E. coli fimh mutants and uses thereof
AssigneePfizer Inc.
InventorsYe Che, Laurent Oliver Chorro, Robert George Konrad Donald, Matthew Curtis Griffor, Natalie Clare Silmon de Monerri
Life of this patent
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Abstract
This disclosure relates to the design of E. coli mutated FimH polypeptides that result in improved biochemical properties and immunogenicity, compositions comprising such polypeptides, and uses thereof.
Claims22
1-10. (canceled)
A nucleic acid molecule comprising a nucleotide sequence that encodes an amino acid sequence of a mutated FimH polypeptide, wherein the mutated FimH polypeptide comprises an amino acid substitution relative to the amino acid sequence of the wild-type FimH polypeptide, wherein the substitution is selected from the group consisting of:
- F1I;
- F1V;
- F1M;
- F1Y;
- F1W;
- P12C;
- G14C;
- G15A;
- G15P;
- G16A;
- G16P;
- A18C;
- P26C;
- V28C;
- Q32C;
- N33C;
- L34N;
- L34S;
- L34T;
- L34D;
- L34E;
- L34K;
- L34R;
- V35C;
- S62C;
- Y64C;
- G65A;
- L68C;
- F71C;
- T86C;
- L107C;
- Y108C;
- L109C;
- V112C;
- S113C;
- A115V;
- G116C;
- V118C;
- A119C;
- A119N;
- A119S;
- A119D;
- A119E;
- A119K;
- A119R;
- A127C;
- L129C;
- F144C;
- V154C;
- V155C;
- V156C;
- T158C;
- and V185I, and wherein the amino acid positions are numbered according to SEQ ID NO:
- 59.
12-23. (canceled)
A nucleic acid molecule comprising a nucleotide sequence that encodes an amino acid sequence of a mutated FimH polypeptide, wherein the mutated FimH polypeptide comprises an amino acid substitution relative to the amino acid sequence of the wild-type FimH polypeptide, wherein the substitution is selected from the group consisting of:
- a) G15A and G16A;
- b) P12C and A18C;
- c) G14C and F144C;
- d) P26C and V35C;
- e) P26C and V154C;
- f) P26C and V156C;
- g) V27A and Q133K;
- h) V28C and N33C;
- i) V28C and P157C;
- j) Q32C and Y108C;
- k) N33C and L109C;
- I) N33C and P157C;
- m) V35C and L107C;
- n) V35C and L109C;
- o) S62C and T86C;
- p) S62C and L129C;
- q) Y64C and L68C;
- r) Y64C and A127C;
- s) L68C and F71C;
- t) V112C and T158C;
- u) S113C and G116C;
- v) S113C and T158C;
- w) V118C and V156C;
- x) A119C and V155C;
- y) L34N and V27A;
- z) L34S and V27A;
- aa) L34T and V27A;
- ab) L34D and V27A;
- ac) L34E and V27A;
- ad) L34K and V27A;
- ae) L34R and V27A;
- af) A119N and V27A;
- ag) A119S and V27A;
- ah) A119T and V27A;
- ai) A119D and V27A;
- aj) A119E and V27A;
- ak) A119K and V27A;
- al) A119R and V27A;
- am) G15A and V27A;
- an) G16A and V27A;
- ao) G15P and V27A;
- ap) G16P and V27A;
- aq) G15A, G16A, and V27A;
- ar) G65A and V27A;
- and
- as) G15A, G16A, V27A, and Q133K, and wherein the amino acid positions are numbered according to SEQ ID NO:
- 59.
A nucleic acid molecule comprising a nucleotide sequence that encodes an amino acid sequence of a mutated FimH polypeptide, wherein the mutated FimH polypeptide comprises the following amino acid substitutions relative to the amino acid sequence of the wild-type FimH polypeptide:
- G15A, G16A, and V27A, and wherein the amino acid positions are numbered according to SEQ ID NO:
- 59.
Dependencies are inferred from the claim text.