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US 10,870,837 B2Granted
Fusion proteins comprising enzyme replacement therapy enzymes
AssigneeDenali Therapeutics Inc.
InventorsAnastasia Henry, Mihalis Kariolis, Cathal Mahon, Adam P. Silverman, Ankita Srivastava
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Abstract
Provided herein are fusion proteins that comprise an enzyme replacement therapy enzyme and an Fc region, as well as methods of using such proteins to treat a lysosomal storage disorder. Methods for transporting agents across the blood-brain barrier are also provided herein.
Claims47
A protein comprising:
- a. a fusion polypeptide comprising a first Fc polypeptide linked to an iduronate 2-sulfatase (IDS) amino acid sequence, wherein the IDS amino acid sequence comprises a sequence having at least 90% identity to SEQ ID NO:
- 92, and wherein the IDS amino acid sequence is linked to the N-terminus of the first Fc polypeptide;
- and
- b. a second Fc polypeptide comprising a sequence having at least 90% identity to SEQ ID NO:
- 151 that is capable of specifically binding to a transferrin receptor.
2 more elements
A protein comprising:
- a. a fusion polypeptide comprising a first Fc polypeptide linked to an iduronate 2-sulfatase (IDS) amino acid sequence, wherein the fusion polypeptide comprises SEQ ID NO:
- 235;
- and
- b. a second Fc polypeptide comprising a sequence having at least 90% identity to SEQ ID NO:
- 151 and having at the following positions with reference to SEQ ID NO:
- 151:
- i. Trp, Leu, or Glu at position 150;
- ii. Tyr at position 154;
- iii. Thr at position 156;
- iv. Glu at position 157;
- v. Trp at position 158;
- vi. Ser or Ala at position 159;
- vii. Ser or Asn at position 160;
- viii. Thr at position 183;
- ix. Glu at position 185;
- x. Glu at position 186;
- and
- xi. Phe at position 191.
15 more elements
A protein comprising:
- a. a fusion polypeptide comprising a first Fc polypeptide linked to an iduronate 2-sulfatase (IDS) amino acid sequence, wherein the IDS amino acid sequence comprises a sequence having at least 90% identity to SEQ ID NO:
- 92, and wherein the IDS amino acid sequence is linked to the N-terminus of the first Fc polypeptide;
- and
- b. a second Fc polypeptide comprising a sequence having at least 90% identity to SEQ ID NO:
- 151 and having the following eight residues at respective positions with reference to SEQ ID NO:
- 151:
- i. Tyr at position 154;
- ii. Thr at position 156;
- iii. Glu at position 157;
- iv. Trp at position 158;
- v. Thr at position 183;
- vi. Glu at position 185;
- vii. Glu at position 186;
- and
- viii. Phe at position 191.
12 more elements
A protein comprising:
- a. a fusion polypeptide comprising a first Fc polypeptide linked to an iduronate 2-sulfatase (IDS) amino acid sequence, wherein the fusion polypeptide is at least 95% identical to SEQ ID NO:
- 235;
- and
- b. a second Fc polypeptide that is at least 95% identical to SEQ ID NO:
- 116.
2 more elements
A protein comprising:
- a. a fusion polypeptide comprising a first Fc polypeptide linked to an iduronate 2-sulfatase (IDS) amino acid sequence, wherein the fusion polypeptide is at least 95% identical to SEQ ID NO:
- 235;
- and
- b. a second Fc polypeptide that is at least 95% identical to the combination of SEQ ID NO:
- 151 and SEQ ID NO:
- 113, wherein SEQ ID NO:
- 113 is at the N-terminus SEQ ID NO:
- 151.
5 more elements
A protein comprising:
- a. a fusion polypeptide comprising a first Fc polypeptide linked to an iduronate 2-sulfatase (IDS) amino acid sequence, wherein the fusion polypeptide is at least 95% identical to SEQ ID NO:
- 235;
- and
- b. a second Fc polypeptide that is at least 95% identical to SEQ ID NO:
- 228.
2 more elements
A protein comprising:
- a. a fusion polypeptide comprising a first Fc polypeptide linked to an iduronate 2-sulfatase (IDS) amino acid sequence, wherein the fusion polypeptide is at least 95% identical to SEQ ID NO:
- 235;
- and
- b. a second Fc polypeptide that is at least 95% identical to SEQ ID NO:
- 229.
2 more elements
A protein comprising:
- a. a fusion polypeptide comprising a first Fc polypeptide linked to an iduronate 2-sulfatase (IDS) amino acid sequence, wherein the fusion polypeptide is SEQ ID NO:
- 235;
- and
- b. a second Fc polypeptide that is SEQ ID NO:
- 116.
2 more elements
A protein comprising:
- a. a fusion polypeptide comprising a first Fc polypeptide linked to an iduronate 2-sulfatase (IDS) amino acid sequence, wherein the fusion polypeptide is SEQ ID NO:
- 235;
- and
- b. a second Fc polypeptide that is the combination of SEQ ID NO:
- 113 and SEQ ID NO:
- 151, wherein SEQ ID NO:
- 113 is at the N-terminus of SEQ ID NO:
- 151.
5 more elements
A protein comprising:
- a. a fusion polypeptide comprising a first Fc polypeptide linked to an iduronate 2-sulfatase (IDS) amino acid sequence, wherein the fusion polypeptide is SEQ ID NO:
- 235;
- and
- b. a second Fc polypeptide that is SEQ ID NO:
- 228.
2 more elements
A protein comprising:
- a. a fusion polypeptide comprising a first Fc polypeptide linked to an iduronate 2-sulfatase (IDS) amino acid sequence, wherein the fusion polypeptide is SEQ ID NO:
- 235;
- and
- b. a second Fc polypeptide that is SEQ ID NO:
- 229.
2 more elements
Dependencies are inferred from the claim text.