Soluble hybrid Fcγ receptors and related methods

• US 8,658,766 B2
• Filed: 06/29/2009
• Issued: 02/25/2014
• Est. Priority Date: 06/27/2008
• Status: Active Grant

• Current Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company)
• Inventors: Birks, Carl W., Fox, Brian A., Rixon, Mark W., Ellsworth, Jeff L.
• Primary Examiner(s): DAHLE, CHUN WU
• Application Number:
  US12/999,564
• Publication Number:
  US 20110217291A1
• Time in Patent Office: 1,702 Days
• Field of Search: None
• US Class Current: 530/350
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 14/70535 Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)

Abstract

Disclosed are soluble hybrid Fcγ receptor (FcγR) polypeptide compositions and related methods of using such polypeptides to treat IgG-mediated and immune complex-mediated inflammation. Also disclosed are related compositions and methods for producing the soluble hybrid FcγR polypeptides.

Claims

1. An isolated, soluble polypeptide comprising

amino acid residues 36-301 of SEQ ID NO:

40.

2. The polypeptide of claim 1, further comprising a secretory signal sequence.

3. An isolated nucleic acid molecule encoding a polypeptide of claim 1.

4. An isolated nucleic acid molecule encoding a polypeptide of claim 2.

5. The nucleic acid molecule of claim 3, wherein the nucleic acid molecule comprises

nucleotides 106-903 of SEQ ID NO:

39.

6. An expression vector comprising the following operably linked elements:

a) a transcription promoter;

b) a DNA segment encoding a polypeptide as in claim 1; and

c) a transcription terminator.

7. The expression vector of claim 6, wherein the DNA segment comprises

nucleotides 106-903 of SEQ ID NO:

39.

8. The expression vector of claim 6, wherein the expression vector further comprises a secretory signal sequence.

9. The expression vector of claim 8, wherein the secretory signal sequence encodes an amino acid sequence selected from the group consisting of amino acid residues 1-35 of SEQ ID NO:

40, amino acid residues 1-42 of SEQ ID NO;

42, amino acid residues 1-20 of SEQ ID NO;

44, amino acid residues 1-20 of SEQ ID NO;

46, amino acid residues 1-35 of SEQ ID NO;

60, amino acid residues 1-16 of SEQ ID NO;

62, amino acid residues 1-19 of SEQ ID NO;

64, and amino acid residues 1-23 of SEQ ID NO;

66.

10. A cultured cell comprising the expression vector of claim 6, wherein the cell expresses the polypeptide encoded by the DNA segment.

11. A cultured cell comprising the expression vector of claim 6, wherein the cell expresses the polypeptide encoded by the DNA segment, and wherein said polypeptide is secreted from the cell.

12. A method of producing a polypeptide comprising:

culturing a cell into which has been introduced an expression vector of claim 6, wherein the cell expresses the polypeptide encoded by the DNA segment; and

recovering the expressed polypeptide.

13. A composition comprising an isolated polypeptide of claim 1 and a pharmaceutically acceptable vehicle.