Method for Detecting Peptides Comprising a Cross-B Structure

Abstract

The invention relates to the field of compositions comprising a protein, more specifically to pharmaceutical compositions. More specifically, the invention relates to the detection and/or removal of conformationally altered proteins and/or molecules comprising a cross-β structure from a pharmaceutical composition or any of its constituents comprising a protein. The present invention discloses that unwanted and/or toxic side effects of pharmaceuticals are caused by proteins present in said pharmaceutical and adopting a cross-b structure conformation. The invention further discloses a method for detecting a protein and/or peptide comprising a cross-β structure in a pharmaceutical composition or any of its constituents comprising a protein, said method comprising, contacting said pharmaceutical composition or any of its constituents comprising a protein with at least one cross-β structure-binding compound resulting in a bound protein and/or peptide comprising a cross-β structure and; detecting whether bound protein and/or peptide comprising a cross-β structure are present in said pharmaceutical composition or any of its constituents comprising a protein. The invention further disclose methods for removing cross-β structures from a pharmaceutical composition and controlling manufacturing a pharmaceutical composition.

1 . A method for detecting a protein and/or peptide comprising a cross-β structure in a pharmaceutical composition or any of its constituents comprising a protein, said method comprising:
 a. contacting said pharmaceutical composition or any of its constituents comprising a protein with at least one cross-β structure-binding compound resulting in a bound protein and/or peptide comprising a cross-β structure, and   b. detecting whether bound protein and/or peptide comprising a cross-β structure are present in said pharmaceutical composition or any of its constituents comprising a protein.   
     
     
         2 . The method according to  claim 1 , wherein said cross-β structure-binding compound is a compound selected from the group of compounds identified in Table 1, Table 2, and Table 3. 
     
     
         3 . A method for controlling a manufacturing process, and/or storage process of a pharmaceutical composition or any of its constituents comprising a protein, said method comprising:
 a. contacting said pharmaceutical composition or any of its constituents comprising a protein with at least one cross-β structure-binding compound resulting in a bound protein and/or peptide comprising a cross-β structure, and   b. detecting whether bound protein and/or peptide comprising a cross-β structure is present in said pharmaceutical composition or any of its constituents comprising a protein at various stages of said manufacturing and/or storage process.   
     
     
         4 . A method for removing a protein and/or peptide comprising a cross-β structure from a pharmaceutical composition or any of its constituents comprising a protein, said method comprising:
 a. contacting said pharmaceutical composition or any of its constituents comprising a protein with at least one cross-β structure-binding compound;   b. allowing binding of said protein and/or peptide comprising across-β structure to said cross-β structure-binding compound, and   c. separating said bound protein and/or peptide comprising a cross-β structure from said pharmaceutical composition or any of its constituents comprising a protein.   
     
     
         5 . The method according to  claim 4 , wherein said cross-β structure-binding compound is a compound according to Table 1, Table 2, or Table 3 or a functional equivalent of any of said compounds. 
     
     
         6 . The method according to  claim 4 , wherein said cross-β binding compound is bound to a second compound. 
     
     
         7 . The method according to  claim 6 , wherein said second compound is bound to a solid phase. 
     
     
         8 . A method for decreasing and/or preventing undesired side effects of a pharmaceutical composition comprising a protein or peptide and/or increasing specific activity per gram protein, said method comprising:
 detecting and removing any unfolded protein or peptide and/or aggregated protein or peptide and/or multimerized protein or peptide comprising a cross-β structure from said pharmaceutical composition or any of its constituents comprising a protein.   
     
     
         9 . A pharmaceutical composition or any of its constituents comprising a protein, obtainable by the method according to  claim 1 . 
     
     
         10 . A kit for carrying out a method for binding a peptide having a cross-β structure that may be found in a pharmaceutical composition, the kit comprising:
 means for contacting the pharmaceutical composition or a constituent thereof with a cross-β structure-binding compound, and   a cross-β structure-binding compound.   
     
     
         11 . A method for influencing the immunogenicity of a protein, the method comprising:
 influencing the formation of at least one cross-β structure in said protein so as to alter the immunogen city of the protein.   
     
     
         12 . The method according to  claim 5 , wherein the cross-β binding compound is bound to a second compound. 
     
     
         13 . The method according to  claim 12 , wherein the second compound is bound to a solid phase. 
     
     
         14 . A pharmaceutical composition or constituent thereof produced by the manufacturing process of the method according to  claim 3 . 
     
     
         15 . A pharmaceutical composition or any constituent thereof resulting from the method according to  claim 4 . 
     
     
         16 . A pharmaceutical composition or any constituent thereof resulting from the method according to  claim 8 .