Methods of use of soluble cd24 for therapy of rheumatoid arthritis

a technology of rheumatoid arthritis and soluble cd24, which is applied in the field of compositions and methods for treating rheumatoid arthritis, can solve the problem of not having a cure for ra, and achieve the effect of improving the effect of ra

Inactive Publication Date: 2013-09-05
ONCOIMMUNE INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006]RA affects 0.5-1% of human populations. Although a number of disease-modifying antirheumatic drugs (DMARDs) are currently available, even the gold standard of biologic DMARDs, the therapeutics targeting the tumor-necrosis factor alpha, lead to 50% improvement according to American College of Rheumatology Improvement Criteria (ACR50) in less than 50% of the patients receiving the treatments. No cure for RA is available. It is therefore necessary to test additional therapeutics for RA. RA is presumed to be autoimmune diseases in the joint, although the cause of the diseases remains largely obscure. A number of studies have implicated T cells in the pathogenesis of rheumatoid arthritis. More recently, it has been demonstrated that transfer of antibodies can cause the development of inflammation of the joints of mice. The pathology of the lesions resembles human rheumatoid arthritis.

Problems solved by technology

No cure for RA is available.

Method used

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  • Methods of use of soluble cd24 for therapy of rheumatoid arthritis
  • Methods of use of soluble cd24 for therapy of rheumatoid arthritis
  • Methods of use of soluble cd24 for therapy of rheumatoid arthritis

Examples

Experimental program
Comparison scheme
Effect test

example 1

Soluble CD24 Proteins

[0055]The extracellular domain of CD24 was fused to IgG1 Fc. The amino acid composition of the CD24 fusion protein is provided in FIG. 1. A replication-defective retroviral vector that drives expression of the CD24Ig fusion protein was then generated. The GPExTM (an acronym for gene product expression) system offers several important advantages, the most important of which is the, on average, >1000 insertions / cell but with only 1 copy / insertion. Moreover, since the retrovirus preferentially inserts into the transcriptional active locus, the GPEx™ resulted in a high level of expression of the targeted protein. Stable cell lines that produce a high yield of CD24Ig were generated. In addition 45 grams of GLP grade products and ˜100 grams of cGMP grade products were produced. The methods used for downstream processing of media harvested from the bioreactor are summarized in the flow chart below (FIG. 2).

Harvest Clarification

[0056]The bioreactor culture media was cla...

example 2

CD24 Pharmacokinetics

[0064]1 mg of CD24IgG1 (CD24Fc) was injected into naïve C57BL / 6 mice and collected blood samples at different timepoints (5 min, 1 hr, 4 hrs, 24 hrs, 48 hrs, 7 days, 14 days and 21 days) with 3 mice in each timepoint. The sera were diluted 1:100 and the levels of CD24Ig was detected using a sandwich ELISA using purified anti-human CD24 (3.3 μg / ml) as the capturing antibody and peroxidase conjugated goat anti-human IgG Fc (5 μg / ml) as the detecting antibodies. As shown in FIG. 4a. The decay curve of CD24Ig revealed a typical biphase decay of the protein. The first biodistribution phase had a half life of 12.4 hours. The second phase follows a model of first-order elimination from the central compartment. The half life for the second phase was 9.54 days, which is similar to that of antibodies in vivo. These data suggest that the fusion protein is very stable in the blood stream. In another study in which the fusion protein was injected subcutaneously, an almost id...

example 3

CD24 for Treating RA

[0065]For decades, it has been assumed that RA is predominantly a T-cell mediated autoimmune diseases. In the last two decades, there is a reawaking on the possible role for antibodies and B lymphocytes in RA pathogenesis. Thus, in addition or rheumatoid factors, a host of autoreactive antibodies have been found in RA patients, although it has not been definitively addressed in human. However, several lines of evidence have demonstrated that in the mouse models, antibodies specific for either ubiquitous or tissue specific antigens are sufficient to cause RA symptoms. For instance, antibodies from the K / BxN TCR transgenic mice were found to be fully capable of transferring RA-like diseases in the new host. Likewise, a cocktail for 4 anti-collagen antibodies is now widely used to induce RA in the mouse. This model is now called CAIA, for collagen antibody-induced arthritis.

[0066]Genetic analyses of CAIA model indicate critical roles for complement. Although other p...

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Abstract

Provided herein is a method of treating rheumatoid arthritis using a CD24 protein. The CD24 protein may include mature human or mouse CD24, as well as a N- or C-terminally fused portion of a mammalian immunoglobulin.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This is a continuation-in-part of U.S. patent application Ser. No. 13 / 643,527, which is the national stage of International Application No. PCT / US 11 / 34282, filed Apr. 28, 2011, which claims the benefit of U.S. Provisional Patent Application No. 61 / 329,078 filed on Apr. 28, 2010, the contents of all which are incorporated herein by reference.FIELD OF THE INVENTION[0002]This invention relates to compositions and methods for treating rheumatoid arthritis.BACKGROUND OF THE INVENTION[0003]This section provides background information which is not necessarily prior art and a general summary of the present disclosure which is not a comprehensive disclosure of its full scope or all of its features.[0004]CD24 is known as the heat-stable antigen. It is expressed as a glycosyl-phosphatidyl-inositol (GPI)-anchored molecule and has a wide distribution in different lineages. Because of the tendency of CD24 to be expressed on immature cells, it has also...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K14/435C07K19/00
CPCC07K14/70596C07K2319/30C07K14/47C07K19/00C07K14/435
Inventor ZHENG, XINCHENGWU, WEILIU, YANGZHENG, PAN
Owner ONCOIMMUNE INC
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