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 .
Election/Restrictions
Applicant’s election without traverse of Group II consisting of claims 2-3, 7-11 and 15-20, in the reply filed on 08/21/2026 is acknowledged.
The requirement is deemed proper and is therefore made FINAL.
Claim Status
Claims 1-20 are pending.
Claims 1, 4-6 and 12-14 are not examined as being part of unelected groups.
Claims 2-3, 7-11 and 15-20 are being examined.
Claim Rejections - 35 USC § 112(b)
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 15-16 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.
Claims 15-16 depends from claim 2, and recite “… one or multiple nucleotides present at the same positions are different from the nucleotides of other DNAs or genes” (emphasis added; line 3-4).
It is not clear to the Examiner what the Applicant imply by the word “other”. It is not clear to the Examiner if the “one or multiple nucleotides present at the same positions” are-
different from the nucleotides within the “multiple genes encoding identical or similar proteins in a cell”, as recited in claim 2, or
different from the nucleotides of the “other” DNA sequences outside the
“multiple genes encoding identical or similar proteins in a cell”.
The nucleotides recognized in the “multiple genes” by the TALE-modifier complex can differ from one another by a few different nucleotides, and still be bound by the TALE. Therefore, it is unclear what is meant by the aforementioned recitation, which indicates that other genes have at least one different nucleotide. The recitation appears to be intended to differentiate the difference between a “multiple gene” and “other” genes. But the nucleotides recognized or tolerated by the RVD do not have to be the same even in the “multiple genes”.
Claim Rejections - 35 USC § 102(a)(1)
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.
Claims 2-3, 7-10, 15-18 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Erkes et al. (Epigenetic features improve TALE target prediction, 2021, BMC Genomics, 22:914).
Erkes et al. teaches transcription activator-like effectors (TALEs) are sequence-specific DNA-binding proteins that bind to host promoters to activate (reads on to “modifying”) the expression of downstream genes (p.1, right column, para 1, line 4-7) comprising a nuclear localization signal, a modular DNA-binding domain, and an activation domain (that act as a complex with other proteins and reads on to “TALE-modifier complex”) while the DNA-binding domain of natural TALEs is composed of 1.5 to 33.5 consecutive repeats, where each repeat binds to one nucleotide of the target box (p.1, right column, para 2, last 4 lines). Each repeat comprises about 34, highly conserved, amino acids (AAs) while the residues at position 12 and 13 are hyper-variable and are called repeat-variable diresidue (RVD) (bridging paragraph between p.1-2). The second residue (13th) of the RVD binds to the target base, while the first residue (12th) has a stabilizing effect (p.2, left column, para 1, line 3-5). The RVD N*, where ‘*’ represents the deletion of the 13th amino acid, is known to preferentially bind to Y (i.e., T or C) (p.2, left column, para 3, line 10-12), as recited in claims 2-3 and 15-16. On the other hand, the RVD “HD” recognizes H (as recited in claims 2-3 and 15-16); with a strong preference for C, while A and T are bound or recognized in decreasing preference (Fig. 1).
Erkes et al. aims at improving the accuracy of TALE target prediction (software) by incorporating data from RNA-seq infection studies of rice leaves (comprising cells) with several Xoo strains (Xanthomonas oryzae pv. Oryzae) and publicly available data from infection studies with several Xoc strains (Xanthomonas oryzae pv. oryzicola) (abstract, line 9-11; p.3, left column, para 4, line 2-7) and also epigenetic features of differentially expressed genes in rice (Huhan3, O. sativa L. ssp. japonica) genome (i.e., nuclear genes), as recited in claims 7-10 and 20, under drought stress vis-à-vis under normal condition (p.2, right column, para 7, line 4-14) into an extended version of PrediTALE, termed EpiTALE (bridging paragraph between left and right column).
Erkes et al. also describes a method to improve prediction accuracy by considering the epigenetic state of the host plant genome (abstract, line 7-8). The basic procedure of score calculation in a sliding window along the input sequences (p.5, right column, last para, line 2-3) while comparing promoterome-wide predictions using 3 Xoo strains and 10 Xoc strains (the bridging paragraph p.5-6). Erkes et al. describes constructing many TALE proteins with many different combinations of RVDs to modify activity of many genes in rice (p. 6, Supplementary File F; Additional File 7). The additional file 7 provides a long list of RDVs including NA and S* (as recited in claims 17-18) in many different combinations with other RVDs. The ability to recognize specific nucleotide(s) is an inherent property of the RVDs including NA and S*, as recited in claim 17-18. This is a constructive reduction to practice and, thus, implied by Erkes et al. to introduce the TALE modifier complex comprising the modified TALE protein having the RVD sequences composed on NA and S*.
The preamble of claims 2-3 reciting, “for modifying multiple genes encoding identical or similar proteins in a cell” does not constitute a claim limitation but a desired goal or intended objective of the claimed method. Claims 2 and 3 encompass the active step of “introducing one type of TALE-modifier complex comprising at least one repeat sequence containing RVD composed of amino acids that recognize or tolerate N, V, H, D, B, R, Y, M, W, S or K, into the cell”. Thus, Erkes et al. meets all the claim limitations of claims 2-3 and 15-16.
Multiple genes (especially homologous gene families) or different alleles of a specific gene encoding identical or similar proteins (due to large-scale genomic duplications) with overlapping functions are well known in the art (Hyams et al., CRISPys: Optimal sgRNA Design for Editing Multiple Members of a Gene Family Using the CRISPR System, 2018, J. Mol. Biol., 430:2184–2195; p. 2184, left column, para 1, line 1-4). The TALE-modifier complex of Erkes et al. would recognize or tolerate any gene comprising the nucleotide differences as discussed above.
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.
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.
Claims 11 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Erkes et al. in view of Cheng et al. (Simple and Rapid Assembly of TALE Modules Based on the Degeneracy of the Codons and Trimer Repeats, 2021, Genes, 12:1761).
Erkes et al. describes a method for activating or modifying multiple genes encoding identical or similar proteins in a cell by introducing a TALE-modifier complex comprising at least one repeat sequence containing RVD composed of amino acids that recognize or tolerate N, V, D, B, R, Y, M, W, S or K, as discussed above.
Before the effective filing date of the invention, it would have been obvious to an ordinarily skilled artisan and the artisan would have been motivated to produce a rice plant, which is a commercially important crop, and seeds thereof (as recited by claim 11) from a genetically edited/modified plant cell (using any standard routine method) comprising a TALE with specific RDVs, as described by Erkes et al.
Regarding claim 19, TALE proteins comprising RDVs with sequence specific DNA binding property are routinely used to fuse various other proteins including endonucleases for various useful functions, as described by Cheng et al. (p.1, para 2, line 4-8).
Conclusion
No claim is allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAY CHATTERJEE whose telephone number is (703)756-1329. The examiner can normally be reached (Mon - Fri) 8.30 am to 5.30 pm..
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J.C.
/Jay Chatterjee/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662
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