Peptides with the capacity to bind to interleukin-10 (il-10)

Abstract

The invention relates to peptides having the capacity to bind to interleukin-10 (IL-10) and their use in the treatment of clinical conditions or pathological disorders associated to IL-10 expression, particularly to a high IL-10 expression, for example, infectious diseases, tumors, cancers and acute damage conditions.

1 . A peptide with the capacity to bind to IL-10 selected from:
 a) a peptide the amino acid sequence of which is selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21; SEQ ID NO: 22; SEQ ID NO: 23; SEQ ID NO: 24; SEQ ID NO: 25; SEQ ID NO: 26; SEQ ID NO: 33; SEQ ID NO: 34; SEQ ID NO: 35 and SEQ ID NO: 36,   b) a variant of a peptide defined in a); and   c) a fragment of a peptide defined in a) or of a variant defined in b), comprising between 5 and 15 consecutive amino acids; and   
       its pharmaceutically acceptable salts. 
     
     
         2 . A peptide according to  claim 1 , selected from the group consisting of the peptides identified as SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52 and SEQ ID NO: 53, and their pharmaceutically acceptable salts. 
     
     
         3 . A peptide according to  claim 1 , wherein said peptide has the capacity to inhibit the biological activity of IL-10 in vitro and/or in vivo. 
     
     
         4 . A peptide according to  claim 3 , selected from the group consisting of the peptides identified as SEQ ID NO: 1, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 19 and SEQ ID NO: 25, a variant or a fragment thereof, and their pharmaceutically acceptable salts. 
     
     
         5 . A nucleic acid sequence encoding a peptide according to any of  claims 1  to  4 . 
     
     
         6 . A gene construct comprising a nucleic acid sequence according to  claim 5 . 
     
     
         7 . A vector comprising a nucleic acid sequence according to  claim 5 , or a gene construct according to  claim 6 . 
     
     
         8 . A host cell comprising a nucleic acid sequence according to  claim 5 , or a gene construct according to  claim 6 , or a vector according to  claim 7 . 
     
     
         9 . A pharmaceutical composition comprising a therapeutically effective amount of a peptide according to any of  claims 1  to  4  together with at least one pharmaceutically acceptable excipient; or a nucleic acid sequence according to  claim 5 , or a gene construct according to  claim 6 , or a vector according to  claim 7 , or a host cell according to  claim 8 , and a pharmaceutically acceptable carrier. 
     
     
         10 . A pharmaceutical composition according to  claim 6 , comprising at least one peptide according to any of  claims 1  to together with, optionally, one or more different IL-10 inhibitor compounds. 
     
     
         11 . A product selected from a peptide according to any of  claims 1  to  4 , a nucleic acid sequence according to  claim 5 , a gene construct according to  claim 6 , a vector according to  claim 7 , and a host cell according to  claim 8 , for the treatment of a clinical condition or pathological disorder presenting IL-10 expression. 
     
     
         12 . A product according to  claim 11 , for the treatment of a clinical condition or pathological disorder presenting IL-10 expression comprising clinical conditions or pathological disorders in which Th1 cell response is inhibited. 
     
     
         13 . A product according to  claim 11 , for the treatment of a clinical condition or pathological disorder presenting IL-10 expression selected from an infectious disease, a tumor, a cancer and an acute damage situation. 
     
     
         14 . A product according to  claim 13 , for the treatment of an infection caused by  Mycobacterium leprae, Mycobacterium tuberculosis, Yersinia pestis, Helicobacter pylori, Candida albicans, Trichophyton rubrum, Aspergillus  sp., or by  Plasmodium falciparum , leishmaniasis, toxoplasmosis; or for the treatment of a Hodgkin's lymphoma, head and neck cancer, melanoma, or basal cell carcinomas and squamous cell carcinomas developed from keratinocytes mutated by UV; or for the treatment of burns and associated sepsis. 
     
     
         15 . A process for producing a peptide according to any of  claims 1  to  4 , which comprises growing a host cell according to  claim 8  under conditions allowing the production of said peptide and, if desired, the recovery of said peptide. 
     
     
         16 . A peptide comprising the amino acid of SEQ ID NO: 8, or a pharmaceutically acceptable salt thereof, wherein said peptide has the capacity to bind to IL-10. 
     
     
         17 . The peptide according to  claim 16 , wherein said peptide is SEQ ID NO: 8, or a pharmaceutically acceptable salt thereof. 
     
     
         18 . An isolated nucleic acid sequence encoding a peptide according to  claim 16 . 
     
     
         19 . A vector comprising a nucleic acid sequence according to  claim 18 . 
     
     
         20 . A host cell comprising a nucleic acid sequence according to  claim 18 . 
     
     
         21 . A pharmaceutical composition comprising a peptide according to  claim 16  together with at least one pharmaceutically acceptable excipient. 
     
     
         22 . The pharmaceutical composition according to  claim 21 , further comprising a different IL-10 inhibitor compound selected from the group consisting of interferon gamma (IFN-γ), ammonium trichloro(dioxoethylene-O,O′) tellurate, 15-deoxy-delta-12,14-prostaglandin J2, chimeric murine anti-human CD20 antibody and combinations thereof. 
     
     
         23 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a nucleic acid sequence according to  claim 18 . 
     
     
         24 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a vector according to  claim 19 . 
     
     
         25 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a host cell according to  claim 20 . 
     
     
         26 . A method of treating colon adenocarcinoma in a subject in need thereof which comprises administering to said subject a peptide of  claim 16  and a peptide comprising the amino acid sequence of SEQ ID NO: 6. 
     
     
         27 . A method of treating melanoma in a subject in need thereof which comprises administering to said subject a peptide of  claim 16 . 
     
     
         28 . A method of treating an infection caused by an hepatitis C virus (HCV) in a subject in need thereof which comprises administering to said subject a peptide of  claim 16 . 
     
     
         29 . A process for producing a peptide which comprises growing a host cell according to  claim 20  under conditions allowing the production of said peptide and optionally the recovery of said peptide.