Polypeptides comprising immunoglobulin single variable domains targeting tnfa and il-23

Abstract

The present technology aims at providing a novel type of drug. Specifically, the present technology provides polypeptides comprising at least three immunoglobulin single variable domains (ISVDs), characterized in that at least one ISVD binds to TNFα and at least two ISVDs bind to IL-23. The present technology also provides nucleic acids, vectors and compositions.

1 . - 8 . (canceled) 
     
     
         9 . A polypeptide that specifically binds TNFα and the p19 subunit of IL-23, wherein the polypeptide comprises or consists of at least three immunoglobulin single variable domains (ISVDs), wherein each of said ISVDs comprises three complementarity determining regions (CDR1 to CDR3, respectively), optionally linked via one or more peptidic linkers; and wherein:
 a) a first ISVD comprises
 i. a CDR1 that is the amino acid sequence of SEQ ID NO: 6 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 6; 
 ii. a CDR2 that is the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 10; and 
 iii. a CDR3 that is the amino acid sequence of SEQ ID NO: 14 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 14; 
 
 b) a second ISVD comprises
 iv. a CDR1 that is the amino acid sequence of SEQ ID NO: 7 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 7; 
 v. a CDR2 that is the amino acid sequence of SEQ ID NO: 11 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 11; and 
 vi. a CDR3 that is the amino acid sequence of SEQ ID NO: 15 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 15; and 
 
 c) a third ISVD comprises
 vii. a CDR1 that is the amino acid sequence of SEQ ID NO: 9 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 9; 
 viii. a CDR2 that is the amino acid sequence of SEQ ID NO: 13 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 13; and 
 ix. a CDR3 that is the amino acid sequence of SEQ ID NO: 17 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 17. 
 
 
     
     
         10 . The polypeptide according to  claim 9 , wherein:
 a) the amino acid sequence of said first ISVD comprises a sequence identity of more than 90% with SEQ ID NO: 2;   b) the amino acid sequence of said second ISVD comprises a sequence identity of more than 90% with SEQ ID NO: 3; and   c) the amino acid sequence of said third ISVD comprises a sequence identity of more than 90% identity with SEQ ID NO: 5.   
     
     
         11 . The polypeptide according to  claim 9 , wherein:
 a) said first ISVD consists of the amino acid sequence of SEQ ID NO: 2;   b) said second ISVD consists of the amino acid sequence of SEQ ID NO: 3; and   c) said third ISVD consists of the amino acid sequence of SEQ ID NO: 5.   
     
     
         12 . The polypeptide according to  claim 9 , wherein said polypeptide further comprises an ISVD binding to human serum albumin which comprises
 i. a CDR1 that is the amino acid sequence of SEQ ID NO: 8 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 8;   ii. a CDR2 that is the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 12; and   iii. a CDR3 that is the amino acid sequence of SEQ ID NO: 16 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 16.   
     
     
         13 . The polypeptide according to  claim 12 , wherein the amino acid sequence of said ISVD binding to human serum albumin comprises a sequence identity of more than 90% with SEQ ID NO: 4. 
     
     
         14 . The polypeptide according to  claim 9 , wherein the polypeptide comprises or consists of the amino acid sequence of SEQ ID NO: 1. 
     
     
         15 . A nucleic acid comprising a nucleotide sequence that encodes a polypeptide according to  claim 9 . 
     
     
         16 . A host or host cell comprising a nucleic acid according to  claim 15 . 
     
     
         17 . A method for producing a polypeptide according to  claim 9 , said method at least comprising the steps of:
 a) expressing, in a suitable host cell or host organism or in another suitable expression system, a nucleic acid encoding the polypeptide; optionally followed by:   b) isolating and/or purifying the polypeptide.   
     
     
         18 . A composition comprising a polypeptide according to  claim 9 . 
     
     
         19 . A method of treating an autoimmune or inflammatory disease, wherein said method comprises administering, to a subject in need thereof, a pharmaceutically active amount of a polypeptide according to  claim 9 , or a composition comprising the same. 
     
     
         20 . The method of  claim 19 , wherein the autoimmune or inflammatory disease is selected from inflammatory bowel disease, such as Crohn's disease and ulcerative colitis, psoriasis, psoriatic arthritis and Hidradenitis suppurativa.