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DNA antibody constructs for use against pseudomonas aeruginosa

A monoclonal antibody and nucleotide sequence technology, applied in the direction of complete cells/viruses/DNA/RNA components, antibodies, DNA/RNA vaccination, etc., can solve the problem of high cost of antibody manufacturing and delivery, and must be reworked every week to every month Application and other issues

Pending Publication Date: 2019-07-30
THE TRUSTEES OF THE UNIV OF PENNSYLVANIA +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, purified antibodies are expensive to manufacture and deliver
Additionally, these antibody therapies must be readministered weekly to monthly – a challenging consideration in treating chronic conditions such as preventing or treating biofilm formation on medical implants

Method used

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  • DNA antibody constructs for use against pseudomonas aeruginosa
  • DNA antibody constructs for use against pseudomonas aeruginosa
  • DNA antibody constructs for use against pseudomonas aeruginosa

Examples

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Effect test

Embodiment 1

[0261] Example 1: Engineered bispecific DNA-encoded IgG antibody (DMAb) in a lethal pneumonia challenge model Pseudomonas aeruginosa

[0262] The studies presented here describe the development and in vivo production and activity analysis of synthetic DMAbs encoding the monospecific anti-PcrV IgG (DMAb-αPcrV) and the clinical candidate bispecific antibody ABC123 (DMAb-BiSPA). In vivo production of DMAbs allows rapid functional and protective titration of both constructs. These DMAbs could maintain similar potency to mAbs produced against biological processes and similarly prevent P. aeruginosa colonization of major organs.

[0263] In the current study, it was demonstrated that mAbs against Pseudomonas aeruginosa can be encoded in the synthetic DNA vector DMAb and produced in vivo by skeletal muscle. Anti-Pseudomonas DMAbs potently bind therapeutic targets and are protective in a mouse model of lethal pneumonia caused by invasive Pseudomonas aeruginosa strains. A...

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Abstract

Disclosed herein are mono and bispecific DNA antibodies (DMAbs) targeting Pseudomonas aeruginosa. Also disclosed herein is a method of generating a synthetic antibody in a subject by administering theDMAbs to the subject. The disclosure also provides a method of preventing and / or treating Pseudomonas aeruginosa infection in a subject using said composition and method of generation.

Description

[0001] Citations to related applications [0002] This application claims priority to US Provisional Application No. 62 / 332,363, filed May 5, 2016, which is hereby incorporated by reference in its entirety. technical field [0003] The present invention relates to a composition comprising recombinant nucleic acid sequences for in vivo production of one or more synthetic antibodies, including anti-PcrV and bispecific anti-PcrV anti-Psl antibodies and functional fragments thereof, and by administering the A method of preventing and / or treating a bacterial infection in a subject using the composition. Background technique [0004] Multidrug resistant (MDR) Pseudomonas spp. are among the most difficult pathogens to treat. Infection with Pseudomonas species is a major cause of acute pneumonia and chronic lung infection in individuals with cystic fibrosis, and is the most common source of infection in burns or other injuries that can lead to septic death. Pseudomonas species can...

Claims

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Application Information

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IPC IPC(8): A61K39/40C07K16/00C07K16/12
CPCA61K39/40C07K16/00C07K16/12C07K16/1214A61K2039/53A61K2039/505C07K2317/31A61P31/04A61K31/407C07K16/30C07K16/2803C12N15/625C12N2840/203C07K16/468
Inventor 大卫·韦纳阿米·帕特尔严健
Owner THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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