151 results about "Chronic lymphocytic leukemia" patented technology

Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38⁺ cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and/or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein, such as multiple myeloma, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia, or the treatment of autoimmune and inflammatory diseases such as systemic lupus, rheumatoid arthritis, multiple sclerosis, erythematosus, and asthma. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38. 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. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

The miR15 and miR16 micro RNA genes are located at 13q14 within a 30 kb region of loss characteristic of cells from certain cancers, such as cells from chronic lymphocytic leukemia or prostate cancer. Chronic lymphocytic leukemia or prostate cancer can be diagnosed by detecting a reduction in miR15 or miR16 gene copy number, by determining miR15 or miR16 gene mutational status, or by detecting a reduction in the RNA transcribed from these genes. The miR15 or miR16 gene products can inhibit the neoplastic or tumorigenic growth of cancers such as chronic lymphocytic leukemia or prostate cancer cells when administered to subjects suffering from these diseases.

This invention is directed to methods and compositions for diagnosis, prognosis and for determining methods of treatment. The physiological status of cells present in a sample (e.g. clinical sample) can be used in diagnosis or prognosis of a condition (e.g. Chronic Lymphocytic Leukemia), in patient selection for therapy, to monitor treatment and to modify or optimize therapeutic regimens. The physiological status of a cell can be determined by comparing the intracellular status of one or more activation elements (e.g. the phosphorylation status of a signaling molecule) in a cell (e.g. a cancer cell) to that of another cell (e.g. a normal cell). The physiological status of a cell can be further classified by adding one or more modulators (e.g. an inhibitor or activator) to the cell in question. In some embodiments, the invention is directed to methods of determining a phenotypic profile of a population of cells.

The present invention provides diagnostic methods and kits for diagnosis of chronic lymphocytic leukemia (CLL) by determining expression levels of isoforms of cyclic nucleotide phosphodiesterases (PDEs) associated with CLL particularly, PDE7B and/or PDE3B, and a ratio of mRNA expression of PDE7B to PDE3B. The present invention provides that CLL lymphocytes uniformly expressed high levels of PDE7B and low levels of PDE3B relative to those of normal lymphocytes. A method of treatment and a pharmaceutical composition for CLL comprising one or more therapeutic agents capable of modulating expression or activity levels of isoforms of PDEs associated with CLL, and/or reversing the ratio of PDE7B/PDE3B mRNA expression levels are also provided.

CD20 is a transmembrane protein of the tetra-spanin family expressed on the surface of B-cells and has been found on B-cells from peripheral blood as well as lymphoid tissues. CD20 expression persists from the early pre-B cell stage until the plasma cell differentiation stage. Conversely, it is not found on hematopoietic stem cells, pro-B cells, differentiated plasma cells or non-lymphoid tissues. In addition to expression in normal B-cells, CD20 is expressed in B-cell derived malignancies such as non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). CD20 expressing cells are known to play a role in other diseases and disorders, including inflammation. The present invention includes anti-CD20 antibodies, forms and fragments, having superior physical and functional properties; immunoconjugates, compositions, diagnostic reagents, methods for inhibiting growth, therapeutic methods, improved antibodies and cell lines; and polynucleotides, vectors and genetic constructs encoding same.

The invention relates generally to compounds which are allosteric modulators (e.g., negative and positive allosteric modulators, allosteric agonists, and ago-allosteric modulators) of the G protein coupled receptor CXCR5. The CXCR5 receptor compounds are derived from the intracellular loops and domains of the CXCR5 receptor. The invention also relates to the use of these CXCR5 receptor compounds and pharmaceutical compositions comprising the CXCR5 receptor compounds in the treatment of diseases and conditions associated with CXCR5 receptor modulation such as autoimmune diseases including lupus, HIV and rheumatoid arthritis, Primary Sjogren's Syndrome, chronic lymphocytic leukemia, Burkitt Lymphoma, colon and breast cancer tumor metastasis, Multiple Sclerosis and compromised immune function.

The present invention provides novel methods and compositions for the diagnosis, prognosis and treatment of chronic lymphocytic leukemia (CLL). The invention also provides methods of identifying anti-CLL agents.

Certain cells, including types of cancer cells such as B-cell lymphomas, T cell lymphomas, Hodgkin's disease and myeloid leukemias, are capable of expressing Toll-like Receptor 9 (TLR9) or Toll-like Receptor 10 (TLR10) mRNA. Immunotargeting using TLR9 or TLR10 polypeptides, nucleic acids encoding for TLR9 or TLR10 polypeptides and anti-TLR9 or anti-TLR10 antibodies provides a method of killing or inhibiting that growth of cancer cells that express the TLR9 or TLR10 protein. Methods of immunotherapy and diagnosis of disorders associated with TLR9 or TLR10 protein-expressing cells, such as B-cell lymphoma, T cell lymphoma, acute myeloid leukemia, Hodgkin's disease, B cell leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia and myelodysplastic syndromes, are described.

This invention is directed to methods and compositions for diagnosis, prognosis and for determining methods of treatment. The physiological status of a cell present in a sample (e.g. clinical sample) can be used in diagnosis or prognosis of a condition (e.g. Chronic Lymphocytic Leukemia), in patient selection for therapy, to monitor treatment and to modify or optimize therapeutic regimens.

The present invention is directed to methods for establishing a composite marker profile for a sample derived from an individual suspected having a neoplastic condition. A composite marker profile of the invention allows for identification of prognostically and therapeutically relevant subgroups of neoplastic conditions and prediction of the clinical course of an individual. The methods of the invention provide tools useful in choosing a therapy for an individual afflicted with a neoplastic condition, including methods for assigning a risk group, methods of predicting an increased risk of relapse, methods of predicting an increased risk of developing secondary complications, methods of choosing a therapy for an individual, methods of determining the efficacy of a therapy in an individual, and methods of determining the prognosis for an individual. In particular, the method of the present invention discloses a method for establishing a composite marker profile that can serve as a prognostic indicator to predict whether the course of a neoplastic condition in a individual will be aggressive or indolent, thereby aiding the clinician in managing the patient and evaluating the modality of treatment to be used. In particular embodiments disclosed herein, the methods of the invention are directed to establishing a composite marker profile for a leukemia selected from the group consisting of Chronic Lymphocytic Leukemia (CLL), Acute Myelogenous Leukemia (AML), Chronic Myelogenous Leukemia (CML), and Acute Lymphocytic Leukemia (ALL).

The invention relates to a bendamustine hydrochloride freeze-dried powder injection and its preparing method. The prepared bendamustine hydrochloride freeze-dried powder injection is used for chronic lymphocytic leukemia (CLL) and in the treating process of rituximab/ MabThera or containing the same, or for inert B cell non hodgkin lymphoma (B-NHL) patients whose illness state still deteriorates during the treatment period in six months. The bendamustine hydrochloride freeze-dried powder injection contains bendamustine hydrochloride and uses the mixed solvent composed of the tertiary butanol and the injection water in the preparation process. The concentration of the bendamustine hydrochloride in the mixed solvents is 5-10 mg/ml. The volume ratio of the solvents is: 5-50% of tertiary butanol and the balance of injection water. The preparation process is that: measuring the tertiary butanol, adding injection water, mixing evenly, cooling to 2-15 DEG C, heat preserving, then adding the bendamustine hydrochloride, stirring to dissolve, filtering, filling, plugging, disking, freeze-drying, pressing the plug, out box, tying and packing.

Methods for treating patients having an early B cell derived acute lymphoblastic leukemia with rapamycin or a derivative thereof are provided. Also provided are methods for treating patients having an early B cell derived acute lymphoblastic leukemia with rapamycin or a derivative thereof in combination with an IL-7 inhibitor. Finally methods for preventing GVHD in ALL patients following a bone marrow transplant are disclosed.

The present invention is based on the seminal discovery that using next generation sequencing, PCR or the like, one of skill in the art can determine the prognosis for or predict responsiveness to a particular therapeutic regimen in a subject diagnosed with CLL.

The invention relates to a bendmustine hydrochloride compound and a method for preparing the same. The bendmustine hydrochloride compound prepared by the method can be used for treating chronic lymphocytic leukemia (CLL) and inertia B-cell non-Hodgkin's lymphoma (B-cell NHL). The bendmustine hydrochloride compound contains bendmustine hydrochloride and hydroxyproyl beta-cyclodextrin, wherein the mass ratio of bendmustine hydrochloride to hydroxyproyl beta-cyclodextrin is 1:1-20. During the preparation process, mixed solvent of tertiary butanol and water for injection can be used, wherein the concentration of bendmustine hydrochloride in the mixed solvent is 5-10mg/mL; the ratio in the solvent (100%) by volume is as follows: 5-50% of tertiary butanol and the balance of water. The preparation process comprises the following steps of: weighing the tertiary butanol, sequentially adding the solvent and the hydroxyproyl beta-cyclodextrin, dissolving, evenly mixing and cooling the mixture to 2-15 DEG C, maintaining the temperature, then adding the bendmustine hydrochloride, stirring until bendmustine hydrochloride dissolves, filtering, filling, stoppering, dishing-up, freeze-drying, corking, out-box, covering and packaging, and finally, the bendmustine hydrochloride compound is obtained.

The present invention relates to methods of treating cancers, e.g., leukemia. More specifically, the present invention relates to methods of treating acute and chronic leukemias including Acute Lymphocytic Leukemia (ALL), Acute Myeloid Leukemia (AML), Chronic Lymphocytic leukemia (CLL), Chronic myeloid leukemia (CML) and Hairy Cell Leukemia, by administration of pharmaceutical compositions comprising HDAC inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The oral formulations of the pharmaceutical compositions have favorable pharmacokinetic profiles such as high bioavailability and surprisingly give rise to high blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.

The invention relates to materials and methods for evaluating the prognosis of a patient presenting with chronic myelogenous leukaemia (CLL) and for CLL therapy.

In the present invention there is provided a pharmaceutical composition for oral administration which comprises bendamustine or a pharmaceutically acceptable, ester, salt or solvate thereof as an active ingredient, and a pharmaceutically acceptable excipient and which shows a dissolution of the bendamustine of at least 60% in 20 minutes, 70% in 40 minutes and 80% in 60 minutes, as measured with a paddle apparatus at 50 rpm according to the European Pharmacopoeia in 500 ml of a dissolution medium at a pH of 1.5, and wherein the pharmaceutically acceptable excipient is either a pharmaceutically acceptable non-ionic surfactant, selected from the group consisting of a polyethoxylated castor oil or derivative thereof and a block copolymer of ethylene oxide and propylene oxide or a pharmaceutically acceptable saccharide selected from the group consisting of one or more of a monosaccharide, a disaccharide, an oligosaccharide, a cyclic oligosaccharide, a polysaccharide and a saccharide alcohol, wherein the ratio by weight of the active ingredient to the saccharide excipient(s) is in the range of 1:1-5. The invention further relates to the above pharmaceutical composition for use for the oral treatment of a medical condition which is selected from chronic lymphocytic leukemia, acute lymphocytic leukaemia, chronic myelocytic leukaemia, acute myelocytic leukaemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, breast cancer, ovarian cancer, small cell lung cancer and non-small cell lung cancer. The invention moreover relates to the above pharmaceutical composition for the above use wherein the dosage regimen comprises at least the administration of a dose of 100 to 600 mg/m2/per person of bendamustine on day 1 and day 2, optionally a dose of 50 to 150 mg/m² i.v. or orally of a corticosteroid on days 1 to 5, and optionally a suitable dose of a further active agent selected from the group consisting of an antibody specific for CD20, an anthracyclin derivative, a vinca alkaloid or a platin derivative; and the repetition of said dosage regimen 4 to 15 times after intervals of two to four weeks.

The invention relates to the technical field of biological pharmacy and particularly discloses a bispecific antibody for CD20 and CD3. The bispecific antibody comprises univalent unit, a single-chainunit and a linker, wherein the univalent unit is a light chain-heavy chain pair with a specific binding capability for an antigen CD20 on the surface of a tumor cell; the single-chain unit can be usedfor specifically binding a CD3 antigen on the surface of an immune cell; the end N of a heavy chain and the end C of a light chain of the single-chain unit are connected by the linker to form a Fab-Fc form; the univalent unit is connected with the single-chain unit through a disulfide bond of a hinge region and a pestle mortar structure of a CH3 structural domain. According to the bispecific antibody, CD20 and CD3 can be specifically bound and the immune effector cell can be targeted to the tumor cell, so that the killing effect of the immune effector cell on the tumor cell is improved; the bispecific antibody can be used for treating CD20 antigen positive B-cell neoplasms, comprising non-Hodgkin lymphoma, chronic lymphocytic leukemia and the like, and has a broad application prospect inthe field of immunotherapy of tumors.

The present invention relates to methods of inducing and maintaining an immune response against a B-cell idiotype in a subject using an autologous anti-idiotypic vaccine. In one embodiment, the immune response is induced and maintained for treatment of a B-cell derived malignancy selected from among non-Hodgkin's lymphoma. Hodgkin's lymphoma, chronic lymphocytic leukemia, multiple myeloma, and mantle cell lymphoma.

The present invention provides a BTK inhibitor compound (having s structure represented by a formula (I)) and uses of the BTK inhibitor compound in medicines. According to the present invention, the compound and the pharmaceutical composition can be used for treatment of diffuse large B-cell lymphoma, follicular lymphoma or chronic lymphocytic leukemia. The formula (I) is defined in the specification.