Granted Patent
B2
US 12,409,195 · App. 16/788,458 · Granted Sep 9, 2025
Bacteria engineered to reduce hyperphenylalaninemia
Inventors:
Dean Falb (Sherborn, MA); Vincent M. Isabella (Cambridge, MA); Jonathan W. Kotula (Somerville, MA); Paul F. Miller (Salem, CT); Yves Millet (Newton, MA); Sarah Rowe (Somerville, MA)
Assignee:
Synlogic Operating Company, Inc.
A61K35/74A61K35/741A61K39/02C07K14/195C07K14/245C12N9/0014C12N9/0022C12N9/88C12N15/70C12Y104/03002C12Y403/01024A61K2035/11A61K38/00Y02A50/30
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Abstract
Genetically engineered bacteria, pharmaceutical compositions thereof, and methods of modulating and treating diseases associated with hyperphenylalaninemia are disclosed.
Claims (11)
1. A nucleic acid sequence comprising one or more gene(s) encoding a phenylalanine ammonia lyase (PAL) and one or more gene(s) encoding a phenylalanine transporter,
wherein the PAL is from Anabaena variabilis (PAL1) or Photorhabdus luminescens (PAL3), wherein the one or more genes encoding the PAL is operably linked to an inducible promoter that is not in nature associated with the one or more genes encoding the PAL, wherein the inducible promoter is induced by low oxygen or anaerobic conditions to enable expression of the PAL in an Escherichia probiotic bacterium;
wherein the one or more genes encoding the phenylalanine transporter are from Acinetobacter calcoaceticus, Salmonella enterica , or Escherichia coli ; and wherein the one or more genes encoding the phenylalanine transporter is operably linked to an inducible promoter that is not in nature associated with the one or more genes encoding the phenylalanine transporter, wherein the inducible promoter is induced by low oxygen or anaerobic conditions to enable expression of the phenylalanine transporter in the bacterium.
2. The nucleic acid sequence of claim 1 , wherein the promoter operably linked to the one or more gene(s) encoding the PAL and the promoter operably linked to the one or more gene(s) encoding the phenylalanine transporter are separate copies of the same promoter sequence.
3. The nucleic acid sequence of claim 1 , wherein the promoter operably linked to the one or more gene(s) encoding the PAL and the promoter operably linked to the one or more gene(s) encoding a phenylalanine transporter are different promoters.
4. The nucleic acid sequence of claim 1 , wherein the promoter operably linked to the one or more gene(s) encoding the PAL and the promoter operably linked to the one or more gene(s) encoding the phenylalanine transporter are induced by environmental conditions found in a mammalian gut.
5. The nucleic acid sequence of claim 4 , wherein the promoter is induced by low-oxygen or anaerobic conditions.
6. The nucleic acid sequence of claim 5 , wherein the promoter is selected from the group consisting of an FNR-responsive promoter, an ANR-responsive promoter, and a DNR-responsive promoter.
7. The nucleic acid sequence of claim 1 , wherein the phenylalanine transporter is PheP.
8. The nucleic acid sequence of claim 1 , wherein the one or more gene(s) encoding the PAL and the one or more gene(s) encoding the phenylalanine transporter are located on a chromosome in the bacterium.
9. The nucleic acid sequence of claim 1 , wherein the one or more gene(s) encoding the PAL and the one or more gene(s) encoding the phenylalanine transporter are located on a plasmid in the bacterium.
Assignments (5)
CORRECTIVE ASSIGNMENT TO CORRECT THE NAME OF THE CONVEYING PARTIES TO BE SYNLOGIC, INC. AND MEERKAT MERGER SUB, INC. PREVIOUSLY RECORDED AT REEL: 053503 FRAME: 0856. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT.
Recorded Oct 30, 2020
From: SYNLOGIC, INC.; MEERKAT MERGER SUB, INC.
To: SYNLOGIC OPERATING COMPANY, INC.
Reel/Frame 054257/0645 →
CORRECTIVE ASSIGNMENT TO CORRECT THE NAME OF THE CONVEYING PARTIES TO BE SYNLOGIC, INC. AND MEERKAT MERGER SUB, INC. PREVIOUSLY RECORDED ON REEL 053503 FRAME 856. ASSIGNOR(S) HEREBY CONFIRMS THE MERGER AND NAME CHANGE.
Recorded Oct 23, 2020
From: SYNLOGIC, INC.; MEERKAT MERGER SUB, INC.
To: SYNLOGIC OPERATING COMPANY, INC.
Reel/Frame 054404/0495 →
CORRECTIVE ASSIGNMENT TO CORRECT THE ENTIRE ASSIGNMENT DOCUMENT NEEDS TO BE REPLACED WITH CORRECT ASSIGNMENT DOCUMENT PREVIOUSLY RECORDED ON REEL 053503 FRAME 0701. ASSIGNOR(S) HEREBY CONFIRMS THE ENTIRE ASSIGNMENT DOCUMENT.
Recorded Sep 4, 2020
From: FALB, DEAN; ISABELLA, VINCENT M.; KOTULA, JONATHAN W.; MILLER, PAUL F.; MILLET, YVES; ROWE, SARAH
To: SYNLOGIC, INC.
Reel/Frame 054147/0818 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 14, 2020
From: FALB, DEAN; ISABELLA, VINCENT M.; KOTULA, JONATHAN W.; MILLER, PAUL F.; ROWE, SARAH; MILLET, YVES
To: SYNLOGIC, INC.
Reel/Frame 053503/0701 →
MERGER AND CHANGE OF NAME
Recorded Aug 14, 2020
From: SYNLOGIC, INC.; MEERKAT MERGER SUB, INC.; SYNLOGIC OPERATING COMPANY, INC.
To: SYNLOGIC OPERATING COMPANY, INC.
Reel/Frame 053503/0856 →
Continuity (4)
Provisional Application
62256052
· Nov 16, 2015
Provisional Application
62161137
· May 13, 2015
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