Granted Patent
B2
US 12,324,831 · App. 17/930,742 · Granted Jun 10, 2025
Isolated polypeptide of the toxin A and toxin B proteins of
Inventors:
Larry R. Ellingsworth (Rockville, MD); David Flyer (Olney, MD); Jing-Hui Tian (Germantown, MD); Steven R. Fuhrmann (Germantown, MD); Stefanie Kluepfel-Stahl (Bethesda, MD); Gregory M. Glenn (Gaithersburg, MD); Kerstin Westritschnig (Vienna, AT)
A61K39/08C07K14/33C07K16/1282A61K2039/53A61K2039/55505A61K2039/55544A61K2039/575C07K2317/76C07K2319/00C07K2319/40C07K2319/55
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Abstract
This present invention provides C-TAB.G5 and C-TAB.G5.1 isolated polypeptides comprising the receptor binding domains of C. difficile toxin A and toxin B as set forth in the amino acid sequences of SEQ ID NO: 2 and SEQ ID NO: 4. The C-TAB.G5 and C-TAB.G5.1 isolated polypeptides may be used to neutralize toxic effects of C. difficile toxin A and/or toxin B.
Claims (26)
1. A method for producing a recombinant polypeptide derived from Clostridium difficile ( C. difficile ) toxins A and B, the method comprising
i) producing a recombinant nucleic acid encoding said polypeptide,
ii) introducing a recombinant nucleic acid encoding said polypeptide into a host cell, and
iii) culturing the host cell under conditions that allow expression of said polypeptide,
wherein the polypeptide comprises a first C-terminal portion from C. difficile toxin A and a second C-terminal portion from C. difficile toxin B, and
wherein the second C-terminal portion from C. difficile toxin B comprises amino acids 1988-2366 corresponding to SEQ ID NO: 8 and does not comprise amino acids 1834-1967 corresponding to SEQ ID NO: 8.
2. The method of claim 1 , wherein the first C-terminal portion from C. difficile toxin A comprises amino acids 2121-2686 corresponding to SEQ ID NO: 6.
3. The method of claim 1 , wherein the first C-terminal portion from C. difficile toxin A comprises amino acids 2276-2710 corresponding to SEQ ID NO: 6.
4. The method of claim 1 , wherein the first C-terminal portion from C. difficile toxin A comprises amino acids 2276-2686 corresponding to SEQ ID NO: 6.
5. The method of claim 1 , wherein the first C-terminal portion from C. difficile toxin A does not comprise amino acids 2687-2710 corresponding to SEQ ID NO: 6.
6. The method of claim 1 , wherein the polypeptide comprises at least 19 repeating units derived from the C-terminal domain of C. difficile toxin A.
7. The method of claim 1 , wherein the polypeptide comprises fewer than 23 repeating units derived from the C-terminal domain of C. difficile toxin B.
8. The method of claim 1 , wherein the polypeptide is capable of inducing neutralizing antibodies against both C. difficile toxins A and B.
9. The method of claim 1 , wherein the polypeptide is useful for the treatment and/or prevention of C. difficile associated disease (CDAD) or infection.
10. The method of claim 1 , wherein the host cell is Escherichia coli ( E. coli ).
11. A method for producing a pharmaceutical composition comprising a recombinant polypeptide derived from Clostridium difficile ( C. difficile ) toxins A and B, the method comprising combining the recombinant polypeptide and a pharmaceutically acceptable carrier or excipient,
wherein the polypeptide comprises a first C-terminal portion from C. difficile toxin A and a second C-terminal portion from C. difficile toxin B, and
wherein the second C-terminal portion from C. difficile toxin B comprises amino acids 1988-2366 corresponding to SEQ ID NO: 8 and does not comprise amino acids 1834-1967 corresponding to SEQ ID NO: 8.
12. The method of claim 11 , wherein the polypeptide comprises the first C-terminal portion from C. difficile toxin A comprising amino acids 2121-2686 corresponding to SEQ ID NO: 6.
13. The method of claim 11 , wherein the polypeptide comprises the first C-terminal portion from C. difficile toxin A comprising amino acids 2276-2710 corresponding to SEQ ID NO: 6.
14. The method of claim 11 , wherein the polypeptide comprises the first C-terminal portion from C. difficile toxin A comprising amino acids 2276-2686 corresponding to SEQ ID NO: 6.
15. The method of claim 11 , wherein the polypeptide comprising the first C-terminal portion from C. difficile toxin A does not comprise amino acids 2687-2710 corresponding to SEQ ID NO: 6.
16. The method of claim 11 , wherein the polypeptide comprises at least 19 repeating units derived from the C-terminal domain of toxin A of C. difficile.
17. The method of claim 11 , wherein the polypeptide comprises fewer than 23 repeating units of the C-terminal domain of toxin B of C. difficile.
18. The method of claim 11 , wherein the composition is capable of inducing neutralizing antibodies against C. difficile toxins A and B.
19. The method of claim 11 , wherein the composition is useful for the treatment and/or prevention of C. difficile associated disease (CDAD) or infection.
Assignments (7)
AMENDED AND RESTATED PATENT SECURITY AGREEMENT
Recorded Mar 31, 2026
From: VALNEVA AUSTRIA GMBH; VALNEVA SE; VALNEVA SWEDEN AB
To: BIOPHARMA CREDIT PLC, AS COLLATERAL AGENT
Reel/Frame 075335/0609 →
RELEASE OF SECURITY INTEREST
Recorded Nov 10, 2025
From: WILMINGTON TRUST, NATIONAL ASSOCIATION, AS ADMINISTRATIVE AGENT
To: VALNEVA AUSTRIA GMBH; VALNEVA SE; VALNEVA USA, INC.
Reel/Frame 073516/0522 →
PATENT SECURITY AGREEMENT
Recorded Oct 20, 2025
From: VALNEVA AUSTRIA GMBH; VALNEVA SE; VALNEVA SWEDEN AB
To: BIOPHARMA CREDIT PLC, AS COLLATERAL AGENT
Reel/Frame 073164/0032 →
SECURITY INTEREST
Recorded Jan 19, 2024
From: VALNEVA SE; VALNEVA AUSTRIA GMBH; VALNEVA USA, INC.; VALNEVA SWEDEN AB
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 066182/0174 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 31, 2023
From: ELLINGSWORTH, LARRY R.; FLYER, DAVID; TIAN, JING-HUI; FUHRMANN, STEVEN R.; KLUEPFEL-STAHL, STEFANIE; GLENN, GREGORY M.
To: INTERCELL USA, INC.
Reel/Frame 064764/0112 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 31, 2023
From: WESTRITSCHNIG, KERSTIN
To: VALNEVA AUSTRIA GMBH
Reel/Frame 064788/0931 →
CHANGE OF NAME
Recorded Aug 31, 2023
From: INTERCELL USA, INC.
To: VALNEVA USA, INC.
Reel/Frame 064788/0961 →
Continuity (6)
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