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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 26, 2026 has been entered.
Claims 3, 6- 7, 9-11, 24, and 29-31 are currently amended. Claims 3, 6-7, 9-11, 16-24, 27, and 29-33 remain pending and are examined herein.
Response to Amendment
The objection to the Specification regarding a descriptive Title is withdrawn in view of amendment.
The objections to the Claims 9 and 29 are withdrawn in view of amendment.
The rejection of Claims 3, 6-7, 9, 18-24 and 27 under 35 U.S.C. 102(a)(1) over U.S. Patent 9988640 issued 6/05/2018 is withdrawn in view of amendment to the claims removing the limitations drawn to SEQ ID NO: 73.
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.
Claims 3, 6-7, 9-11, 16-24, 27, and 29-33 remain 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.
Claims 3, 6, 7, 29, recite “a functional variant or functional fragment or orthologue” of Nic3 gene selected from SEQ ID No. 118, 124 or 127; Claim 11 recites “a functional variant or functional fragment or orthologue” of SEQ ID NO: 118, 120, 124, or 127. These claims are deemed indefinite, along with their respective dependent claims for the failure to correct the deficiency.
Firstly, the issue with “functional variant or functional fragment” is discussed. It is not clear what “function” the “variant” or “fragment” must possess. The Specification has not provided any definition to this effect. As disclosed, the genes represented by SEQ ID NO: 118, 120, 124, or 127 are “Nic3 genes” as they are genes located in a unique chromosomal location of the Nicotiana tobacco genome. As disclosed, the lack of these genes (loci) or virus-induced silencing of these genes leads to reduced amount of alkaloid and/or tobacco specific nitrosamine (TSNA) precursor in a tobacco plant. These genes, as disclosed, encodes a “LRR, Disease resistance protein” (SEQ ID NO: 118, 120), or a “NB-ARC, Disease resistance protein” (SEQ ID NO: 124, 127) (Specification, Table 3). The Specification has not defined or described which part, component, fragment, domain, or structural features of these “disease resistance proteins”, or functions thereof, are responsible for maintaining, increasing, or decreasing any tobacco alkaloids or TSNA precursors. Consequently, it is not clear which “variant” or “fragment” has the required function to achieve an increase or decrease in tobacco alkaloids or TSNA precursors once such a “variant” or “fragment” is increased or decreased. For example, while SEQ ID NO: 118 is described in the Specification as “LRR, Disease resistance protein”, it contains only a recognized LRR domain compared with similar disease resistance proteins and lack other domains critical for functional disease resistance proteins, such as NB 9nucleotide binding) domain. Thus, it is not clear whether these so called “disease resistance proteins” represented by the listed SEQ IDs really have any function in disease resistance; and further, whether such function in disease resistance should be retained by the claimed “functional variant or functional fragment” or not. Without understanding how, functionally, the incomplete disease resistance proteins are involved in alkaloid metabolism, from the instant Specification or the state of the art, it is unclear what “functional variant or functional fragment” are encompassed by the claim scope.
Secondly, the issue with “orthologue” is discussed. As discussed above, the recited SEQ IDs represent unique genomic loci. Applicant has provided evidence, that these loci are linked to the phenotypes in alkaloid metabolism. The “orthologue”, regardless the definition—which in and by itself a term the invokes indefiniteness, would be a different locus somewhere else in the genome. As disclosed, there is no evidence that these other loci are associated with alkaloid metabolism. Therefore, it is not clear what these “orthologue” would or should be. For example, is an NB-LRR type of disease resistance protein, or any or them, or a particular one of them, an “orthologue” of SEQ ID NO: 118 (120) which is an incomplete R protein with only LRR domain? One cannot say. Additionally, the claims are drawn to a narrow scope of “Nic3” genes which are limited to a specific genomic region, as well as broader scope where “Nic3” genes could be (orthologues that are located) somewhere else in the genome.
Therefore, the metes and bounds of the claims are not clear.
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.
Claims 3, 6, 7, and claims 10, 16-24, 27 and 32-33 dependent thereupon remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for decreasing the content of alkaloid and/or TSNA precursor in a tobacco plant by decreasing the expression of a Nic3 gene selected from SEQ JD No. 118, 124 or 127, does not reasonably provide enablement for i) increasing the content of alkaloid and/or TSNA precursor in a tobacco plant, or ii) decreasing the content of alkaloid and/or TSNA precursor in a tobacco plant by decreasing the activity of a Nic3 gene selected from SEQ JD No. 118, 124 or 127; or iii) by increasing or decreasing the expression or activity of any sequence which has at least 90% identity thereto or a functional variant or functional fragment or orthologue. 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.
An “analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.” MPEP 2164.01. “A conclusion of lack of enablement means that. . . the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention [i.e. commensurate scope] without undue experimentation.” In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); MPEP 2164.01.
In In re Wands, 858 F.2d 731,8 USPQ2d 1400 (Fed. Cir. 1988), several factors implicated in determination of whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is “undue” are identified. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). No single factor is independently determinative of enablement; rather “[i]t is improper to conclude that a disclosure is not enabling based on an analysis of only one of the above factors while ignoring one or more of the others.” MPEP 2164.01. Likewise, all factors may not be relevant to the enablement analysis of any individual claim.
The instant claims are broad in scope in the following aspects:
The claims encompass increasing the content of alkaloids or TSNA precursors by increasing the expression or activity of the recited genes and variants.
The claims encompass decreasing the content of alkaloids or TSNA precursors by decreasing the activity of the recited genes and variants;
The claims encompass sequences having 90% identity to the recited SEQ IDs;
The claims encompass function variants or fragments or orthologues of the recited SEQ IDs.
In contrast to the broad scopes of the claims, the Specification has provided teachings of genetic mapping of a “Nic3” locus associated with reduced nicotine levels, and identification of candidate genes encompassed in the “Nic3” locus (Examples 1-4). It has shown that virus-induced silencing of a few of the candidate genes, namely, genes represented by nucleotide sequences SEQ ID NO: 118 (Nitab4.5_0002683 g0080.2), 124 (Nitab4.5_0005412 g00l0.2) and 127 (Nitab4.5_0005412 g0020.2), led to a decrease in nicotine content as compared to nic1nic2 tobacco line (Example 7 and data shown in Fig. 9).
As disclosed, the genes represented by SEQ ID NO: 118 (Nitab4.5_0002683 g0080.2), 124 (Nitab4.5_0005412 g00l0.2) and 127 (Nitab4.5_0005412 g0020.2), are annotated as various “disease resistance proteins”. As discussed above, the encoded proteins do not resemble the complete R proteins that share the most similar structural elements. For example, SEQ ID NO: 118 only encodes (part of) a typical LRR domain. It should be noted that the Specification, while providing an annotation in Table 3, had not provided any teachings regarding the activity of the Nic3 genes represented by SEQ ID NO: 118 (120), 124 or 127, let alone those variants, fragments, orthologues or 90% identities.
The Specification has not taught any enabling guidance of increasing nicotine content, or contents of any alkaloids or TSNA precursors, by increasing the expression or activity of any of the Nic3 genes represented by SEQ ID NO: 118 (120), 124 or 127, let alone those variants, fragments, orthologues or 90% identities.
The Specification has not taught any enabling guidance of decreasing nicotine content, or contents of any alkaloids or TSNA precursors, by decreasing the activity of any of the Nic3 genes represented by SEQ ID NO: 118 (120), 124 or 127, let alone those variants, fragments, orthologues or 90% identities.
The Specification has not taught any enabling guidance of decreasing nicotine content, or contents of any alkaloids or TSNA precursors, by decreasing the expression or activity of any variants, fragments, orthologues or 90% identities of any of the Nic3 genes represented by SEQ ID NO: 118 (120), 124 or 127.
It would have been unpredictable to attempt to achieve an increase in nicotine content, or contents of any alkaloids or TSNA precursors, by increasing the expression or activity of any of the Nic3 genes represented by SEQ ID NO: 118 (120), 124 or 127, let alone those variants, fragments, orthologues or 90% identities, based on the association of reduced nicotine content associated with the absence or silencing of the Nic3 genes represented by SEQ ID NO: 118 (120), 124 or 127.
Even when the knockout mutant has a clear informative phenotype, overexpression can still be valuable because it can generate completely unexpected or variable phenotypes. For example, Ramamoorthy (Ramamoorthy, Rengasamy, Shu-Ye Jiang, and Srinivasan Ramachandran. "Oryza sativa cytochrome P450 family member OsCYP96B4 reduces plant height in a transcript dosage dependent manner." PLoS One 6.11 (2011): e28069.) teaches that while mutant or silencing lines of rice OsCYP96B4 shows semi-dwarf phenotype, overexpressing OsCYP96B4 could lead to either slightly increased plant height or drastically reduced plant height (Fig. 6).
Regarding increasing alkaloid or TSNA precursor contents, neither the Specification nor the state arts have provided enabling teachings to resolve the unpredictability of increasing the expression of the poorly understood roles played by the (partial) “disease resistance proteins” in the Nic3 locus in alkaloid metabolism.
Regarding the point of decreasing the activity of the Nic3 genes represented by SEQ ID NO: 118 (120), 124 or 127, the Specification has not provided any enabling teachings. It is unpredictable what “activities” of these (partial) “disease resistance proteins” in the Nic3 locus have in alkaloid metabolism. While virus-mediated silencing of these genes led to the claimed phenotype, it is not clear whether such manifestation is due to any activity of the encoded proteins or from other undisclosed and poorly understood mechanisms. To this end, neither the Specification nor the state arts have provided enabling teachings. It is unpredictable whether any other mechanisms or methods that are broadly encompassed by the claimed “decreasing activity”, e.g, mutations in the LRR domain, would lead to the desired phenotypes.
Regarding orthologues, it is noted that as discussed above, the Nic3 genes represented by SEQ ID NO: 118 (120), 124 or 127, are located in a specific genomic locus that has been taught by the Specification as responsible for the traits in nicotine biosynthesis. However, the alleged orthologues encompass genes in other parts of the tobacco genome—which has no relation with nicotine biosynthesis, as proven genetically by the Specification; or genes in other organisms tan tobacco, the modification of which would have no relation with nicotine biosynthesis in tobacco. Therefore, it would be unpredictable how increasing or decreasing the expression or activity of the orthologues would impact alkaloid metabolism in a tobacco plant.
Similarly, the genes having 90% of sequence identity with any of SEQ IDs would encompass other tobacco genes or other genes in other plants. It would be unpredictable how increasing or decreasing the expression or activity of the orthologues would impact alkaloid metabolism in a tobacco plant.
Regarding the “function variants or function fragments”, it is unpredictable which fragments or variants are responsible for the claimed traits. The Specification has not provided any enabling teaching regarding the structural features critical and sufficient for the nicotine accumulation traits. It would be unpredictable how increasing or decreasing the expression or activity of the variants or fragments would impact alkaloid metabolism in a tobacco plant.
Thus, in view of the unpredictability associated with combinatorial substitutions in a protein, the lack of enabling guidance from either the instant disclosure or the art, and breath and diversity of the embodiments encompassed by the claimed genus, the lack of sufficient working examples, and the level of the art at the time of the invention, one of ordinary skill in the art must rely on undue trial and error experimentation to make and test the numerous embodiments, in order to make and/or use the invention within the full scope of these Claims.
For at least this reason, the Specification does not teach a person with skill in the art how to make and/or use the subject matter within the full scope of these Claims.
Conclusion
No claims are allowed.
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WEIHUA . FAN
Primary Examiner
Art Unit 1663
/WEIHUA FAN/Primary Examiner, Art Unit 1663
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