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 of Group I in the reply filed on 9/2/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 9/2/2025. Claim Rejections - 35 USC § 112 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- 6, 8, 9 and 11- 15 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. When the claims are analyzed in light of the specification, the instant invention encompasses any nucleotide sequence encoding a polypeptide with ribonuclease III activity, which is at least 50% identical to SEQ ID NO: 20 or 22. Further, the claims encompass any substitutions at the nucleotide positions identified in Table 2 that, when the substitutions are present, reduce or eliminate regulation of expression of an mRNA transcribed from SEQ ID NO: 20 by a member of an miRNA family listed in Table 2. The relationship between SEQ ID NOs: 20, 22 and 23 are as follows (as taught on pg. 12 lines 7-24 of the specification): SEQ ID NO: 20 is the nucleotide sequence for a Δhel-DICER1 construct. SEQ ID NO: 22 is the nucleotide sequence for an exemplary OptiDicer construct and is 75% identical to SEQ ID NO: 20 . The 25% difference between SEQ ID NO: 20 and 22 is that SEQ ID NO: 22 is engineered to be pan-miRNA-resistant by comprising 33 introduced silent mutations which are detailed in Fig. 16 and with additional codon optimization (pg. 66 lines 24-32 and Fig. 16 of the specification). SEQ ID NO: 23 is the amino acid sequence encoded by SEQ ID NO: 22. Regarding function, the claims recite that the claimed nucleotide sequence must encode a polypeptide sequence with ribonuclease III activity (SEQ ID NOs: 20 and 22-claim 1) and with respect to SEQ ID NO: 20 have the additional function of reducing or eliminating regulation of expression of an mRNA transcribed from SEQ ID NO: 20 by a member of a miRNA family listed in Table 2 (claims 2, 3 and 5) . However, the specification provides no description of any sequences other than the full-length sequence set forth in SEQ ID NO: 20 and SEQ ID NO: 22, that would indicate possession at the time of filing for a nucleic acid sequence encoding a polypeptide having ribonuclease III activity. In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their structure. In the instant case, only SEQ ID NO s : 20 and 22 ( nucleotide sequence ) are sufficiently described to indicate possession of nucleic acid sequence s that encode a protein with ribonuclease III activity . The specification does not provide any disclosure as to what the complete structure would be of any nucleic acid sequence other than the full-length sequences disclosed in the specification that encode a protein with ribonuclease III activity . The specification teaches no structural analysis for said nucleic acid sequence s or the protein encoded. This is significant since the claims recite a function for the produced protein. However, the only disclosed protein that has ribonuclease III activity is the one encoded by full-length nucleotide sequence set forth in SEQ ID NO s: 20 and 22. As of the filing date, there was no known or disclosed correlation between a structure other than SEQ ID NO s : 20 and 22 and the proteins they code for . There is no general knowledge in the art about regarding the activity of ribonuclease III to suggest that general similarity of structure confers the activity. The structure of the nucleotide sequence is significant since Applicant has shown that even three silent mutations can have a major impact on the function of the produced protein as it relates expression in human RPE cells (see Example 4 and lines 14-23 in particular ). When Applicant made an additional 30 silent mutations (exemplified in SEQ ID NO: 22 and detailed in Fig. 16), Applicant was able to express human DICER1 in human RPE cells (Example 4 lines 24-32). This is significant because the claims encompass any mutation in the positions of SEQ ID NO: 20 in Table 2. Further, with respect to claim 4 and the mutations being silent, this would also not provide support for the claimed nucleotide sequence. While it has been generally assumed in the art that silent mutations do not alter the function of the encoded polypeptide, the art teaches that even silent mutations can significantly alter the structure and function of the encoded protein. For example, Bali et al. (2015, Int. J. Biochem . Cell Biol., Vol. 64, pgs. 58-74) teaches that silent (aka synonymous) mutations can alter proteins translation, protein folding and introduce mRNA folding and splicing defects (pgs. 4-12). Similarly, Sholtis S. (2022, Eberly College of Science, pgs. 1-5) teaches: We used to use ‘synonymous’ and ‘silent’ interchangeably to describe mutations that don’t change a protein’s sequence because it was thought that they wouldn’t alter the function of the protein,” said Ed O’Brien, professor of chemistry and a co-hire of the Institute for Computational and Data Sciences at Penn State, and one of the leaders of the research team. “But, we ’ ve known for some time now that not all synonymous mutations are silent. Over two decades ago, it was shown that synonymous mutations could reduce the activity of proteins, but it was still unknown what was happening at the molecular level to cause this change.” (pg. 3 parag . 1). In this regard, the claims require the function of a reduction or elimination of regulation of expression of an mRNA transcribed from SEQ ID NO: 20 by a member of an miRNA family listed in Table 2. However, even within the ranges of nucleotides set forth in table two and the breadth and combinations of substitutions encompassed by the claims the claimed nucleotide sequence encompasses thousands of different nucleotide sequences that may or not exhibit the claimed function. Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only characteristic described, is that the full-length nucleotide sequences set forth in SEQ ID NOs: 20 and 22 encode a polypeptide with ribonuclease III activity and with respect to the function of a reduction or elimination of regulation of expression of an mRNA transcribed from SEQ ID NO: 20 by a member of an miRNA family listed in Table 2, only the nucleotide sequence set forth in SEQ ID NO: 22 is sufficiently described. The specification does not teach any other identifying characteristics such as domains relating to function/activity or any other related sequences that would guide the artisan to contemplate other nucleic acid sequences that would be encoded by less than the full sequence s set forth in SEQ ID NO s : 20 and 22 . Th e function of the protein is related to the structure of the nucleic acid, which as stated above, the specification has only disclosed the full-length sequences set for th in SEQ ID NO s : 20 and 22 . However, the claims are not limited to any particular nucleotide sequence, but rather any combination of nucleotides present in a sequence that is at least 50% identical to the sequence set forth in SEQ ID NOs: 20 and 22 . Since this nucleotide sequence is relative to the amino acid sequence it encodes, the encoded protein must exhibit the claimed functions . The skilled artisan could not rely upon the disclosure in the specification such that the specification would sufficiently describe that Applicant was in possession of any sequences less than 100% identical to the nucleotide sequences set forth in SEQ ID NOs: 20 and 22 at the time of filing. While the structure and function of the full-length human DICER1 protein and nucleotide sequence is known, the specification has not described any other structural characteristics of a nucleic acid sequence that encodes an a polypeptide having ribonuclease III activity and exhibits a reduction or elimination of regulation of expression of an mRNA transcribed from SEQ ID NO: 20 by a member of an miRNA family listed in Table 2 . Applicants' attention is directed to the decision in Vas-Cath Inc. v. Mahurkar , 19USPQ2d 1111, which clearly states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116). With the exception of the sequences referred to above, the skilled artisan cannot envision the detailed chemical structure of the encompassed polynucleotides, and therefore conception is not achieve regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The nucleic acid itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Therefore, only the full-length nucleotide sequences set forth in SEQ ID NOs: 20 and 22 meet the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicants effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641,1646 (1998). In conclusion, this limited information is not deemed sufficient to reasonably convey to one skilled in the art that applicant is in possession of the genus of nucleic acid sequences encoding polypeptide with ribonuclease III activity thereof as embraced by the claims. 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 appl icant regards as his invention. Claims 2 and 5-8 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 2 and 5 are indefinite. Claims 2 and 5 recite the limitation of “ Table 2 ” with respect to claiming a range of nucleotide substitutions in SEQ ID NO: 20 , however the limitations of the said table should be recited in the claims. Specifically, MPEP § 2173.05(s) states, “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant' s convenience.” Ex parte Fressola , 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). 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. Claim(s) 1 and 11-15 is/are rejected under 35 U.S.C. 1 02(a)(1) as being FILLIN "Insert either—clearly anticipated—or—anticipated—with an explanation at the end of the paragraph." \d "[ 3 ]" anticipate by Chakr a borty et al. (US Pat. No. 9,220,775 B2, issued 10/29/2015) . Regarding claim 1, Chakr a borty et al. teach a nucleotide sequence (SEQ ID NO: 220724) which is 99.9% identical to instant SEQ ID NO: 20 and encodes a polypeptide with ribonuclease III activity, wherein the polypeptide is 99.9% identical to SEQ ID NO: 23. Regarding claims 11 and 12, Chakr a borty teaches that a vector can comprise the nucleotide sequence (col. 117 lines 43-46). Regarding claim 13, Chakraborty teaches that a host cell can comprise the vector (col. 332 lines 42-58). Regarding claim 14, Chakraborty teaches that pharmaceutical composition can comprise the vector and pharmaceutically acceptable diluent (col. 304 lines 40-62). Regarding claim 15, Chakraborty teaches that their nucleotide sequence can be introduced into a cell (col. 96 lines 36-47). Thus the teachings of Chakraborty clearly anticipate the invention of claims 1 and 11-15. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT DAVID A MONTANARI whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-3108 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-Tr 8-6 . 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Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /DAVID A MONTANARI/ Examiner, Art Unit 1632