IP Library › Granted Patent US 12,742,174
Granted Patent B2
US 12,742,174 · App. 18/688,480 · Granted Sep 22, 2026

Modulating alkaloid profiles in

Inventors: Lucien Bovet (Neuchatel, CH); Aurore Hilfiker (Neuchatel, CH); Kacper Piotr Kaminski (Neuchatel, CH)
Assignee: Philip Morris Products S.A.
C12N15/8243C12N9/88C12Y401/01019
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,742,174
App. No.
18/688,480
Granted
Sep 22, 2026
Kind
B2
Abstract

A non-naturally occurring or transgenic Nicotiana tabacum plant cell encompassing a heterologous polynucleotide that encodes arginine decarboxylase (ADC) and a method for producing such a cell are provided. Transgenic Nicotiana tabacum plants, plant parts, and plant tissues including these cells and plant materials and biomass produced by these cells and plants cells forming such a plant are provided. Materials produced by this plant, including plant leaves, flowers, seeds, extracts, and other plant biomass obtained from this plant including materials that have altered alkaloid levels are disclosed. Also provided are smoking articles including various tobacco products containing these materials.

Claims (26)

1 . A transgenic Nicotiana tabacum plant cell comprising a heterologous polynucleotide sequence that encodes a heterologous polypeptide sequence selected from:

a) a polypeptide sequence having at least 97% sequence identity to SEQ ID NO: 2, wherein the amino acid at position 31 is G, 40 is L, 63 is C, 296 is E, 355 is S, 417 is S, 429 is Y, 438 is S, 652 is M, 658 is D, 661 is M, 700 is D, 707 is I, and 730 is V; and

b) a polypeptide sequence having at least 97.5% sequence identity to SEQ ID NO: 4, wherein the amino acid at position 12 is A, 37 is I, 87 is M, 151 is F, 317 is V, 378 is E, 429 is V, 530 is V, and 680 is V;

wherein the heterologous polynucleotide sequence is operably linked to a promotor directing expression of the heterologous polypeptide sequence.

2 . The transgenic Nicotiana tabacum plant cell according to claim 1 , wherein the heterologous polypeptide sequence is a polypeptide sequence having at least 97% sequence identity to SEQ ID NO: 2, wherein the amino acid at position 31 is G, 40 is L, 63 is C, 296 is E, 355 is S, 417 is S, 429 is Y, 438 is S, 652 is M, 658 is D, 661 is M, 700 is D, 707 is I, and 730 is V.

3 . The transgenic Nicotiana tabacum plant cell according to claim 1 , wherein the heterologous polypeptide sequence is a polypeptide sequence having at least 97.5% sequence identity to SEQ ID NO: 4, wherein the amino acid at position 12 is A, 37 is I, 87 is M, 151 is F, 317 is V, 378 is E, 429 is V, 530 is V, and 680 is V.

4 . A transgenic Nicotiana tabacum plant comprising a plurality of plant cells according to claim 1 .

5 . The transgenic Nicotiana tabacum plant according to claim 4 , wherein levels of nicotine and nornicotine are decreased in the plant compared to an otherwise identical control Nicotiana tabacum plant not comprising cells comprising the heterologous polynucleotide.

6 . The transgenic Nicotiana tabacum plant according to claim 5 , wherein levels of nicotine and nornicotine are decreased in the plant by at least 20% compared to an otherwise identical control Nicotiana tabacum plant not comprising cells comprising the heterologous polynucleotide.

7 . The transgenic Nicotiana tabacum plant according to claim 6 , wherein levels of anabasine and anatabine are from 90% to 110% the levels of anabasine and anatabine in an otherwise identical control Nicotiana tabacum plant not comprising cells comprising the heterologous polynucleotide.

8 . The transgenic Nicotiana tabacum plant cell according to claim 1 , wherein the heterologous polypeptide sequence comprises SEQ ID NO: 2 or SEQ ID NO: 4.

9 . A plant material comprising a transgenic Nicotiana tabacum plant that comprises the plant cell according to claim 1 ,

wherein the plant material is a cured or dried plant material, and

wherein the cured or dried plant material is flue-cured, fire-cured, smoke-cured, sun-cured, or air-cured.

10 . A tobacco product or smoking article comprising the transgenic Nicotiana tabacum plant material according to claim 9 .

11 . A transgenic Nicotiana tabacum plant cell comprising a heterologous polynucleotide sequence that encodes a heterologous polypeptide sequence having at least at least 97.5% sequence identity to SEQ ID NO: 6, wherein the amino acid at position 90 is M, 203 is F, 296 is E, 342 is V, 380 is Q, 441 is G, 619 is N, 628 is S, 663 is D, 664 is H, 680 is L, 698 is S, and 715 is S;

wherein the heterologous polynucleotide sequence is operably linked to a promotor directing expression of the heterologous polypeptide sequence.

12 . A transgenic Nicotiana tabacum plant comprising a plurality of plant cells according to claim 11 .

13 . The transgenic Nicotiana tabacum plant according to claim 12 , wherein levels of nicotine and nornicotine are increased in the plant compared to an otherwise identical control Nicotiana tabacum plant not comprising cells comprising the heterologous polynucleotide.

14 . The transgenic Nicotiana tabacum plant according to claim 13 , wherein levels of nicotine and nornicotine are increased in the plant by at least 20% compared to an otherwise identical control Nicotiana tabacum plant not comprising cells comprising the heterologous polynucleotide.

15 . The transgenic Nicotiana tabacum plant according to claim 14 , wherein levels of anabasine and anatabine are increased by at least 25% relative to the levels of anabasine and anatabine in an otherwise identical control Nicotiana tabacum plant not comprising cells comprising the heterologous polynucleotide.

16 . The transgenic Nicotiana tabacum plant cell according to claim 11 , wherein the heterologous polypeptide sequence comprises SEQ ID NO: 6.

17 . A plant material comprising a transgenic Nicotiana tabacum plant that comprises the plant cell according to claim 11 ,

wherein the plant material is a cured or dried plant material, and

wherein the cured or dried plant material is flue-cured, fire-cured, smoke-cured, sun-cured, or air-cured.

18 . A tobacco product or smoking article comprising the transgenic Nicotiana tabacum plant material according to claim 17 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 1, 2024
From: BOVET, LUCIEN; HILFIKER, AURORE; KAMINSKI, KACPER PIOTR
To: PHILIP MORRIS PRODUCTS S.A.
Reel/Frame 066615/0278 →
Priority Claims (1)
EP 21196023 · Sep 10, 2021 · regional
Continuity (1)
Related Publication 20240368615A1 · Nov 7, 2024
References Cited (31)
US 10405571B2 · Adams · 2019 [cited by examiner]
US 20070034220A1 · Pandolfino · 2007 [cited by applicant]
US 20150007364A1 · Maor et al. · 2015 [cited by applicant]
US 20180153207A1 · Pandolfino · 2018 [cited by applicant]
US 20190085354A1 · Maor et al. · 2019 [cited by applicant]
WO WO0067558A1 · 2000 [cited by applicant]
WO WO2005018307A1 · 2005 [cited by applicant]
WO WO2013118120A2 · 2013 [cited by applicant]
Bortolotti et al, 2004, Physiol. Plantarum 120 (1), 84-92. [cited by examiner]
Burtin et al, 1997, Biochem. J., 325, 331-337. [cited by examiner]
Martinez et al, 2020, Planta, 251(92), 1-14. [cited by examiner]
Sisson, 1990, Beitrage zur Tabakforschung International, 14(6), 327-339. [cited by examiner]
Sierro et al, 2013, Genome Biol. 14:R60.1-R60.17. [cited by examiner]
International Search Report & Written Opinion mailed on Dec. 7, 2022 in PCT/EP2022/074368 filed on Sep. 1, 2022 (17 pages). [cited by applicant]
European Search Report dated Feb. 8, 2022, 2022 in EP Application 21196023.2 filed on Sep. 10, 2021, (9 pages. [cited by applicant]
Anonymous et al: “TSA: Nicotiana benthamiana isotig04028.Nb_leaf mRNA sequence—Nucleotide—NCBI”, Sep. 30, 2012 (Sep. 30, 2012), XP055888501, 2 pages. [cited by applicant]
Zenkner Fernanda Fleig et al: “Nicotine Biosynthesis in Nicotiana: A Metabolic Overview”, Tobacco Science, 56, Apr. 1, 2019 (Apr. 1, 2019), pp. 1-9, XP055888894. [cited by applicant]
Bunsupa S. et al., Molecular Evolution and Functional Characterization of a Bifunctional Decarboxylase Involved in Lycopodium Alkaloid Biosynthesis. Plant Physiol. Aug. 2016:171(4):2432-44. doi: 10.1104/pp. 16.00639. Ep… [cited by applicant]
DeBoer KD et al., RNAi-mediated down-regulation of ornithine decarboxylase (ODC) leads to reduced nicotine and increased anatabine levels in transgenic [cited by applicant]
Furer V. et al., [cited by applicant]
Kaminski KP et al., Alkaloid chemophenetics and transcriptomics of the [cited by applicant]
Keeler RF et al., Teratogenicity and toxicity of wild tree tobacco, [cited by applicant]
Lee YS et al., Identification of essential active-site residues in ornithine decarboxylase of [cited by applicant]
Tiburcio AF et al., Effect of polyamine biosynthetic inhibitors on alkaloids and organogenesis in tobacco callus cultures. Plant Cell Tissue Organ Cult. 1987; 9:111-20. doi: 10.1007/BF00044246. PMID: 11539719. [cited by applicant]
Welch KD et al., A study on embryonic death in goats due to [cited by applicant]
Sanchez-Rangel D. et al., Simultaneous Silencing of Two Arginine Decarboxylase Genes Alters Development in [cited by applicant]
Masgrau C. et al., Inducible overexpression of oat arginine decarboxylase in transgenic tobacco plants. Plant J. Mar. 1997;11(3):465-73. doi: 10.1046/j.1365-313x.1997.11030465. x. PMID: 9107036. [cited by applicant]
Burtin D. et al., Overexpression of arginine decarboxylase in transgenic plants. Biochem J. Jul. 15, 1997;325 ( Pt 2)(Pt 2):331-7. doi: 10.1042/bj3250331. PMID: 9230111; PMCID: PMC1218565. https://pmc.ncbi.nlm.nih.gov/a… [cited by applicant]
Chintapakorn Y. et al., Antisense-mediated reduction in ADC activity causes minor alterations in the alkaloid profile of cultured hairy roots and regenerated transgenic plants of Nicotiana tabacum. Phytochemistry. Oct. … [cited by applicant]
Urano K. et al., [cited by applicant]
Noury M. et al., A transgenic rice cell lineage expressing the oat arginine decarboxylase (adc) cDNA constitutively accumulates putrescine in callus and seeds but not in vegetative tissues. Plant Mol Biol. Jul. 2000;43(… [cited by applicant]