Bibliographic Details
| Title: |
Interleukin-1 Muteins Linked to Virus-Like Particles to Treat IL-1 Associated Diseases |
| Document Number: |
20110091411 |
| Publication Date: |
April 21, 2011 |
| Appl. No: |
12/443344 |
| Application Filed: |
March 29, 2007 |
| Abstract: |
The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a composition comprising an ordered and repetitive antigen array, wherein the antigen is an IL-1 mutein. More specifically, the invention provides a composition comprising a virus-like particle, and at least one IL-1 mutein linked thereto. The invention also provides a process for producing the composition. The compositions of the invention are useful in the production of vaccines for the treatment of inflammatory diseases, and chronic autoimmune diseases, genetic diseases and cardiovascular diseases. The composition of the invention efficiently induces immune responses, in particular antibody responses. Furthermore, the compositions of the invention are particularly useful to efficiently induce self-specific immune responses within the indicated context. |
| Inventors: |
Bachmann, Martin F. (Seuzach, CH); Spohn, Gunther (Zurich, CH); Tissot, Alain (Zurich, CH) |
| Assignees: |
Cytos Biotechnology AG (Zurich-Schlieren, CH) |
| Claim: |
1. A composition comprising: (a) a virus-like particle (VLP) with at least one first attachment site; and (b) at least one antigen with at least one second attachment site; wherein said at least one antigen is an IL-1 mutein, and wherein said IL-1 mutein comprises at least one mutated amino acid sequence derived from a wild type amino acid sequence, wherein said wild type amino acid sequence is an IL-1 beta amino acid sequence selected from the group consisting of: (1) position 3 to 11 of SEQ ID NO:64; (2) position 46 to 56 of SEQ ID NO:64; (3) position 88 to 109 of SEQ ID NO:64; and (4) position 143 to 153 of SEQ ID NO:64; or wherein said wild type amino acid sequence is an IL-1 alpha amino acid sequence selected from the group consisting of: (5) position 9 to 20 of SEQ ID NO:63; (6) position 52 to 62 of SEQ ID NO:63; (7) position 94 to 113 of SEQ ID NO:63; and (8) position 143 to 153 of SEQ ID NO:63; and wherein said at least one mutated amino acid sequence is characterized by an amino acid exchange in one, two or three positions as compared to said wild type amino acid sequence it is derived from; or wherein said at least one mutated amino acid sequence is characterized by a deletion of one to four consecutive amino acids of said wild type amino acid sequence it is derived from; and wherein (a) and (b) are linked through said at least one first and said at least one second attachment site. |
| Claim: |
2.-7. (canceled) |
| Claim: |
8. The composition of claim 1, wherein said at least one mutated amino acid sequence is characterized by an amino acid exchange in exactly one position as compared to said wild type amino acid sequence it is derived from. |
| Claim: |
9. The composition of claim 8, wherein said wild type amino acid sequence is position 143 to 153 of SEQ ID NO:64 or position 143 to 153 of SEQ ID NO:63. |
| Claim: |
10. The composition of claim 9, wherein said exactly one position is position 145 of SEQ ID NO:64 or position 145 of SEQ ID NO:63. |
| Claim: |
11. The composition of claim 10, wherein said amino acid exchange is an exchange of aspartic acid (D) to an amino acid selected from the group consisting of lysine (K), tyrosine (Y), phenylalanine (F), asparagine (N) and arginine (R). |
| Claim: |
12.-13. (canceled) |
| Claim: |
14. The composition of claim 1, wherein said IL-1 mutein is an IL-1 beta mutein, wherein said IL-1 beta mutein comprises or consists of a polypeptide having an amino acid sequence, wherein said amino acid sequence differs from the amino acid sequence of SEQ ID NO:64 in 1 to 4 amino acid residues. |
| Claim: |
15. The composition of claim 14, wherein said IL-1 beta mutein comprises or consists of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:131 to SEQ ID NO:140 and SEQ ID NO:205 to SEQ ID NO:209. |
| Claim: |
16. The composition of claim 14, wherein said IL-1 beta mutein comprises or consists of a polypeptide having the amino acid sequence of SEQ ID NO:136. |
| Claim: |
17.-19. (canceled) |
| Claim: |
20. The composition of claim 1, wherein said VLP comprises, or alternatively consists of, recombinant coat proteins, mutants or fragments thereof, of an RNA bacteriophage. |
| Claim: |
21. The composition of claim 1, wherein said VLP is a VLP of an RNA bacteriophage. |
| Claim: |
22. The composition of claim 1, wherein said VLP is a VLP of RNA bacteriophage Qβ. |
| Claim: |
23. The composition of claim 1, wherein said first attachment site is linked to said second attachment site via at least one non-peptide covalent bond. |
| Claim: |
24. The composition of claim 1, wherein said first attachment site is an amino group of a lysine, and wherein said second attachment site is a sulfhydryl group of a cysteine. |
| Claim: |
25.-27. (canceled) |
| Claim: |
28. The composition of claim 1, wherein only one of said second attachment sites associates with said first attachment site through at least one non-peptide covalent bond leading to a single and uniform type of binding of said IL-1 mutein to said virus-like particle, wherein said only one second attachment site that associates with said first attachment site is a sulfhydryl group, and wherein said IL-1 mutein and said core particle interact through said association to form an ordered and repetitive antigen array. |
| Claim: |
29.-30. (canceled) |
| Claim: |
31. The composition of claim 1, wherein said IL-1 mutein is SEQ ID NO:136. |
| Claim: |
32.-35. (canceled) |
| Claim: |
36. A pharmaceutical composition comprising: (a) the composition of claim 1; and (b) a pharmaceutically acceptable carrier. |
| Claim: |
37.-43. (canceled) |
| Claim: |
44. The composition of claim 20, wherein said recombinant coat proteins consist of the amino acid sequence of SEQ ID NO:3. |
| Claim: |
45. The composition of claim 10, wherein said amino acid exchange is an exchange of aspartic acid (D) to lysine (K). |
| Claim: |
46. A method of treating a disease in an animal, said method comprising administering the composition of claim 1 to said animal, wherein said disease is selected from the group consisting of: (a) vascular diseases; (b) inherited IL-1-dependent inflammatory diseases; (c) chronic autoimmune inflammatory diseases; (d) bone and cartilage degenerative diseases; (e) allergic diseases; and (f) neurological disease. |
| Claim: |
47. The method of claim 46, wherein said animal is a human. |
| Current U.S. Class: |
424/852 |
| Current International Class: |
61; 07; 61; 61; 61; 61; 61; 61; 61 |
| Accession Number: |
edspap.20110091411 |
| Database: |
USPTO Patent Applications |
