US2013243768A1PendingUtilityA1

Multimeric proteins and methods of making and using same

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Assignee: PERLAN THERAPEUTICS INCPriority: Jul 19, 2001Filed: Mar 11, 2013Published: Sep 19, 2013
Est. expiryJul 19, 2021(expired)· nominal 20-yr term from priority
Inventors:Fang FangGuang-Xiang LuoLori KohlstaedtCatherine Helen Charles
A61P 31/14A61P 25/06A61P 31/12A61P 31/16A61P 27/16A61P 29/00C07K 14/4705C12N 15/62C07K 2319/00A61K 38/00C07K 2319/02C07K 16/2821A61P 11/06C07K 14/001C07K 2319/73A61P 11/00
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Claims

Abstract

The invention provides multimerization polypeptides capable of conferring formation of multimers when the multimerization polypeptide is linked to a molecule, such as a heterologous polypeptide sequence.

Claims

exact text as granted — not AI-modified
1 .- 112 . (canceled) 
     
     
         113 . A multimerization polypeptide comprising an amino acid sequence selected from the group consisting of (i) SEQ ID NO: 159; and (ii) SEQ ID NO: 159, wherein one or more of amino acid positions 1, 4, 8, 11, 15, 18, 22, 25, and 29 is substituted with leucine, isoleucine, or valine. 
     
     
         114 . The multimerization polypeptide of  claim 113 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 159. 
     
     
         115 . The multimerization polypeptide of  claim 114 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 159, wherein one or more of amino acid positions 1, 4, 8, 11, 15, 18, 22, 25, and 29 is substituted with leucine, isoleucine, or valine. 
     
     
         116 . The multimerization polypeptide of  claim 114 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO: 159. 
     
     
         117 . The multimerization polypeptide of  claim 115 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO: 159, wherein one or more of amino acid positions 1, 4, 8, 11, 15, 18, 22, 25, and 29 is substituted with leucine, isoleucine, or valine. 
     
     
         118 . A chimeric protein comprising a heterologous polypeptide fused to the N-terminus of the multimerization polypeptide of  claim 113 . 
     
     
         119 . The chimeric protein of  claim 118 , wherein the heterologous polypeptide is selected from the group consisting of a binding protein, enzyme, receptor, ligand, nucleic acid binding protein, growth regulatory factor, differentiative factor, and chemotactic factor. 
     
     
         120 . The chimeric protein of  claim 119 , wherein the binding protein comprises an antigen binding polypeptide. 
     
     
         121 . The chimeric protein of  claim 120 , wherein the antigen binding polypeptide comprises at least one antibody variable domain. 
     
     
         122 . The chimeric protein of  claim 121 , wherein the antibody variable domain is human or humanized. 
     
     
         123 . The chimeric protein of  claim 120 , wherein the antigen binding polypeptide comprises a single chain antibody, Fab, Fab′, (Fab′) 2 , or Fv antibody subsequence. 
     
     
         124 . The chimeric protein of  claim 120 , wherein the antigen binding polypeptide comprises a multispecific or multifunctional antibody. 
     
     
         125 . The chimeric protein of  claim 120 , wherein the antigen binding polypeptide binds to ICAM-1 or an epitope thereof. 
     
     
         126 . The chimeric protein of  claim 118 , wherein said chimeric protein contains a linker between the heterologous polypeptide and multimerization polypeptide. 
     
     
         127 . The chimeric protein of  claim 126 , wherein the linker comprises a hinge domain. 
     
     
         128 . The chimeric protein of  claim 126 , wherein the linker comprises an amino acid sequence set forth in any of SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 47. 
     
     
         129 . The chimeric protein of  claim 126 , wherein the linker comprises an amino acid sequence having a length of from about 5 to 20 amino acids. 
     
     
         130 . The chimeric protein of  claim 126 , wherein the linker comprises an amino acid sequence having a length of from about 10 to 30 amino acids. 
     
     
         131 . The chimeric protein of  claim 126 , wherein the linker comprises an amino acid sequence having a length of from about 25 to 50 amino acids. 
     
     
         132 . The chimeric protein of  claim 126 , wherein the linker comprises an amino acid sequence having a length of from about 30 to 60 amino acids. 
     
     
         133 . The chimeric protein of  claim 126 , wherein the linker comprises an amino acid sequence having a length of from about 50 to 75 amino acids. 
     
     
         134 . A polypeptide oligomer comprising at least two chimeric proteins of  claim 118 . 
     
     
         135 . The polypeptide oligomer of  claim 134  that is a tetramer. 
     
     
         136 . The polypeptide oligomer of  claim 135  that is homomeric tetramer. 
     
     
         137 . A pharmaceutical formulation comprising the chimeric protein of  claim 118  and a pharmaceutical carrier. 
     
     
         138 . The pharmaceutical formulation of  claim 137 , wherein the pharmaceutical carrier is a sterile, aqueous solution. 
     
     
         139 . The pharmaceutical formulation of  claim 138 , wherein the pharmaceutical carrier is an ointment, salve, gel, or cream. 
     
     
         140 . A kit comprising the pharmaceutical formulation of  claim 138  in a container. 
     
     
         141 . The kit of  claim 140 , further comprising instructions for administration of the pharmaceutical formulation.

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