The present invention provides a polypeptides comprising a heavy chain domain 2 (HD2) from IgM or IgE and at least one pharmaceutically active moiety, complexes thereof and their use for therapy and prophylaxis.

The present invention provides a polypeptides comprising a heavy chain domain 2 (HD2) from IgM or IgE and at least one pharmaceutically active moiety, complexes thereof and their use for therapy and prophylaxis.

Aspects of the invention provide methods for harnessing the potential of proteins that occur naturally (e.g., in humans) and that have serious but finite toxicity. Aspects of the invention relate to a quantitative systems-biological and structural approach to design a class of chimeric proteins that avoid the toxicity of protein drugs while retaining their desired activities. In particular, chimeric proteins containing a variant form of a natural protein fused to a targeting moiety may be administered to a subject to target a signal (e.g., induction of apoptosis) to particular cells without having a generalized toxic effect in the subject.

Aspects of the invention provide methods for harnessing the potential of proteins that occur naturally (e.g., in humans) and that have serious but finite toxicity. Aspects of the invention relate to a quantitative systems-biological and structural approach to design a class of chimeric proteins that avoid the toxicity of protein drugs while retaining their desired activities. In particular, chimeric proteins containing a variant form of a natural protein fused to a targeting moiety may be administered to a subject to target a signal (e.g., induction of apoptosis) to particular cells without having a generalized toxic effect in the subject.

The present system and method are useful for the removal of immune inhibitors such as soluble TNF receptors from the body fluid of cancer patients. In some embodiments, soluble TNF-Receptors 1 and 2 are selectively removed from plasma at 80% or more efficiency. In some embodiments, the system includes an immobilized capture ligand of a single chain TNFα. The system and method are useful for the treatment of different cancer types, stages and severity.

The present system and method are useful for the removal of immune inhibitors such as soluble TNF receptors from the body fluid of cancer patients. In some embodiments, soluble TNF-Receptors 1 and 2 are selectively removed from plasma at 80% or more efficiency. In some embodiments, the system includes an immobilized capture ligand of a single chain TNFα. The system and method are useful for the treatment of different cancer types, stages and severity.

The present invention discloses a tumor necrosis factor-related apoptosis-inducing ligand variant, which is a fusion protein of a tumor necrosis factor-related apoptosis-inducing ligand and an F3 peptide. The F3 peptide is fused to the N-terminus or C-terminus of the tumor necrosis factor-related apoptosis-inducing ligand by a linker. The present invention also discloses a nucleotide sequence, as well as a recombinant vector and a recombinant bacterium comprising same, and also discloses a preparation method and use of the foregoing variant. The tumor necrosis factor-related apoptosis-inducing ligand variant is prepared by means of genetic engineering in the present invention, characterized in that its affinity for tumor cells, ability to induce apoptosis in tumor cells, tumor targeting property and in vivo anti-tumor effect are significantly better than those of the tumor necrosis factor-related apoptosis-inducing ligand. Accordingly, this variant displays good therapeutic effects on tumor treatment and has promising prospects in clinical application.

The present invention discloses a tumor necrosis factor-related apoptosis-inducing ligand variant, which is a fusion protein of a tumor necrosis factor-related apoptosis-inducing ligand and an F3 peptide. The F3 peptide is fused to the N-terminus or C-terminus of the tumor necrosis factor-related apoptosis-inducing ligand by a linker. The present invention also discloses a nucleotide sequence, as well as a recombinant vector and a recombinant bacterium comprising same, and also discloses a preparation method and use of the foregoing variant. The tumor necrosis factor-related apoptosis-inducing ligand variant is prepared by means of genetic engineering in the present invention, characterized in that its affinity for tumor cells, ability to induce apoptosis in tumor cells, tumor targeting property and in vivo anti-tumor effect are significantly better than those of the tumor necrosis factor-related apoptosis-inducing ligand. Accordingly, this variant displays good therapeutic effects on tumor treatment and has promising prospects in clinical application.

Herein is reported a method for the production of a polypeptide that is biologically active as n-mer comprising a nucleic acid encoding a fusion polypeptide according to the following formula (B.sub.n-CS.sub.o-I.sub.s-CS.sub.p-FC-CS.sub.q-I.sub.t-CS.sub.r-B.sub.m).sub.u, wherein B denotes a polypeptide that is biologically active as n-mer and forms non-defined aggregates/multimers upon expression in the absence of a fused Fc-region, FC denotes a heavy chain Fc-region polypeptide, CS denotes a cleavage site, and I denotes an intervening amino acid sequence, wherein FC does not substantially bind to an Fc-receptor, recovering the fusion polypeptide from the cell or the cultivation medium, optionally cleaving the fusion polypeptide with a protease, and thereby producing a polypeptide that is biologically active as n-mer and forms non-defined aggregates/multimers upon expression in the absence of a fused Fc-region.

Herein is reported a method for the production of a polypeptide that is biologically active as n-mer comprising a nucleic acid encoding a fusion polypeptide according to the following formula (B.sub.n-CS.sub.o-I.sub.s-CS.sub.p-FC-CS.sub.q-I.sub.t-CS.sub.r-B.sub.m).sub.u, wherein B denotes a polypeptide that is biologically active as n-mer and forms non-defined aggregates/multimers upon expression in the absence of a fused Fc-region, FC denotes a heavy chain Fc-region polypeptide, CS denotes a cleavage site, and I denotes an intervening amino acid sequence, wherein FC does not substantially bind to an Fc-receptor, recovering the fusion polypeptide from the cell or the cultivation medium, optionally cleaving the fusion polypeptide with a protease, and thereby producing a polypeptide that is biologically active as n-mer and forms non-defined aggregates/multimers upon expression in the absence of a fused Fc-region.