Ser. No. 11/433,069, also hereby incorporated by reference, teaches various random libraries of ligands that may be prepared and screened against biological samples having disease-associated biomarkers including antibodies and antibodies associated with autoimmune diseases. The present invention, on the other hand, is directed to a method of screening a library of ligands against autoantibodies that are known to be associated with a particular autoimmune disease in order to find antigen surrogates that are useful in binding to the autoantibody to prevent it from causing or acerbating the particular autoimmune disease. In addition, such ligands can also be used as diagnostics to screen individuals for autoimmune diseases and conditions. In a preferred embodiment, the present invention is directed to screening a library of cyclic peptoid ligands against at least one autoantibody associated with an autoimmune disease. U.S. patent application Ser. No. 12/905,605, hereby incorporated by reference, teaches the preparation of cyclic peptoid libraries. In another preferred embodiment, the screen can be a combination screen in which B-cells, T-cells or other cells which produce or cause the production of such antibodies are screened against a library of ligands to find high affinity ligands for such B-cells or T-cells pursuant to the methods disclosed in patent application Ser. No. 12/789,711 wherein said ligands are highly selective for B-cells producing such autoantibodies and/or T-cells which help stimulate the production of such antibody producing cells yet not selective for healthy cells or cells not associated with such autoimmune disorders. The methods used to pull such B-cells and/or T-cells out of the blood or fluid of patients in need of treatment thereof is combined with treatment of such patient having such autoimmune disorder with a high affinity ligand found pursuant to the methods disclosed herein by screening a ligand library against known autoantibodies associated with the disease in order to remove and/or mitigate the effects of the autoantibodies produced from such B-cells or assisted in such production by T-cells. The size of the library to screen against these known autoantibodies may range from 10,000 to millions of ligands depending upon the support system. Ligand libraries are prepared by methods disclosed in the art. Such references may be found in, for example, U.S. Ser. No. 11/433,069 which is hereby incorporated by reference.
USPTO Backgrounds
USPTO Backgrounds