Methods and compositions for the prevention and treatment of anemia
First Claim
1. An analog of human erythropoietin comprising the amino acid sequence of human erythropoietin from residues 1-165 as shown in SEQ ID NO:
- 1 except for one or more amino acid changes which provide for one or more additional glycosylation site(s) as compared to human erythropoietin, wherein one additional site is introduced at position 52, 53, 55, 86 or 114 and an N-linked carbohydrate chain is attached at said one additional site.
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Abstract
Methods for increasing and maintaining hematocrit in a mammal comprising administering a hyperglycosylated analog of erythropoietin are disclosed. An analog may be administered less frequently than an equivalent molar amount of recombinant human erythropoietin to obtain a comparable target hematocrit and treat anemia. Alternatively, a lower molar amount of a hyperglycosylated analog may be administered to obtain a comparable target hematocrit and treat anemia. Also disclosed are new hyperglycosylated erythopoietin analogs, methods of production of the analogs, and compositions comprising the analogs.
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Citations
21 Claims
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1. An analog of human erythropoietin comprising the amino acid sequence of human erythropoietin from residues 1-165 as shown in SEQ ID NO:
- 1 except for one or more amino acid changes which provide for one or more additional glycosylation site(s) as compared to human erythropoietin, wherein one additional site is introduced at position 52, 53, 55, 86 or 114 and an N-linked carbohydrate chain is attached at said one additional site.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
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10. An analog of human erythropoietin comprising the amino acid sequence from residues 1-165 as shown in SEQ ID NO:
- 1 except for Asn at position 30, Thr at position 32, Asn at position 55, Thr at position 57, Val at position 87, Asn at position 88, Thr at position 90, Asn at position 114, Thr at position 116, and any one or more of Pro at position 124, Thr at position 125 and/or Thr at position 126.
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11. An analog of human erythropoietin comprising the amino acid sequence from residues 1-165 as shown in SEQ ID NO:
- 1 except for the amino acid changes selected from the group consisting of;
Asn52 Thr54 Epo; Asn53 Thr55 Epo; Asn30 Thr32 Val87 Asn88 Thr90 Thr125 Epo; Asn114 Thr116 Epo; Asn30 Thr32 Asn53 Thr55 Val87 Asn88Thr90 Epo; Asn55 Thr57 Epo; Asn86 Val87 Thr88 Epo; Ala87 Asn88 Thr90 Epo; Val87 Asn88 Ser90 Epo; Val87 Asn88 Gly89 Thr90 Epo; Asn30 Thr32 Asn53 Thr55 Epo; Asn30 Thr32 Asn114 Thr116 Epo; Asn30 Thr32 Asn53 Thr55 Val87 Asn88 Thr90 Asn114 Thr116 Epo; Asn30 Thr32 Asn55 Thr57 Epo; Asn30 Thr32 Asn55 Thr57 Val87 Asn88 Thr90 Epo; Asn30 Thr32 Asn55 Thr57 Asn114 Thr116 Epo; Asn30 Thr32 Val87 Asn88 Thr90 Asn114 Thr116 Epo; Asn30 Thr32 Asn55 Thr57 Val87 Asn88 Thr90 Asn114 Thr116 Epo; Asn30 Thr32 Asn55 Thr57 Val87 Asn88 Thr90 Pro124 Thr125 Thr126 Epo; Asn30 Thr32 Asn55 Thr57 Asn114 Thr116 Pro124 Thr125 Thr126 Epo; and Asn30 Thr32 Asn55 Thr57 Val87 Asn88 Thr90 Asn114 Thr116 Pro124 Thr125 Thr126 Epo.
- 1 except for the amino acid changes selected from the group consisting of;
Specification