US2023416323A1PendingUtilityA1
Erythropoietin and analogs for veterinary use

Assignee: KINDRED BIOSCIENCES INCPriority: Jun 6, 2017Filed: May 30, 2023Published: Dec 28, 2023
Est. expiryJun 6, 2037(~10.9 yrs left)· nominal 20-yr term from priority
Inventors:Hangjun Zhan Lam Nguyen Yongzhong Li Qingyi Chu Estela Garcia-Murillo Victoria Leitman Stephen Sundlof Richard Chin Shyr Jiann Li
C07K 14/505A61K 47/60A61K 47/26A61P 7/06A61K 38/00
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References
Claims
Abstract

Provided are various embodiments relating to feline erythropoietin (EPO) polypeptide analogs with one or more additional glycosylation sites and methods of producing and using the same to treat anemia in companion animals. Also provided are various embodiments relating to EPO polypeptides having a mutation in the second binding site, polypeptides comprising an extracellular domain of EPO receptor, and methods of using the same for treating polycythemia in mammals.
Claims

exact text as granted — not AI-modified
1 . An erythropoietin (EPO) polypeptide comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 13 except for the presence of at least one N-linked glycosylation site not present in SEQ ID NO: 2 or SEQ ID NO: 13, wherein the N-linked glycosylation site comprises the sequence asparagine-xaa-serine or asparagine-xaa-threonine, wherein xaa is any amino acid except proline, and wherein one N-linked glycosylation site does not overlap with another N-linked glycosylation site. 
     
     
         2 . The EPO polypeptide of  claim 1 , wherein each of the at least one N-linked glycosylation site is present at:
 a) a position selected from position 47-49, 55-57, 56-58, 60-62, 61-63, 79-81, 82-84, 91-93, 92-94, 97-99, 98-100, 99-101, 112-114, 113-115, 114-116, 115-117, 116-118, 137-139, 140-142, 141-143, 142-144, 143-145, 144-146, 145-147, 146-148, 147-149, 148-150, 149-151, 150-152, 161-163, 162-164, 184-186, and 186-188 of SEQ ID NO: 2; or   b) a position selected from position 21-23, 29-31, 30-32, 34-36, 35-37, 53-55, 56-58, 65-67, 66-68, 71-73, 72-74, 73-75, 86-88, 87-89, 88-90, 89-91, 90-92, 111-113, 114-116, 115-117, 116-118, 117-119, 118-120, 119-121, 120-122, 121-123, 122-124, 123-125, 124-126, 135-137, 136-138, 158-160, and 162-164 of SEQ ID NO: 13.   
     
     
         3 . The EPO polypeptide of  claim 1  comprising valine at a position corresponding to position 113 of SEQ ID NO: 4. 
     
     
         4 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 47 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 48 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 49 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 21 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 22 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 23 of SEQ ID NO: 13. 
 
     
     
         5 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 55 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 56 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 57 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 29 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 30 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 31 of SEQ ID NO: 13. 
 
     
     
         6 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 56 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 57 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 58 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 30 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 31 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 32 of SEQ ID NO: 13. 
 
     
     
         7 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 60 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 61 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 62 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 34 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 35 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 36 of SEQ ID NO: 13. 
 
     
     
         8 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 61 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 62 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 63 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 35 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 36 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 37 of SEQ ID NO: 13. 
 
     
     
         9 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 79 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 80 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 81 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 53 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 54 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 55 of SEQ ID NO: 13. 
 
     
     
         10 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 82 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 83 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 84 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 56 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 57 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 58 of SEQ ID NO: 13. 
 
     
     
         11 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 91 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 92 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 93 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 65 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 66 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 67 of SEQ ID NO: 13. 
 
     
     
         12 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 92 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 93 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 94 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 66 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 67 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 68 of SEQ ID NO: 13. 
 
     
     
         13 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 97 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 98 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 99 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 71 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 92 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 73 of SEQ ID NO: 13. 
 
     
     
         14 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 98 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 99 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 100 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 72 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 73 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 74 of SEQ ID NO: 13. 
 
     
     
         15 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 99 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 100 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 101 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 73 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 74 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 75 of SEQ ID NO: 13. 
 
     
     
         16 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 112 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 113 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 114 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 86 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 87 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 88 of SEQ ID NO: 13. 
 
     
     
         17 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 113 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 114 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 115 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 87 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 88 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 89 of SEQ ID NO: 13. 
 
     
     
         18 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 114 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 115 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 116 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 88 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 89 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 90 of SEQ ID NO: 13. 
 
     
     
         19 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 115 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 116 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 117 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 89 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 90 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 91 of SEQ ID NO: 13. 
 
     
     
         20 . The EPO polypeptide of  claim 1  comprising:
 a) asparagine at a position corresponding to position 115 of SEQ ID NO: 2, any amino acid except proline at a position corresponding to position 116 of SEQ ID NO: 2, and serine or threonine at a position corresponding to position 117 of SEQ ID NO: 2; or 
 b) asparagine at a position corresponding to position 89 of SEQ ID NO: 13, any amino acid except proline at a position corresponding to position 90 of SEQ ID NO: 13, and serine or threonine at a position corresponding to position 91 of SEQ ID NO: 13. 
 
     
     
         21 .- 138 . (canceled)
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