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 .
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 04/09/2024 has been considered by the Examiner inasmuch as foreign documents have been submitted into the file wrapper in English.
Claim Status
The preliminary amendment filed April 09, 2024 has been entered. Claims 5-6, 9-12, 15, 17-20, 26-30, 32-34, 38-48 and 54-58 are canceled.
Thus, claims 1-4, 7-8, 13-14, 16, 21-25, 31, 35-37, 49-53 and 59 as amended are examined on the merits herein.
Claim Objections
Claims 1-4, 7 and 31 are objected to because of the following informalities:
(i) Claim 1, line 4; Claim 2, line 1; Claim 3, line 1; Claim 4, line 1 and Claim 7, line 4 each recite “a salt thereof” when referring to “the nucleotide mRNA cap”. However, each recitation of “a salt thereof” as discussed above is the second recitation of this limitation, the first recitation is within claim 1, line 1.
Therefore, to promote clarity the Examiner respectfully suggests replacing the word “a” with the word “the” within the recited claims above.
(ii) Claim 31, lines 1-2, recite the phrase “the anion exchange chromatography” which the Examiner respectfully notes is inconsistent with the recitation of “the anion exchange system” which is recited in claim 25, line 2. The Examiner respectfully notes claim 31 depends from claim 25.
Therefore, to promote clarity the Examiner respectfully suggests replacing the word “chromatography” with the word “system” as discussed above.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-4, 7-8, 13-14, 16, 21-25, 31, 35-37, 49-53 and 59 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.
(i) Claim 1, line 3, recites “collecting and combining one or more mixtures” and then further recites in line 5 the recitation “removing the contaminants from the combined mixtures”.
However, based on the recitations above the Examiner respectfully notes the scope of the claim is unclear and indefinite in view of the recitation of “one mixture” as recited above; as the Examiner respectfully notes one mixture cannot be combined as recited.
Additionally, the scope of the claim is unclear and indefinite as to whether or not “one mixture” is required in view of the recitation of “the combined mixtures” within line 5 of claim 1.
Therefore, claim 1 is unclear and indefinite as to what is being claimed, for example does the method require:
(a) collecting a mixture comprising the nucleotide mRNA cap, or a salt thereof, and one or more contaminants, and removing the contaminants from said mixture to provide a first mixture; or
(b) collecting and combining two or more mixtures comprising the nucleotide mRNA cap, or a salt thereof, and one or more contaminants, and removing the contaminants from said combined mixture to provide a first mixture.
Claims 2-4, 7-8, 13-14, 16, 21-25, 31, 35-37, 49-53 and 59 are included in this rejection as they either depend from or rely on the method of claim 1.
In the interest of compact prosecution the Examiner will interpret the phrase “one or more mixtures” to mean:
(a1) one mixture is collected comprising the nucleotide mRNA cap or a salt thereof, and one or more contaminants, and removing said contaminants from said mixture to provide a first mixture; or
(b1) two or more mixtures are collected and combined comprising the nucleotide mRNA cap or a salt thereof, and one or more contaminants, and removing said contaminants from said combined mixture to provide a first mixture.
(ii) Claim 50 recites the limitation "the fourth mixture" in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 50 depends from claim 1 which does not recite the limitation of a “fourth mixture”.
Claims 51-53 and 59 are included in this rejection as all of these claims depend from claim 50.
In the interest of compact prosecution, the Examiner will interpret claim 50 will depend from claim 35 to provide proper antecedent basis for the limitation of “the fourth mixture” as the Examiner respectfully notes this limitation is first recited in claim 35, line 3.
(iii) Claim 25 recites the limitation "the ion exchange chromatography system" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 25 which depends from claim 23 does not recite said system as discussed above. The Examiner respectfully notes claim 23 only recites the limitation “ion exchanging” when referring to the second mixture, see line 3.
Claim 31 is included in this rejection as it depends from claim 25.
In the interest of compact prosecution the Examiner will interpret claim 25 as depending from claim 24 which is the first recitation of the limitation “an ion exchange chromatography system” as recited in line 2 of the claim.
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.
(I) Claims 1-3, 7-8, 13, 16, 21-25, 31, 35-37 and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Su et al. (Published 19 March 2021, CN-112521437-A, IDS filed 04/09/2024, English Machine Translation, PTO-892) in view of Geiger et al. (Published 20 August 2020, WO-2020165158-A1, PTO-892).
Regarding claims 1-3, 7-8, 13, 16, 21-25, 31, 35-37 and 49, Su teaches recovering anti-reverse cap analogues in the in-vitro transcription process of mRNA (e.g. recycling mRNA nucleotide cap or a salt thereof from an mRNA preparation, required in claim 1, lines 1-2), see pg. 6, paragraph 1, line 1.
Su teaches said recovery method comprises separating the anti-reverse cap analogues in a reaction liquid through a high-performance liquid chromatography (HPLC) to obtain crude anti-reverse cap analogues, purifying, concentrating (e.g. concentrating, required in claim 1, last line of the claim) and drying the crude anti-reverse cap analogues in sequence to obtain the anti-reverse cap analogues, see pg. 6, paragraph 1, lines 2-4.
The Examiner respectfully notes the teaching of Su above correspond to the limitation of collecting one mixture comprising the nucleotide mRNA cap or a salt thereof and one or more contaminants, required in claim 1, lines 3-4 as interpreted by the Examiner in the 112 rejection above, see pg. 5, paragraph (a)(1)).
The Examiner also respectfully notes the words “separating” and “purifying” the crude anti-reverse cap analogues within the reaction liquid corresponds to the limitation of removing the contaminants from the mixture to provide a first mixture, required in claim 1, line 5, as interpreted by the Examiner in the 112 rejection above, see pg. 5, paragraph (a)(1)).
Su teaches the anti-reverse cap analog includes m7G(5')ppp(5')(2'OMeA)pG, see pg. 6, paragraph 2, line 1. The Examiner respectfully notes the recitation of m7G(5')ppp(5')(2'OMeA)pG of Su meets all structural limitations of compound A as recited in claims 2-3.
Su teaches the anti-reverse cap analog was purified by dialysis, see pg. 2, background, paragraph 5.
Su teaches by utilizing the size difference of molecular weight, the method of dialysis can remove chromatographic mobile phase impurities contained in a sample after chromatographic purification, effectively remove other small molecular impurities and residual solvent, and achieve the aim of purifying and recycling the obtained anti-reverse cap analogue, see pg. 3, paragraph 6.
Su teaches primary recovery of anti-reverse cap analogs using reverse phase high performance liquid chromatography, see pg. 3, second paragraph from the bottom of the page, example 1.
Su teaches in Fig. 3 a liquid chromatogram of the remaining mixture after the RNA transcription reaction, where the mixture can be seen to contain residual NTP (e.g. NTPs, required in claim 23, line 2) and anti-reverse cap analogs, and the two substances can be clearly separated and collected according to the peak-off time of the anti-reverse cap analog, see pg. 3, last paragraph of the page – pg. 4, first paragraph.
Su teaches in Fig. 4 a liquid chromatogram of the finally recovered and purified anti-reverse cap analogue, in which no other impurity peaks can be observed, and only the anti-reverse cap analogue peak is observed, indicating the recovered anti-reverse cap analogue has a high purity, see pg. 4, first paragraph.
Su teaches the chromatography comprises ion exchange chromatography (e.g. ion-exchanging, required in claim 23, line 3; claims 24-25 and claim 31) or reversed-phase high-performance liquid chromatography, see pg. 6, paragraph 3.
With respect to the limitation “wherein the anion exchange chromatography comprises exchanging N,N-dimethyloctylammonium (DMOA) for NH4+”, required in claim 31; the Examiner reasonably interprets this limitation to be a physical limitation resulting from the ion exchange chromatography system used to separate the nucleotide phosphates (NTPs) from the mixture as recited in claim 23. Since Su teaches using reverse phase high performance liquid chromatography for recovery of anti-reverse cap analogs by separating and removing NTPs in Figs. 3 and 4 above; and since Su teaches chromatography comprises ion exchange chromatography or reversed-phase high-performance liquid chromatography; the physical limitation as discussed above is met by the teachings of Su above.
Although, Su does not explicitly teach where the reaction liquid is (a) desalted to provide a second mixture as required in claim 1, last line of the claim and claim 16; (b) where removing comprises removing macromolecules and proteins, required in claims 7-8 and 13; and (c) concentrating and de-salting the third mixture to provide a fourth mixture, required in claims 35-37 and 49-53.
However, in the same field of endeavor of isolating mRNA caps, with respect to limitations (a)-(c), Geiger teaches purifying mRNA comprising the purification of precipitated mRNA molecules from a suspension that comprises said precipitated molecules. The suspension comprising precipitated mRNA molecules can be obtained for example from in vitro transcription. Thus, precipitated mRNA molecules have to be purified from components of in vitro transcription. See pg. 7, first full paragraph.
Geiger teaches 5’ caps and 5’ cap analogs can be comprised in the suspension used for preforming step (Ia) for example in case the mRNA molecules have been transcribed in vitro and have been co-transcriptionally capped. Hence, step (Ia) is advantageous for removing components from in vitro transcriptions mixtures from precipitated mRNA molecules, see pg. 9, first full paragraph.
Geiger teaches step (Ia) is performed using tangential flow filtration (TFF) (e.g. filtration, required in claim 8), see pg. 1, first paragraph.
Geiger teaches tangential flow filtration is a filtration method where a solution or suspension comprising the target molecule such as mRNA molecules is passed through a filter membrane, see pg. 2, second paragraph.
Geiger teaches when applying in step (Ia) a molecular-weight cut off (MWCO) in the range of 1kDa to 750 kDa, the TFF can be referred to as ultrafiltration, whereas in the case of applying an MWCO in the range of 0.05 µm to 0.65 µm, the TFF can be referred to as microfiltration (e.g. the molecular-weight cut off, required in claim 13, last line of the claim; claims 21-22; and claim 49), see pg. 25, second paragraph.
Geiger teaches TFF can be performed using a capsule, a cassette, a cassette holder, or a hollow fiber module as a filter device (e.g. the filter, required in claim 13, line 2), see pg. 24, third paragraph.
Geiger teaches it has been particularly found that by applying said method mRNA molecule hydrolysis products, abortive mRNA molecules (e.g. macromolecules, required in claim 7, line 3 and claim 8), proteins (e.g. proteins, required in claim 7, line 3 and claim 8) and salts (e.g. desalting, required in claim 1, last line of the claim and claim 16) are efficiently removed, see pg. 4, second paragraph.
Geiger teaches RNA molecules are preferably purified by applying an additional purification step for example anion exchange chromatography and/or reverse-phase chromatography, see pg. 3, second paragraph.
With respect to the sequence of purification steps within claims 1, 8, 16, 23-24 and 35-37, it would have been well within the scope of the artisan through routine experimentation and optimization to separate the anti-reverse cap analogues taught by the combination of Su and Geiger and therefore to have designed and arrived at the claimed invention as required in claims 1, 8, 16, 23-24 and 35-37 as the combination of Su and Geiger already teach filtration, ion exchange chromatography and reverse-phase chromatography to remove one or more contaminants from a reaction liquid of in-vitro transcribed mRNA and mRNA caps, including macromolecules, proteins and salts as discussed above. See MPEP 2144.04, section IV, C. “selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results”.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have incorporated limitations (a)-(c) as taught by Geiger into the recovery method as taught by Su above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to purify the crude anti-reverse cap analogues as taught by Su above. One of ordinary skill in the art would have had a reasonable expectation of success of incorporating limitations (a)-(c) as taught by Geiger into the recovery method of Su as discussed above, as both Su and Geiger are drawn to separating and purifying mRNA molecules having been transcribed in vitro, having been co-transcriptionally capped, and wherein the reaction liquid of said in vitro transcription comprises 5’ caps and 5’ cap analogs as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
(II) Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Su et al. (Published 19 March 2021, CN-112521437-A, IDS filed 04/09/2024, English Machine Translation, PTO-892) and Geiger et al. (Published 20 August 2020, WO-2020165158-A1, PTO-892) as applied to claims 1-3, 7-8, 13, 16, 21-25, 31, 35-37 and 49 above, and further in view of Bancel et al. (Published 28 January 2016, US-20160024547-A1, PTO-892).
Su and Geiger address claims 1-3, 7-8, 13, 16, 21-25, 31, 35-37 and 49 as written above. Although, Su and Geiger do not explicitly teach said mRNA nucleotide cap is Compound G, required in claim 4.
However, in the same field of endeavor of the in-vitro transcription process of mRNA, Bancel teaches the production of an RNA transcript, e.g., mRNA, in an in-vitro transcription reaction to generate the RNA transcript; where the RNA transcript is capped via enzymatic capping; resulting in the production of homogeneous RNA transcripts with high purity and potency; and wherein the RNA transcript is purified via chromatographic methods, see paragraph [0010].
Bancel teaches in Figure 3 an exemplary mRNA cap structure according to one embodiment depicted as,
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419
651
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, see figure 3.
Bancel teaches recombinant vaccinia virus capping enzyme and recombinant 2′-O-methyltransferase enzyme can create a canonical 5′-5′-triphosphate linkage between the 5′-terminal nucleotide of an mRNA and a guanine cap nucleotide wherein the cap guanine contains an N7 methylation and the 5′-terminal nucleotide of the mRNA contains a 2′-O-methyl. Such a structure is termed the Cap1 structure. This cap results in a higher translational-competency and cellular stability and a reduced activation of cellular pro-inflammatory cytokines, as compared, e.g., to other 5′ cap analog structures known in the art, see paragraph [0071].
The Examiner respectfully notes the teachings of Bancel within the previous paragraph corresponds to Figure 3 above.
Bancel teaches the polynucleotide includes n number of linked nucleosides having formula (Ib) depicted as,
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186
166
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, wherein U is O, see paragraph [0181]; “---” is a single bond, see paragraph [0182]; R1=R3’=R3”=R4 is H, see paragraph [0183]; R5 is hydroxy or optionally substituted alkoxy, see paragraph [0184]; Y1=Y2=Y3 is O, see paragraph [0185]; and Y4 is hydroxy, see paragraph [0186].
The Examiner respectfully notes the choices described above within formula (Ib) correspond to the RNA linked to the m7GTP within the exemplary cap structure of figure 3 shown above.
Bancel teaches “n”, which the Examiner respectfully notes corresponds to “n” as recited in the exemplary mRNA cap structure of Figure 3, is an integer from 1 to 100,000, see paragraph [0186]; and “B”, which the Examiner respectfully notes corresponds to “B” as recited in the exemplary mRNA cap structure of Figure 3, is a nucleobase, see paragraph [0188].
Bancel teaches B is a nucleobase selected from the group consisting of cytosine, guanine, adenine and uracil, see paragraph [0397].
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the invention’s effective filing date to have used the teachings of Bancel as a starting point and to have specifically chosen guanine as the nucleobase corresponding to the Cap1 position of the exemplary mRNA cap as depicted in Figure 3 above as one of ordinary skill in the art would have been motivated to make this specific selection in order to create a mRNA cap that results in a higher translational-competency and cellular stability and a reduced activation of cellular pro-inflammatory cytokines as taught by Bancel above.
Moreover, it would have been prima facie obvious to one of ordinary skill in the art at the invention’s effective filing date to have chosen from the restricted nucleobases of cytosine, guanine, adenine and uracil taught by Bancel above as the nucleobases for the additional nucleotides linked to the Cap1 structure, which is specifically chosen to be guanine as discussed above, within the mRNA cap of Figure 3 of Bancel, and thus arrive at the claimed Compound G as required in instant claim 4, as the Examiner respectfully notes the additional nucleobases attached to the Cap1 structure of Compound G recited within instant claim 4 are adenine and guanine respectively.
One of ordinary skill in the art would have been motivated to create a mRNA cap that results in a higher translational-competency and cellular stability and a reduced activation of cellular pro-inflammatory cytokines as taught by Bancel above.
One of ordinary skill in the art would have had a reasonable expectation of success as Bancel exemplifies the mRNA cap structure of Figure 3, teaches the required number of nucleotides within the mRNA cap; and the specific nucleobases that are recited within compound G of instant claim 4 as discussed above.
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have included the mRNA cap as taught by Bancel into the recovery method of mRNA cap analogues as taught by Su above as within the scope of the artisan as combining prior art elements according to known compositions and methods to yield predictable results. One of ordinary skill in the art would have been motivated to incorporate the anti-reverse cap analogues of Bancel in the in-vitro transcription process of mRNA of Su above in order to create mRNA products with higher translational-competency and cellular stability and a reduced activation of cellular pro-inflammatory cytokines as taught by Bancel; and therefore to have used the recovery method of anti-reverse cap analogues within the method of Su for the express purpose of recovering the mRNA caps of Bancel because of their properties within mRNA products as discussed above.
One of ordinary skill in the art would have had a reasonable expectation of success of incorporating the mRNA caps taught by Bancel into the method of Su; as both Su and Bancel are drawn to the in-vitro transcription process of mRNA using mRNA caps; and Su is drawn to recovering mRNA caps after the in-vitro transcription process of mRNA which include caps containing m7GTP as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
(III) Claims 14, 50-53 and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Su et al. (Published 19 March 2021, CN-112521437-A, IDS filed 04/09/2024, English Machine Translation, PTO-892) and Geiger et al. (Published 20 August 2020, WO-2020165158-A1, PTO-892) as applied to claims 1-3, 7-8, 13, 16, 21-25, 31, 35-37 and 49 above, and further in view of Gaeta (Published 22 May 2020, WO-2020102570-A1, PTO-892).
Su and Geiger address claims 1-3, 7-8, 13, 16, 21-25, 31, 35-37 and 49.
Geiger further exemplifies filter membranes used for mRNA molecule purification include unmodified polyethersulfone (PES), polyvinylidene fluoride (PVDF), cellulose acetate, ultra-high MW polyethylene (UPE), polyfluorotetraethylene (PTFE), polypropylene and combinations thereof (e.g. the type of filter, required in claim 51), see pg. 24, fourth paragraph.
Additionally, the Examiner respectfully reiterates that Geiger teaches when applying in step (Ia) a molecular-weight cut off (MWCO) in the range of 0.05 µm to 0.65 µm, the TFF can be referred to as microfiltration (e.g. the molecular-weight cut off, required in claim 52), see pg. 25, second paragraph.
Moreover, with respect to the sequence of purification steps within claim 50, the Examiner respectfully reiterates the position within the previous 103 rejections discussed above that it would have been well within the scope of the artisan through routine experimentation and optimization to separate the anti-reverse cap analogues taught by the combination of Su and Geiger and therefore to have designed and arrived at the claimed invention required in claim 50 as the combination of Su and Geiger already teach filtration, ion exchange chromatography and reverse-phase chromatography to remove one or more contaminants from a reaction liquid of in-vitro transcribed mRNA and mRNA caps, including macromolecules, proteins and salts as discussed above. See MPEP 2144.04, section IV, C. “selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results”.
Although, Su and Geiger do not teach adjusting the pH and concentration as required in claims 14, 50-53 and 59.
However, in the same field of endeavor of RNA purification, Gaeta teaches a ribonucleic acid (RNA) preservation composition, preferably in liquid form, where the composition can stabilize RNA in a biological sample and/or render the biological sample a viable source of RNA for purification and analysis, see pg. 15, paragraph [0082], lines 23-27.
Gaeta teaches the composition provides the advantageous properties of chemical stabilization of nucleic acids, particularly ribonucleic acid (RNA), the inhibition of nucleases, including ribonucleases, and microbial growth, see paragraph [0082], lines 27-30.
Gaeta teaches the composition can also have a pH of 4-7 and/or an acid q.s. to a pH of 4-7, see paragraph [0014], lines 22-23. Gaeta teaches an acid(s) can be added to the composition to adjust (i.e. decrease) the pH of the composition, and adjusting the pH of the composition can affect the stability of RNA and/or other (macromolecules) in the sample, see paragraph [00129], lines 31-33.
With respect to limitations (a) “adjusting the concentration and pH” required in claim 50, last line of the claim; and (b) the concentration is adjusted to the recited concentration range as required in claim 53; the Examiner reasonably interprets both limitations (a)-(b) are physical limitations well within the scope of the artisan in the process of purifying the reaction liquid containing the in-vitro transcribed mRNA and mRNA caps as taught by the combination of Su, Geiger and Gaeta; and since Su teaches concentrating the liquid containing the crude anti-reverse cap analogues; and Gaeta teaches a liquid ribonucleic acid (RNA) preservation composition with a pH of 4-7 having the advantageous property of chemical stabilization of nucleic acids, particularly ribonucleic acid (RNA), for use in RNA purification and analysis; and where it’s a known consideration in the prior art that adjusting the pH of the composition can affect the stability of RNA as taught by Gaeta; the Examiner reasonably interprets the physical limitations (a)-(b) are met by the combined teachings of Su, Geiger and Gaeta as discussed above.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have adjusted the pH between 4-7 as taught by Gaeta of the reaction liquid containing the anti-reverse cap analogues in the recovery method as taught by Su above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to have adjusted the pH between 4-7 of the reaction liquid of Su during the recovery process of Su because Gaeta teaches a ribonucleic acid (RNA) preservation composition, preferably in liquid form which provides the advantageous property of chemical stabilization of nucleic acids, particularly ribonucleic acid (RNA).
One of ordinary skill in the art would have had a reasonable expectation of success to have made the addition as discussed above; as Su teaches recovering anti-reverse cap analogues in the in-vitro transcription process of mRNA; and Gaeta teaches adjusting the pH of the composition can affect the stability of RNA and is drawn to compositions for ribonucleic acid (RNA) preservation preferably in liquid form where the composition can stabilize RNA in a sample and render the sample a viable source of RNA for purification and analysis as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
Conclusion
No claims are allowed in this action.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691