DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Elections/Restrictions
Applicant's election, without traverse, of Group II, encompassed by claims 7, 8, 10-12, and 29 in the reply filed on 06/15/2026 is acknowledged. Applicant recites that “new claim 32 depends from claim 7 and encompasses Group II” (see Applicant Remarks page 9).
Claims 1, 3, 5, 13, 16, 18, 19, 21-23, 27, 28, and 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) to GB Application No. 2205149.4, filed April 7, 2022. The certified copy has been filed in this application.
The effective filing date is April 7, 2022.
Status of the Claims
Amendments dated 06/15/2026 are entered:
Claim 24 is canceled without prejudice or disclaimer.
Claims 1, 3, 5, 7, 8, 10-13, 16, 18, 19, 21-23, 27-29, 31, and 32 are pending.
Claims 1, 3, 5, 13, 16, 18, 19, 21-23, 27, 28, and 31 are withdrawn.
Claims 7, 8, 10-12, 29, and 32 are examined herein.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/07/2024 and 05/13/2025 are acknowledged and are being considered by the Examiner.
A signed copy of the list of references cited is included with this Office Action.
Claim Objections
Claims 7-8, 12, 29 and 32 are objected to because of the following informalities:
“TSNA” is used as abbreviation in the claims set without first being defined in the claims.
Line 3 of claim 7 should recite “tobacco-specific nitrosamine (TSNA)” instead of “TSNA”.
Claim 10 is objected to because of the following informalities:
Line 3 of should recite “pseudooxynicotine (PON)” instead of “PON”.
Claim 29 is objected to because of the following informalities:
Referencing the withdrawn claim 28.
Claim 32 is objected to because of the following informalities:
Line 1 should recite “The tobacco plant or part thereof or a tobacco cell or cell culture according to claim 7” instead of “A tobacco plant or part thereof or a tobacco cell or cell culture according to claim 7”.
Claim Interpretations
Regarding claims 7, 8, 10-12, 29, and 32, Specification para 0091 defines the term “Homeodomain-like, MYB domain protein” as referring to as “a protein comprising a homeodomain-like MYB domain.”
Regarding claims 7, 8, 10-12, 29, and 32, the Specification defines the term “activity” as referring to “any functionality of the Homeodomain-like, MYB domain protein” in para 0126 and in para 0135 defines “expression” of a gene as referring to “the degree to which the information encoded in the gene is converted to a functionality.”
Regarding claims 7, 8, 10-12, 29, and 32, Specification 0087 defines the term “modifying” or “modified” as meaning “a plant (e.g. a tobacco plant) or nucleic acid sequence that has been altered or changed.”
Regarding claims 7, 8, 10-12, 29, and 32, Specification para 0240 recites that the term “tobacco-specific nitrosamine” or “TSNA” “has its usual meaning in the art, namely a nitrosamine which is found only in tobacco industry products or other nicotine-containing products. Suitably the at least one tobacco-specific nitrosamine may be N′-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N′-nitrosoanatabine (NAT) or N-nitrosoanabasine (NAB).”
Regarding claims 7, 8, 10-12, 29, and 32, Specification para 0241 defines the term “precursor thereto” “when used in relation to at least one tobacco-specific nitrosamine refers to one or more chemicals or compounds of a tobacco plant that give rise to the formation of a tobacco-specific nitrosamine or are involved in the nitrosation reaction leading to tobacco-specific nitrosamine production.” This term, “precursor thereto,” is being given the broadest reasonable interpretation of being synonymous with the term “precursor” as recited in claims 7, 8, 10-12, 29, and 32.
Regarding claim 8, Specification para 0305 defines the term “plant propagation material” as referring to “any plant matter taken from a plant from which further plants may be produced.” In the same para, the specification adds the following:
“Suitably, a plant propagation material may be selected from a seed, plant calli and plant clumps. Suitably the plant propagation material may be a seed. Suitably, the plant propagation material may be plant calli. Suitably the plant propagation material may be plant clumps.”
Regarding claims 29 and 32, Specification para 0458 defines the term “homologue” as meaning “an entity having a certain homology with the subject amino acid sequences and the subject nucleotide sequences.”
Regarding claims 29 and 32, Specification para 0157 defines the term “mutation” as referring to “a variation in the nucleotide sequence encoding the amino acid sequence or in the amino acid sequence compared to the sequence shown as SEQ ID No. 3, or an amino acid sequence which has at least 80% …sequence identity thereto.”
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7-8, 12, 29, and 32 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. All dependent claims are included in these rejections unless they contain a limitation that overcomes the deficiencies of the parent claim from which they depend. Details are listed below.
In claims 7-8, 12, 29, and 32, the metes and bounds of the term “a precursor of a TSNA” is unclear. The definition and examples given in Specification paras 0240-0241 do not clarify what structures are encompassed by this term, because practically all plant processes and biosynthetic pathways are interconnected and can be considered a precursor of a TSNA. It is suggested the specific TSNA precursors be recited.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Written Description
Claims 7-8, 10-12, 29, and 32 rejected under 35 U.S.C. 112(a) first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. All dependent claims are included in these rejections unless they contain a limitation that overcomes the deficiencies of the parent claim from which they depend. Details are listed below.
“[T]he test for sufficiency is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Ariad Pharm., Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010). To satisfy the written description requirement of 35 USC 112, first paragraph, the specification must describe the invention in sufficient detail so “that one skilled in the art can clearly conclude that the inventor[s] invented the claimed invention as of the filing date sought.” Lockwood
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v. Am. Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). “[The written description] inquiry is a factual one and must be assessed on a case-by-case basis.” Purdue Pharma L.P. v. Faulding, Inc., 230 F.3d 1320, 1323 (Fed. Cir. 2000). “In order to satisfy the written description requirement, the disclosure as originally filed does not have to provide in haec verba support for the claimed subject matter at issue.” Id. Nonetheless, the disclosure must convey with reasonable clarity to those skilled in the art that the inventor was in possession of the invention. Id., (“Put another way, one skilled in the art, reading the original disclosure, must immediately discern the limitation at issue in the claims.”) While the written description requirement does not demand either examples or an actual reduction to practice, actual “possession” or reduction to practice outside of the specification is not enough. Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1352 (Fed. Cir. 2010). Rather, it is the specification itself that must demonstrate possession. Id.
Appearance of a claim in the specification in ipsis verbis does not guarantee that the written description requirement is satisfied, see, e.g., Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 968 (Fed. Cir. 2002), nor does a failure to meet that standard require a finding that a claim does not comply with the written description requirement, In re Edwards, 568 F.2d 1349, 1351-52 (Fed. Cir. 1978). All that is required is that the specification demonstrate to a person of ordinary skill in the art that the inventor was in possession of the invention. Carnegie Mellon Univ. v. Hoffmann-La Roche Inc., 541 F.3d 1115, 1122 (Fed. Cir. 2008).
The claims are broadly drawn to a tobacco plant or part thereof or a tobacco cell or cell culture, having been modified to modulate or decrease the activity or expression of a Homeodomain-like, MYB domain protein and comprising decreased alkaloid and or TSNA precursor content in comparison to an unmodified plant or unmodified cell or cell culture.
Applicant has reduced to practice:
Example 1, “Virus-Induced Gene Silencing (VIGS) of Nitab4.5 0005842q0010.2 [(i.e., a gene encoding Homeodomain-like, MYB domain protein) ] Decreases Alkaloid Content in Leaves.” Nitab4.5 0005842q0010.2 has genomic sequence of SEQ ID NO: 1, the coding sequence of SEQ ID NO: 2, and the amino acid sequence of SEQ ID NO: 3 using the 300-nucleotide cDNA fragment with SEQ ID NO: 43. the genomic sequence SEQ ID NO: 1
In para 0496, “VIGS of Nitab4.5_0005842g0010.2 in tobacco leads to a decrease in alkaloid content in the tobacco leaves, in particular a decrease in nicotine, nornicotine, anabasine, PON and anatabine content.”
Applicant has not reduced to practice:
Modification of the activity or expression of a Homeodomain-like, MYB domain protein or nucleotide or amino acid sequence with at least 80% identity to SEQ ID NO:1-3, or a functional variants, functional fragments, orthologues, or homologue thereof, other than SEQ ID NOs: 1-3.
If alkaloid content can be increased and TSNA precursors maintained or reduced (i.e., the plant comprising decreased alkaloid and/or TSNA precursor content).
Modulation of a Homeodomain-like, MYB domain protein’s activity in a plant.
Modification of any kind to modulate or decrease the activity or expression of a Homeodomain-like, MYB domain protein, other than VIGS.
Any plant propagation material obtained from the tobacco plant comprising modulated or decreased activity or expression of a Homeodomain-like, MYB domain protein from the heritable modification.
Regarding claims 28-29, any plant part with modulated Homeodomain-like, MYB domain protein activity or expression and decreased alkaloid and/or TSNA precursor content, other than tobacco leaves.
The instant claims recite decreased alkaloid and/or TSNA precursor content in comparison to an unmodified plant. With the VIGS modification of Example 1, the instant disclosure describes silencing of Nitab4.5 0005842q0010.2 (i.e., a gene encoding Homeodomain-like, MYB domain protein). The results of the relative content of pyridine alkaloids were determined by LC-MS/MS, for analytes nicotine, anabasine, anatabine, nornicotine, PON (Specification paras 0495-0496). Alkaloid content of 5-week-old tobacco leaves silenced for Nitab4.5_0005997g0050.2 is shown in Fig. 1. Although the Applicant claims that VIGS of Nitab4.5_0005997g0050.2 leads to a decrease in alkaloid content in leaves, tobacco plants synthesize other alkaloids not listed in the specification or addressed in this disclosure. Cotinine and β-nicotyrine, are identified as “tobacco minor alkaloids” and are described on page 2 paragraph 2 in Chen (Chen, Peter X., et al. "Analysis of minor alkaloids in tobacco: a collaborative study." BEITRAGE ZUR TABAKFORSCHUNG INTERNATIONAL 21.7 (2005): 369).
Given the limited description in the instant specification of a few alkaloids in tobacco plants, a skilled artisan would not have reasonably recognized Applicant to be in possession of the full metes and bounds of the claims at the time the application was filed.
Modifications, including mutations, insertions, deletions, and/or substitutions, can have varying
effects on gene expression. Ge (Ge, Fang, et al. "Review of computational methods and database sources for predicting the effects of coding frameshift small insertion and deletion variations." ACS omega 9.2 (2024): 2032-2047) teaches, for example, silent (i.e. synonymous) mutations may not change the protein structure and thus do not result in increased gene expression, while others, such as frameshift mutations, can cause a premature stop codon resulting in a truncated protein that is not functional (see page 1 paragraph 1). Al Aboud (Al Aboud, NM., et al. Genetics, Epigenetic Mechanism. [Updated 2023 Aug 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532999) teaches, in the section title “Cellular,” that modifications to alter gene expression or activity includes epigenetic changes through alterations in the chromosome, rather than the DNA sequence, and regulating gene expression through chemical modifications. Modification may refer to the alteration of the peptide or gene encoding the peptide by any means, including merely natural modifications. Such modifications may or may not result in an increase or decrease in activity or expression of a Homeodomain-like, MYB domain protein, however, there is not sufficient structure to indicate that any modification would result in the function of increasing or decreasing activity or expression of a Homeodomain-like, MYB domain protein in a reliable and predictable manner.
As the Applicant only provides the one example of the VIGS technique, which is a small species in the large genus of “modification”, all possible modifications are not reduced to practice. Further, it appears that Applicant reduced to practice decreasing activity Homeodomain-like, MYB domain protein through silencing (i.e. reduction in expression) and thus the plant comprises decreased nicotine content (see Example 1). This is not equivalent to decreasing the activity of a Homeodomain-like, MYB domain protein without decreasing expression (activity or expression).
Further still, modulating, which may be defined as increasing (see, claim interpretation) activity or expression of a Homeodomain-like, MYB domain protein would logically not have the same effect on the alkaloid and/or TSNA precursor content based on the data of Example 1. Therefore, the genus clause of modulating the Homeodomain-like, MYB domain protein activity or expression, as claimed in claim 28 incorporated by claim 29, is not supported by an adequate structure to claim the function, description of a sufficient number of species, and is not reduced to practice. Undue experimentation would be required to confirm that the structure of the mutation or modification performs the function of modulating or decreasing expression and/or activity of a Homeodomain-like, MYB domain protein resulting in decreased alkaloid and/or TSNA content. The instant disclosure lacks sufficient variety of species to reflect the variance within the genus of modification.
VIGS can serve as an alternative to mutant collections or stable transgenic plants to allow the characterization of gene functions in a wide range of angiosperm species, but is a generally a transient method of genetic transformation. This was described in the abstract of Lange (Lange, Matthias, et al. "Virus-induced gene silencing (VIGS) in plants: an overview of target species and the virus-derived vector systems." Virus-Induced gene silencing: Methods and protocols (2013): 1-14.). Applicant has not reduced to practice VIGS in any tissue other than leaves. Applicant has not provided any examples of a plant, plant propagation material, or any sort of processed leaf or product produced from the tobacco leaves with the VIGS modification. As VIGS are known to be transient and no examples of a plant grown from the tobacco plant with the modification with modulated or decreased activity or expression of FAD synthetase or decreased alkaloid content are reduced to practice, Applicant has not sufficiently linked the structure to the function.
As in the claim interpretation, Applicant's definition Homeodomain-like, MYB domain protein covers a large range of evolutionarily related sequences of amino acids and nucleotides sharing a common ancestor and exhibiting similarity in sequence, structure, or function. The instant disclosure provides a singular example of VIGS of Nitab4.5_0005842g0010.2 purportedly reducing alkaloid content in leaves (Example 1). The VIGS construct uses a 300-nucleotide cDNA fragment of Nitab4.5_0005842g0010.2 (SEQ ID NO: 43). The results show a significant decrease in some alkaloids, but not all possible alkaloids in tobacco (refer to Chen , page 2 paragraph 2). Applicant’s description of “homologues of SEQ ID NOs: 1, 2 and 3” in Table 1 is acknowledged. However, the identification of homologues does not in and of itself guarantee they share same functionality as SEQ ID NOs: 1-3. Homologue testing in Example 3 simply states that the effects of the homologues of SEQ ID NO: 3, namely those listed in Table 1, are tested in assays as described in the above example. Additionally, Table 1 does not provide all nucleotide and amino acid sequences with 80% similarity to SEQ ID NOs: 1-3 and the specification does not display any data describing the influence of VIGS on these homologous genes or on, putatively downstream, alkaloid and/or TSNA precursor content.
A related homolog, orthologue or sequence with 80% similarity to Homeodomain-like, MYB domain protein is a broad term for any character, gene, or structure that shares a common ancestral origin. Though Xu (Xu, Zilong, et al. 2023. "Phylogenetic Inference of Homologous/Orthologous Genes Among Distantly Related Plants." Bio-protocol 13.23.; see page 2 para 1) teaches that homologous/orthologous genes among different plants typically perform similar or equivalent functions, a representative number of species was not described to represent the claimed entire genus of modulating or decreasing the activity or expression of the vastness of the Homeodomain-like, MYB domain protein genus. Sufficient structure was not provided of the homolog-related peptides that share a common ancestor and still maintain the same function in the claims.
Björklund (Björklund, Åsa K., et al. "Domain rearrangements in protein evolution." Journal of molecular biology 353.4 (2005): 911-923) teaches on page 1 paragraphs 1-2 that “proteins are composed of domains, recurrent protein fragments with distinct structure, function and/or evolutionary history” and that “it has been estimated that single-domain proteins from the same domain family have a 67% chance of having similar functions, whereas the corresponding number for two-domain proteins with just one of the domains in common [i.e., homologues or functional variants or functional fragments] is 35%.” Applicant does not provide working examples of a functional variant or functional fragment or orthologue or homologue as recited in claim 29, which incorporates claim 28, and of a homologue as recited in claim 32. Due to the functional unpredictability of all orthologous or homologous sequences, and functional fragments and variants thereof, undue experimentation would be required to ensure that all variants and fragments of the claimed sequences still maintained the functionality of reducing the alkaloid and/or TSNA precursor content since Applicant has not done so.
The Specification fails to provide an adequate written description to support the breadth of the claims. Therefore, one skilled in the art would not have recognized Applicants to be in possession of the claimed invention at the time the application was filed. See Written Description guidelines published in 2008 online at https://www.uspto.gov/ sites/default/files/web/menu/written.pdf.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 7, 8, 10-12, 29, and 32 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bian (Bian S, et al. NtMYB305a binds to the jasmonate-responsive GAG region of NtPMT1a promoter to regulate nicotine biosynthesis. Plant Physiol. 2022 Jan 20;188(1):151-166. doi: 10.1093/plphys/kiab458. PMID: 34601578; PMCID: PMC8774768., published 2022 Jan 20) taken with the evidence of NCBI Reference Sequence: XP_016506729.1 (PREDICTED: myb-related protein 305-like [Nicotiana tabacum], published 2016).
Regarding claims 7 and 10-11, Bian teaches:
in the abstract that “NtMYB305a is a positive regulator of nicotine biosynthesis in tobacco” (i.e., a tobacco plant).
“RNAi-mediated gene-silenced plants (NtMYB305a-RI) exhibiting over 70% suppression of NtMYB305a transcription (Figure 5A)” (i.e., having been modified to decrease the activity or expression of a Homeodomain-like, MYB domain protein)( para bridging pages 156-157).
“an ∼40% decrease [“in the nicotine content”] in NtMYB305a-RI plants compared to the control plant levels (Figure 5C)” (i.e., claim 7 recitation of “and comprising decreased alkaloid and or TSNA precursor content in comparison to an unmodified plant,” claims 10-11 limitation wherein the nicotine content is decreased) (para bridging pages 157-158).
Regarding claims 8 and 12, Bian teaches:
That “the vector for RNAi-mediated gene silencing of NtMYB305a… [is] introduced into Agrobacterium tumefaciens LBA4404 and then used to transform tobacco plants as described previously (Wang et al., 2014)” (page 162, col 1, 1st full para)
“NtMYB305a-RI plants were propagated by crossing wild-type tobacco plants with pollen grains from the dehisced anthers of NtMYB305a-RI plant” and that sterilized “tobacco seeds were germinated on 1/2 Murashige and Skoog (MS) medium with the desired antibiotics for 1 week” (i.e., plant propagation material obtained from the tobacco plant according to claim 7, comprising modulated or decreased activity or expression of the Homeodomain-like, MYB domain protein, and decreased alkaloid and/or TSNA precursor content in comparison to a plant propagation material obtained from an unmodified tobacco plant) (page 162, col 1, 1st and 2nd full para).
that tobacco seeds germinated antibiotic containing medium are “then cultured in liquid 1/2 MS medium (refreshed each week) for 4 more weeks” where the germinated seeds are at this point considered plants (i.e., a plant grown from the tobacco plant or part thereof or tobacco cell or cell culture according to claim 7, the plant or the crop comprising decreased activity or expression of the Homeodomain-like, MYB domain protein, or decreased alkaloid and/or TSNA precursor content in comparison to a plant or a crop bred or grown from an unmodified tobacco plant (page 162, col 1, 1st and 2nd full para).
The above teaching reads on claim 8 because transformation with Agrobacterium tumefaciens followed by germination on media with antibiotics indicates that surviving transgenic plants harbor within their genomes the antibiotic resistance gene and the nucleotides of interest, in this case RNAi-mediated gene silencing of NtMYB305a, from the parental transgenic plant, absent evidence to the contrary. As such the plants grown from Bian’s seeds meet the limitations of claim 12.
Claim 29, which depends from claim 28 and thus incorporates it, is drawn to
A mutant plant or progeny or seed thereof comprising the nucleic acid molecule of claim 28, wherein the mutation comprises a heritable mutation, wherein said heritable mutation decreases the activity or expression of Homeodomain-like, MYB domain protein and wherein the mutant plant has decreased alkaloid content and/or modulated content of a TSNA or a precursor of a TSNA relative to a comparable plant which does not carry said heritable mutation
The “nucleic acid molecule of claim 28” as recited in claim 29 is
A nucleic acid molecule comprising a mutation in a nucleotide sequence encoding a Homeodomain-like, MYB domain protein which:
a) encodes an amino acid sequence as set out in SEQ ID No. 3; or a functional variant or functional fragment or orthologue of SEQ ID No. 3; or a sequence which has at least 80% identity to SEQ ID No. 3; or a homologue of SEQ ID No. 3; or
b) comprises a sequence as set out in SEQ ID No. 1 or 2; or a functional variant or functional fragment or orthologue of SEQ ID No. 1 or 2; or a nucleic acid sequence which has at least 80% identity to SEQ ID No. 1 or 2; or a homologue of SEQ ID No. 1 or 2, , wherein the activity or expression of the encoded Homeodomain-like, MYB domain protein is modulated or decreased.
The rejection of claims 29 and 32 is made on the grounds that MYB305a is a homologue of SEQ ID No. 3. See Specification para 0458 and/or Claim Interpretations, above, for a definition of homologue.
Regarding the incorporated limitations of claim 28, Bian teaches the “Gene accessions in NCBI GenBank of NtMYB305a.1 is LOC107821652 (Supplemental Figure S1 caption). NCBI Reference Sequence: XP_016506729.1 , title “PREDICTED: myb-related protein 305-like [(]Nicotiana tabacum[)],” published 2016) is the amino acid sequence of the polypeptide encoded by the gene at LOC107821652. NCBI Reference Sequence: XP_016506729.1 shares more than 50% identity with SEQ ID NO: 3 (data not shown)., is interpreted as being a homolog of SEQ ID NO: 3, and, having functionality of the Homeodomain-like MYB domain protein in the nicotine biosynthesis pathway, is a functional variant of SEQ ID NO: 3 As such, LOC107821652 meets the claim 28 limitation of “a nucleotide sequence encoding a Homeodomain-like, MYB domain protein which encodes a functional variant or functional fragment or orthologue of SEQ ID No. 3; or a homologue of SEQ ID No. 3.
By virtue of not being 100% identical to SEQ ID NO: 3, NCBI Reference Sequence: XP_016506729.1 contains mutation (i.e., a nucleic acid molecule containing a mutation a nucleotide sequence encoding a Homeodomain-like, MYB domain protein which encodes a functional variant or functional fragment or orthologue of SEQ ID No. 3; or a homologue of SEQ ID No. 3). See claim interpretations above or Specification para 0157 for Applicant's definition of the term “mutation.”
Further, regarding the “mutation” limitation as defined in Specification para 0157, Bian teaches a “∼300-bp coding sequence of NtMYB305a” (i.e., a deletion mutation in a nucleotide sequence encoding a Homeodomain-like, MYB domain protein which encodes a functional variant or functional fragment or orthologue of SEQ ID No. 3; or a homologue of SEQ ID No. 3)(page 162, col 1, 1st full para). Bian also teaches that plants comprising this mutated nucleotide “(NtMYB305a-RI) exhibit[] over 70% suppression of NtMYB305a transcription” (i.e., “wherein the… expression of the encoded Homeodomain-like, MYB domain protein is …decreased”) (para bridging pages 156-157).
Regarding claim 29, Bian teaches introducing a vector containing the ~300-bp coding sequence of NtMYB305a (i.e., the mutation) into Agrobacterium tumefaciens LBA4404 to transform tobacco plants in order to make NtMYB305a-RI plants (page 162, col 1, 1st full para). Furthermore, Bian teaches that NtMYB305a-RI plants are propagated by crossing wild-type tobacco with pollen from the transformed plants and selecting progeny on antibiotic medium (page 162, col 1, 1st full para), which inherently and expressly demonstrates that the genetic modification, the ~300-bp coding sequence of NtMYB305a, is stable and heritable in the progeny, absent evidence to the contrary. This reads on the claim 29 recitation of “a mutant of a plant carrying a heritable mutation in a nucleotide sequence which… encodes a Homeodomain-like, MYB domain protein which encodes… a functional variant or functional fragment or orthologue of SEQ ID No. 3; …or a homologue of SEQ ID No. 3.”
Regarding further limitations recited in claim 29, Bian teaches:
NtMYB305a-RI plants exhibit “over 70% suppression of NtMYB305a transcription” (i.e., “wherein said heritable mutation decreases the activity or expression of Homeodomain-like, MYB domain protein”) (para bridging pages 156-157).
“an ∼40% decrease [“in the nicotine content”] in NtMYB305a-RI plants compared to the control plant levels ” (i.e., “and wherein the mutant plant has decreased alkaloid content… relative to a comparable plant which does not carry said heritable mutation”) (para bridging
Claim 32 depends from claim 7, the limitations of which have been discussed above, and further limits claim 7 with the clause “wherein the Homeodomain-like, MYB domain protein… comprising… a homologue of SEQ ID No. 3… has been modified.” Specification para 0087 defines the term “modifying” or “modified” as meaning “a plant (e.g. a tobacco plant) or nucleic acid sequence that has been altered or changed.” Bian teaches NtMYB305a-RI plants, plants which comprise a modified nucleotide sequence of the nucleotide sequence encoding the Homeodomain-like, MYB domain protein MYB305a, which is a homologue of SEQ ID NO: 3. This reads on the with the clause “wherein the Homeodomain-like, MYB domain protein… comprising… a homologue of SEQ ID No. 3… has been modified.”
Thus, Bian anticipates the claimed invention.
Conclusion
No claims allowed.
References Cited but not Applied
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Qin (Qin, Y., et al. Transcriptome analysis reveals key genes involved in the regulation of nicotine biosynthesis at early time points after topping in tobacco (Nicotiana tabacum L.). BMC Plant Biol 20, 30 (2020). https://doi.org/10.1186/s12870-020-2241-9) teaches that 69 MYB transcription factor (TF) genes including newly identified genes “might be involved in nicotine biosynthesis, since all of these TF families have been described as functioning in the regulation of plant secondary metabolism [and] are therefore good targets for further experiments” (para bridging page 6-7; page 10, col 2, last full para).
Examiner’s Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YVETTE B TAMUKONG whose telephone number is (571)272-1040. The examiner can normally be reached M-Th 730-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bratislav Stankovic can be reached at (571) 270-0305. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YVETTE B. TAMUKONG/ Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/ Supervisory Patent Examiner, Art Units 1661 & 1662
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