Compositions and Methods for Treating Celiac Sprue Disease
OwnerJustin Bloomfield SIEGEL, David BAKER +1inventors
InventorsJustin Bloomfield SIEGEL, David BAKER, Ingrid Swanson PULTZ
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Abstract
The invention provides compositions and methods for treating celiac sprue.
Claims29
A method for treating celiac sprue, comprising administering to a subject with celiac sprue an amount effective to treat the celiac sprue of one or more polypeptides comprising or consisting of the amino acid sequence of a polypeptide selected from the group consisting of SEQ ID NOS:
- 75, 74, 76-89, 95, 97-98, 102-111, or processed versions thereof.
An isolated polypeptide selected from the group consisting of a polypeptide comprising the amino acid sequence selected from the following group, or processed versions thereof:
- (a) SEQ ID NO:
- 95, wherein one, two, three, four, five, six, seven, eight, nine, ten, or all eleven of the following are true:
- (i) AA residue 116 is V or D;
- (ii) AA residue 255 is S, K, or G;
- AA residue 284 is D;
- (iv) AA residue 285 is T;
- (v) AA residue 286 is A, T, or N;
- (vi) AA residue 312 is S;
- (vii) AA residue 347 is N;
- (viii) AA residue 350 is T or A;
- (ix) AA residue 351 is N or G;
- (x) AA residue 354 is D;
- and (xi) AA residue 361 is S or H;
- (b) SEQ ID NO:
- 75, wherein one, two, three, four, five, six, seven, eight, nine, ten, or all eleven of the following are true:
- (i) AA residue 106 is D;
- (ii) AA residue 246 is S, K, or G;
- (iii) AA residue 275 is D;
- (iv) AA residue 276 is S;
- (v) AA residue 277 is A, T, or N;
- (vi) AA residue 303 is S;
- (vii) AA residue 338 is S;
- (viii) AA residue 341 is T or A;
- (ix) AA residue 342 is N or G;
- (x) AA residue 345 is Q or D;
- and (xi) AA residue 352 is S or H;
- (c) SEQ ID NO:
- 76, wherein one, two, three, four, five, six, seven, eight, nine, ten, or all eleven of the following are true:
- (i) AA residue 120 is D;
- (ii) AA residue 259 is S, K, or G;
- (iii) AA residue 288 is D;
- (iv) AA residue 289 is T;
- (v) AA residue 290 is A, T, or N;
- (vi) AA residue 316 is S;
- (vii) Al residue 351 is S or N;
- (viii) AA residue 354 is A;
- (ix) AA residue 355 is N or G;
- (x) AA residue 358 is D;
- and (xi) AA residue 365 is S or H;
- (d) SEQ ID NO:
- 78;
- (e) SEQ ID NO:
- 79, wherein one, two, three, four, five, six, seven, eight, nine, ten, or all eleven of the following are true:
- (i) AA residue 107 is V or D;
- (ii) AA residue 245 is S, K, or G;
- (iii) AA residue 274 is D;
- (iv) AA residue 275 is T;
- (v) AA residue 276 is A, T, or N;
- (vi) AA residue 302 is S;
- (vii) AA residue 337 is S or N;
- (viii) AA residue 340 is T or A;
- (ix) AA residue 341 is N or G;
- (x) AA residue 344 is Q or D;
- and (xi) AA residue 351 is S or H;
- (f) 80, wherein one, two, three, four, five, six, seven, eight, nine, ten, or all eleven of the following are true:
- (i) IA residue 76 is V or D;
- (ii) AA residue 206 is S, K, or G;
- (iii) All residue 235 is D;
- (iv) IA residue 236 is S;
- (v) AA residue 237 is A, T, or N;
- (vi) AA residue 262 is S;
- (vii) AA residue 297 is S or N;
- (viii) AA residue 300 is T or A;
- (ix) AA residue 301 is N or G;
- (x) AA residue 302 is Q or D;
- and (xi) AA residue 309 is S or H;
- (g) SEQ ID NO:
- 81, wherein one, two, three, four, five, six, seven, eight, nine, ten, or all eleven of the following are true:
- (i) AA residue 105 is D;
- (ii) AA residue 244 is S or K;
- (iii) AA residue 272 is D;
- (iv) AA residue 273 is S;
- (v) AA residue 274 is A, T, or N;
- (vi) AA residue 299 is S;
- (vii) AA residue 334 is N;
- (viii) AA residue 337 is T or A;
- (ix) AA residue 338 is N or G;
- (x) AA residue 341 is Q or D;
- and (xi) AA residue 348 is S or H;
- (h) SEQ ID NO:
- 82, wherein one, two, three, four, five, six, seven, eight, nine, ten, or all eleven of the following are true:
- (i) AA residue 106 is V or D;
- (ii) AA residue 244 is S, K, or G;
- (iii) AA residue 273 is D;
- (iv) AA residue 274 is T;
- (v) AA residue 275 is A, T, or N;
- (vi) AA residue 301 is S;
- (vii) AA residue 336 is N;
- (viii) AA residue 339 is T or A;
- (ix) AA residue 340 is N or G;
- (x) AA residue 343 is D;
- and (viii) AA residue 350 is S or H;
- (i) SEQ ID NO:
- 83, wherein one, two, three, four, five, six, seven, eight, nine, ten, or all eleven of the following are true:
- (i) AA residue 107 is V or D;
- (ii) AA residue 245 is S, K, or G;
- (iii) AA residue 274 is D;
- (iv) AA residue 275 is T;
- (v) AA residue 276 is A, T, or N;
- (vi) AA residue 302 is S;
- (vii) AA residue 337 is N;
- (viii) AA residue 340 is T or A;
- (ix) AA residue 341 is N or G;
- (x) AA residue 344 is Q or D;
- and (xi) AA residue 351 is S or H;
- (j) SEQ NO:
- 84, wherein one, two, three, four, five, six, seven, eight, nine, ten, or all eleven of the following are true:
- (i) AA residue 104 is V or D;
- (ii) AA residue 241 is S, K, or G;
- (iii) AA residue 270 is D;
- (iv) AA residue 271 is S;
- (v) AA residue 272 is D, A, T, or N;
- (vi) AA residue 398 is S;
- (vii) AA residue 33 is S;
- (viii) AA residue 336 is A;
- (ix) AA residue 337 is N or G;
- (x) AA residue 340 is D;
- and (xi) AA residue 347 is S or H;
- (k) SEQ ID NO:
- 85, wherein one, two, three, four, five, six, seven, eight, nine, ten, or all eleven of the following are true:
- (i) AA residue 104 is D;
- (ii) AA residue 245 is S, K, or G;
- (iii) AA residue 274 is D;
- (iv) AA residue 275 is S;
- (v) AA residue 276 is A, T, or N;
- (vi) AA residue 302 is S;
- (vii) AA residue 337 is S or N;
- (viii) AA residue 340 is T or A;
- (ix) AA residue 341 is N or G;
- (x) AA residue 344 is Q or D;
- and (xi) AA residue 351 is S or H;
- (l) SEQ ID NO:
- 86, wherein one, Iwo, three, four, five, six, seven, eight, nine, ten, or all eleven of the following are true:
- (i) AA residue 118 is V or D;
- (ii) AA residue 250 is K, or G;
- (iii) AA residue 279 is D;
- (iv) AA residue 280 is S;
- (v) AA residue 281 is A, T, or N;
- (vi) AA residue 307 is S;
- (vii) AA residue 342 is S or N;
- (viii) AA residue 345 is A;
- (ix) AA residue 346 is N or G;
- (x) AA residue 349 is Q or D;
- and (xi) AA residue 356 is S or H;
- (m) SEQ ID NO:
- 87, wherein one, two, three, four, live, six, seven, eight, nine, ten, or all eleven of the following are true:
- (i) AA residue 121 is V or D;
- (ii) AA residue 253 is S, K, or C;
- (iii) AA residue 282 is D;
- (iv) AA residue 283 is S;
- (v) AA residue 284 is A, T, or N;
- (vi) AA residue 310 is S;
- (vii) AA residue 345 is S;
- (viii) AA residue 348 is T or A;
- (ix) AA residue 349 is N or G;
- (x) AA residue 352 is Q or D;
- and (xi) AA residue 357 is S or H;
- (n) SEQ NO:
- 88, wherein one, two, three, four, five, six, seven, eight, nine, or all ten of the following are true:
- (i) AA residue 111 is S, K, or C;
- (ii) AA residue 139 is D;
- (iii) AA residue 140 is T or S;
- (iv) AA residue 141 is D, A, T, or N;
- (v) AA residue 164 is S;
- (vi) AA residue 199 is S or N;
- (vii) AA residue 202 is T or A;
- (viii) AA residue 203 is N or G;
- (ix) AA residue 204 is Q or D;
- and (x) AA residue 211 is S or H;
- and
- (o) SEQ ID NO:89.
A composition, comprising
- (a) one or more polypeptides comprising the amino acid sequence of a polypeptide selected from the group consisting of SEQ ID NOs:
- 74-89, 95, 97-99, and 102-111, or processed versions thereof;
- and
- (b) one or more further polypeptides comprising an amino acid sequence selected from the group consisting of:
- (A) an amino acid sequence at least 75% identical to the arnrno acid sequence of SEQ D NO:35, wherein
- (i) the polypeptide degrades a PQPQLP (SEQ ID NO:34) peptide at pH 4;
- and
- (ii) residue 278 is Ser, residue 78 is Glu, and residue 82 is Asp
- (B) an an amino acid sequence at least 75% identical to the amino acid sequence of SEQ ID NO:1, wherein
- (i) the polypeptide degrades a PQPQLP (SEQ ID NO:34) peptide at pH 4;
- and
- (ii) residue 467 is Ser, residue 267 is Glu, and residue 271 is Asp.
Dependencies are inferred from the claim text.