Coiled coil immunoglobulin fusion proteins and compositions thereof

Abstract

Disclosed herein are immunoglobulin fusion proteins comprising a first antibody region, a first therapeutic agent, and a first connecting peptide; wherein the first therapeutic agent is attached to the first antibody region by the connecting peptide; and wherein the connecting peptide does not comprise a region having beta strand secondary structure. The connecting peptide may comprise an extender peptide. The extender peptide may have an alpha helical secondary structure. The connecting peptide may comprise a linker peptide. The linker peptide may not comprise any secondary structure. Also disclosed herein are compositions comprising the immunoglobulin fusion proteins and methods for using the immunoglobulin fusion proteins for the treatment or prevention of a disease or condition in a subject.

1 - 101 . (canceled) 
     
     
         102 . An immunoglobulin fusion protein comprising an antibody variable domain region, a first extender fusion region, and a second extender fusion region, wherein the first extender fusion region comprises a GLP1 peptide, and the second extender fusion region comprises an FGF21 peptide. 
     
     
         103 . The immunoglobulin fusion protein of  claim 102 , wherein the antibody variable domain region comprises an amino acid sequence at least 95% identical to the variable domain of SEQ ID NO: 31. 
     
     
         104 . The immunoglobulin fusion protein of  claim 102 , comprising an amino acid sequence at least 95% identical to SEQ ID NO: 29. 
     
     
         105 . The immunoglobulin fusion protein of  claim 102 , wherein the GLP1 peptide comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 228. 
     
     
         106 . The immunoglobulin fusion protein of  claim 102 , wherein the GLP1 peptide comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 232. 
     
     
         107 . The immunoglobulin fusion protein of  claim 102 , wherein the FGF21 peptide comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 234. 
     
     
         108 . The immunoglobulin fusion protein of  claim 102 , comprising an amino acid sequence at least about 95% identical to SEQ ID NO: 31. 
     
     
         109 . The immunoglobulin fusion protein of  claim 102 , wherein the first extender fusion region comprises a first linker peptide comprising (GGGGS)n, wherein n is from 1 to 5. 
     
     
         110 . The immunoglobulin fusion protein of  claim 109 , wherein n is 3. 
     
     
         111 . The immunoglobulin fusion protein of  claim 109 , wherein the second extender fusion region comprises a second linker peptide comprising the sequences of SEQ ID NO: 179 and SEQ ID NO: 180. 
     
     
         112 . The immunoglobulin fusion protein of  claim 111 , wherein the second linker peptide comprises the sequence of GGGGSGGGSGGGGS. 
     
     
         113 . The immunoglobulin fusion protein of  claim 109 , comprising a heavy chain and a light chain, wherein the antibody variable domain region is part of the heavy chain. 
     
     
         114 . The immunoglobulin fusion protein of  claim 113 , wherein the light chain comprises a kappa light chain comprising the amino acid sequence of SEQ ID NO: 28. 
     
     
         115 . The immunoglobulin fusion protein of  claim 102 , comprising a heavy chain and a light chain, wherein the antibody variable domain region is part of the heavy chain, and wherein the heavy chain comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 25. 
     
     
         116 . The immunoglobulin fusion protein of  claim 115 , wherein the first extender fusion region comprises a first linker peptide comprising (GGGGS)n, wherein n is from 1 to 5, and wherein the second extender fusion region comprises a second linker peptide comprising the sequences of SEQ ID NO: 179 and SEQ ID NO: 180. 
     
     
         117 . The immunoglobulin fusion protein of  claim 115 , wherein the light chain comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 19. 
     
     
         118 . An immunoglobulin fusion protein comprising an antibody variable domain region and a first extender fusion region, wherein the antibody variable domain region comprises an amino acid sequence at least 95% identical to the variable domain of SEQ ID NO: 31, and wherein the first extender fusion region comprises a GLP1 peptide. 
     
     
         119 . The immunoglobulin fusion protein of  claim 118 , comprising an IgG1 heavy chain comprising an amino acid sequence at least about 95% identical to SEQ ID NO: 31, wherein the first extender fusion region comprises a first linker peptide that connects the GLP1 peptide to the antibody variable domain region, the first linker peptide comprising (GGGGS)n, wherein n is from 1 to 5, and wherein the GLP1 peptide comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 228 or SEQ ID NO: 232. 
     
     
         120 . An immunoglobulin fusion protein comprising an antibody variable domain region and a first extender fusion region, wherein the antibody variable domain region comprises an amino acid sequence at least 95% identical to the variable domain of SEQ ID NO: 31, and wherein the first extender fusion region comprises an FGF21 peptide. 
     
     
         121 . The immunoglobulin fusion protein of  claim 120 , comprising an IgG1 heavy chain comprising an amino acid sequence at least about 95% identical to SEQ ID NO: 31, wherein the first extender fusion region comprises a first linker peptide that connects the FGF21 peptide to the C-terminal end of the IgG1 heavy chain, wherein the first linker peptide comprises the sequences of SEQ ID NO: 179 and SEQ ID NO: 180, and wherein the FGF21 peptide comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 234.