Nicotine degrading enzyme variants
AssigneeAntidote Therapeutics, Inc.
InventorsMatthew W. Kalnik, Thomas Thisted, Charles C. Reed
Life of this patent
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Abstract
Described are nicotine-degrading enzyme variants that exhibit increased nicotine-degrading activity and/or decreased immunogenicity relative to the wild-type NicA2 enzyme, compositions comprising the variants, and methods using them.
Claims27
A nicotine-degrading enzyme variant comprising an amino acid sequence that is a variant of the amino acid sequence of the wild-type NicA2 enzyme set forth in SEQ ID NO:
- 1, wherein the variant sequence has at least 90% sequence identity to a sequence selected from (i) SEQ ID NO:
- 1 and (ii) SEQ ID NO:
- 1 having an N-terminal deletion of up to 52 amino acids, and wherein the variant sequence comprises at least one substitution at one or more of positions 104, 106, 107, 249, 355, and 426 of SEQ ID NO:
- 1, provided that the substitution at position 104 is selected from F104R, F104K, F104I, F104S and F104T, the substitution at position 106 is G106A, the substitution at position 107 is A107G, and the substitution at position 355 is selected from F355H, F355K, and F355E.
A nicotine-degrading enzyme variant comprising an amino acid sequence selected from SEQ ID NO:
- 5, SEQ ID NO:
- 6, SEQ ID NO:
- 7, SEQ ID NO:
- 9, SEQ ID NO:
- 10, SEQ ID NO:
- 28, SEQ ID NO:
- 12, SEQ ID NO:
- 16, SEQ ID NO:
- 19, SEQ ID NO:
- 20, SEQ ID NO:
- 21, SEQ ID NO:
- 22, SEQ ID NO:
- 23, SEQ ID NO:
- 24, SEQ ID NO:
- 25, SEQ ID NO:
- 26, and SEQ ID NO:
- 27.
A nicotine-degrading enzyme variant comprising an amino acid sequence that is a variant of the amino acid sequence of the wild-type NicA2 enzyme set forth in SEQ ID NO:
- 1, wherein the variant sequence has at least one substitution selected from the group consisting of F163A, Y214A, Y218A, Y242A, M246A, E249A, F353V, W364V, F353A, F355A, and W364A, and comprises an N-terminal deletion of 1-52 amino acids relative to SEQ ID NO:
- 1.
Dependencies are inferred from the claim text.