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
Applicant’s claim to priority from provisional applications 63/181,802 filed 04/29/2021 and 63/141,865 filed 01/26/2021 are hereby acknowledged.
Application Status
Claims 1, 3-15, 17, 19-48 are cancelled. Accordingly, claims 2, 16, 18, and 49-51 are pending and are under examination in this office action.
Any objection or rejection not reiterated herein is rendered moot by amendments and therefore withdrawn.
Applicant’s arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
The following rejections are maintained from Office Action dated 09/22/2025.
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 non-obviousness.
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.
Claim 2 is rejected under 35 U.S.C. §103 as being unpatentable over Chen (Chen, L-H. et al. "Structure and function of a bacterial mRNA stabilizer: analysis of the 5' untranslated region of ompA mRNA". Journal of Bacteriology, Vol. 173, No. 15 (1991), pp: 4578-4586), Rosenbaum (Rosenbaum, V. et al. "Co-existing structures of an mRNA stability determinant; The 5' region of the Escherichia coli and Serratia marcescens ompA mRNA". Journal of Molecular Biology, Vol. 229 (1993), pp: 656-670), Wu (Wu, Y-J. et al. "Folding a stable RNA pseudoknot through rearrangement of two hairpin structures". Nucleic Acids Research, Vol. 42, No. 7 (2014), pp: 4505-4515) and Cao (Cao, S. et al. “Predicting structures and stabilities for H-type pseudoknots with interhelix loops”. RNA, Vol. 15 (2009), pp: 696-706.).
Regarding claim 2, Chen teaches a nucleic acid comprising a protective element (PEL) located in a bacterial (i.e. a non-viral sequence) mRNA and a protected sequence (see title and abstract).
Chen teaches a sequence in the 5’ untranslated region (5’UTR) of ompA mRNA that is a stabilizer of the mRNA. Chen teaches a synthetic and expressed sequence 5’UTR and constructing a hybrid gene comprising the 5’UTR of Serratia ompA gene with a bla gene encoding β-lactamase (see pSOB2 plasmid construct, page 4579, left column, second paragraph).
Chen teaches that this RNA segment, either alone or in concert with an associated protein, appears to function directly to protect the ompA transcript from cleavage by an RNase that is sensitive to structural features near the 5’ end of mRNA (see page 4578, right column, second paragraph). Chen teaches that despite extensive divergence in nucleic acid sequences , the 5’UTR of ompA mRNA is an effective mRNA stabilizer in the three species studied, Escherichia coli (E.coli), Serratia marcescens, and Enterobacter aerogenes (see page 4578, right column, third paragraph).
Chen teaches that the 5’UTR sequence has two hairpins as secondary structures (see Figure 1) and below:
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Chen teaches that this 5’UTR is a stabilizer and extends mRNA accumulation in the cell and the half-life. Chen teaches that without this segment the ompA mRNA half-life drops rapidly in growing cells from 15 to 20 minutes down to just 3.6 minutes (see page 4581, right column, “The Serratia and Enterobacter ompA 5’UTRs function in E.coli as mRNA stabilizers” section). Chen teaches that fusing a bla gene encoding β-lactamase with the 5’UTR results in protecting the chimeric mRNA (sob2) produced from degradation as well. Chen teaches a half-life of 15 +/- 2minutes for the hybrid mRNA, compared to wild-type bla mRNA, which is 3minutes (see page 4583, left column, second paragraph).
Therefore, Chen teaches a nucleic acid structure, i.e. 5’UTR OmpA, that possess the capacity of protecting a heterologous sequence, i.e. that is not part of the protected sequence, from degradation.
Chen teaches the possibility of obtaining more than two hairpins as secondary structures in a 5’UTR ompA that is slightly longer (197 nucleotides (nt) versus 158 nt). See Figure 2 and below:
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Chen does not teach a pseudoknot motif. However, Rosenbaum teaches the possibility of the 5’UTR of ompA mRNA as having a pseudoknot, explaining the enhanced stability of the ompA mRNA (see title and abstract; see Figure 3 and below):
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Rosenbaum did not teach an experimental success to support the teaching in the experimental conditions tested. However, Rosenbaum presented theoretical arguments in favor of a pseudoknot in 5’UTR ompA mRNA, explaining protective activity for enhanced stability of mRNA (see page 664, section (ii) “Test for the predicted pseudoknot structure”). Rosenbaum also suggests compromises in experimentation protocols that might affect the results at the time (see page 663, right column, section (c )). Rosenbaum also teaches that the hairpin structures are the fastest formation, but lowest stability (page 669, right column, first paragraph).
Wu teaches that a stable pseudoknot can be synthesized from a two hairpins-structure (see title and abstract). Wu teaches that Escherichia coli (E.coli) rpsO operator mRNA folds into double-hairpin or pseudoknot structures (see page 4508, left column, “Results” section). Wu teaches that manipulating the level of Magnesium can alter the structure of mRNA. Wu teaches that the population of pseudoknot mRNAs increases with an increase in magnesium concentrations (see page 4506, right column, lines 1-2).
Wu also teaches that mutating single bases can favor the formation of pseudoknot in the RNA (see figure 3).
Wu also teaches a pseudoknot comprising a 1st segment, a 2nd segment, a 3rd segment, a 4th segment, a 5th segment and a 6th segment, wherein the 1st segment that hybridizes to the 3rd segment to form a first structured region comprising a 1st duplex, and wherein the 2nd segment hybridizes to the 5th segment to form a 2nd duplex. See Figure 1A and below:
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Cao teaches that the presence of internal stem-loop, also called “interhelix loop”, confers thermostability to the pseudoknot (see page 703, Figure 8). Cao teaches in the form of interhelix loop, a duplex issued from hybridization between two sub-segments within a structured region. Cao teaches using the R2 retrotransposon pseudoknot, that the interhelix loop is the last to be “unzipped”, denatured, when tested from temperatures ranging from 20 ⁰C to 100 ⁰C (see Figure 8).
Therefore, Examiner interprets that at least one interhelix loop in addition to the pseudoknot would confer more stability and more of a mechanical blockage at physiological temperatures.
Therefore, it would have been obvious to one with ordinary skills, before the effective filing date, to have tried and designed a pseudoknot from the 5’UTR sequence taught by Chen and Rosenbaum, and substituted the double hairpins- structure with a pseudoknot taught by Wu. Rosenbaum teaches that it is possible to obtain a pseudoknot from the 5’UTR of ompA mRNA, as it is predicted to be present in appropriate conditions supplemented with magnesium. Wu predicts that mutating one or more nucleotide can be favorable to pseudoknot formation. Cao teaches that adding interhelix loop , i.e. elongating the sequence, can give rise to a more thermostable structure. Chen teaches that elongating the sequence can give rise to a third hairpin (see figure 2). One with ordinary skills in the art, combining the teachings of Chen, Rosenbaum, Wu and Cao could have performed modifications to the 5’UTR region of ompA mRNA and obtain a potent and stable protective element comprising a 1st duplex, a second duplex and a 3rd duplex formed within a 2nd structured region by hybridization between two sub-segments of the 6th segment. Therefore, one with ordinary skills in the art motivated in harnessing the potential of this structure for prolonging the half-life of a synthetic nucleic acid sequence and stabilizing it, could have performed this modification with a reasonable expectation of success and arrived at the claimed invention.
Claims 49 and 50 are rejected under 35 U.S.C. §103 as being unpatentable over Chen (Chen, L-H. et al. "Structure and function of a bacterial mRNA stabilizer: analysis of the 5' untranslated region of ompA mRNA". Journal of Bacteriology, Vol. 173, No. 15 (1991), pp: 4578-4586), Rosenbaum (Rosenbaum, V. et al. "Co-existing structures of an mRNA stability determinant; The 5' region of the Escherichia coli and Serratia marcescens ompA mRNA". Journal of Molecular Biology, Vol. 229 (1993), pp: 656-670), Wu (Wu, Y-J. et al. "Folding a stable RNA pseudoknot through rearrangement of two hairpin structures". Nucleic Acids Research, Vol. 42, No. 7 (2014), pp: 4505-4515) and Cao (Cao, S. et al. “Predicting structures and stabilities for H-type pseudoknots with interhelix loops”. RNA, Vol. 15 (2009), pp: 696-706.), as applied to claim 2 above, and in further view of Han (Han, K. et al. Nucleic Acids Research, Vol. 31, No. 13 (2003), pp: 3432-3440; previously cited).
The rejection of claim 2 is described above. The elements of claim 2 are rendered obvious by the combination of references Chen, Rosenbaum, Wu and Cao.
Regarding claim 49, the combination of references Chen, Rosenbaum, Wu and Cao does not render elements of claim 49 obvious.
However, Han teaches the design/drawing of pseudoknots, and specifically these elements. Han teaches elements of claim 2 as well.
Regarding claims 2 and 49, Han also teaches a 1st segment, a 2nd segment, a 3rd segment, a 4th segment, a 5th segment and a 6th segment; See figure 6A, page 3437, reproduced below with the elements identified.
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Han teaches a 1st segment that hybridizes to the 3rd segment to form a first structured region comprising a 1st duplex:
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Han teaches a 2nd segment that hybridizes to the 5th element to form a 2nd duplex:
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Han teaches a 3rd duplex formed within the second structured region by hybridization between two sub-segments of the 4th segment. Han further teaches a 6th segment.
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Han also teaches that the 1st structured region additionally comprises one or more intra-segment base-pairs (i.e. base pairing, homology region) within the 3rd segment (see figure 6A).
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Regarding claim 50, Han teaches that the 2nd structured region additionally comprises one or more intra-segment base pairs within the 4th segment, see figure 6A:
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It would have been obvious to one with ordinary skills in the art, before the effective filing date, to have substituted the structure of the 5’UTR of ompA mRNA taught by Chen, modified by Rosenbaum, Wu and according to the teachings of Cao for more thermostability, with a pseudoknot as taught by Han in figure 6A. One motivated in designing a structure efficient in avoiding decay of mRNA or any other therapeutic noncoding RNA introduced in a cell under living cells conditions could have combined the teachings of Chen, Rosenbaum, Wu, Cao and Han. Chen teaches the activity of 5’UTR of ompA mRNA, Rosenbaum predicts that the 5’UTR of ompA mRNA comprises a pseudoknot and Rosenbaum, Wu, Cao and Han’s teachings all pertain to pseudoknots, their design and/or stability. One with ordinary skills in the art, motivated in ensuring stability of the 5’UTR ompA mRNA pseudoknot could have performed modifications to Chen/Rosenbaum pseudoknot according to Han’s designs with a reasonable expectation of success and arrived at the claimed invention.
Claims 16, 18 and 51 is rejected under 35 U.S.C. §103 as being unpatentable over Chen (Chen, L-H. et al. "Structure and function of a bacterial mRNA stabilizer: analysis of the 5' untranslated region of ompA mRNA". Journal of Bacteriology, Vol. 173, No. 15 (1991), pp: 4578-4586), Rosenbaum (Rosenbaum, V. et al. "Co-existing structures of an mRNA stability determinant; The 5' region of the Escherichia coli and Serratia marcescens ompA mRNA". Journal of Molecular Biology, Vol. 229 (1993), pp: 656-670), Wu (Wu, Y-J. et al. "Folding a stable RNA pseudoknot through rearrangement of two hairpin structures". Nucleic Acids Research, Vol. 42, No. 7 (2014), pp: 4505-4515), Cao (Cao, S. et al. “Predicting structures and stabilities for H-type pseudoknots with interhelix loops”. RNA, Vol. 15 (2009), pp: 696-706) and Han (Han, K. et al. Nucleic Acids Research, Vol. 31, No. 13 (2003), pp: 3432-3440; previously cited).
Regarding claims 16, 18 and 51, Chen teaches a nucleic acid comprising a protective element (PEL) located in a bacterial (i.e. a non-viral sequence) mRNA and a protected sequence (see title and abstract).
Chen teaches a sequence in the 5’ untranslated region (5’UTR) of ompA mRNA that is a stabilizer of the mRNA. Chen teaches a synthetic and expressed sequence 5’UTR and constructing a hybrid gene comprising the 5’UTR of Serratia ompA gene with a bla gene encoding β-lactamase (see pSOB2 plasmid construct, page 4579, left column, second paragraph).
Chen teaches that this RNA segment, either alone or in concert with an associated protein, appears to function directly to protect the ompA transcript from cleavage by an RNase that is sensitive to structural features near the 5’ end of mRNA (see page 4578, right column, second paragraph). Chen teaches that despite extensive divergence in nucleic acid sequences , the 5’UTR of ompA mRNA is an effective mRNA stabilizer in the three species studied, Escherichia coli (E.coli), Serratia marcescens, and Enterobacter aerogenes (see page 4578, right column, third paragraph).
Chen teaches that the 5’UTR sequence has two hairpins as secondary structures (see Figure 1).
Chen teaches that this 5’UTR is a stabilizer and extends mRNA accumulation in the cell and the half-life. Chen teaches that without this segment the ompA mRNA half-life drops rapidly in growing cells from 15 to 20 minutes down to just 3.6 minutes (see page 4581, right column, “The Serratia and Enterobacter ompA 5’UTRs function in E.coli as mRNA stabilizers” section). Chen teaches that fusing a bla gene encoding β-lactamase with the 5’UTR results in protecting the chimeric mRNA (sob2) produced from degradation as well. Chen teaches a half-life of 15 +/- 2minutes for the hybrid mRNA, compared to wild-type bla mRNA, which is 3minutes (see page 4583, left column, second paragraph).
Therefore, Chen teaches a nucleic acid structure, i.e. 5’UTR OmpA, that possess the capacity of protecting a heterologous sequence, i.e. that is not part of the protected sequence, from degradation.
Chen teaches the possibility of obtaining more than two hairpins as secondary structures in a 5’UTR ompA that is slightly longer (197 nucleotides (nt) versus 158 nt). See Figure 2 and below:
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Chen does not teach a pseudoknot motif. However, Rosenbaum teaches the possibility of the 5’UTR of ompA mRNA as having a pseudoknot, explaining the enhanced stability of the ompA mRNA (see title and abstract; see Figure 3 and below):
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Rosenbaum did not teach an experimental success to support the teaching in the experimental conditions tested. However, Rosenbaum presented theoretical arguments in favor of a pseudoknot in 5’UTR ompA mRNA, explaining the protective activity and enhanced stability of mRNA (see page 664, section (ii) “Test for the predicted pseudoknot structure”). Rosenbaum also suggests compromises in experimentation protocols that might affect the results at the time (see page 663, right column, section (c )). Rosenbaum also teaches that the hairpin structures are the fastest formation, but lowest stability (page 669, right column, first paragraph).
Wu teaches that a stable pseudoknot can be synthesized from a two hairpins-structure (see title and abstract). Wu teaches that Escherichia coli (E.coli) rpsO operator mRNA folds into double-hairpin or pseudoknot structures (see page 4508, left column, “Results” section). Wu teaches that manipulating the level of Magnesium can alter the structure of mRNA. Wu teaches that the population of pseudoknot mRNAs increases with an increase in magnesium concentrations (see page 4506, right column, lines 1-2).
Wu also teaches that mutating single bases can favor the formation of pseudoknot in the RNA (see figure 3).
Wu also teaches a pseudoknot comprising a 1st segment, a 2nd segment, a 3rd segment, a 4th segment, a 5th segment and a 6th segment, wherein the 1st segment that hybridizes to the 3rd segment to form a first structured region comprising a 1st duplex, and wherein the 2nd segment hybridizes to the 5th segment to form a 2nd duplex. See Figure 1A and below:
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Cao teaches that the presence of internal stem-loop, also called “interhelix loop”, confers thermostability to the pseudoknot (see page 703, Figure 8). Cao teaches in the form of interhelix loop, a duplex issued from hybridization between two sub-segments within a structured region. Cao teaches using the R2 retrotransposon pseudoknot, that the interhelix loop is the last to be “unzipped”, denatured, when tested from temperatures ranging from 20 ⁰C to 100 ⁰C (see Figure 8).
Therefore, Examiner interprets that at least one interhelix loop in addition to the pseudoknot would confer more stability and more of a mechanical blockage at physiological temperatures.
Regarding claim 16 specifically, Han teaches the design of elements comprising a pseudoknot motif. Han teaches a motif comprising 4 segments and 2 duplexes (H-type pseudoknot); see figure 1C and 2 (A to D), page 3433 (reproduced below).
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Han teaches a 1st segment that hybridizes to the 3rd segment to form a structured region comprising a 1st duplex:
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-Han teaches a 2nd segment that hybridizes to the 4th segment to form a 2nd duplex:
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Regarding claim 18 specifically, Han teaches in figure 6A, a 1st, a 2nd , a 3rd, a 4th , a 5th and a 6th segment. Han also teaches that the 4th segment hybridizes to the 6th segment to form a 2nd structured region comprising a 3rd duplex (see picture below).
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The claim using the term “comprising” is an open-ended term, therefore Han teaches the structure claimed.
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It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the synthetic nucleic acid construct taught by Chen/Rosenbaum to contain a functional pseudoknot as taught by Wu, Cao and Han to act as a mechanical block, that inhibits degradation of a protected sequence where the RNA pseudoknot is not part of the protected sequence, as described by Chen. Chen specifically teaches that a protective RNA double hairpin structure, as taught in figures 1 and 2, is capable of protecting the recombinant nucleic acid construct against endonucleases, in view of the stability of the hybrid mRNA. However, one motivated in obtaining protection against cellular endonucleases or other viral endonucleases or exonucleases would be motivated in searching for alternatives structures, stable in solution and thermostable, which are taught by Rosenbaum, Wu, Cao and Han. A person of ordinary skill in the art would have been motivated to do so in order to control degradation of specific RNA species when using different types of cells, and building resistance to different types of nucleases. A person of ordinary skill in the art would have had a reasonable expectation of success because Chen introduces the concept of mRNA protection and stability using RNA hairpin structures present in the 5’UTR of ompA mRNA; Rosenbaum suggests that the protection is due to a pseudoknot in 5’ UTR of the sequence to be protected; and both Rosenbaum, Wu, Cao and Han are drawn to RNA pseudoknots. Therefore, utilizing the RNA pseudoknots of Han such that it is located on 5’ end to a sequence that one desired to protect, as described by Chen, would have resulted in the predictable outcome of a mechanical block that inhibits degradation of the protected sequence and where the RNA pseudoknot is not part of the protected sequence.
Regarding claim 51, Han also teaches the structure claimed in claim 16 ( a pseudoknot motif comprising a 1st segment, a 2nd segment, a 3rd segment and a 4th segment), wherein the structured region additionally comprises one or more intra-segment base pairs within the 1st segment (see figure 3 D, page 3434) or one or more intra-segment base pairs within the 3rd segment (see figures 3A, 3B, and 3C):
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Han teaches additional intra-segment base pairs in the 1st segment
and/or intra-segment base pairs within the 1st segment interspersed between inter-segment base pairs between the 1st and 3rd segments (figure 3D):
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Han also teaches additional intra-segment base pairs within the 3rd segment
(figures 3A, AB and 3C) and/or intra-segment base pairs within the 3rd segment interspersed between inter-segment base pairs between the 1st and 3rd segments (3C):
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Therefore, the combination of references Chen, Rosenbaum, Wu, Cao and Han renders obvious the elements of claim 51 as well.
Response to Applicant’s Arguments
Applicant’s arguments, see “Remarks” on pages 5-9, filed 01/22/2026, with respect to the rejections of claims 2,16,18 and 49-51 under 35 U.S.C. § 103 have been fully considered, but are not persuasive.
Applicant argues against Chen on pages 5-8, then states “When an obviousness determination relies on the combination of two or more references, there must be some suggestion or motivation to combine references”, “the theoretically predicted pseudoknot in E. coli could not be confirmed experimentally” and “the absence of any experimental result pointing towards its existing argues against an additional tertiary structure folding”. Applicant also argues that “ such a modification would impermissibly change the operation of and defeat the purpose of Chen, particularly where Chen didn’t even appear to know how their system worked”.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Chen teaches elements in the 5’UTR of OmpA mRNA that have a specific property as a mRNA stabilizer (see title). Chen shows that stabilizer elements exist in Nature. Modifying something that occurs naturally using Synthetic Biology for therapeutic goals is obvious. Rosenbaum’s studies suggest that there is a potential pseudoknot predicted using computational method, although not demonstrated via experimentation (see abstract). This suggestion, made clear in the abstract of Rosenbaum, alone, is sufficient for one with ordinary skills in the art, to be motivated in synthesizing a protective element based upon the structure described in Chen.
The experimental methods may not have been optimized enough to synthesize and test an artificial pseudoknot based upon the structure described as a mRNA stabilizer in 1991 and 1993. However, Cao, in 2009, provides approaches to design and predict stability of pseudoknots, stating that “quantitative prediction of pseudoknot structure and its stability is essential in order to unveil the mechanisms of RNA functions and in order to design therapeutic strategies for the diseases” (see page 696, right column). Further, Wu, in 2014, presents with ways to transform hairpins into pseudoknots.
By 2012, one of ordinary skills in the art such as Lei Qi (Qi, Lei. “Scalable genetic system design using synthetic RNA regulators”, University of California, Berkeley, 2012) was capable to use the knowledge of hairpins laid out by Carrier (Carrier, T.A. et al. “Library of synthetic 5’ secondary structures to manipulate mRNA stability in Escherichia coli”. Biotechnol. Prog. Vol 15, No. 1 (1999), pp: 58-64) and synthesize a pseudoknot motif (see page 90, section 5.8 “Discussion on the design principles”).
Lei Qi states (page 90, section 5.8): “In this work, we have demonstrated two alternative designs to rationally engineer natural ncRNAs to sense ligands by fusing them with RNA aptamers. The ISI0 and pT181 ncRNAs are both highly structured and likely to represent a class of ncRNA regulators whose function highly depends on the structure38. In our designs, we fused RNA aptamer sequences to the 5' end of the
ncRNA molecules in the similar architecture as natural riboswitches. We introduced mutations into different locations in different designs to disrupt the ncRNA structure: the mutations were on the aptamer loop region to form pseudoknots with the ncRNA loop (pseudoknot design); or the mutations were on the ncRNA lower stem region to make this region exchangeable between alternative conformations (strand exchange design). In both designs, ligand binding eliminated disruptions on the ncRNA hairpin and activated its function.”
Evolution from Qi’s thesis lead to a patent (Liu, C. et al. US 9,593,338 B2, published March 14, 2017) entitled “Synthetic transcriptional control elements and methods of generating and using such elements”. Liu states “Specifically, the unbound aptamer domain forms a disruptive pseudoknot with the RNA-OUT domain, which is untied when theophylline binds the aptamer; this allows RNA-OUT to hybridize with RNA-IN and repress translational initiation” (see column 59, lines 58-62).
The current rejection are based on the obviousness of someone of ordinary skills before the effective filing date of 01/26/2021, to have the motivation and ability to transform a 5’UTR known as a natural mRNA stabilizer into a pseudoknot, as suggested by Rosenbaum and practiced by Wu.
Broadening the search to RNA-based synthetic regulatory elements generally, lead to Carrier, Qi and Liu; these references show the state of the art in Synthetic Biology from 2012; they present efficient use of hairpins and pseudoknots in the art. Therefore, this shows that the level of skills in the art is high, and that there was motivation to use hairpins and modify them to lead to RNA-based synthetic regulatory elements.
Therefore, the rejections are maintained.
Conclusion
No claim is 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.
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/A.D./Examiner, Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636