Polynucleotides encoding novel PCSK9 variants

• US 20100003736A1
• Filed: 06/23/2009
• Published: 01/07/2010
• Est. Priority Date: 06/30/2006
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Chen, Jian, Parker, Rex Arnold, Miao, Bowman, Mintier, Gabriel A., Feder, John N.
• Granted Patent: US 7,846,706 B2
• Time in Patent Office: Days
• US Class Current: 435/188
• 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 16/40 against enzymes
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C12N 9/6424 Serine endopeptidases (3.4.21)
• CPC Class Codes: C12Y 302/01008 Endo-1,4-beta-xylanase (3.2.1.8)
• CPC Class Codes: C12Y 304/21061 Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

The present invention provides novel polynucleotides encoding PCSK9b and PCSK9c polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these novel PCSK9b and PCSK9c polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.

Claims

1-22. -22. (canceled)

23. An isolated polypeptide comprising a sequence selected from the group consisting of:

(a) an isolated polypeptide comprising amino acids 1 to 315 of SEQ ID NO;

2;

(b) an isolated polypeptide comprising amino acids 2 to 315 of SEQ ID NO;

2;

(c) an isolated polypeptide encoded by nucleotides 250 to 1194 of SEQ ID NO;

1; and

(d) an isolated polypeptide encoded by nucleotides 253 to 1194 of SEQ ID NO;

1

24. The isolated polypeptide of claim 23, wherein said polypeptide is (a).

25. The isolated polypeptide of claim 23, wherein said polypeptide is (b).

26. The isolated polypeptide of claim 23, wherein said polypeptide is (c).

27. The isolated polypeptide of claim 23, wherein said polypeptide is (d).

28. An isolated polypeptide produced by a method comprising:

(a) culturing an isolated recombinant host cell comprising a vector that comprises the region encoding the polypeptide of claim 23 under conditions such that the polypeptide of claim 23 is expressed; and

(b) recovering said polypeptide.

29. The isolated polypeptide of claim 23 further comprising a heterologous polypeptide sequence.

30. The isolated polypeptide of claim 29, wherein said heterologous polypeptide is the Fc domain of an immunoglobulin.

31. An isolated polypeptide comprising the polypeptide encoded by the plasmid PCSK9-b in ATCC Deposit No. PTA-7622.

32. An isolated polypeptide consisting of amino acids 10 to 256 of SEQ ID NO:

2, wherein said polypeptide is capable of lowering the level of LDL uptake in mammalian cells in which said polypeptide is recombinately expressed.

33. An isolated polypeptide comprising amino acids 1 to 279 of SEQ ID NO:

2, wherein said polypeptide is capable of lowering the level of LDL uptake in mammalian cells in which said polypeptide is recombinately expressed.

34. An isolated polypeptide comprising amino acids 37 to 315 of SEQ ID NO:

2, wherein said polypeptide is capable of lowering the level of LDL uptake in mammalian cells in which said polypeptide is recombinately expressed.

35. An isolated polypeptide comprising amino acids 2 to 284 of SEQ ID NO:

2, wherein said polypeptide is capable of lowering the level of LDL uptake in mammalian cells in which said polypeptide is recombinately expressed.

36. An isolated polypeptide comprising amino acids 16 to 315 of SEQ ID NO:

2, wherein said polypeptide is capable of lowering the level of LDL uptake in mammalian cells in which said polypeptide is recombinately expressed.