DNA encoding OSK1 toxin peptide analogs and vectors and cells for combinant expression

• US 20090305399A1
• Filed: 10/25/2007
• Published: 12/10/2009
• Est. Priority Date: 10/25/2006
• Status: Active Grant

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Nguyen, Hung Q., Miranda, Leslie P., McGivern, Joseph G., Sullivan, John K., Walker, Kenneth W., Hu, Shaw-Fen Sylvia, Gegg, Colin V. JR.
• Granted Patent: US 7,834,164 B2
• Time in Patent Office: Days
• US Class Current: 435/325
• 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: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• 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: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/43522 from scorpions
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/31 fusions, other than Fc, for prolonged plasma life, e.g. albumin

Abstract

Disclosed is a composition of matter comprising an OSK1 peptide analog, and in some embodiments, a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises the composition and a pharmaceutically acceptable carrier. Also disclosed are DNAs encoding the inventive composition of matter, an expression vector comprising the DNA, and host cells comprising the expression vector. Methods of treating an autoimmune disorder and of preventing or mitigating a relapse of a symptom of multiple sclerosis are also disclosed.

Claims

1. A DNA encoding an OSK1 peptide analog comprising an amino acid sequence of the formula:

2. The DNA of claim 1, wherein Xaa¹¹, Xaa²⁷, and Xaa³² are each independently selected from Ser, Thr, Ala, Gly, Leu, Ile, Val, Met, Cit, Homocitrulline, Oic, Pro, Hyp, Tic, D-Tic, D-Pro, Guf, and 4-Amino-Phe, Thz, Aib, Sar, Pip, Bip, Phe, Tyr, Lys, His, Trp, Arg, N^α

Methyl-Arg;

homoarginine, 1-Nal, 2-Nal, Orn, D-Orn, Asn, Gln, Glu, Asp, α

-aminoadipic acid, and para-carboxyl-phenylalanine.

3. The DNA of claim 1, wherein Xaa ¹², Xaa¹⁵, Xaa²⁹, Xaa³⁰, and Xaa³⁴ are each independently selected from Ala, Gly, Leu, Ile, Val, Met, Oic, Pro, Hyp, Tic, D-Tic, D-Pro, Thz, Aib, Sar, Pip, Bip, Phe, Tyr, Ser, Thr, Asn, Gln, Glu, Asp, α

-aminoadipic acid, and para-carboxyl-phenylalanine.

4. The DNA of claim 1, wherein Xaa¹⁶, Xaa¹⁹ and Xaa²⁰ are each independently selected from Lys, His, Arg, Trp, Arg, N^α

Methyl-Arg;

homoarginine, 1-Nal, 2-Nal, Orn, D-Orn, Cit, N^α

-Methyl-Cit, Homocitrulline, His, Ala, Gly, Leu, Ile, Val, Met, Oic, Pro, Hyp, Tic, D-Tic, D-Pro, Thz, Aib, Sar, Pip, Bip, Phe, Ser, Thr, Guf, and 4-Amino-Phe.

5. The DNA of claim 1, wherein Xaa³⁶ and Xaa³⁷, if present, are each independently selected from Pro, Ala, Gly, Leu, Ile, Val, Met, Oic, Hyp, Tic, D-Tic, D-Pro, Thz, N^α

-Methyl-Cit, Homocitrulline, Aib, Sar, Pip, Tyr, Thr, Ser, Phe, Trp, 1-Nal, 2-Nal, and Bip.

6. The DNA of claim 1, wherein Xaa³⁸ is selected from Lys, His, Orn, Trp, D-Orn, Arg, N^α

Methyl-Arg;

homoarginine, Cit, Na-Methyl-Cit, Homocitrulline, His, Guf, and 4-Amino-Phe.

7. The DNA of claim 1, wherein the OSK1 peptide analog comprises one or more additional amino acid residues at its N-terminal or C-terminal, or both.

8. The DNA of claim 7, further comprising a coding sequence of a polypeptide half-life extending moiety operably linked 5′

or 3′

to the coding sequence of the OSK1 peptide analog.

9. The DNA of claim 8, wherein the half-life extending moiety is selected from a human serum albumin protein domain, an albumin-binding protein, a transthyretin protein domain, a thyroxine-binding globulin, a human Fc domain, a CH2 domain of Fc, and a Fc domain loop.

11. An expression vector comprising the DNA of claim 1, claim 8, or claim 10.

12. A host cell comprising the expression vector of claim 11.

13. The host cell of claim 12, wherein the cell is a eukaryotic cell.

14. The host cell of claim 13, wherein the cell is a mammalian cell.

15. The host cell of claim 12, wherein the cell is a prokaryotic cell.

10. A DNA encoding an OSK1 peptide analog that comprises an amino acid sequence selected from SEQ ID NOS:

1391 through 4912, 4916, 4920 through 5006, 5009, 5010, and 5012 through 5015 as set forth in Tables 7A-J, or a pharmaceutically acceptable salt of the OSK1 peptide analog.