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 .
Applicants’ arguments and amendments filed on 6/23/2026 have been entered.
Claims 1, 2 and 5 have been amended.
In view of Applicants arguments and amendments to the claims the 112(b) and 102(a)(1) rejections are withdrawn.
Claims 1-15 are examined in the instant application.
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 remain 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 for reasons of record in the Non-Final Office Action mailed on 12/23/2025 (and repeated as amended below). 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 NOs: 20 and 22 (nucleotide sequence) are sufficiently described to indicate possession of nucleic acid sequences 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 sequences 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 NOs: 20 and 22. As of the filing date, there was no known or disclosed correlation between a structure other than SEQ ID NOs: 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 sequences set forth in SEQ ID NOs: 20 and 22. The 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 forth in SEQ ID NOs: 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.
Response to Arguments
Applicant’s Arguments
Applicants argue in amendment that claim 1 recites inter alia that the polypeptide has the amino acid sequence of SEQ ID NO: 23, this immediately informs one of ordinary skill in the art of precisely what the amino acid sequence of the polypeptide is. From this, one of ordinary skill in the art would be appropriately apprised of each and every nucleotide sequence that falls within the scope of amended claim 1.
The Non-final Office Action also cites references discussing potential functional
consequences associated with synonymous or "silent" mutations. However, applicant respectfully submits that such references do not support the conclusion that the amended claims lack adequate written description support. Although synonymous mutations may, in some circumstances, affect translational efficiency, expression levels, folding kinetics, or other biological properties, synonymous mutations nevertheless preserve the encoded amino acid sequence by definition. Here, the amended claims are directed to nucleotide sequence modifications specifically described in the application and associated with the disclosed engineering strategy relating to SEQ ID NOs: 20 and 22, rather than arbitrary synonymous substitutions across an undefined sequence space.
Moreover, the application as filed does not merely hypothesize the use of silent mutations generally. Rather, the application specifically discloses engineered nucleotide modifications, including introduced mutations associated with miRNA resistance and codon optimization strategies used to generate the disclosed constructs. Thus, applicant is not seeking protection for all conceivable synonymous sequence variants, but instead for a specifically described and exemplified set of sequence modifications grounded in the teachings of the application as filed.
Examiner’s Response
While Applicant’s arguments have been fully considered they are not found persuasive. The issue remains that the claimed encoded polypeptide requires ribonuclease III activity and the specification does not teach possession of a nucleotide sequence that is any 75% sequence identity with SEQ ID NO: 20 or 22 and encodes a functional polypeptides with said activity. While synonymous mutations preserve the encoded amino acid sequence, the specification does not support any sequence with 75% sequence identity with SEQ ID NO: 20 or 22 and encodes a functional polypeptides with said activity.
Thus for the reasons above and of record the rejection is maintained.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID A MONTANARI whose telephone number is (571)272-3108. The examiner can normally be reached M-Tr 8-6.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. 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
/ANOOP K SINGH/Primary Examiner, Art Unit 1632
Prosecution Insights