IP Library › Granted Patent US 12,404,307
Granted Patent B2
US 12,404,307 · App. 17/686,110 · Granted Sep 2, 2025

Methods and compositions for use of recombinant bacterial effector proteins as anti-inflammatory agents

Inventors: Frank J. Rauscher (Wayne, PA); Peter Mondics (Newtown Square, PA)
Assignees: The Wistar Institute of Anatomy and Biology; Innate Biologics LLC
C07K14/255C07K14/25A61K38/00C07K2319/03C07K2319/30C07K2319/70
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Quick Facts
Patent No.
US 12,404,307
App. No.
17/686,110
Granted
Sep 2, 2025
Kind
B2
Abstract

Provided herein are methods and compositions comprising a set of paired peptides comprising a first bacterial effector polypeptide or fragment thereof linked to a second bacterial effector polypeptide or fragment thereof. The paired peptides can be linked to a protein transduction domain. The compositions can be formulated as pharmaceuticals. The compositions are useful for the treatment of inflammatory disorders.

Claims (14)

1. A composition comprising a set of paired peptides, wherein the set of paired peptides is linked to a protein transduction domain, and wherein the set of paired peptides comprises a first bacterial effector polypeptide linked to a second bacterial effector polypeptide, wherein the protein transduction domain is a YopM protein transduction domain, an SspH1 protein transduction domain, or an 1paH protein transduction domain wherein the protein transduction domain and the set of paired peptides comprise a fusion protein and the amino acid sequence of the fusion protein is at least 85% identical to the sequence set forth in SEQ ID NO. 10, 13, 16, 19, 22, or 24.

2. The composition of claim 1 , wherein the first bacterial effector polypeptide and second bacterial effector polypeptide are different.

3. The composition of claim 1 , wherein a first bacterial effector polypeptide and the second bacterial effector polypeptide are immunomodulatory.

4. The composition of claim 1 , wherein the first bacterial effector polypeptide and the second bacterial effector polypeptide recognize a different molecular target or modulate a different inflammatory pathway.

5. The composition of claim 4 , wherein the inflammatory pathway is the NFKB pathway, the JNK pathway, the p38 pathway or the STING pathway.

6. The composition of claim 1 , wherein a linker is positioned between the first bacterial effector polypeptide and the second bacterial effector polypeptide.

7. The composition of claim 1 , wherein the protein transduction domain is a YopM protein transduction domain.

8. The composition of claim 7 , wherein the protein transduction domain comprises SEQ ID NO. 5.

9. The composition of claim 1 , wherein

(a) the first bacterial effector polypeptide is a YopM polypeptide or an NLeE polypeptide; or

(b) the second bacterial effector polypeptide is a YopM polypeptide or an NLeE polypeptide.

10. The composition of claim 1 , wherein the first bacterial effector polypeptide is a YopM polypeptide and the second bacterial effector polypeptide is an NLeE polypeptide.

11. A fusion protein comprising a set of paired peptides, wherein the set of paired peptides comprises a first bacterial effector polypeptide linked to a second bacterial effector polypeptide wherein the amino acid sequence of the fusion protein is at least 85% identical to the sequence set forth in SEQ ID NO. 10, 13, 16, 19, 22, or 24.

12. A composition comprising a protein transduction domain polypeptide linked to a first bacterial effector polypeptide and at least one additional bacterial effector polypeptides wherein the first bacterial effector polypeptide is a polypeptide having 90% sequence identity to an amino acid sequence set forth in the group consisting of SEQ ID NOs 3, 89, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, and 79 and the at least one additional effector polypeptide is a polypeptide having 90% sequence identity to an amino acid sequence set forth in the group consisting of SEQ ID NOs. 3, 89, 42, 44,46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, and 79.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 23, 2024
From: INNATE BIOLOGICS, INC.
To: THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY
Reel/Frame 069662/0320 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 23, 2024
From: RAUSCHER, FRANK J.
To: THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY
Reel/Frame 069662/0330 →
Continuity (3)
Continuation 16964762
Provisional Application 62622068 · Jan 25, 2018
Related Publication 20220306702A1 · Sep 29, 2022
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