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 .
Claims
The amendments received on May 4, 2026, have been entered. Claims 3 and 9 have been canceled and claims 29 and 30 have been newly added. Claims 1, 2, 4-8, and 10-30 are pending. Claims 4, 7, 8, and 10-28 are withdrawn for being directed to non-elected inventions. Claims 1,, 2, 5, 6, 29, and 30 are examined in this Office Action.
Objections and Rejections That Are Withdrawn
The objections to claims 1 and 6 are withdrawn in light of Applicant’s amendments to the claims.
The portion of the written description rejection under 35 USC 112(a) that was directed to the breadth of the claimed eukaryotic organism not being supported by the possession/reduction to practice in only Arabidopsis is withdrawn in light of Applicant’s amendments to the claims which are now limited to plants and seeds.
The rejection of claim(s) 1 and 2 under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by McCallus is withdrawn in light of Applicant’s amendments to the claims.
The rejection of claim(s) 1-4 under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Jiang is withdrawn in light of Applicant’s amendments to the claims.
Claim Rejections - 35 USC § 112
Indefiniteness
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 1 and 2 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 requires the RNA fragments (RF) to be a transfer RNA (tRNA)-derived fragment, and it is unclear how one would define any particular RNA fragment as being tRNA-derived. Being derived from something is a limitation on how something is made. It is defining a starting material. However, there are no limitations as to how many changes can be made relative to a starting tRNA sequence. For this reason, it is unclear what polynucleotide sequence would qualify as a tRNA-derived sequence. Claims 5, 6, 29, and 30 require sequences with at least 75% identity to SEQ ID NOs: 1-4, therefore the metes and bounds are clear. This is why those particular claims are not included in this rejection.
Claim 2 recites the limitation "said eukaryotic organism" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 1 from which claim 2 depends was amended to delete all recitations of “eukaryotic organism”.
Inadequate Written Description
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 1, 2, 5, 6, 29, and 30 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. All dependent claims are included in these rejections unless they include a limitation that overcomes the deficiencies of the parent claim. Applicant’s arguments in the response received on May 4, 2026,were fully considered but were not found to be persuasive.
The claims are broadly drawn to a method of modulating a stress response in a plant or seed against an environmental stress, said method comprising:
introducing an RNA fragment (RF) or an antisense polynucleotide to said plant or seed, wherein the RF is a transfer RNA (tRNA)-derived RNA fragment and comprises:
a sequence recognition site, wherein the sequence recognition site comprises a reverse complement sequence of a nucleotide sequence of the plant or seed, and a stem loop structure, wherein the stem loop structure comprises: a paired region comprising paired RNA nucleotides, and an unpaired region comprising unpaired RNA nucleotides in the form of a loop, and
wherein the antisense polynucleotide comprises a nucleotide sequence that is complementary to the reverse complement sequence of the RF; and
wherein the RF or the antisense polynucleotide modulates the stress response against the environmental stress (claim 1); including wherein the RF is SEQ ID NO: 1, 2, 3, or 4 or a sequence with at least 75% identity to any one of SEQ ID NOs: 1-4 (claims 5, 6, 29, and 30).
Applicants describe fragments of tRNAs for the amino acids alanine, aspartate, glutamate, and glycine that induce expression of the Pathogenesis-related 1 (PR1) defense gene in Arabidopsis (Spec 21-26; Figure 9B). PR1 is known to be involved in plants’ responses to certain pathogens.
Applicant describe the sequences of the four tRNAs as SEQ ID NOs: 1-4 (Figure 9A). Applicants do not describe any RFs with at least 75% identity to any one of SEQ ID NOs: 1-4 other than the 100% identity RFs described in Figure 9A and in the sequence listing and sequences with 3 or 4 mismatches (Spec 23 ¶ 98, and Figures). SEQ ID NO: 1 consists of 31 nucleotides, therefore, changing 4 of the nucleotides results in a polynucleotide with 87% identity to SEQ ID NO: 1.
Applicants do not describe any tRNA-derived RNA fragments or antisense nucleotides other than fragments of tRNAs for the mentioned amino acids, alanine, aspartate, glutamate, and glycine. Applicant’s own data in Figure 4B demonstrate that the constructs targeting histidine, leucine, cysteine and proline did not have any effect.
Applicants describe the effector-triggered immunity to Pseudomonas syringae pv. tomato (Pst) in Arabidopsis increasing nuclear-localized tRNAs (Spec 4).
PR1 gene is known in the art to be involved in responses to a variety of pathogens, however, there are no reports in the art of PR1 being involved in other environmental stresses, such as: heat, cold, drought, high salinity, high wind (for plants); disease, malnutrition, thirst, hypoxia, emotional stress (humans). Applicant has not described an RF being effective for modulating any stress response other than the PR1 expression which is involved in the plant pathogen response.
Given the extremely large breadth encompassed by the claims and the vast difference between what is claimed and what was reduced to practice in the instant application, the specification and drawings do not provide an adequate written description across the full breadth of the claims.
Applicant argues that they have described 800 genes, including over 500 defense genes, were are induced by the claimed RFs (Resp 9-10). This is not persuasive, however, because looking at the referenced figure (Figure 7A), the only RF tested was SEQ ID NO: 1 which comprises a fragment of the aspartate tRNA. None of the claims except for claim 30 are limited to this sequence or this tRNA for aspartate.
Applicant argues that they have described constructs with up to four mismatches that continued to have PR1-inducing activity (Resp 10). This is not persuasive because claim 1 does not even require any sequence identity to any tRNA sequence at all, and claim 5 requires only 75% identity whereas the mismatches that were reduced to practice only go as low as 87% identity.
Claim Rejections - 35 USC § 102
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 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.
Anticipation by Carrington
Claim(s) 1 and 2 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Carrington et al (US Patent No. 8,816,061 B2; issued on Aug. 26, 2014). Applicant’s arguments in the response received on May 4, 2026, were fully considered but were not found to be persuasive.
Carrington claims a method for silencing or attenuating expression of a target gene by introducing or expressing into a plant (a eukaryotic organism) an engineered single-stranded RNA transcript wherein the transcript has an initiator sequence that has the same sequence as a micro RNA or siRNA present in a plant (claims 15 and 19). Carrington claims this method wherein the target gene is a plant endogene, transgene, or a gene from a plant infecting pathogen; including wherein the pathogen is a virus, fungi, bacteria, insect, or nematode (claims 17 and 18). A plant endogene, a transgene, or a gene from a plant infecting pathogen is indistinguishable from a tRNA-derived RNA fragment that can have an unlimited number of alterations relative to the starting tRNA sequence. Carrington claims wherein this method results in disease resistance, herbicide resistance, resistance against biotic or abiotic stress, or improved nutritional value (claims 24 and 25, emphasis added). With regard to the limitation of forming a stem loop structure, miRNAs inherently form stem loop structures (Carrington Figure 8B) therefore a single-stranded RNA with the same sequence as a microRNA would inherently form a stem loop.
Applicant argues that Carrington uses single-stranded RNA transcripts that contain an miRNA/siRNA target site (“initiator sequence”) which then exploits endogenous RISC/Dicer machinery (Resp 11). This is not persuasive, however, because Carrington claim that the initiator sequence comprised within the claimed RNA transcription has the same sequence as a micro RNA or siRNA present in a plant. For this reason, the initiator is not merely a target site, but actually comprises the same sequence as a microRNA or siRNA.
Applicant argues that Carrington does not teach or suggest an RF that is a tRNA-derived RF (Resp 11). This is not persuasive, however, because, as discussed above in the indefiniteness rejection, it is unclear what limitations are put on the polynucleotide sequence being claimed due to being derived from a tRNA. This is merely a limitation on how the RF was produced, but there is no limit with regard to how many additions, deletions, and/or substitutions can be made relative to a starting tRNA sequence.
Applicant argues that the rejection of claim 2 is moot in view of the cancellation of that claims (Resp 11). Claim 2 was not actually canceled.
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.
Obvious Over Asha, Arshad, and Zhu
Claim(s) 1 and 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Asha et al. ((2016) Frontiers in Plant Science; Vol. 7; p. 1-16) in view of Arshad et al. ((2017) Frontiers in Plant Science; Vol. 8; pp. 1-15) and further in view of Zhu et al. ((2018) Science China – Life Sciences; Vol. 61; pp. 155-161).
The claims are directed to a method of modulating a stress response in a plant or seed against an environmental stress, said method comprising:
introducing an RNA fragment (RF) or an antisense polynucleotide to said plant or seed, wherein the RF is a transfer RNA (tRNA)-derived RNA fragment and comprises:
a sequence recognition site, wherein the sequence recognition site comprises a reverse complement sequence of a nucleotide sequence of the plant or seed, and a stem loop structure, wherein the stem loop structure comprises: a paired region comprising paired RNA nucleotides, and an unpaired region comprising unpaired RNA nucleotides in the form of a loop, and
wherein the antisense polynucleotide comprises a nucleotide sequence that is complementary to the reverse complement sequence of the RF; and
wherein the RF or the antisense polynucleotide modulates the stress response against the environmental stress.
Asha teaches that the 5’AlaCGC transfer RNA fragment (tRF) is upregulated in black pepper in response to a Phytophthora capsica pathogen infection (Asha 1 abstract). Asha teaches that multiple tRFs were found to target defense-responsive mRNAs which are critical in signaling responses leading to the activation of pathogenesis related (PR) proteins (Id. 13). Asha teaches that the evaluation of these candidate small RNAs (i.e. tRFs) in plant pathogen interaction will lead to advanced disease resistant strategies with wider application in the improvement of stress tolerance in plants (Id. 14). The stem loop structure and paired and unpaired regions are inherent structural properties of the 5’AlaCGC tRF and other tRFs.
Asha does not teach introducing a tRF to a plant or seed.
Arshad teaches overexpression of miRNA156 as a method of affecting abiotic stress in alfalfa plants and improving biomass in alfalfa grown under salinity stress (Arshad 1 abstract; 3 Experimental Design; 4 Results). Overexpression is one way to introduce a desired RNA sequence.
Zhu teaches that tRFs (they call these transfer RNA-derived small RNAs or tsRNAs) regulate gene expression at the transcriptional and/or post-transcriptional levels (Zhu 155 abstract). Zhu teaches multiple tRFs that have been identified in plants, including some which are induced by different stresses (Id. 157 Table 1). Zhu teaches that deciphering the functional roles of tRFs that are associated with a stress response could be particularly valuable to agriculture (Id. 160). Zhu teaches that tRFs can be categorized as niRNA/siRNA-like and miRNA/siRNA-unlike according to their biogenesis and function mechanisms (Id. 158). Zhu mentions overexpressing or knocking down single tRF species and mentions the need to do this without disturbing tRNA maturation as well as other small RNA species (Id.).
At the time the instant application was filed, it would have been obvious and within the scope of one of ordinary skill in the art to overexpress the tRFs taught by Asha in an approach analogous to the approach utilized by Arshad for miRNA156. One would have been motivated to do so because Arshad accomplished an improvement in biomass in plants overexpressing miRNA156 and exposed to salt stress. One would also be motivated to overexpress in plants the tRFs taught by Asha because Zhu teaches the need to determine how to overexpress tRFs without disturbing tRNA maturation as well as other small RNA species. One would expect that overexpression of the tRFs taught by Asha would modulate a stress response, in particular the pathogen responses that were specifically taught by Asha. One would expect overexpression of other tRFs to modulated other stress responses because Zhu teaches multiple tRFs that are induced by different stress conditions.
Obvious Over Asha, Arshad, Zhu, and GenBank Accessions
Claim(s) 5, 6, 29, and 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Asha et al. ((2016) Frontiers in Plant Science; Vol. 7; p. 1-16) in view of Arshad et al. ((2017) Frontiers in Plant Science; Vol. 8; pp. 1-15) and further in view of Zhu et al. ((2018) Science China – Life Sciences; Vol. 61; pp. 155-161), as applied to claims 1 and 2, above, and further in view of any one of Akama, K. ((2006) GenBank Accession AB005780; p. 1), Akama, K. ((2007) GenBank Accession AB005786; p. 1 – referred to hereafter as Akama2), Jeddeloh et al. ((1999) GenBank Accession AF143940; pp. 1-3), and Cosset et al. ((2006) GenBank Accession AJ012212; p. 1).
The claims are directed to a method of modulating a stress response in a plant or seed against an environmental stress, said method comprising:
introducing an RNA fragment (RF) or an antisense polynucleotide to said plant or seed, wherein the RF is a transfer RNA (tRNA)-derived RNA fragment and comprises:
a sequence recognition site, wherein the sequence recognition site comprises a reverse complement sequence of a nucleotide sequence of the plant or seed, and a stem loop structure, wherein the stem loop structure comprises: a paired region comprising paired RNA nucleotides, and an unpaired region comprising unpaired RNA nucleotides in the form of a loop, and
wherein the antisense polynucleotide comprises a nucleotide sequence that is complementary to the reverse complement sequence of the RF; and
wherein the RF or the antisense polynucleotide modulates the stress response against the environmental stress;
wherein the RF is selected from the group consisting of SEQ ID NO: 1, 2, 3, or 4, or a sequence with at least 75% identity to any one of SEQ ID NOs: 1-4.
Asha, Arshad, and Zhu teach introducing a tRF into a plant to modulate a stress response (see rejection of claims 1 and 2, above).
Asha, Arshad, and Zhu do not teach any one of SEQ ID NOs: 1-4.
Each of SEQ ID NOs: 1-4 was already known in the art to be a sequence of a tRNA (Akama, Akama2, Jeddeloh, and Cosset). SEQ ID NO: 1 was known as a fragment of the tRNA-Asp from Arabidopsis (Akama). SEQ ID NO: 2 was known as a fragment of the tRNA-Glu (Akama2). SEQ ID NO: 3 was known as a fragment of the tRNA-Glu from Arabidopsis (Jeddeloh). SEQ ID NO: 4 was known as a fragment of the tRNA-Gly (UCC) from Arabidopsis.
Asha teaches that the Asp tRF and the Gly tRF were found to be overexpressed in Arabidopsis during phosphate deprivation (Asha 2).
Zhu teaches that the Glu tRFs were expressed in flowers and phloem (Zhu 157 Table 1).
Zhu teaches that tRFs in plants are involved in various biological processes, such as cell proliferation, tumer genesis, stress response, and intergenerational epigenetic inheritance (Zhu 155 abstract). Zhu teaches that multiple tRFs were cloned from the phloem sap of pumpkin by a researcher named Zhang (Id. 156). Zhu teaches that a study in barley showed six tRFs were increased in expression and four tRFs were reduced in expression in shoots with a nitrogen deficiency (Id. 158).
At the time the instant application was filed, it would have been obvious and within the scope to overexpress the tRFs taught by Akama, Akama2, Jeddeloh and/or Cosset in a plant to determine the effect such overexpression would confer in the plant. The modulation of a stress response would naturally flow in the overexpressing plants when the plants are subjected to the particular type of stress that the overexpressed tRF is involved with. None of the instant SEQ ID NOs are novel, and each sequence was already known to be a subsequence of a tRNA sequence. One of ordinary skill in the are would have predicted that overexpression of any one of the tRFs would modulate some kind of stress response in some kind of plant. For this reason, the instant claims are obvious over the prior art.
Summary
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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CATHY KINGDON
Primary Examiner
Art Unit 1663
/CATHY KINGDON/Primary Examiner
A.U.1663
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