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
1. Claims 1-17 and 21-23 are pending and under examination on the merits.
Claims 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 07, 2025.
Response to Arguments – Objections to the Drawings
2. Applicant’s amendments filed November 18, 2025 have overcome the objections of record.
Response to Arguments – Nucleotide and/or Amino Acid Sequence Disclosures
3. Applicant’s amendments filed November 18, 2025 have overcome the objections of record.
Response to Arguments – Objections to the Specification
4. Applicant’s amendments filed November 18, 2025 have overcome the objections of record. However, said amendments have necessitated new grounds of objection.
Objections to the Specification
5. The disclosure is objected to because of the following:
In [0036], the final line contains what appears to be two incomplete sentences. It is unclear what is intended by the recitation of “Cr., Chlamydomonas reinhardtii.”
Appropriate correction is required.
Response to Arguments – Claim Objections
6. Applicant’s amendments filed November 18, 2025 have overcome the objections of record. However, said amendments have necessitated new grounds for objection.
Claim Objections
7. Claim 17 is objected to because the recitation of a “nuclear-encoded gene within a same photosynthetic plant” should be amended to “nuclear-encoded gene within the same photosynthetic plant” to clarify the antecedent basis of the recitation. Furthermore, it is recommended the phrase “that has” be amended to “comprising”, “consisting of”, or “consisting essentially of” as appropriate (see MPEP 2111.03).
Appropriate correction is required.
Response to Arguments – Claim Rejections - 35 USC § 112(b)
8. Applicant’s amendments filed November 18, 2025 have overcome the rejections of record.
Response to Arguments – Double Patenting
9. Applicant’s amendments filed November 18, 2025 have overcome the rejections of record.
Response to Arguments – Claim Rejections - 35 USC § 102
10. Applicant’s amendments filed November 18, 2025 have overcome the rejections of record. However, said amendments have necessitated new grounds for rejection under 35 U.S.C. 103.
Response to Arguments – Claim Rejections - 35 USC § 103
11. Applicant’s amendments filed November 18, 2025 have been carefully considered but do not overcome all the rejections of record.
Regarding the rejection of claim 14 as being unpatentable over Zhang et al. (Science. 2015; 347(6225):991-994 (previously cited)) further in view of Grimm and Kay (Molecular Therapy. 2007; 15(5):878-888 (previously cited)), Applicant traverses the rejection and argues primarily that Zhang does not teach silencing an endogenous nuclear-encoded plant gene (Applicant’s remarks dated 11/18/2025, pp. 02-03) and that Grimm’s teachings regarding a combinatorial gene silencing attempt in HIV is irrelevant to, and does not anticipate, combinatorial gene silencing in plastids (Applicant’s remarks dated 11/18/2025, pp. 04-05). Applicant’s argument is only partially persuasive because the combination of Zhang and Grimm does not teach a method wherein plastid-encoded dsRNAs silences a plant gene. However, the claim is also directed to a method of silencing an endogenous pathogen gene. As stated in the previous action, Zhang teaches a method for expressing a plastid-encoded dsRNA that silences an endogenous nuclear-encoded gene in a pathogen (Abstract; p. 992, Fig. 1; p. 993, Fig. 2-Fig. 3). Additionally, Grimm teaches introducing a plurality of RNAi constructs to silence a target gene in a pathogen (p. 880, left column, second full paragraph). The combination of Zhang and Grimm teaches a method of introducing a DNA construct into a plant plastid to impart a beneficial trait to the plant (e.g., pathogen resistance) and further comprising introducing a plurality of DNA constructs into a plant plastid genome to silence one or more endogenous pathogen genes. Even though Grimm does not teach introducing a plurality of constructs into a plant plastid, the construction of combinatorial expression vectors is routine for one of ordinary skill in the art. One of ordinary skill would be capable of designing and introducing multiple expression constructs into a host cell or organelle with a reasonable expectation of success. Though the process of Applicant’s invention may be distinct from the teachings of the prior art due to Applicant’s assertion that the plastid-encoded dsRNAs are exported from the plastids to target endogenous nuclear-encoded plant genes, claim 14 is not limited to this feature (i.e., the silencing of a nuclear plant gene) because one may alternatively silence a pathogen gene. As stated above, the combination of Zhang and Grimm teaches a method of introducing a plurality of DNA constructs into a plant plastid genome to silence one or more endogenous pathogen genes to impart pathogen resistance to the plant (e.g., pathogen resistance). Even if Applicant recites steps or features to which the prior art is silent, Applicant’s invention does not produce any surprising or unexpected results when compared to the teachings of Zhang and Grimm. Both Applicant’s invention and the combination of Zhang and Grimm result in the expression of plastid-encoded RNAi constructs that inhibit the growth of plant pests and pathogens. See MPEP 716.02 and MPEP 2143. Accordingly, the rejection of claim 14 is maintained.
Claim Rejections - 35 USC § 103
12. 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.
13. Claims 1-2, 4-8, 10-11, 15-17 and 21-23 are rejected under 35 U.S.C. 103 as being as being unpatentable over Davuluri et al. (Nat Biotechnol. 2005; 23:890–895 (U)) in view of He et al. (Journal of Experimental Botany. 2020; 71(9):2670-2677 (V)) as evidenced by Cognat et al. (Nucleic Acids Res. 2017; 45(6):3460–3472 (W)).
Regarding claim 1, Davuluri teaches a method of introducing a DNA construct, which encodes a dsRNA construct for RNAi, into a plant genome to silence the nuclear-encoded DET1 gene of said plant to impart a beneficial trait to the plant (i.e., increased lycopene and β-carotene; Abstract).
Davuluri does not teach introducing a DNA construct into a plant plastid.
However, He teaches a method of introducing a DNA construct into a plant plastid genome to silence the nuclear-encoded β-actin gene of the Colorado potato beetle larvae to impart pathogen resistance to the plant (Abstract; p. 2672, “Potato plastid transformation”; p. 2672, “Effect of dsRNAs of different lengths on RNAi efficacy in Colorado potato beetle larvae”; p. 2673, “Generation and molecular characterization of transplastomic potato plants expressing dsACTs”).
Cognat discloses the transport of plastid-encoded RNAs from the plastids to the cytosol (Abstract; p. 3469, right column, first full paragraph) to regulate nuclear gene expression (p. 3460, right column, first full paragraph).
Therefore, regarding claim 1, the combination of Davuluri and He, as evidenced by Cognat, teaches a method of introducing a DNA construct into a plant plastid genome to silence an endogenous nuclear-encoded gene of said plant or a plant pathogen to impart a beneficial trait to the plant.
Similarly, regarding claim 8, the combination of Davuluri and He teaches a method for controlling expression of a nuclear-encoded gene in a plant comprising expressing a plastid-encoded dsRNA that silences an endogenous nuclear-encoded gene in the same plant to produce a transformed plant line expressing a selected trait. Thus, the combination of Davuluri and He also teaches a transformed photosynthetic plant cell wherein the plant cell expresses the plastid-encoded dsRNA that silences the endogenous nuclear-encoded gene within the same plant and wherein the plant cell exhibits a selected non-naturally-occurring trait; therefore, claim 10 is also rendered obvious.
Similarly, regarding claim 11, the combination of Davuluri and He teaches a method for controlling expression of a nuclear-encoded gene in a plant comprising expressing a plastid-encoded sense-strand RNA that silences an endogenous nuclear-encoded gene in the same plant to produce a transformed plant line expressing a selected trait. The Office notes that the dsRNA taught by Davuluri comprises both sense and antisense strands (p. 894, “Construction of plasmids.”).
Similarly, regarding claim 17, the combination of Davuluri and He teaches a transformed photosynthetic plant cell comprising a plastid-encoded dsRNA that enables accumulation of small RNAs capable of silencing a nuclear-encoded gene within the same photosynthetic plant for imparting a selected trait to the photosynthetic plant.
Similarly, regarding claim 21, the combination of Davuluri and He teaches a method for controlling expression of a nuclear-encoded gene within a plant comprising expressing a plastid-encoded antisense-strand RNA construct that silences activity of an endogenous nuclear-encoded gene within that plant to produce a transformed plant line expressing a selected trait. Thus, the combination of Davuluri and He also teaches a transformed photosynthetic plant cell wherein the plant cell expresses the plastid-encoded antisense RNA construct that silences the endogenous nuclear-encoded gene within the same plant and wherein the plant cell exhibits a selected non-naturally-occurring trait; therefore, claim 23 is also rendered obvious.
Regarding claims 1, 8, 11, 17, and 21 the level of ordinary skill in the plant biotechnology art is high as evidenced by Davuluri, He, and Cognat. It would have been prima facie obvious for one of ordinary skill in the art to modify the teachings of Davuluri by the teachings of He to introduce a DNA construct into a plant plastid to silence an endogenous nuclear-encoded gene of said plant for the following reasons: 1) Davuluri teaches that RNAi-based silencing of the nuclear-encoded DET1 gene increases the presence of the desirable and beneficial compounds lycopene and β-carotene; 2) He teaches that dsRNAs introduced into the plastid genome accumulate to high levels due to the polyploidy of plastids within an individual cell, which increases the effectiveness of subsequently induced RNAi (p. 2671, left column, second full paragraph); 3) chloroplasts are maternally inherited, which allows the stable inheritance and segregation of the RNAi-induced DNA construct; and 4) it is known in the art that plastid RNAs can escape the plastid to regulate nuclear gene expression. Because of the aforementioned reasons, one of ordinary skill in the art would be reasonably motivated to modify the teachings of Davuluri by the teachings of He to introduce a DNA construct into a plant plastid, wherein said construct would accumulate to high levels due to polyploidy of plastids, to silence an endogenous nuclear-encoded gene of said plant to impart a beneficial trait to the plant. Accordingly, one of ordinary skill in the art would have been motivated to produce the claimed invention(s) with a reasonable expectation of success and without any surprising or unexpected results.
Regarding claim 2, in addition to the teachings discussed above, Davuluri teaches the expression of a double-stranded RNA (Abstract).
Regarding claim 4, in addition to the teachings discussed above, Davuluri teaches silencing the activity of an endogenous nuclear gene (Abstract).
Regarding claim 5, in addition to the teachings set forth above, Davuluri teaches using hairpin/stem loop promoters (Abstract; p. 894, “Construction of plasmids.”). However, He teaches using convergent promoters (p. 992, third paragraph, last sentence) and hairpin stem/loop dsRNA constructs for creating the plastid-encoded dsRNA that produces small RNAs (p. 992, third paragraph; p. 992, Fig. 1, see caption for Fig. 1A).
Regarding claims 6-7, Davuluri teaches a DNA construct which produces a dsRNA construct which comprises both a sense (claim 6) and antisense strand (claim 7; p. 894, “Construction of plasmids.”).
Regarding claims 15-16, the teachings of Davuluri and He are as discussed above. Davuluri does not teach silencing an essential gene in a pathogen. However, He teaches a method for controlling a plant pathogen that is susceptible to small RNAs via expression of a dsRNA which silences an essential gene in the pathogen (Abstract). The Office notes Applicant’s definition of pathogens includes insects[0007].
Regarding claim 17, in addition to the teachings discussed above, He teaches a transformed photosynthetic plant cell having a plastid-encoded dsRNA that enables accumulation of small RNAs capable of silencing a nuclear-encoded gene (i.e., the β-actin gene of the Colorado potato beetle) for imparting a selected trait to the photosynthetic plant (i.e., resistance to the beetle; Abstract; p. 992, Fig. 1; p. 993, Fig. 2-Fig. 3).
Accordingly, the claimed invention is anticipated by the prior art.
14. Claims 3 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Davuluri et al. (Nat Biotechnol. 2005; 23:890–895 (U)) in view of He et al. (Journal of Experimental Botany. 2020; 71(9):2670-2677 (V)), and further in view of Grimm and Kay (Molecular Therapy. 2007; 15(5):878-888 (previously cited)), as evidenced by Cognat et al. (Nucleic Acids Res. 2017; 45(6):3460–3472 (W)).
Regarding claims 3 and 14, the teachings of Davuluri and He are as discussed above in the rejection of claims 1-2, 4-8, 10-11, 15-17 and 21-23 under 35 U.S.C. 103. Davuluri does not teach introducing a plurality of DNA constructs.
Grimm teaches the introduction of a plurality of DNA constructs encoding RNAi constructs to silence a pathogen gene (p. 880, left column, second full paragraph).
The combination of Davuluri, He, and Grimm teaches a method of introducing a DNA construct into a plant plastid to impart a beneficial trait to the plant (e.g., pathogen resistance) and further comprising introducing a plurality of DNA constructs into a plant plastid genome to silence one or more endogenous pathogen genes.
The level of ordinary skill in the RNA biotechnology art is high as evidenced by Davuluri, He, and Grimm. As discussed above in the rejection of claims 1-2, 4-8, 10-11, 15-17 and 21-23 under 35 U.S.C. 103, it would have been prima facie obvious to combine the teachings of Davuluri and He. It would have been prima facie obvious for one of ordinary skill in the art to introduce a plurality of DNA constructs as taught by Grimm to silence a nuclear-encoded gene(s) in a plant pathogen (as taught by He). One would have been motivated to do so because He teaches the effectiveness of a targeting a single gene; one of ordinary skill in the art would predict, with a reasonable expectation of success, that targeting multiple genes using the method of Zhang would result in more effective resistance. Therefore, one of ordinary skill in the art would be motivated by the combinatorial approach to RNA-based gene silencing taught by Grimm to introduce a plurality of silencing constructs to increase silencing and reduce the chance of targets avoiding silencing (p. 880, left column, second full paragraph, lns. 1-10). Even if Applicant recites steps or features to which the prior art is silent, Applicant’s invention does not produce any surprising or unexpected results when compared to the teachings of He and Grimm. Both Applicant’s invention and the combination of He and Grimm result in the expression of plastid-encoded RNAi constructs that inhibit the growth of plant pests and pathogens. See MPEP 716.02 and MPEP 2143. Accordingly, one of ordinary skill in the art would have been motivated to produce the claimed invention with a reasonable expectation of success and without any surprising or unexpected results.
15. Claims 9 and 12 are rejected under 35 U.S.C. 103 as being as being unpatentable over Davuluri et al. (Nat Biotechnol. 2005; 23:890–895 (U)) in view of Zhang et al. (Science. 2015; 347(6225):991-994 (previously cited)).
Regarding claims 9 and 12, the teachings of Davuluri are as discussed above in the rejection of claims 1-2, 4-8, 10-11, 15-17 and 21-23 under 35 U.S.C. 103. Davuluri does not teach introducing a DNA construct into a plant plastid.
Regarding claim 9, Zhang teaches a method of introducing a DNA construct encoding dsRNAs into a plant plastid genome to silence the nuclear-encoded β-actin gene of the Colorado potato beetle larvae to impart pathogen resistance to the plant, selecting a recipient plant cell, transforming a plant cell by introduction of a plastid transformation vector effecting expression of a plastid-encoded RNA construct capable of silencing activity of a nuclear-encoded gene to the plant cell, and regenerating a plant from cells expressing a selected trait (Abstract; p. 992, second paragraph and Fig. 1; p. 993, Fig. 2-Fig. 3).
The combination of Davuluri and Zhang teaches a method for controlling expression of a nuclear-encoded gene in a plant comprising expressing a plastid-encoded dsRNA that silences an endogenous nuclear-encoded gene in the same plant to produce a transformed plant line expressing a selected trait and further selecting a recipient plant cell, transforming a plant cell by introduction of a plastid transformation vector effecting expression of a plastid-encoded RNA construct capable of silencing activity of a nuclear-encoded gene to the plant cell, and regenerating a plant from cells expressing the selected trait.
The level of ordinary skill in the plant biotechnology art is high as evidenced by Davuluri and Zhang. It would have been prima facie obvious for one of ordinary skill in the art to modify the teachings of Davuluri by the teachings of Zhang to introduce a DNA construct into a plant plastid to silence an endogenous nuclear-encoded gene of said plant for the following reasons: 1) Davuluri teaches that RNAi-based silencing of the nuclear-encoded DET1 gene increases the presence of the desirable and beneficial compounds lycopene and β-carotene; 2) Zhang teaches that dsRNAs introduced into the plastid genome accumulate to high levels, which increases the effectiveness of subsequently induced RNAi (p. 991, second paragraph); and 3) chloroplasts are maternally inherited, which allows the stable inheritance and segregation of the RNAi-induced DNA construct. Because of the aforementioned reasons, one of ordinary skill in the art would be reasonably motivated to modify the teachings of Davuluri by the teachings of Zhang to introduce a DNA construct into a plant plastid, wherein said construct would accumulate to high levels due to polyploidy of plastids, to silence endogenous nuclear gene to impart a beneficial trait to the plant. Accordingly, one of ordinary skill in the art would have been motivated to produce the claimed invention(s) with a reasonable expectation of success and without any surprising or unexpected results.
Regarding claim 12, the combined teachings of Davuluri and Zhang are as discussed above in the rejection of claim 9 under 35 U.S.C. 103. The combination of Davuluri and Zhang teaches a method for controlling expression of a nuclear-encoded gene in a plant comprising expressing a plastid-encoded sense-strand RNA construct that silences activity of an endogenous nuclear-encoded gene within the same plant to produce a transformed plant line expressing the selected trait and further comprising selecting a recipient plant cell, transforming the plant cell by introduction of a plastid transformation vector effecting expression of the plastid-encoded sense strand RNA construct capable of silencing activity of a nuclear-encoded gene within the same plant cell, and regenerating the plant from cells expressing the selected trait.
Conclusion
16. No claim is allowed.
17. Applicant’s amendment necessitated the new grounds of rejection presented in this office action. Accordingly, THIS ACTION IS MADE FINAL. 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.
Examiner’s Contact Information
18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEQUANTARIUS JAVON SPEED whose telephone number is (703)756-4779. The examiner can normally be reached M-F; 9AM-5PM ET.
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/DEQUANTARIUS JAVON SPEED/Junior Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663