IP Library › Granted Patent US 12,377,136
Granted Patent B2
US 12,377,136 · App. 17/813,984 · Granted Aug 5, 2025

Polynucleotides encoding porphobilinogen deaminase for the treatment of acute intermittent porphyria

Inventors: Paolo Martini (Boston, MA); Stephen Hoge (Brookline, MA); Kerry Benenato (Sudbury, MA); Vladimir Presnyak (Manchester, NH); Lei Jiang (Cambridge, MA); Iain McFadyen (Arlington, MA); Ellalahewage Sathyajith Kumarasinghe (Harvard, MA); Antonio Fontanellas Roma (Pamplona, ES); Pedro Berraondo Lopez (Pamplona, ES); Matias Antonio Avila Zaragoza (Pamplona, ES); Lin Tung Guey (Lexington, MA); Staci Sabnis (Medford, MA)
Assignees: ModernaTX, Inc.; Fundacion Para La Investigacion Medica Aplicada
A61K38/45A61K48/0033A61K48/005A61P7/08C12N9/1085C12N15/88C12Y205/01061
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Quick Facts
Patent No.
US 12,377,136
App. No.
17/813,984
Granted
Aug 5, 2025
Kind
B2
Abstract

The invention relates to mRNA therapy for the treatment of Acute Intermittent Porphyria (AIP). mRNAs for use in the invention, when administered in vivo, encode human porphobilinogen deaminase (PBGD), isoforms thereof, functional fragments thereof, and fusion proteins comprising PBGD. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to affect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of PBGD expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient PBGD activity in subjects, namely porphobilinogen and aminolevulinate (PBG and ALA).

Claims (11)

1. A method of treating an acute Porphyria attack in a human subject in need thereof, the method comprising administering to the human subject a lipid nanoparticle comprising a therapeutically effective amount of a messenger RNA (mRNA) encoding a porphobilinogen deaminase (PBGD) polypeptide, wherein the mRNA comprises an open reading frame comprising the nucleotide sequence set forth in SEQ ID NO: 102 or SEQ ID NO: 104, and wherein the human subject has acute intermittent Porphyria.

2. The method of claim 1 , wherein the mRNA comprises at least one chemically modified nucleobase.

3. The method of claim 2 , wherein the at least one chemically modified nucleobase is selected from the group consisting of pseudouracil, N1-methylpseudouracil, 1-ethylpseudouracil, 2-thiouracil, 4′-thiouracil, 5-methylcytosine, 5-methyluracil, 5-methoxyuracil, and any combination thereof.

4. The method of claim 3 , wherein the at least one chemically modified nucleobase is 5-methoxyuracil.

5. The method of claim 4 , wherein at least 95% of uracil in the mRNA is 5-methoxyuracil.

6. The method of claim 4 , wherein 100% of uracil in the mRNA is 5-methoxyuracil.

7. The method of claim 3 , wherein the at least one chemically modified nucleobase is N1-methylpseudouracil.

8. The method of claim 1 , wherein the lipid nanoparticle is administered intravenously.

9. The method of claim 1 , wherein the lipid nanoparticle is administered to the human subject about once every two weeks.

10. The method of claim 1 , wherein the open reading frame comprises the nucleotide sequence set forth in SEQ ID NO: 102.

11. The method of claim 1 , wherein the open reading frame comprises the nucleotide sequence set forth in SEQ ID NO: 104.

Assignments (3)
SECURITY INTEREST Recorded Nov 19, 2025
From: MODERNATX, INC.
To: ARES CAPITAL CORPORATION, AS AGENT
Reel/Frame 073634/0354 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 26, 2022
From: MARTINI, PAOLO; HOGE, STEPHEN; BENENATO, KERRY; PRESNYAK, VLADIMIR; JIANG, LEI; MCFADYEN, IAIN; KUMARASINGHE, ELLALAHEWAGE SATHYAJITH; GUEY, LIN TUNG; SABNIS, STACI
To: MODERNATX, INC.
Reel/Frame 060629/0699 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 26, 2022
From: FONTANELLAS ROMA, ANTONIO; BERRAONDO LOPEZ, PEDRO; AVILA ZARAGOZA, MATIAS ANTONIO
To: FUNDACION PARA LA INVESTIGACION MEDICA APLICADA
Reel/Frame 060629/0750 →
Priority Claims (1)
EP 17382259 · May 9, 2017 · regional
Continuity (2)
Continuation 16302339
Related Publication 20230112986A1 · Apr 13, 2023
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