Invented by Stacey R. Dillon, Jane A. Gross, Keith B. Elkon, University of Washington, Zymogenetics Inc

The market for Levels BCMA protein expression in B cells and treatment of systemic lupus by using BCMA Systemic lupus erythematosus (SLE), commonly referred to as lupus, is a chronic autoimmune disease that affects multiple organs and tissues in the body. It is characterized by the production of autoantibodies that attack healthy cells and tissues, leading to inflammation and damage. While there is no cure for lupus, researchers and pharmaceutical companies are constantly exploring new treatment options to improve the quality of life for patients. One potential avenue for the treatment of lupus is targeting B-cell maturation antigen (BCMA) protein expression in B cells. BCMA is a cell surface receptor that plays a crucial role in the survival and activation of B cells, which are responsible for producing antibodies. In lupus, B cells become overactive and produce autoantibodies that contribute to the disease progression. Recent studies have shown that BCMA expression is elevated in B cells of lupus patients compared to healthy individuals. This finding has opened up new possibilities for targeted therapies that aim to modulate BCMA levels and reduce B-cell activity in lupus. The market for BCMA protein expression in B cells is rapidly growing as researchers and pharmaceutical companies recognize its potential in lupus treatment. Several approaches are being explored to target BCMA, including monoclonal antibodies, small molecules, and gene therapies. Monoclonal antibodies are one of the most promising strategies for BCMA targeting. These antibodies can bind to BCMA on B cells, leading to their depletion or modulation of their activity. Clinical trials are currently underway to evaluate the safety and efficacy of BCMA-targeting monoclonal antibodies in lupus patients. Another approach involves the use of small molecules that can inhibit BCMA signaling pathways. These molecules can interfere with the interaction between BCMA and its ligands, preventing B-cell activation and autoantibody production. While small molecules are still in the early stages of development, they hold great potential for targeted lupus therapy. Gene therapies are also being explored to modulate BCMA expression in B cells. By using gene editing techniques, researchers can potentially decrease BCMA levels or modify its function to reduce B-cell activity in lupus. Although gene therapies are still in the experimental stage, they offer a promising avenue for personalized treatment options in the future. The market for BCMA-targeted therapies in lupus is expected to grow significantly in the coming years. As more research is conducted and clinical trials yield positive results, pharmaceutical companies will likely invest in the development and commercialization of BCMA-targeting drugs. The potential market size for these therapies is substantial, considering the high prevalence of lupus worldwide and the lack of effective treatment options. However, challenges remain in the development of BCMA-targeted therapies for lupus. Safety concerns, potential side effects, and the need for personalized approaches are some of the factors that need to be addressed. Additionally, regulatory approval and reimbursement issues may also impact the market growth. In conclusion, the market for BCMA protein expression in B cells and its potential for the treatment of systemic lupus is expanding rapidly. The elevated levels of BCMA in lupus patients provide a unique opportunity for targeted therapies that aim to modulate B-cell activity and reduce autoantibody production. While challenges exist, the growing interest in BCMA-targeted therapies and the potential benefits for lupus patients make this an exciting area of research and development.

The University of Washington, Zymogenetics Inc invention works as follows

The present invention is a method for measuring the level of BCMA within a biological sample and specifically on the surface of the B cells. These diagnostic tests are used to predict whether an individual is likely to develop or suffer from an autoimmune disorder, such as SLE. They can also be used for treatment of an individual who has been diagnosed with a clinically confirmed autoimmune condition. This diagnostic test predicts a patient’s response to a particular drug treatment. In particular, treatment with BLyS inhibitors alone or in combination with immune suppressive drugs.

Background for Levels BCMA protein expression in B cells and treatment of systemic lupus by using BCMA

The TNFR family consists of a number of integral membrane glycoprotein receptors that, in conjunction with their respective ligands, regulate interactions between different hematopoietic cell lineages. The TNFR family consists a number integral membrane glycoproteins receptors that, together with their respective ligands regulate interactions between hematopoietic cells lineages.

The development of BLyS or APRIL antagonists is aimed at blocking the binding of these ligands with the receptor family members. This binding can lead to a number of effects, including but not limited to, B-cell survival, Ig switching, increased B-cell antigen presentation cell function and survival of malignant cells. These molecules can also bind and block APRIL’s effect on B cells, and other immune system components (Dillon et. al.). (2006) Nat. Rev. Rev. 5, 235-246). Molecules that have been developed to affect B cell function by interfering with BLyS and/or APRIL binding include BLyS antibodies such as Lymphostat-B (Belimumab) (Baker et al, (2003) Arthritis Rheum, 48, 3253-3265 and WO 02/02641); receptor-extracellular domain/Fc domain fusions proteins such as TACI-Ig, including one particular embodiment, atacicept (U.S. Patent Application No. WO 05/0000351, BAFF-R -Fc, BCMA-Ig, or other fusions proteins using receptor extracellular domains. APRIL and BLyS antagonists can also include molecules that rely on the BLyS-binding ability to prevent binding to receptors, such as AMG623, receptor antibodies and other molecules described in WO 03/035846 or WO 02/16312.

There is a need for further identification in the field of TNFR family member cell surface expression patterns that are statistically related to autoimmune diseases, such as Systemic Lupus Erythromatosus.” This information is useful for identifying people who are at risk of developing autoimmune disease, those in an active state, as well as for identifying patients that will respond to BLyS or APRIL antagonist treatments. This invention meets this need by providing an expression pattern on the cell surface associated with autoimmune disorders and diagnostic tests that determine this pattern. The expression pattern is increased BCMA expression in B cells of those with autoimmune disease compared to healthy control.

The present invention is a screening method for TNFR members on B cell surfaces. This measurement can be used as a test for diagnosing SLE and other autoimmune diseases. These diagnostic tests are helpful in predicting a person’s likelihood to have a condition that is associated with autoimmune activity such as SLE. The invention also provides methods to determine appropriate treatment for individuals with an autoimmune condition, such as SLE.

The invention also provides methods of treating individuals with autoimmune conditions, which generally include detecting high BCMA levels on cells as compared with levels on B cells in healthy controls and selecting the most effective treatment plan for those clinically diagnosed. The detection of high BCMA levels on B cells can also be used to predict the likelihood of a patient responding to a particular drug treatment, such as BLyS or APRIL antagonists. The invention also provides methods for predicting the likelihood of a patient responding to BLyS or APRIL antagonists, either alone or in combination, during treatment for autoimmune conditions, such as SLE.

Very specifically, the present invention describes a method of detecting increased BCMA protein expression on the surface of B cells of an individual comprising measuring a first level of BCMA protein expression in a biological sample and comparing that level to a second level of BCMA protein expression present on the surface of B cells of a healthy individual and determining the first level is increased as compared to the second level, wherein said increased BCMA protein expression is associated with an autoimmune disease. The autoimmune disease in the present invention can be selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener’s disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud’s syndrome, Sjorgen’s syndrome and glomerulonephritis. In particular, the autoimmune disease is SLE.

The present invention describes a treatment method for an individual with an autoimmune disorder. This involves analyzing a sample of biological material from an individual with an autoimmune condition to determine whether or not there are elevated BCMA expression levels in their B cells. Treatment plans can include administration of a BLyS inhibitor. The BLyS inhibitor can also be an APRIL inhibitor. This method allows the selection of an autoimmune disease from a group that includes rheumatoid, juvenile, and adult rheumatoid, as well as lupus, lupus-nephritis, Wegener’s, inflammatory, and bowel diseases, ITP, TTP, IgA, IgM, and vasculitis. SLE is the specific autoimmune disease.

The autoimmune disease can be selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener’s disease, inflammatory bowel disease, thrombotic throbocytopenic purpura, autoimmune thrombocytopenia, multiple sclerosis, psoriasis The autoimmune diseases include rheumatoid, juvenile, and systemic lupus. SLE is the specific autoimmune disease. The present invention can also include a method of drug treatment that involves the administration of a BLyS inhibitor, and said BLyS inhibitor can be an APRIL inhibitor.

The present invention also encompasses an in vitro method of detecting increased BCMA protein expression on the surface of B cells of an individual, comprising measuring the level of BCMA protein expression on the surface of B cells in a test biological sample from the individual; comparing that level to the level of BCMA protein expression on the surface of B cells in a sample from a healthy control; and determining whether the level of BCMA protein expression on the surface is B cells in the test biological sample is increased as compared to the level in the control sample; wherein said increased BCMA protein expression is associated with an autoimmune disease. The autoimmune disease in this method can be selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener’s disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud’s syndrome, Sjorgen’s syndrome and glomerulonephritis. In particular, the autoimmune disease is SLE.

In a further embodiment of the invention, an in vitro treatment plan selection method is provided. This includes analyzing a biological sample of an individual with an autoimmune diagnosis in vitro for the presence or lack of elevated BCMA on their B-cells, with the presence of increased BCMA being associated with the clinical diagnoses of an autoimmune disorder. This method can involve the use of a BLyS inhibitor and the BLyS inhibitor can also be an APRIL inhibitor. “The autoimmune disease may be chosen from a group that includes rheumatoid, juvenile, and systemic lupus.

SLE is a specific autoimmune disorder.

The autoimmune disease can be selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener’s disease, inflammatory bowel disease, thrombotic throbocytopenic purpura, autoimmune thrombocytopenia, multiple sclerosis, psoriasis The autoimmune diseases include rheumatoid, juvenile, and systemic lupus. The autoimmune disease in particular is SLE. The present invention may include a BLyS inhibitor and this BLyS inhibitor can also be an APRIL inhibitor.

Finally the present invention contemplates a BLys inhibitor for use in treating an autoimmune disorder in a patient who has high levels of BCMA on B cells. The antagonist could be a BLyS-antibody, such as Lymphostat B. The antagonist can also be a receptor-extracellular domain/Fc domain fusion protein selected from the group consisting of TACI-Ig, BCMA-Ig, and BAFF-R-Ig. In particular, the receptor-extracellular domain/Fc domain fusion protein can be TACI-Ig, such as atacicept.

The following description of the invention provides a more detailed explanation of these and other aspects.

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