Alpha-galactosidase protein for enzyme replacement therapy (ert) and methods of use
AssigneeThe Medical College of Wisconsin, Inc.
InventorsJeffrey A. Medin, Simone Scalia
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Abstract
The present disclosure provides less immunogenic mutant α-galactosidase A protein (α-gal), methods of making, and methods of use. The less immunogenic mutant α-gal of the present invention provides a reduced immune response when administered to a subject. Methods of treating Fabry in a subject are also provided, the methods comprising administering the disclosed less immunogenic mutant α-gal.
Claims18
A less immunogenic mutant α-galactosidase A protein (α-gal) comprising one or more amino acid changes in one or more antigenic epitopes, wherein the one or more antigenic epitopes are selected from the group consisting of
- (a)
- (SEQ ID NO:
- 2;
- position 45-50 of α-gal),
- LHWERF
- (b)
- (SEQ ID NO:
- 3;
- position 55-64 of α-gal),
- DCQEEPDSCI
- (c)
- (SEQ ID NO:
- 4;
- position 69-79 of α-gal),
- FMEMAELMVSEQ
- (d)
- (SEQ ID NO:
- 5;
- position 82-88 of α-gal),
- KDAGYEY
- (e)
- (SEQ ID NO:
- 6;
- position 92-97 of α-gal),
- DDCWMA
- (f)
- (SEQ ID NO:
- 7;
- position 103-113 of α-gal),
- EGRLQADPQRF
- (g)
- (SEQ ID NO:
- 8;
- position 141-145 of α-gal),
- TCAGF
- (h)
- (SEQ ID NO:
- 9;
- position 153-159 of α-gal),
- DIDAQTF
- (i)
- (SEQ ID NO:
- 10;
- position 165-172 of α-gal),
- DLLKFDGC
- (j)
- (SEQ ID NO:
- 11;
- position 178-182 of α-gal),
- ENLAD
- (k)
- (SEQ ID NO:
- 12;
- position 198-204 of α-gal),
- IVYSCEW
- (l)
- (SEQ ID NO:
- 13;
- position 205-212 of α-gal),
- PLYMWPFQ
- and
- (m)
- (SEQ ID NO:
- 14;
- position 222-226 of α-gal),
- YCNHW
- (n)
- (SEQ ID NO:
- 15;
- position 235-239 of α-gal),
- SWKSI
- (o)
- (SEQ ID NO:
- 16;
- position 243-252 of α-gal),
- LDWTSFNQER
- (p)
- (SEQ ID NO:
- 17;
- position 253-257 of α-gal),
- IVDVA
- (q)
- (SEQ ID NO:
- 18;
- position 263-268 of α-gal),
- NDPDML
- (r)
- (SEQ ID NO:
- 19;
- position 309-313 of α-gal),
- ALLQD
- (s)
- (SEQ ID NO:
- 20;
- position 330-337 of α-gal),
- QLRQGDNF
- (t)
- (SEQ ID NO:
- 21;
- position 338-346 of α-gal),
- EVWERPLSG
- (u)
- (SEQ ID NO:
- 22;
- position 349-355 of α-gal),
- WAVAMIN
- AND
- (v)
- (SEQ ID NO:
- 23;
- position 358-365 of α-gal),
- EIGGPRSY
- wherein the mutant α-gal retains enzymatic function and is less immunogenic than the non-mutated α-gal.
Dependencies are inferred from the claim text.