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Methods of treating lupus using CD4 antibodies

An antibody and lupus technology, applied in the field of treating lupus with CD4 antibody, can solve dangerous and complicated problems

Inactive Publication Date: 2009-05-27
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, removing large amounts of blood during treatment is a dangerous and complicated process

Method used

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  • Methods of treating lupus using CD4 antibodies
  • Methods of treating lupus using CD4 antibodies
  • Methods of treating lupus using CD4 antibodies

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

Example 1: Treatment of lupus with non-depleting CD4 antibodies alone or in combination

[0230] A series of experiments are listed below to demonstrate that non-depleting CD4 antibodies are effective in preclinical models of SLE. The performance of the antibody is compared to exemplary standards of care and experimental treatments.

[0231] NZBxW F1 mice exhibit spontaneous lupus-like nephropathy, providing a useful preclinical efficacy model of SLE (see, e.g., Theofilopoulos (1992) "Murine models of systemic lupus erythematosus (murine models of systemic lupus erythematosus)", selected from Systemic Lupus Erythematosus (Systemic Lupus Erythematosus), Lahita (ed.) Churchill Livingstone, New York, 121-194). Figure 5 Schematic representation of disease progression with age in this model. Observed symptoms included the development of ds-DNA antibodies, proteinuria, renal histopathology, elevated blood urea nitrogen (BUN), and increased mortality. Arrows indicate the time point...

Embodiment 2

Example 2: Treatment of multiple sclerosis with non-depleting CD4 antibodies

[0254] Listed below is a series of experiments demonstrating the efficacy of non-depleting CD4 antibodies in preclinical models of MS. The performance of the antibodies is compared to exemplary standards of care and experimental treatments.

[0255] Experimental allergic encephalomyelitis (EAE) is an inflammatory disorder of the central nervous system (CNS) similar to MS; in both diseases, demyelination leads to impaired nerve conduction and paralysis. Relapsing and relapsing EAE induced by injection of proteolipid protein (PLP) peptides into SJL / J mice provides a useful preclinical efficacy model of MS (see, e.g., Miller and Karpus (1996) "Experimental Autoimmune Encephalomyelitis in the Mouse (Experimental Allergic Encephalomyelitis in Mice)" In Current Protocols in Immunology, Coligan et al (eds), John Wiley & Sons, and Sobel et al, (1990)" Acute experimental allergic encephalomyelitis in SJL / J ...

Embodiment 3

Example 3: The combination of CD4 antibody and MMF treats lupus

[0273] Listed below is a series of experiments demonstrating the efficacy of non-depleting CD4 antibodies alone or in combination with mycophenolate mofetil in preclinical models of SLE.

[0274] The NZB x W F1 mouse model of SLE is as described in Example 1. In this model, the preclinical efficacy of a non-depleting CD4 antibody (YTS177, described above) was compared with that of a nonbinding control antibody (described above), mycophenolate mofetil ( or MMF, current therapeutics) and the combination of CD4 antibody and MMF.

[0275] Treatment of NZB x NZW mice was started at 9 months of age. The mice were screened for proteinuria and randomly grouped according to their proteinuria scores. At the start of the experiment, each treatment group consisted of 15 mice, 73% of which showed proteinuria levels >300 mg / dl. (Note that this disease state is more severe than that at the start of treatment in the experim...

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Abstract

Methods of treating lupus, including systemic lupus erythematosus, cutaneous lupus erythmetosus, and lupus nephritis, are provided. The methods involve administration of a combination of a non-depleting CD4 antibody and another compound used clinically or experimentally to treat lupus. Methods of treating lupus nephritis by administration of a non-depleting CD4 antibody that results in an improvement in renal function and / or a reduction in proteinuria or active urinary sediment are also provided. Methods of treating multiple sclerosis by administration of a non-depleting CD4 antibody, optionally in combination with another compound used clinically or experimentally to treat MS, are described. Methods of treating transplant recipients and subjects with rheumatoid arthritis, asthma, psoriasis, Crohn's disease, ulcerative colitis, and Sjogren's syndrome are also provided.

Description

[0001] Cross References to Related Applications [0001] This application is a non-provisional utility patent application claiming priority to and benefit of an earlier provisional patent application: USSN 60 / 783535, filed March 16, 2006 by Bryan Irving, entitled "METHODS OF TREATING LUPUS USING CD4 ANTIBODIES" (Methods of Treating Lupus Using CD4 Antibodies), and USSN 60 / 873881, filed Dec. 7, 2006, by Bryan Irving, entitled "METHODS OF TREATING LUPUS USING CD4 ANTIBODIES" (Methods of Treating Lupus with CD4 Antibodies), out of For all purposes, each is incorporated by reference in its entirety. field of invention [0002] The present invention relates to methods of using non-depleting CD4 antibodies, alone or in combination with other compounds, to treat lupus and other autoimmune disorders in mammalian subjects. Background of the invention [0003] Autoimmune diseases, such as systemic lupus erythematosus (SLE), myasthenia gravis, multiple sclerosis, and idiopathic thromb...

Claims

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Application Information

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IPC IPC(8): A61K39/395C07K16/28
Inventor B·欧文
Owner GENENTECH INC
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