4658 results about "Tyrosine" patented technology

The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. “Protuberances” are constructed by replacing small amino acid side chains from the interface of the first polypeptide with larger side chains (e.g. tyrosine or tryptophan). Compensatory “cavities” of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.

The present invention relates to novel cytoplasmic tyrosine kinases isolated from megakaryocytes (megakaryocyte kinases or MKKs) which are involved in cellular signal transduction pathways and to the use of these novel proteins in the diagnosis and treatment of disease. The present invention further relates to specific megakaryocyte kinases, designated MKK1, MKK2 and MKK3, and their use as diagnostic and therapeutic agents.

Compounds of Formula I-a

and all pharmaceutically-acceptable forms thereof, are described herein.

The variables R₁, R₂, R₃, Z₁, Q, and A shown in Formula I-a are defined herein. Pharmaceutical compositions containing one or more compounds of Formula I-a, or a pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein. Methods of treating patients suffering from certain diseases responsive to inhibition of tyrosine kinase activity are also given. In certain embodiments the diseases are responsive to inhibition of Btk activity and/or B-cell proliferation. Such methods comprise administering to such patients an amount of a compound of Formula I-a effective to reduce signs or symptoms of the disease. These diseases include cancer, an autoimmune and/or inflammatory disease, or an acute inflammatory reaction. Thus methods of treatment include administering a sufficient amount of a compound or salt as provided herein to decrease the symptoms or slow the progression of these diseases. Other embodiments include methods of treating other animals, including livestock and domesticated companion animals, suffering from a disease responsive to inhibition of kinase activity. Methods of treatment include administering a compound of Formula I-a as a single active agent or administering a compound of Formula I-a in combination with one or more other therapeutic agent. A method for determining the presence of Btk in a sample, comprising contacting the sample with a compound or form thereof of Formula I-a under conditions that permit detection of Btk activity, detecting a level of Btk activity in the sample, and therefrom determining the presence or absence of Btk in the sample.

This invention relates to a method for prevention and treatment of aging, age-related disorders and/or age-related manifestations including atherosclerosis, peripheral vascular disease, coronary artery disease, osteoporosis, type 2 diabetes, dementia and some forms of arthritis and cancer in a subject comprising administering to said subject, separately, sequentially or simultaneously a therapeutically effective dosage of each component or combination of statins, bisphosphonates, cholesterol lowering agents or techniques, interleukin-6 inhibitor/antibody, interleukin-6 receptor inhibitor/antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor/antibody, tyrosine kinases inhibitors/antibodies, serine/threonine kinases inhibitors/antibodies, mitogen-activated protein (MAP) kinase inhibitors/antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors/antibodies, Nuclear factor κB (NF-κB) inhibitors/antibodies, IκB kinase (IKK) inhibitors/antibodies, activator protein-1 (AP-1) inhibitors/antibodies, STAT transcription factors inhibitors/antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof, administered separately, in sequence or simultaneously. Inhibition of the signal transduction pathway for Interleukin 6 mediated inflammation is key to the prevention and treatment of atherosclerosis, peripheral vascular disease, coronary artery disease, aging, age-related disorders and/or age-related manifestations including osteoporosis, type 2 diabetes, dementia and some forms of arthritis and tumors. Inhibition of Interleukin 6 mediated inflammation may be achieved indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion or by direct inhibition of the signal transduction pathway utilizing interleukin-6 inhibitor/antibody, interleukin-6 receptor inhibitor/antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor/antibody, tyrosine kinases inhibitors/antibodies, serine/threonine kinases inhibitors/antibodies, mitogen-activated protein (MAP) kinase inhibitors/antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors/antibodies, Nuclear factor κB (NF-κB) inhibitors/antibodies, IκB kinase (IKK) inhibitors/antibodies, activator protein-1 (AP-1) inhibitors/antibodies, STAT transcription factors inhibitors/antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof. Said method for prevention and treatment of said disorders is based on inhibition of Interleukin-6 inflammation through regulation of cholesterol metabolism, isoprenoid depletion and/or inhibition of the signal transduction pathway

Biodegradable polymer compositions that degrade in vivo into non-toxic residues are described. In part, the present invention is directed to such polymers containing phosphorus and desaminotyrosyl L-tyrosine linkages in the polymer backbone. Processes for preparing such polymers, compositions containing such polymers and biologically active substances, articles useful for implantation or injection into the body fabricated from the compositions, and methods for controllably releasing biologically active substances using the polymers, are also described.

A method for modifying silk polymer by coupling a chemical moiety to a tyrosine residue of a silk polymer is described herein for the purpose of altering the physical properties of the silk protein. Thus, silk proteins with desired physical properties can be produced by the methods described herein. These methods are particularly useful when the introduction of cells to a mammal is desired, since modifications to the silk protein affect the physical properties and thus the adhesion, metabolic activity and cell morphology of the desired cells. The silk protein can be modified to produce, or modify, a structure that provides an optimal environment for the desired cells.

Skin care compositions containing N-acyl amino acid, particularly N-acyl derivatives of Phenylalanine or Tyrosine, their isomers, or their salts; at least one other skin care active selected from sugar amines, vitamin B₃, retinoids, peptides, dialkanoyl hydroxyproline, hexamidine, salicylic acid, and phytosterol; and a dermatologically acceptable carrier for the N-acyl amino acid and the skin care active. The invention further relates to methods for regulating the condition of mammalian keratinous tissue wherein the methods each comprise the step of topically applying to the keratinous tissue of a mammal needing such treatment, a safe and effective amount of the skin care composition of the invention.

Biocompatible polyarylates of tyrosine-derived diphenol compounds and poly(alkylene oxide) dicarboxylic acids, articles formed therefrom and therapeutic uses are disclosed.

This invention relates to a method for prevention and treatment of Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, and age-related disorders including Osteoporosis, Arthritis, Type II Diabetes, Dementia and Alzheimer's disease in a subject comprising administering to said subject a therapeutically effective dosage of each component or combination of statins, bisphosphonates, cholesterol lowering agents or techniques, interleukin-6 inhibitor/antibody, interleukin-6 receptor inhibitor/antibody, gp130 protein inhibitor/antibody, tyrosine kinases inhibitors/antibodies, STAT transcription factors inhibitors/antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof, administered separately, in sequence or simultaneously. Inhibition of the signal transduction pathway for Interleukin 6 mediated inflammation is key to the prevention and treatment of atherosclerosis, peripheral vascular disease, coronary artery disease, aging and age-related disorders including osteoporosis, type 2 diabetes, dementia and some forms of arthritis and tumors. Inhibition of Interleukin 6 mediated inflammation may be achieved indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion or by direct inhibition of the signal transduction pathway including interleukin-6 inhibitor/antibody, interleukin-6 receptor inhibitor/antibody, gp130 protein inhibitor/antibody, tyrosine kinases inhibitors/antibodies, STAT transcription factors inhibitors/antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof. Said method for prevention and treatment of said disorders is based on inhibition of Interleukin-6 inflammation through regulation of cholesterol metabolism, isoprenoid depletion and inhibition of the signal transduction pathway.

The present invention relates to a method and transdermal pharmaceutical composition for preventing or reducing the likelihood of calcium deficiency or imbalances caused by calcium deficiency. The transdermal pharmaceutical composition includes a therapeutically effective amount of a pharmaceutically acceptable salt of calcium and a pharmaceutically acceptable carrier constituting a pluronic lecithin organogel. In addition to calcium, the transdermal pharmaceutical composition may also contain a therapeutically effective amount of: (1) a pharmaceutically acceptably salt of other minerals such as magnesium, zinc, selenium, manganese, or chromium; (2) a vitamin such as vitamin A, vitamin D, vitamin C, vitamin E or B-complex vitamins, choline, lecithin, inositol, PABA, biotin, or bioflavomoids; (3) a carotenoid such as lycopene or lutein; (4) a hormone such as dehydroepiandrosterone, progesterone, pregnenolone, or melatonin; (5) an amino acid such as arginine, glutamine, lysine, phenylalanine, tyrosine, GABA, tryptophan, carnitine, or acetyl-l-carnitine; (6) a fatty acid such as a fish oil or flax seed oil; (7) a vita-nutrient such as coenzyme Q10; (8) a cartilage building nutrient such as glucosamine, chondroitin, or MSM, (9) a herb such as ginkgo biloba, echinacea, 5-HTP, St. John's wort, or saw palmetto; or (9) any combination thereof. The transdermal pharmaceutical composition may be topically administered to a human to prevent or reduce the likelihood of calcium deficiency or imbalances caused by calcium deficiency such as hypertension, high cholesterol, colon and rectal cancer, osteomalacia, rickets, osteoporosis, cardiovascular disease, preeclampsia, tooth decay, and premenstrual syndrome.

The present invention relates to methods for the prevention and treatment of chronic inflammatory diseases, cancer, and involuntary weight loss. In the practice of the present invention patients are enterally administered HMB alone or alternatively in combination with eicosapentaenoic (20:5 ω-3), FOS, carnitine and mixtures thereof. HMB may be added to food products comprising a source of amino-nitrogen enriched with large neutral amino acids such as leucine, isoleucine, valine, tyrosine, threonine and phenylalanine and subtantially lacking in free amino acids.

A dietary supplement of mitochondrial nutrients is designed for relieving stress, preventing and improving stress-related disorders, such as chronic fatigue syndrome, diabetes, age-associated cognitive dysfunction and diseases (Parkinson's and Alzheimer's disease). The supplement composition has the following nutrients: B vitamins (cyanocobalamin 2-1,000 ug, thiamin 1-1,000 mg, niacin 15-2,000 mg, pyridoxine 1-1,000 mg, Pantothenate 5-150 mg, folic acid 400-40,000 ug), alpha-tocopherol 10-800 mg, ascorbic acid 50-10,000 mg, calcium 20-2,000 mg, vitamin A 200-10,000 ug, alpha-lipoic acid 100-1,000 mg, N-acetyl cysteine 100-3,000 mg, L-carnosine 100-9,000 mg, tyrosine 100-9,000 mg, vanillin 10-100 mg, phosphatidylserine 10-800 mg, resveratrol 10-50 mg, dehydroepiandrosterone 1-50 mg, and melatonin 0.1-3 mg, all of which have been individually used experimentally or clinically for relieving stress, preventing and treating age- and stress-related disorders and diseases but no combination of these compounds has been used. Many embodiments also contain at least one adjunct ingredient such as coenzyme Q 10-200 mg, acetyl-L-carnitine 100-2,000 mg, choline 50-1,000 mg, and creatine 100-2,000 mg.

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.

The present invention relates to development of efficacious intravitreal pharmaceutical compositions comprising a poorly water soluble agent with anti-angiogenic and/or anti vascular leakage properties in a therapeutically effective amount and a co-solvent in a suitable amount to treat or prevent diseases due to ocular neovascularization and enhanced vascular permeability. Other aspects of the invention details the development of efficacious compositions for the treatment of the said diseases via periocular, topical and oral administration.

A method to inhibit the growth of tumors in human patients, comprising treating the human patients with an effective amount of a combination of radiation and a non-radiolabeled protein receptor tyrosine kinase inhibitor, the overexpression of which can lead to tumorigenesis.

The invention discloses a preparation method of Roxadustat. The preparation steps are as follows: the Roxadustat is prepared from tyrosine through esterification, etherification, cyclization, dehydrogenation, oxidative rearrangement and acylation reaction. The preparation method has the advantages that the raw materials are easily obtained; the process is simple; and the preparation method is economic and environmental-friendly, and is suitable for industrialized production.

The invention relates to processes for preparing compounds having the formula,

• • and crystalline forms thereof, wherein Ar is aryl or heteroaryl, L is an optional alkylene linker, and R₂, R₃, R₄, and R₅, are as defined in the specification herein, which compounds are useful as kinase inhibitors, in particular, inhibitors of protein tyrosine kinase and p38 kinase.