Methods of treating antibody-mediated pathologies using agents which inhibit CD 21

An antibody-mediated technology, applied in the direction of antibodies, pharmaceutical formulations, chemical instruments and methods, etc., can solve the problems of limited research on the role of CD21

Inactive Publication Date: 2004-07-07
LA JOLLA PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0019] Although these studies investigated the involvement of the B cell activating receptors CD40 and CD152 in a mouse model of SLE, there is limited research on the role of CD21 in the ongoing immune response

Method used

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  • Methods of treating antibody-mediated pathologies using agents which inhibit CD 21
  • Methods of treating antibody-mediated pathologies using agents which inhibit CD 21
  • Methods of treating antibody-mediated pathologies using agents which inhibit CD 21

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0146] Example 1 Use of sCD21 to reduce the level of anti-dsDNA antibodies

[0147] C57 / B6 mice were sensitized with a model T cell-dependent antigen, which was coupled to (CA) at a ratio of 3.8 moles of oligonucleotide / mole of KLH 10 -(TG) 10 Composed of 20-mer double-stranded oligonucleotides on the keyhole: hemocyanin (KLH) (ON-KLH).

[0148] Mice were bled and subsequently administered intraperitoneally with 50 μg of alum-precipitated ON-KLH together with 2 × 10 9 A sacrificed Bordetella pertussis (B.Pertussis) organism was immunized. Fourteen days later, the mice were boosted with intraperitoneal administration of 10 μg ON-KLH. At the time of booster immunization, mice received 300 μg soluble CD21 (sCD21; Hebell et al. (1991) Science 254: 102) intravenously and 300 μg sCD21 intraperitoneally. Control mice received PBS. For the next 3 days, mice received 300 μg of sCD21 or PBS intravenously per day.

[0149] Mice were bled 7 days after the boost and IgG levels specif...

Embodiment 2

[0152] Example 2 Use of anti-CD21 antibody to reduce the level of anti-dsDNA antibody

[0153] BALB / c mice were sensitized with a model T cell-dependent antigen, which was coupled to (CA) at a ratio of 3.8 moles of oligonucleotide / mole of KLH 10 -(TG) 10 Composed of 20-mer double-stranded oligonucleotides on the keyhole: hemocyanin (KLH) (ON-KLH).

[0154] Table 2

[0155] The post / pre antibody level ratio decreased by 45% in the antibody treated group compared to the PBS treated group. Example 3A Use of anti-CD21 antibody to reduce the level of anti-dsDNA antibody in a spontaneous model of lupus

Embodiment 3A

[0155] The post / pre antibody level ratio decreased by 45% in the antibody treated group compared to the PBS treated group. Example 3A Use of anti-CD21 antibody to reduce the level of anti-dsDNA antibody in a spontaneous model of lupus

[0156] NZB / WF1(H-2 d / z ) mouse strains provide an autoimmune model to study the complex mechanisms that control the onset of autoimmunity in lupus. The animals were F1 cross progeny of NZB / B1NJ female and NZW / LacJ male mice, and they were obtained from Jackson Laboratories (Bar Harbor, Maine). The mice developed a chronic inflammatory disease of unknown origin that could be strongly influenced by genetic factors. Autoimmunity reflected by high levels of circulating anti-nuclear antibodies (including anti-double-stranded DNA antibodies); autoantibodies against RNA-protein complexes (such as RNP and Sm), ssDNA, histones, chromatin, erythrocytes, and cardiolipin; Immune complex formation and deposition in the kidney leading to proteinuria; and ...

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Abstract

The present invention provides methods of treating antibody-mediated pathologies, such as autoimmune diseases (eg, SLE, ITP, and thyroiditis), by ameliorating one or more symptoms of the antibody-mediated pathology using agents that inhibit CD21 / C3d interaction. The invention also provides methods for delaying the development of antibody-mediated lesions using agents that inhibit CD21 / C3d interaction.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 60 / 292,132 (filed May 17, 2001), which is hereby incorporated by reference in its entirety. technical field [0003] The present invention relates to the field of antibody-mediated pathologies such as autoimmune diseases. More specifically, the invention relates to methods of treating patients with antibody-mediated pathologies, such as autoimmune diseases, and methods of delaying the progression of antibody-mediated pathologies using agents that interfere with CD21 / C3d interaction. Background of the invention [0004] Antibody-mediated pathologies include a variety of conditions including autoimmune disease, xenograft rejection, allograft rejection, graft versus host disease, and immune responses to continuously administered therapeutic proteins. Antibody-mediated pathology is characterized by the overproduction of autoantibodies that lead to i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K39/395A61P5/16A61P37/02A61P37/06C07K14/725C07K16/28
CPCC07K16/2896A61K2039/505A61P37/00A61P37/02A61P37/06A61P5/16
Inventor M·D·林尼克M-A·坎贝尔
Owner LA JOLLA PHARMA
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