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Compositions and methods for treating clostridium difficile-associated diseases

A clostridium difficile and composition technology, applied in the field of antibodies or antigenic fragments thereof, isolated polypeptides, and vectors containing the nucleic acid molecule, can solve the increased morbidity and mortality of Clostridium difficile-related diseases, prolonged Hospitalization time, additional medical expenses, etc.

Inactive Publication Date: 2016-06-22
NAT INST OF HEALTH REPRESENTED BY THE SEC OF THE DEPT OF HEALTH & HUMAN SERVICES NAT INST OF HEALTH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Clostridium difficile-associated disease results in additional medical costs and prolonged hospital stays
Significantly increased morbidity and mortality from Clostridium difficile-associated disease due to altered virulence of the resulting strain

Method used

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  • Compositions and methods for treating clostridium difficile-associated diseases
  • Compositions and methods for treating clostridium difficile-associated diseases
  • Compositions and methods for treating clostridium difficile-associated diseases

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Embodiment Construction

[0039] The present invention relates to a novel polypeptide comprising the receptor binding domain (RBD) of Clostridium difficile (Cd) toxin A (tcdA). Unexpectedly, such polypeptides, especially when expressed in lipidated form, are highly immunogenic and capable of inducing immunity against Cd challenge in animal models.

[0040] Polypeptides comprising one or more CdtcdA functional domains, and nucleic acids encoding the polypeptides are described below.

[0041] An exemplary polypeptide comprises a C-terminal portion of tcdA that includes the receptor binding domain (RBD) of tcdA, ie, tcdA-RBD or RBD. Listed below are the nucleic acid sequence (SEQ ID NO: 1) encoding tcdA-RBD and the amino acid sequence (SEQ ID NO: 2) of tcdA-RBD. The putative receptor binding region within the RBD is shown in SEQ ID NO: 2 as underlined.

[0042] tcdA-RBD nucleic acid sequence (SEQ ID NO: 1)

[0043] TTTAATAGCGAGAATGAACTGGATCGTGATCATCTGGGCTTCAAAATCATCGATAATAAAACCTATTATTATGATGAAGATAGCAAAC...

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Abstract

The invention provides compositions and methods for treating clostridium difficile-associated diseases. Described herein are isolated polypeptides each containing one or more receptor-binding sites of toxin A (tcdA) of Clostridium difficile (Cd), nucleic acids encoding the polypeptides, and methods of using the polypeptides and nucleic acids.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 61 / 782,390, filed March 14, 2013, the entire contents of which are incorporated herein by reference. Background technique [0003] Clostridium difficile (Cd) is an emerging pathogen causing opportunistic infections in hospitals and is the main cause of human antibiotic-associated diseases such as pseudomembranous colitis and diarrhea. [0004] The main pathogenic effect of Clostridium difficile is through two large protein toxins, toxin A (tcdA) and toxin B (tcdB), which destroy intestinal epithelial cells. tcdA and tcdB, are large protein toxins (250 to 308 kDa) with multiple functional domains. Early in the pathogenic process, the receptor-binding domain (RBD) of Clostridium difficile (Cd) first binds carbohydrates located on the surface of colonic epithelial cells. tcdA and / or tcdB enter cells through receptor-mediated endocytosis and destroy ...

Claims

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Application Information

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IPC IPC(8): C07K14/33A61K39/08A61K39/39A61P31/04A61P37/04C07K19/00C12N15/31G01N33/569
CPCA61K39/08A61K39/39A61K2039/543A61K2039/55544A61K2039/55566A61P31/04A61P37/04C07K14/33C07K2319/40C12N2799/026G01N33/56911G01N2333/33
Inventor 庄再成黄瑞鑫冷治湘
Owner NAT INST OF HEALTH REPRESENTED BY THE SEC OF THE DEPT OF HEALTH & HUMAN SERVICES NAT INST OF HEALTH
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