Isolated nucleotide sequences encoding GDF traps

• US 9,932,379 B2
• Filed: 07/27/2016
• Issued: 04/03/2018
• Est. Priority Date: 08/14/2008
• Status: Active Grant

• Current Assignee: Acceleron Pharma Inc. (Merck & Co., Inc.)
• Original Assignee: Acceleron Pharma Inc. (Merck & Co., Inc.)
• Inventors: Seehra, Jasbir, Pearsall, Robert Scott, Kumar, Ravindra
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US15/221,341
• Publication Number:
  US 20160326228A1
• Time in Patent Office: 615 Days
• Field of Search: 536 235
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/179 for growth factors; for growth regulators
• CPC Class Codes: A61K 38/1796 for hormones for neuromediators A61K38/1787
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 39/39533 against materials from animals
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07K 14/475 Growth factors; Growth regulators
• CPC Class Codes: C07K 14/495 Transforming growth factor [TGF]
• CPC Class Codes: C07K 14/505 Erythropoietin [EPO]
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• 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

Abstract

In certain aspects, the present invention provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.

Claims

1. A method for producing a variant ActRIIB polypeptide, comprising:

a) culturing a cell under conditions suitable for expression of the polypeptide, and

b) recovering the polypeptide expressed by the cell;

wherein the cell comprises a nucleic acid;

wherein the nucleic acid comprises a nucleic acid sequence that hybridizes to the complement of nucleotides 76-396 of SEQ ID NO;

30 in the presence of 6.0×

sodium chloride/sodium citrate (SSC) at 45°

C. followed by a wash in 0.2×

SSC at 65°

C., wherein the nucleic acid sequence encodes a polypeptide that comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO;

1.

2. The method of claim 1, wherein the nucleic acid hybridizes to the complement of the nucleotide sequence of SEQ ID NO:

30 in the presence of 6.0×

sodium chloride/sodium citrate (SSC) at 45°

C. followed by a wash in 0.2×

SSC at 65°

C.

3. The method of claim 1, wherein the nucleic acid comprises nucleotides 76-396 of SEQ ID NO:

30.

4. The method of claim 1, wherein the nucleic acid comprises the nucleotide sequence of SEQ ID NO:

30.

5. The method of claim 1, wherein the nucleic acid comprises a nucleotide sequence encoding a polypeptide comprising amino acids 26-132 of SEQ ID NO:

26.

6. The method of claim 1, wherein the nucleic acid comprises a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:

26.

7. The method of claim 1, wherein the nucleic acid further comprises a nucleotide sequence encoding a tissue plasminogen activator (TPA) leader sequence.

8. The method of claim 1, wherein the nucleic acid is operably linked to one or more regulatory sequences.

9. The method of claim 1, wherein the variant polypeptide comprises the amino acid sequence of SEQ ID NO:

28.

10. The method of claim 1, wherein the cell is a mammalian cell.

11. The method of claim 1, wherein the cell is a CHO cell.

12. The method of claim 1, wherein the variant polypeptide comprises an amino acid sequence consisting of SEQ ID NO:

28.