59 results about "Clostridium difficile toxin A" patented technology

Antibodies that specifically bind to toxins of C. difficile, antigen binding portions thereof, and methods of making and using the antibodies and antigen binding portions thereof are provided herein.

The invention relates to monoclonal antibodies capable of recognizing and neutralizing epitopes from the ligand domain, the translocation domain or the catalytic domain of the enterotoxin (toxin A) and cytotoxin (toxin B) from Clostridium difficile, as well as their production and therapeutic and prophylactic applications to diseases caused by said toxins.

A composition for treating a subject is provided. The composition includes dimeric or polymeric secretory IgA therapeutic. Formulating agents are mixed with the dimeric or polymeric secretory IgA to yield a dosing form of a capsule, tablet, and a suppository. A process for manufacturing a medicament for the treatment of C. difficile associated disease in a human is also provided wherein dimeric or polymeric IgA is modified with secretory component to form a dimeric or polymeric secretory IgA therapeutic. The dimeric or polymeric secretory IgA therapeutic is then mixed with formulating agents to create a capsule, tablet, or suppository dosing form. The therapeutic is amenable to enrobement directly through microencapsulation or the dosing form is coated with an enteric coating. A method of C. difficile treatment with the therapeutic is also provided that is amenable to supplementation with concurrent or prior antibiotic administration.

Glycans are identified which have high affinity for C. difficile toxin A. They share one of two saccharide backbones and may have additional side chains. The backbones are galactose-β1-3 N-acetyl-D-glucosamine-β-1-3-galactose-β-1-4-N-acetyl-D-glucosamine and galactose-α-1-3-galactose-β-1-4-N-acetyl-D-glucosamine. The ligands may be used therapeutically, prophylactically, and diagnostically.

Antibodies that specifically bind to toxins of C. difficile, antigen binding portions thereof, and methods of making and using the antibodies and antigen binding portions thereof are provided herein.

The present invention relates to methods and compositions for reducing the risk and severity of C. difficile infection. It is based, at least in part, on the discovery that a restricted fraction of the gut microbiota, including the bacterium Clostridium scindens, contributes substantially to resistance against C. difficile infection. Without being bound by any particular theory, it is believed that this is achieved through the biosynthesis of secondary bile acids.

The invention belongs to the technical field of biomedicines and relates to a clostridium difficile exotoxin B amino-terminal gene sequence with optimized codon and a nucleic vaccine of the clostridium difficile exotoxin B. The gene sequence with optimized codon gives consideration to the preferences of the codon in the mammalian cell and the escherichia coli. The related vaccine of the clostridium difficile comprises the exotoxin B amino-terminal gene sequence with optimized codon and a eukaryotic expression vector pJW4303. The clostridium difficile exotoxin B amino-terminal gene sequence with optimized codon not only can be used for constructing the nucleic vaccine, effectively simulates the immune system of the host after immunizing the mammals so that the specific humoral immune response is generated and shows that the specific antibodies have good protective effects in the in vivo and in vitro models, but also is suitable for carrying out prokaryotic expression on the protein in the escherichia coli and lays the foundation for obtaining the protein in quantity.

The subject invention pertains to the use of certain bacterial strains, particularly butyrogenic bacteria, for preparing a composition to treat and / or prevent Clostridium difficile infection. In particular, the invention relates to the use of butyrate-producing anaerobic fermenters of gut commensals in pharmaceutical or food compositions.

Attenuated microorganisms expressing Clostridium difficile antigen(s), and methods of using the same for vaccination of patients are disclosed The invention provides an attenuated microorganism expressing an immunogenic portion of a C difficile Toxin A C-terminal repeat region and / or a C difficile Toxin B C-terminal repeat region The microorganism is an attenuated Salmonella comprising an integrated gene expression cassette that directs the expression of the immunogenic peptide from an in vivo inducible promoter.

The present invention relates to engineered Clostridium difficile type IV pilin (tfp) genes, type IV pilin proteins which can serve as a diagnostic marker for identification of patients infected with C. difficile, and vaccines comprising type IV pilin proteins, antigenic fragments and variants thereof for therapeutic interventions.

A composition and kit for detecting Clostridium difficile including a primer set for detecting a strain of Clostridium difficile, and a method of detecting Clostridium difficile by using the same.

Decoy nucleic acid sequences comprising a binding site for a target transcription factor, wherein the binding site is not operably linked to a gene, and wherein the transcription factor comprises a regulator of expression of a gene or genes in Clostridium difficile encoding one or more of: (i) a cellular growth factor; (ii) a cellular toxin; (iii) a cellular sporulation factor; (iv) a cellular stress response; and / or (v) a cellular essential gene are described. Uses of the decoys in antibacterial complexes for the treatment of bacterial infections are also described.

This present invention describes the derivation and selection of antibodies capable of neutralising the major exotoxins; TcdA and TcdB of Clostridium difficile. The invention also describes novel neutralisation and antigen binding properties of individual Mabs and mixtures thereof.

The invention discloses an LAMP detection method of clostridium difficile binary toxin and special primers and kit for the LAMP detection method. The LAMP detection method comprises the following steps: designing the primers according to specificity conserved genes cdtA and cdtB of clostridium difficile, performing LAMP amplification under the guide of the obtained primers by taking the genome DNA of a sample to be tested as a template, and further rapidly and quantitatively detecting whether the sample to be tested carries the clostridium difficile binary toxin according to the color change of reaction liquid or the turbidity change of the reaction liquid. By adopting the LAMP detection method, clostridium difficile cdtA or / and cdtB can be independently or simultaneously detected, rapid, convenient, synchronous, efficient, high-specificity and high-sensitivity detection under an isothermal condition can be achieved without complex instruments, a novel technical platform can be provided for clostridium difficile binary toxin detection and toxin classification, clinical diagnosis and treatment can be instructed, fulminant diffusion of clostridium difficile high-toxicity strains can be prevented, the method can be used for screening and detecting the clostridium difficile binary toxin in primary medical treatment and public health departments and disease prevention and control centers and has a wide market prospect and relatively great economic and social benefits.

There is provided inter alia a polypeptide comprising an immunoglobulin chain variable domain which binds to Clostridium difficile toxin A.

The present invention provides novel human-derived monoclonal antibodies specifically binding to toxins produced by Clostridium difficile (toxin A and toxin B), respectively, and having excellent neutralizing activity, and antigen-binding fragments thereof. The present invention also provides a pharmaceutical composition for the treatment of Clostridium difficile infection comprising any of the antibodies or antigen-binding fragments thereof.

It is described a Clostridium difficile (C-difficile) toxins A and / or B as a target for therapy, including passive immunotherapy, and particularly prevention of C-difficile intoxication in human or other animals. It is also described a polypeptide comprising a portion of C-difficile toxins A and / or B sequence being an epitope for anti-toxins A and / or B antibody. It disclosed a method for generating a neutralizing antibody directed against C-difficile toxins A and / or B. It is also provided a novel formulation that combines key toxins A and / or B epitope antibodies, located in three key domains of toxins A and / or B, for neutralisation of the toxins A and / or B, at any stage of toxins A and / or B intoxication related to C-difficile infection. The novel formulation of toxins A and / or B epitope antibodies are useful in immunotherapy, for 10 therapeutic and / or prophylactic mediation of C-difficile intoxication.

The application relates to Clostridium difficile cell surface polysaccharides, compositions comprising Clostridium difficile cell surface polysaccharides, and includes kits, methods and uses thereof.

A method is provided for the purification of Clostridium difficile Toxin A antigen comprising reacting impure Toxin A with immobilized mono-specific polyclonal antibodies. The polyclonal antibodies are coupled to a hydrazide group containing matrix such as hydrazide activated agarose gel. The immobilized antibody is specific for Toxin A and will greatly purify Toxin A from a Toxin A containing solution. Antibodies raised to Toxin A purified according to the method are of higher activity than antibodies produced from prior art purified Toxin A.

A composition of Lactobacillus fermentum GMNL-296 and a use of Lactobacillus fermentum GMNL-296 for producing a composition to improve the infection symptoms of Clostridium difficile are provided. The Lactobacillus fermentum GMNL-296 is to promote the expression of anti-inflammatory cytokine IL-10 and Treg cell related transcription factors, so that the infection symptoms of weight loss and intestinal abnormalities are improved.

In one aspect, the invention provides a DNA molecule. The DNA molecule includes a nucleotide sequence that encodes the receptor-binding domain of Clostridium difficile toxin A or toxin B in which at least about 10% of the in-frame codons for each amino acid residue has a higher percentage use in the human genome than the corresponding in-frame codons of C. difficile toxin A or toxin B having a known sequence. Methods for generating antibodies to Clostridium difficile toxin A or toxin B, methods for reducing the risk of a C. difficile infection, and methods for treating a C. difficile are also provided.

The invention discloses a live bacterial vaccine for controlling intestinal infection caused by positive clostridium difficile of clostridium difficile toxin A, wherein the vaccine contains thymidylate synthetase ThyA gene defective recombined lactic streptococci; and tests of the vaccine verify that the vaccine is safe and effective. The invention also discloses a preparation method of the live bacterial vaccine, and a use of the live bacterial vaccine in the preparation of medicines for controlling the intestinal infection caused by the positive clostridium difficile of the clostridium difficile toxin A.

Novel, antibody-based binding agents derived from human and camelid immunoglobulins are described. These binding agents recognize and bind with specificity to Clostridium difficile toxin A and / or toxin B and in some cases exhibit toxin neutralizing activity. These binding agents can be used to treat or prevent primary and recurrent CDI. The binding agents include camelid VHH peptide monomers, linked groups of VHH peptide monomers, VHH peptide monomers joined to antibody Fc domains, and VHH peptide monomers joined to IgG antibodies.

The present invention relates to a new bacteriocin, to microbial strains which can produce it and to uses of the bacteriocin and the strains. The bacteriocin is effective against Clostridium difficile and Listeria monocytogenes amongst other organisms.

The present invention relates to an antibody having specificity for an immunogenic determinant consisting of the pentasaccharide repeating unit of the Clostridium difficile glycopolymer PS-I: α-L-Rhap-(1→3)-β-D-Glcp-(1→4)-[α-L-Rhap-(1→3)]-α-D-Glcp-(1→2)-α-D-Glcp or a fragment thereof. Said antibody is able to prevent and treat diseases caused by C. difficile. The present invention further pertains to a method of treating or preventing a disease caused by the pathogen Clostridium difficile, which comprises administering to a subject said antibody or a vaccine composition comprising said antibody.

This invention relates to prophylactic and / or therapeutic application of microorganism species that are, for example, administered orally as delayed release formulation designed to release its microbial content to the distal small intestine and / or colon in high quantities and density, which is a “normalized” approach to repopulate the colonic flora as a method of prevention and / or treatment of, for example, Clostridium difficile colitis.

The invention belongs to the technical field of gene detection, and specifically relates to a fluorescent PCR detection method for clostridium difficile toxin genes, as well as a primer and a kit of the fluorescent PCR detection method. The primer has good corresponding specificity, proper length and efficiency in transcription, and can not form a secondary structure, the primer contains complementation of not more than four continuous four basic groups; the testing coincidence rate obtained by adopting the primer is 98.6%, and the detection sensitivity can achieve 100copies / mL. According to the detection method, clostridium difficile DNA in a specimen, such as an excrement specimen, can be easily and conveniently extracted, and the genes of clostridium difficile toxins A and B are detected; the specific amplification primer and a fluorescence probe are adopted, so that the detection sensitivity and the specificity are greatly improved, the defect of insufficient specificity existing in an antibody and a cultivation detection method is overcome, and the problem of misdetection is also solved.

Disclosed are methods and compositions for reducing toxicity associated with infection by Clostridium difficile by inhibiting Clostridium difficile toxin B (TcdB) and / or toxin A (TcdA). Such compounds include ebselen compounds, namely ebselen and its salts, ebselen functional analogues and ebselen structural analogues, as well as certain amide derivatives. This includes Formula I, e.g. 1-methyl-3-phenylpropylamine, Formula II, e.g., 2,2′-diselane-1,2-diylbis[N-(2,4-difluorophenyl)benzamide]; and Formula III, e.g. 2-(2-methoxy-5-methylphenyl)-1, 2-benzoselenazol-3-one. The present compositions may be comprised in a colon-retentive formulation that increases residence of and / or release of the compound in the area where the infection is active.