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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/26/2026 has been entered.
Claim Status
Claims 97-99 are amended. Claims 106-116 are new.
Claims 1, 4, 6, 8-9, 11-12, 20, 22, 91-116 are examined on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62319220, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The application fails to provide support for the claims under examination, since there is no disclosure regarding SEQ ID NO 8-18. Therefore, the effective filling date of claim 94, is deemed to be 04/06/2017, the filling date of the application 15480617.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites "an /d or" in lines 6-7
Appropriate correction is required.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4, 6, 8-9, 11-12, 20, 22 and 91-116 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4,-8, 11-13, 16-20, 22, and 25-30 of U.S. Patent No. 10,858,385 (cited as reference on IDS filed 10/22/2021) in view of Zale et al. (Biochemistry, 1986), Kawai et al (“Kawai”, JP2005160446A, cited as reference on IDS filed 10/22/2021. English translation is provided), Schulte et al. (“Schulte” WO 03/038117 A2, cited as reference on IDS filed 10/22/2021) and Kawasaki (“Kawasaki”, WO 91/05058).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to cell-free methods of producing ribonucleic acid (RNA).
Claim 1 of the ‘385 patent is drawn to the steps of “(a) incubating (i) cellular RNA, wherein the cellular RNA comprises ribosomal RNA, messenger RNA, and/or transfer RNA, and (ii) a ribonuclease to produce 5′ nucleoside monophosphates (NMPs); (b) eliminating the ribonuclease; and (c) incubating the 5′ NMPs with polyphosphate kinase (PPK), polyphosphate, deoxyribonucleic acid (DNA) template encoding a RNA of interest, and RNA polymerase to produce the RNA of interest.” Claim 1 of the ‘385 patent does not require elimination of the ribonuclease by heating the mixture. However, Zale et al. (Biotechnology and Bioengineering,1983) teaches thermal inactivation of ribonuclease in the temperature range from 50 to 95°C and at pH 1.25-8.0 strictly obeys first- order kinetics (e.g., paragraph 4th, page 2223). It would have been obvious to one of ordinary skills in the art to include the heating as the method to achieve the outcome of inactivation of the ribonuclease in the “385 patent. Accordingly, instant claims 1, 4 and 8 are not patentably distinct from claim 1 of the ‘385 patent.
Claim 2 of the ‘385 patent depends from claim 1 and limits the ribonuclease to Nuclease P1 or RNase R. Accordingly, instant claims 6 and 102 are not patentably distinct from claim 2 of the ‘385 patent.
Claim 11 of “385 patent is drawn to the steps of “(a) incubating (i) cellular RNA and (ii) a ribonuclease to produce 5' nucleoside monophosphates (NMPs); (b) eliminating the ribonuclease; and (c) NMP kinase, at least one NDP kinase, at least one polyphosphate kinase (PPK), polyphosphate, deoxyribonucleic acid (DNA) template encoding a RNA of interest, and RNA polymerase to produce the RNA of interest”. Claim 11 of the ‘385 patent does not require elimination of the ribonuclease by heating the mixture. However, Zale et al. (Biochemistry, 1986) teaches that ribonucleases can be irreversible eliminated by heat to 90 C (e.g., paragraph 1st, page 5435). It would have been obvious to one of ordinary skills in the art to include the heating for inactivation of the ribonuclease in the “385 patent, in order to provide a step for inactivation of the ribonuclease in the “385 patent. Accordingly, instant claims 1, 4, 8, 105-106, 109-110, 114 are not patentably distinct from claim 11 of the ‘385 patent.
Claim 16 of the ‘385 patent dependents of claim 11, and limits the NMP kinase to an AMP kinase, a CMP kinase, a UMP kinase, or a GMP kinase. Accordingly, instant claim 9, 107 and 108 are not patentably distinct from claims 16 of the ‘385 patent.
Claim 18 of the ‘385 patent dependents of claim 11, and limits the one NDP kinase from Aquifex aeolicus (SEQ ID NO: 16). Accordingly, instant claim 11 is not patentably distinct from claim 18 of the ‘385 patent.
Claim 19 of the ‘385 patent dependent of claim 11, and limits the PPK to a PPK1 family enzyme or a PPK2 family enzyme. Accordingly, instant claims 12 and 92 are not patentably distinct from claim 19 of the ‘385 patent.
Claim 17 of the ‘385 patent dependents of claim 16, and limits the NMP kinase is AMP kinase from Thermus thermophilus (SEQ ID NO: 12), CMP kinase from Thermus thermophilus (SEQ ID NO: 13), UMP kinase from Pyrococcus furiosus (SEQ ID NO: 14), and/or GMP kinase from Thermotoga maritima (SEQ ID NO: 15). Accordingly, instant claim 91 is not patentably distinct from claim 17 of the ‘385 patent.
Claim 20 of the ‘385 patent dependent of claim 19, and limits the one PPK to a Class III PPK2 enzyme from Deinococcus geothermalis (SEQ ID NO: 1). Accordingly, instant claims 93 and 94 are not patentably distinct from claim 20 of the ‘385 patent.
SEQ ID NO 1 of “385” has 100% identity with SEQ ID NO 10 of the instant claims (see alignment).
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Claim 21 of the ‘385 patent dependents of claim 11, and limits the polyphosphate from the group consisting of tetrapolyphosphates, pentapolyphosphates, and hexametaphosphates. Accordingly, instant claims 95-96 are not patentably distinct from claim 21 of the ‘385 patent.
Claim 22 of “385 patent that depends of claim 11, is drawn to the step of “(c) comprises an enzyme preparation or cell lysate obtained from cells that produce the PPK, the NMP kinase, the NDP kinase, the deoxyribonucleic acid (DNA) template, and/or the RNA polymerase. Accordingly, instant claims 110, 114 are not patentably distinct from claim 22 of the ‘385 patent.
“385” does not teach the T7 RNA polymerase, SP6 RNA polymerase, and T3 RNA polymerase, as required by the instant claim 20. “385” does not teach the energy source adenosine triphosphate (ATP) or an ATP regeneration system, as required by the instant claim 22. “385” does not teach RNA of interest is a single and double strand RNA, as required by the instant claims 98-99. “385” does not teach purifying the RNA of interest, as required by the instant claims 100-101. “385 does not teach the thermostable RNA polymerase and/or a thermostable kinase, as required by the instant claim 104. “385” does not teach manganese chloride (MnCl2) and/or magnesium sulfate (MgSO4), as required by the instant claims 97, 112 and 116. “385” does not teach RNA of interest is produced at a concentration of at least 1 g/L, as required by the instant claim 111. However, this is cured by Kawai, Schulte and Kawasaki.
Regarding claims 20, 97-99, 104, 112 and 116, Kawai teaches a method for efficiently synthesizing RNA, comprising adding dimethyl sulfoxide (DMSO) and/or betaine to an RNA polymerase reaction solution (e.g., paragraph 0006, item 1). Kawai teaches that RNA refers to (ribosomal RNA, mRNA, siRNA, shRNA, miRNA) (e.g., paragraph 0009) (it reads on single and double-stranded RNA). Kawai teaches the RNA polymerase is preferably any RNA polymerase selected from T7 RNA polymerase, SP6 RNA polymerase, and T3 RNA polymerase. Particularly preferred is T7 RNA polymerase, more particularly preferred is a thermostable T7 RNA polymerase (e.g., paragraph 0006, item 6). Kawai teaches that in order to increase the RNA synthesis rate, the Mg ion concentration in the reactant composition has been increased to the 12mM or higher and/or the NTP concentration has been increased to the 12mM or higher, and certain results such as an increase in yield have been obtained (e.g., paragraph 0017).
Regarding claim 22, Schulte teaches compositions and methods are provided for the enhanced in vitro synthesis of nucleic acid molecules. A system is provided for the in situ phosphorylation of nucleoside monophosphates (NMPs) into nucleoside triphosphates (NTPs). This phosphorylation of NMPs in the reaction mix is driven by ATP. Also present in the reaction mix is an energy generating system for generation of ATP from AMP and ADP. Depending upon the ATP regeneration system chosen, use of this NTP supply system can prevent a net increase in free phosphate as a result of NTP hydrolysis, and also permits the use of relatively inexpensive nucleoside monophosphates in place of the triphosphates (e.g., line 1, page 3). Schulte teaches In vitro synthesis as used herein refers to the cell-free synthesis of nucleic acids in a reaction mix comprising biological extracts and/or defined reagents (e.g., line 27, page 3). Schulte teaches that the concentrations of T7 RNA polymerase, DNA template, NTP and MgCl2 proved to be significantly correlated with the yield of tRNA(Trp) (e.g., line 1, page 2). Schulte teaches the production of mRNA from NMPs, which have a lower affinity for magnesium. This system allows effective mRNA synthesis at the low magnesium concentrations required for eukaryotic translation (e.g., line 29, page 4). Schulte teaches methods of the invention find particular use in coupled reactions of transcription and translation, for protein synthesis with eukaryotic cell extracts (e.g., line 25, page 4).
Regarding claims 100-101 and 111, Kawasaki teaches methods for synthesizing, screening, and selecting high numbers of novel genes and polypeptides. The methods generally comprise the steps of (a) constructing an in vitro expression unit comprising a 5' untranslated region containing an RNA polymerase binding sequence, a ribosome binding sequence, and a translation initiation signal, the expression unit being capable of producing mRNA ( (e.g., line 10, page 3). Kawasaki teaches transcription of novel genes. Approximately 5-10 μg of mRNA is expected. Generally, with T7 RNA polymerase, nearly 10 times this level of RNA is synthesized: however, the conditions for the capping reaction limit mRNA production in this case. The DNA is removed with DNase I, provided in the kit. The capped mRNA is phenol/chloroform extracted and precipitated with ethanol. The RNA is resuspended in 10 μl of TE and stored at 0-4C (e.g., line 23, page 33, example 2) (It reads on 1g/L of mRNA).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teachings of “385” - A method for producing ribonucleic acid (RNA) comprising: (a) incubating (i) cellular RNA, wherein the cellular RNA comprises ribosomal RNA, messenger RNA, and/or transfer RNA, and (ii) a ribonuclease to produce 5' nucleoside monophosphates (NMPs); (b) eliminating the ribonuclease by heating; and c) incubating the 5' NMPs with polyphosphate kinase (PPK), polyphosphate, deoxyribonucleic acid (DNA) template encoding a RNA of interest, and RNA polymerase to produce the RNA of interest; with the teachings of Kawai –a method for efficiently synthesizing RNA (single and double-stranded RNA), where the RNA polymerase is selected from T7 RNA polymerase, SP6 RNA polymerase, and T3 RNA polymerase or a thermostable T7 RNA polymerase; with the teachings of Schulte - methods for the enhanced in vitro synthesis of nucleic acid molecules, an ATP mediated ATP regeneration system; and the teachings of Kawasaki – a method for constructing an in vitro expression unit containing an RNA polymerase capable of producing mRNA with a yield of 1 g/L after purification; for someone skilled in the art would have been obvious to use these teachings to achieve the predictable result of obtaining a method for producing ribonucleic acid (RNA) comprising: (a) incubating (i) cellular RNA, wherein the cellular RNA comprises ribosomal RNA, messenger RNA, and/or transfer RNA, and (ii) a ribonuclease to produce 5' nucleoside monophosphates (NMPs); (b) eliminating the ribonuclease by heating; and c) incubating the 5' NMPs with polyphosphate kinase (PPK), polyphosphate, RNA polymerase and deoxyribonucleic acid (DNA) template encoding a RNA of interest to yield the RNA of interest at 1 g/L.
One of ordinary skill in the art before the effective filing date of the invention would have been motivated to do so in order to develop a cell-free method for synthesizing RNA.
Claims 1, 4, 6, 8-9, 11-12, 20, 22, 91-116 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 10,954,541 (“541”, cited as reference on IDS filed 10/22/2021) in view of Kawai et al (“Kawai”, JP2005160446A, cited as reference on IDS filed 10/22/2021. English translation is provided) and Kawasaki (“Kawasaki”, WO 91/05058).
This rejection is made to address the response to the reply filed 05/28/2026.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to cell-free methods of producing ribonucleic acid (RNA).
Claim 1 of the ‘541 patent is drawn to the steps of “(a) incubating a cell lysate mixture that comprises cellular RNA, an enzyme that depolymerizes RNA, a thermostable kinase, and a thermostable RNA polymerase, and producing a cell lysate mixture that comprises nucleoside monophosphates; (b) heating the cell lysate mixture produced in step (a) to a temperature that inactivates or partially inactivates the enzymes that depolymerize RNA and enzymes that degrade nucleotides and/or nucleic acids, without completely inactivating the thermostable kinases and thermostable RNA polymerases, and producing a cell lysate mixture that comprises nucleoside monophosphates, a thermostable kinase, and a RNA polymerase; and ( c) incubating the cell lysate mixture produced in (b) in the presence of an energy source and a deoxyribonucleic acid (DNA) template encoding a RNA of interest, producing nucleoside triphosphates, and producing a cell lysate mixture that comprises the RNA of interest”.
Claim 1 of the ‘541 patent is narrower in scope than instant claims 1, 103 and 104. Thus, claim 1 of the ‘541 patent anticipates instant claims 1, 103 and 104.
Claim 4 of the ‘541 patent depends from claim 3 (depends of claim 1) and limits the ribonuclease to Nuclease P1 or RNase R. Accordingly, claim 4 of the “541 patent anticipates instant claims 6, 102 and 105.
Claim 5 of the ‘541 patent depends from claim 1 and limits the thermostable kinase is selected from the group consisting of
thermostable nucleoside monophosphate kinases, thermostable
nucleoside diphosphate kinases, and thermostable polyphosphate kinases. Accordingly, claim 5 of the “541 patent anticipates instant claims 8 and 106.
Claim 6 of the ‘541 patent depends from claim 5 (depends of claim 1) and limits the thermostable nucleoside monophosphate kinases are selected from the group consisting of thermostable uridylate kinases, thermostable cytidylate kinases, thermostable guanylate kinases, and thermostable adenylate kinases. Accordingly, claim 6 of the “541 patent anticipates instant claims 9, 91 and 107-108.
Claim 8 of the ‘541 patent depends from claim 5 and limits the thermostable nucleoside diphosphate kinases are selected from the group
consisting of thermostable Aquifex aeolicus nucleoside diphosphate kinases encoded by a ndk gene (AaNdk). Accordingly, claim 8 of the “541 patent anticipates instant claim 11.
Claim 9 of the ‘541 patent depends from claim 5 and limits the thermostable polyphosphate kinases are selected from the group consisting of thermostable polyphosphate kinase 1 (PPKl) enzymes and thermostable polyphosphate kinase 2 (PPK2) enzymes. Accordingly, claim 9 of the “541 patent anticipates instant claims 12 and 92.
Claim 18 of the ‘541 patent depends from claim 17 (depends from claim 1) and limits the thermostable DNA-dependent RNA polymerase is selected from the group consisting of thermostable T7 RNA polymerases,
thermostable SP6 RNA polymerases, and thermostable T3 RNA polymerases. Accordingly, claim 18 of the “541 patent anticipates instant claim 20.
Claim 19 of the ‘541 patent depends from claim 1 and limits the energy source is adenosine triphosphate (ATP) or polyphosphate. Accordingly, claim 19 of the “541 patent anticipates instant claim 22.
Claim 10 of the ‘541 patent depends from claim 9 and limits the thermostable PPKl enzymes are thermostable Thermosynechococcus
elongatus PPKl enzymes. Accordingly, claim 10 of the “541 patent anticipates instant claim 92.
Claim 12 of the ‘541 patent depends from claim 11 and limits the thermostable Class III PPK2 enzymes are selected from the group consisting of Meiothermus ruber, Meiothermus silvanus, Deinacoccus
geothermalis, Thermosynechococcus elongatus, Anaerolinea thermophila, Caldilinea aerophila, Chlorobaculum tepidum, Oceanithermus profundus, Roseiflexus castenholzii, Roseiflexus sp., and Truepera radiovictrix PPK2 enzymes. Accordingly, claim 12 of the “541 patent anticipates instant claim 93.
Claim 15 of the ‘541 patent depends from claim 11 and limits the thermostable Class III PPK2 enzymes comprise an amino acid sequence
that is at least 70% identical to the amino acid sequence identified by any one of SEQ ID NO: 8-18. Accordingly, claim 15 of the “541 patent anticipates instant claim 94.
Claim 19 of the ‘541 patent depends from claim 1 and limits the energy source is adenosine triphosphate (ATP) or polyphosphate. Accordingly, claim 19 of the “541 patent anticipates instant claim 95.
Claim 21 of the ‘541 patent depends from claim 1 and limits the polyphosphate is hexametaphosphate. Accordingly, claim 21 of the “541 patent anticipates instant claim 96.
Claim 28 of the ‘541 patent depends from claim 1 and limits the RNA of interest is a double-stranded RNA. Accordingly, claim 28 of the “541 patent anticipates instant claim 98.
Claim 27 of the ‘541 patent depends from claim 1 and limits the RNA of interest is a single-stranded RNA. Accordingly, claim 27 of the “541 patent anticipates instant claim 99.
Claim 29 of the ‘541 patent depends from claim 1 and limits the temperature of step (b) is 50° C.-80° C. Accordingly, claim 29 of the “541 patent anticipates instant claim 97.
Claim 20 of the ‘541 patent depends from claim 1 and limits the nucleotide triphosphates are produced using polyphosphate, nucleoside
monophosphates, and polyphosphate kinase. Accordingly, claim 20 of the “541 patent anticipates instant claim 109.
Claim 26 of the ‘541 patent depends from claim 1 and limits the DNA template encoding the RNA of interest is added to the cell lysate mixture of step (c). Accordingly, claim 26 of the “541 patent anticipates instant claim 110.
Claim 24 of the ‘541 patent depends from claim 1 and limits at least one purified enzyme or fusion enzyme is added to the cell lysate mixture
of step (c), and wherein the at least one purified enzyme or fusion enzyme is selected from the group consisting of enzymes that depolymerize RNA, thermostable kinases, and thermostable polymerases RNA, under conditions that result in production of nucleoside triphosphates and polymerization of the nucleoside triphosphates to produce a cell lysate
mixture that comprises the RNA of interest. Accordingly, claim 24 of the “541 patent anticipates instant claim 114.
“541 does not teach manganese chloride (MnCl2) and/or magnesium sulfate (MgSO4), as required by the instant claims 112 and 116. “541” does not teach purifying the RNA of interest, as required by the instant claims 100-101. “541” does not teach RNA of interest is produced at a concentration of at least 1 g/L, as required by the instant claim 111. However, this is cured by Kawai and Kawasaki.
Regarding claims 112 and 116, Kawai teaches a method for efficiently synthesizing RNA, comprising adding dimethyl sulfoxide (DMSO) and/or betaine to an RNA polymerase reaction solution (e.g., paragraph 0006, item 1). Kawai teaches that in order to increase the RNA synthesis rate, the Mg ion concentration in the reactant composition has been increased to the 12mM or higher and/or the NTP concentration has been increased to the 12mM or higher, and certain results such as an increase in yield have been obtained (e.g., paragraph 0017).
Regarding claims 100-101 and 111, Kawasaki teaches methods for synthesizing, screening, and selecting high numbers of novel genes and polypeptides. The methods generally comprise the steps of (a) constructing an in vitro expression unit comprising a 5' untranslated region containing an RNA polymerase binding sequence, a ribosome binding sequence, and a translation initiation signal, the expression unit being capable of producing mRNA ( (e.g., line 10, page 3). Kawasaki teaches transcription of novel genes. Approximately 5-10 μg of mRNA is expected. Generally, with T7 RNA polymerase, nearly 10 times this level of RNA is synthesized: however, the conditions for the capping reaction limit mRNA production in this case. The DNA is removed with DNase I, provided in the kit. The capped mRNA is phenol/chloroform extracted and precipitated with ethanol. The RNA is resuspended in 10 μl of TE and stored at 0-4C (e.g., line 23, page 33, example 2) (It reads on 1g/L of mRNA).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teachings of “541” -cell-free method of biosynthesizing ribonucleic acid (RNA) of interest, the method comprising:
(a) incubating a cell lysate mixture that comprises cellular RNA, an enzyme that depolymerizes RNA, a thermostable kinase, and a thermostable RNA polymerase, and producing a cell lysate mixture that comprises nucleoside
monophosphates; (b) heating the cell lysate mixture produced in step (a) to
a temperature that inactivates or partially inactivates the enzymes that depolymerize RNA and enzymes that degrade nucleotides and/or nucleic acids, without completely inactivating the thermostable kinases and thermostable RNA polymerases, and producing a cell lysate mixture that comprises nucleoside monophosphates, a thermostable kinase, and a RNA polymerase; and (c) incubating the cell lysate mixture produced in (b) in
the presence of an energy source and a deoxyribonucleic acid (DNA) template encoding a RNA of interest, producing nucleoside triphosphates, and producing a cell lysate mixture that comprises the RNA of interest; with the teachings of Kawai –a method for efficiently synthesizing RNA, where the RNA polymerase is selected from T7 RNA polymerase, SP6 RNA polymerase, and T3 RNA polymerase or a thermostable T7 RNA polymerase; and the teachings of Kawasaki – a method for constructing an in vitro expression unit containing an RNA polymerase capable of producing mRNA with a yield of 1 g/L after purification; for someone skilled in the art would have been obvious to use these teachings to achieve the predictable result of obtaining a method for producing ribonucleic acid (RNA) comprising: (a) incubating the cell lysate that comprises the cellular RNA with a ribonuclease to produce 5' nucleoside monophosphates (NMPs); (b) heating the cell lysate to inactivate the ribonuclease; and c) incubating the 5' NMPs with polyphosphate kinase (PPK), polyphosphate, RNA polymerase, deoxyribonucleic acid (DNA) template encoding a RNA of interest to yield the RNA of interest at 1 g/L.
One of ordinary skill in the art before the effective filing date of the invention would have been motivated to do so in order to develop a cell-free method for synthesizing RNA.
Response to Arguments
The arguments are not found persuasive for the reasons given in the advisory action mailed 5/28/2026.
Conclusion
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/JULIO WASHINGTON GOMEZ RODRIGUEZ/ Examiner, Art Unit 1637
/Jennifer Dunston/ Supervisory Patent Examiner, Art Unit 1637
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