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 1-11 are pending.
Claims 1-11 are examined on the merits.
Claim Objections
Claim 7 is objected to because “ribonucleotideprotein” appears to be a typographical error. Appropriate correction to “ribonucleoprotein” is required.
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.
Written Descriptions
Claims 1-3, 6 and 9-11 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.
The Federal Circuit has clarified the application of the written description requirement. The court stated that a written description of an invention "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials". University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). The court also concluded that "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not description of that material". Id. Further, the court held that to adequately describe a claimed genus, Patent Owner must describe a representative number of the species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus". Id.
The claims are rejected for lacking adequate written description support regarding the broad scope of the following.
Claims 1 and 6 broadly encompass compositions and methods for inducing parthenocarpy through inhibition of SlTPP4 expression, inhibition of SlTPP4 protein activity, or mutagenesis of the SlTPP4 gene. Claims 2 and 9 further encompass a broad genus of SlTPP4 expression inhibitors, including antisense nucleotides, siRNA, shRNA, miRNA, ribozymes, DNAzymes, and peptide nucleic acids (PNS). Claim 3 encompasses a broad genus of SlTPP4 protein activity inhibitors, including compounds, peptides, peptide mimetics, substrate analogs, aptamers, and antibodies.
The specification describes SlTPP4 RNAi lines and CRISPR/Cas9-generated SlTPP4 mutants (pa0062-0066, and pa0071-0074). However, with respect to the broad genus of expression inhibitors recited in claims 2 and 9, the specification does not disclose representative species for antisense nucleotides, siRNA, shRNA, miRNA, ribozymes, DNAzymes, or PNAs, nor does it provide common structural features sufficient to identify members of the claimed genus. Rather, there inhibitor classes are merely identified as possible alternatives (pa0017-0019 and pa0041).
The deficiency is more pronounced for claim 3. Although the specification identifies compounds, peptides, peptide mimetics, substrate analogs, aptamers, and antibodies as possible SlTPP4 protein activity inhibitors (pa0020-0022), the specification does not disclose any actual SiTPP4 protein activity inhibitor, peptide sequence, compound structure, aptamer sequence, antibody, epitope, binding site, or other identifying structural characteristic that would demonstrate possession of the claimed genus.
Accordingly, the specification discloses only limited species of SlTPP4 inhibition, namely RNAi-mediated suppression and CRISPR/Cas9-mediated mutagenesis, but claims broadly encompass any SlTPP4 expression inhibitor and any SlTPP4 protein activity inhibitor. Because the specification neither provides a representative number of species nor identifies common structural characteristics sufficient to define the claimed genera, it does not reasonably convey possession of the full scope of the claimed subject matter.
In addition, claims 1, 6, 10 and 11 are not limited to tomato plants. Rather, the claims broadly encompass inducing parthenocarpy in any plant, and claim 10 broadly recites a transgenic plant or plant part exhibiting a parthenocarpic phenotype by the method of claim 6. However, the specification provides working examples only for tomato SlTPP4 suppression or mutagenesis in tomato. The specification does not provide representative examples across other plant species, nor does it identify structural or functional features showing the inhibition or mutation of tomato SlTPP4 would induce parthenocarpy across the full scope of “a plant”. The deficiency is also present in claim 11 because the claim broadly encompasses any transgenic plant or plant part containing one of the specific mutant SlTPP4 nucleotide sequences of SEQ ID NO: 5-11, without being limited to tomato. The specification does not show possession of such mutant SlTPP4 genes functioning to induce parthenocarpy across plants generally.
Therefore, the specification fails to satisfy the Written description for claims 1-3, 6 and 9-11.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang (Huijuan Zhang et. al., Frontiers in Plant Science (2016) Volume 7, Article 1176, pp1-18), with evidence from Rojas-Gracia (Pilar Rojas-Gracia et. al., New Phytologist (2017) 214: 1198–1212).
Claim 1 recites a composition for inducing parthenocarpy in a plant, comprising, a S1TPP4 gene expression inhibitor, a S1TPP4 protein activity inhibitor, or a S1TPP4 gene mutagen, wherein the SlTPP4 protein comprises the amino acid sequence of SEQ ID NO: 2, and the S1TPP4 gene encodes the S1TPP4 protein.
Under the broadest reasonable interpretation consistent with the specification, the phrase “composition for inducing parthenocarpy” requires a composition that is reasonably capable of inducing or affecting parthenocarpy when used in a plant, but does not require that the prior art expressly disclose using the composition to induce parthenocarpy. Further, the phrase “SlTPP4 gene expression inhibitor” encompasses nucleic-acid-based silencing agents capable of reducing expression of the SlTPP4 gene, including VIGS constructs.
Zhang discloses tomato trehalose-related genes, including SlTPP4 (Solyc04g072920), which encodes a 365 amino acid TPP protein. Sequence alignment analysis demonstrates that Zhang’s SlTPP4 protein is 100% identical to SEQ ID NO: 2 of the instant application (p5 Table 1, also see alignment below). Zhang further discloses virus-induced gene silencing (VIGS) constructs directed against individual tomato TPS/TPP family genes, including a TRV-SlTPP4 construct (p12 fig 7), wherein the TRV-SlTPP4 construct is used to suppress expression of the SlTPP4 gene. Under BRI, the disclosed TRV-SlTPP4 construct constitutes an SlTPP4 gene expression inhibitor.
Further, Rojas-Gracia demonstrates that TRV-based VIGS in tomato can be performed by Agrobacterium inoculation of cotyledons (p1200, left column, pa4), resulting in systemic silencing effects that persist into later stages of plant development and affect fruit-set phenotypes (p1119, Materials and Methods; Fig 1 and Fig 4). This further supports the applicability of TRV/VIGS-mediated gene silencing in tomato beyond localized leaf assays.
Therefore, the composition of Zhang is a composition that is capable of inducing or affecting parthenocarpy in a tomato plant.
Accordingly, claim 1 is anticipate with Zhang.
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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.
Under the broadest reasonable interpretation consistent with the specification, the phrase “SlTPP4 gene expression inhibitor” encompasses any agent capable of reducing expression of the SlTPP4 gene, including nucleic acid-based silencing agents. The phrase “SlTPP4 protein activity inhibitor” encompasses any agent capable of reducing or inhibiting the biological activity of the SlTPP4 protein. The phrase “SlTPP4 gene mutagen” encompasses any agent or system capable of introducing a mutation into the SlTPP4 gene, including CRISPR/Cas-based genome-editing systems.
Claims 1-2, 6, and 9 are rejected under 35 U.S.C. §103 as being unpatentable over Zhang (Huijuan Zhang et. al., Frontiers in Plant Science (2016) Volume 7, Article 1176, pp1-18) in view of Rojas-Gracia (Pilar Rojas-Gracia et. al., New Phytologist (2017) 214: 1198–1212).
Claim 1 recites a composition for inducing parthenocarpy in a plant, comprising, a S1TPP4 gene expression inhibitor, a S1TPP4 protein activity inhibitor, or a S1TPP4 gene mutagen, wherein the SlTPP4 protein comprises the amino acid sequence of SEQ ID NO: 2, and the S1TPP4 gene encodes the S1TPP4 protein.
Under the broadest reasonable interpretation, a composition “for inducing parthenocarpy” encompasses compositions reasonably capable of affecting biological pathways known to regulate fruit initiation, fruit set, or parthenocarpy development and does not require that the composition itself be expressly disclosed in the prior art as having been previously used to induce parthenocarpy.
Zhang teaches tomato trehalose-related genes, including SlTPP4/Solyc04g072920, which encodes a 365 amino acid TPP protein (p5 Table 1, also see alignment below), and identifies SlTPP4 as a member of the tomato TPP gene family (p5 Table 1). The amino acid sequence of Zhang’s SlTPP4 (Solyc04g072920) is 100% identical to the SEQ ID NO: 2 of the instant application. Zhang further teaches use of virus-induced gene silencing (VIGS) to suppress tomato TPS/TPP family genes (p3 VIGS Vector Construction and Agroinfiltration; Fig 3). Thus, Zhang teaches a composition capable of inhibiting expression of SlTPP4, namely a nucleic-acid-based gene silencing construct.
Rojas-Gracia teaches that VIGS-mediated suppression of tomato developmental regulators can induce parthenocarpic fruit development and specifically teaches that VIGS-mediated silencing of SlSPL/HYD promoted parthenocarpic fruit development (p1198 Summary; p1202 Fig 1; p1205 Fig 4; P1204 pa 3-6; p1204 Hormonal basis of the parthenocarpic phenotype in hyd mutants).
A POSITA would have been motivated to apply the known tomato VIGS approach taught by Zhang to the tomato gene SlTPP4 in view of Rojas-Gracia’s teaching that VIGS-mediated suppression of tomato genes involved in fruit-set regulatory pathways can induce parthenocarpic fruit development, with a reasonable expectation of obtaining altered fruit-set and parthenocarpy phenotypes.
Accordingly, claim 1 is prima facie obvious over Zhang and Rojas-Gracia.
Claim 2 recites the composition of claim 1, wherein the SlTPP4 gene expression inhibitor is selected from the group consisting of an antisense nucleotide, small interfering RNA (siRNA), short hairpin RNA (shRNA), micro-RNA (miRNA), ribozyme, DNAyzme, and peptide nucleic acids (PNAs), which bind complementarily to a sequence of the S1TPP4 gene, a sequence complementary to the sequence of the SITPP4 gene, or a fragment of the mRNA sequence of the SITPP4 gene, thereby inhibiting expression of the SlTPP4 gene.
Zhang teaches suppression of tomato TPS/TPP genes using virus-induced gene silencing technology (VIGS), thereby demonstrating that reduction of expression of tomato TPS/TPP genes was known in the art (p3 VIGS Vector Construction and Agroinfiltration; Fig 3).
Antisense nucleotides, siRNA, miRNA, ribozymes, DNAzymes, and peptide nucleic acids were well-known alternative gene-silencing technologies for reducing expression of a target gene through sequence-specific interaction with the target nucleic acid. It would have been obvious to substitute any of these known gene-silencing approaches for the VIGS-mediated suppression taught by Zhang because each represents a recognized method for achieving the same objective, namely reduction of expression of the target gene.
Accordingly, claim 2 is prima facie obvious over Zhang and Rojas-Gracia.
Claim 6 recites the method for inducing parthenocarpy in a plant, comprising a step of inducing a loss-of-function mutation in a gene encoding a SlTPP4 protein comprising the amino acid sequence of SEQ ID NO: 2, or inhibiting expression of the gene, or inhibiting an activity of the SlTPP4 protein.
For the same reason set forth with respect claim 1, Zhang teaches VIGS-mediated silencing of tomato TPS/TPP family genes, including SlTPP4. It would have been obvious to induce a loss-of-function in SlTPP4, inhibit SlTPP4 expression, or inhibit SlTPP4 protein activity to alter SLTPP4/T6P-mediated developmental signaling and thereby induce parthenocarpy.
Accordingly, claim 6 is prima facie obvious over Zhang, and Rojas-Gracia.
Claim 9 recites the method of claim 6, wherein the inhibiting of expression of the gene is achieved by a nucleic-acid-based inhibitor, such as antisense nucleotide, small interfering RNA (siRNA), short hairpin RNA (shRNA), micro- RNA (miRNA), ribozyme, DNAyzme, and peptide nucleic acids (PNAs).
Because the phrase “such as” introduces non-limiting examples, the claim encompasses other nucleic-acid-based inhibitors. Zhang teaches a TRV-SlTPP4 VIGS construct for silencing SlTPP4 expression, which is a nucleic-acid-based inhibitor.
Accordingly, claim 9 is prima facie obvious over Zhang, and Rojas-Gracia.
Claims 4-5, 7-8 and 10 are rejected under 35 U.S.C. §103 as being unpatentable over Zhang (2016) and in view of Rojas-Gracia (2017) as applied claims 1 and 6, and further in view of Claeys (Hannes Claeys et. al., Nature Plants (2019)5(4): 352–357).
Claims 1 and 6 as the teaching of Zhang, and Rojas-Gracia is discussed above.
Claim 4 is interpreted as depend of claim 1.
Claims 7 and 10 are interpreted as depend of claim 6.
Claim 4 recites the composition of claim 1, wherein the SlTPP4 gene mutagen is a CRISPR/Cas-type genome-editing system comprising a guide RBA specific for the SlTRP4 gene and an endonuclease. Claim 5 recites the composition of claim 4, wherein the target nucleotide sequence of the SlTPP4 gene consists of the nucleotide sequence of SEQ ID NO: 3 or SEQ ID NO: 4.
For the same reason set forth with respect claim 1, Zhang teaches the known tomato SlPPT4 gene, Claeys teaches that TPP4 regulates reproductive meristem determinacy, and that loss of maize TPP4, including EMS-derived tpp4 alleles and CRISPR/Cas9-induced tpp4 mutants, alters inflorescence branching and reproductive meristem development (Abstract; Fig 1A-1E; p4 Generation of CRISPR/Cas9-induced mutants). Therefore, it would have been obvious to mutate the known SlTPP4 gene using the recited CRISPR/Cas-type system and targeted sequence. Furthermore, the selection of SEQ ID NO:4 or 3 as guide RNA target sequences within the known SkTPP4 gene constitutes no more than the routine selection of a target site within a known gene for CRISPR/Cas-mediated mutagenesis.
Accordingly, claims 4-5 are prima facie obvious over Zhang, Rojas-Gracia and Claeys.
Claims 7 and 8 recite the method of claim 6, wherein the loss-of-function is induced using a CRISPR/Cas-type system comprising a guide RNA specific to SlTPP4 and an endonuclease, and wherein the target nucleotide sequence is SEQ ID NO: 3 or SEQ ID NO:4.
For the same reasons set forth with respect to claims 1 and 6, it would have been obvious to mutate the known SlTPP4 gene using the recited CRISPR/Cas-type system and target sequences. Furthermore , the selection of SEQ ID NO: 3 or SEQ ID NO:4 as target sequence represents merely the routine selection of a guide RNA target site within the known SlTPP4.
Accordingly, claims 7 and 8 are prima facie obvious over Zhang, Rojas-Gracia and Claeys.
Claim 10 recites transgenic plant or plant part exhibiting a parthenocarpic phenotype produced by the method of claim 6.
For the same reasons set forth with respect to claim 6, it would have been obvious to produce a transgenic plant or plant part by reducing SITPP4 expression or activity, or mutating SITPP4, to induce parthenocarpy. Rojas-Gracia teaches that tomato plants and fruit tissues can exhibit parthenocarpic/ seedless fruit development when a reproductive-development gene is disrupted or silenced (p1198, Summary and Introduction). Therefore, the claimed transgenic plant or plant part exhibiting a parthenocarpic phenotype would have been obvious.
Accordingly, claim 10 is prima facie obvious over Zhang, Rojas-Gracia and Claeys.
Claim 3 is rejected under 35 U.S.C. §103 as being unpatentable over Zhang (2016) in view of Rojas-Gracia (2017) as applied claim 10, and Liu (Chunliang Liu et. al., European Journal of Medicinal Chemistry (2017) Vol 128, pp274-286).
Claim 1 as the teaching of Zhang, and Rojas-Gracia is discussed above.
Claim 3 is interpreted as depend of claim 1.
Claim 3 recites the composition of claim 1, wherein the S1TPP4 protein activity inhibitor is selected from the group consisting of a compound, a peptide, a peptide mimetic, a substrate analog, an aptamer, and an antibody, which bind to the SlTPP4 protein.
For the same reasons set forth with respect to claim 1, Liu teaches rationally designed reversible inhibitor of trehalose-6-phospate phosphatases, including aryl D-glucopyranoside 6-sulfate substrate-analog compounds, and taches that the inhibitors bind to and inhibit T6PPP/TPP enzyme activity (p274 Abstract). Therefore, in view of Zhang’s teaching of the known tomato SlTPP4 protein, it would have been obvious to use a known TPP inhibitory compound or substrate analog as an SlTPP4 protein activity inhibitor to reduce TPP activity and alter T6P-mediated developmental signaling, with reasonable expectation of success.
Accordingly, claim 10 is prima facie obvious.
Conclusion
No claims are allowed.
Claims 1-11 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YANXIN SHEN whose telephone number is (571)272-7538. The examiner can normally be reached Monday-Friday.
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/YANXIN SHEN/Examiner, Art Unit 1663
/WEIHUA FAN/Primary Examiner, Art Unit 1663
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