Abstract: The present invention relates to the use of an anti-EpCAM antibody for the manufacture of a medicament for the treatment of metastatic breast cancer. The present invention further relates to a method of treating metastatic breast cancer comprising administering said anti-EpCAM antibody.

Abstract: The present invention relates to a human monoclonal antibody or fragment thereof which specifically binds to and neutralizes primate GM-CSF.

Abstract: The present invention relates to antibodies. Specifically, the present invention relates to antibodies composed of novel combinations of inter-species antibody domains (“domain-grafted antibodies”). The present invention further relates to compositions comprising such domain-grafted antibodies, as well as methods for producing such domain-grafted antibodies. Finally, the present invention relates to methods of evaluating the in vivo biological effect of such domain-grafted antibodies as well as uses of such domain-grafted antibodies for cross-species evaluation of the in vivo activity antibodies intended for human therapy.

Abstract: Described are novel single-chain multifunctional polypeptides comprising at least two binding sites specific for the CD19 and CD3 antigen, respectively. Further provided are polypeptides, wherein the above-described polypeptide comprises at least one further domain, preferably of pre-determined function. Furthermore, polynucleotides encoding said polypeptides as well as to vectors comprising said polynucleotides and host cells transformed therewith and their use in the production of said polypeptides are described. In addition, compositions, preferably pharmaceutical and diagnostic compositions are provided comprising any of the afore-described polypeptides, polynucleotides or vectors. Described is also the use of the afore-mentioned polypeptides, polynucleotides and vectors for the preparation of pharmaceutical compositions for immunotherapy, preferably against B-cell malignancies such as non-Hodgkin lymphoma.

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 method of identifying binding site domains that retain the capacity of binding to an epitope when positioned C-terminal of at least one further domain in a recombinant bi- or multivalent polypeptide. The present invention further relates to a kit comprising components such as panels of recombinant vectors of bacterial libraries transfected with a panel of recombinant vectors which is useful in carrying out the method of the invention. Furthermore, binding site domains and fusion proteins obtainable by the method of the invention as well as antibody-like molecules comprising such domains and proteins are described. Furthermore, pharmaceutical and diagnostic compositions containing the above-described fusion proteins and polypeptides are provided.

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 a (poly)peptide construct consisting of at least two domains of at least two pluralities of domains wherein one of said domains or pluralities of domains comprises a de-immunized autoreactive antigen or (a) fragment(s) thereof specifically recognized by the Ig receptors of an autoreactive B-cells and wherein a/the further domain or plurality of domains comprises an effector molecule capable of interacting with and/or of activating NK-cells, T-cells, macrophages, monocytes and/or granulocytes. Preferably, said (poly)peptide construct consisting of at least two domains comprises a de-immunized autoreactive antigen or (a) fragment which is MOG or (a) fragment(s) thereof and a second domain comprising an effector molecule is an anti-CD3 receptor or an Fc-part of an immunoglobulin. The invention also relates to compositions comprising the compounds of the invention.

Abstract: The present invention discloses bispecific antibodies comprising two antibody variable domains on a single polypeptide chain, wherein a first portion of the bispecific antibody is capable of recruiting the activity of a human immune effector cell by specifically binding to an effector antigen on the human immune effector cell, the first portion consisting of one antibody variable domain, and a second portion of the bispecific antibody specifically binding to a target antigen other than the effector antigen, the target antigen on a target cell other than the human immune effector cell, the second portion comprising one antibody variable domain.

Abstract: The present invention relates to a method for the amplification of mRNA of a sample, comprising the steps of i.) generating cDNA from polyadenylated RNA employing at least one primer hybridizing to said polyadenylated RNA and comprising a 5? poly(C) or a 5? poly(G) flank; ii.)(aa) if present, removing non-hybridized, surplus primer(s) and/or surplus dNTPs; ii.)(ab) 3? tailing of said generated cDNA with a poly(G) tail when in step i.(a) primer(s) comprising a 5? poly(C) flank was employed or a poly(C) tail when in step i.(a) primer(s) comprising a 5? poly(G) flank was employed; or ii.)(b) 3? tailing of said generated cDNA with a poly(G) tail when in step i.(a) primer(s) comprising a 5? poly(C) flank was employed or a poly(C) tail when in step i.(a) primer(s) comprising a 5? poly(G) flank was employed using an RNA-ligase, irrespective of the presence or absence of surplus primer(s) and/or surplus dNTPs; and iii.

Abstract: The present invention provides an anti-human antibody or fragment thereof that is low or not immunogenic in humans. In particular, the antibodies or fragments are directed to human tumor antigens, preferably to the human tumor antigen 17-1A, also known as EpCAM, EGP or GA 733-2. Also provided are pharmaceutical compositions comprising the aforementioned antibodies or fragments thereto.

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: Described are novel single-chain multifunctional polypeptides comprising at least two binding sites specific for the CD19 and CD3 antigen, respectively. Further provided are polypeptides, wherein the above-described polypeptide comprises at least one further domain, preferably of pre-determined function. Furthermore, polynucleotides encoding said polypeptides as well as to vectors comprising said polynucleotides and host cells transformed therewith and their use in the production of said polypeptides are described, In addition, compositions, preferably pharmaceutical and diagnostic compositions are provided comprising any of the afore-described polypeptides, polynucleotides or vectors. Described is also the use of the afore-mentioned polypeptides, polynucleotides and vectors for the preparation of pharmaceutical compositions for immunotherapy, preferably against B-cell malignancies such as non-Hodgkin lymphoma.

Abstract: Disclosed is a method for the isolation and purification of polypeptides expressed in host cells by recombinant DNA techniques. A fused polypeptide is produced containing a desired polypeptide fused to additional amino acids. The additional amino acids define a leader sequence having properties exploitable in purification, a hinge region, and a cleavage site. The hinge region is cysteine-free and has a secondary structure which serves to expose the cleavage site to a selected endopeptidase. The method of the invention involves the production of a fused polypeptide which may be efficiently isolated by exploiting the properties of the leader sequence, and then efficiently cleaved at the cleavage site in an appropriate aqueous environment by virtue of the influence of the hinge on the cleavage agent/cleavage site reaction and other properties of the fused polypeptide.

Abstract: The present invention relates to a polypeptide construct comprising at least one CDR3 region, wherein at least one of said at least CDR3 regions comprises at least one substitution in the amino acid sequence YYDDHY (SEQ ID NO.1) and wherein said at least one substitution comprises: in the first position of SEQ ID NO.1 a substitution from Y to H; in the second position of SEQ ID NO. 1 a substitution from Y to S, from Y to N, from Y to F or from Y to H; in third position of SEQ ID NO. 1 a substitution from D to N or from D to E; in the forth position of SEQ ID NO. 1 a substitution from D to Q, from D to A, from D to V, from D to E or from D to G; in the fifth position of SEQ ID NO. 1 a substitution from H to Q, from H to P, from H to Y, from H to R or from H to N; or in the sixth position a substitution from Y to N.

Abstract: The invention is directed to chimeric polypeptides, e.g., bispecific antibodies, comprising a chemokine receptor binding domain and a T cell surface polypeptide or cell toxin binding domain, nucleic acids that encode them, and methods of making and using them. The chimeric polypeptides of the invention can include, be bound to, or attached to, a cell toxin. The invention is also directed to pharmaceutical compositions and methods for making and using them, including the treatment of immunological disorders, such as autoimmune diseases, and for the targeted elimination of cells, e.g., T lymphocytes and other cells latently infected with a primate immunodeficiency virus, such as a human immunodeficiency virus, e.g., HIV-1.

Abstract: The present invention relates to a novel method for the amplification of DNA, this method being particularly useful for the amplification of the DNA or the whole genome of a single cell, chromosomes or fragments thereof. Described is also the use of the method in DNA analysis for medical, forensic, diagnostic or scientific purposes, like comparative genomic hybridization (CGH)-, fluorescence in situ hybridization (FISH)-, polymerase chain reaction (PCR)-, single strand conformation polymorphism (SSCP)-, DNA sequence-, “loss of heterozygosity” (LOH)-, fingerprint- and/or restriction fragment length polymorphism (RFLP)-analysis.

Abstract: Described is a method for the production of an anti-human antigen receptor that is low or not immunogenic in humans comprising the steps of selecting a combination of functionally rearranged VH and VL immunoglobulin chains wherein at least said VH chain is derived from essentially unprimed mature human B-lymphocytes or from essentially anergic human B cells and said VL chain in derived from a naturally occurring human B cell repertoire, said chains being expressed from a recombinant vector and using an in vitro display system for binding to a human antigen.