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 .
Priority
This application was filed July 17, 2025, and is a 371 application of PCT/US24/42648 filed on August 16, 2024, which claims benefit to the provisional application 63/520,597 filed on august 16, 2023.
Election/Restrictions
Applicant’s election without traverse of Group I: claims 53-74, 79, and 80, Species election: Adenine nucleobase, promoter proximal sequence length of at least 5 nucleotides, SEQ ID NO: 6, and T7 promoter species in the reply filed on Dec. 22, 2025, is acknowledged.
Claims 54, 65-66, 72-79, and 81 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 22 Dec. 2025.
Claim Status
Claims 53-81 are pending in this application and claims 54, 65-66, 72-79, and 81 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Currently, claims 53, 55-64, 67-71, and 80 are under examination in this application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on August 26, 2025, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
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.
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 55 and 56 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 55 and 56 recite “a comparable reference promoter proximal sequence”. The phrase "comparable" renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "or the like" or “to be likened to another”), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d). Thus, it is unclear what is a “comparable reference” promoter proximal sequence, and what the term “comparable” means in relation to the promoter proximal sequence.
In order to expedite prosecution, the term comparable will be defined as any promoter proximal sequence.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 64 and 67 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 64, which ultimately depends from claim 53, wherein the T7 promoter comprises: (a) the sequence of SEQ ID NO: 6. However, SEQ ID NO: 6 does not contain four or more consecutive nucleotides having an adenine nucleobase (see Table 1: Exemplary promoter proximal sequence with T7 promoter, Spec. page 32). Therefore, claim 64 is not within the scope of claim 53. Therefore, claim 64 fails to include all the limitations of the claim upon which it depends because it does not contain four or more consecutive nucleotides having an adenine nucleobase (see e.g. Specification page 32, table 1).
Claim 67 recites “the polynucleotide of claim 53, wherein the sequence encoding the target is situated 3’ of the promoter proximal sequence”. However, claim 53 recites “(iii) a sequence encoding a target operably linked to a 3’ end of (ii)”, where (ii) is the promoter proximal sequence, which does NOT narrow the scope of claim 53 where the target sequence is already encoded at 3’ of the promoter proximal sequence. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 53, 57-63, 67-71, and 80 are rejected under 35 U.S.C. 103 as being unpatentable over Getts et al., (US2008/0160581A1, published 2008), in view of Felletti, et al. (Elife 10: e71611, published 2021), and Collins et al., (WO2010/075441A1, published 2010, hereinafter as “Collins”).
Applicant has elected the species of four consecutive adenine nucleobase, and the specifications states that Table 1: Exemplary promoter proximal sequence with T7 promoter (i.e. SEQ ID NO: 9) (see Spec. e.g. Table 1, page 32). Furthermore, the specification recites that the recombinant polynucleotide of any one of the preceding embodiments (i.e. embodiment 53, SEQ ID NO: 9), wherein the sequence encoding the target is situated 3' of the promoter proximal sequence (see Spec. para, 364-372, pages 60-61).
Regarding claims 53, 57-61, 67-68 and 70-71, Getts discloses a recombinant polynucleotide sequence, comprising: (i) a promoter sequence comprising a 5′ end and a 3′ end; (ii) a promoter proximal sequence adjacent to the 3′ end of the promoter sequence, wherein the promoter proximal sequence comprises four or more consecutive nucleotides having an adenine nucleobase (see sequence results below, Result 3 from Feb. 5, 2026, us-19-272-607a-9.rni, where database (Dd) SEQ ID NO: 5 is 96% local similarity and 82% query (Qy) match to Applicant’s SEQ ID NO: 9)(see e.g. para. 36, Example 1 and 5), and (iii) a sequence encoding a target (i.e. sense RNA molecule (sRNA))(para. 4-5, 13-14, 27-29)) operably linked to a 3′ end of (ii) (see e.g. para. 36, Example 1 and 4-6).
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Getts is silent regarding an adenine at position 18, and therefore does not explicitly teach 100% of SEQ ID NO: 9 (see results above).
However, the prior art of Felletti discloses that AGG functions as a Shine-Dalgarno (SD)-like sequence (see e.g. page 6 and 15). Additionally, the prior art of Collin discloses that the SD sequence in bacteria are strong sequences that are rich in purines (A's,G's), which facilitate proper initiation of protein synthesis (see e.g. para. 239).
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the recombinant polynucleotide of Getts and incorporated an additional adenine in SEQ ID NO: 9 in order to create “AGG” motif in the sequence (as taught by Felletti) because a person of ordinary skill in the art would have wanted to ensure to facilitate proper initiation. Since Felletti discloses that a short “AGG motif” would function like a "Shine-Dalgarno" (SD)-like sequence (see e.g. pages 6 and 15), and Collin’s discloses that SD sequence in bacteria would facilitate proper initiation of protein synthesis (see e.g. para. 239), therefore, it would have been obvious for a person of ordinary skill in the art to have combine known prior art elements (i.e. the SD sequence) to yield predictable results with a reasonable expectation of success. Moreover, an artisan of ordinary skill in the art of (i.e. recombinant polynucleotide technology) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Regarding claim 57-61, as discussed above, Getts discloses wherein the promoter proximal sequence is at least 5 to at least 12 nucleotides in length (see SEQ ID 9 results above, see e.g. para. 4-5, 13-14, 27-29 and 36, Example 1 and 4-6).
Regarding claim 62-63, as discussed above, Getts discloses wherein the promoter is an RNA polymerase promoter, bacteriophage promoter is a T7 promoter, and the T7 promoter comprises: the sequence of SEQ ID NO: 9 (see SEQ ID 9 results above, see e.g. para. 4-5, 13-14, 27-29 and 36, Example 1 and 4-6).
Regarding claim 69, as discussed above, Getts discloses further comprising a polyadenylation signal sequence (see e.g. para. 112 and 193)(see SEQ ID 9 results above, see e.g. para. 4-5, 13-14, 27-29 and 36, Example 1 and 4-6).
Regarding claim 80, as discussed above, Getts discloses a sequence encoding a target (i.e. sense RNA molecule (sRNA)), corresponding to a polyribonucleotide (para. 4-5, 13-14, 27-29, 36, Example 1 and 4-6). Further, Getts discloses a kits for the generation of the sRNA molecules (see e.g. para. 13, 16, 30, 46-47, Example 7), which corresponds to a pharmaceutical composition comprising a polyribonucleotide (see Specification page 57, para. 308)
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 55-56, are rejected under 35 U.S.C. 103 as being unpatentable over Getts et al., (US2008/0160581A1, published 2008), in view of Felletti, et al. (Elife 10: e71611, published 2021), and Collins et al., (WO2010/075441A1, published 2010, hereinafter as “Collins”), as applied to claims 53, 57-63, 67-71, and 80 above, and further in view of Eroschenko et al., (US2020/0224194A1, published 2020) and Namdev, et al. ( Indian Journal of Clinical Biochemistry 34.3: 357-360, published 2019).
The teachings of Getts et al., apply here as indicated above.
Regarding claim 55-56, as discussed above, Getts discloses a promoter proximal sequence (i.e. SEQ ID NO: 9) with a melting temperature at 37°C (see e.g. para. 43-44, Examples 1-6).
Getts does not explicitly disclose wherein when paired with a complementary sequence of nucleotides, the promoter proximal sequence has a lower melting temperature than a comparable reference promoter proximal sequence, wherein the comparable reference promoter proximal sequence comprises: (i) a lesser number of consecutive nucleotides comprising an adenine nucleobase or non-natural variants thereof as compared to the promoter proximal sequence.
However, the prior art of Eroshenko discloses a tetO (i.e. comparable reference) promoter proximal sequence having an annealing temperature of 95°C to 50°C and a T7 promoter proximal sequence having an annealing temperature of 50°C. (see e.g. paras. 77, 90, 297-302, and 390, Example 1).
Accordingly, it would have been obvious for a person of ordinary skill in the art to have the recombinant polynucleotide of Getts with a lower melting temperature than that of a comparable reference promoter proximal sequence as taught by Eroshenko because Getts discloses a promoter proximal sequence having a lower melting temperature (see e.g. para. 43-44, Examples 1-6). Furthermore, the prior art of Namdev discloses that the induction of the T7 promoter at high temperature may not lead to increased protein expression (see e.g. page 357). As discussed above, Getts discloses using a T7 promoter proximal sequence with consecutive nucleotides having an adenine nucleobase. Further, both Getts and Eroshenko discloses using a T7 promoter. Thus, a person of skill in the art would have had predictable results with a reasonable expectation of success. Moreover, an artisan of ordinary skill in the art of (i.e. recombinant polynucleotide technology) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPHINE GONZALES whose telephone number is (571)272-1794. The examiner can normally be reached M-Th: 9AM - 5:00PM (EST). 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, Doug Schultz can be reached at 571-272-0763. 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.
JOSEPHINE GONZALES
Examiner
Art Unit 1631
/JOSEPHINE GONZALES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631