The present disclosure is directed to a method of treating neurological disorder comprising peripheral administration to a patient in need thereof a DN-TNF polypeptide that inhibits the activity of soluble TNF- but not transmembrane TNF-α.

The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases.

The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases.

The present invention provides a particle comprising a polypeptide and at least one antigen, and a composition comprising thereof.

The present invention provides a particle comprising a polypeptide and at least one antigen, and a composition comprising thereof.

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.

Herein is reported a method for producing an antibody-multimer-fusion polypeptide comprising (a) an antibody heavy chain and an antibody light chain, and (b) a first fusion polypeptide comprising in N- to C-terminal direction a first part of a non-antibody multimeric polypeptide, an antibody heavy chain CH1 domain or an antibody light chain constant domain, an antibody hinge region, an antibody heavy chain CH2 domain and an antibody heavy chain CH3 domain, and a second fusion polypeptide comprising in N- to C-terminal direction the second part of the non-antibody multimeric polypeptide and an antibody light chain constant domain if the first polypeptide comprises an antibody heavy chain CH1 domain or an antibody heavy chain CH1 domain if the first polypeptide comprises an antibody light chain constant domain, wherein (i) the antibody heavy chain of (a) and the first fusion polypeptide of (b), (ii) the antibody heavy chain of (a) and the antibody light chain of (a), and (iii) the first fusion polypeptide of (b) and the second fusion polypeptide of (b) are each independently of each other covalently linked to each other by at least one disulfide bond, characterized in that the antibody-multimer-fusion is expressed by a recombinant mammalian cell obtained by transfecting a mammalian cell with the expression cassettes for the antibody heavy chain, the antibody light chain, the first fusion polypeptide and the second fusion polypeptide at a stoichiometric ratio of 1:1:2:1.

Embodiments of the disclosure include methods and compositions for treatment or reduction in risk of coagulopathy of any kind, including associated with inflammation. In specific embodiments, the coagulopathy is associated with upregulated production of tissue factor in the individual. In specific embodiments, the coagulopathy is in an individual that has SARS-CoV-2 infection or is at risk for having SARS-CoV-2 infection. In specific embodiments, the methods and compositions include fibroblasts, and/or modified fibroblasts, and/or derivatives of fibroblasts, including those fibroblasts exposed to TNF-alpha or one or more other inflammatory agents before activation of the fibroblasts.

The present invention relates to a cytokine trimer domain in which a first monomer and a second monomer linked by linker (dimer) and a third monomer are coupled by a knob-into-hole and a novel type of fusion protein in which antibody and cytokine trimer domains are linked (receptor-antibody conjugated (cell) engager, RACE) prepared by replacing a constant region (Fc) of an antibody with the cytokine trimer domain, and RACE according to the present invention exhibits superior binding ability to the target receptor than the parent antibody as well as excellent simultaneous binding ability to the antigen and the target receptor, which can be usefully utilized as a bispecific pharmaceutical composition.