US2022133853A1PendingUtilityA1

Methods and compositions for treating ulcers

74
Assignee: ACCELERON PHARMA INCPriority: Jun 13, 2014Filed: Oct 29, 2021Published: May 5, 2022
Est. expiryJun 13, 2034(~7.9 yrs left)· nominal 20-yr term from priority
Inventors:Kenneth M. Attie
C07K 14/475A61K 38/00A61K 38/179C07K 2319/30A61K 31/17C07K 2319/90A61P 17/02C07K 16/22A61K 31/4196C07K 2319/31C12Y 207/1103C07K 2317/31A61K 38/1793A61K 31/16C07K 2319/32A61K 38/45C07K 2317/52A61K 45/06C07K 19/00A61K 31/4422A61K 47/6811A61K 38/1816C07K 14/71A61P 7/06C07K 2317/76C07K 14/715
74
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Claims

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

exact text as granted — not AI-modified
1 . A method for treating or preventing a cutaneous ulcer in a subject that has chronic anemia, comprising administering to the subject an ActRII antagonist, wherein the polypeptide comprises an amino acid sequence that is at least 85% identical to the sequence of amino acids 29-109 of SEQ ID NO: 1. 
     
     
         2 - 56 . (canceled) 
     
     
         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 at least 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.

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