The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
1. The Office acknowledges the receipt of Applicant’s amendment filed September 10, 2025. Claims 33, 35-40, 42 and 44-52 are pending and are examined in the instant application.
All previous rejections not set forth below have been withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is made FINAL.
Double Patenting
2. Claims 33, 35-40, 42 and 44-52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35-45 of copending Application No.17/795409 (hereafter ‘409), which are directed to cured tobacco plant material and tobacco product having the same knockout genes as the cured tobacco plant material and tobacco product of the instant application. The claims of ‘409 are narrower in scope than the claims of the instant application. The claims of ‘409 recite 5 specific knockout mutant genes, and the claims of the instant application recite one specific knockout gene and four non-specific knockout genes. The species (the five specific knockout genes of ‘409) renders obvious the genus (one specific knockout gene and four non-specific knockout genes of the instant application). Additionally, because both claim sets recite the same knockout genes, the cured tobacco plant material and tobacco product of the instant application would inherently produce an anatabine level greater than the anatabine level of a control cured tobacco plant material and tobacco product. No additional treatment or processing of the cured tobacco is disclosed to increase the anatabine level. Both applications require five knockout genes to decrease the nicotine level and to increase the anatabine level. The Supreme Court explained long ago that “[i]t is not invention to perceive that the product which others had discovered had qualities they failed to detect.” Gen. Elec. Co. v. Jewel Incandescent Lamp Co., 326 U.S. 242, 249 (1945). ‘409 also teaches flue cured tobacco (claim 36), Burley tobacco (claim 37), BU 64 (Burley 64) (claim 46), sun-cured tobacco (claim 36), a tobacco blend (claim 38), a tobacco product (claim 41), a cigarette (claim 42), smokeless tobacco product (claim 43), loose leaf chewing tobacco (claim 44), and reconstituted tobacco (claim 45). It would have been obvious to include a flavoring or a filler such as expanded tobacco or non-tobacco plant material, as these are known in the prior art [0197].
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s Traversals
Applicant requests that the provisional nonstatutory double patenting rejection be withdrawn in view of the claim amendments filed in ‘409.
Response to Applicant’s Traversals
Applicant’s traversal is unpersuasive because the species (the five specific knockout genes of ‘409) renders obvious the genus (one specific knockout gene and four non-specific knockout genes of the instant application). Accordingly, the rejection is maintained.
Claim Rejections - 35 USC § 103
3. Claims 33, 35-40, 42 and 44-52 are rejected under 35 U.S.C. 103 as being unpatentable over Kudithipudi, C. (US Publication No. 20150322451 (previously cited)).
Kudithipudi teaches a cured tobacco plant material from a tobacco plant comprising five mutated PMT genes [0095]:
(a) a first knockout mutant allele in a PMT1α gene, wherein a wildtype allele of the PMT1α gene encodes the polypeptide of SEQ ID NO:2 which has 100% sequence identity to Applicant’s SEQ ID NO:12; and
(b) a second knockout mutant allele in a PMT1β gene, wherein a wildtype allele of the PMT1β gene encodes the polypeptide of SEQ ID NO:4 which has 98.5% sequence identity to Applicant’s SEQ ID NO:11; and
(c) a third knockout mutant allele in a PMT2 gene, wherein a wildtype allele of the PMT2 gene encodes the polypeptide of SEQ ID NO:6 which has 100% sequence identity to Applicant’s SEQ ID NO:13; and
(d) a fourth knockout mutant allele in a PMT3 gene, wherein a wildtype allele of the PMT3 gene encodes the polypeptide of SEQ ID NO:8 which has 100% sequence identity to Applicant’s SEQ ID NO:14; and
(e) a fifth knockout mutant allele in a PMT4 gene, wherein a wildtype allele of the PMT4 gene encodes the polypeptide of SEQ ID NO:10 which has 100% sequence identity to Applicant’s SEQ ID NO:15;
wherein the tobacco leaf has significantly less nicotine levels than a control tobacco leaf ([0011], [0012], [0032], [0072], [0074], [0076], Table 3, Examples 7 and 8).
Kudithipudi further teaches that the mutations would disrupt gene expression, either “significantly reduce or essentially eliminate the amount of PMT mRNA or polypeptide or the activity of PMT in the plant” [0076]. It should be noted that the claims do not require SEQ ID Nos. 11-15, because these are wildtype polypeptide sequences. The claims require mutated sequences of the genes encoding SEQ ID Nos. 11-15. Kudithipudi further teaches flue-cured tobacco [0009], Burley tobacco [0009], tobacco variety BU 64 [0068], air-cured tobacco [0084], a tobacco blend [0084], cigarette [0011], smokeless tobacco product [0011], loose leaf chewing tobacco [[0011], flavoring [0085], fillers [0085], reconstituted tobacco filler (milled or comminuted) [0084], expanded tobacco [0084], and non-tobacco plant material filler such as binders, plasticizers, stabilizers and flavorings [0085].
Kudithipudi does not teach SEQ ID NO:432 as the mutant PMT1α allele or reduced mold infection such as Cladosporium. Kudithipudi teaches deletion mutations to produce knockout PMT mutants ([0069], [0073], [0074], [0095]).
Even though Kudithipudi does not specifically teach SEQ ID NO:432 as part of the mutant PMT1α allele, there is no effect on the end use of the claimed cured tobacco products. That is, whether the knockout mutant allele comprises SEQ ID NO:432, which is an indel acat four-nucleotide deletion mutation of the PMT1α gene (Table 12A), or the knockout mutant allele comprises a deletion of other nucleotides of the PMT1α gene, as taught by Kudithipudi, does not produce an unexpected and practically significant difference on the end-use cured tobacco products. See Ex Parte C (27 USPQ2d 1492 (Bd. Pat. App. & Inter. 1992)), Ex Parte McGowen (Application No. 14996093, P.T.A.B. Jun 15, 2020) and MPEP 716.02(b). Applicant does not disclose an unexpected and practically significant or utilitarian difference between cured tobacco products from a plant comprising the indel acat four-nucleotide deletion mutation (SEQ ID NO:432) and a plant comprising a different knockout mutation as taught by Kudithipudi. Kudithipudi states that methods of making mutations to reduce expression of endogenous genes such as PMT genes are known in the art ([0069], [0070]). Kudithipudi teaches loss-of-function mutations including a mutation to create a stop codon resulting in a truncated polypeptide, a mutation in one or more of the highly conserved regions, mutations that disrupt a catalytic domain or binding domain, insertions, deletions and substitutions of nucleotides, and random or site-specific mutagenesis ([0069]-[0074]). A mutation such as Applicant’s indel acat four-nucleotide deletion would cause a frameshift in the reading frame, create a stop codon and result in a truncated polypeptide and a loss of function, which is taught by Kudithipudi. Specifically, Kudithipudi further states that Fig. 2 discloses the methyltransferase domains are from amino acid position 211 to amino acid position 320 [0071]. SEQ ID NO:432 has a four-nucleotide deletion which would cause a frameshift mutation at amino acid position 138 of SEQ ID NO:12 resulting in a downstream stop codon before the methyltransferase domain of Kudithipudi, thereby disrupting the catalytic domain (see mutant allele SEQ ID NO:432 and reference allele SEQ ID NO:464 in Fig. 12A). Thus, knockout mutations are well-known in the art, and the choice of an indel mutation such as Applicant’s SEQ ID NO:432 or another deletion or knockout mutation to disrupt the catalytic / binding domain as taught by Kudithipudi is a matter of design choice well within the means of one of ordinary skill in the art without any surprising or unexpected results. Even though Kudithipudi teaches knockouts of all five PMT genes, Kudithipudi is silent with regard to their level of nicotine in a tobacco leaf. However, the examples and data presented for a single knockout mutant PMT3 RNAi show a significant reduction in nicotine levels (Tables 2 and 4; Figs. 6, 7, 8 and 10). Thus, the claimed nicotine level of a tobacco leaf comprising all five knockout PMT mutants would be inherently less than 0.25% of the nicotine level from a control tobacco plant, absent evidence that SEQ ID NO:432 in combination with the other four generic knockout PMT mutants produce a different result from five knockout PMT mutants that does not utilize SEQ ID NO:432. With regard to the reduced mold infection such as Cladosporium of the cured tobacco, this is an inherent property of cured tobacco obtained from a plant that has the mutant PMT alleles (specification [0131]-[00133]) and is not due to an additional treatment or processing of the cured tobacco. Thus, the cured tobacco obtained from a plant that has the mutant PMT alleles of Kudithipudi would also exhibit reduced mold infection such as Cladosporium. Accordingly, absent a showing of surprising and unexpected results with regard to SEQ ID NO:432 in combination with four other knockout PMT mutants, the claimed invention is prima facie obvious in view of the prior art.
Applicant’s Traversals
Applicant traverses primarily the following. (1) The Examiner has not pointed to any portion of Kudithipudi that asserts or even suggests that “>0.15” is the detection limit for nicotine. (2) The Examiner has provided no evidence that tobacco plants having knockout mutations in five PMT genes necessarily possess the recited reduction in nicotine level as compared to a control plant, and none of the RNAi plants provided in Kudithipudi exhibit less than 0.25% of the nicotine level of a control plant. (3) Ex Parte C (27 USPQ2d 1492 (Bd. Pat. App. & Inter. 1992)), and Ex Parte McGowen (U.S. Patent Application No. 14/996,093, P.T.A.B Jun. 15, 2020) are non-precedential holdings and do not contain underlying facts that are analogous to the instant application and currently amended claims; and Applicant complied with MPEP 716.02(b) by demonstrating that the claimed subject matter can unexpectedly provide tobacco material with less than 0.25% of the nicotine level of a control tobacco plant (Tables 13A and 13B). (4) It is unclear how one of ordinary skill in the art would determine if a mutation falls within the metes and bounds of the claims without SEQ ID Nos: 11-15 as comparator sequences, or how one of ordinary skill in the art would have been able to generate the claimed subject matter by following Kudithipudi when a gene encoding a polypeptide of SEQ ID NO: 11 was unknown at the time of filing.
Response to Applicant’s Traversals
Applicant’s traversals have been considered but are deemed unpersuasive for the following reasons. With regard to traversal (1), if a nicotine level is indicated as being >0.15 when other nicotine levels are indicated by an actual value, one skilled in the art would reasonably conclude that levels below 0.15 are undetectable at the time the invention was made, or readings below 0.15 may be imprecise. Since the prior art publication inventor and Applicant are the same, Applicant is in the best position to clarify what the “>0.15” denote. Nevertheless, the >0.15 nicotine level is not particularly relevant here because it only refers to a knockout PMT3 mutant, and the amended claims recite “less than 0.25% of the nicotine level from a control tobacco plant” with regard to a plant having all five knockout PMT mutants. With regard to traversal (2), even though Kudithipudi teaches knockouts of all five PMT genes, Kudithipudi is silent with regard to their level of nicotine in a tobacco leaf. Because the knockout PMT3 mutant of Kudithipudi showed a significant reduction in nicotine levels, one skilled in the art would reasonably conclude that knockout mutants of all five PMT genes would further reduce the nicotine levels to Applicant’s claimed “less than 0.25%”. Applicant provided no evidence that SEQ ID NO:432 (PMT1α indel knockout mutant) in combination with four generic knockout PMT mutants would produce the claimed “less than 0.25%” nicotine level when compared to five knockout PMT mutants that do not utilize SEQ ID NO:432. Line CS120 is not commensurate in scope with the claims because it contains specific knockout mutations in all five PMT genes. The claims only require one specific knockout PMT mutation (PMT1α indel knockout mutant having SEQ ID NO:432) and four generic knockout PMT genes. If other lines having five knockout PMT genes do not produce the claimed “less than 0.25%” nicotine level, the claims should be amended accordingly to recite embodiments that would result in the “less than 0.25%” nicotine level. With regard to traversal (3), Ex Parte C and Ex Parte McGowen support the Office’s position that Applicant does not disclose an unexpected and practically significant or utilitarian difference between cured tobacco products from a plant comprising the indel acat four-nucleotide deletion mutation (SEQ ID NO:432) and a plant comprising one of the numerous knockout mutations taught by Kudithipudi. Ex Parte C states “there is a burden on the patent applicant to establish not only that the differences in results achieved are in fact “unexpected and unobvious” but also to establish that the differences are of practical significance.” Ex Parte McGowen supports the Office’s position that Applicant simply followed the teachings of Kudithipudi (five knockout PMT mutants to reduce the nicotine level in a tobacco plant) to arrive at the claimed invention. Applicant’s traversal with regard to MPEP 716.02(b) is not on point because the claims do not recite the specific embodiments (five specific knockout PMT mutants as shown for line CS120) that result in the surprising and unexpected “less than 0.25%” nicotine level when compared to that of other five knockout PMT mutants. With regard to traversal (4), the claims are drawn to a product and not to a method. Applicant’s SEQ ID NO:11 is not required. A knockout mutant PMT1β gene of Kudithipudi is indistinguishable from Applicant’s generic “knockout mutant allele in a PMT1b gene”. Accordingly, the rejection is maintained.
Conclusion
4. No claim is allowed.
5. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
6. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHUONG T BUI whose telephone number is (571)272-0793. The examiner can normally be reached on M-F 8am-5pm.
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/PHUONG T BUI/Primary Examiner, Art Unit 1663
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