Bimer or an oligomer of a dimer, trimer, quadromer or pentamer of recombinant fusion proteins

Abstract

The invention relates to oligomers of a dimer, trimer, quatromer or pentamer of recombinant fusion proteins. Said oligomers are characterized in that the recombinant fusion proteins have at least one component A and at least one component B, whereby component A contains a protein or a protein segment with a biological function, in particular with a ligand function for antibodies, for soluble or membranous signal molecules, for receptors or an antibody, or an antibody segment, and component B contains a protein or a protein segment which dimerizes or oligomerizes the dimer, trimer, quatromer or pentamer of the recombinant fusion protein, without the action of third-party molecules. The invention also relates to the use of dimers or oligomers of this type for producing a medicament, to the fusion proteins which cluster in dimers or oligomers and to their DNA sequence and expression vectors or host cells comprising this DNA sequence.

1 . A bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins characterized by the recombinant fusion proteins having at least one component A and at least one component B, wherein component A comprises a protein or a protein segment with biological function, in particular with ligand function for antibodies, for soluble or membrane-bound signal molecules or for receptors or an antibody or segment of an antibody and component B comprises a protein or a protein segment selected from the group consisting of the family of C1q proteins and the collectins, which bimerizes or oligomerizes the dimer, trimer, quadromer or pentamer of the recombinant fusion protein without the effect of third molecules. 
     
     
         2 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 1  characterized by the component A of the recombinant fusion proteins in the dimer, trimer, quadromer or pentamer being identical or different. 
     
     
         3 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 1  characterized by the component A of the recombinant fusion proteins being a peptide hormone, a growth factor, a cytokine, an interleukin, a segment thereof or a functional derivative of the above-mentioned sequences. 
     
     
         4 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 1  characterized by the component A of the recombinant fusion proteins being a cytokine from the family of TNF cytokines, a segment of such a TNF cytokine or a functional derivative of the above-mentioned sequences. 
     
     
         5 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 4  characterized by the component A of the recombinant fusion proteins being a TNF cytokine or a segment of a TNF cytokine selected from the group consisting of CD40L, FasL, TRAIL, TNF-a, CD30L, OX40L, RANKL, TWEAK, Lta, Ltab2, LIGHT, CD27L, 41-BB, 
       GITRL, APRIL, EDA, VEGI and BAFF, or a functional derivative of the above-mentioned sequences. 
     
     
         6 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 1  characterized by the component A of the recombinant fusion proteins being an antigen or a segment of an antigen of viral, bacterial or protozoological pathogens. 
     
     
         7 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 6  characterized by the component A of the recombinant fusion proteins being a surface antigen or a segment of a surface antigen of a viral, bacterial or protozoological pathogen. 
     
     
         8 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 1  characterized by the component A of the recombinant fusion proteins being an amino acid sequence coupled to a receptor agonist or to a receptor antagonist. 
     
     
         9 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 1  characterized by the component B of the recombinant fusion proteins containing a multimerizing and oligomerizing segment or a functional derivative of such a segment of a protein, selected from the group consisting of C1q, MBP, SP-A, SP-D, BC, CL43 and ACRP30, or containing the collagen domain of the EDA protein or a functional derivative thereof. 
     
     
         10 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 9  characterized by the component B containing an amino acid sequence, as shown in  FIG. 6A  for the sequence of amino acids 18 to 111 of mACRP30 or a functional derivative thereof, or containing an amino acid sequence, as shown in  FIG. 6B  for the sequence of amino acids 18 to 108 of hACRP30 or a functional derivative thereof, whereby  FIGS. 6A and 6B , respectively is part of the claim. 
     
     
         11 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 1  characterized by the component B containing a sequence of 8 to 20 amino acids which bimerizes or oligomerizes dimers or multimers of recombinant fusion proteins. 
     
     
         12 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 11  characterized by the component B forming one or more disulfide bridges. 
     
     
         13 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 12  characterized by the component B containing the amino acid sequence LEGSTSNGRQCAGIRL or a functional derivative of this sequence. 
     
     
         14 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 11  characterized by the component B containing the sequence LEGSTSNGRQSAGIRL or a functional derivative of this sequence. 
     
     
         15 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 1  characterized by the multimerized and oligomerized fusion proteins having antigenic segments for detecting and crosslinking by antibodies. 
     
     
         16 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 1  characterized by the recombinant fusion proteins having a linker sequence between component A and component B. 
     
     
         17 . The bimer or oligomer of dimers, trimers, quadromers or pentamers of recombinant fusion proteins according to  claim 1  characterized by the recombinant fusion proteins having two or more different components B. 
     
     
         18 . A medicament comprising a pharmaceutical composition of a bimer or oligomer according to  claim 1 . 
     
     
         19 . Method of treatment of a disorder or disease comprising administration of a bimer or oligomer according to claim wherein the disorder or disease is a hyperinflammatory disorders, autoimmune diseases, diseases based on hyperapoptotic or hypoapoptotic disorders, infectious diseases, viral infectious diseases, tumors, in particular tumors of the lymphatic system, and/or endocrinological disorders. 
     
     
         20 . A vaccine comprising a bimer or oligomer according to  claim 1  wherein the vaccine is for active or passive immunization against infectious diseases. 
     
     
         21 . A vaccine according to  claim 20  for vaccination against German measles, measles, poliomyelitis, rabies, tetanus, diphtheria, BCG, malaria, yellow fever, HIV or influenza. 
     
     
         22 . A vaccine according to  claim 20  which is formulated for parenteral or oral administration. 
     
     
         23 . A method for in-vitro diagnosis comprising applying a bimer or oligomer according to  claim 1  to an in-vitro protein-based derivative. 
     
     
         24 . A fusion protein characterized by the recombinant fusion protein containing a component A and a component B, whereby component A contains a protein or a protein segment with biological function, in particular ligand function for antibodies or receptors or an antibody or segment of an antibody or for soluble or membrane-bound signal molecules, and component B contains a multimerizing and oligomerizing segment or a functional derivative of such a segment of a protein, selected from the group consisting of the family of the C1q proteins and the collectins. 
     
     
         25 . The fusion protein according to  claim 24  characterized by the component B of the fusion protein containing a multimerizing and oligomerizing segment of a protein or a functional derivative of the same, selected from the group consisting of C1q, MBP, SP-A, SP-D, BC, CL43 and ACRP30, or containing the collagen domain of the EDA protein or a functional derivative thereof. 
     
     
         26 . A DNA sequence characterized by the DNA sequence encoding the fusion protein according to  claim 24 . 
     
     
         27 . An expression vector characterized by the expression vector containing the DNA sequence according to  claim 26 . 
     
     
         28 . A host cell characterized by the host cell being transfected with an expression vector according to  claim 27 .