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 .
Claim Status
In the reply on 18 June 2026 Applicant has canceled claims 2-5, 7. 10-11, 13, 15, 17-21, 23-25, 27-30, 33-49, 51-52, 54-135, 137-178, 180-184, 186-187.
Therefore, claims 1, 6, 8, 9, 12, 14, 16, 22, 26, 31, 32, 50, 53, 136, 179, 185, 188 are herein pending in the application.
Election/Restrictions
Applicant’s election without traverse of without traverse, the Group I claims, drawn to a nucleic acid sequence comprising at least one 5' UTR and at least one coding region encoding at least one therapeutic peptide or protein and at least one first miRNA binding site sequence located in 5' direction relative to the coding region in the reply filed on 18 June 2026 is acknowledged.
Claims 185 and 188 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 6, 8, 9, 12, 14, 16, 22, 26, 31, 32, 50, 53, 136, 179 are under current examination.
Priority
This application was filed 11/01/2023 and is a 371 application of PCT/EP2022/061863 filed on 05/03/2022, which claims benefit to the foreign application foreign priority to PCT/EP2021/061553 filed on 05/03/2021. Thus, the earliest possible priority for the instant application is 05/03/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/01/2023 and 02/05/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner and the signed and initialed PTO Forms 1449 are mailed with this action.
Objection to Drawings
The Specification discloses “poplietal lymph nodes (FIG. 11D)” in [0907] ¶ of US20240229075A1. However, drawing Filed on 01 November 2023 do not 11D. Therefore, appropriate correction of drawing is required to ensure the consistency between the specification and the drawing.
MPEP 608.02(p) states “Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.”
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 6, 9, 12, 14, 16, 22, 26, 31, 32, 136 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation.
Claim 1 is directed to a nucleic acid sequence comprising 5' UTR and coding region encoding therapeutic peptide or protein, miRNA binding site sequence located in 5' direction. The instant specification teaches that the miRNA binding site may be complementary to only a portion of a mi RNA, e.g., to a portion 1, 2, 3 or 4 nucleotides shorter that a naturally occurring miRNA (SPEC p. 13 lns 17-19). Therefore, the broadest reasonable interpretation of the instant claim is a nucleic acid sequence comprising a 5' UTR and a coding region that encodes a natural product forms the foundational architecture of microRNA. The analysis is as follows:
Step 1: The claim is directed to a nucleic acid sequence, which is a composition and a statutory category of matter (Step 1: YES).
Step 2A, prong 1: The claim reads on a nucleic acid sequence. The closest naturally occurring counterpart would be a nucleic acid sequence generated without artificial manipulation or intervention. There is no indication or evidence in the specification that the claimed nucleic acid sequence differs physically, structurally, or functionally from naturally-occurring a nucleic acid sequence. Thus, the claimed cell does not have markedly different characteristics from what occurs in nature and is a “product of nature” exception. Accordingly, the claim is directed to an exception (Step 2A, prong 1: YES).
Step 2A, prong 2: The claim is directed to a product and does not recite any structure that serves to integrate the composition into a practical application, except claim 8 (cap structure), 50, 53, and 179 (Step 2A, prong 2: NO).
Step 2B: There are no additional elements required by the claim.
Therefore, claim 1 does not qualify as eligible subject matter and is rejected under 35 U.S.C. 101 and dependent claims 6, 9, 12, 14, 16, 22, 26, 31, 32, 136.
Claim Rejections - 35 USC § 102
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.
Claims 1, 6, 9, 12, 14, 16, 26, 31, 50, 53, 136, 179 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hoge et al. (US2018256628, cited in IDS filed 11/01/2023; hereinafter “Hoge”).
Regarding claims 1, 12, 14, and 16, Hoge discloses a nucleic acid sequence encoding a therapeutic protein (i.e., human erythropoietin (hEPO)) and a miR142-3p binding site located in 5' direction relative to the coding region [0068], [0168], namely at positions p1, p2 or p3 of the 5'-UTR (Figure 34; [0115], Example 9; SEQ ID Nos: 55-57, [0483]).
Regarding claim 6, Hoge discloses that the first miRNA binding site sequence is located in 5' direction relative to the 5' UTR [0197].
Regarding claim 9, Hoge discloses a miR binding site in one of three different insertion sites within the 5' UTR of the mRNA construct. The 5'UTR sequence used 1s shown below: GGGAAATAAGAG-P1-AGAAAAGAAGAGTA-P2-AGAA GAAATATA-P3-AGAGCCACC (SEQ ID NO: 53), with the three possible insertions sites (Pl, P2, P3). The sequences of 5' UTRs having a miR-142-3p binding site inserted into either Pl, P2 or P3 are shown in SEQ ID NOs: 55-57, respectively [0483]. Therefore, POSITA would anticipate that the miRNA binding site sequence is located in 5' direction relative to the 5' UTR and at least one first miRNA binding site sequence is located within the 5' UTR.
Regarding claim 26, Hoge discloses that the nucleic acid sequence additionally comprising 3' UTR [0005].
Regarding claim 31, Hoge discloses that the nucleic acid sequence comprises poly(A) sequence comprising 140 adenosine nucleotides [0429], [0445].
Regarding claims 50 and 53, Hoge discloses that the sequence comprises at least one modified nucleotide wherein the nucleotide analog is selected from pseudouridine or N-1-methylpseudouridine [0011]-[0013].
Regarding claims 136 and 179, Hoge discloses that the pharmaceutical composition comprising the nucleic acid sequence as discloses above, additionally comprising pharmaceutically acceptable excipients, carriers, diluents and/or vehicles [0076], [0228]. Hoge Further discloses this pharmaceutical composition are desirable, dividing, shaping and/or packaging the product into a desired single- or multi-dose unit [0230]. Therefore, POSITA would have anticipated to use the pharmaceutical composition comprising the nucleic acid sequence as a kit for applying or administration of the components.
Accordingly, Hoge anticipates the instant claims 1, 6, 9, 12, 14, 16, 26, 31, 50, 53, 136, 179.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1, 6, 8, 9, 12, 14, 16, 22, 26, 31, 32, 50, 53, 136, 179 are rejected under 35 U.S.C. 103 as being unpatentable over Hoge et al. (US2018256628, cited in IDS filed 11/01/2023; hereinafter “Hoge”), in view of Ylösmäki et al., (Journal of Virology, Nov. 2008, p. 11009–11015; cited in IDS filed 11/01/2023; hereinafter “Ylösmäki”).
As stated above, with respect to claims 1, 6, 9, 12, 14, 16, 26, 31, 50, 53, 136, 179 Hoge discloses a nucleic acid sequence encoding a therapeutic protein (i.e., human erythropoietin (hEPO)) and a miR142-3p binding site located in 5' direction relative to the coding region [0068], [0168], namely at positions p1, p2 or p3 of the 5'-UTR (Figure 34; [0115], Example 9; SEQ ID Nos: 55-57, [0483]).
Regarding claim 8, Hoge discloses that the mmRNA constructs contained a Cap 1 5' Cap structure (7mG(5')ppp(5')NlmpNp) [0463], still Hoge is silent to the location of miRNA binding site. However, such was known in the prior art.
[AltContent: textbox ([img-media_image1.png]
Fig.1 of Ylösmäki)]With respect to claims 8, 22 and 32, Ylösmäki discloses a nucleic acid sequence having a 5' and a 3' UTR, a coding region encoding luciferase and a miR122 target site in the 5' or the 3' UTR. Ylösmäki demonstrates that suppression takes place in but not A549 cells. SEQ ID NO: 249 of the present application is shown in Fig. 1 (abstract; p. 11010, left-hand column, 3-4 ¶; p. 11010, right-hand column, 3-4 ¶; Fig. 1).
MPEP 2143 (B) states that simple substitution of one known element for another to obtain predictable results. The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). Accordingly, it would have been obvious to practice the nucleic acid sequence comprising of Hoge and substitute the miRNA binding site location and sequence as taught by Ylösmäki with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Ylösmäki because tissue-specific miRNA expression patterns can be exploited also to engineer the tropism of DNA virus replication and may help to overcome liver toxicity associated with the systemic delivery of oncolytic adenoviruses (p. 11010 left hand col. 1st ¶). The POSITA would have a reasonable expectation of success in combining the teachings of Hoge and Ylösmäki because each of these teachings successfully generated composition that can regulate the liver expression with miRNA binding sites. Therefore, the products and method as taught by Hoge et al. in view of Ylösmäki et al. would have been prima facie obvious over the product of the instant application. In regard to the reasonable expectation of success in doing so, substitute miRNA binding site sequence comprising the miR122 nucleic acid sequence (Fig. 1A) of Ylösmäki had a reasonable expectation of success since the steps thereof required no more than recombinant DNA and cell culture technology.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is 571-272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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