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 1-23 are pending and examined.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g., see p. 48, line 15). Applicant is required to delete all embedded hyperlinks and/or other forms of browser-executable code. See MPEP §608.01.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement (e.g., see p. 51). 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
In claim 41, the limitation --a-- should be inserted prior the limitation “modification” in part (A).
Appropriate action is advised.
Claim Rejections - 35 USC § 103
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 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 1-3, 6-8, 10-15 and 19-23 is/are 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).
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 1-3, 6-8, 10-15 and 19-23 are drawn to a tobacco product comprising tobacco from a Nicotiana plant that is modified 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, 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 as encompassed by instant claims 1 (A), 2 and 3 (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 as encompassed by instant claims 1(B)(i) and 13(B)(i) (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% as in instant claims 6, 7 and 8 (see Abstract; see also p. 2013, Figure 3; see also p. 2015, Figure 6).
Kajikawa et al does not teach tobacco products comprising tobacco from 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 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).
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.
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 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.
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 1-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 and 14 of U.S. Patent No. 10,590,429 (referred to herein as ‘429). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 29-42 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.
‘429 claims a tobacco product comprising tobacco from a plant comprising reduced 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, a method of making said plant comprising reduced nicotinic alkaloid, and products produced therefrom.
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 because ‘492 claims methods to produce the plants as claimed and products derived from said plants in addition to products that are encompassed by the instant claims.
Claims 1-23 are 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 1-23 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.
‘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.
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.
Claims 1-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of Patent No. US 11,753,649 (referred to herein as ‘649). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-23 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.
‘649 claims a Nicotiana plant part modified to reduce activity 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, and a method of making said plant comprising reduced nicotinic alkaloid, and products produced therefrom.
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 ‘649 claims the plant parts comprising the same mutations and thus the same plant as instantly claimed which would yield products having reduced levels of the nicotinic alkaloid.
Claims 1-23 are 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 1-23 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.
‘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.
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.
Conclusion
No claim is allowed.
Claims 4, 5, 9 and 16-18 appear to be free of the prior art because it fails to reasonably teach or suggest arriving at SEQ ID NO: 2 and 3 as instantly claimed. The closest prior art is Kajikawa et al (2011, Plant Physiology, 155:2010-2022) which discloses a nucleotide sequence having 92% sequence identity to SEQ ID NO: 2 of the instant invention (see Attachment A).
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 as encompassed by instant claims 29 (A), 30 and 31 (see p. 2011, col. 1, penultimate ¶; see also p. 2012, col. 2, last ¶; 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 ¶ entitled “Sequence data”), and 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).
However, Kajikawa et al does not teach tobacco products produced from 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.
The closest prior art is also Goossens et al (2003, PNAS, 100:8595-8600), which teaches the nucleotide sequence of Genbank Accession No. AM851017 having 86% sequence identity to SEQ ID NO: 3.
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
ATTACHMENT A
Alignment of Genbank Accession No. AB604221 with SEQ ID NO: 1 of the instant invention
AB604221
LOCUS AB604221 1704 bp mRNA linear PLN 08-APR-2011
DEFINITION Nicotiana tabacum BBLd mRNA for berberine bridge enzyme-like
protein, complete cds.
ACCESSION AB604221
VERSION AB604221.1
KEYWORDS .
SOURCE Nicotiana tabacum (common tobacco)
ORGANISM Nicotiana tabacum
Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
Spermatophyta; Magnoliophyta; eudicotyledons; Gunneridae;
Pentapetalae; asterids; lamiids; Solanales; Solanaceae;
Nicotianoideae; Nicotianeae; Nicotiana.
REFERENCE 1
AUTHORS Kajikawa,M., Shoji,T., Kato,A. and Hashimoto,T.
TITLE Vacuole-localized berberine bridge enzyme-like proteins are
required for a late step of nicotine biosynthesis in tobacco
JOURNAL Plant Physiol. 155 (4), 2010-2022 (2011)
PUBMED 21343426
REMARK DOI:10.1104/pp.110.170878
REFERENCE 2 (bases 1 to 1704)
AUTHORS Kajikawa,M. and Hashimoto,T.
TITLE Direct Submission
JOURNAL Submitted (12-DEC-2010) Contact:Masataka Kajikawa Nara Institute of
Science and Technology, Graduate School of Biological Sciences;
8916-5, Ikoma, Takayama-cho, Nara 630-0192, Japan
FEATURES Location/Qualifiers
source 1..1704
/organism="Nicotiana tabacum"
/mol_type="mRNA"
/cultivar="petit havana SR1"
/db_xref="taxon:4097"
gene 1..1704
/gene="BBLd"
CDS 1..1704
/gene="BBLd"
/codon_start=1
/product="berberine bridge enzyme-like protein"
/protein_id="BAK18781.1"
/translation="MKRNISMFLQLLLIILMMISFLFTSLLVPSVSATTLNTISTCLI
NYKVSNFSVYPTRNHAGNSYYNLLDFSIQNLRFAACSKPKPTVIIVPESKEQLVSSVL
CCRQGSYEIRVRCGGHSYEGTSSVSFDGSPFVVIDLMKLDGVSVDVDSETAWVQGGAT
LGQTYYAISRASNVHGFSAGSCPTVGVGGHISGGGYGFLSRKYGLAADNVVDALLVDA
EGRLLDRKAMGEEIFWAIRGGGGGIWGIIYAWKIRLLKVPKTVTSFIIPRPGSKRYVS
QLVHKWQLVAPKLEDEFYLSISMSSPSKGNIPIEINAQFSGFYLGTKTEAISILNEAF
SELGVLEGDCKEMSWIESTLFFSELNDVANSSDVSRLKERYFENKSYFKAKSDYVKTP
ISVGGIMTALNVLEKEPNGHVILDPYGGAMQRISEEAIA FPHRKGNLFGIQYLVVWKE
KDNNNIVKSNIGYIEWIREFYNTMAPHVSSSPRAAYVNYMDLDLGVMDDYLLPCTSTT
ASANHAVERARVWGEKYFLNNYDRLVKAKTKIDPLNVFRHQQGIPPLFASMQEYTYSS
K"
Query Match 100.0%; Score 1704; DB 126; Length 1704;
Best Local Similarity 100.0%;
Matches 1704; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGAAACGAAATATATCCATGTTTCTTCAGCTTCTGCTCATTATTCTGATGATGATCAGC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGAAACGAAATATATCCATGTTTCTTCAGCTTCTGCTCATTATTCTGATGATGATCAGC 60
Qy 61 TTCTTATTTACTTCTCTTCTTGTACCTTCGGTCTCTGCAACAACTCTCAATACCATTTCC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TTCTTATTTACTTCTCTTCTTGTACCTTCGGTCTCTGCAACAACTCTCAATACCATTTCC 120
Qy 121 ACCTGTTTAATCAATTACAAAGTCAGTAACTTCTCTGTTTACCCAACAAGGAATCATGCT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ACCTGTTTAATCAATTACAAAGTCAGTAACTTCTCTGTTTACCCAACAAGGAATCATGCT 180
Qy 181 GGTAATAGTTACTATAACTTGCTTGATTTCTCCATTCAGAATCTCCGATTCGCAGCGTGC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GGTAATAGTTACTATAACTTGCTTGATTTCTCCATTCAGAATCTCCGATTCGCAGCGTGC 240
Qy 241 TCTAAACCAAAACCAACTGTCATTATCGTACCAGAGAGCAAGGAGCAGCTGGTGAGCAGC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TCTAAACCAAAACCAACTGTCATTATCGTACCAGAGAGCAAGGAGCAGCTGGTGAGCAGC 300
Qy 301 GTTCTGTGTTGCAGACAAGGCTCGTATGAAATCAGAGTAAGGTGCGGTGGACACAGTTAT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GTTCTGTGTTGCAGACAAGGCTCGTATGAAATCAGAGTAAGGTGCGGTGGACACAGTTAT 360
Qy 361 GAAGGGACTTCATCAGTTTCCTTTGATGGTTCCCCATTTGTGGTCATTGATTTGATGAAA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GAAGGGACTTCATCAGTTTCCTTTGATGGTTCCCCATTTGTGGTCATTGATTTGATGAAA 420
Qy 421 TTAGACGGCGTTTCAGTGGATGTGGATTCAGAAACCGCGTGGGTACAGGGCGGCGCTACA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 TTAGACGGCGTTTCAGTGGATGTGGATTCAGAAACCGCGTGGGTACAGGGCGGCGCTACA 480
Qy 481 CTTGGCCAGACTTATTATGCCATTTCCCGAGCCAGCAACGTTCATGGATTTTCAGCTGGT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CTTGGCCAGACTTATTATGCCATTTCCCGAGCCAGCAACGTTCATGGATTTTCAGCTGGT 540
Qy 541 TCTTGCCCAACAGTTGGGGTTGGCGGGCACATTTCCGGGGGTGGTTACGGATTTTTATCC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 TCTTGCCCAACAGTTGGGGTTGGCGGGCACATTTCCGGGGGTGGTTACGGATTTTTATCC 600
Qy 601 AGAAAATATGGACTTGCTGCTGATAACGTGGTGGATGCTCTTCTTGTTGATGCGGAAGGA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 AGAAAATATGGACTTGCTGCTGATAACGTGGTGGATGCTCTTCTTGTTGATGCGGAAGGA 660
Qy 661 CGGCTATTAGACCGCAAAGCCATGGGAGAAGAAATCTTTTGGGCCATCAGAGGTGGAGGT 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 CGGCTATTAGACCGCAAAGCCATGGGAGAAGAAATCTTTTGGGCCATCAGAGGTGGAGGT 720
Qy 721 GGAGGAATTTGGGGAATCATTTACGCCTGGAAAATCCGATTGCTCAAAGTGCCCAAGACC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GGAGGAATTTGGGGAATCATTTACGCCTGGAAAATCCGATTGCTCAAAGTGCCCAAGACC 780
Qy 781 GTGACCAGTTTCATAATCCCTAGGCCTGGCTCCAAACGATATGTGTCCCAACTAGTTCAC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GTGACCAGTTTCATAATCCCTAGGCCTGGCTCCAAACGATATGTGTCCCAACTAGTTCAC 840
Qy 841 AAATGGCAACTTGTTGCACCAAAGTTAGAGGATGAATTTTATCTATCGATCTCCATGAGC 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 AAATGGCAACTTGTTGCACCAAAGTTAGAGGATGAATTTTATCTATCGATCTCCATGAGC 900
Qy 901 TCTCCTAGTAAAGGAAACATTCCTATTGAAATAAATGCCCAATTCAGCGGATTTTACCTA 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 TCTCCTAGTAAAGGAAACATTCCTATTGAAATAAATGCCCAATTCAGCGGATTTTACCTA 960
Qy 961 GGTACAAAAACCGAAGCCATTTCCATCTTGAATGAGGCCTTTTCGGAGTTGGGAGTTCTG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 GGTACAAAAACCGAAGCCATTTCCATCTTGAATGAGGCCTTTTCGGAGTTGGGAGTTCTG 1020
Qy 1021 GAAGGTGACTGCAAAGAAATGAGTTGGATTGAATCAACACTTTTCTTCTCCGAATTAAAT 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GAAGGTGACTGCAAAGAAATGAGTTGGATTGAATCAACACTTTTCTTCTCCGAATTAAAT 1080
Qy 1081 GACGTTGCGAATTCCTCCGATGTCTCTCGTTTGAAAGAGCGTTACTTTGAAAACAAATCA 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 GACGTTGCGAATTCCTCCGATGTCTCTCGTTTGAAAGAGCGTTACTTTGAAAACAAATCA 1140
Qy 1141 TACTTCAAAGCCAAATCAGACTATGTGAAGACCCCAATTTCAGTGGGTGGGATTATGACG 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 TACTTCAAAGCCAAATCAGACTATGTGAAGACCCCAATTTCAGTGGGTGGGATTATGACG 1200
Qy 1201 GCTCTTAATGTTCTTGAGAAAGAACCCAACGGACATGTCATCTTGGACCCTTATGGTGGA 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 GCTCTTAATGTTCTTGAGAAAGAACCCAACGGACATGTCATCTTGGACCCTTATGGTGGA 1260
Qy 1261 GCCATGCAAAGAATTAGTGAGGAAGCTATTGCTTTCCCTCATAGAAAGGGTAACCTTTTC 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 GCCATGCAAAGAATTAGTGAGGAAGCTATTGCTTTCCCTCATAGAAAGGGTAACCTTTTC 1320
Qy 1321 GGAATTCAATATCTAGTAGTGTGGAAAGAAAAGGACAATAATAATATTGTCAAGAGCAAT 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 GGAATTCAATATCTAGTAGTGTGGAAAGAAAAGGACAATAATAATATTGTCAAGAGCAAT 1380
Qy 1381 ATTGGGTACATAGAGTGGATAAGAGAGTTTTACAATACAATGGCACCCCATGTTTCAAGT 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 ATTGGGTACATAGAGTGGATAAGAGAGTTTTACAATACAATGGCACCCCATGTTTCAAGT 1440
Qy 1441 TCACCTAGGGCAGCTTATGTCAACTACATGGATCTGGACCTTGGAGTGATGGACGACTAC 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 TCACCTAGGGCAGCTTATGTCAACTACATGGATCTGGACCTTGGAGTGATGGACGACTAC 1500
Qy 1501 TTATTGCCATGTACTAGTACTACTGCGTCTGCTAATCATGCCGTGGAGAGAGCAAGGGTC 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 TTATTGCCATGTACTAGTACTACTGCGTCTGCTAATCATGCCGTGGAGAGAGCAAGGGTC 1560
Qy 1561 TGGGGTGAAAAGTATTTCTTGAATAACTATGATAGATTGGTCAAAGCTAAGACAAAAATT 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 TGGGGTGAAAAGTATTTCTTGAATAACTATGATAGATTGGTCAAAGCTAAGACAAAAATT 1620
Qy 1621 GACCCACTAAACGTTTTTCGACATCAACAGGGCATCCCTCCTTTGTTCGCCTCAATGCAA 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 GACCCACTAAACGTTTTTCGACATCAACAGGGCATCCCTCCTTTGTTCGCCTCAATGCAA 1680
Qy 1681 GAGTATACCTATAGTAGTAAATGA 1704
||||||||||||||||||||||||
Db 1681 GAGTATACCTATAGTAGTAAATGA 1704
Alignment of Genbank Accession No. AM851017 with SEQ ID NO: 3 of the instant invention
AM851017
LOCUS AM851017 1946 bp mRNA linear PLN 04-SEP-2007
DEFINITION Nicotiana tabacum mRNA for berberine bridge enzyme like protein
(T440 gene).
ACCESSION AM851017
VERSION AM851017.1
KEYWORDS berberine bridge enzyme like protein; T440 gene.
SOURCE Nicotiana tabacum (common tobacco)
ORGANISM Nicotiana tabacum
Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
Spermatophyta; Magnoliophyta; eudicotyledons; Gunneridae;
Pentapetalae; asterids; lamiids; Solanales; Solanaceae;
Nicotianoideae; Nicotianeae; Nicotiana.
REFERENCE 1
AUTHORS Goossens,A., Hakkinen,S.T., Laakso,I., Seppanen-Laakso,T.,
Biondi,S., De Sutter,V., Lammertyn,F., Nuutila,A.M., Soderlund,H.,
Zabeau,M., Inze,D. and Oksman-Caldentey,K.M.
TITLE A functional genomics approach toward the understanding of
secondary metabolism in plant cells
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 100 (14), 8595-8600 (2003)
PUBMED 12826618
REFERENCE 2
AUTHORS Haekkinen,S., Tilleman,S., Witek,A., De Sutter,V., Rischer,H.,
Vanhoutte,I., Van Onckelen,H., Hilson,P., Inze,D.,
Oksman-Caldentey,K.M. and Goossens,A.
TITLE Functional characterisation of genes involved in pyridine alkaloid
biosynthesis in tobacco
JOURNAL Unpublished
REFERENCE 3 (bases 1 to 1946)
AUTHORS Goossens,A.
TITLE Direct Submission
JOURNAL Submitted (03-SEP-2007) Goossens A., Plant Systems Biology,
VIB/UGent, Technologiepark 927, Gent, B-9052, BELGIUM
FEATURES Location/Qualifiers
source 1..1946
/organism="Nicotiana tabacum"
/mol_type="mRNA"
/db_xref="taxon:4097"
/cell_line="BY-2"
/tissue_type="suspension cell culture"
gene 1..1946
/gene="T440"
CDS 15..1721
/gene="T440"
/codon_start=1
/product="berberine bridge enzyme like protein"
/protein_id="CAO99130.1"
/db_xref="GOA:A7WPL6"
/db_xref="InterPro:IPR006094"
/db_xref="InterPro:IPR012951"
/db_xref="InterPro:IPR016166"
/db_xref="InterPro:IPR016167"
/db_xref="InterPro:IPR016168"
/db_xref="UniProtKB/TrEMBL:A7WPL6"
/translation="MFPLIILISFSLTSLSATATSGAGGGVANLYTCLIDHNVHNFSI
YPTKNDQSSSNYFNLLDFSLQNLRFAASYMPKPTVIILPNSKEELVSTILCCRQASYE
IRVRCGGHSYEGTSYVSFDGSPFVIVDLMKLDEVSVDLDSETAWAQGGATIGQIYYAI
AKVSDVHAFSAGSGPTVGSGGHISGGGFGLLSRKFGLAADNVVDALLIDADGRLLDRK
AMGEDVFWAIRGGGGGNWGIIYAWKIRLLKVPKIVTTCMIYRPGSKQYVAQLLQKWQI
VTPNLVDDFTLGVLLRPADLPADMKYGNSTPIEIFPQFNALYLGPKTEVLSISNEEFP
ELGVKNDECKEMTWIESALFFSELADINGNSSNDISRLKERYMDGKGFFKGKTDYVKK
PVSMDGMLTFLVELEKNPKGYLVFDPYGGAMDKIDDQAIA FPHRKGNLFAIQYLAQWN
EEDDYKSDVYMEWIRGFYNTMTPFVSSSPRGAYINYLDMDLGVNMDDDYLLRNASSRN
SSSSVDAVERARAWGEMYFLHNYDRLVKAKTQIDPLNVFRHEQSIPPMLGSTQEHKYS
SE"
Query Match 86.6%; Score 1470.8; DB 128; Length 1946;
Best Local Similarity 92.3%;
Matches 1560; Conservative 0; Mismatches 127; Indels 3; Gaps 1;
Qy 1 ATGTTTCCAATCATAATTCTGATCAGCTTTTCATTTACTTTCCTCTTTGCTAGTGTTACT 60
||||||||| ||||||||||||||||||||||| |||||| ||||| ||||| || |||
Db 15 ATGTTTCCACTCATAATTCTGATCAGCTTTTCACTTACTTCCCTCTCTGCTACTGCAACT 74
Qy 61 AGTGGAGCAGGA---GGAGTTACAAATCTTTCCACCTGTTTAATCAACCACAATGTCCAT 117
|||||||||||| |||||| ||||||||| ||||||||||||| ||||||||||||||
Db 75 AGTGGAGCAGGAGGTGGAGTTGCAAATCTTTACACCTGTTTAATCGACCACAATGTCCAT 134
Qy 118 AACTTCTCTATTTACCCCACAAAGAATGATCAAAGTAGTAGTAATTACTTTAACTTGCTC 177
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 135 AACTTCTCTATTTACCCCACAAAGAATGATCAAAGTAGTAGTAATTACTTTAACTTGCTC 194
Qy 178 GATTTTTCCCTTCAGAATCTTCGATTTGCTGCATCTTACATGCCGAAACCAACGGTCATT 237
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 195 GATTTTTCCCTTCAGAATCTTCGATTTGCTGCATCTTACATGCCGAAACCAACGGTCATT 254
Qy 238 ATCCTACCAAACAGCAAAGAGGAGCTCGTGAGTACCATTCTTTGTTGCAGACAAACATCT 297
|| ||||||||||||||||||||||||||||| ||||||||||||||||||||| | |||
Db 255 ATTCTACCAAACAGCAAAGAGGAGCTCGTGAGCACCATTCTTTGTTGCAGACAAGCTTCT 314
Qy 298 TATGAAATCAGAGTAAGGTGCGGAGGACACAGTTACGAGGGAACTTCTTACGTTTCCTTT 357
||||||||||||||||||||||||||||| ||||||||||||||||||||||||||||||
Db 315 TATGAAATCAGAGTAAGGTGCGGAGGACATAGTTACGAGGGAACTTCTTACGTTTCCTTT 374
Qy 358 GACGGTTCCCCTTTCGTGATCGTTGACTTGATGAAATTAGACGACGTTTCAGTAGATTTG 417
||||||||||| |||||||||||||||||||||||||||||||| |||||||||||||||
Db 375 GACGGTTCCCCGTTCGTGATCGTTGACTTGATGAAATTAGACGAAGTTTCAGTAGATTTG 434
Qy 418 GATTCCGAAACAGCTTGGGCTCAGGGCGGCGCAACAATTGGCCAAATTTATTACGCCATT 477
||||| ||||| ||||||||||||||||||||||||||||||||||||||||||||||||
Db 435 GATTCTGAAACTGCTTGGGCTCAGGGCGGCGCAACAATTGGCCAAATTTATTACGCCATT 494
Qy 478 TCCAGGGTTAGTGACGTTCATGCATTTTCAGCAGGTTCGGGACCAACAGTAGGATCTGGA 537
||| ||| |||||||||||||||||||||||||||||||||||||||||||||||||||
Db 495 GCCAAGGTAAGTGACGTTCATGCATTTTCAGCAGGTTCGGGACCAACAGTAGGATCTGGA 554
Qy 538 GGTCATATTTCAGGTGGCGGCTTTGGACTAATGTCCAGAAAATTCGGACTCGCTGCTGAT 597
||||||||||||||||||||||||||||| | || ||||||||||||||||||||||||
Db 555 GGTCATATTTCAGGTGGCGGCTTTGGACTTTTATCTAGAAAATTCGGACTCGCTGCTGAT 614
Qy 598 AGTGTCGTTGATGCTCTTCTAATTGATGCTGAAGGACGGTTATTAGACCGGAAAGCCATG 657
| |||||||||||||||||| || |||||||| || |||||||||||||| |||||||||
Db 615 AATGTCGTTGATGCTCTTCTTATCGATGCTGATGGGCGGTTATTAGACCGAAAAGCCATG 674
Qy 658 GGAGAAGACGTATTTTGGGCAATCAGAGGTGGCGGCGGTGGAAATTGGGGAATTATTTAT 717
||||||||||| ||||||||||||||||||||||| || |||||||||||||||||||||
Db 675 GGAGAAGACGTGTTTTGGGCAATCAGAGGTGGCGGAGGAGGAAATTGGGGAATTATTTAT 734
Qy 718 GCCTGGAAAATTCGATTACTCAAAGTGCCTAAAATCGTAACAACTTGTATGATCTATAGG 777
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 735 GCCTGGAAAATTCGATTACTCAAAGTGCCTAAAATCGTAACAACTTGTATGATCTATAGG 794
Qy 778 CCTGGATCCAAACAATACGTGGCTCAACTACTTCAGAAATGGCAAATAGTTACTCCAAAT 837
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 795 CCTGGATCCAAACAATACGTGGCTCAACTACTTCAGAAATGGCAAATAGTTACTCCAAAT 854
Qy 838 TTGGCCGATGATTTTACTCTAGGAGTACTCATGAGACCTATAGATCTGCGGGCGGATATG 897
|||| ||||||||||||||||||||||||| |||||||| |||||| | ||||||||||
Db 855 TTGGTCGATGATTTTACTCTAGGAGTACTCTTGAGACCTGCAGATCTACCGGCGGATATG 914
Qy 898 AATTACGGAAATACTACTCCTATTGAAACATTTCCCCAATTCAATGCACTTTATTTGGGT 957
|| || || || | |||||||||||||| |||||||||||||||||||||||||||||||
Db 915 AAATATGGCAACAGTACTCCTATTGAAATATTTCCCCAATTCAATGCACTTTATTTGGGT 974
Qy 958 CCAAAAACTGAAGCGGTTTCCATATTAAATGAGGCATTTCCAGAGCTGGACGCTAAGAAT 1017
||||||||||||| |||| |||| ||||||| |||||| ||||||| || |||||||
Db 975 CCAAAAACTGAAGTCCTTTCTATATCGAATGAGGAATTTCCGGAGCTGGGCGTTAAGAAT 1034
Qy 1018 GATGACGCCAAAGAAATGACTTGGATTGAGTCAGCACTTTTCTTTTCCGAATTAGATAAC 1077
||||| ||| |||||||||||||| ||||||||||||||||| |||||||||| | ||
Db 1035 GATGAGTGCAAGGAAATGACTTGGATAGAGTCAGCACTTTTCTTCTCCGAATTAGCTGAC 1094
Qy 1078 GTATTCGGGAACTCCTCTGACGATATCTCCCGTTTGAAAGAACGCTACATGGACGCAAAA 1137
| |||||| |||||| | |||||||||||| |||||||||| |||||||||| ||||
Db 1095 ATTAACGGGAATTCCTCTAATGATATCTCCCGTCTGAAAGAACGTTACATGGACGGAAAA 1154
Qy 1138 ACTTTCTTCAAAGGCAAATCAGATTTTGTGAAGACTCCATTTTCAATGGACGCGATGATG 1197
|||||||||||||||| | || | |||||||| ||| |||||||||| | |||| |
Db 1155 GGTTTCTTCAAAGGCAAAACGGACTATGTGAAGAAGCCAGTTTCAATGGATGGGATGCTA 1214
Qy 1198 ACAGCTCTTGTTGAACTCGAGAAAAACCCCAAGTCATTCCTTGTCTTCGATCCTTATGGC 1257
||| |||||||||||||||||||||||| ||| || |||||||| ||||| ||||||
Db 1215 ACATTTCTTGTTGAACTCGAGAAAAACCCGAAGGGATATCTTGTCTTTGATCCATATGGC 1274
Qy 1258 GGAGTCATGGACAAGATTAGTGATCAAGCTATTGCTTTCCCTCATCGAAAGGGTAACCTT 1317
|||| |||||||||||| ||||||||||||||| ||||||||| |||||||||| |||
Db 1275 GGAGCCATGGACAAGATCGATGATCAAGCTATTGCGTTCCCTCATAGAAAGGGTAATCTT 1334
Qy 1318 TTCGCGGTTCAATATTATGCATTTTGGAACGAAGAGGACGATGCCAAGAGCAACGAGTAC 1377
|||||| |||||||| ||| ||||| |||||||||||| ||||||| | | |||
Db 1335 TTCGCGATTCAATATCTAGCACAGTGGAATGAAGAGGACGATTACAAGAGCGATGTTTAC 1394
Qy 1378 ATAGAGTGGACAAGGGGATTTTACAATAAAATGGCGCCTTTTGTTTCAAGCTCGCCAAGG 1437
|| ||||||| ||| ||||||||||||| |||| |||| |||||||||||||||||||||
Db 1395 ATGGAGTGGATAAGAGGATTTTACAATACAATGACGCCCTTTGTTTCAAGCTCGCCAAGG 1454
Qy 1438 GGAGCTTATATCAACTACTTGGATATGGATCTTGGAGTGAATATGGACGACGACTACTTA 1497
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1455 GGAGCTTATATCAACTACTTGGATATGGATCTTGGAGTGAATATGGACGACGACTACTTA 1514
Qy 1498 CTGCGAAATGCTAGTAGTCGTAGTTCTTCTTCCTCTGTTGATGCTGTGGAGAGAGCTAGA 1557
|||||||||||||||||||||| |||||||||||||||||||||||||||||||||||||
Db 1515 CTGCGAAATGCTAGTAGTCGTAATTCTTCTTCCTCTGTTGATGCTGTGGAGAGAGCTAGA 1574
Qy 1558 GCGTGGGGTGAAATGTATTTCTTGCATAACTATGATAGGTTGGTTAAAGCTAAGACACAA 1617
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1575 GCGTGGGGTGAAATGTATTTCTTGCATAACTATGATAGGTTGGTTAAAGCTAAGACACAA 1634
Qy 1618 ATTGATCCACTAAATGTTTTTCGACATGAACAGAGTATACCTCCTATGCTTGGTTCAACG 1677
||||||||||| ||||||||||||||||||||||||||||||||||||||||||||||||
Db 1635 ATTGATCCACTTAATGTTTTTCGACATGAACAGAGTATACCTCCTATGCTTGGTTCAACG 1694
Qy 1678 CAAGAGCACA 1687
|||||||| |
Db 1695 CAAGAGCATA 1704
Prosecution Insights