Il-6 activity inhibitor

• US 6,004,813 A
• Filed: 11/10/1997
• Issued: 12/21/1999
• Est. Priority Date: 05/11/1995
• Status: Expired due to Term

• Current Assignee: Merck Serono SA (Merck & Co., Inc.)
• Original Assignee: Applied Research Systems ARS Holding NV (Merck & Co., Inc.)
• Inventors: Pezzotti, Annarita, Serlupi-Crescenzi, Ottaviano
• Primary Examiner(s): Degen, Nancy
• Assistant Examiner(s): McGarry, Sean
• Application Number:
  US08/945,726
• Time in Patent Office: 771 Days
• Field of Search: 435/6, 435/320.1, 435/375, 435/377, 435/455, 536/24.1, 536/23.1, 536/24.5, 514/44
• US Class Current: 435/375
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 14/4705 stimulating, promoting or activating activity

Abstract

The invention relates to a nucleotide sequence, which is able to inhibit the IL-6 activity, its use in therapy as well as pharmaceutical compositions containing it.

In particular, it relates to a nucleotide sequence which comprises:

i) at least one nucleotide sequence that is an APRE element of general formula ZXMYKGKAA, wherein Z represents T or G or can also be absent, X represents T or can also be absent, M represents C or A, Y represents C or T and K represents T or G,

in conjunction with

ii) at least one nucleotide sequence constituting a transcription factor binding site other than the APRE element, such as those present in promoter regions.

Claims

1. A nucleotide sequence which inhibits IL-6 activity, that comprises:

i) at least one nucleotide sequence that is an APRE element of general formula ZXMYKGKAA, wherein Z represents T or G or can also be absent, X represents T or can also be absent, M represents C or A, Y represents C or T and K represents T or G;

ii) at least one nucleotide sequence constituting a transcription factor binding site other than the APRE element.

2. The nucleotide sequence according to claim 1, wherein (i) is the nucleotide sequence TTCTGGGAA.

3. The nucleotide sequence according to claim 1, wherein (ii) is selected from the group consisting of TATA Box, binding site for transcription factor AP-1, binding site for transcription factor AP-2, binding site for transcription factor HNF-1, binding site for transcription factor SP-1, binding site for transcription factor NF-KB, binding site for transcription factor Oct-1, binding site for transcription factor E-2, and binding site for transcription factor SRF.

4. The nucleotide sequence according to claim 1, wherein the APRE element (i) is repeated at least 2 times.

5. The nucleotide sequence according to claim 4, wherein the APRE element is repeated from 3 to 10 times.

6. The nucleotide sequence according to claim 4, wherein the APRE element is repeated 8 times.

7. The nucleotide sequence according to claim 1, wherein the sequence (i) comprises at least two different APRE elements.

8. The nucleotide sequence according to claim 1, wherein the sequence (ii) comprises at least two different oligonucleotide sequences constituting a transcription factor binding site.

9. The nucleotide sequence according to claim 8, wherein the sequence (ii) is the SV40 early promoter.

10. The nucleotide sequence according to claim 1, as reported in SEQ ID NO:

1.

11. A plasmid vector containing the nucleotide sequence of claim 1.

12. A composition comprising the nucleotide sequence according to claim 1 together with one or more pharmaceutically acceptable carriers and/or excipient.

13. A composition comprising the plasmid according to claim 11 together with one or more pharmaceutically acceptable carriers and/or excipients.

14. A method for inhibiting IL-6 activity, comprising the step of introducing the nucleotide sequence of claim 1 into cells to inhibit IL-6 activity in the cells.