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 .
Election/Restrictions
1. Applicant's election with traverse of Group VII, claims 1, 12 (part), 16 (part), 17, 45, and CYP82E3 allele and SEQ ID NO: 5 is acknowledged. Election of species election of nicotine ≤0.35% (Election A), and LAFC53 (Election B) are also acknowledged
Applicant’s arguments are carefully considered but are deemed to be unpersuasive.
First, it is important to note that the instant application is a national stage entry of a PCT Application (PCT/US2023/062580, filed 02/14/2023) and is subject to restriction requirement under 35 U.S.C. 121 and 372.
It is maintained that the inventions listed as Groups I-XLII do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features.
RESTRICTION AMONG GROUPS I–XLII IS PROPER
Contrary to Applicant’s arguments, it is important to note that common feature is known. The linking feature — a tobacco cultivar having reduced nicotinic alkaloids — is not an STF under PCT Rule 13.2 because Kudithipudi et al. (WO 2020/154466 A1) expressly discloses tobacco plants with reduced nicotinic alkaloids produced by breeding and transgenic approaches. See paragraphs [003], [052]–[053], [077]–[078], [0124], [0175]. A known feature cannot serve as the STF regardless of how individual groups achieve that result. Applicant’s “means vs. result” argument fails. For a structural feature to serve as a common STF, it must be shared across the groups it purports to link. No single CYP82E variant or allelic feature is common to all 42 groups. Groups I-II recite only nic1/nic2 alleles; Group IX recites only tobacco products; Groups XXVI-XXIX lack specific CYP82E mutations; Groups XXX, XXXV-XXXVI involve unrelated gene suppression. The only feature common to all groups is the known functional result. Kudithipudi et al. is not cited to anticipate each group’s specific structural features — it is cited solely to show the common linking feature is not novel.
PARTIAL UNITY ARGUMENTS ARE UNPERSUASIVE
CYP82E3 and CYP82E2 subsets: Applicant proposes unity among CYP82E3 groups (VII, VIII, XXII–XXV, XXXIII–XXXIV, XXXVII–XXXVIII, XLI–XLII) and CYP82E2 groups (III–VI, XIV–XXI, XXXI–XXXII, XXXIX–XL) based on shared functional enzyme activity. This is unpersuasive for two reasons. First, the functional roles of CYP82E2 and CYP82E3 as nicotine N-demethylases in tobacco are known in the prior art. See Gavilano et al. (Journal of Agricultural and Food Chemistry, 54:9071-9078, 2006, see in particular, Figs. 1-6, Tables 1-3) and Siminszky et al. (PNAS, 102(41):14919-14924, 2005; See in particular, abstract, Tables and Figures). A known functional enzyme activity cannot serve as the STF. Second, within each proposed subset, the groups recite structurally distinct features — C330W mutation, SEQ ID NO: 6, K375E, L422W, SEQ ID NOs: 2–4 — which are distinct chemical entities constituting separate inventive concepts. Practical search overlap does not establish legal unity under PCT Rule 13.1.
Applicant’s argument about claim 46 is found persuasive. Thus upon further consideration, restriction between SEQ ID NOs: 5 and 6 is withdrawn. Accordingly, Groups VII and VIII are rejoined.
Applicant’s arguments regarding Election B (tobacco lines) is found persuasive. Accordingly, restriction for electing single species from Election B is withdrawn.
Applicants are advised that if any claims including all the limitations of an allowable claim examined here are presented in a continuation or divisional application, such claims may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
SPECIES RESTRICTIONS MAINTAINED
Election A (alkaloid species). Nicotine, nornicotine, anatabine, and anabasine are structurally distinct compounds with distinct quantitative thresholds recited in the claims. Species-specific prior art analysis is required for each. Restriction is maintained.
It is noted no election was made from Election B and Election C. It is also noted that elected Group of claim do not recite these species.
Regarding Applicant’s arguments about method claims, it must be noted that the examiner has required restriction between product and process claims. Where applicant elects claims directed to the product, and a product claim is subsequently found allowable, withdrawn process claims that depend from or otherwise include all the limitations of the allowable product claim will be rejoined in accordance with the provisions of MPEP § 821.04. Process claims that depend from or otherwise include all the limitations of the patentable product will be entered as a matter of right if the amendment is presented prior to final rejection or allowance, whichever is earlier. Amendments submitted after final rejection are governed by 37 CFR 1.116; amendments submitted after allowance are governed by 37 CFR 1.312.
In the event of rejoinder, the requirement for restriction between the product claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103, and 112. Until an elected product claim is found allowable, an otherwise proper restriction requirement between product claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowed product claim will not be rejoined. See “Guidance on Treatment of Product and Process Claims in light of In re Ochiai, In re Brouwer and 35 U.S.C. § 103(b),” 1184 O.G. 86 (March 26, 1996). Additionally, in order to retain the right to rejoinder in accordance with the above policy, Applicant is advised that the process claims should be amended during prosecution either to maintain dependency on the product claims or to otherwise include the limitations of the product claims. Failure to do so may result in a loss of the right to rejoinder.
Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Claims 1-4, 8, 9, 11, 12, 16-23, 29, 31, 32, 36-38, 43-51, 62-66, and 68-72 are pending. Claims 5-7, 10, 13-15, 24-28, 30, 33-35, 39-42, 52-61 and 67 are cancelled by the Applicant.
Accordingly, claims 1, 12 (part), 16 (part), 17, 45 and 46 drawn to CYP82E3 allele and SEQ ID NOs: 5 and 6 are examined on merits in this Office action. Thus claims 2-4, 8, 9, 11, 18-23, 29, 31, 32, 36-38, 43-44, 47-51, 62-66, and 68-72 and SEQ ID NOs. other than SEQ ID NOs: 5 and 6 recited in the claims are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected inventions. This restriction is made FINAL.
Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be amended in compliance with 37 CFR 1.48(b) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. Any amendment of inventorship must be accompanied by a request under 37 CFR 1.48(b) and by the fee required under 37 CFR 1.17(i).
Claim Objections
2. Claims 12 and 16 are objected to because of the following informalities:
Claim 12 and 16 are objected for having non-elected subject matter CYP82E2 allele..
Appropriate action is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
3. Claims 1, 12, 16, 17, 45 and 46 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claims read on naturally occurring tobacco plant, plant cell, or progeny. Under Step 1 of the Alice/Mayo framework (see Alice Corp. v. CLS Bank Int’l, 573 U.S. 208 (2014); Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012)), the claims are directed to a statutory category (a plant, seed, or cell). For example, Shoji et al. (The plant cell, 22:3390-3409, 2010; see in particular, abstract, introduction at pages 3390-3391) who teach existence of naturally occurring nic1 and/or nic2 mutants of tobacco having reduced levels of nicotinic alkaloid.
However, under Step 2A, Prong One, the claims are directed to a judicial exception because they recite a naturally occurring product and/or naturally occurring genetic variations.
Claim 1 recites a “tobacco cultivar… comprising reduced levels of at least one nicotinic alkaloid compared to a corresponding naturally-occurring tobacco plant.” The claim does not require any structural modification beyond a reduced metabolite level relative to a natural comparator. A tobacco plant having a naturally occurring variation in alkaloid content constitutes a product of nature. Merely identifying or selecting a plant with a naturally occurring phenotype does not render the plant markedly different from what exists in nature. See Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013).
Claims 12, 16, and 45 further recite the presence of a “functional CYP82E3 allele,” increased nicotine N-demethylation activity, and specific point mutations (C330W) relative to a wild type sequence. These limitations describe naturally occurring genetic variants and associated enzymatic activity. Naturally occurring mutations and alleles are products of nature even if newly discovered. See Myriad, 569 U.S. at 590 (“a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated”).
It is noted that the claims do not recite that the mutations are non-naturally occurring, engineered, or otherwise markedly different from naturally occurring alleles. Absent such limitation, the recited mutations encompass naturally occurring polymorphisms. A plant containing naturally occurring mutations remains a natural product. See In re Roslin Institute (Edinburgh), 750 F.3d 1333 (Fed. Cir. 2014) (cloned animals genetically identical to naturally occurring animals are not patent eligible because they are not markedly different).
Claim 17 recites progeny plants, seeds, or cells produced from the tobacco cultivar of claim 1. Because the parent cultivar is a product of nature, progeny and seeds likewise constitute natural products. The claim does not recite additional characteristics that would render them markedly different from naturally occurring counterparts.
Under Step 2A, Prong Two, the claims do not integrate the judicial exception into a practical application. The claims merely recite the plant and its natural genetic or phenotypic characteristics without additional elements that impose meaningful limits on the exception.
Under Step 2B, the claims do not recite additional elements that amount to significantly more than the judicial exception. There is no recitation of a non-conventional genetic engineering step, a specific transformation, or other inventive concept beyond the natural product itself. The claims therefore fail to add an inventive concept sufficient to transform the nature-based product into patent-eligible subject matter.
See also MPEP § 2106.04(b) and 2106.04(c) which explains that naturally occurring products and their natural characteristics are not patent eligible unless they are markedly different from what exists in nature.
Accordingly, claims 1, 12, 16, 17, 45, and 46 are rejected under 35 U.S.C. § 101 as being directed to patent-ineligible subject matter.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
4. Claims 1, 12, 16, 17, 45 and 46 are rejected under 35 U.S.C. 112, 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(s), at the time the application was filed, had possession of the claimed invention.
The Federal Circuit has recently clarified the application of the written description requirement. The court stated that a written description of an invention "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). The court also concluded that "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material." Id. Further, the court held that to adequately describe a claimed genus, Patent Owner must describe a representative number of the species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus." Id.
Finally, the court held:
A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNAs, defined by nucleotide sequence, falling within the scope of the genus or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. Id.
See also MPEP Section 2163, page 174 of Chapter 2100 of the August 2005 version, column 1, bottom paragraph, where it is taught that
[T]he claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.
See also Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ 2d 1016 at 1021, (Fed. Cir. 1991) where it is taught that a gene is not reduced to practice until the inventor can define it by "its physical or chemical properties" (e.g. a DNA sequence).
Claims are broadly drawn to a tobacco cultivar, or any part thereof, comprising reduced levels of at least one nicotinic alkaloid compared to a corresponding naturally-occurring tobacco plant, or part thereof, or wherein the cultivar comprises a functional CYP82E3 allele, or wherein nicotine N-demethylation activity of proteins encoded by the CYP82E3 is increased compared to a naturally-occurring tobacco plant, or a progeny plant, seed, or cell produced from the tobacco cultivar, or wherein the CYP82E3 allele comprises a nucleotide sequence encoding a C330W point mutation relative to a wild type CYP82E3 amino acid sequence set forth in SEQ ID NO: 5, or wherein mutated SEQ ID NO: 5 is set forth in SEQ ID NO: 6.
The breadth of claim 1 encompasses any tobacco cultivar having reduced levels of any nicotinic alkaloid. The breadth of claim 12 encompasses any functional CYP82E3 allele in any tobacco cultivar having reduced levels of any nicotinic alkaloid. The breadth of claim 45 encompasses any functional CYP82E3 allele having a nucleotide sequence encoding a C330W point mutation when compared with a wild type CYP82E3 sequence as set forth in SEQ ID NO: 5, and claim 46 is directed to such mutant CYP82E3 protein having the amino acid sequence as set forth in SEQ ID NO: 6.
The specification, however only describes alkaloid analysis of some tobacco genotypes having variable levels of nicotine, nornicotine, anatabine, and anabasine (see Table 1). Transgenic tobacco plants that are genetically modified by reducing expression activity of key genes nic1/nic2 to obtain low levels of nicotinic alkaloid (as encompassed by the breadth and scope of claims) are not described. Likewise transgenic plants or genetically modified plants with increased expression of CYP82E3 sequence as set forth in SEQ ID NO: 5 or any functional CYP82E3 allele having a nucleotide sequence encoding a C330W point mutation when compared with a wild type CYP82E3 sequence as set forth in SEQ ID NO: 5 and having amino acid sequence as set forth in SEQ ID NO: 6 as encompassed by the breadth and scope of the claims is not described. The specification at example 2 provides a prophetic guidance how to make site directed mutation(s) in CYP82E3 gene using CRISPR/cas9 editing system. However, tobacco plants with such genetic modification are not obtained.
In light of breadth and scope of the claims as described above, the claims encompasses a large genus having species with unknown structures.
The specification does not disclose a representative number Applicant’s broadly claimed genus.
In light of above, one of skill in the art would not recognize that Applicant was in possession of the necessary common attributes or features of the genus in view of the disclosed species. Since the disclosure fails to describe the common attributes that identify members of the genus, and because the genus is highly variant, wild type SEQ ID NO: 5 (CYP82E3), mutant CYP82E3 as set forth in SEQ ID NO: 6 or wild type nic1/nic2 alleles are insufficient to describe the claimed genus.
Therefore, given the lack of written description in the specification with regard to the structural and functional characteristics of the claimed compositions, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed.
Accordingly, there is lack of adequate description to inform a skilled artisan that applicant was in possession of the claimed invention at the time of filing. See Written Description guidelines published in Federal Register/Vol.66, No. 4/Friday, January 5, 2001/Notices; p. 1099-1111.
5. Claims 1, 12, 16, 17, 45 and 46 are rejected under 35 under first paragraph of 35 U.S.C. 112(a), because the specification, while being enabling enabled to make cultivars obtainable through the specific breeding strategies and germplasm described, does not reasonably provide enablement for any tobacco cultivar with reduced levels of any nicotinic alkaloid, regardless of genetic background or mechanism of reduction.The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The claimed invention is not supported by an enabling disclosure taking into account the Wands factors. In re Wands, 858/F.2d 731, 8 USPQ2d 1400 (Fed. Cir. 1988). In re Wands lists a number of factors for determining whether or not undue experimentation would be required by one skilled in the art to make and/or use the invention. These factors are: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples of the invention, the nature of the invention, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art, and the breadth of the claim.
Claims are broadly drawn to a tobacco cultivar, or any part thereof, comprising reduced levels of at least one nicotinic alkaloid compared to a corresponding naturally-occurring tobacco plant, or part thereof, or wherein the cultivar comprises a functional CYP82E3 allele, or wherein nicotine N-demethylation activity of proteins encoded by the CYP82E3 is increased compared to a naturally-occurring tobacco plant, or a progeny plant, seed, or cell produced from the tobacco cultivar, or wherein the CYP82E3 allele comprises a nucleotide sequence encoding a C330W point mutation relative to a wild type CYP82E3 amino acid sequence set forth in SEQ ID NO: 5, or wherein mutated SEQ ID NO: 5 is set forth in SEQ ID NO: 6.
The breadth of claim 1 encompasses any tobacco cultivar having reduced levels of any nicotinic alkaloid made by any method. The breadth of claim 12 encompasses any functional CYP82E3 allele in any tobacco cultivar having reduced levels of any nicotinic alkaloid using any method. The breadth of claim 45 encompasses any functional CYP82E3 allele having a nucleotide sequence encoding a C330W point mutation when compared with a wild type CYP82E3 sequence as set forth in SEQ ID NO: 5, whereas claim 46 is the mutant (C330W point mutation in SEQ ID NO: 5) amino acid sequence as set forth in SEQ ID NO: 6, and having reduced levels of any nicotinic alkaloid made by any method.
The specification, however only provides guidance on alkaloid analysis of some tobacco genotypes having variable levels of nicotine, nornicotine, anatabine, and anabasine (see Table 1). Transgenic tobacco plants that are genetically modified by reducing expression activity of key genes nic1/nic2 to obtain low levels of nicotinic alkaloid (as encompassed by the breadth and scope of claims) are not described. Likewise transgenic plants or genetically modified plants with increased expression of CYP82E3 sequence as set forth in SEQ ID NO: 5 or any functional CYP82E3 allele having a nucleotide sequence encoding a C330W point mutation when compared with a wild type CYP82E3 sequence as set forth in SEQ ID NO: 5 and having amino acid sequence as set forth in SEQ ID NO: 6 as encompassed by the breadth and scope of the claims is not described. The specification at example 2 provides a prophetic guidance how to make site directed mutation(s) in CYP82E3 gene using CRISPR/cas9 editing system. However, tobacco plants with such genetic modification are not obtained.
As discussed above Claim 1 broadly recites any tobacco cultivar comprising reduced levels of at least one nicotinic alkaloid compared to a corresponding wild-type tobacco plant. While, the specification describes low-nicotine cultivars generated through conventional breeding by crossing low-nicotine mutant lines and selecting progeny. However, the claim is not limited to the disclosed breeding methods or specific genetic backgrounds. It encompasses any tobacco cultivar with reduced levels of any nicotinic alkaloid, regardless of genetic background or mechanism of reduction.
As discussed above, Claims 12 and 16 require a functional CYP82E3 allele and increased nicotine N-demethylation activity relative to a naturally occurring plant.
The specification provides prophetic guidance regarding the use of CRISPR/Cas systems and guide RNAs to introduce point mutation into SEQ ID NO: 5. However, no genome-edited or transgenic plants are reported as having been made, and no working examples demonstrate successful introduction of mutations or confirmed increases in enzymatic activity in planta.
As discussed above, Claim 45 recites a CYP82E3 allele comprising a nucleotide sequences encoding C330W point mutation relative to SEQ ID NO: 5. Claim 46 recites a CYP82E3 allele comprising nucleotide sequences encoding the amino acid sequence having C330W point mutation and having the amino acid sequence of SEQ ID NO: 6.
The specification provides only prophetic instruction for introducing such mutations via CRISPR/Cas technology. No actual plants comprising these specific mutation(s) are described, and no experimental data demonstrate successful editing, stable inheritance, or the asserted functional consequences. It is important to note that the breadth and scope of claims encompass using f ZFNs, Meganucleases, Base editors, CAST (CRISPR-transposases), ADAR RNA editing and unspecified recombinases to achieve desired point mutation(s)
As discussed, Claim 17 recites progeny plants, seeds, or cells produced from the cultivar of claim 1. Because claim 1 is not enabled across its full scope, claim 17 likewise lacks enablement to the extent it encompasses non-enabled embodiments, including genome-edited plants not actually made or demonstrated.
The art of plant metabolic engineering and genome editing is recognized as unpredictable, particularly with respect to enzyme activity, metabolic pathway flux, and phenotypic outcomes across diverse plant genetic backgrounds. See for example, Facchini, P.J., “Alkaloid Biosynthesis in Plants: Biochemistry, Cell Biology, Molecular Regulation, and Metabolic Engineering Applications,” Annual Review of Plant Physiology and Plant Molecular Biology, 52:29–66 (2001) (teaching complexity and regulation of alkaloid biosynthetic pathways, see for example, abstract, introduction, page 55, ); Also see Xu et al., “Wild tobacco genomes reveal the evolution of nicotine biosynthesis”, PNAS, 114(23):6133-6138, 2017, who teach that genomic studies of wild tobacco species demonstrate that nicotine biosynthesis evolved through gene duplications, transcription factor evolution, and lineage-specific regulatory changes, highlighting the complex genetic architecture underlying alkaloid production. Such evolutionary complexity further supports the difficulty of predicting outcomes when modifying tobacco alkaloid biosynthetic genes. See in particular, abstract, introduction at pages 6133-6134; and results and discussion at pages 6134-6138.
The complexity of the nicotine biosynthesis pathway can be seen from the following figure, wherein multiple regulatory genes are involved in the synthesis of nicotine (obtained from Wu et al. Current Biology, Volume 41, pages 1-10, 2025; https://doi.org/10.1016/j.cpb.2024.100431, Figure 2).
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Given the documented complexity of alkaloid biosynthesis and its regulation, and the variability of metabolic expression across cultivars and environments, the disclosure does not enable the full scope of the claim without undue experimentation.
In the absence of guidance and given the known variability in genome editing efficiency, genotype dependence, off-target effects, and downstream metabolic consequences in plants, undue experimentation would be required to achieve the claimed functional outcomes across the full breadth of cultivars encompassed by the claims.
Given the breadth of the claims, the limited working examples, and the recognized unpredictability of plant metabolic engineering and genome editing, undue experimentation would be required to practice the full scope of the claimed invention.
Accordingly, claims 1, 12, 16, 17, 45, and 46 are rejected under 35 U.S.C. § 112(a) for lack of enablement.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
6. Claims 1 and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9, 10, 13, 22 and 23 of copending Application No. 19/419,918 (‘918 thereafter).
Although the claims at issue are not identical, they are not patentably distinct from each other because the subject matter claimed in copending ‘918 claims 9, 10, 13, 22 and 23 is encompassed by instant claims 1 and 17. Instant claims 1 and 17 are directed to genus, whereas copending ‘918 claims 9, 10, 13, 22 and 23 are species, accordingly a species anticipates the genus. For example, the breadth of claim 1 encompasses any tobacco cultivar having reduced levels of any nicotinic alkaloid achieved by any means, whereas, copending ‘918 claim 9 requires reducing expression of MYC2a gene and/or NIC1 gene which is a species and thus anticipates the genus of instant claims 1 and 17.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 102
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.
7. Claim(s) 1 and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hibi et al. (The Plant Cell, 6(5):723-735, 1994).
Hibi et al. disclose tobacco plants carrying mutations at the NIC1 and NIC2 loci that result in reduced nicotine accumulation relative to wild-type plants. Hibi et al. further disclose that nic1 and nic2 mutant lines exhibit substantially lower nicotine levels compared to corresponding wild-type tobacco. Hibi et al. also disclose that these mutant lines are stable genetic lines and are propagated as tobacco plants. As nicotine is a nicotinic alkaloid, and because Hibi et al. expressly disclose tobacco plants having reduced nicotine levels relative to wild type, Hibi et al. thus disclose a tobacco cultivar comprising reduced levels of at least one nicotinic alkaloid compared to a naturally occurring tobacco plant. Hibi et al. further disclose stable inheritance of the low-nicotine phenotype through nuclear loci. Progeny plant, seed or cell derived from nic1/nic2 mutant plants inherit the reduced nicotine trait because the reference clearly disclose using pre-existing genetic stocks of nic mutant plant lines carrying nic1/nic2 mutations. These genetic stocks are creating through breeding analysis involving plant progenies and seeds derived thereof. The progeny plants, seed or cell derived from Hibi et al.’s low-nicotine lines would thus inherently possess reduced nicotine levels. See in particular, abstract; Table1; Figure 1; inheritance analysis, gene expression studies, results and discussion at pages 725-732, materials and methods at page 733.
Accordingly, Hibi et al. anticipates the claimed invention.
8. Claims 1, 12, 16, 17 and 45 are rejected under 35 U.S.C. §103 as being anticipated by Chakrabarti et al. (New Phytologist, 175:565-574, 2007).
Chakrabarti et al. disclose tobacco plants (N. tomentosiformis) and seeds derived thereof comprising a functional CYP82E3 allele with high nicotine N-demethylase (NND) activity. The reference further disclose that increased NND activity is due to C330W mutation in CYP82E3 protein. Increased NND activity of CYP82E3 disclosed in the reference resulted in increased conversion rate of nicotine to nornicotine. Increased conversion will inherently imply decrease in low nicotine (a nicotinic alkaloid). See in particular, 3rd paragraph of left column at page 566, 2nd paragraph of right column at page 568, 2nd paragraphs of left and right columns at page 571, Figure 2 at page 572, 1st paragraph of left column at page 572.
Accordingly, Chakrabarti et al. anticipated the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
9. Claims 1, 12, 16, 17, 45 and 46 are rejected under 35 U.S.C. §103 as being unpatentable over Hibi et al. (The Plant Cell, 6(5):723-735, 1994) in view of Gavilano et al. (Journal of Biological Chemistry, 282 :249-256, 2007)
Hibi et al. teach tobacco plants carrying mutations at the NIC1 and NIC2 loci that result in reduced nicotine accumulation relative to wild-type plants. Hibi et al. further teach that nic1 and nic2 mutant lines exhibit substantially lower nicotine levels compared to corresponding wild-type tobacco. Hibi et al. also teach that these mutant lines are stable genetic lines and are propagated as tobacco plants. As nicotine is a nicotinic alkaloid, and because Hibi et al. expressly disclose tobacco plants having reduced nicotine levels relative to wild type, Hibi et al. thus teach a tobacco cultivar comprising reduced levels of at least one nicotinic alkaloid compared to a naturally occurring tobacco plant. Hibi et al. further teach stable inheritance of the low-nicotine phenotype through nuclear loci. The reference clearly teach using pre-existing genetic stocks of nic mutant plant lines carrying nic1/nic2 mutations. Accordingly, Hibi expressly teaches a tobacco plant comprising reduced levels of at least one nicotinic alkaloid compared to a corresponding naturally occurring tobacco plant, as required by claim 1. These genetic stocks are creating through breeding analysis involving plant progenies and seeds derived thereof. Hibi et al. further teach that these genetic traits are heritable and maintained in stable tobacco lines used for propagation and analysis, thereby rendering obvious progeny plants, seeds, and cells derived from such cultivars as recited in claim 17. See in particular, abstract; Table 1; Figure 1; inheritance analysis, gene expression studies, results and discussion at pages 725-732, materials and methods at page 733.
Hibi does not disclose a CYP82E3 allele, does not disclose a CYP82E3 C330W substitution, and does not disclose altered nicotine N-demethylation activity associated with CYP82E3.
Gavilano et al. teach functional characterization of CYP82E family nicotine N-demethylase genes. Gavilano et al. teach that CYP82E3 originates from the Nicotiana tomentosiformis ancestral genome and that the NtomCYP82E3 allele encodes a functional nicotine N-demethylase enzyme. Gavilano expressly teach GenBank accession EF042306 as the genomic sequence of NtomCYP82E3. Gavilano et al. further teach that sequence analysis predicts a tryptophan residue at position 330, and that this C330W substitution is associated with functional nicotine N-demethylase activity. Gavilano further teach that NtomCYP82E3 contains two amino acid substitutions relative to wild-type CYP82E3: K118N and C330W. Importantly, Gavilano et al. expressly teach that heterologous expression of NtomCYP82E3 in yeast demonstrates nicotine N-demethylase activity comparable to the C330W CYP82E3 mutant, and concludes that the K118N polymorphism is neutral with respect to enzyme function. Thus, Gavilano et al., identifies C330W as the functionally relevant substitution responsible for CYP82E3 activity and expressly characterizes K118N as non-contributory to enzymatic function. See in particular, Abstract; pp. 253–254; Tables 1-4, 3rd paragraph from bottom of right column at page 252, Figs. 4-5.
Accordingly, Gavilano et al. teach a functional CYP82E3 allele comprising a nucleotide sequence encoding a C330W substitution relative to wild-type CYP82E3, and further teaches increased nicotine N-demethylation activity associated with the encoded protein.
The results of sequence homology between GenBank database accession no. EF042306 and instant SEQ ID NO: 6 is shown as below:
RESULT 2
C82E3_NICTO
ID C82E3_NICTO Reviewed; 518 AA.
AC A1YJE2;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 09-APR-2025, entry version 57.
DE RecName: Full=Nicotine N-demethylase CYP82E3 {ECO:0000303|PubMed:17102129};
DE Short=NND {ECO:0000303|PubMed:17102129};
DE EC=1.14.14.- {ECO:0000269|PubMed:17102129};
DE AltName: Full=Cytochrome P450 82E3 {ECO:0000303|PubMed:17102129};
DE Short=NtomCYP82E3 {ECO:0000303|PubMed:17102129};
GN Name=CYP82E3 {ECO:0000303|PubMed:17102129};
OS Nicotiana tomentosiformis (Tobacco).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; lamiids; Solanales; Solanaceae; Nicotianoideae; Nicotianeae;
OC Nicotiana.
OX NCBI_TaxID=4098;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=17102129; DOI=10.1074/jbc.m609512200;
RA Gavilano L.B., Coleman N.P., Bowen S.W., Siminszky B.;
RT "Functional analysis of nicotine demethylase genes reveals insights into
RT the evolution of modern tobacco.";
RL J. Biol. Chem. 282:249-256(2007).
CC -!- FUNCTION: Involved in the biosynthesis of pyridine alkaloid natural
CC products, leading mainly to the production of anabasine, anatabine,
CC nicotine and nornicotine, effective deterrents against herbivores with
CC antiparasitic and pesticide properties (neurotoxins); nornicotine
CC serves as the precursor in the synthesis of the carcinogen compound N'-
CC nitrosonornicotine (NNN) (PubMed:17102129). Catalyzes the demethylation
CC of nicotine to form nornicotine (PubMed:17102129).
CC {ECO:0000269|PubMed:17102129}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-nicotine + reduced [NADPH--hemoprotein reductase] + O2 =
CC (S)-nornicotine + formaldehyde + oxidized [NADPH--hemoprotein
CC reductase] + H2O + H(+); Xref=Rhea:RHEA:70999, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16842, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:59806, ChEBI:CHEBI:190184;
CC Evidence={ECO:0000269|PubMed:17102129};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71000;
CC Evidence={ECO:0000269|PubMed:17102129};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=48.1 uM for nicotine {ECO:0000269|PubMed:17102129};
CC Vmax=7.1 nmol/min/mg enzyme with nicotine as substrate
CC {ECO:0000269|PubMed:17102129};
CC -!- PATHWAY: Alkaloid biosynthesis; nicotine biosynthesis.
CC {ECO:0000269|PubMed:17102129}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in leaves. {ECO:0000269|PubMed:17102129}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in green leaves but rapidly fades
CC out during senescence. {ECO:0000269|PubMed:17102129}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. CYP82E2 subfamily.
CC {ECO:0000305}.
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DR EMBL; EF042306; ABM46919.1; -; Genomic_DNA.
DR AlphaFoldDB; A1YJE2; -.
DR SMR; A1YJE2; -.
DR GeneID; 104103346; -.
DR KEGG; nto:104103346; -.
DR OrthoDB; 1055148at2759; -.
DR BRENDA; 1.14.14.B11; 3648.
DR UniPathway; UPA00107; -.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0042179; P:nicotine biosynthetic process; IEA:UniProtKB-UniPathway.
DR FunFam; 1.10.630.10:FF:000026; Cytochrome P450 82C4; 1.
DR Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR InterPro; IPR050651; Plant_Cytochrome_P450_Monoox.
DR PANTHER; PTHR47947; CYTOCHROME P450 82C3-RELATED; 1.
DR PANTHER; PTHR47947:SF1; CYTOCHROME P450 82E3; 1.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; Cytochrome P450; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Alkaloid metabolism; Heme; Iron; Isopeptide bond; Membrane; Metal-binding;
KW Monooxygenase; Oxidoreductase; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..518
FT /note="Nicotine N-demethylase CYP82E3"
FT /id="PRO_0000455784"
FT TRANSMEM 2..22
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 458
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CROSSLNK 254
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9SZU1"
SQ SEQUENCE 518 AA; 59601 MW; 1E35CA3C8E795258 CRC64;
Query Match 99.4%; Score 2722; Length 518;
Best Local Similarity 99.6%;
Matches 516; Conservative 0; Mismatches 2; Indels 0; Gaps 0;
Qy 1 MVFPVEAIVGLVTFTFLFYFLWTKKSQKPSKPLPPKIPGGWPVIGHLFYFDDDGDDRPLA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MVFPVEAIVGLVTFTFLFYFLWTKKSQKPSKPLPPKIPGGWPVIGHLFYFDDDGDDRPLA 60
Qy 61 RKLGDLADKYGPVFTFRLGLPLVLVVSSYEAIKDCFSTNDAIFSNRPAFLYGEYLGYKNA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||| ||
Db 61 RKLGDLADKYGPVFTFRLGLPLVLVVSSYEAIKDCFSTNDAIFSNRPAFLYGEYLGYNNA 120
Qy 121 MLFLANYGSYWRKNRKLIIQEVLSASRLEKFKHVRFARIQTSIKNLYTRIDGNSSTINLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 MLFLANYGSYWRKNRKLIIQEVLSASRLEKFKHVRFARIQTSIKNLYTRIDGNSSTINLT 180
Qy 181 DWLEELNFGLIVKMIAGKNYESGKGDEQVERFKKAFKDFMILSMEFVLWDAFPIPLFKWV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DWLEELNFGLIVKMIAGKNYESGKGDEQVERFKKAFKDFMILSMEFVLWDAFPIPLFKWV 240
Qy 241 DFQGHVKAMKRTFKDIDSVFQNWLEEHIKKREKIMEVGTEGNEQDFIDVVLSKMSNEYLG 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 DFQGHVKAMKRTFKDIDSVFQNWLEEHIKKREKIMEVGTEGNEQDFIDVVLSKMSNEYLG 300
Qy 301 EGYSRDTVIKATVFSLVLDAADTVALHINCGMALLINNQNALKKAQEEIDTKVGKDRWVE 360
||||||||||||||||||||||||||||| ||||||||||||||||||||||||||||||
Db 301 EGYSRDTVIKATVFSLVLDAADTVALHINWGMALLINNQNALKKAQEEIDTKVGKDRWVE 360
Qy 361 ESDIKDLVYLQAIVKEVLRLYPPGPLLVPHENVEDCVVSGYHIPKGTRLFANVMKLQRDP 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 ESDIKDLVYLQAIVKEVLRLYPPGPLLVPHENVEDCVVSGYHIPKGTRLFANVMKLQRDP 420
Qy 421 KLWSNPDKFNPERFIARDIDFHGQHYEYIPFGSGRRSCPGMTYALQVEHLTMAHLIQGFN 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 KLWSNPDKFNPERFIARDIDFHGQHYEYIPFGSGRRSCPGMTYALQVEHLTMAHLIQGFN 480
Qy 481 YRTPTDEPLDMKEGAGITIRKVNPVKVIITPRLAPELY 518
||||||||||||||||||||||||||||||||||||||
Db 481 YRTPTDEPLDMKEGAGITIRKVNPVKVIITPRLAPELY 518
As to claim 12, the combination renders obvious a tobacco cultivar comprising a functional CYP82E3 allele.
As to claim 16, Gavilano et al. expressly teach that the C330W substitution restores nicotine N-demethylase activity, thereby increasing enzymatic activity relative to wild-type CYP82E3.
As to claim 17, progeny plants, seeds, and cells derived from the combined tobacco cultivar would have been obvious as routine and naturally flowing products of plant propagation.
As to claim 45, Gavilano et al. expressly disclose a CYP82E3 allele corresponding to EF042306 encoding a protein containing the C330W substitution relative to wild-type CYP82E3, thereby rendering the claimed allele obvious.
As to claim 46, Gavilano et al. disclose the complete amino acid sequence of the NtomCYP82E3 protein encoded by EF042306, which differs from wild-type CYP82E3 by two substitutions: K118N and C330W. Because Gavilano et al. expressly teach that the K118N substitution is functionally neutral and does not affect nicotine N-demethylase activity, the only functionally relevant structural difference between the disclosed sequence and wild-type CYP82E3 is the C330W substitution. Accordingly, the CYP82E3 protein of claim 46 would have been obvious over Gavilano et al. because the prior art expressly discloses the identical functional enzyme variant and identifies no functional significance for the additional K118N substitution.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to combine the teachings of Hibi et al. and Gavilano et al. Hibi et al. provide tobacco germplasm having a heritable low-alkaloid phenotype resulting from alterations in nicotine biosynthesis pathways. Gavilano et al. provide a structurally and functionally characterized CYP82E3 allele that confers nicotine N-demethylase activity through a defined amino acid substitution. Both references are directed to genetic and enzymatic regulation of nicotine alkaloid metabolism in tobacco. A person of ordinary skill in the art would have been motivated to introduce the functional CYP82E3 allele of Gavilano et al. into the tobacco genetic background of Hibi et al. to obtain plants possessing both reduced alkaloid accumulation and defined nicotine demethylation activity.
The combination represents the predictable use of prior art elements according to their established functions. Hibi et al. provide a stable heritable low-alkaloid tobacco background, while Gavilano et al. provide a defined enzyme variant with experimentally validated functional activity. One of ordinary skill in the art would have had a reasonable expectation of success in combining these teachings using routine plant breeding or genetic transformation techniques.
One of ordinary skill in the art would have been motivated to employ a functional CYP82E3 allele because the prior art recognized CYP82E3 as a member of the CYP82E nicotine N-demethylase family and taught that restoration of CYP82E3 activity increased conversion of nicotine to nornicotine. A skilled artisan interested in modifying tobacco alkaloid composition, studying nicotine metabolism, or producing tobacco plants exhibiting altered nicotine-to-nornicotine ratios would have found it obvious to utilize the functional CYP82E3 allele disclosed in the art. Because CYP82E3’s biochemical role and the effect of restoring its activity were known, use of a functional CYP82E3 allele to obtain a tobacco plant having reduced levels of at least one nicotinic alkaloid, namely nicotine, would have represented the predictable application of a known gene according to its established function, with a reasonable expectation of success.
Obviously one of skilled in the art prior to earliest filing date of instantly claimed invention would have been motivated to combine the low-nicotine trait with a functional CYP82E3 allele to create tobacco varieties having a desired alkaloid composition and improved commercial value for specific tobacco products. To modify the nicotine/nornicotine profile of low-nicotine tobacco, thereby producing commercially desirable tobacco with tailored alkaloid characteristics would have ultimate commercial goal.
The rejection is consistent with KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007), because the claimed subject matter merely combines known tobacco germplasm with reduced alkaloid content and a known functional CYP82E3 enzyme variant, yielding predictable results in nicotine alkaloid metabolism.
Conclusion
10. Claims 1, 12, 16, 17, 45 and 46 are rejected.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Vinod Kumar whose telephone number is (571) 272-4445. The examiner can normally be reached on 8.30 a.m. to 5.00 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad A. Abraham can be reached on (571) 270-7058 The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/VINOD KUMAR/Primary Examiner, Art Unit 1663
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