Vhh polypeptides that bind to clostridium difficile toxin b and methods of use thereof
AssigneeTrustees of Tufts College
InventorCharles B. SHOEMAKER
Life of this patent
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Abstract
Polypeptide products, methods, pharmaceutical compositions, and kits are provided for treating a subject exposed to, or at risk for exposure to, C. difficile microbial pathogens and toxin B produced by C. difficile (TcdB) pathogens. The methods, compositions and kits include a single domain, anti-TcdB VHH polypeptide (antibody), or toxin B binding portion thereof, that specifically binds to and/or neutralizes TcdB and treats or prevents illness and disease associated with C. difficile infection and TcdB intoxication. The anti-TcdB VHHs, or toxin B binding portion thereof, may be recombinantly produced.
Claims21
-104. (canceled)
A polypeptide that specifically binds to C. difficile toxin B (TcdB), or a TcdB-binding portion thereof, wherein the polypeptide comprises three complementarity determining regions (CDRs), CDR1, CDR2 and CDR3, and four VHH framework regions (FRs), FR1, FR2, FR3 and FR4, with the general structure FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4,
- wherein CDR1 comprises amino acids X1-X8, wherein X1 is G or E, or a conservative amino acid substitution thereof;
- X2 is R or A, or a conservative amino acid substitution thereof;
- X3 is G or N, or a conservative amino acid substitution thereof;
- X4 is P or L, or a conservative amino acid substitution thereof;
- X5 is G, or a conservative amino acid substitution thereof;
- X6 is I, or a conservative amino acid substitution thereof;
- X7 is N, or a conservative amino acid substitution thereof;
- and X8 is V or A, or a conservative amino acid substitution thereof;
- wherein CDR2 comprises amino acids X1-X7, wherein X1 is Q, or a conservative amino acid substitution thereof;
- X2 is T, or a conservative amino acid substitution thereof;
- X3 is G, or a conservative amino acid substitution thereof;
- X4 is G, or a conservative amino acid substitution thereof;
- X5 is T, R, or S, or a conservative amino acid substitution thereof;
- X6 is T or L, or a conservative amino acid substitution thereof;
- and X7is N or S, or a conservative amino acid substitution thereof;
- and
- wherein CDR3 comprises amino acids X1-X9, wherein X1 is Y, or a conservative amino acid substitution thereof;
- X2 is L or Q, or a conservative amino acid substitution thereof;
- X3 is K, or a conservative amino acid substitution thereof;
- X4 is K or R, or a conservative amino acid substitution thereof;
- X5 is W, or a conservative amino acid substitution thereof;
- X6 is R, or a conservative amino acid substitution thereof;
- X7 is D or N, or a conservative amino acid substitution thereof;
- X8 is E, Q, D, or R, or a conservative amino acid substitution thereof;
- and X9 is Y, or a conservative amino acid substitution thereof;
- wherein the conservative amino acid substitution constitutes a substitute or replacement amino acid residue having similar or identical charge, hydrophobicity, and/or size.
Dependencies are inferred from the claim text.