30 results about "NOD2" patented technology

The present invention relates to intracellular signalling molecules, in particular the Nod2 protein and nucleic acids encoding the Nod2 protein. The present invention provides isolated nucleotide sequence encoding Nod2, isolated Nod2 peptides, antibodies that specifically bind Nod2, methods for the detection of Nod2, and methods for screening compounds for the ability to alter Nod2 associated signal transduction. The present invention also provides Nod2 variant alleles. The present invention further provides methods of identifying individuals at increased risk of developing Crohn's disease.

The present invention provides a method of diagnosing or predicting susceptibility to a clinical subtype of Crohn's disease characterized by fibrostenosing disease by determining the presence or absence in an individual of a fibrostenosis-predisposing allele linked to a NOD2 / CARD15 locus, where the presence of the fibrostenosis-predisposing allele is diagnostic of or predictive of susceptibility to the clinical subtype of Crohn's disease characterized by fibrostenosing disease. In a method of the invention, the clinical subtype of Crohn's disease can be, for example, characterized by fibrostenosing disease independent of small bowel involvement. The invention also provides a method of optimizing therapy in an individual by determining the presence or absence in the individual of a fibrostenosis-predisposing allele linked to a NOD2 / CARD15 locus, diagnosing individuals in which the fibrostenosis-predisposing allele is present as having a fibrostenosing subtype of Crohn's disease, and treating the individual having a fibrostenosing subtype of Crohn's disease based on the diagnosis.

The present invention provides a method of diagnosing or predicting susceptibility to a clinical subtype of Crohn's disease characterized by fibrostenosing disease by determining the presence or absence in an individual of a fibrostenosis-predisposing allele linked to a NOD2 / CARD15 locus, where the presence of the fibrostenosis-predisposing allele is diagnostic of or predictive of susceptibility to the clinical subtype of Crohn's disease characterized by fibrostenosing disease. In a method of the invention, the clinical subtype of Crohn's disease can be, for example, characterized by fibrostenosing disease independent of small bowel involvement. The invention also provides a method of optimizing therapy in an individual by determining the presence or absence in the individual of a fibrostenosis-predisposing allele linked to a NOD2 / CARD15 locus, diagnosing individuals in which the fibrostenosis-predisposing allele is present as having a fibrostenosing subtype of Crohn's disease, and treating the individual having a fibrostenosing subtype of Crohn's disease based on the diagnosis.

The present invention relates to the use of a TLR9 agonist and / or a TLR4 antagonist and / or a NOD2 agonist for treatment or prevention of disorders involving TLR4 activation, such as systemic sepsis and necrotizing enterocolitis.

This invention provides methods of diagnosis, predicting and diagnosing susceptibility to, predicting disease progression and treatment of inflammatory bowel disease (IBD), including Crohn's disease and / or subtypes of Crohn's disease (CD) and / or Ulcerative Colitis (UC). In one embodiment, a method of the invention is practiced by determining the presence or absence of the genetic variants NOD2, TLR8, TLR2, CARD8, CARD15 and / or JAK3 to diagnose, predict and diagnose susceptibility and predict disease progression in an individual. In another embodiment, a method of the invention is practiced by determining the presence or absence of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and / or pANCA in an individual. In another embodiment, the invention further associates the presence or absence of the risk variants with the expression of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and / or pANCA for the diagnosis, prediction of susceptibility, prediction of disease progression and / or treatment of IBD, including CD and / or UC.

The invention provides a method of diagnosing or predicting susceptibility to a clinical subtype of Crohn's disease in a subject having Crohn's disease by determining the presence or absence of IgA anti-I2 antibodies in the subject, where the presence of the IgA anti-I2 antibodies indicates that the subject has a clinical subtype of Crohn's disease. In one embodiment, a method of the invention is practiced by further determining the presence or absence in the subject of a NOD2 variant, anti-Saccharomyces cerevisiae antibodies (ASCA), IgA anti-OmpC antibodies, or perinuclear anti-neutrophil cytoplasmic antibodies (pANCA). The methods of the invention can be used to diagnose or predict susceptibility to a clinical subtype of Crohn's disease, for example, a fibrostenotic subtype, a subtype characterized by the need for small bowel surgery, or a subtype characterized by the absence of features of ulcerative colitis.

The present invention relates to a pharmaceutical composition for the prevention or treatment of immune disorders and inflammatory diseases, comprising stem cells that are generated by culturing stem cells expression Nucleotide-binding Oligomerization Domain protein 2 (NOD2) with a NOD2 agonist or a culture thereof. More particularly, the present invention relates to a method for suppressing immune responses or inflammatory responses of a subject, comprising the step of administering the pharmaceutical composition, the stem cells or culture thereof to the subject, a method for preparing an immunosuppressive drug or an anti-inflammatory drug using the stem cells or culture thereof, a method for preparing PGE2 or TGF-β1 comprising the step of culturing NOD2-expressing stem cells in culture medium with a NOD2 agonist, a graft comprising stem cells expressing NOD2 and the NOD2 agonist, a method for preparing the graft, a composite comprising stem cells expressing NOD2 and the NOD2 agonist, and a culture generated by culturing the NOD2-expressing stem cells with a NOD2 agonist.

The present invention relates to the use of a TLR9 agonist and / or a TLR4 antagonist and / or a NOD2 agonist for treatment or prevention of disorders involving TLR4 activation, such as systemic sepsis and necrotizing enterocolitis.

The present invention relates to the use of a TLR9 agonist and / or a TLR4 antagonist and / or a NOD2 agonist for treatment or prevention of disorders involving TLR4 activation, such as systemic sepsis and necrotizing enterocolitis.

The present invention relates to intracellular signaling molecules, in particular the Nod2 protein and nucleic acids encoding the Nod2 protein. The present invention provides methods of identifying modulators of Nod2 signaling. In particular, the present invention additionally provides methods of screening immune modulators such as adjuvants using Nod2. The present invention further provides methods of altering Nod2 signaling.

The present invention relates to intracellular signaling molecules, in particular the Nod2 protein and nucleic acids encoding the Nod2 protein. The present invention provides methods of identifying modulators of Nod2 signaling. In particular, the present invention additionally provides methods of screening immune modulators such as adjuvants using Nod2. The present invention further provides methods of altering Nod2 signaling.

Methods for screening compounds for treating sepsis are disclosed. The present methods and compositions are targeting NOD2 mediated signaling pathway and the agents identified by the present methods are qualified as drug candidates for clinical development. Further Methods and composition for treating sepsis are disclosed.

The present invention is a method for isolating bioactive molecules secreted by probiotic bacteria such as Lactobacillus rhamnosus, and methods for using such bioactive molecules to activate NOD2, decrease expression of inflammatory molecules, inhibit replication of human immunodeficiency virus (HIV), stimulate expression of Apolipoprotein A-IV, modulate diet-associated weight gain and prevent mucosal transmission of HIV.

This invention provides methods of diagnosis, predicting and diagnosing susceptibility to, predicting disease progression and treatment of inflammatory bowel disease (IBD), including Crohn's disease and / or subtypes of Crohn's disease (CD) and / or Ulcerative Colitis (UC). In one embodiment, a method of the invention is practiced by determining the presence or absence of the genetic variants NOD2, TLR8, TLR2, CARD8, CARD15 and / or JAK3 to diagnose, predict and diagnose susceptibility and predict disease progression in an individual. In another embodiment, a method of the invention is practiced by determining the presence or absence of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and / or pANCA in an individual. In another embodiment, the invention further associates the presence or absence of the risk variants with the expression of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and / or pANCA for the diagnosis, prediction of susceptibility, prediction of disease progression and / or treatment of IBD, including CD and / or UC.

A multi-protein pyocin-like structure derived from a bacteriophage or a bacteriocin that includes a chimeric tail fiber having a protein receptor binding domain capable of recognizing Lipid A. A multiprotein pyocin-like structure, derived from a bacteriophage or a bacteriocin that includes a chimeric tail fiber capable of recognizing and binding MurNac-L-Ala-D-Glu. A phage including a chimeric tail fiber that binds Lipid A. A plasmid encoding a chimeric ail fiber that binds MurNac-L-Ala-D-Glu. A plasmid encoding a chimeric tail fiber that binds Lipid A. A chimeric bacteriocin or bacteriophage derived tail fiber that includes the amino terminal of the human bactericidal / permeability-increasing protein (BPINTD)—A chimeric bacteriophage or bacteriocin derived tail fiber also includes a binding domain encoding the mammalian Nod2cτD—An antibacterial agent includes a bacteriocidal / permeability-increasing protein receptor domain that binds to Lipid A. An antibacterial agent also includes Nod2 carboxyl-terminus receptor domain that binds MurNac-L-Ala-D-Glu.

The present invention provides a method of diagnosing or predicting susceptibility to Crohn's disease in an individual by determining the presence or absence in the individual of a disease-predisposing haplotype containing a JW1 variant allele at the NOD2 / CARD15 locus, where the presence of the disease-predisposing haplotype is diagnostic of or predictive of susceptibility to Crohn's disease.

The present invention relates to a pharmaceutical composition for the prevention or treatment of immune disorders and inflammatory diseases, comprising stem cells that are generated by culturing stem cells expression Nucleotide-binding Oligomerization Domain protein 2 (NOD2) with a NOD2 agonist or a culture thereof. More particularly, the present invention relates to a method for suppressing immune responses or inflammatory responses of a subject, comprising the step of administering the pharmaceutical composition, the stem cells or culture thereof to the subject, a method for preparing an immunosuppressive drug or an anti-inflammatory drug using the stem cells or culture thereof, a method for preparing PGE2 or TGF-β1 comprising the step of culturing NOD2-expressing stem cells in culture medium with a NOD2 agonist, a graft comprising stem cells expressing NOD2 and the NOD2 agonist, a method for preparing the graft, a composite comprising stem cells expressing NOD2 and the NOD2 agonist, and a culture generated by culturing the NOD2-expressing stem cells with a NOD2 agonist.

This invention provides methods of diagnosis, predicting and diagnosing susceptibility to, predicting disease progression and treatment of inflammatory bowel disease (IBD), including Crohn's disease and / or subtypes of Crohn's disease (CD) and / or Ulcerative Colitis (UC). In one embodiment, a method of the invention is practiced by determining the presence or absence of the genetic variants NOD2, TLR8, TLR2, CARD8, CARD15 and / or JAK3 to diagnose, predict and diagnose susceptibility and predict disease progression in an individual. In another embodiment, a method of the invention is practiced by determining the presence or absence of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and / or pANCA in an individual. In another embodiment, the invention further associates the presence or absence of the risk variants with the expression of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and / or pANCA for the diagnosis, prediction of susceptibility, prediction of disease progression and / or treatment of IBD, including CD and / or UC.

The present invention relates to intracellular signalling molecules, in particular the Nod2 protein and nucleic acids encoding the Nod2 protein. The present invention provides isolated nucleotide sequence encoding Nod2, isolated Nod2 peptides, antibodies that specifically bind Nod2, methods for the detection of Nod2, and methods for screening compounds for the ability to alter Nod2 associated signal transduction.

The present disclosure provides a novel combination of a NOD2 agonist with an immunotherapeutic agent for the treatment of cancer. The disclosure also comprises methods of treatments wherein a pharmaceutical composition of NOD2 agonist is used in combination with an immunotherapeutic agent. A pharmaceutical composition comprises of NOD2 agonist and an immunotherapeutic agent comprising PD-1 axis antagonist or CTLA4 antagonist with a pharmaceutically acceptable diluent or carrier.

The invention provide methods for early detection of a reduced risk of developing cancer, which comprises detecting the absence of a series of genetic polymorphisms associated with a predisposition of developing cancer, including the polymorphisms of the genes BRCA1, BRCA2, CARD15 (NOD2), CHEK2, CDKN2A (P16), CYP1B1, FGFR2 (KGFR2), MAP3K1 (MEKK1), p53 (TP53), TNRC9, XPD (ERCC2) and the genetic marker Rs6983267, in a biological sample from the analyzed subject, wherein the absence of the genetic polymorphisms is indicative of significantly decreased risk of developing, at least, breast cancer.

The present invention relates to a pharmaceutical composition for the prevention or treatment of immune disorders and inflammatory diseases, comprising stem cells that are generated by culturing stem cells expressing Nucleotide-binding Oligomerization Domain protein 2 (NOD2) or a culture thereof. More particularly, the present invention relates to a method for suppressing immune responses or inflammatory responses of a subject, comprising the step of administering the pharmaceutical composition, the stem cells or culture thereof to the subject, a method for preparing an immunosuppressive drug or an anti-inflammatory drug using the stem cells or culture thereof, a graft comprising stem cells expressing NOD2, a method for preparing the graft, a composite comprising stem cells expressing NOD2, and a culture generated by culturing the NOD2-expressing stem cells.

Disclosed is a new treatment for reducing amyloid beta (Aβ), for treating Alzheimer's disease (AD), for improvement of cognitive disorder or learning and memory disorder associated with AD and for the treatment of multiple sclerosis. It was found that a NOD2 agonist could improve phagocytosis of Aβ across the blood brain barrier, to be scavenged by increased concentration of patrolling monocytes caused by the NOD2 agonist, removing Aβ from circulation, thereby preventing its eventual deposit. Also disclosed is a composition for such use.

The present invention provides N-acetyl-muramic acid (NAM) derivatives having Formula I, wherein Xa is selected from the group consisting of X1-X59, Ya is selected from the group consisting of H, monophosphate, uridine diphosphate and ethyl azide linker prepared from 2-azido-ethanol, and Za is selected from the group consisting of OH, an ethylene diamine coupled fluorophore, a peptide and a peptide with an ethylene diamine coupled fluorophore, wherein the peptide is selected from the group consisting of a monopeptide, a dipeptide, a tripeptide and a pentapeptide. Also provided are methods for synthesizing NAM derivatives and methods for modulating Nod2 in cells, modifying bacterial cell wall or modulating innate immune response by a subject to bacterial cells upon exposure to NAM derivatives.

Bronchial remodelling is a prominent feature of severe asthma and a potential therapeutic target. Some data indicate that Th17 cytokines in particular IL-22 may be involved in remodelling processes in vitro, and in skin remodelling in vivo. The aim of the inventors was to evaluate if Th17 cytokines are involved in bronchial remodelling in a severe model of allergic asthma, and if this was amplified by co-sensitization with NOD2 agonist, MDP, a ligand favouring Th17 polarization. Dog allergen challenge led to a predominant neutrophilic infiltration in Broncho-alveolar lavage (BAL), increased dog-specific IgE production, airways hyperresponsiveness, and increased Th17 cytokine production. Increased bronchial remodeling was observed in dog allergen challenged mice compared to control. IL-22 deficiency decreased airway hyperresponsiveness, bronchial mucus production as well as peribronchial collagen deposition, in the allergen-challenged group. Th17 cytokines in particular IL-22 participate in the bronchial remodeling in a chronic model of neutrophilic asthma, and may represent a therapeutic target in severe asthma.

The present invention provides N-acetyl-muramic acid (NAM) derivatives having Formula I, wherein Xa is selected from the group consisting of X1-X59, Ya is selected from the group consisting of H, monophosphate, uridine diphosphate and ethyl azide linker prepared from 2-azido-ethanol, and Za is selected from the group consisting of OH, an ethylene diamine coupled fluorophore, a peptide and a peptide with an ethylene diamine coupled fluorophore, wherein the peptide is selected from the group consisting of a monopeptide, a dipeptide, a tripeptide and a pentapeptide. Also provided are methods for synthesizing NAM derivatives and methods for modulating Nod2 in cells, modifying bacterial cell wall or modulating innate immune response by a subject to bacterial cells upon exposure to NAM derivatives.

This invention provides methods of diagnosis, predicting and diagnosing susceptibility to, predicting disease progression and treatment of inflammatory bowel disease (IBD), including Crohn's disease and / or subtypes of Crohn's disease (CD) and / or Ulcerative Colitis (UC). In one embodiment, a method of the invention is practiced by determining the presence or absence of the genetic variants NOD2, TLR8, TLR2, CARD8, CARD15 and / or JAK3 to diagnose, predict and diagnose susceptibility and predict disease progression in an individual. In another embodiment, a method of the invention is practiced by determining the presence or absence of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and / or pANCA in an individual. In another embodiment, the invention further associates the presence or absence of the risk variants with the expression of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and / or pANCA for the diagnosis, prediction of susceptibility, prediction of disease progression and / or treatment of IBD, including CD and / or UC.