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 .
Status of Claims
Claims 13-17 and 19-31 are pending and examined. Claims 1-12 and 18 have been cancelled.
Specification
The objection to the specification is withdrawn in light of the amendments.
Claim Rejections - 35 USC § 112
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.
Claim 17 is 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.
Claim 17 is drawn to modifying at least two of BBLa, BBLb and BBLc: there is insufficient antecedent basis for this limitation as the claim from which 17 depends is not directed to more than one BBLa, BBLb or BBLc.
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.
Claims 13-15 and 19-23 REMAIN rejected, and claims 17 and 24-31 are NOW rejected, under 35 U.S.C. 103 as being unpatentable over Kajikawa et al (2011, Plant Physiology, 155:2010-2022) in view of Dewey et al (2013, Phytochemistry, 94:10-27) and in further view of Lopez (2011, “Developing Non-GMO Tobacco Cultivars with Lower Alkaloid Content Using a Reverse Genetics Strategy”, Thesis for Masters of Science, North Carolina State University Raleigh, North Carolina) and Kudithipudi et al (Pub. No. US 2015/0322451 A1).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 13-15, 17 and 19-31 are drawn to a method of producing a Nicotiana plant comprising a modification to reduce the activity of at least one of BBLa, BBLb and BBLc and that comprises a mutation in a polynucleotide having the nucleotide sequence of SEQ ID NO: 1 and wherein the modification is carried out with a meganuclease, wherein the nicotinic alkaloid content is reduced by at least 97% as compared to a plant not comprising said modifications and mutation, and a method of producing said plant by combining in a Nicotiana plant comprising said modifications and said mutations.
Kajikawa et al teach that BBLs are required for the synthesis of nicotine, anatabine, anabasine and anatalline as evidenced by suppressing expression of BBLa, b and c in tobacco hairy roots, plants and plant cells (p. 2011, col. 1, penultimate par.; see also p. 2012, col. 2, last par.; see p. 2014).
Kajikawa et al also teach that BBLd corresponding to Genbank Accession No. AB604221 and having 100% sequence identity with SEQ ID NO: 1 of the instant invention was known in the art (p. 2020 beginning at paragraph entitled “Sequence data”).
Kajikawa et al teach that when expression of BBL genes was suppressed that nicotinic alkaloid content was reduced, in particular, nicotine production was highly reduced, and in some instance by at least 97% (see Abstract; see also p. 2013, Figure 3; see also p. 2015, Figure 6).
Kajikawa et al does not teach a Nicotiana plant that is modified to reduce the activity of at least one of BBLa, BBLb, BBlc and which further comprises a mutation in at least one endogenous polynucleotide having the nucleotide sequence of SEQ ID NO: 1.
Dewey et al teach that although other genes of the alkaloid biosynthetic pathway could also be targeted to produce low nicotine varieties, the down-regulation of many of these is accompanied by undesirable side effects, such as plant lethality or the production of other alkaloids. Dewey et al teach that the A622 gene impacts the synthesis of the entire suite of tobacco pyridine alkaloids (p. 17, col. 1, penultimate par).
However, targeting the BBL gene family is a promising target because plants display a low leaf alkaloid profile without negatively impacting plant growth and development (p. 23, col. 2, penultimate par.). In fact, even a novel alkaloid that accumulates as a result of BBL gene inhibition only occurs in root but not the leaf. Dewey et al teaches that it is known that frame shift mutations abolish protein activity (p. 19, col. 2, last ¶ bridging p. 20).
Dewey et al teaches that there is a need to reduce nicotine levels in tobacco products because of the negative health and economic consequences associated with smoking tobacco products (p. 1, col. 1, par. 1).
Lopez teaches that BBL genes will be the most favorable targets for developing tobacco plants with significantly reduced levels of nicotine and other pyridine alkaloids, and that the identification of knockout mutations within the three most highly transcribed BBL genes provides a means of producing low alkaloid tobacco plants that are not considered to be genetically modified and thus avoid the hurdles involved with the release of transgenic crops (see Abstract).
Kudithipudi et al teach that it was known in the art that genes involved in alkaloid biosynthesis can be targeted for mutagenesis using TALENs (e.g., see Example 7).
Therefore, prior to the effective filing date of the instant invention, it would have been prima facie obvious to one of ordinary skill in the art to try to reduce the activity of BBLa, BBLb and BBLc as taught by Kajikawa et al in addition to mutating a polynucleotide having about 97% to 100% sequence identity to SEQ ID NO: 1 (i.e., a BBLd gene) because the art recognizes that suppressing expression of the BBL gene family is a promising target for producing low nicotine tobacco products, the importance of which is addressed supra in Dewey et al.
Moreover, there are a finite number of identified, predictable potential solutions to lower nicotine content: target the BBLa, b, c and d genes, the nucleotide sequences of which were known in the art.
One would have found it obvious to use a meganuclease such as TALENs and to target an upstream region of a FAD binding domain for obtaining said plant because to do so is a design choice in so far as the use of TALENs and other mutagenesis techniques inhibit expression of genes of interest with a reasonable expectation of success (i.e., they are functionally interchangeable).
Furthermore, one would have a reasonable expectation of success in doing so because the art teaches the successful inhibition of the BBLa, b, and c genes, and because predictable methods for inhibiting gene expression, for example, EMS mutagenesis or TILLING as taught by Lopez, could be used to generate non-transgenic tobacco plants and products such as cigarettes as encompassed by instant claims 10 and 11, the importance of which is discussed above.
One would be motivated to target each gene copy of the aforementioned BBL gene family members in order to ensure that no nicotine is produced. Because this plant would be structurally indistinguishable from that as instantly claimed (i.e., it comprises reduced activity in the BBLa, b and c genes and a mutation in the polynucleotide sequence of SEQ ID NO: 1), it is necessarily follows that said plant will have the nicotinic alkaloid contents as instantly claimed.
One would be further motivated to reduce the expression of a polynucleotide encoding an additional nicotinic alkaloid biosynthetic enzyme such as A622 as encompassed by instant claim 20 because the art recognizes that it impacts the synthesis of the entire suite of tobacco pyridine alkaloids and could therefore further reduce nicotinic alkaloid levels when combined in a plant with reduced BBL a, b and c levels.
Response to Arguments
Applicant traverses the rejection of the claims because claim 18 was cited as being free of the art and has been incorporated into instant claim 13 (Applicant reply dated 10 September 2026, p. 12, section IV).
This argument is not persuasive because previously presented claim 18 depended upon previously presented claim 16 which was deemed free of the art. Instant claim 13 does not include any of the limitations of previously presented claim 16.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 13-17 and 19-23 REMAIN rejected, and claims 24-31 are NOW rejected, on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of Patent No. US 11,214,813 (referred to herein as ‘813). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 13-17 and 19-31 are drawn to a method of producing a tobacco product from a Nicotiana plant that is modified to reduce the activity of at least one of BBLa, BBLb, BBLc and comprises a mutation in a combination of polynucleotides having at least 97% sequence identity to SEQ ID NO: 1, 2 and 3 wherein the modification is made using a meganuclease.
‘813 claims a Nicotiana plant that is modified to reduce activity of at least one of BBLa, BBLb, BBLc and comprises a mutation in a combination of polynucleotides having at least 97% sequence identity to SEQ ID NO: 1, 2 and 3, and a method of making said plant comprising reduced nicotinic alkaloid. ‘813 teaches that modification to BBL genes can be made using meganucleases (col. 12, last ¶).
Therefore, prior to the effective filing date of the instant invention it would have been prima facie obvious to one of ordinary skill in the art to arrive at the product from the plant as instantly claimed because ‘813 claims the same plant as instantly claimed which would yield products having reduced levels of the nicotinic alkaloid and because a “modification” as claimed overlaps in scope with the teachings and claims of ‘813.
Response to Arguments
Applicant traverse the rejection because ‘813 does not refer to meganuclease in the claims (Applicant reply dated 10 September 2026, p. 12 section V).
This argument is not persuasive because ‘813 generally claims a modification which the specification teaches may be made using a meganuclease and thus renders the instant claims obvious.
Claims 13-17 and 19-23 REMAIN rejected, and claims 24-31 are NOW rejected, on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,270,038 (referred to herein as ‘038). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-17 and 19-31 are drawn to a method of producing a tobacco product from a Nicotiana plant that is modified to reduce the activity of at least one of BBLa, BBLb, BBLc and comprises a mutation in a combination of polynucleotides having at least 97% sequence identity to SEQ ID NO: 1, 2 and 3 wherein the modification is made using a meganuclease.
‘038 claims a method of producing a tobacco product comprising tobacco from a Nicotiana plant comprising combining modifications that reduce at least one of BBLa, BBLb, BBLc and that comprises a mutation in a combination of polynucleotides having at least 97% sequence identity to SEQ ID NO: 1, 2 and 3. ‘038 teaches that modification to BBL genes can be made using meganucleases (col. 12, last ¶).
Therefore, prior to the effective filing date of the instant invention it would have been prima facie obvious to one of ordinary skill in the art to arrive at the products produced by the methods as instantly claimed and the methods because ‘038 claims methods to produce the plants as claimed and products derived from said plants and because a “modification” as claimed overlaps in scope with the teachings and claims of ‘038.
Response to Arguments
Applicant traverse the rejection because ‘038 does not refer to meganuclease in the claims (Applicant reply dated 10 September 2026, p. 12 section V).
This argument is not persuasive because ‘038 generally claims a modification which the specification teaches may be made using a meganuclease and thus renders the instant claims obvious.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JASON DEVEAU-ROSEN whose telephone number is (571)272-2828. The examiner can normally be reached 7:30am - 4pm.
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/JASON DEVEAU ROSEN/Primary Examiner, Art Unit 1662
