113 results about "Anti cd20" patented technology

This invention describes methods of using anti-B cell antibodies, preferably anti-CD20 antibodies, and most preferably Rituximab, to treat B cell lymphomas of the brain, especially primary central nervous system lymphomas (PCNSLs), and to prevent meningeal relapse. The antibodies can be administered intrathecally alone, or in combination with other chemotherapeutics, such as methotrexate, or other anti-B cell antibodies to treat PCNSL in both immunocompromised and non-immunocompromised patients. These antibodies can also be used to diagnose patients with CNS lymphoma, especially in immunocompromised patients.

Methods for the treatment of lymphoma by administration of a B cell-specific antibody are described. The invention encompasses providing to a patient both unlabeled antibodies and antibodies labeled with a radioisotope. A principal advantage of the method is that tumor responses can be obtained in a radiometric dose range that does not require hematopoietic stem cell replacement as an adjunct therapy also described is a composition useful in the treatment of lymphoma.

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).

Disclosed herein are therapeutic treatment protocols designed for the treatment of B cell lymphoma. These protocols are based upon therapeutic strategies which include the use of administration of immunologically active mouse / human chimeric anti-CD20 antibodies, radiolabeled anti-CD20 antibodies, and cooperative strategies comprising the use of chimeric anti-CD20 antibodies and radiolabeled anti-CD20 antibodies.

Disclosed herein are therapeutic treatment protocols designed for the treatment of B cell lymphoma. These protocols are based upon therapeutic strategies which include the use of administration of immunologically active mouse / human chimeric anti-CD20 antibodies, radiolabeled anti-CD20 antibodies, and cooperative strategies comprising the use of chimeric anti-CD20 antibodies and radiolabeled anti-CD20 antibodies.

A combination antibody therapy for treating B cell malignancies using an immunoregulatory antibody, especially an anti-B7, anti-CD23, or anti-CD40L antibody and a B cell depleting antibody, especially anti-CD19, anti-CD20, anti-CD22 or anti-CD37 antibody is provided. Preferably, the combination therapy will comprise anti-B7 and anti-CD20 antibody administration.

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).

Disclosed herein are therapeutic treatment protocols designed for the treatment of B cell lymphoma. These protocols are based upon therapeutic strategies which include the use of administration of immunologically active mouse / human chimeric anti-CD20 antibodies, radiolabeled anti-CD20 antibodies, and cooperative strategies comprising the use of chimeric anti-CD20 antibodies and radiolabeled anti-CD20 antibodies.

The present invention provides humanized, chimeric and human anti-CD20 antibodies and CD 20 antibody fusion proteins that bind to a human B cell marker, referred to as CD20, which is useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies and autoimmune diseases, and methods of treatment and diagnosis.

The present invention provides methods for treating, reducing the severity, or inhibiting the growth of cancer (e.g., a B-cell cancer such as Hodgkin's lymphoma or acute lymphoblastic leukemia). The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to programmed death 1 (PD-1) receptor in combination with a therapeutically effective amount of a bispecific antibody that specifically binds to CD20 and CD3.

The present invention provides materials and methods for treatment of diseases involving aberrant B-cell activity, using a CD20-specific binding molecule, in particular, antibodies or antigen binding fragment thereof. The compositions disclosed herein is useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies and autoimmune diseases.

The present invention provides methods for treating, reducing the severity, or inhibiting the growth of acute lymphoblastic leukemia. The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of a bispecific antibody that specifically binds to CD20 and CD3.

A combination antibody therapy for treating B cell malignancies using an immunoregulatory antibody, especially an anti-B7, anti-CD23, or anti-CD40L antibody and a B cell depleting antibody, especially anti-CD19, anti-CD20, anti-CD22 or anti-CD37 antibody is provided. Preferably, the combination therapy will comprise anti-B7 and anti-CD20 antibody administration.

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.

A murine anti-CD20 monoclonal antibody having cell growth inhibitory activities is disclosed. Cell growth inhibitory activities include apoptosis against human CD20 antigen expressing cells in culture of the CD20 antigen expressing cells without effector cells. The anti-CD20 monoclonal antibody is incorporated into chimeric anti-CD20 monoclonal antibodies in which the amino acid sequences of the variable regions of the anti-CD20 monoclonal antibody and the amino acid sequences of the constant regions of human immunoglobulin are fused. Also a humanized anti-CD20 monoclonal antibody is described which includes all of the variable region CDRs of the H chain of the anti-CD20 monoclonal antibody and all of the variable region CDRs of the L chain of the anti-CD20 monoclonal antibody and an amino acid sequence of human immunoglobulin. A nucleotide sequence encoding the amino acid sequence of the chimeric or humanized anti-CD20 monoclonal antibody can be expressed in mammalian cells.

A combination antibody therapy for treating B cell malignancies using an immunoregulatory antibody, especially an anti-B7, anti-CD23, or anti-CD40L antibody and a B cell depleting antibody, especially anti-CD19, anti-CD20, anti-CD22 or anti-CD37 antibody is provided. Preferably, the combination therapy will comprise anti-B7 and anti-CD20 antibody administration.

Disclosed herein are methods of depleting peripheral blood B cells in a human host comprising administering to the host an immunologically active anti-CD20 antibody in an amount effective to deplete peripheral blood B cells in the host.

This invention concerns methods for the treatment of intermediate and high-grade non-Hodgkins lymphomas, comprising the administration of anti-CD20 monoclonal antibodies and fragments thereof. Particular embodiments include the administration of chimeric anti-CD20 antibody, either alone or in combination with radiolabeled antibodies or chemotherapy. The invention is particularly useful for lymphomas characterized by a high number of circulating B cells, possibly bone marrow involvement, bulky disease, or the involvement of extralymphatic organs or sites.

Glycan-optimized monoclonal antibodies that specifically bind CD20 antigen and which have improved effector function are provided. The anti-CD20 antibodies of the invention have a glycosylation pattern that results in an antibody composition having predominately the G0 glycoform, and thus comprise N-glycans that lack fucose (i.e., afucosylated) and galactose residues attached thereto. In some embodiments, these anti-CD20 antibodies comprise the light chain and heavy chain sequences of the rituximab anti-CD20 antibody, and thus represent afucosylated rituximab. Methods for producing these glycan-optimized anti-CD20 antibodies are also provided.

The present invention relates to the recombinant method used for the production of soluble form of an antibody that binds to CD20 for treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma (NHL). The treatment will comprise the use of immunologically active anti-CD20 antibodies; or radiolabeled anti-CD20 antibodies and or cooperative strategies where both labeled and non-labeled antibodies will be used for treatment of NHL. The procedure describes the de novo synthesis of the nucleic acid sequence encoding anti-CD20, transformation of the constructed nucleic acid sequences into competent bacteria and the sub-cloning of the same into mammalian expression vectors for expression of the desired protein. DNA constructs comprising the control elements associated with the gene of interest has been disclosed. The nucleic acid sequence of interest has been codon optimized to permit expression in the suitable mammalian host cells.

The invention provides therapeutic or diagnostic antibodies with modified N— or C-terminal sequences that are enriched with lysine or tyrosine residues. These lysine or tyfosine residues can be used to couple radioisotopes, cytotoxic agents, or detectable labels. The increased stoichiometric ratios of these agents in the antibody conjugates lead to improved therapeutic efficacy or enhanced detection sensitivity. Non-limiting examples of antibodies suitable for the present invention include anti-CD22, anti-ErbB2, anti-VEGF, anti-EGFR, anti-VEGFR, anti-Her-3, anti-Her-4, anti-CEA, anti-CTLA-4, anti-CD4, anti-CD3, anti-CD20, anti-TNF-a, anti-CD11a, anti-Lewis Y antigen, anti-TrailR, anti-IL2R, anti-CD30, anti-CD146, anti-CD147, anti-alpha V integrin beta, anti-CD19, anti-GD2, anti-3H11, anti-EBV, anti-HIV, anti-HBV, anti-HCV, and other disease-specific antibodies.

New combined therapeutic regimens for treatment of B-cell lymphomas are disclosed which comprise in particular administration of anti-CD20 antibodies to patients having low-, intermediate- or high-grade non-Hodgkins lymphomas.

The invention discloses an anti- CD20 tetravalent antibody and a preparation method as well as application thereof, in particular the invention disclsoes an anti- CD20 tetravalent antibody C2B8(ScFvHL)4-Fc and 2F2(ScFvHL)4-Fc, and the preparation method as well as the use thereof in the preparation of drugs for inhibiting B-cell lymphoma.

Methods for treating a human patient for an inflammatory or autoimmune disease that is associated with CD40-expressing cells are provided, where the human patient is heterozygous or homozygous for FcgammaRIIIa-158F (genotype V / F or F / F). Also provided are methods of inhibiting antibody production by B cells in a human patient who is heterozygous or homozygous for FcgammaRIIIa-158F (genotype V / F or F / F). The methods comprise administering to the human patient a therapeutically or prophylactically effective amount of an anti-CD40 antibody. Methods and kits for identifying a human patient with an inflammatory or autoimmune disease that is treatable with an anti-CD40 antibody and which is non-responsive or refractory to treatment with rituximab (Rituxan(R)), as well as methods and kits for selecting an antibody therapy for treatment of a human patient having an inflammatory or autoimmune disease that is non-responsive or refractory to treatment with rituximab (Rituxan(R)), are also provided. The methods of the present invention find use in treatment of inflammatory diseases and autoimmune diseases that are associated with CD40-expressing cells. These methods are particularly advantageous with respect to inflammatory diseases and autoimmune diseases that are associated with cells expressing both CD40 and CD20, as the methods enable the treatment of patients having an inflammatory or autoimmune disease that is non-responsive or refractory to therapy with other therapeutic agents such as anti-CD20 antibodies.