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Methods of treating RSV infections and related conditions

A technology of A4B4L1FR-S28R and A4B4-F52S, applied in chemical instruments and methods, antiviral agents, pharmaceutical formulations, etc., can solve problems such as impaired lung function

Inactive Publication Date: 2010-03-31
MEDIMMUNE LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, nearly 2.4 million U.S. adults have been shown to have impaired lung function, suggesting an underdiagnosis of COPD

Method used

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  • Methods of treating RSV infections and related conditions
  • Methods of treating RSV infections and related conditions
  • Methods of treating RSV infections and related conditions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0399] Example 1: MEDI-524 treatment modulates RSV-induced cytokine response

[0400] After infection, MEDI-524 was added to RSV-infected epithelial cells to observe whether the administration of antibodies can regulate the release of cytokines from RSV-infected cells. The test was conducted at two infection time points, one was 1 hour after infection and the other was 12 hours after infection.

[0401] 12 hours time point: Inoculate 2ml HEp-2 (9th passage) cells in 2-12 wells at a density of 5x10 5 Cells / well, culture for about 1 day to confluence. The confluent Hep-2 cells were infected with RSV A virus (WVB032302) MOI=1. After 12 hours of infection, control antibody MEDI-507 (20ug / ml) or MEDI-524 (52405G-0964) (20ug / ml) was added to the appropriate wells. Then at 37℃ / 5%CO 2 Incubate the cells for 6 and 24 hours. Centrifuge at 1500 rpm for 5 minutes at 6 or 24 hours to collect the supernatant and store it at -80°C until use.

[0402] 1 hour time point: Inoculate 2ml HEp-2P10 c...

Embodiment 2

[0404] Example 2: MEDI-524-mediated THP-1 activation

[0405] Experiments were performed to determine whether MEDI-524 treatment can modulate the chemokine response of activated THP-1 cells in response to RSV-infected cells.

[0406] Inoculate 2ml HEp-2 cells (passage 8) in 4-12 wells at a density of 5x10 5 Cells / well. Use IFN-γ (500U / ml final concentration, 15 μl for 15 ml) to activate the 14th generation (3x10 5 Cells / ml, 15ml) and the 27th passage (3.0x10 5 Cells / ml, 15ml) THP-1 cells for 48 hours.

[0407] After culturing for about 36 hours, use RSV A (8x10 6 pfu / ml) HEp-2 cells confluent in 12 wells were infected with MOI=1. After 12-15 hours, aspirate the infection medium and rinse once with FACS buffer (1xPBS containing 2% FBS). Dilute the control antibodies MEDI-507, MEDI-524 (52405G-0336, 10.2mg / ml) or MEDI-524Fab'2 (KS011107, 2.75mg / ml) with FACS buffer to a final concentration of 20ug / ml, and add them to each well . After incubating for 15 minutes at room temperature,...

Embodiment 3

[0410] Example 3: THP-1 phagocytosis mediated by MEDI-524

[0411] Experiments were performed to determine whether MEDI-524 treatment can mediate the phagocytosis of RSV-infected cells by monocytes.

[0412] Stain HEp-2 cells with lipophilic dyes: count the 5th generation HEp-2 cells at 1x10 6 Cells / ml are resuspended in HBSS in a 50ml conical tube. Next, add 2.5ul blue dye per ml of HBSS cell suspension ( DiD cell labeling solution, #V22887, Yingjie The cells were incubated at 37°C for 20 minutes, and the 50 ml conical tube was inverted 3 times every 5 minutes. The cells were washed 4 times with HBSS at 1700 rpm for 5 minutes. Resuspend the cells in complete medium and seed them in a 12-well plate with a seeding density of 5x10 5 Cells / well, seeding volume 2 ml (cells are confluent within 48 hours).

[0413] Activation of THP-1 cells: Use 500U / ml IFN-γ (12ul, for 12ml THP-1 cells) to activate the 19th generation of THP-1 cells (3x10 5 Cells / ml, 12ml), incubated at 37°C for 48 h...

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PUM

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Abstract

The present invention provides methods for managing, treating and / or ameliorating a respiratory syncytial virus (RSV) infection (e.g., acute RSV disease, or a RSV upper respiratory tract infection (URI) and / or lower respiratory tract infection (LRI)), and / or a symptom or a long-term respiratory condition relating thereto (e.g., asthma, wheezing, reactive airway disease (RAD), or chronic obstructive pulmonary disease (COPD)) in a subject, comprising administering to said human an effective amount of one or more antibodies that immunospecifically bind to one or more RSV antigens with a high affinity and / or high avidity and further comprise a modified IgG constant domain, or FcRn-binding fragment thereof, to not only decrease RSV infection, but also decrease the pro-inflammatory epithelial cell immune responses in order to mitigate the later development of asthma and / or wheezing and / or COPD in said patient.

Description

[0001] 1 Introduction [0002] The present invention relates to a composition comprising an antibody or a fragment thereof that immunologically specifically binds to RSV antigen, and a method for using the composition to treat or ameliorate symptoms and / or long-term consequences associated with respiratory syncytial virus (RSV) infection. Specifically, the present invention relates to a method for treating or ameliorating the symptoms and / or long-term consequences associated with RSV infection, the method comprising administering to a human subject an effective amount of one or more antibodies or fragments thereof that immunologically specifically bind to RSV antigens , So that the antibody or antibody fragment reaches a certain serum titer in the human subject. The present invention provides an Fc-modified antibody that binds to respiratory syncytial virus (RSV) antigen with high affinity and / or high affinity immunologically specifically. The present invention also provides a me...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/00A61K39/00A61K39/42
CPCA61K2039/545C07K2317/565C07K2317/77C07K2317/732C07K16/1027A61K2039/505C07K2317/72C07K2317/56A61P11/00A61P31/12A61P31/14A61P37/04
Inventor S·克里希南J·叙齐P·基纳G·洛松斯H·吴W·达拉夸B·里克特
Owner MEDIMMUNE LLC
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