Combined use of GDF traps and erythropoietin receptor activators to increase red blood cell levels

• US 10,689,427 B2
• Filed: 10/11/2018
• Issued: 06/23/2020
• 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:
  US16/157,261
• Publication Number:
  US 20190263876A1
• Time in Patent Office: 621 Days
• 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 treating a hypoproliferative anemia in a subject in need thereof;

comprising administering to the subject a polypeptide comprising an amino acid sequence that is at least 90% identical to the sequence of amino acids 29-109 of SEQ ID NO;

1, wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO;

1, wherein the polypeptide binds to GDF11 and/or myostatin; and

wherein the hypoproliferative anemia is an anemia associated with a hypometabolic state.

2. The method of claim 1, wherein the hypometabolic state is selected from the group consisting of:

Addison'"'"'s disease, hypothyroidism, hyperparathyroidism, male castration, and reduced dietary intake of protein.

3. The method of claim 1, wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to the sequence of amino acids 29-109 of SEQ ID NO:

1.

4. The method of claim 1, wherein the acidic amino acid is glutamic acid.

5. The method of claim 1, wherein the acidic amino acid is aspartic acid.

6. The method of claim 1, wherein the polypeptide binds to GDF11.

7. The method of claim 1, wherein the polypeptide binds to myostatin.

8. The method of claim 1, wherein the polypeptide further comprises a constant region of an immunoglobulin.

9. The method of claim 8, wherein the constant region is derived from an IgG heavy chain.

10. The method of claim 8, wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to SEQ ID NO:

28.

11. The method of claim 8, wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to SEQ ID NO:

28.

12. The method of claim 8, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:

28.

13. A method for treating an acute post-hemorrhagic anemia in a subject in need thereof;

comprising administering to the subject a polypeptide comprising an amino acid sequence that is at least 90% identical to the sequence of amino acids 29-109 of SEQ ID NO;

1, wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO;

1, wherein the polypeptide binds to GDF11 and/or myostatin.

14. The method of claim 13, wherein the acute post-hemorrhagic anemia results from trauma or postpartum hemorrhage.

15. A method for treating a hypoproliferative anemia in a subject in need thereof;

comprising administering to the subject a polypeptide comprising an amino acid sequence that is at least 90% identical to the sequence of amino acids 29-109 of SEQ ID NO;

1, wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO;

1, wherein the polypeptide binds to GDF11 and/or myostatin; and

wherein the hypoproliferative anemia is a chronic iron-deficiency anemia.

16. The method of claim 15, wherein the disordered red blood cell maturation is associated with the formation of undersized (microcytic), oversized (macrocytic), misshapen, or abnormally colored (hypochromic) red blood cells.

17. A method for treating an anemia associated with disordered red blood cell maturation in a subject in need thereof;

comprising administering to the subject a polypeptide comprising an amino acid sequence that is at least 90% identical to the sequence of amino acids 29-109 of SEQ ID NO;

1, wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO;

1, wherein the polypeptide binds to GDF11 and/or myostatin.