Immunogenic composition
AssigneeGloxosmithkline Biologicals, S.A.
InventorCindy Castado
Life of this patent
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Abstract
The present invention relates to fusion proteins comprising fragments from toxin A and/or toxin B of Clostridium difficile, wherein the polypeptide elicits antibodies that neutralize toxin A or toxin B or both.
Claims67
A polypeptide comprising a first fragment and a second fragment, wherein
- (i) the first fragment is a toxin A repeating domain fragment;
- (ii) the second fragment is a toxin B repeating domain fragment;
- (iii) the first fragment has a first proximal end;
- (iv) the second fragment has a second proximal end;
- and
- wherein the first fragment and the second fragment are adjacent to one another and wherein the polypeptide elicits antibodies that neutralize toxin A or toxin B or both.
The polypeptide of any preceding claim wherein the first fragment and/or the second fragment comprise more than 25%, 30%, 35%, 38% or 40% beta sheet structure.
The polypeptide of any preceding claim wherein the first proximal end is within a short repeat.
The polypeptide of any preceding claim wherein the second proximal end is within a short repeat.
The polypeptide of any preceding claim wherein the first proximal end does not disrupt a short repeat-long repeat-short repeat portion.
The polypeptide of any preceding claim wherein the second proximal end does not disrupt a short repeat-long repeat-short repeat portion.
The polypeptide of any preceding claim wherein the first proximal end and the second proximal end do not disrupt short repeat-long repeat-short repeat portions.
The polypeptide of any preceding claim wherein the first proximal end is not within amino acids 1878-1940, 2012-2074, 2146-2208, 2258-2322, 2394-2456, 2507-2569 or 2598-2660 of toxin A.
The polypeptide of any preceding claim wherein the second proximal end is not within amino acids 1881-1942, 2012-2074, 2144-2208 or 2278-2339 of toxin B.
The polypeptide of any preceding claim wherein the first fragment comprises at least 100, 250, 400 or 450 amino acids.
The polypeptide of any preceding claim with the second fragment comprises at least 100, 200, 300 or 400 amino acids.
The polypeptide of any preceding claim wherein the first proximal end is within repeat portion VIII (amino acids 2645-2710) of toxin A.
The polypeptide of any preceding claim wherein the second proximal end is within repeat portion I (amino acids 1834-1926) of toxin B.
The polypeptide of any preceding claim wherein the second proximal end is within amino acids 1860-1878, 1854-1876.
The polypeptide of any preceding claim wherein the polypeptide further comprises a linker.
The polypeptide of any preceding claim wherein the polypeptide is part of a larger fusion protein.
The polypeptide of any preceding claim wherein the polypeptide comprises an immunogenic fragment of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7 SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25 or SEQ ID NO:27.
The polypeptide of any preceding claim wherein the polypeptide comprises an immunogenic fragment of at least 500, 600, 700, 750, 800, 850 or 900 amino acids of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7 SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25 or SEQ ID NO:27.
The polypeptide of any preceding claim wherein the polypeptide comprises a variant of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7 SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25 or SEQ ID NO:27.
The polypeptide of any preceding claim wherein the polypeptide comprises more than 450, 475, 500, 525, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825 or 850 amino acids from toxin A.
The polypeptide of any preceding claim wherein the polypeptide comprises less than 850, 825, 800, 775, 750, 725, 700, 675, 650, 625, or 600 amino acids from toxin A.
The polypeptide of any preceding claim wherein the polypeptide comprises more than 350, 375, 400, 425, 450, 475, 500 or 525 amino acids from toxin B.
The polypeptide of any preceding claim wherein the polypeptide comprises less than 525, 500, 475, or 450 amino acids from toxin B.
A polypeptide comprising:
- (i) SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33 or SEQ ID NO:34 or SEQ ID NO:35;
- (ii) A variant having at least 90%, 95%, 98%, 99% or 100% similarity to SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33 or SEQ ID NO:34 or SEQ ID NO:35;
- or
- (iii) A fragment of at least 250, 280, 300, 350, 380, 400, 430, 450, 480, 500, 530, 550, 580, or 600 amino acids of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33 or SEQ ID NO:34 or SEQ ID NO:35.
Dependencies are inferred from the claim text.