Cytokine synthesis inhibitory factor (IL-10) and pharmaceutical compositions thereof

• US 6,217,857 B1
• Filed: 06/05/1995
• Issued: 04/17/2001
• Est. Priority Date: 06/28/1989
• Status: Expired due to Term

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Schering Corporation (Merck & Co., Inc.)
• Inventors: Mosmann, Timothy R., Vieira, Paulo J. M., Moore, Kevin W., Bond, Martha W.
• Primary Examiner(s): MERTZ, PREMA MARIA
• Application Number:
  US08/464,110
• Time in Patent Office: 2,143 Days
• Field of Search: 424/85.1, 424/85.2, 514/2, 514/12, 514/8, 435/69.52, 435/71.1, 435/71.2, 435/172.3, 435/240.2, 435/252.3, 435/471, 435/325, 435/320.1, 530/351
• US Class Current: 424/85.2
• 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: C07K 14/5428 IL-10
• CPC Class Codes: C07K 16/244 Interleukins [IL]
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Mammalian genes and proteins, designated cytokine synthesis inhibitory factors (CSIF'"'"'s, now known as Interleukin-10 (IL-10)), are provided which are capable of inhibiting the synthesis of cytokines associated with delayed type hypersensitivity responses, and which, together with antagonists, are useful in treating diseases associated with cytokine imbalances, such as leishmaniasis and other parasitic infections, and certain immune disorders including MHC associated autoimmune diseases caused by excessive production of interferon-γ.

Claims

1. An isolated polypeptide comprising the amino acid sequence:

SPGQGTQSEN SCTHFPGNLP NMLRDLRDAF SRVKTFFQMK

DQLDNLLLKE SLLEDFKGYL GCQALSEMIQ FYLEEVMPQA

ENQDPDIKAH VNSLGENLKT LRLRLRRCHR FLPCENKSKA

VEQVKNAFNK LQEKGIYKAM SEFDIFINYI EAYMTMKIRN.

2. An isolated immunogenic polypeptide consisting of 6 to 30 consecutive amino acids from the polypeptide of claim 1.

3. A pharmaceutical composition comprising a polypeptide of claim 1 and a pharmaceutically acceptable carrier.

4. The pharmaceutical composition of claim 3, which is formulated for parenteral administration.

5. A pharmaceutical composition comprising the polypeptide of claim 4 and a pharmaceutically acceptable carrier.

6. The pharmaceutical composition of claim 5 which is formulated for parenteral administration.

7. A method of making an antibody by immunizing a non-human animal with the polypeptide of claim 1.

8. A method of making an antibody by immunizing a non-human animal with the polypeptide of claim 2.

9. A polypeptide encoded by a polynucleotide which exhibits at least 90% homology to the polynucleotide defined by nucleotides 87 to 566 in FIGS. 4A-4C, wherein the homology is determined by Needleham and Wunsch algorithm using default parameter settings.

10. A pharmaceutical composition comprising the polypeptide of claim 9 and a pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10 which is formulated for parenteral administration.

12. A method of making an antibody by immunizing a non-human animal with the polypeptide of claim 9.

13. An isolated polypeptide comprising the amino acid sequence:

QYSREDNNCT HFPVGQSHML LELRTAFSQV KTFFQTKDQL

DNILLTDSLM QDFKGYLGCQ ALSEMIQFYL VEVMPQAEKH

GPEIKEHLNS LGEKLKTLRM RLRRCHRFLP CENKSKAVEQ

VKSDFNKLQD QGVYKAMNEF DIFINCIEAY MMIKMKS.

14. An isolated, immunogenic polypeptide comprising 6 to 12 consecutive amino acids from SPGQGTQSEN SCTHFPGNLP N.

15. A pharmaceutical composition comprising the polypeptide of claim 14 and a pharmaceutically acceptable carrier.

16. The pharmaceutical composition of claim 15 which is formulated for parenteral administration.

17. A method of making an antibody by immunizing a non-human animal with the polypeptide of claim 14.

18. An isolated immunogenic polypeptide comprising the consecutive amino acids PDIKAH.

19. A pharmaceutical composition comprising the polypeptide of claim 18 and a pharmaceutically acceptable carrier.

20. The pharmaceutical composition of claim 19 which is formulated for parenteral administration.

21. A method of making an antibody by immunizing a non-human animal with the polypeptide of claim 18.

22. An isolated immunogenic polypeptide comprising the consecutive amino acids TMKIRN.

23. A pharmaceutical composition comprising the polypeptide of claim 22 and a pharmaceutically acceptable carrier.

24. The pharmaceutical composition of claim 23 which is formulated for parenteral administration.

25. A method of making an antibody by immunizing a non-human animal with the polypeptide of claim 22.