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Methods of use of soluble cd24 for treating systemic lupus erythematosus

A CD24, lupus technology, applied in chemical instruments and methods, pharmaceutical formulations, allergic diseases, etc., can solve problems such as unmet medical needs and slow development progress

Pending Publication Date: 2019-11-15
ONCOIMMUNE INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, compared with other autoimmune and allergic diseases, the development of drugs for the treatment of SLE is progressing slowly, and there is an urgent and unmet medical need to identify new therapeutic targets

Method used

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  • Methods of use of soluble cd24 for treating systemic lupus erythematosus
  • Methods of use of soluble cd24 for treating systemic lupus erythematosus
  • Methods of use of soluble cd24 for treating systemic lupus erythematosus

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0087] CD24 pharmacokinetics in mice

[0088] 1 mg CD24Fc (CD24Fc) was injected into naive C57BL / 6 mice and at different time points (5 minutes, 1 hour, 4 hours, 24 hours, 48 ​​hours, 7 days, 14 days and 21 days) Blood samples were collected from 3 mice per time point. Sera were diluted 1:100 and levels of CD24Fc were detected using a sandwich ELISA using purified anti-human CD24 (3.3 μg / ml) as capture antibody and peroxidase-conjugated goat anti-human IgG Fc (5 μg / ml) as a detection antibody. Such as image 3 shown in a. The decay curve of CD24Fc reveals the typical biphasic decay of the protein. The first biodistribution phase has a half-life of 12.4 hours. The second phase follows the model of first-order elimination from the central compartment. The half-life of the second phase was 9.54 days, which is similar to the half-life of antibodies in vivo. These data suggest that the fusion protein is very stable in the bloodstream. In another study in which the fusion pr...

example 2

[0090] CD24 for the treatment of RA

[0091] For decades, it has been postulated that rheumatoid arthritis (RA) is primarily a T cell-mediated autoimmune disease. Over the past two decades, there has been a renewed appreciation of the possible role of antibodies and B lymphocytes in the pathogenesis of RA. Thus, in addition to rheumatoid factor, many autoreactive antibodies have been found in RA patients, although it has not been definitively resolved in humans. However, several lines of evidence have demonstrated that antibodies specific to ubiquitous or tissue-specific antigens are sufficient to cause RA symptoms in mouse models. For example, antibodies from K / BxN TCR transgenic mice were found to be fully capable of transferring RA-like disease in new hosts. Likewise, a mixture of 4 anti-collagen antibodies is now widely used to induce RA in mice. This model is now called CAIA for collagen antibody-induced arthritis.

[0092] Genetic analysis of the CAIA model indicates...

example 3

[0107] Variant CD24 has improved activity over wild-type CD24

[0108] This example shows that the CD24 polypeptide (SEQ ID NO: 1) (CD24Fc) of human CD24 containing the polymorphic amino acid deleted at position 57 is more effective than the CD24 polypeptide (SEQ ID NO: 2) (CD24Fc) containing wild-type CD24. V Fc) is more effective for the treatment of RA.

[0109] method

[0110] Antibodies, fusion proteins and other materials

[0111]CD24Fc and CD24vFc are manufactured by OncoImmune, Inc.; Bovine Type II Collagen, Cat. No. 20022, Chondrex Inc., Redmond, WA; Mixture of 4 anti-collagen mAbs for BALB / c Cat. No. CIA-MAB-50 and for C57BL CIA-MAB-2C / 6 mouse, MD Bioproducts, St. Paul, MN; Chicken Type II Collagen, Cat. No. 20011, Chondrex Inc., Redmond, WA; Complete Freund's Adjuvant: Cat. No. 7008, Chondrex Inc., Redmond, WA, with heat-inactivated Mycobacterium tuberculosis H37 Ra (non-viable) at a concentration of 1 mg / ml; Complete Freund's Adjuvant: Cat. No. 7023, Chondrex In...

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Abstract

The present invention relates to the use of a CD24 protein for treating Systemic Lupus Erythematosus (Lupus, SLE).

Description

technical field [0001] The present invention relates to compositions and methods for the treatment of systemic lupus erythematosus (SLE) and related manifestations. Background technique [0002] Systemic lupus erythematosus (lupus, SLE) is the most common autoimmune disease and has a strong gender bias towards females. SLE is a chronic inflammatory connective tissue disease that can affect the joints and many organs, including the skin, heart, lungs, kidneys and nervous system. It is a complex disease with varying clinical manifestations; however, not everyone with systemic lupus erythematosus has all symptoms. Typically, lupus is characterized by periods of disease called flares, and healthy periods or remissions. It is difficult to estimate how many people have the disease because its symptoms vary widely and its onset is often unclear. While SLE usually first affects people between the ages of 15 and 45, it can also occur during childhood or later in life. Many more w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K39/00C07K14/705
CPCC07K14/70596A61K38/177A61P37/00A61P37/06C07K2319/30C07K2319/00C07K2319/91C07K16/2803A61K39/3955C07K14/4713C07K14/475C07K19/00A61K38/18
Inventor Y.刘P.郑M.德文波特
Owner ONCOIMMUNE INC