METHODS AND COMPOSITIONS FOR TREATING ULCERS

• US 20180194834A1
• Filed: 11/21/2017
• Published: 07/12/2018
• Est. Priority Date: 06/13/2014
• Status: Active Grant

• Current Assignee: Acceleron Pharma Inc. (Merck & Co., Inc.)
• Original Assignee: Acceleron Pharma Inc. (Merck & Co., Inc.)
• Inventors: Attie, Kenneth M.
• Granted Patent: US 10,487,144 B2
• Time in Patent Office: 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 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• 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 38/179 for growth factors; for growth regulators
• CPC Class Codes: A61K 38/1793 for cytokines; for lymphokines; for interferons
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 38/45 Transferases (2)
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07K 14/475 Growth factors; Growth regulators
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• CPC Class Codes: C07K 14/715 for cytokines; for lymphokines; for interferons
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 19/00 Hybrid peptides , i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/52 : Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• 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
• CPC Class Codes: C07K 2319/32 : fusions with soluble part of a cell surface receptor, "decoy receptors"
• CPC Class Codes: C07K 2319/90 : containing a motif for post-translational modification
• CPC Class Codes: C12Y 207/1103 : Receptor protein serine/threonine kinase (2.7.11.30)

Abstract

The present disclosure provides compositions and methods for treating or preventing ulcers in subjects having low red blood cell levels and/or hemoglobin levels (e.g, anemia). In some embodiments, the compositions of the disclosure may be used to treat or prevent ulcers associated with anemia.

Claims

1. A method for treating a cutaneous ulcer in a subject that has a hemoglobinopathy anemia, comprising administering to the subject an ActRIIB antagonist.

57. The method of claim 1, wherein the polypeptide comprises 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.

58. The method of claim 1, wherein the polypeptide is a fusion protein further comprising an immunoglobulin Fc domain.

59. The method of claim 58, wherein the fusion protein further comprises a linker domain positioned between the polypeptide and the immunoglobulin Fc domain.

60. The method of claim 1, wherein the polypeptide comprises one or more amino acid modifications selected from:

a glycosylated amino acid, a PEGylated amino acid, a farnesylated amino acid, an acetylated amino acid, a biotinylated amino acid, and an amino acid conjugated to a lipid moiety.

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

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

1.

62. The method of claim 1, wherein the polypeptide comprises amino acids 29-109 of SEQ ID NO:

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

1.

63. The method of claim 1, wherein the polypeptide comprises an amino acid sequence that is at least 85% identical to the sequence of amino acids 25-131 of SEQ ID NO:

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

1.

64. The method of claim 1, wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to the sequence of amino acids 25-131 of SEQ ID NO:

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

1.

65. 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 25-131 of SEQ ID NO:

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

1.

66. The method of claim 1, wherein the polypeptide comprises amino acids 25-131 of SEQ ID NO:

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

1.

67. The method of claim 1, wherein the polypeptide comprises an amino acid sequence that is at least 85% identical to SEQ ID NO:

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

1.

68. The method of claim 1, wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to SEQ ID NO:

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

1.

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

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

1.

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

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

1.

71. The method of claim 1, wherein the polypeptide inhibits signaling by GDF8 in a cell-based assay.

72. The method of claim 1, wherein the polypeptide inhibits signaling by GDF11 in a cell-based assay.

73. The method of claim 1, wherein the amino acid at the position corresponding to position 79 of SEQ ID NO:

1 is an aspartic acid.

74. The method of claim 1, wherein the amino acid at the position corresponding to position 79 of SEQ ID NO:

1 is a glutamic acid.

75. The method of claim 1, wherein the polypeptide binds GDF8.

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

2-56. -56. (canceled)