Back to results
US 9,802,988 B2Granted
Engineered type IV pilin of Clostridium difficile
AssigneeUniversity of Maryland, Baltimore
InventorMichael Donnenberg
Life of this patent
Estimating the term…
Abstract
The present invention relates to engineered Clostridium difficile type IV pilin (tfp) genes, type IV pilin proteins which can serve as a diagnostic marker for identification of patients infected with C. difficile, and vaccines comprising type IV pilin proteins, antigenic fragments and variants thereof for therapeutic interventions.
Claims15
A pharmaceutical composition comprising an isolated polypeptide comprising
- i) a Clostridium difficile type IV pilin or an antigenic fragment or variant thereof, wherein the variant is recognized by an antibody that binds the C. difficile type IV pilin, wherein the isolated C. difficile type IV pilin or antigenic fragment or variant thereof is recombinantly produced, wherein the variant has at least 90% sequence identity to the type IV pilin, wherein the type IV pilin is selected from the group consisting of:
- a. SEQ ID NO:46;
- b. SEQ ID NO:
- 47;
- c. SEQ ID NO:48;
- d. SEQ ID NO:50;
- e. SEQ ID NO:51;
- f. SEQ ID NO:52;
- g. SEQ ID NO:63;
- h. SEQ ID NO:65;
- i. SEQ ID NO:
- 66;
- j. SEQ ID NO:
- 67;
- k. SEQ ID NO:69;
- l. SEQ ID NO:
- 71;
- m. SEQ ID NO:73;
- n. SEQ ID NO:74;
- o. SEQ ID NO:
- 75;
- p. SEQ ID NO:78;
- q. SEQ ID NO:79;
- r. SEQ ID NO:
- 81;
- s. SEQ ID NO:83;
- t. SEQ ID NO:85;
- u. SEQ ID NO:
- 87;
- v. SEQ ID NO:88;
- and
- w. SEQ ID NO:89;
- wherein the antigenic fragment is selected from the group consisting of:
- i. an amino-terminal truncation mutant of the type IV pilin, wherein the number of amino terminal amino acids missing from the fragment ranges from 1-100 amino acids;
- ii. a carboxyl-terminal truncation mutant of the type IV pilin, wherein the number of carboxyl terminal amino acids missing from the fragment ranges from 1-100 amino acids;
- and
- iii. an internal fragment of the type IV pilin lacking both the amino and carboxyl terminal amino acids and being 10-100 amino acid residues in length;
- and
- ii) an affinity tag sequence to facilitate purification.
36 more elements
A pharmaceutical composition for inducing an immune response against Clostridium difficile comprising at least one isolated polypeptide comprising
- i) a C. difficile type IV pilin or an antigenic fragment or variant thereof, wherein the variant is recognized by an antibody that binds the C. difficile type IV pilin, wherein the isolated C. difficile type IV pilin or antigenic fragment or variant thereof is recombinantly produced, wherein the variant has at least 90% sequence identity to the type IV pilin, wherein the type IV pilin is selected from the group consisting of:
- a. SEQ ID NO:46;
- b. SEQ ID NO:
- 47;
- c. SEQ ID NO:48;
- d. SEQ ID NO:50;
- e. SEQ ID NO:51;
- f. SEQ ID NO:52;
- g. SEQ ID NO:53;
- h. SEQ ID NO:
- 54;
- i. SEQ ID NO:55;
- j. SEQ ID NO:56;
- k. SEQ ID NO:
- 57;
- l. SEQ ID NO:58;
- m. SEQ ID NO:59;
- n. SEQ ID NO:
- 60;
- o. SEQ ID NO:63;
- p. SEQ ID NO:65;
- q. SEQ ID NO:
- 66;
- r. SEQ ID NO:67;
- s. SEQ ID NO:69;
- t. SEQ ID NO:
- 71;
- u. SEQ ID NO:73;
- v. SEQ ID NO:74;
- w. SEQ ID NO:
- 75;
- x. SEQ ID NO:78;
- y. SEQ ID NO:79;
- z. SEQ ID NO:
- 81;
- aa. SEQ ID NO:83;
- bb. SEQ ID NO:85;
- cc. SEQ ID NO:
- 87;
- dd. SEQ ID NO:88;
- and
- ee. SEQ ID NO:89;
- wherein the antigenic fragment is selected from the group consisting of:
- i. an amino-terminal truncation mutant of the type IV pilin, wherein the number of amino terminal amino acids missing from the fragment ranges from 1-100 amino acids;
- ii. a carboxyl-terminal truncation mutant of the type IV pilin, wherein the number of carboxyl terminal amino acids missing from the fragment ranges from 1-100 amino acids;
- and
- iii. an internal fragment of the type IV pilin lacking both the amino and carboxyl terminal amino acids and being 10-100 amino acid residues in length;
- ii) an affinity tag sequence to facilitate purification;
- and
- iii) an enzymatic cleavage sequence.
47 more elements
A pharmaceutical composition for inducing an immune response against Clostridium difficile comprising an isolated polypeptide comprising
- i) an antigenic fragment of a C. difficile type IV pilin, wherein the antigenic fragment is recombinantly produced, wherein the antigenic fragment is selected from the group consisting of:
- a. amino acids 35-173 of SEQ ID NO:46;
- b. amino acids 35-173 of SEQ ID NO:47;
- c. amino acids 35-173 of SEQ ID NO:48;
- d. amino acids 31-116 of SEQ ID NO:50;
- e. amino acids 31-116 of SEQ ID NO:51;
- f. amino acids 32-162 of SEQ ID NO:52;
- g. amino acids 31-267 of SEQ ID NO:53;
- h. amino acids 36-272 of SEQ ID NO:54;
- i. amino acids 36-272 of SEQ ID NO:55;
- j. amino acids 36-272 of SEQ ID NO:56;
- k. amino acids 31-267 of SEQ ID NO:57;
- l. amino acids 31-267 of SEQ ID NO:58;
- m. amino acids 31-267 of SEQ ID NO:59;
- n. amino acids 31-267 of SEQ ID NO:60;
- o. amino acids 34-175 of SEQ ID NO:63;
- p. amino acids 34-175 of SEQ ID NO:65;
- q. amino acids 34-175 of SEQ ID NO:66;
- r. amino acids 34-175 of SEQ ID NO:67;
- s. amino acids 34-175 of SEQ ID NO:69;
- t. amino acids 42-188 of SEQ ID NO:71;
- u. amino acids 43-189 of SEQ ID NO:73;
- v. amino acids 42-188 of SEQ ID NO:74;
- w. amino acids 42-188 of SEQ ID NO:75;
- x. amino acids 40-186 of SEQ ID NO:78;
- y. amino acids 40-186 of SEQ ID NO:79;
- z. amino acids 40-186 of SEQ ID NO:81;
- aa. amino acids 32-124 of SEQ ID NO:83;
- bb. amino acids 28-120 of SEQ ID NO:85;
- cc. amino acids 28-120 of SEQ ID NO:87;
- dd. amino acids 33-512 of SEQ ID NO:88;
- and
- ee. amino acids 32-174 of SEQ ID NO:89;
- and
- ii) an affinity tag sequence to facilitate purification.
32 more elements
Dependencies are inferred from the claim text.