650 results about "TOLLIP" patented technology

A 5-membered heteroaromatic ring compound represented by the formula [I]

wherein V is CH or N; W is S or O; R¹ and R² are each H etc.; X is —N(R⁴)—, —O—, —S—, —SO₂—N(R⁵)—, —CO—N(R⁷)— etc.; L is

wherein R²⁰, R²¹, R²² and R²⁵ are each H etc.; E is aryl or heteroaromatic ring group; R is —COOH etc.; B is aryl etc.; R³ is H etc.; Y is —C(R¹³)(R¹⁴)—N(R¹²)—C(R¹³)(R¹⁴)—O—, —N(R¹¹)—, —O— etc.; A is alkylene; and Z is aryl etc., a prodrug thereof and a pharmaceutically acceptable salt thereof. The compound [I] has a superior protein tyrosine phosphatase 1B inhibitory activity and is useful as a therapeutic agent for diabetes, diabetic complications, hyperlipidemia, obesity and the like.

Disclosed are synthetic nanocarrier compositions, and related methods, comprising therapeutic protein APC presentable antigens and immunosuppressants that provide tolerogenic immune responses specific to therapeutic proteins.

This invention relates to modified nucleic acid compositions encoding cell-penetrating polypeptides to provoke an innate immune response in a cell and methods of delivering protein-binding partners to target cells.

Protein complexes are provided comprising at least one interacting pair of proteins. The protein complexes are useful in screening assays for identifying compounds effective in modulating the protein complexes, and in treating and/or preventing diseases and disorders associated with the protein complexes and/or their constituent interacting members.

The present invention relates to an azole compound represented by the formula [I]

wherein W is S or O; R is —COOR⁷, —X¹-A¹-COOR⁷ (R⁷ is H, alkyl) or tetrazolyl; R¹, R², R³ and R⁴ are H and the like; A is —(CH₂)_m—X— (X is —N(R⁸)—, —C(R⁹)(R¹⁰)—, —CO— or —CO—N(R⁸)—); B is aryl or aromatic heterocyclic group; R⁵ is H and the like; R⁶ is —(Y)_s1-(A²)_s-Z (Y is —O—, —S(O)_t—, —N(R¹³)—, —N(R¹⁴)—CO—, —N(R¹⁴)—SO₂—, —SO₂—N(R¹⁴)— and the like, A² is alkylene, and Z is cycloalkyl, aryl, aromatic heterocyclic group, indanyl, piperazinyl, a prodrug thereof or a pharmaceutically acceptable salt thereof. The compound [I] of the present invention has a protein tyrosine phosphatase 1B inhibitory activity, and is useful as a therapeutic agent for diabetes, a therapeutic drug for diabetic complications or a therapeutic drug for hyperlipidemia.

This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel ecdysone receptor/invertebrate retinoid X receptor-based inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large-scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

The present invention relates to a method for predicting the risk of a subject developing a cardiovascular event comprising detecting at least one biomarker in (a sample of) the cardiovascular system from said subject, wherein said biomarker comprises at least one protein selected from the group consisting of Tumor Necrosis Factor Alpha Precursor; Lysosomal-associated Membrane Protein (1); Interleukin-5 Precursor; Interleukin-6 Precursor; C-C Motif Chemokine (2) Precursor; C-C Motif Chemokine (5) Precursor RANTES; Cathepsin L1 Precursor; Adenylate Kinase (1); Leukotriene B4 Receptor (1); Complement Factor D; Secreted Phosphoprotein (1); Small Inducible Cytokine A17 Precursor; C-X-C Motif Chemokine (10) Precursor; Tumor Necrosis Factor Ligand Superfamily Member (11)(RANKL); C-C Motif Chemokine (18) Precursor; 72 kDa Type IVCollagenase Precursor; Neutrophil Collagenase Precursor; fatty acid binding protein (4); calpain (2), (m/II) large subunit; Macrophage Migration Inhibitory Factor; Cathepsin S Precursor; Interleukin (13) Precursor; and soluble ICAM-1.

The use of a compound for the manufacture of a medicament for the prophylaxis or treatment of: A. a disease state or condition mediated by a kinase which is BCR-abl, VEGFR, PDGFR, EGFR, Flt3, JAK (e.g. JAK2 or JAK3), C-abl, PDK1, Chk (e.g. Cbk1 or Chk2), FGFR (e.g. FGFR3), Ret, Eph (e.g. EphB2 or EphB4), or Src (e.g. cSrc); or B. a cancer in which the cancer cells thereof contain a drug resistant kinase mutation which is: (a) a threonine gatekeeper mutation; or (b) a drug-resistant gatekeeper mutation; or (c) an imatinib resistant mutation; or (d) a nilotinib resistant mutation; or (e) a dasatinib resistant mutation; or (f) a T670I mutation in KIT; or (g) a T674I mutation in PDGFR; or (h) T790M mutation in EGFR; or (i) a T315I mutation in abl; or C. a cancer which expresses a mutated molecular target which is a mutated form of BCRabl, c-kit, PDGF, EGF receptor or ErbB2; or D. a disease mediated by a kinase containing a mutation in a region of the protein that binds to or interacts with other cancer agents but does not bind to or interact with the compounds of formula (I) or (I′), for example a mutated kinase selected from c-abl, c-kit, PDGFR including PDGFR-beta and PDGFR-alpha, and ErbB family members such as EGFR (ErbB1), HER2 (ErbB2), ErbB3, and ErbB4, members of the Ephrin receptor family including EphA1, EphA2, EphA3, EphA4, EphA5, EphA8, EphA10, EphB1, EphB2, EphB3, EphB5, EphB6, c-Src and kinases of the JAK family such as TYK2; wherein the compound is a compound of the formula (I or I′): or a salt, solvate, tautomer or N-oxide thereof wherein R^0′, R¹, R^1′, R^2′, R^3′, R^4′, A′, X′, E, A and M are as defined in the claims.

Methods of treating autoimmune disorders, coronary artery disease, allergy symptoms, allograft rejection sepsis/toxic shock are disclosed. Some methods comprise administering one or more regulatory compositions to activate the T suppressor cells by increasing the acetylation level and/or protein level of FOXP3 in combination with a T suppressor stimulus and/or an antigen. Some methods comprise administering one or more regulatory compositions to activate the T suppressor cells by increasing the acetylation level and/or protein level of FOXP3. Some methods comprise administering soluble GITR or antibodies that bind to GITR ligand. Methods of treating cancer, infectious diseases, and immune deficiency are also disclosed as are vaccination methods. The methods comprise administering one or more regulatory compositions to inactivate the T suppressor cells by reducing the acetylation level and/or protein level of FOXP3. Improved vaccines and vaccination methods are disclosed. Methods of identifying compounds that are useful to modulate acetylation level and/or protein level of FOXP3 and treat diseases are disclosed.

The present invention relates to isolated polypeptides comprising: (i) a protein transduction domain consisting of ZEBRA or a fragment thereof that retains the capacity of internalization, (ii) at least one CD4⁺ epitope; and (iii) at least one CD8⁺ epitope. It also relates to antigen presenting cells loaded with said polypeptides, and the use thereof in immunotherapy including prevention and/or treatment of cancers or infectious diseases.

The invention discloses a sensor preparation method based on an ECL-RET action between GO and GQDs and an application on kinas detection, and belongs to the field of electrochemiluminescence (ECL). The preparation method comprises the following steps: coating chitosan on the surface of an electrode, and orderly assembling graphene quantum dots and polypeptides onto the surface of the electrode through a covalent interaction. Under the actions of protein kinase and triphosadenine, the polypeptides carry out phosphorylation reactions, through the specific recognition action between an antibody and an antigen, oxidized graphene conjugated with a phosphorylated antibody is assembled to the phosphorylated serine sites of the polypeptide, thus the distance between the oxidized graphene and the graphene quantum dots is narrowed down, so that the electrochemiluminescence (ECL) of graphene quantum dots is quenched. The larger the concentration of protein kinase is, the more phsophorylated sites are generated on the polypeptide modified electrode surface, the more oxidized graphene is assembled on a sensing interface, the stronger the electrochemiluminescence quenching effect of graphene quantum dots will be, and thus the high sensitive detection on protein kinase is achieved.

The present invention provides an antihuman TNF-α antibody activity lowering inhibitor comprising a protein source(s) and/or carbohydrate source(s), in the treatment of inflammatory bowel syndrome with repeated administration of anti-TNF-α antibody; and a kit preparation wherein a freeze-dried antihuman TNF-α antibody and the activity lowering inhibitor in the above repeated administration of the anti-TNF-α antibody are separately contained in a plastic container so that they can communicate with each other. According to the present invention, in the drug therapy to the patients with inflammatory bowel syndrome, therapeutic agents which inhibit the inflammation for long periods without accompanying serious side effects can be provided.

This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel substitution mutant receptors and their use in a nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

The invention discloses a rudimental immune antibody which is used to detect organic phosphorus pesticide residue and its application, the character of the invention is using diethyl phosphonic acid acetic acid as hapten, produce artificial immunogen through coupling with bovine serum albumin(BSA), and produce several clone antibody through immune Zelanian giant blanc or produce mono clone antibody through chmice immune, cell amalgamation, filtration, clone planting and other steps, the several and single antibody can be used to indirect emulative ELISA, direct ELISA, or immune test paper to detect the rudimental phosphorus pesticide. The excellences of the invention including: the selected hapten has several organic phosphorus pesticides general structure, the structure reforming is not necessary, it can immune animal after coupling with protein, it can also be used to detect organic phosphorus pesticide in food and water source, this show the rapid and convenient of the immune detecting tehchnology.

The present invention provides for methods for immunizing actively against autologous carcinoembryonic antigen (CEA). The method encompasses that the immune system is engaged with variant CEA which is either administered as a protein vaccine, or is effected expressed by nucleic acid vaccination or live-viral vaccination. Preferred embodiments include immunization with variants that include at least one foreign T-helper epitope introduced in the CEA sequence. Also disclosed is variant proteins, DNA, vectors, and host cells useful for practising the method of the invention.

An integrative pathway modeling approach and ranking/evaluating algorithms based on disease-specific pathway models can predict drug efficacy for patients based on their gene expression profiles. A disease-specific pathway model is first constructed with proteins and drugs important to the disease by using computational connectivity maps (C-Maps). Through the pathway model-based ranking algorithm, ideal drugs or optimized drug combination can be discovered for a patient to modulate the gene expression profile of this patient close to those in healthy individuals at pathway-level.

Disclosed is a method of directing a cellular immune response against an HIV-infected cell in a mammal involving administering to the mammal an effective amount of therapeutic cells which express a membrane-bound, proteinaceous chimeric receptor comprising (a) an extracellular portion which includes a fragment of CD4 which is capable of specifically recognizing and binding the HIV-infected cell but which does not mediate HIV infection and (b) an intracellular portion which is capable of signalling the therapeutic cell to destroy the receptor-bound HIV-infected cell. Also disclosed are cells which express the chimeric receptors and DNA and vectors encoding the chimeric receptors.

Liver-directed gene transfer can induce immunological tolerance to a polypeptide associated with the expression of a therapeutic nucleic acid. Hepatic expression of a transgene induces tolerance to the expression product of the transgene, or to post-translational product related to transgene expression, thereby ameliorating or eliminating the immune responses associated with gene therapy and protein replacement, respectively, independent of the genetic background of the subject.

Methods and compositions are provided for diagnosing lung cancer in a mammalian subject by use of three or more selected genes, e.g., a gene expression profile, from the peripheral blood mononuclear cells (PBMC) of the subject which is characteristic of disease, a stage of the disease, or enables prognosis of recurrence of disease. The gene expression profile includes three or more genes of Table I, Table II, Table III, Table IV, Table V, Table VI or Table VII herein. Detection of changes in expression in the selected genes forming the gene expression profile from that of a reference gene expression profile are correlated with non-small cell lung cancer (NSCLC). One composition for use in such diagnosis includes three or more PCR primer-probe sets, wherein each primer-probe set amplifies a different polynucleotide sequence from the gene expression profile. Another composition for similar use contains a plurality of polynucleotides immobilized on a substrate, which probes hybridize to three or more gene expression products from genes in the gene expression profile. Still another composition involves detection of the protein expression products of genes from the gene expression profile.