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 .
This is a Final Office Action in response to amendment filed on 07/16/2026.
Claim Status
Claims 1-10, and 12-16 are pending. Claim 11 is cancelled. Claim 1 is amended. Claims 12 and 13 are updated for dependency. Claims 1-10, and 12-16 are examined on the merits.
Response to Amendment
The rejection of Claims 1 and 2 rejected under 35 USC § 102(a)(1) is withdrawn in view of amendment to the claims. However, claims 1 and 2 are now rejected under 35 U.S.C. §103 for the reasons set forth below.
The rejection of Claim 11 rejected under 35 USC § 103 is withdrawn in view of cancellation to the claims.
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 1-10, and 12-16 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 recites “injecting, with a needle syringe, the polynucleotide, nucleoprotein complex, nanoparticle or plant viral nanoparticle into a stem or a petiole of the plant, thereby inserting it into the vascular system of the plant”. It is unclear whether the pronoun “it” refers to the needle of the needle syringe or to the injected polynucleotide, nucleoprotein complex, nanoparticle, or plant viral nanoparticle. Under the former interpretation, the claim requires insertion of the needle into the vascular system; under the later interpretation, the claim requires insertion of the recited material into the vascular system. Because these interpretations impose materially different limitations, the scope of claim 1 cannot be determined with reasonable certainty. Accordingly, one of ordinary skill in the art cannot ascertain the metes and bounds of claims 1 with reasonable certainty.
Dependent claims 2-10, and 12-16 are included in this rejection because they do not include additional limitations to resolve the ambiguity.
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.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wu (Jian Wu et. al., PLOS Pathogens, (2019)15 (10))
Claim 1 recites the method for inserting a polynucleotide, a nucleoprotein complex, a nanoparticle or a plant viral nanoparticle into a vascular system of a plant, comprising injecting, with a needle syringe, the polynucleotide, nucleoprotein complex, nanoparticle or plant viral nanoparticle into a stem or a petiole of the plant, thereby inserting it into the vascular system of the plant.
Under the broadest reasonable interpretation, amended claim 1 is interpreted as requiring that the needle of the syringe be inserted into the vascular system of the plant. Specifically, the newly added phrase “with a needle syringe”, when read together with “thereby inserting it into the vascular system of the plant”, reasonably permits the pronoun “it” to refer to the needle used for the injection. Thus, the claim requires more than merely injecting material into a stem or petiole; it requires more than merely injecting material into a stem or petiole; it requires positioning or penetrating the needle into the plant’s vascular system so that the recited material is delivered therein.
The limitation requiring insertion of the needle into the vascular system was introduced by amendment and was not addressed in the prior rejection. Accordingly, the prior anticipation rejection may be maintained only if Wu expressly or inherently discloses insertion of the syringe needle into the plant vascular system.
Wu discloses a method for inserting a polynucleotide into a vascular system of a plant. Specifically, Wu discloses that linear and circular forms of U178G/U179G PSTVd RNA inoculum were injected into vascular tissues of Nicotiana benthamiana plants by needle puncture of stems and petioles, and that needle-puncture inoculation of the circular RBA resulted in successful systemic infection (p12, pa3, “Needle puncture inoculation enables systemic spread of PSTVd U178G/U179G between different cell types”).
Wu further discloses that circular wild-type PSTVd and U178G/U179G RBA transcripts were inoculated by multiple needle-puncture injections into Nicotiana benthamiana stems and petioles using a 10ul syringe (p21, pa3 , “Plant and protoplast preparation and inoculation”)
Thus, Wu discloses injecting, with a needle syringe, a polynucleotide into a stem or petiole of a plant, thereby inserting the polynucleotide into the vascular system of the plant, as required by claim 1. Claim 1 is anticipated by Wu.
Claim 2 recites the method of claim 1, wherein the polynucleotide is DNA or RNA.
Accordingly, claim 2 is anticipated by Wu.
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.
Claims 1-2 are rejected under 35 U.S.C. §103 as being unpatentable over Dalakouras (Athanasios Dalakouras et. al., Frontiers in Plant Science (2018 ) Volume 9, Article 1253, pp1-11).
Claim 1 recites the method for inserting a polynucleotide, a nucleoprotein complex, a nanoparticle or a plant viral nanoparticle into a vascular system of a plant, comprising injecting, with a needle syringe, the polynucleotide, nucleoprotein complex, nanoparticle or plant viral nanoparticle into a stem or a petiole of the plant, thereby inserting it into the vascular system of the plant.
Under the broadest reasonable interpretation consistent with the specification, claim 1 does not requires transformation, stable integration, systemic movement, expression, or any particular biological result beyond physical insertion into the plant vascular system. The term “inserting” is interpreted as introducing or delivering the recited material into the plant vascular system by injection. The term “stem” is interpreted broadly as the main structural axis or above-ground plant body portion that supports leaves and vascular tissue, and therefore includes woody stems/trunks where applicable. Thus, claim 1 reads on a method in which DNA, RNA, viral particles, nanoparticles, or nucleoprotein material is injected into a plant stem, trunk, or petiole such that the material enters vascular tissue.
Dalakouras teaches a method for delivering exogenous RNA molecules, including hairpin RNAs (hrRNAs) and small interfering RNAs (siRNAs), into plants by trunk injection and/or petiole absorption. hrRNAs and siRNAs are polynucleotides (p1, Abstract; p3, Delivery of hpRNA by Trunk Drilling and Injection ).
Dalakouras further teaches drilling holes into the plant trunk and gently applying the hpRNA through the holes using a 1 mL insulin syringe without a needle (p3, right column, pa2). Thus, Dalakouras teaches introducing a polynucleotide into a plant stem/trunk using a syringe so that the polynucleotide enters the plant vascular system, but differs from the claimed invention in that the tissue opening is formed using a drill and the syringe is used without its attached needle.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the needle of the syringe to penetrate the stem and deliver the hpRNA solution, rather than first drilling a hole and subsequently introducing the solution through the hole using the syringe without its needle. Both the drill and the syringe needle perform the same relevant function of penetrating the exterior plant tissue to create an access path for delivery of the polynucleotide into internal plant tissue. Such modification merely substitutes the tissue-penetrating instrument while achieving the same purpose taught by Dalakouras, namely introducing the hpRNA into the stem so that it enters the plant vascular system. A person of ordinary skill in the art would have had a reasonable expectation of success because Dalakouras expressly demonstrates that hpRNA introduced through the stem opening enters the vascular system and is transported to tissue distant from the application site.
Accordingly, claim 1 would have been obvious over Dalakouras.
Claim 2 recites the method of claim 1, wherein the polynucleotide is DNA or RNA.
Accordingly, claim 2 would have been obvious over Dalakouras.
Claims 3, 6-10, 12-13, and 15-16 are rejected under 35 U.S.C. §103 as being unpatentable over Dalakouras (2018) as apply to claim 1, in view of Trolinder (Norma L. Trolinder et. al., US5994624A, Application of 1997-10-20, Publication of 1999-11-30).
Claim 1 as the teachings of Dalakouras is discussed above.
Claim 3, 6-11, and 15 are interpreted as dependent of claim 1.
Under BRI, claim 3 broadly recites that the “polynucleotide” may comprise or be associated with a nucleoprotein complex, a nanoparticle or plant viral nanoparticle, plasmid/protein complex, plasmid, polymer-condensed plasmid, or viral vector, optionally with a linker such as a Lys linker. The claim does not requires a specific sequence, particle structure, vector backbone, linker chemistry, or transformation result.
Dalakouras teaches delivery of exogenous RNA molecules into plants by trunk injection and petiole absorption (p1, Abstract; p3, Delivery of hpRNA by Trunk Drilling and Injection ), and further teaches that conventional plant RNAi delivery approaches include transgenes and viral vectors for producing dsRNA molecules in plants (p2, left column, paragraph 1).
Trolinder teaches injection-based delivery of nucleic-acid/vector material into plant tissue (claim 1). Trolinder further teaches that the introduced polynucleotide may comprise a plasmid used for plant transformation (p6, line50-55).
It would have been obvious to a person of ordinary skill in the art at the time of the invention to utilize plasmids and viral vectors, as taught by Trolinder, in the RNA delivery methods of Dalakouras because plasmids and viral vectors were conventional delivery and transformation vehicles for introducing exogenous polynucleotides into plants. Or of ordinary skill in the art would have reasonably expected that such known plant transformation vectors could be used in the delivery approaches of Dalakouras to facilitate introduction of nucleic acids into plant vascular tissues.
Therefore, claim 3 is prima facie obvious over Dalakouras and Trolinder.
Claim 6 recites the method of claim 1, wherein the polynucleotide further comprises a transgene or a polynucleotide encoding a transgene, optionally wherein the polynucleotide further comprises a marker gene, a therapeutic gene, a biologics, or a nanoparticle.
Trolinder teaches a vector comprising a nucleic acid molecule capable of conferring a desired phenotypic trait to a plant (claim 1). Such a nucleic acid corresponds to a transgene or polynucleotide encoding a transgene (claim 16). Trolinder also teaches trait-conferring genes such as selectable marker genes, herbicide resistance genes, insect resistance genes, and fiber- specific genes (claims 11-15).
Claim 6 is obvious over Dalakouras and Trolinder.
Claim 7 recites the method of claim 1, wherein the polynucleotide further comprises a transgene or a polynucleotide encoding a transgene, optionally wherein the polynucleotide further comprises a marker gene, a therapeutic gene, a biologics, or a nanoparticle, and wherein the needle of the syringe comprises from about 8 mm×31 G, any needle that penetrates/can penetrate the tissue can potentially be used. Claim 8 recites the method of claim 1, and add limitation to claim 7, further limits the syringe to being loaded with from about 1 μg to about 50 μg of polynucleotide per mL of carrier. Claim 9 recites the method of claim 1, wherein the polynucleotide further comprises a transgene which is selected from a marker gene, a therapeutic gene, or a biologic. Claim 10 recites the method of claim 1, wherein the plant is N. benthamiana, N. tabacum.
Dalakouras teaches applying RNA solution into plant trunk/stem tissue using a syringe (p1, Abstract; p3, Delivery of hpRNA by Trunk Drilling and Injection ), and Trolinder teaches injection of nucleic-acid/vector material into plant tissue, including marker genes, herbicide resistance genes, insect resistance genes, and fiber- specific genes (Claims 1, 11-15). Selecting a needle size capable of penetrating the plant tissue would have been routine optimization. The claim is broad because it recites “any needle that penetrates/can penetrate the tissue”.
Dalakouras teaches delivering measured RNA solutions into plants, including 1 mL 500 µg hpRNA for trunk delivery; 200 µl 50 µg hpRNA and 200 µl 10 µg siRNA for N. benthamiana delivery. The correlated concentrations are 500 µg/mL, 250 µg/mL, and 50 µg /mL of carrier respectively (p3-5, fig 2-4).
Claims 7-10 are prima facie obvious in view of Dalakouras and Trolinder.
Claim 12 recites the method of claim 11, wherein the needle of the syringe comprises from about 8 mm×31 G, any needle that penetrates/can penetrate the tissue can potentially be used. Claim 13 recites the method of claim 11, wherein the syringe is loaded with from about 1 μg to about 50 μg of polynucleotide per mL of carrier.
Dalakouras teaches that delivered RNA molecules are transported through vascular tissue, including xylem, after trunk/stem injection and petiole delivery (p1, Abstract; p3, Delivery of hpRNA by Trunk Drilling and Injection ). Trolinder teaches injection-based delivery of nucleic-acid/vector material into plant tissue (claim 1). Therefore, contacting and inserting the polynucleotide into the plant vascular system using a syringe would have been obvious.
Dalakouras teaches delivering RNA solutions into N. benthamiana with 50 µg /mL siRNA of carrier(p5, fig 4).
Accordingly, claims 12-13 are prima facie obvious in view of Dalakouras and Trolinder.
Claim 15 recites the method of claim 1, further comprising growing the plant until expression is established, 3-10 days post inoculation with polynucleotide or nucleoprotein complex or 7-20 days when inoculating with a nanoparticle or plant viral nanoparticle.
Dalakouras teaches monitoring leaves at 1-, 3-, and 10-days post-application and detecting systemically transported RNA (p1, Abstract; p2, Fig 1). Thus, growing the plant until expression or delivery is established over several days would have been obvious.
Claim 16 recites the method of claim 15, further comprising isolating the polynucleotide, nucleoprotein complex, or plant viral nanoparticle from the plant.
Dalakouras teaches harvesting plant leaves after RNA delivery and extracting total RNA for Northern blot analysis (p2, Fig 1(A)). Therefore, isolating the delivered polynucleotide from the plant would have been obvious.
Claims 4-5 are rejected under 35 U.S.C. §103 as being unpatentable over Dalakouras (2018) in view of Trolinder (US5994624A, Publication of 1999-11-30) as apply to claim 3, and further in view of Lindbo (John A. Lindbo, Plant Physiology (2007) Vol. 145, pp. 1232–1240).
Claim 3 as the teachings of Dalakouras and Trolinder (US5994624A) is discussed above.
Claims 4 and 5 are interpreted as dependents of claim 3.
Claim 4 recites the method of claim 3, wherein the viral vector is or is derived from tobacco mosaic virus (TMV), cowpea mosaic virus, or potato virus X. Claim 5 recites the method of claim 3, wherein the plasmid is or is derived from an agrobacterium Ti (tumor inducing) plasmid, a plant viral-derived expression plasmid (based on tobacco mosaic virus (TMV), cowpea mosaic virus or potato virus X)
Dalakouras teaches delivery of exogenous RNA molecules into plants by trunk injection and petiole absorption, resulting in systemic vascular transport through the xylem (p1, Abstract; p3, Delivery of hpRNA by Trunk Drilling and Injection ), Trolinder teaches injection-based delivery of Agrobacterium cells harboring a vector comprising a nucleic acid molecule capable of conferring a desired phenotypic trait to a plant (claim 1). Lindbo teaches TMV-based RNA expression vectors for transient expression of foreign proteins in plants (p1232 Abstract).
It would have been obvious to use a TMV-derived viral vector in the vascular delivery method because TMV vectors were known plant-compatible expression vectors for introducing and expressing heterologous nucleic acid sequences in plants. The combination merely uses a known plant viral vector as the delivered nucleic-acid/vector format in a known plant vascular delivery method, with the predictable result of plant expression or delivery of the encoded sequence. A POSITA would have been motivated to select these known vector to deliver and express a desired nucleic acid sequence in plants, with a reasonable expectation of success based on the known use of both Agrobacterium vectors and TMV-derived expression vectors in plant transformation/expression systems.
Claim 14 is rejected under 35 U.S.C. §103 as being unpatentable over Dalakouras (2018) and Trolinder (US5994624A) as apply to claim 13, in view of Lam (Patricia Lam et. al., Scientific Reports (2016) 6:23803, pp1-8).
Claim 13 as the teachings of Dalakouras and Trolinder (US5994624A) is discussed above.
Claim 14 is interpreted as dependent of claim 13.
Claims 14 recites the method of claim 13, wherein the carrier comprises a buffer solution at a pH of from about 7.2 to about 7.6, or alternatively about 7.4.
Claim 14 is rejected for the same reasons set forth above with respect to claim 13, and further because Lam teaches that coat protein preparations and synthesized RNA transcripts were combined at a final concentration of 1.3 μg/μL and 50 ng/μL, respectively, in 75 mM sodium phosphate buffer (pH 7.2) (p5, paragraph 5). Thus, Lam teaches using a buffered TMV nanoparticles composition (pH7.2) for delivery /inoculation of plant viral material into plants (p5, paragraph 5). Therefore, the buffer limitation of claim 14 would have been prima facie obvious.
Response to Applicant’s Remarks:
Applicant’s arguments filed 07/16/2026 have been fully considered.
Applicant argues that Dalakouras does not disclose injecting a polynucleotide into a stem or petiole using a needle syringe because Dalakouras forms an opening in the plant trunk with a drill and subsequently applies the hpRNA solution through the drilled opening using a syringe without a needle. Applicant further argues that the petiole-absorption embodiment of Dalakouras uses passive uptake rather than needle-syringe injection.
The arguments are persuasive with respect to the previous rejection of claims 1 and 2 under USC § 102 over Dalakouras. Dalakouras does not expressly disclose that the RNA solution is delivered using a needle attached to the syringe. Accordingly, the previous anticipation rejection over Dalakouras is withdrawn.
However, Applicant’s arguments do not establish the patentability of claims 1 and 2 under USC § 103. As set forth in the present rejection, Dalakouras teaches introducing an RNA polynucleotide into the vascular system of a plant through an opening formed in the stem or trunk and dispensing the RNA solution through the opening using an insulin syringe. The difference between Dalakouras and amended claim 1 is that Dalakouras separately forms the tissue opening with a drill and then applies the RNA solution using the syringe without its needle, whereas amended claim 1 use the needle of the syringe to penetrate the plant tissue and deliver the material. It would have been obvious to one of ordinary skill in the art to use the needle attached to the insulin syringe to penetrate the stem and deliver the RNA solution, rather than using a separate drill to form the opening and then dispensing the solution through that opening with the syringe. The proposed modification would merely substitute one known tissue-penetrating instrument for another and would combine the penetration and delivery operations into a single step. The modification would retain Dalakouras’s delivered metatrail, target stem tissue, vascular-delivery pathway, and intended result of introducing the RNA into the plant vascular system.
Applicant argues that Trolinder fails to disclose injection into a stem or petiole using a needle syringe and expressly discourages direct needle injection. These arguments have been considered but are moot with respect to the present rejection because the present rejection claims 1 and 2 under USC § 103 does not rely upon Trolinder to provide the needle-syringe limitation. Rather, the rejection is based on the modification of Dalakouras’s disclosed trunk-delivery method using the attached needle of the disclosed insulin syringe.
Applicant also argues that there would have been no motivation to combine Dalakouras and Trolinder because the references involve different tissue, mechanisms, and purposes. This argument is likewise moot because the present rejection does not rely upon a combination of Dalakouras and Trolinder. The rationale for modifying Dalakouras arises from Dalakouras’s own teaching of forming an opening in a plant stem and applying an RNA solution into that opening using an insulin syringe. Using the syringe needle itself to form the access path and deliver the solution would have predictably reduced the separate drilling and dispensing operations to a single delivery operation.
Applicant further alleges unexpected results, including successful systemic infection, comparable expression yields, reduced tissue damage form petiole injections, and advantages associated with aseptic pharmaceutical manufacturing. There arguments are not persuasive.
First, claim 1 and 2 do not requires a particular degree of systemic infection, expression yield, absence of tissue damage, aseptic manufacturing condition, or pharmaceutical-production result. The asserted advantages therefore are not commensurate in scope with the claims.
Second , claim 1 broadly encompasses injection into either a stem or petiole. Applicant acknowledges that stem injection resulted in necrotic tissue and plant death, while relying on the allegedly improve results obtained from petiole injection. Thus, the asserted results are not shown to extend across the full scope of claim 1, which expressly encompasses stem injection.
Third, the comparison between the claimed method and mechanical or spray inoculation does not establish that the presently claimed difference over Dalakouras – using a syringe needle instead of a drill to access internal stem tissue-produced the alleged results. Applicant has not established a sufficient nexus between the asserted advantages and the particular feature relied upon to distinguish the claims from Dalakouras.
Accordingly, Applicant’s arguments do not overcome the rejection of claims 1 and 2 under 35 U.S.C. § 103 over Dalakouras.
Conclusion
No claims are 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.
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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