6898 results about "Antagonist" patented technology

Methods of treating cancer and infectious diseases utilizing a treatment regimen comprising administering a compound that reduces inhibitory signal transduction in T cells, in combination with a potentiating agent, such as cyclophosphamide, to produce potent T cell mediated responses, are described. Compositions comprising the PD-1 antagonists and potentiating agents useful in the methods of the invention are also disclosed.

Methods are provided for treating a subject for a condition caused by an abnormality in the subject's autonomic nervous system. In accordance with the subject methods, at least a portion of a subject's autonomic nervous system is pharmacologically modulated with at least one aldosterone antagonist in a manner that is effective to treat the subject for the condition. Also provided are systems and kits for use in practicing the subject methods.

Methods and compositions for treating an infection or disease that results from (1) failure to elicit rapid T cell mediated responses, (2) induction of T cell exhaustion, T cell anergy or both, or (3) failure to activate monocytes, macrophages, dendritic cells and / or other APCs, for example, as required to kill intracellular pathogens. The method and compositions solve the problem of undesired T cell inhibition by simultaneously inhibiting the PD-1 ligands, PD-L1 and PD-L2. The immune response can be modulated by providing antagonists which bind with different affinity, by varying the dosage of agent which is administered, by intermittent dosing over a regime, and combinations thereof, that provides for dissociation of agent from the molecule to which it is bound prior to being administered again. In some cases it may be particularly desirable to stimulate the immune system, then remove the stimulation.

Erythropoietin receptor agonist and antagonist antibodies and their use in enhancing erythropoiesis are disclosed.

The present invention discloses combined therapies for treating hematologic malignancies, including B cell lymphomas and leukemias or solid non-hematologic tumors, comprising administration of anti-cytokine antibodies or antagonists to inhibit the activity of cytokines which play a role in perpetuating the activation of B cells. The administration of such antibodies and antagonists, particularly anti-IL10 antibodies and antagonists, is particularly useful for avoiding or decreasing the resistance of hematologic malignant cells or solid tumor cells to chemotherapeutic agents and anti-CD20 or anti-CD22 antibodies. The invention also provides combination therapies for solid tumors having B cell involvement comprising the administration of an anti-cytokine antibody and a B cell depleting antibody such as RITUXAN(R).

A preventive or therapeutic agent for treating bowel disease, including Crohn's disease and ulcerative colitis, where the agent has as an active ingredient an antibody directed against IL-6 receptor which is an interleukin-6 antagonist.

A pharmaceutical dosage form that is safeguarded against abuse containing at least one active substance that is susceptible to abuse and at least two of the following constituents (a) through (d): (a) at least one substance that irritates the nasal and / or pharyngeal region; (b) at least one viscosity increasing agent that together with a required minimum quantity of an aqueous liquid forms a gel in an extract obtained from the dosage form, which gel can still be discerned after being introduced into an additional quantity of aqueous liquid; (c) at least one antagonist for the at least one active substance that is susceptible to abuse; and (d) at least one emetic.

The present invention relates to a novel Neutrokine-alpha, and a splice variant thereof designated Neutrokine-alphaSV, polynucleotides and polypeptides which are members of the TNF family. In particular, isolated nucleic acid molecules are provided encoding the human Neutrokine-alpha and / or Neutrokine-alphaSV polypeptides, including soluble forms of the extracellular domain. Neutrokine-alpha and / or Neutrokine-alphaSV polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of Neutrokine-alpha and / or Neutrokine-alphaSV activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.

The present invention relates to inhibitors of 11-β hydroxyl steroid dehydrogenase type 1, antagonists of the mineralocorticoid receptor (MR), and pharmaceutical compositions thereof. The compounds of the invention can be useful in the treatment of various diseases associated with expression or activity of 11-β hydroxyl steroid dehydrogenase type 1 and / or diseases associated with aldosterone excess.

Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to, and inhibit A class of Eph receptors, antagonize the effects of growth factors on the growth and survival of tumor cells, and which have minimal agonistic activity or are preferentially devoid of agonist activity. Said antibodies and fragments thereof may be used in the treatment of tumors that express elevated levels of A class of Eph receptors, such as breast cancer, colon cancer, lung cancer, ovarian carcinoma, synovial sarcoma and pancreatic cancer, and said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of A class of Eph receptors. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate are disclosed are all embodiments of the invention. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the A class of Eph receptors.

Topical compositions and methods for treating pain. The invention provides oil-in-water emulsions comprising an antidepressant; an NMDA-receptor antagonists; a lipophilic component; water; and a surfactant. The compositions induce a local-anesthetic effect when topically administered to intact skin thereby treating or preventing pain, for example, neuropathic pain.

The present invention relates to novel colon or colon cancer related polynucleotides and the polypeptides encoded by these polynucleotides herein collectively known as "colon or colon cancer antigens," and the use of such colon or colon cancer antigens for detecting disorders of the colon, particularly the presence of colon cancer and colon cancer metastases. More specifically, isolated colon or colon cancer associated nucleic acid molecules are provided encoding novel colon or colon cancer associated polypeptides. Novel colon or colon cancer polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human colon or colon cancer associated polynucleotides and / or polypeptides. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and / or prognosing disorders related to the colon, including colon cancer, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention further relates to methods and / or compositions for inhibiting the production and function of the polypeptides of the present invention.

The invention provides methods and compositions for modulating the HGF / c-met signaling pathway, in particular by regulating c-met dimerization and / or binding of ligand to c-met using a c-met antagonist that disrupts c-met multimerization.

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O)2—, —C(═O)—, —O—, —C(R6)(R7)—, —N(R5)— or —C(═N(R5))—; X is —O—, —N(R5)— or —C(R6)(R7)—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O)2—, —C(═O)— or —C(═NR5)—; U is a bond, —S(O)—, —S(O)2—, —C(O)—, —O—, —P(O)(OR15)—, —C(═NR5)—, —(C(R6)(R7))b— or —N(R5)—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, U is not —S(O)—, —S(O)2—, —O—, or —N(R5)—; provided that when X is —N(R5)— and W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

The present invention discloses combined therapies for treating hematologic malignancies, including B cell lymphomas and leukemias or solid non-hematologic tumors, comprising administration of anti-cytokine antibodies or antagonists to inhibit the activity of cytokines which play a role in perpetuating the activation of B cells. The administration of such antibodies and antagonists, particularly anti-IL10 antibodies and antagonists, is particularly useful for avoiding or decreasing the resistance of hematologic malignant cells or solid tumor cells to chemotherapeutic agents and anti-CD20 or anti-CD22 antibodies.The invention also provides combination therapies for solid tumors having B cell involvement comprising the administration of an anti-cytokine antibody and a B cell depleting antibody such as RITUXAN® (rituximab).

Compositions of a cyclooxygenase inhibitor and a calcium channel antagonist in a liquid carrier. The composition may be administered the the urinary tract during urological diagnostic, interventional, surgical and other medical procedures. One disclosed composition comprises ketoprofen and nifedipine in a liquid irrigation carrier, and includes a solubilizing agent, stabilizing agents and a buffering agent.

The present invention provides for compounds of formula (I)-(XIII), as well as pharmaceutically acceptable salts thereof, metabolites thereof, pro-drugs thereof, and pharmaceutical kits that include such compounds. The present invention also provides for the compounds of formula (I)-(XIII) for use in medical therapy or diagnosis. The present invention also provides for the use of the compounds of formula (I)-(XIII) in treating cancer in mammals (e.g., humans), as well inhibiting tumor cell growth in such mammals. The present invention also provides for methods of inhibiting FAS. The methods include contacting FAS with an effective amount of a compound of formula (I)-(XIII). The present invention also provides for methods of inhibiting the TE domain of the FAS. The methods include contacting the thioesterase TE domain of the FAS with an effective amount of a compound of formula (I)-(XIII). The present invention also provides for methods of treating cancer in mammals, as well as methods of inhibiting tumor cell growth in such mammals. The methods include administering a compound of formula (I)-(XIII) to a mammal in need of such treatment.

Topically applicable pharmaceutical / dermatological / cosmetic compositions well suited for the therapeutic treatment or care of sensitive human skin, hair, mucous membranes, nails and / or the scalp, in particular for reducing or avoiding the skin-irritant side effects of a variety of bioactive agents, for example the alpha -hydroxy acids, comprise a therapeutically / cosmetically effective amount of at least one calcitonin gene related peptide ("CGRP") antagonist, e.g., CGRP 8-37 or an anti-CGRP antibody.

The invention provides methods of screening for a compound for promoting wakefulness in a mammal. The method is practiced by providing a compound that is a PrRP receptor agonist and determining the ability of the compound to promote wakefulness. Also provided by the invention are methods of screening for a compound for promoting sleep in a mammal. The methods are practiced by providing a compound that is a PrRP receptor antagonist and determining the ability of the compound to promote sleep. In addition, the invention provides a method of promoting wakefulness in a mammal. The method is practiced by administering to a mammal an effective amount of a PrRP receptor agonist. The invention further provides a method of promoting sleep in a mammal. The method is practiced by administering to a mammal an effective amount of a PrRP receptor antagonist.

Peptide sequences capable of binding to insulin and / or insulin-like growth factor receptors with either agonist or antagonist activity and identified from various peptide libraries are disclosed. This invention also identifies at least two different binding sites, which are present on insulin and insulin-like growth factor receptors, and which selectively bind the peptides of this invention. As agonists, the peptides of this invention may be useful for development as therapeutics to supplement or replace endogenous peptide hormones. The antagonist peptides may also be developed as therapeutics.

A preventive and therapeutic agent for psoriasis comprising an interleukin-6 (IL-6) antagonist such as, for example, an antibody against IL-6 receptor.

Specific Cytokine Antagonists, including TNF antagonists and / or Interleukin-1 antagonists, are used as novel therapeutic agents for the treatment of hearing loss, including presbycusis and other forms of sensorineural hearing loss. The present invention provides a method for inhibiting the action of TNF and / or IL-1 antagonists for treating hearing loss in a human by administering a TNF antagonist and / or an IL-1 antagonist for reducing the inflammation affecting the auditory apparatus of said human, or for modulating the immune response affecting the auditory apparatus of said human, by administering a therapeutically effective dosage level to said human of a TNF antagonist and / or an IL-1 antagonist. Administration may be systemic, through the subcutaneous, intramuscular, oral, or intravenous routes; or by delivering an anatomically localized application in the region of the head. The TNF antagonist is selected from the group consisting of etanercept, infliximab, D2E7, CDP 571, or thalidomide; and the IL-1 antagonist is either IL-1 RA or IL-1R type II receptor. Antiviral agents may be added for treating certain patients.

A preventive or therapeutic agent for inflammatory bowel disease such as Crohn's disease and ulcerative colitis said agent comprising as an active ingredient an interleukin-6 (IL-6) antagonist such as an antibody directed against IL-6 receptor.

Methods and compositions for inhibiting interleukin-21 (IL-21) / IL-21 receptor (MU-1) activity using antagonists of IL-21 or IL-21 receptor (“IL-21R” or “MU-1”), are disclosed. IL-21 / IL-21R antagonists can be used to induce immune suppression in vivo, e.g., for treating, ameliorating or preventing autoimmune or inflammatory disorders, including, e.g., inflammatory bowel disease (IBD), rheumatoid arthritis (RA), transplant / graft rejection, psoriasis, asthma, fibrosis, and systemic lupus erythematosus (SLE).

A therapeutic agent for spinal cord injury, a modulator of differentiation of neural stem cells and an inhibitor of differentiation into glia cells comprising an interleukin-6 antagonist as an active ingredient.

Described herein are chimeric Newcastle disease viruses engineered to express an agonist of a co-stimulatory signal of an immune cell and compositions comprising such viruses. Also described herein are chimeric Newcastle disease viruses engineered to express an antagonist of an inhibitory signal of an immune cell and compositions comprising such viruses. The chimeric Newcastle disease viruses and compositions are useful in the treatment of cancer. In addition, described herein are methods for treating cancer comprising administering Newcastle disease viruses in combination with an agonist of a co-stimulatory signal of an immune and / or an antagonist of an inhibitory signal of an immune cell.

The invention pertains to murine TLR9 and related TLR9s which include murine-specific amino acids, as well as nucleic acids which encode those polypeptides. The present invention also includes fragments and biologically functional variants of the murine TLR9. The invention further relates to methods of using such murine and non-murine TLR9 nucleic acids and polypeptides, especially in methods for screening for agonists and antagonists of immunostimulatory CpG nucleic acids. Also included are murine TLR9 inhibitors which inhibit murine TLR9 activity by inhibiting the expression or function of murine TLR9. In a further aspect the present invention pertains to murine TLR7 and murine TLR8, as well as related TLR7 and TLR8 molecules which include murine-specific amino acids, as well as nucleic acids which encode those polypeptides. The present invention also includes fragments and biologically functional variants of the murine TLR7 and TLR8. Methods are included for screening for ligands of TLR7 and TLR8, as well as for inhibitors and agonists and antagonists of signaling mediated by TLR7 and TLR8.