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 .
Priority
This application claims priority to a European Patent Application No. 21168638.1 filed April 15, 2021.
Examiner’s Note: The examiner did not see a certified document in the file wrapper to which this application can claim priority to.
Response to Previous Communication
In response to the communication received on 05/07/2026, from Oyvind Dahle, the election of Group III, Claims 21-22, is acknowledged.
Because Applicants did not distinctly and specifically point out supposed errors in the restriction requirement, the election has been treated as an election without traverse. See MPEP § 818.03(a).
Status of Claims
Claims 1-20 and 23 are canceled.
Claims 24-40 are added.
Claims 21-22 and 24-40 are pending.
Claim 40 is withdrawn for consideration for being drawn to unelected subject matter.
Claims 21-22 and 24-39 are examined herein.
Claim Objection
Claim 1 is objected to for adding a space between “com” and “prises” in lines 2 and 10.
In line 5 of Claim 22, the conjunction “and” should be replaced with ---or---; because (i) and (ii) are interpreted to be recited in the alternative.
Claim 25 appears to have an unnecessary space between “where” and “in”.
Claim 32 uses a “-“ after the name of some amino acids but not others.
The term “agrobacterium” should be capitalized and italicized: ---Agrobacterium---.
Appropriate correction is required.
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.
Claim 33 is 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.
Regarding Claim 33, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present
Instant Claim 33 recites the narrower limitation of a FT gene then states the FT gene can be optionally mutated or truncated which is the broader statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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.
Claims 21-22, 25-26, 30-31, and 33-39 are rejected under 35 U.S.C. 103 as being unpatentable over the teachings of WO 2021041001 A2 (Voytas) in view of Liu, Huawei, and Baohong Zhang. "Virus-based CRISPR/Cas9 genome editing in plants." Trends in Genetics 36.11 (2020): 810-813 (see IDS filed 12/14/2023).
Voytas is directed to “Methods and materials for increasing somatic and germline genome editing …. For example, provided herein are methods and materials for using augmented sgRNAs to increase somatic and germline genome editing” as was recited in the abstract. Regarding instant Claim 21, Voytas’ Claims 24-26 are drawn to a method for generating a plant (i.e. with modified meristem cells) comprising delivering (i.e. providing of Claim 21 (i)) an augmented sgRNA (i.e. single-guide RNAs or guide RNA) and a sequence encoding an RNA guided gene editing reagent (i.e. a Cas9 CRISPR-nuclease i.e. Coding RNA) to a plant. The Claim further recites the augmented sgRNA comprises a sequence targeted to a specific genomic DNA sequence and a first mobile RNA sequence. The RNA guided genome editing reagent (i.e. Coding RNA) also comprises a second mobile RNA sequence (i.e. mobile element). The mobile RNA sequence (i.e. mobile element) can be used to translocate RNA (guide or coding) to the meristem as was described on page 14 lines 21-24. These claims and teachings appear to address the limitations of Claim 21 (ii) except the composition of fusing these components to create an editing RNA.
Claims 36-38 of Voytas teach the augmented sgRNA can be delivered via Agrobacterium while page 3 line 12 teaches the sgRNA can be delivered (i.e. transfected) via a viral vectors as was directed to in instant Claims 22 and 25. Page 21 lines 7-11 teach the augmented sgRNAs, or guide RNAs with mobile elements, can be incorporated into viral vectors, which can be introduced into plants. Viruses that have been harnessed for use as vectors include Tobacco Rattle Virus (TRV) as was recited in immediate Claim 26. The mobile elements of instant Claim 30 are clearly described by Voytas on page 14 lines 22-25. Table 1 appears to teach tRNA-like or mRNA (i.e. gene transcripts) can be used to promote mobility in plants and teaches the limitations of Claim 31. This table also includes FT and GAI transcripts of Claim 33. The limitations of immediate Claim 34 were addressed in Voytas’ Claim 24 which recites “the augmented sgRNA comprises (i) a sequence targeted to the specific genomic DNA sequence and (ii) a first [in this case second] mobile RNA sequence [which transports the guide RNA]”. Cleavable spacer elements, as recited in Claim 36, are disclosed on page 13 lines 31-32 while placement of the mobile element (i.e. Claim 37) is addressed on page 19 lines 11-14 recite “a mobile RNA sequence can be located 5' of an sgRNA sequence, and can be any appropriate distance away from the sgRNA sequence within an augmented sgRNA molecule.” Multiple guide RNAs being encoded on the same vector is described on page 37 line 28-29 as directed to in Claims 38 while Claim 39 is made obvious by example 9 and Figure 12 where a plant was transformed to express two guide RNAs for the same AG locus (i.e. gene).
Voytas et al 2021 does not appear to explicitly discuss fusing the sgRNA (i.e. guide RNA) and sequence coding the CRISPR-nuclease to form an editing RNA as is recited in instant Claims 21 and 35.
However, Liu et al 2020 teaches a recent study1 demonstrated “genome- editing efficiency can be significantly increased to 65–100% if the gRNAs are fused to a mobile RNA sequence, such as truncated FLOWERING LOCUS T (FT)… It may therefore be possible to fuse the Cas9/ gRNA system with a mobile RNA sequence, and then use the corresponding engineered SYNV virus to infect plants, thus
achieving genome editing completely independently of tissue culture ”. The fusion of the mobile RNA sequences to Cas9 and gRNA sequences implies the creation of the editing RNA drawn to in Claims 21 and 35.
It would have been prima facie obvious to combine the teachings of Voytas et al 2021 in view of Liu et al 2020 to generate a method that produces a meristem cell having a targeted genomic modification by providing a plant with a vector expressing a CRISPR-nuclease coding RNA, guide RNAs, and one or multiple mobile elements which may or may not be fused to form an editing RNA. One having ordinary skill in the art would have a reasonable expectation of success as all the components were known in the art and the use of mobile elements have already been demonstrated to aid in improving genome editing efficiency as disclosed by Liu et al 2020 on page 3 paragraph 1. The motivation for creating such a method is described by Voytas et al 2021 which states “For many plant species, protocols for regenerating plants from somatic cells are not available, and even in those species with established protocols, success often is genotype dependent. In addition to being technically challenging, the whole process can be very time consuming; it can take from several months to a year to generate an edited plant from the somatic cells that receive the editing reagents”. A method which generates genomically modified meristem plant cells without the need for regeneration and tissue culture would save considerable time and money as genetically modified seeds can be harvested instead. The number of guide RNAs (i.e. Claim 38), which genes they target (i.e. Claim 39), and placement of mobile elements and cleavable spacer sequences (i.e. Claims 36-37) are all design choices as the criticality of such composition does not appear to be explicitly stated.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over the teachings of Voytas in view of Liu et al 2020 as applied to claim 21 above, and further in view of Osakabe, Yuriko, et al. "Optimization of CRISPR/Cas9 genome editing to modify abiotic stress responses in plants." Scientific reports 6.1 (2016): 26685.
Claim 24 draws dependence from Claim 21 which was previously rejected based on the teachings of Voytas in view of Liu et al 2020 (see above).
Voytas and Liu et al 2020 do not explicitly teach the use of a CRISPR-nuclease comprising a nuclear localization signal (NLS).
Osakabe et al 2016 is also directed to optimization of CRISPR/CAS genome editing in plants without off-target effects in plant genomes. Page 2 paragraph 4 recites “Multiple nuclear localization signal (NLS) sequences control nuclear import tightly, and Cas9 with NLS sequences at both N- and C-termini has been shown to ensure efficient nuclear targeting”. Figure 1 also demonstrates CAS9 (i.e. a CRISPT-nuclease) fused to a NLS.
It would have been prima facie obvious to combine the teachings of Voytas in view of Liu et al 2020 and Osakabe et al 2016 to include a CRISPR-nuclease comprising a NLS in an vector that encodes an editing RNA for use in a method for targeted genomic modification of meristem cells. Because NLS have been shown to ensure efficient nuclear targeting, one of ordinary skill in the art would have a reasonable expectation of success. The motivation for why such a method is desirable was described previously.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over the teachings of Voytas in view of Liu et al 2020 as applied to claim 26 above, and further in view of Baltes, Nicholas J., et al. "DNA replicons for plant genome engineering." The Plant Cell 26.1 (2014): 151-163.
Claim 27 draws dependence from Claim 26 which was previously rejected based on the teachings of Voytas in view of Liu et al 2020 (see above).
Voytas and Liu et al 2020 do not explicitly teach a virus that has a deletion in a sequence encoding the coat protein.
Baltes et al 2014 is directed to using geminivirus-based replicons for transient expression of sequence-specific nucleases (zinc-finger nucleases, transcription activator–like effector nucleases, and the clustered, regularly interspaced, short palindromic repeat/Cas system). Page 2 paragraphs 1-2 teaches “To develop an efficient and facile vector system for plant genome engineering, we focused our efforts on the geminiviruses. Geminiviruses are a large family of plant viruses… Methods to engineer geminiviruses for protein expression include the full virus and deconstructed virus strategies. Under the full virus strategy, geminiviruses retain most or all of the features required for replication and systemic infection of the host plant. Heterologous sequence can be introduced within the genome by replacing [i.e. deletion] the coat protein gene (coat protein is not required for cell-to-cell movement in some bipartite begomoviruses”. Page 2 paragraph 4 also recites “Under the deconstructed virus strategy, limiting or undesired virus functions are removed, and only the useful blocks are kept. For example, to circumvent genome size constraints imposed by the plasmodesmata, movement protein and coat protein sequences are removed, whereas the cis- and trans-acting replicational elements are retained”.
It would have been prima facie obvious to combine the teachings of Voytas in view of Liu et al 2020 and Baltes et al 2014 to use a virus engineered with a deletion in a sequence encoding the coat protein to transfect a plant cell with a vector that encodes an editing RNA for use in a method for targeted genomic modification of meristem cells. One of ordinary skill would have a reasonable expectation of success as geminivirus-based replicons (with deletions in sequences encoding coat proteins) enable highly efficient genome engineering (see page 2 paragraph 5). The motivation for why such a method is desirable was described previously.
Claims 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over the teachings of Voytas in view of Liu et al 2020 as applied to claim 26 above, and further in view of Zhu, Haocheng, Chao Li, and Caixia Gao. "Applications of CRISPR–Cas in agriculture and plant biotechnology." Nature Reviews Molecular Cell Biology 21.11 (2020): 661-677.
Claims 28-29 draw dependence from Claim 26 which was previously rejected based on the teachings of Voytas in view of Liu et al 2020 (see above).
Voytas and Liu et al 2020 do not explicitly teach a circular naked nucleic acid molecule (i.e. Claim 28) or a DNA molecule coupled to a carrier (i.e. Claim 29)
Zhu et al 2020 is a review article on application of CRISPR-Cas in plant transformations. Figure 3A demonstrates plasmid DNA (i.e. naked circular nucleic acid molecule of Claim 28) can be directly delivered (i.e. provided) into the plant cell using Nanoparticles or biolistic bombardment. Additionally, page 15 paragraph 5 recites delivery methods (i.e. carriers) of CISPR-Cas reagents can include nanomaterials such as Carbon nanotubes (i.e. inorganic nanoparticle) or cell-penetrating peptides which were limitations of Claim 29.
It would have been prima facie obvious to combine the teachings of Voytas in view of Liu et al 2020 and Zhu et al 2020 to use circular naked DNA or inorganic nanoparticles or cell-penetrating peptides in a method for targeted genomic modification of meristem cells. One of ordinary skill in the art would have recognized these compositions are known in the art for introducing sequences encoding the nuclear editing elements (i.e. CRISPR-nuclease and guide RNA) and have a reasonable expectation of success in using them. The motivation for why such a method is desirable was described previously.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over the teachings of Voytas in view of Liu et al 2020 as applied to claim 31 above, and further in view of Ellison, Evan E., et al. "Multiplexed heritable gene editing using RNA viruses and mobile single guide RNAs." Nature plants 6.6 (2020): 620-624 (see IDS filed 12/14/2023).
Claim 32 draws dependence from Claim 31 which was previously rejected based on the teachings of Voytas in view of Liu et al 2020 (see above).
Voytas and Liu et al 2020 does not teach the use of a methionine-, glycine-, threonine-, arginine-, lysine- or glutamine-tRNA.
Ellison et al 2020 is directed to using mobile single guide RNAs fused to mobile elements (i.e. FT and tRNA). The paragraph bridging page 3 and page 4 recites “Flowering Lucust is not the only RNA that moves between cells. Plant phloem exudates contain many transfer RNA-like sequences capable of cell-to-cell movement”. Ellison et al 2020 disclosed methionine, glycine, and isoleucine tRNAs (i.e. Claim 32) improved editing efficiency when fused to the 3’ end of the guide RNAs.
It would have been prima facie obvious to combine the teachings of Voytas in view of Liu et al 2020 and Ellison et al 2020 to use methionine or glycine tRNA as a mobile element in a method for targeted genomic modification of meristem cells. One having ordinary skill in the art would have a reasonably high expectation of success as these sequences are known to promote transport of RNA between cells (i.e. to meristem). The motivation for why such a method is desirable was described previously.
As described above, the combined teachings of the cited references Voytas et al 2021, Liu et al 2020, Osakabe et al 2016, Baltes et al 2014, Zhu et al 2020, and Ellison et al 2020, together with the general knowledge and the state of the art, make the instant claims obvious. For example, the use of vectors (i.e. naked DNA, Agrobacterium, and viruses) and editing RNA components (i.e. coding RNA, guide RNAs, mobile elements, nuclear localization signals, and cleavable spacer sequences) were known in the art and are routinely used at the time the instant application was filed. Similarly, modifications to them would be mere design choice and routine optimizations of the methods taught by the cited references and the general state of the art, absent evidence to the contrary.
Conclusion
No claims are allowed.
Communications
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE W MEYER whose telephone number is (571)272-3733. The examiner can normally be reached Monday - Friday 8:00 am- 5:00 pm.
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/GEORGE W MEYER/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662
1 Ellison, Evan E., et al. "Multiplexed heritable gene editing using RNA viruses and mobile single guide RNAs." Nature plants 6.6 (2020): 620-624 (see IDS filed 12/14/2023).
Prosecution Insights