Method for treating C. acnes bacteria-associated diseases

Patent metadata

Field	Value
Publication number	US-12414962-B2
Application number	US-202418782965-A
Country	US
Kind code	B2
Filing date	Jul 24, 2024
Priority date	Jul 24, 2023
Publication date	Sep 16, 2025
Grant date	Sep 16, 2025

Abstract

The present invention concerns a method for treating or preventing a Cutibacterium acnes bacteria-associated disease in a subject, said method comprising modulating, in particular reducing, in said subject, the ratio of the amount of C. acnes bacteria of a newly identified category called α-type to the amount of C. acnes bacteria of newly identified category called β-type, the α-type category efficiently defining acne-associated strains and the β-type defining non acne-associated strains.

First claim

I claim:

1. A method for treating a Cutibacterium acnes bacteria-associated disease in a subject, said method comprising reducing the ratio of the amount of α-type C. acnes bacteria to the amount of β-type C. acnes bacteria in the subject by administering to the subject a nucleic acid encoding a programmable nuclease, prime editor, or base editor designed to specifically target said α-type C. acnes bacteria at a nucleotide selected from one
of the following nucleotide variants in the hem locus:
in the hemA gene: T173, A479, T506, A614, T629, C671, T971, A989, T1085, and T1094, wherein the positions are defined with reference to sequence SEQ ID NO: 3 and wherein the first nucleotide in the sequence is indexed as 0,
in the hemB gene: C142, A155, A176, A183, C224, C245, G248, T281, G311, C314, T346, C374, G377, C452, T626, C683, A693, A720, C738, C794, A920, T944, T992, G1022, and T1031, wherein the positions are defined with reference to sequence SEQ ID NO: 4 and wherein the first nucleotide in the sequence is indexed as 0,
in the hemC gene: G77, A96, C149, A233, T236, T255, A257, A260, C317, A347, T425, T437, A464, A486, A487, C488, A524, A545, A590, T605, A644, A665, C710, C713, A737, A770, A776, T785, T802, G830, C842, T845, G855, C893, A896, C897, G902, G908, A941, and A947, wherein the positions are defined with reference to sequence SEQ ID NO: 5 and wherein the first nucleotide in the sequence is indexed as 0,
in the hemD gene: T11, T41, T50, A150, T155, G159, G176, T257, C266, T278, G323, A324, T362, T367, T374, G387, A398, A399, T407, G422, G425, G432, A446, A459, T464, G595, T617, T643, A644, and C680, wherein the positions are defined with reference to sequence SEQ ID NO: 6 and wherein the first nucleotide in the sequence is indexed as 0,
in the hemE gene: T241, T476, A530, T704, A728, G767, T834, A867, A872, A882, and A957, wherein the positions are defined with reference to sequence SEQ ID NO: 7 and wherein the first nucleotide in the sequence is indexed as 0,
in the hemH gene: T11, T23, A48, T89, C188, G338, T464, T470, G536, T548, T608, G626, T632, T641, T671, T674, C683, C689, A740, G745, G787, A797, T893, A898, T1034, T1039, T1046, C1071, G1095, C1109, T1153, T1358, G1496, C1511, C1527, G1532, T1598, T1712, A1850, G1901, A1926, C1931, and C1997, wherein the positions are defined with reference to sequence SEQ ID NO: 8 and wherein the first nucleotide in the sequence is indexed as 0,
in the hemL gene: T107, C197, T229, A242, C310, A338, A374, T389, G392, T442, C467, G470, C482, G518, and C641, wherein the positions are defined with reference to sequence SEQ ID NO: 9 and wherein the first nucleotide in the sequence is indexed as 0, and
in the hemY gene: A89, A236, A354, C383, C392, A395, T398, T465, T474, C521, T538, C566, A593, A767, T782, G863, G920, T927, A932, G935, C979, G989, C1019, T1055, G1091, T1136, G1143, G1152, T1166, T1172, A1176, T1184, C1199, C1205, G1268, G1278, T1295, T1318, A1336, G1343, C1346, G1355, T1359 and C1395, wherein the positions are defined with reference to sequence SEQ ID NO: 10 and wherein the first nucleotide in the sequence is indexed as 0,

wherein the nucleic acid sequence of the hem locus is at least 97% identical to the sequence SEQ ID NO: 1; and
wherein β-type C. acnes bacteria are C. acnes bacteria which are not α-type C. acnes bacteria.

2. The method according to claim 1 , wherein said method comprises specifically reducing the amount of α-type C. acnes bacteria on the skin of said subject.

3. The method according to claim 1 , wherein said method comprises administering to said subject a therapeutically effective amount of a phage, recombinant phage, packaged phagemid, plasmid, DNA- or RNA-containing vesicle, or engineered bacteria comprising said nucleic acid encoding a programmable nuclease, prime editor, or a base editor designed to specifically target said α-type C. acnes bacteria.

4. The method according to claim 3 , wherein said programmable nuclease is selected from the group consisting of CRISPR-Cas nucleases, TALENs, zinc finger nucleases, and engineered meganuclease.

5. The method according to claim 4 , wherein said programmable nuclease is a CRISPR-Cas nuclease.

6. The method according to claim 5 , wherein said phage, recombinant phage, packaged phagemid, plasmid, DNA- or RNA-containing vesicle, or engineered bacteria, further encodes a guide RNA designed to specifically target said α-type C. acnes bacteria.

7. The method according to claim 6 , wherein said guide RNA is designed to specifically target the hem locus of said α-type C. acnes bacteria selected from the group consisting of SEQ ID Nos: 13-16.

8. The method according to claim 3 , wherein said administration is a topical administration.

9. The method according to claim 1 , wherein said nucleic acid encodes a base editor or a prime editor.

10. The method according to claim 1 , wherein said method comprises increasing the amount of β-type C. acnes bacteria in said subject on the skin of said subject.

11. The method according to claim 1 , wherein said C. acnes bacteria-associated disease is a C. acnes bacteria-associated inflammatory disease.

12. The method according to claim 1 , wherein said C. acnes bacteria-associated disease is acne vulgaris.

13. A method for treating a C. acnes bacteria-associated disease in a subject, said method comprising specifically reducing the expression of at least one hem locus protein in α-type C. acnes bacteria in said subject by administering to said subject a nucleic acid encoding a programmable nuclease, prime editor, or base editor designed to specifically target said α-type C. acnes bacteria at a nucleotide selected from one
of the following nucleotide variants in the hem locus:
in the hemA gene: T173, A479, T506, A614, T629, C671, T971, A989, T1085, and T1094, wherein the positions are defined with reference to sequence SEQ ID NO: 3 and wherein the first nucleotide in the sequence is indexed as 0,
in the hemB gene: C142, A155, A176, A183, C224, C245, G248, T281, G311, C314, T346, C374, G377, C452, T626, C683, A693, A720, C738, C794, A920, T944, T992, G1022, and T1031, wherein the positions are defined with reference to sequence SEQ ID NO: 4 and wherein the first nucleotide in the sequence is indexed as 0,
in the hemC gene: G77, A96, C149, A233, T236, T255, A257, A260, C317, A347, T425, T437, A464, A486, A487, C488, A524, A545, A590, T605, A644, A665, C710, C713, A737, A770, A776, T785, T802, G830, C842, T845, G855, C893, A896, C897, G902, G908, A941, and A947, wherein the positions are defined with reference to sequence SEQ ID NO: 5 and wherein the first nucleotide in the sequence is indexed as 0,
in the hemD gene: T11, T41, T50, A150, T155, G159, G176, T257, C266, T278, G323, A324, T362, T367, T374, G387, A398, A399, T407, G422, G425, G432, A446, A459, T464, G595, T617, T643, A644, and C680, wherein the positions are defined with reference to sequence SEQ ID NO: 6 and wherein the first nucleotide in the sequence is indexed as 0,
in the hemE gene: T241, T476, A530, T704, A728, G767, T834, A867, A872, A882, and A957, wherein the positions are defined with reference to sequence SEQ ID NO: 7 and wherein the first nucleotide in the sequence is indexed as 0,
in the hemH gene: T11, T23, A48, T89, C188, G338, T464, T470, G536, T548, T608, G626, T632, T641, T671, T674, C683, C689, A740, G745, G787, A797, T893, A898, T1034, T1039, T1046, C1071, G1095, C1109, T1153, T1358, G1496, C1511, C1527, G1532, T1598, T1712, A1850, G1901, A1926, C1931, and C1997, wherein the positions are defined with reference to sequence SEQ ID NO: 8 and wherein the first nucleotide in the sequenc

Assignees

• Eligo Bioscience

Inventors

• Havranek Jan

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• A61P17/10

  Anti-acne agents · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q1/6883

  for diseases caused by alterations of genetic material · CPC title