DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 47-66 are pending and the claims are examined in this office action.
Claim Rejections - 35 USC § 112 -written description requirements
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.
Claims 47-49, 51-58, 60-66 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Breadth of the Claim
Claims 47 and 58 encompass any nucleic acid sequence encoding an amino acid sequence at least 95% identical to an amino acid sequence consisting of SEQ ID NO: 19.
Claims 49 and 60 encompass any nucleic acid sequence, the nucleic acid sequence is at least 95% identical to the nucleic acid sequence of SEQ ID NOs: 14 and 24.
What is Described in the Specification
Applicant describes the following:
Transcription factors involved in regulation of trichome initiation and development were used as query in a search of the National Center for Biotechnology Information (NCBI) database wherein MYB and C2H2 transcription factors were identified and list of candidate genes that are trichome-specific and involved in metabolite transport (SEQ ID NOs: 13-27 and 34-36) were curated as in Table 1 (page 89, paragraph 00210).
The candidate genes identified in Example 1 (e.g. SEQ ID NOs: 13-27 and 34-36) were cloned using the PCR Cloning System with GATEWAY Technology (ThermoFisher Scientific, Catalog Number 12535029) wherein the cloned genes are subsequently subcloned into a GATEWAY expression vector, where the subcloned gene is fused with GREEN FUORESCENCE PROTEIN (G3GFP) operably linked to a CaMV 35S promoter. See Figure 2. (page 89, paragraph 00210).
Each of the vector were separately transformed into tobacco cells of variety TN90 and Imzir Ego in separate experiments (page 90, paragraph 00211-00212).
When grown during vegetative stage of growth, transgenic plants comprising NtMYB86, NtGIS, or NbGIS show an increase in the number of glandular trichomes per unit area (i.e. increased trichrome density) in leaf and stem tissues. (See Figures 5-7) (page 91, paragraph 00218).
Difference Between What was described and What is Claimed
Applicant has not described any tobacco plant comprising a nucleic acid sequence encoding any amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO: 19 would have a greater average trichome density.
Applicant has not described a tobacco plant comprising a nucleic acid sequence encoding any amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO: 19 would have at least 110 glandular trichomes per square centimeter (claim 57).
Analysis
The purpose of the written description is to ensure that the inventor had possession at the time the invention was made, of the specific subject claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
Applicant has not described a plant comprising a nucleic acid sequence encoding any amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO: 19 would have a greater average trichome density compared to a control plant. Applicant teaches transgenic plants comprising NtGIS, or NbGIS show an increase in the number of glandular trichomes per unit area (i.e. increased trichrome density) in leaf and stem tissues. (See Figures 7) (page 91, paragraph 00218), which are full length and not an amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO: 19. SEQ ID NO:19 is 217 amino acid long, any amino acid sequence that is at least 95% identical to an amino acid sequence of SEQ ID NO: 19 would have ~10 amino acid changes (i.e. insertion, deletion and substitution) in the SEQ ID NO:19 that would lead to genus of at least 2010 different proteins molecules. Instead applicant has not described any other protein that would have increase trichome density when transferred with a heterologous promoter other than SEQ ID NO:19. For example Sun et al. (Published: 2015, Journal: New Phytologist 206: 220–230) teaches C2H2 zinc finger protein finger protein GLABAROUS INFLORESCENCE STEMS (GIS) functions in a GA signal to control trichome formation in inflorescence organs which acts upstream of GL1 and downstream of SPY to regulate shoot maturation (page 220, last paragraph). Therefore, the gene is involved in networks of genes. Sun et al. teaches the variants (i.e. TDNA insertion mutants (page 221, left paragraph 2) of GIS3 genes would have decreased trichome density in stem (see Figure 1 and 2, see figure 1 below) and flowers (see figure 3). Furthermore, Liu et al. (Plant Published: 2018, Journal: Molecular Biology 98:153–167) teaches C2H2-type zinc finger domain, which contains the conserved QALGGH motif (Fig. 1a). Therefore, there is dearth of description of any variants with at least 95% identical to an amino acid sequence consisting of SEQ ID NO: 19 would have a greater average trichome density.
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Applicant has not described any tobacco plant nucleic comprising acid sequence encoding an amino acid sequence at least 95% identical to an amino acid sequence consisting of SEQ ID NO: 19 would have at least 110 glandular trichomes per square centimeter (claim 57). For example, Tian et al. (Published: 2018, Journal: International journal of molecular sciences 19(6), 1733) teaches a plant non-specific lipid transfer proteins (nsLTPs) belong to a large multigene family that possesses complex physiological functions wherein in Barassica rapa the lipid transfer protein 2 (BraLTP2) effects on trichome development (page 1, Abstract). Tian et al. teaches Trichome density of 35S::BraLTP2 plant leaves was significantly higher (p < 0.05) when compared with the WT (see Figure 5 below) (page 12, paragraph 2) wherein the maximum number of trichomes per square centimeter was not more than 40.
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Therefore, there is dearth of description of a tobacco plant comprising SEQ ID NO:19 would have produced at least 100 trichomes per square centimeter by virtue of example (claim 57).
Furthermore, applicant has not described any other sequence with at least 95% identity to SEQ ID NO:19 that would have increased average trichome density.
Summary of alignment of SEQ ID NO:19 to pubpaa__le40000 database:
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Given the large size and structural diversity associated with the claimed genus, Applicant’s disclosure is not representative of the claimed genus as a whole. This point is particularly relevant because, as discussed above, the prior art speaks to the disconnection between the structure of the broadly claimed variants and the recited specific function.
Thus, based on the analysis above, Applicant has not met either of the two elements of the written description requirement as set forth in the court's decision in Eli Lilly. As a result, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed.
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.
Anticipated by Rutqvist et al.
Claims 58-63 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Rutqvist et al. (Published: 2011; Journal: Harm Reduction Journal 8:11, pages 1-9); as evidenced by Xing et al. (Published Year: 2009, Journal: Natural Product Communications, Vol. 4(8), pages: 1093-1094).
The claims are drawn to a fire- or sun-cured tobacco material.
Regarding claims 58-63, It would not need to have any DNA from the plant or the required protein because “material from” does not require any DNA or protein to be retained. Thus, any cured tobacco material for example extract of a tobacco plant would be indistinguishable from other extract that does not has any DNA to distinguish, unless it is stated in claim that the material comprises at least one cell comprising the DNA. See Product by process analysis (MPEP 2113).
Applicant defines “As used herein, "tobacco product" is defined as any product made or derived from tobacco that is intended for human use or consumption (page 61, paragraph 00177). Therefore, a nicotine or other chemical derived from the modified tobacco would be a tobacco product.
Rutqvist et al. teaches fire-cured tobacco (page 6, right paragraphs 1, 3) and sun cured tobacco (page 7, left paragraph 3).
A fire cured material does not need to comprise the recited nucleic acid to make it inventive from the any other cured tobacco product.
Therefore, the fire cured tobacco of Rutqvist et al. anticipate the claims.
Anticipated by Digard et al.
Claims 64-66 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Digard et al. (Published Year: 2013, Journal: Nicotine and Tobacco Research, Vol. 15, pages: 255-261); as evidenced by Xing et al. (Published Year: 2009, Journal: Natural Product Communications, Vol. 4(8), pages: 1093-1094).
The claims are drawn to a cured tobacco material consisting of a tobacco product consisting of moist snuff, snus, smokeless tobacco product etc.
Regarding claims 64-66, Applicant defines “As used herein, "tobacco product" is defined as any product made or derived from tobacco that is intended for human use or consumption (page 61, paragraph 00177). Therefore, a nicotine or other chemical derived from the modified tobacco would be a tobacco product.
Digard et al. teaches a smokeless tobacco product as a snus and nicotine gum (Digard, page 255, Abstract) that comprises nicotine as a component (Digard, page 256, left paragraph 3, Table 2). Since the claim does not require the presence of the specific recited protein, the highly processed product would have been indistinguishable from any of the snus or nicotine gum.
Furthermore, Xing et al. shows the evidence that extraction of nicotine from waste tobacco wherein the purity can be above 99% (Xing, page 1093, Abstract). Furthermore, Xing teaches Nicotine is the principal alkaloid, which accounts for approximately 95% of the total alkaloids in tobacco (Xing, page 1093, left paragraph 1).
Hence Digard’s nicotine gum anticipates the claims.
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 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.
Obvious over Liu et al.
Claims 47-57 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Published Year: 2018, Journal: Plant Molecular Biology, Volume:98, pages: 153-167).
Claims are drawn to a modified tobacco plant comprising a heterologous promoter operably linked to a nucleic acid sequence encoding at least 95% identical to the SEQ ID NO:19 where in at least one leaf of the modified tobacco plant comprises greater average trichome density.
Regarding claims 47-48, Liu et al. teaches a modified tobacco plant comprising NbGIS wherein the 35S:NbGIS lines exhibited much higher densities of trichome on leaves, main stems, lateral branches and sepals than WT plants, while NbGIS:RNAi lines had the opposite phenotypes in tobacco (page153, Abstract).
Liu et al. teaches NtGIS_XP_016468579.1 which appear to be the applicant’s SEQ ID NO:19 that has all the disclosed residues identical (see snippet of figure 1 a below). Liu et al. teaches C2H2-type domain found in GIS proteins is conserved in different plant species (page 164, left paragraph 1) and the C2H2 transcription factor plays key role in controlling trichome initiation both in Arabidopsis and tobacco (page 64, right last paragraph).
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Thus, it would have been obvious before effective date of filling of the invention to a skilled in the art to combine the teachings of Liu et al. to develop a tobacco plant transformed with heterologous 35S promoter operatively linked to the NtGIS gene encoding the NtGIS protein and screen for the resulting transgenic plants for differences in the number of glandular trichomes as taught by Liu et al. leading to the predictable results of the tobacco plant with heterologous 35S promoter operatively linked to the SEQ ID NO:19 (i.e. NtGIS) that would have increase trichome density.
Regarding claims 49-50, since SEQ ID NO:14 encodes SEQ ID NO:19, the nucleic acid sequence would have been identical to the nucleotides of NtGIS taught by Liu et al.
Regarding claim 53, promoter 35S is a constitutive promoter (Spec, page 55, paragraph 00151).
Regarding claims 54-56, the greater average trichome density would have been either in abaxial or adaxial side of the leaf. Liu et al. Figure 5 showed the increase in glandular trichome density in the over expressed NbGIS-OE lines. Furthermore, the higher density would have been inherent property of the Liu et al.’s NtGIS protein when expressed in the tobacco plant under heterologous promoter.
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Regarding claim 57, Liu et al. page 159, Figure 3 b showed trichome density of at least 1000 trichomes.
Obvious over Liu et al. and further in view of Cho et al.
Claims 47 and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Published Year: 2018, Journal: Plant Molecular Biology, Volume:98, pages: 153-167), and further in view of Cho et al. (Published: 2001, Journal: Mol. Cells, Vol. 11, No. 3, pp. 326-333).
Claim 47 is drawn to a modified tobacco plant comprising a heterologous promoter operably linked to a nucleic acid sequence encoding at least 95% identical to the SEQ ID NO:19 where in at least one leaf of the modified tobacco plant comprises greater average trichome density. Claim 52 is drawn to the tobacco plant is male sterile plant.
Regarding claim 47, Liu et al. developed a tobacco plant transformed with heterologous 35S promoter operatively linked to the NtGIS gene encoding the NtGIS protein (i.e. SEQ ID NO: 19) and someone skilled in the art would screen for the transgenic plant for differences in the number of glandular trichomes as Liu et al. leading to the predictable results of the tobacco plant with heterologous 35S promoter operatively linked to the SEQ ID NO:19 (i.e. NtGIS) that would have increase trichome density.
Regarding claims 51-52, Cho et al. teaches a male sterile N. tabacum cv. Samsun which is oriental variety (accessed https://trueleafmarket.com/products/tobacco-seeds-black-sea-samsun-tobacco-seeds, accessed on 07/08/2026) (page 326, Abstract). Cho et al. teaches in tobacco breeding male sterility is crucial for hybrid seed production (page327, left paragraph 3).
Therefore, someone skilled in the art would transfer the Liu et al. taught SEQ ID NO:19 to the male sterile N. tabacum cv. Samsun that would be useful also for hybrid seed production.
Obvious over Liu et al. and further in view of Danehower et al.
Claims 58-64 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Published Year: 2018, Journal: Plant Molecular Biology, Volume:98, pages: 153-167), and further in view of Danehower et al. (Published: 1987; Journal: Tob. Sci. 32:49-52).
Claim is drawn to a cured tobacco material from a modified tobacco plant comprising a heterologous promoter operably linked to a nucleic acid sequence encoding at least 95% identical to the SEQ ID NO:19 where in at least one leaf of the modified tobacco plant comprises greater average trichome density.
Regarding claims 58-64, Liu et al. developed a tobacco plant transformed with heterologous 35S promoter operatively linked to the NtGIS gene encoding the NtGIS protein (i.e. SEQ ID NO: 19) and someone skilled in the art would screen for the transgenic plant for differences in the number of glandular trichomes as Liu et al. leading to the predictable results of the tobacco plant with heterologous 35S promoter operatively linked to the SEQ ID NO:19 (i.e. NtGIS) that would have increase trichome density.
Liu et al. does not teach cured tobacco product for example cigarette.
Danehower et al teaches method of flue or sun curing Galpao and samsun tobacco which are used for production of cigarette (page 50, left paragraph 1- 6, page 49, right last paragraph).
Therefore, it would have been obvious to make a sun cured tobacco from the Galpao and samsun cultivars that would have been transformed with the NtGIS gene taught by Liu et al. to produce cigarette.
Obvious over Liu et al. and further in view of Liu et al.
Claims 65-66 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Published Year: 2018, Journal: Plant Molecular Biology, Volume:98, pages: 153-167), and further in view of Rutqvist et al. (Published: 2011; Journal: Harm Reduction Journal 8:11, pages 1-9).
Regarding claim 65-66, Liu et al. to developed a tobacco plant transformed with heterologous 35S promoter operatively linked to the NtGIS gene encoding the NtGIS protein (i.e. SEQ ID NO: 19) and screen for the transgenic plant for differences in the number of glandular trichomes as Liu et al. leading to the predictable results of the tobacco plant with heterologous 35S promoter operatively linked to the SEQ ID NO:19 (i.e. NtGIS) that would have increase trichome density.
Liu et al. does not teach making smokeless tobacco product.
Rutqvist et al. teaches production of snus from tobacco (page 4, left paragraphs 5-6).
Therefore, it would have been obvious to make a smokeless tobacco product as snus from the tobacco plant that would have been transformed with the NtGIS gene taught by Liu et al. to produce snus.
Summary
No claim is allowed.
Examiner’s Contact Information
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/SANTOSH SHARMA/Examiner, Art Unit 1663
/DAVID H KRUSE/Primary Examiner, Art Unit 1663
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