Abstract: Provided are pharmaceutical means and methods for the prevention, treatment or amelioration of indolent or aggressive B cell non-Hodgkin lymphoma (B NHL) and B cell leukemia comprising the administration of a bispecific single chain antibody construct to a subject in the need thereof and the use of said bispecific single chain antibody construct for the preparation of a pharmaceutical composition for the prevention, treatment or amelioration of indolent or aggressive B cell non-Hodgkin lymphoma (B NHL) and B cell leukemia, whereby said construct is to be administered for at least 1 week in specified daily doses. Moreover, the invention relates to kits comprising a bispecific single chain antibody construct to be used in accordance with this invention.

Abstract: The disclosure provides a method for assessing the risk of potential adverse effects for a human patient mediated by the administration of a CD19×CD3 bispecific antibody to said patient comprising determining the ratio of B cells to T cells of said patient. The disclosure also provides a method for administering a CD19×CD3 bispecific antibody to a human patient having a B:T cell ratio of about 1:5 or lower, comprising administering doses in a dosing regimen. This dosing regimen can be applied in methods for treating malignant CD19 positive lymphocytes or for ameliorating and/or preventing an adverse effect mediated by the administration of said bispecific antibody. The Also provided is a pharmaceutical package or kit comprising a first dose and a second dose and optionally a third dose of said antibody.

Abstract: Described herein is a bispecific molecule containing an Fc polypeptide chain and immunoglobulin variable regions. Also provided are pharmaceutical formulations comprising such molecules, nucleic acids encoding such molecules, host cells containing such nucleic acids, methods of making such molecules, and methods of using such molecules.

Abstract: The present invention provides a cytotoxically active CD3 specific binding construct comprising a first domain specifically binding to human CD3 and an Ig-derived second binding domain. Furthermore, a nucleic acid sequence encoding a CD3 specific binding construct of the invention is provided. Further aspects of the invention are vectors and host cells comprising said nucleic acid sequence, a process for the production of the construct of the invention and composition comprising said construct. The invention also provides the use of said constructs for the preparation of pharmaceutical compositions for the treatment of particular diseases, a method for the treatment of particular diseases and a kit comprising the binding construct of the invention.

Abstract: The present invention relates to a method for assessing (analyzing) the risk of potential adverse effects for a human patient mediated by the administration of a CD19×CD3 bispecific antibody to said patient comprising determining the ratio of B cells to T cells of said patient, wherein a ratio of about 1:5 or lower is indicative for a risk of potential adverse effects for said patient. Accordingly, the present invention relates a method (dosage regimen) for administering a CD19×CD3 bispecific antibody to a human patient having a B:T cell ratio of about 1:5 or lower, comprising (a) administering a first dose of said antibody for a first period of time; and consecutively (b) administering a second dose of said antibody for a second period of time, wherein said second dose exceeds said first dose. In some embodiments, a third dose of said antibody is administered for a third period of time.

Abstract: The present invention provides a pharmaceutical composition comprising a bispecific single chain antibody construct. Said bispecific single chain antibody construct is characterized to comprise or consist of at least two domains, whereby one of said at least two domains specifically binds to human EpCAM and comprises at least one CDR-H3 region comprising the amino acid sequence NXID antigen and a second domain binds to human CD3 antigen. The invention further provides a process for the production of the pharmaceutical composition of the invention, a method for the prevention, treatment or amelioration of a tumorous disease and the use of the disclosed bispecific single chain antibody construct and corresponding means in the prevention, treatment or amelioration of a tumorous disease.

Abstract: The present invention provides a method for the preparation of a human binding molecule, fragment or derivative thereof which specifically binds to the human CD3 complex. Furthermore, the invention provides a human binding molecules specifically binding to the human CD3 complex and means comprising said human binding molecules.

Abstract: The present invention provides a cytotoxically active CD3 specific binding construct comprising a first domain specifically binding to human CD3 and an Ig-derived second binding domain. Furthermore, a nucleic acid sequence encoding a CD3 specific binding construct of the invention is provided. Further aspects of the invention are vectors and host cells comprising said nucleic acid sequence, a process for the production of the construct of the invention and composition comprising said construct. The invention also provides the use of said constructs for the preparation of pharmaceutical compositions for the treatment of particular diseases, a method for the treatment of particular diseases and a kit comprising the binding construct of the invention.

Abstract: The present invention provides a cytotoxically active CD3 specific binding construct comprising a first domain specifically binding to human CD3 and an IG-derived second binding domain. Furthermore, a nucleic acid sequence encoding a CD3 specific binding construct is provided. Further aspects of the invention are vectors and host cells comprising the nucleic acid sequences, a process for the production of the construct and composition comprising the construct. The invention also provides the use of the constructs for the preparation of pharmaceutical compositions for the treatment of particular diseases, a method for the treatment of particular diseases and a kit comprising the binding construct of the invention.

Abstract: The present invention provides a pharmaceutical composition comprising a bispecific single chain antibody construct. Said bispecific single chain antibody construct is characterized to comprise or consist of at least two domains, whereby one of said at least two domains specifically binds to human EpCAM and comprises at least one CDR-H3 region comprising the amino acid sequence NXID antigen and a second domain binds to human CD3 antigen. The invention further provides a process for the production of the pharmaceutical composition of the invention, a method for the prevention, treatment or amelioration of a tumorous disease and the use of the disclosed bispecific single chain antibody construct and corresponding means in the prevention, treatment or amelioration of a tumorous disease.

Abstract: The invention relates to a humanized monoclonal antibody or fragment thereof which specifically binds to human interlukin-2 (IL2), whereby said humanized monoclonal antibody neutralizes the activity of human IL2 by binding to the human IL2 prior to, during, and/or subsequent to the binding of the human IL2 to the human IL2-receptor, and wherein the light chain variable region of the humanized monoclonal antibody comprises in its second framework region the contiguous amino acid sequence KAPKA at amino acid positions 42-46.

Abstract: The present invention relates to a pharmaceutical composition comprising a bispecific single chain antibody construct comprising binding domains specific for human CD3 and human CD19, wherein the corresponding variable heavy chain regions (VH) and the corresponding variable light chain regions (VL) regions are arranged, from N-terminus to C-terminus, in the order VH(CD19)-VL(CD19)-VH(CD3)-VL(CD3) or VH(CD3)-VL-(CD3)-VH(CD19)-VL (CD19). Processes for the production of the pharmaceutical compositions and medical/pharmaceutical uses for the specific bispecific single chain antibody molecules bearing specificities for the human CD3 antigen and the human CD19 antigen are also disclosed.

Abstract: The present invention provides a cytotoxically active CD3 specific binding construct comprising a first domain specifically binding to human CD3 and an Ig-derived second binding domain. Furthermore, a nucleic acid sequence encoding a CD3 specific binding construct of the invention is provided. Further aspects of the invention are vectors and host cells comprising said nucleic acid sequence, a process for the production of the construct of the invention and composition comprising said construct. The invention also provides the use of said constructs for the preparation of pharmacutical compositions for the treatment of particular diseases, a method for the treatment of particular diseases and a kit comprising the binding construct of the invention.

Abstract: The invention relates to a humanized monoclonal antibody or fragment thereof which specifically binds to human interleukin-2 (IL2), wherein said humanized monoclonal antibody neutralizes the activity of human IL2 by binding to said human IL2 prior to, during, and/or subsequent to the binding of said human IL2 to the human IL2-receptor, and wherein the light chain variable region of said humanized monoclonal antibody comprises in its second framework region the contiguous amino acid sequence KAPKA at amino acid positions 42-46.

Abstract: The present invention relates to a pharmaceutical composition comprising a bispecific single chain antibody construct, said bispecific single chain antibody construct comprising binding domains specific for human CD3 and human CD19, wherein the corresponding variable heavy chain regions (VH) and the corresponding variable light chain regions (VL) regions are arranged, from N-terminus to C-terminus, in the order, VH(CD19)-VL(CD19)-VH(CD3)-VL(CD3), VH(CD3)-VL-(CD3)-VH(CD19)-VL(CD19) or VH(CD3)-VL(CD3)-VL(CD19)-VH(CD19). Furthermore, processes for the production of said pharmaceutical compositions as well as medical/pharmaceutical uses for the specific bispecific single chain antibody molecules bearing specificities for the human CD3 antigen and the human CD19 antigen are disclosed.

Abstract: The present invention relates to a method of identifying a B cell carrying a surface immunoglobulin molecule having a binding site for an antigen of interest comprising contacting a sample putatively containing said B cell with the antigen of interest wherein said antigen is labeled with a first label and with a receptor specifically binding to said surface immunoglobulin molecule wherein said receptor is labeled with a second label and wherein said first label, when being brought into a spatial proximity of between 10 and 100 Angstrom with said second label emits a detectable signal upon activation of said second label by an external source and assessing the presence of said detectable signal, wherein said presence is, in turn, indicative of the B cell carrying a surface molecule having a binding site for the antigen of interest.

Abstract: The present invention relates to recombinant seven-trans-membrane receptor, whereby the amino terminus of said recombinant receptor is located on an extracellular side and the carboxy-terminus is located on an intracellular side of a membrane, comprising at least two detectable labels, whereby a first of said at least two detectable labels is or is located on the carboxy-terminus and whereby a second of said at least two labels is or is located on the first or third intracellular loop or whereby a first of said at least two labels is or is located on the third intracellular loop. Furthermore, nucleic acid molecules encoding said recombinant seven-transmembrane receptors are described as well as vector and host cells comprising the same. Furthermore, the present invention provides for identification and screening methods for molecules or compounds which are capable of modifying the biological end of pharmacological function of seven-transmembrane receptor proteins.

Abstract: The invention provides CD3 specific binding molecules and nucleic acid sequences encoding said CD3 specific binding molecules. Further aspects of the invention are vectors and host cells comprising said nucleic acid sequence, a process for the production of the construct of the invention and compositions comprising said construct. The invention also provides the use of said constructs for the preparation of pharmacutical compositions for the treatment of particular diseases, a method for the treatment of particular diseases and a kit comprising the binding construct of the invention.

Abstract: The present invention relates to a composition for the selective elimination of autoreactive B-cells comprising at least one (poly)peptide construct consisting of at least two domains wherein one of said domains comprises an autoreactive antigen or (a) fragments(s) thereof specifically recognized by the Ig receptors of said autoreactive B-cells and wherein one of said domains comprises an effector molecule capable of interacting with and/or of activating NK-cells, T-cells, macrophages, monocytes and/or granulocytes and/or capable of activating the complement system.

Abstract: The present invention relates to the use of a an inhibitor for the interferon &ggr; signaling pathway for the preparation of a pharmaceutical composition for the treatment or prevention of restenosis. Furthermore, the present invention provides for a method for the identification of an inhibitor of the IFN-&ggr; signaling pathway.