DETAILED ACTION
CONTINUED EXAMINATION UNDER 37 CFR 1.114 AFTER FINAL REJECTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 of RCE and amendment filed on March 18, 2026 have been entered. The claims pending in this application are claims 1, 4, 9, 10, 14, 18-20, 25, 28-31, 34, 35, and 53. Claims 1, 4, 9, 10, 14, 18-20, 25, 28-31, 34, 35, and 53 will be examined.
Drawings
Some words or numbers in Figure 1, 15A and 15 B cannot be recognized. Applicant is required to submit new Figure 1, 15A and 15 B in response to this office action. No new matter may be introduced in the required drawing. 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).
Specification
The disclosure is objected to because of the following informality: since case 16/196,664 now is US Patent No. 11,059,841, applicant is required to update this information in paragraph [0001] of the specification.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: (1) “1 gram per batch or greater” in the preamble should be “1 gram or more than 1 gram per batch”; (2) “precipitated mRNA” in step (b) should be “the precipitated mRNA”; and (3) “the membrane” in step (c) should be “a membrane of the membrane filtration”.
Claim 4 or 9 is objected to because of the following informality: “the step of” should be “said”.
Claim 10 is objected to because of the following informality: “polyethersulfone (mPES) (not modified), polyethersulfone (mPES) hollow fiber membrane, polyvinylidene fluoride (PVDF), cellulose acetate, nitrocellulose, MCE (mixed cellulose esters), ultra-high MW polyethylene (UPE), polyfluorotetraethylene (PTFE), nylon, and combination thereof” should be “polyethersulfone (mPES) membrane, polyethersulfone (mPES) hollow fiber membrane, polyvinylidene fluoride (PVDF) membrane, cellulose acetate membrane, nitrocellulose membrane, membrane made by mixed cellulose esters (MCE), ultra-high MW polyethylene (UPE) membrane, polyfluorotetraethylene (PTFE) membrane, nylon membrane, and combination thereof”.
Claim 28 is objected to because of the following informality: “a scale of or greater than 10 gram, 100 gram, 1 kg, 10 kg, or 100 kg per batch” should be “a scale of 10 gram, 100 gram, 1 kg, 10 kg, or 100 kg or more than 10 gram, 100 gram, 1 kg, 10 kg, or 100 kg per batch”.
Claim 29 or 30 is objected to because of the following informality: “tail” should be “a tail”.
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, 9, 10, 14, 18-20, 25, 28-31, 34, 35, and 53 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.
Claim 1 is rejected as vague and indefinite in view of the preamble. Since claim 1 does not indicate the amount of a biological sample which is used for purifying mRNA in a batch, it is unclear why the method recited in claim 1 can be used for purifying mRNA at a scale of 1 gram or more than 1 gram per batch. Please clarify.
Claim 20 recites the limitation “the purified mRNA solution” in the claim. There is insufficient antecedent basis for this limitation in the claim because there is no phrase “a purified mRNA solution” in claims 1, 18, and 19. Furthermore, since claim 1 does not indicate that a elution buffer comprises enzyme reagents used in in vitro synthesis, it is unclear why the purified mRNA solution can contain enzyme reagents used in in vitro synthesis. Please clarify.
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.
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, 9, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Aviv et al., (Proc. Nat. Acad. Sci., 69, 1408-1412, 1972) in view of Mitsuhashi (US 2004/0072193 A1, published on April 15, 2004).
Regarding claims 1 and 9, Aviv et al., teach a method of purifying messenger RNA (mRNA), comprising (a) precipitating mRNA from an impure preparation (ie., precipitating crude polysomal RNA comprising mRNA); (b) subjecting the impure preparation comprising the precipitated mRNA to a purification process, wherein the purification process is direct flow filtration; (c) capturing the precipitated mRNA on a column (ie., oligo(dT)-cellulose column)
(d) washing the captured precipitated mRNA; and (e) eluting the captured precipitated mRNA from the column by re-solubilizing the mRNA as recited in claim 1 wherein said precipitating mRNA further comprises a step of treating the impure preparation with absolute ethanol as recited in claim 9 (see pages 1408 and 1409).
Aviv et al., do not disclose purifying mRNA at a scale of 1 gram or more than 1 gram per batch by subjecting the impure preparation comprising precipitated mRNA to a purification process involving membrane filtration wherein the purification process involving membrane filtration is direct flow filtration, capturing the precipitated mRNA on the membrane, and eluting the captured precipitated mRNA from the membrane by re-solubilizing the mRNA as recited in steps (b), (c), and (e) of claim 1 wherein the mRNA is purified at a scale of 10 gram, 100 gram, 1 kg, 10 kg, or 100 kg or more than 10 gram, 100 gram, 1 kg, 10 kg, or 100 kg per batch as recited in claim 28.
Mitsuhashi teaches that mRNA from nucleoplasm is purified using an oligo-(dT) membrane, column, or bead (see paragraph [0042]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods as recited in claims 1 and 28 by purifying mRNA at a scale of 1 gram or more than 1 gram per batch comprising subjecting the impure preparation comprising precipitated mRNA to a purification process involving membrane filtration, capturing the precipitated mRNA on the membrane, and eluting the captured precipitated mRNA from the membrane by re-solubilizing the mRNA wherein the purification process involving membrane filtration is direct flow filtration and the mRNA is purified at a scale of 10 gram, 100 gram, 1 kg, 10 kg, or 100 kg or more than 10 gram, 100 gram, 1 kg, 10 kg, or 100 kg per batch in view of the prior arts of Aviv et al., and Mitsuhashi. One having ordinary skill in the art would have been motivated to do so because Mitsuhashi teaches that mRNA from nucleoplasm is purified using an oligo-(dT) membrane, column, or bead (see paragraph [0042]) and the simple substitution of one kind of mRNA purification material (ie., the oligo-(dT) cellulose column taught by Aviv et al.,) from another kind of mRNA purification material (ie., the oligo-(dT) membrane taught by Mitsuhashi) during the process of performing the methods recited in claims 1 and 28, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made since the mRNA purification material taught by Aviv et al., and the mRNA purification material taught by Mitsuhashi are used for the same purpose (ie., purifying mRNA) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 1 and 28 by purifying mRNA from a biological sample by optimizing the amount of the biological sample and substituting the mRNA purification material taught by Aviv et al., with the mRNA purification material taught by Mitsuhashi in view of the prior arts of Aviv et al., and Mitsuhashi such that the mRNA is purified at a scale of 10 gram, 100 gram, 1 kg, 10 kg, or 100 kg or more than 10 gram, 100 gram, 1 kg, 10 kg, or 100 kg per batch.
Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09.
Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955).
More particularly, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Where the general conditions of a claim are disclosed in the prior art, it is not inventive, in the absence of an unexpected result, to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Aviv et al., in view of Mitsuhashi as applied to claims 1, 9, and 28 above, and further in view of Thivolet (US 2002/0132772 A1, published on September 19, 2002).
The teachings of Aviv et al., and Mitsuhashi have been summarized previously, supra.
Aviv et al., and Mitsuhashi do not disclose that the step of precipitating mRNA involves treating the impure preparation with a solution comprising a reagent selected from the group consisting of lithium chloride, potassium chloride, guanidinium chloride, guanidinium thiocyanate, guanidinium isothiocyanate, ammonium acetate and combinations thereof as recited in claim 4 wherein the reagent is guanidinium thiocyanate as recited in claim 5.
Thivolet teaches to precipitate total RNA using 4 M guanidinium thiocyanate (see paragraph ([0027]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods as recited in claims 4 and 5 by precipitating mRNA comprising treating the impure preparation with a solution comprising a reagent selected from the group consisting of lithium chloride, potassium chloride, guanidinium chloride, guanidinium thiocyanate, guanidinium isothiocyanate, ammonium acetate and combinations thereof wherein the reagent is guanidinium thiocyanate in view of the prior arts of Aviv et al., Mitsuhashi, and Thivolet. One having ordinary skill in the art would have been motivated to do so because Thivolet has successfully precipitated total RNA using 4 M guanidinium thiocyanate (see paragraph [0027]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 4 and 5 by precipitating mRNA comprising treating the impure preparation with a solution comprising guanidinium thiocyanate in view of the prior arts of Aviv et al., Mitsuhashi, and Thivolet in order to enhance the precipitation of mRNA from the polysomal RNA taught by Aviv et al..
Claims 10 are rejected under 35 U.S.C. 103 as being unpatentable over Aviv et al., in view of Mitsuhashi as applied to claims 1, 9, and 28 above, and further in view of Zhang et al., (US 2004/0137484 A1, published on July 15, 2004).
The teachings of Aviv et al., and Mitsuhashi have been summarized previously, supra.
Aviv et al., and Mitsuhashi do not disclose that the membrane is selected from the group consisting of polyethersulfone (mPES) membrane, polyethersulfone (mPES) hollow fiber membrane, polyvinylidene fluoride (PVDF) membrane, cellulose acetate membrane, nitrocellulose membrane, membrane of mixed cellulose esters (MCE), ultra-high MW polyethylene (UPE) membrane, polyfluorotetraethylene (PTFE) membrane, nylon membrane, and combination thereof as recited in claim 10.
Zhang et al., teach that RNA is isolated using a nitrocellulose membrane comprising oligo(dT) Capture/Amp-probe-1 probes (see paragraph [0203]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the method as recited in claim 10 by purifying mRNA using a membrane comprising oligo(dT) probes wherein the membrane is a nitrocellulose membrane in view of the prior arts of Aviv et al., Mitsuhashi, and Zhang et al.. One having ordinary skill in the art would have been motivated to do so because Zhang et al., have successfully isolated RNA using a nitrocellulose membrane comprising oligo(dT) Capture/Amp-probe-1 probes (see paragraph [0203]) and the simple substitution of one kind of mRNA purification material (ie., the oligo-(dT) membrane taught by Mitsuhashi) from another kind of mRNA purification material (ie., the nitrocellulose membrane comprising oligo(dT) Capture/Amp-probe-1 probes taught by Zhang et al.,) during the process of performing the method recited in claim 10, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made since the mRNA purification material taught by Mitsuhashi and the mRNA purification material taught by Zhang et al., are used for the same purpose (ie., purifying mRNA) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the method recited in claim 10 by purifying mRNA using a nitrocellulose membrane comprising oligo(dT) Capture/Amp-probe-1 probes in view of the prior arts of Aviv et al., Mitsuhashi, and Zhang et al..
Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09.
Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955).
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Aviv et al., in view of Mitsuhashi as applied to claims 1, 9, and 28 above, and further in view of Ongena et al., (US 2008/0102493 A1, published on May 1, 2008).
The teachings of Aviv et al., and Mitsuhashi have been summarized previously, supra.
Aviv et al., and Mitsuhashi do not disclose that the eluting step comprises re-solubilizing the captured precipitated mRNA with RNAse-free water as recited in claim 14.
Ongena et al., teach that a final product such as RNA on a membranes is eluted with any suitable elution buffer, e.g. water, Tris-EDTA buffer (TE) and a suitable buffer for eluting the RNA product may include an RNase free buffer such as RNase free water (see paragraphs [0026] to [0031]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the method as recited in claim 14 by re-solubilizing the captured precipitated mRNA with RNAse-free water in view of the prior arts of Aviv et al., Mitsuhashi, and Ongena et al.. One having ordinary skill in the art would have been motivated to do so because Ongena et al., teach that a final product such as RNA on a membranes is eluted with any suitable elution buffer, e.g. water, Tris-EDTA buffer (TE) and a suitable buffer for eluting the RNA product may include an RNase free buffer such as RNase
free water (see paragraphs [0026] to [0031]) and the simple substitution of one kind of elution buffer (ie., the elution buffer such as 0.01 M Tris-HCl taught by Aviv et al.,) from another kind of elution buffer (ie., the elution buffer such as RNase free water taught by Ongena et al.,) during the process of performing step (e) of claim 1, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made since the elution buffer taught by Aviv et al., and the elution buffer taught by Ongena et al., are used for the same purpose (ie., eluting mRNA) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the method recited in claim 14 by re-solubilizing the captured precipitated mRNA with RNAse-free water in view of the prior arts of Aviv et al., Mitsuhashi, and Ongena et al., in view of the prior arts of Aviv et al., Mitsuhashi, and Ongena et al., in order to reduce or prevent degradation of the captured precipitated mRNA.
Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09.
Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955).
Claims 18, 30, 31, and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Aviv et al., in view of Mitsuhashi as applied to claims 1, 9, and 28 above, and further in view of Gallie (Genes & Development, 5, 2108-2116, 1991).
The teachings of Aviv et al., and Mitsuhashi have been summarized previously, supra.
Aviv et al., and Mitsuhashi do not disclose that the mRNA is in vitro synthesized and the impure preparation comprises an in vitro mRNA synthesis reaction mixture as recited in claim 18, the mRNA is purified after a cap and a tail are added to the mRNA (ie., capped poly (A)+ mRNA) as recited in claim 30, the mRNA is purified after a cap is added as recited in claim 31, and synthesizing mRNA in vitro and purifying the in vitro synthesized mRNA using a method according to claim 1 as recited in claim 53.
Gallie teaches in vitro synthesizing mRNA containing a cap and a poly (a) tail (see abstract and pages 2108 and 2109).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods as recited in claims 18, 30, 31, and 53 by synthesizing mRNA in vitro and purifying the in vitro synthesized mRNA using the method of claim 1 wherein the impure preparation comprises an in vitro mRNA synthesis reaction mixture and the mRNA is purified after a cap and tail are added to the mRNA in view of the prior arts of Aviv et al., Mitsuhashi, and Gallie. One having ordinary skill in the art would have been motivated to do so because Gallie teaches in vitro synthesizing mRNA containing a cap and a poly (a) tail (see abstract and pages 2108 and 2109) and the simple substitution of one kind of mRNA (ie., the polysomal RNA comprising mRNA taught by Aviv et al.,) from another kind of mRNA (ie., the in vitro synthesizing mRNA containing a cap and a poly (a) tail taught by Gallie) during the process of performing methods of claims 18 and 53, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made since the mRNA taught by Aviv et al., and the mRNA taught by Gallie are used for the same purpose (ie., mRNA purification) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 18, 30, 31, and 53 by synthesizing mRNA in vitro and purifying the in vitro synthesized mRNA taught by Gallie using the method according to claim 1 such that the impure preparation comprising an in vitro mRNA synthesis reaction mixture and the mRNA is purified after a cap and tail are added to the mRNA in view of the prior arts of Aviv et al., Mitsuhashi, and Gallie.
Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09.
Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955).
Claims 19, 20, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Aviv et al., in view of Mitsuhashi and Gallie as applied to claims 1, 9, 18, 28, 30, 31, and 53 above, and further in view of Goldman et al., (Science, 324, 927 and 928, 2009).
The teachings of Aviv et al., Mitsuhashi, and Gallie have been summarized previously, supra.
Aviv et al., Mitsuhashi, and Gallie do not disclose that the impure preparation comprises prematurely aborted RNA sequences and/or enzyme reagents used in in vitro synthesis as recited in claim 19, the purified mRNA solution contains less than 1% of prematurely aborted RNA sequences as recited in claim 20, and the prematurely aborted RNA sequences comprise less than 15 bases as recited in claim 25.
Goldman et al., teach that during transcription initiation in vitro, prokaryotic and eukaryotic RNA polymerase (RNAP) can engage in abortive initiation-the synthesis and release of short (2 to 15 nucleotides) RNA transcripts-before productive initiation (see abstract).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods as recited in claims 19, 20, and 25 wherein the impure preparation comprises prematurely aborted RNA sequences and/or enzyme reagents used in in vitro synthesis, the purified mRNA solution contains less than 1% of prematurely aborted RNA sequences, and the prematurely aborted RNA sequences comprise less than 15 bases in view of the prior arts of Aviv et al., Mitsuhashi, and Goldman et al.. One having ordinary skill in the art would have been motivated to do so because Goldman et al., teach that during transcription initiation in vitro, prokaryotic and eukaryotic RNA polymerase (RNAP) can engage in abortive initiation-the synthesis and release of short (2 to 15 nucleotides) RNA transcripts-before productive initiation (see abstract) and Mitsuhashi teaches that mRNA from nucleoplasm is purified using an oligo-(dT) membrane (see paragraph [0042]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 19, 20, and 25 using in vitro synthesizing mRNA containing a cap and a poly (a) tail taught by Gallie by substituting the polysomal RNA comprising mRNA taught by Aviv et al., from the in vitro synthesizing mRNA containing a cap and a poly (a) tail taught by Gallie in view of the prior arts of Aviv et al., Mitsuhashi, and Goldman et al., such that the impure preparation comprises prematurely aborted RNA sequences and/or enzyme reagents used in in vitro synthesis, the prematurely aborted RNA sequences comprise less than 15 bases and the purified mRNA solution contains less than 1% of prematurely aborted RNA sequences based on removing the prematurely aborted RNA sequences using the oligo-(dT) membrane taught by Mitsuhashi.
Claim 29 are rejected under 35 U.S.C. 103 as being unpatentable over Aviv et al., in view of Mitsuhashi and Gallie as applied to claims 1, 9, 18, 28, 30, 31, and 53 above, and further in view of Balaban et al.,(US 2001/0018642 A1, published on August 30, 2001) and ISSA et al., (US 2016/0024141 A1, priority date: March 15, 2013).
The teachings of Aviv et al., Mitsuhashi, and Gallie have been summarized previously, supra.
Aviv et al., Mitsuhashi, and Gallie do not disclose that the mRNA is purified before a cap and tail are added to the mRNA as recited in claim 29.
Balaban et al., teach to increase concentration of mRNA by precipitating the mRNA (see paragraph [0024]).
ISSA et al., teach to purify mRNA using a membrane-based ion exchange sorbent comprising a positively-charged functional group (see abstract, paragraph [0055], and claim 1).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods as recited in claim 29 by precipitating the in vitro synthesized mRNA without a cap and a tail taught by Gallie and purifying the precipitated in vitro synthesized mRNA using a membrane-based ion exchange sorbent comprising a positively-charged functional group taught by ISSA et al., in view of the prior arts of Aviv et al., Mitsuhashi, Gallie, Balaban et al., and ISSA et al.. One having ordinary skill in the art would have been motivated to do so because Gallie teaches in vitro synthesizing mRNA without a cap and a poly (a) tail (see abstract and pages 2108 and 2109), Balaban et al., teach to increase concentration of mRNA by precipitating the mRNA (see paragraph [0024]),
ISSA et al., teach to purify mRNA using a membrane-based ion exchange sorbent comprising a positively-charged functional group (see abstract, paragraph [0055], and claim 1), the simple substitution of one kind of mRNA (ie., the polysomal RNA comprising mRNA taught by Aviv et al.,) from another kind of mRNA (ie., the in vitro synthesizing mRNA without a cap and a poly (a) tail taught by Gallie) and the simple substitution of one kind of purification material (ie., the oligo-(dT) membrane taught by Mitsuhashi) from another kind of purification material (ie., the membrane-based ion exchange sorbent comprising a positively-charged functional group taught by ISSA et al.,) during the process of performing method of claim 29, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made since the mRNA taught by Aviv et al., and the mRNA taught by Gallie and the purification material taught by Mitsuhashi) and the purification material taught by ISSA et al., are used for the same purpose (ie., mRNA purification) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the method recited in claim 29 by precipitating the in vitro synthesized mRNA without a cap and a tail taught by Gallie and purifying the precipitated in vitro synthesized mRNA using a membrane-based ion exchange sorbent comprising a positively-charged functional group taught by ISSA et al., in view of the prior arts of Aviv et al., Mitsuhashi, Gallie, Balaban et al., and ISSA et al., in order to increase a concentration of the mRNA from an impure preparation and purify mRNA without a cap and a tail.
Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09.
Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955).
Claims 34 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Aviv et al., in view of Mitsuhashi as applied to claims 1, 9, and 28 above, and further in view of Hoerr et al., (US 2008/0171711 A1, published on July 17, 2008).
The teachings of Aviv et al., and Mitsuhashi have been summarized previously, supra.
Aviv et al., and Mitsuhashi do not disclose that the mRNA comprises one or more modifications to enhance stability as recited in claim 34 and the one or more modifications comprises modified nucleotide as recited in claim 35.
Hoerr et al., teach that the modification of a mRNA such as increasing G/C content of a mRNA increases the stability of the mRNA (see paragraphs [0078] to [0080]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods as recited in claims 34 and 35 wherein the mRNA comprises one or more modifications to enhance stability and the one or more modifications comprises modified nucleotide in view of the prior arts of Aviv et al., Mitsuhashi, and Hoerr et al.. One having ordinary skill in the art would have been motivated to do so because Hoerr et al., teach that the modification of a mRNA such as increasing G/C content of a mRNA increases the stability of the mRNA (see paragraphs [0078] to [0080]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 34 and 35 by modifying the precipitated mRNA taught by Aviv et al., by increasing G/C content of the mRNA in view of the prior arts of Aviv et al., Mitsuhashi, and Hoerr et al., in order to enhance stability of the mRNA taught by Aviv et al..
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.
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Claims 1, 4, 5, 9, 10, 14, 18-20, 28, and 53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No.12,060,381 B2.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the examined claims in this instant application are either anticipated by, or would have been obvious over, the reference claims. See 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); and, In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). Although claims 1, 4, 5, 9, 10, 14, 18-20, 28, and 53 in this instant application are not identical to claims 1-33 of U.S. Patent No.12,060,381 B2, since the content of U.S. Patent No.12,060,381 B2 teaches that
“[I]n some embodiments, the mRNA is purified at a scale of or greater than 1 gram, 5 gram, 10 gram, 15 gram, 20 gram, 25 gram, 30 gram, 35 gram, 40 gram, 45 gram, 50 gram, 75 gram, 100 gram, 150 gram, 200 gram, 250 gram, 300 gram, 350 gram, 400 gram, 450 gram, 500 gram, 550 gram, 600 gram, 650 gram, 700 gram, 750 gram, 800 gram, 850 gram, 900 gram, 950 gram, 1 kg, 2.5 kg, 5 kg, 7.5 kg, 10 kg, 25 kg, 50 kg, 75 kg, or 100 kg per batch. As shown in the examples below, a batch comprising purified mRNA in the amount of 10 gram or greater (25 gram or more) can be achieved easily with the methods of the invention” (see column 3), claims 1-33 of U.S. Patent No.12,060,381 B2 are directed to the same subject matter and fall entirely within the scope of claims 1, 4, 5, 9, 10, 14, 18-20, 28, and 53 in this instant application. In other words, claims 1, 4, 5, 9, 10, 14, 18-20, 28, and 53 in this instant application are anticipated by claims 1-33 of U.S. Patent No.12,060,381 B2.
Response to Arguments
In page 5, second paragraph bridging to page 6, third paragraph of applicant’s remarks, applicant argues that “the ‘381 patent does not qualify as an obviousness-type double patenting reference. Therefore, Applicant respectfully requests reconsideration and withdrawal of this rejection”.
The arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection because applicant has not either filed a terminal disclaimer or indicated why U.S. Patent No.12,060,381 B2 cannot qualify as an obviousness-type double patenting reference.
Claims 1, 4, 5, 9, 10, 14, 18-20, 28, 30, 31, and 53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11,174,500 B2. Although the conflicting claims are not identical, they are not patentably distinct from each other because the examined claims in this instant application are either anticipated by, or would have been obvious over, the reference claims. See 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); and, In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). Although claims 1, 4, 5, 9, 10, 14, 18-20, 28, 30, 31, and 53 in this instant application are not identical to claims 1-25 of U.S. Patent No. 11,174,500 B2, since the content of U.S. Patent No. 11,174,500 B2 teaches that “[I]n some embodiments, a filter suitable for the invention is a membrane filter”, “[I]n some embodiments, a filter suitable for the invention is a depth filter. In some embodiments, the depth filter has a pore size or pore diameter that is substantially smaller than the precipitated mRNA and larger than the soluble mRNA or contaminants”, “[I]n some embodiments, a filter is made of an inert material. In some embodiments, an inert material suitable for the invention is polypropylene. In some embodiments, an inert material is modified polyether sulfone (mPES). In some embodiments, an inert material is polyether sulfone (PES). In some embodiments, an inert material is polyvinylidene fluoride (PVDF). In some embodiments, an inert material is cellulose. In some embodiments, an inert material is diatomaceous earth. In some embodiments, the inert material is polytetrafluoroethylene (PTFE). In some embodiments, the inert material is nitrocellulose. In some embodiments, the inert material is polyethylene. In some embodiments, the inert material is polyacrylonitrile. In some embodiments, the inert material is polycarbonate. In some embodiments, the inert material is nylon”, “[I]n some embodiments, the step of precipitating the mRNA comprises use of ethanol to precipitate the mRNA”, “[F]or example, a suitable method of precipitating mRNA from an impure preparation involves treating the impure preparation with a denaturing reagent such that the mRNA precipitates. Exemplary denaturing reagents suitable for the invention include, but are not limited to, lithium chloride, sodium chloride, potassium chloride, guanidinium chloride, guanidinium
thiocyanate, guanidinium isothiocyanate, ammonium acetate and combinations thereof. Suitable reagent may be provided in a solid form or in a solution”, “[I]n some embodiments, at least about 0.5 grams of RNA is purified. In some embodiments, at least about 1 gram of RNA is purified. In some embodiments, at least about 10 grams of RNA is purified. In some embodiments, at least about 50 grams of RNA is purified. In some embodiments, at least about 100 grams of RNA is purified. In some embodiments, at least about 1 kilograms of RNA is purified”, “[P]urification of the mRNA using the depth filter in each purification step involved three processes following precipitation of the mRNA: (1) loading of precipitated mRNA, (2) washing of the captured mRNA and (3) elution of mRNA from the membrane” and “[F]or each of the IVT Purification and the C/T Purification steps, recovery of mRNA from the depth filter was performed by recirculating RNase Free Water at 37° C., with frequent measurement of mRNA concentration of the filtrate pool to determine the point of saturation. Upon reaching the saturation level, the filtrate pool was replaced with a fresh RNase Free Water to elute the remaining mRNA. This step was performed until the concentration of mRNA in the filtrate pool was negligible. FIG. 18A and FIG. 18B show the recovery of mRNA (in terms of concentration) in the filtrate as a function of recirculation time” (see columns 2-5, 23, 24, 48 and 49) and prematurely aborted RNA sequences are removed by the method of claim 1 of U.S. Patent No. 11,174,500 B2, claims 1-25 of U.S. Patent No. 11,174,500 B2 are directed to the same subject matter and fall entirely within the scope of claims 1, 4, 5, 9, 10, 14, 18-20, 28, 30, 31, and 53 in this instant application. In other words, claims 1, 4, 5, 9, 10, 14, 18-20, 28, 30, 31, and 53 in this instant application are anticipated by claims 1-25 of U.S. Patent No. 11,174,500 B2.
Claims 1, 4, 5, 9, 10, 14, 18-20, 28, 30, 31, and 53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,084,702 B2. Although the conflicting claims are not identical, they are not patentably distinct from each other because the examined claims in this instant application are either anticipated by, or would have been obvious over, the reference claims. See 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); and, In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). Although claims 1, 4, 5, 9, 10, 14, 18-20, 28, 30, 31, and 53 in this instant application are not identical to claims 1-18 of U.S. Patent No. 12,084,702 B2, since the content of U.S. Patent No. 12,084,702 B2 teaches that “[I]n some embodiments, a filter suitable for the invention is a membrane filter”, “[I]n some embodiments, a filter suitable for the invention is a depth filter. In some embodiments, the depth filter has a pore size or pore diameter that is substantially smaller than the precipitated mRNA and larger than the soluble mRNA or contaminants”, “[I]n some embodiments, the step of precipitating the mRNA comprises use of ethanol to precipitate the mRNA”, “[F]or example, a suitable method of precipitating mRNA from an impure preparation involves treating the impure preparation with a denaturing reagent such that the mRNA precipitates. Exemplary denaturing reagents suitable for the invention include, but are not limited to, lithium chloride, sodium chloride, potassium chloride, guanidinium chloride, guanidinium
thiocyanate, guanidinium isothiocyanate, ammonium acetate and combinations thereof. Suitable reagent may be provided in a solid form or in a solution”, “[I]n some embodiments, at least about 0.5 grams of RNA is purified. In some embodiments, at least about 1 gram of RNA is purified. In some embodiments, at least about 10 grams of RNA is purified. In some embodiments, at least about 50 grams of RNA is purified. In some embodiments, at least about 100 grams of RNA is purified. In some embodiments, at least about 1 kilograms of RNA is purified”, “[P]urification of the mRNA using the depth filter in each purification step involved three processes following precipitation of the mRNA: (1) loading of precipitated mRNA, (2) washing of the captured mRNA and (3) elution of mRNA from the membrane” and “[F]or each of the IVT Purification and the C/T Purification steps, recovery of mRNA from the depth filter was performed by recirculating RNase Free Water at 37° C., with frequent measurement of mRNA concentration of the filtrate pool to determine the point of saturation. Upon reaching the saturation level, the filtrate pool was replaced with a fresh RNase Free Water to elute the remaining mRNA. This step was performed until the concentration of mRNA in the filtrate pool was negligible. FIG. 18A and FIG. 18B show the recovery of mRNA (in terms of concentration) in the filtrate as a function of recirculation time” (see columns 2-5, 23, 24, 48 and 49) and prematurely aborted RNA sequences are removed by the method of claim 1 of U.S. Patent No. 12,084,702 B2, claims 1-18 of U.S. Patent No. 12,084,702 B2 are directed to the same subject matter and fall entirely within the scope of claims 1, 4, 5, 9, 10, 14, 18-20, 28, 30, 31, and 53 in this instant application. In other words, claims 1, 4, 5, 9, 10, 14, 18-20, 28, 30, 31, and 53 in this instant application are anticipated by claims 1-18 of U.S. Patent No. 12,084,702 B2.
Claim 25 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 12,060,381 B2 or claims 1-25 of U.S. Patent No. 11,174,500 B2 or claims 1-18 of U.S. Patent No. 12,084,702 B2 in view of Goldman et al..
Although claims 1-33 of U.S. Patent No. 12,060,381 B2 or claims 1-25 of U.S. Patent No. 11,174,500 B2 or claims 1-18 of U.S. Patent No. 12,084,702 B2 do not teach that the prematurely aborted RNA sequences comprise less than 15 bases as recited in claim 25, Goldman et al., teach that during transcription initiation in vitro, prokaryotic and eukaryotic RNA polymerase (RNAP) can engage in abortive initiation-the synthesis and release of short (2 to 15 nucleotides) RNA transcripts-before productive initiation (see abstract).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the method as recited in claim 25 wherein the prematurely aborted RNA sequences comprise less than 15 bases in view of claims 1-33 of U.S. Patent No. 12,060,381 B2 or claims 1-25 of U.S. Patent No. 11,174,500 B2 or claims 1-18 of U.S. Patent No. 12,084,702 B2 and Goldman et al.. One having ordinary skill in the art would have been motivated to do so because Goldman et al., teach that during transcription initiation in vitro, prokaryotic and eukaryotic RNA polymerase (RNAP) can engage in abortive initiation-the synthesis and release of short (2 to 15 nucleotides) RNA transcripts-before productive initiation (see abstract). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the method recited in claim 25 using in vitro synthesizing mRNA in view of claims 1-33 of U.S. Patent No. 12,060,381 B2 or claims 1-25 of U.S. Patent No. 11,174,500 B2 or claims 1-18 of U.S. Patent No. 12,084,702 B2 such that the prematurely aborted RNA sequences comprise only less than 15 bases.
Response to Arguments
In page 6, fourth to sixth paragraphs of applicant’s remarks, applicant argues that “[A]pplicant respectfully disagrees and traverses this rejection. Applicant respectfully disagrees and traverses this rejection. For the reasons discussed above and incorporated herein, the ‘381 patent does not qualify as NSDP reference to the instant application. Further, the Office has failed to identify, with specificity, the clear and certain unjustified extension of rights in allowing the instant application to proceed to grant. In view of the above, the '381 patent does not qualify as an obviousness-type double patenting reference. In view of the above, the ‘381 patent does not qualify as an obviousness-type double patenting reference”.
The arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection because applicant has not either filed a terminal disclaimer or indicated why U.S. Patent No.12,060,381 B2 cannot qualify as an obviousness-type double patenting reference to reject claim 1.
Claims 29 or 30 or 31 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 12,060,381 B2 in view of Gallie.
Although claims 1-33 of U.S. Patent No. 12,060,381 B2 do not teach that the mRNA is purified before a cap and a tail are added to the mRNA as recited in claim 29, the mRNA is purified after a cap and a tail are added to the mRNA as recited in claim 30, and the mRNA is purified after a cap is added to the mRNA as recited in claim 31, Gallie teaches in vitro synthesized Luciferase mRNAs which have four different species: uncapped poly(A)-, uncapped poly(A)+, capped poly(A)-, and capped poly(A)+ (see pages 2108 and 2109).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods as recited in claim 29 or 30 or 31 wherein the mRNA is purified before a cap and a tail are added to the mRNA or the mRNA is purified after a cap or a tail are added to the mRNA or the mRNA is purified after a cap is added to the mRNA in view of claims 1-33 of U.S. Patent No. 12,060,381 B2 and Gallie. One having ordinary skill in the art would have been motivated to do so because Gallie teaches in vitro synthesized Luciferase mRNAs which have four different species: uncapped poly(A)-, uncapped poly(A)+, capped poly(A)-, and capped poly(A)+ (see pages 2108 and 2109) and the simple substitution of one kind of mRNA (ie., the mRNA from an impure preparation taught by claim 1 of U.S. Patent No. 12,060,381 B2) from another kind of mRNA (ie., Luciferase mRNA having uncapped poly(A)- or Luciferase mRNA having capped poly(A)+ or Luciferase mRNA capped poly(A)- taught by Gallie) during the process of performing method of claim 1 of U.S. Patent No. 12,060,381 B2, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made since the mRNA taught by claim 1 of U.S. Patent No. 12,060,381 B2 and the mRNA taught by Gallie are used for the same purpose (ie., mRNA purification) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to purify Luciferase mRNA having uncapped poly(A)- or Luciferase mRNA having capped poly(A)+ or Luciferase mRNA capped poly(A)- taught by Gallie using the method of claim 1 of U.S. Patent No. 12,060,381 B2 in view of claims 1-33 of U.S. Patent No. 12,060,381 B2 and Gallie in order to perform the method recited in claims 29 or 30 or 31 of this instant application.
Claims 29 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11,174,500 B2 or claims 1-18 of U.S. Patent No. 12,084,702 B2 in view of Gallie.
Although claims 1-25 of U.S. Patent No. 11,174,500 B2 or claims 1-18 of U.S. Patent No. 12,084,702 B2 do not teach that the mRNA is purified before a cap and a tail are added to the mRNA as recited in claim 29, Gallie teaches in vitro synthesized Luciferase mRNAs which have four different species: uncapped poly(A)-, uncapped poly(A)+, capped poly(A)-, and capped poly(A)+ (see pages 2108 and 2109).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods as recited in claim 29 wherein the mRNA is purified before a cap and a tail are added to the mRNA in view of claims 1-25 of U.S. Patent No. 11,174,500 B2 or claims 1-18 of U.S. Patent No. 12,084,702 B2 and Gallie. One having ordinary skill in the art would have been motivated to do so because Gallie teaches in vitro synthesized Luciferase mRNAs which have four different species: uncapped poly(A)-, uncapped poly(A)+, capped poly(A)-, and capped poly(A)+ (see pages 2108 and 2109) and the simple substitution of one kind of mRNA (ie., the mRNA from an impure preparation taught by claim 1 of U.S. Patent No. 11,174,500 B2 or U.S. Patent No. 12,084,702 B2) from another kind of mRNA (ie., Luciferase mRNA having uncapped poly(A)- taught by Gallie) during the process of performing method of claim 1 of U.S. Patent No. 11,174,500 B2 or U.S. Patent No. 12,084,702 B2, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made since the mRNA taught by claim 1 of U.S. Patent No. 11,174,500 B2 or U.S. Patent No.12,084,702 B2
and the mRNA taught by Gallie are used for the same purpose (ie., mRNA purification) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to purify Luciferase mRNA having uncapped poly(A)- taught by Gallie using the method of claim 1 of U.S. Patent No. 11,174,500 B2 or U.S. Patent No. 12,084,702 B2 in view of claims 1-25 of U.S. Patent No. 11,174,500 B2 or claims 1-18 of U.S. Patent No. 12,084,702 B2 and Gallie in order to perform the method recited in claims 29 of this instant application.
Claims 34 and 35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 12,060,381 B2 or claims 1-25 of U.S. Patent No. 11,174,500 B2 or claims 1-18 of U.S. Patent No. 12,084,702 B2 in view of Hoerr et al., or Karikó et al., (Molecular Therapy, 16, 1833-1840, 2008).
Although claims 1-33 of U.S. Patent No. 12,060,381 B2 or claims 1-25 of U.S. Patent No. 11,174,500 B2 or claims 1-18 of U.S. Patent No. 12,084,702 B2 do not teach that the mRNA comprises one or more modifications to enhance stability as recited in claim 34 and the one or more modifications comprises modified nucleotide as recited in claim 35, Hoerr et al., teach that the modification of a mRNA such as increasing G/C content of a mRNA increases the stability of the mRNA (see paragraphs [0078] to [0080]) or Karikó et al., teach that incorporating pseudouridine, a naturally occurring modified nucleoside, into mRNA not only suppresses RNA-mediated immune activation in vitro and in vivo, but also enhances stability and translational capacity of the mRNA (see page 1833).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods as recited in claims 34 and 35 wherein the mRNA comprises one or more modifications to enhance stability and the one or more modifications comprises modified nucleotide in view of claims 1-33 of U.S. Patent No. 12,060,381 B2 or claims 1-25 of U.S. Patent No. 11,174,500 B2 or claims 1-18 of U.S. Patent No. 12,084,702 B2 and Hoerr et al., or Karikó et al.. One having ordinary skill in the art would have been motivated to do so because Hoerr et al., teach that the modification of a mRNA such as increasing G/C content of a mRNA increases the stability of the mRNA (see paragraphs [0078] to [0080]) while Karikó et al., teach that incorporating pseudouridine, a naturally occurring modified nucleoside, into mRNA not only suppresses RNA-mediated immune activation in vitro and in vivo, but also enhances stability and translational capacity of the mRNA (see page 1833). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in clams 34 and 35 of this instant application by modifying the nucleotides of the mRNA taught by claim 1 of U.S. Patent No. 12,060,381 B2 or U.S. Patent No. 11,174,500 B2 or U.S. Patent No. 12,084,702 B2 based on increasing its G/C content or incorporating pseudouridine into the mRNA taught by claim 1 of U.S. Patent No. 12,060,381 B2 or U.S. Patent No. 11,174,500 B2 or U.S. Patent No. 12,084,702 B2 in view of claims 1-33 of U.S. Patent No. 12,060,381 B2 or claims 1-25 of U.S. Patent No. 11,174,500 B2 or claims 1-18 of U.S. Patent No. 12,084,702 B2 and Hoerr et al., or Karikó et al., in order to enhance stability of the mRNA taught by claim 1 of U.S. Patent No. 12,060,381 B2 or U.S. Patent No. 11,174,500 B2 or U.S. Patent No. 12,084,702 B2.
Response to Arguments
In page 7, fourth to sixth paragraphs of applicant’s remarks, applicant argues that “[A]pplicant respectfully disagrees and traverses this rejection. Applicant respectfully disagrees and traverses this rejection. For the reasons discussed above and incorporated herein, the ‘381 patent does not qualify as NSDP reference to the instant application. Further, the Office has failed to identify, with specificity, the clear and certain unjustified extension of rights in allowing the instant application to proceed to grant. In view of the above, the '381 patent does not qualify as an obviousness-type double patenting reference. In view of the above, the ‘381 patent does not qualify as an obviousness-type double patenting reference”.
The arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection because applicant has not either filed a terminal disclaimer or indicated why U.S. Patent No.12,060,381 B2 cannot qualify as an obviousness-type double patenting reference to reject claim 1.
Conclusion
No claim is allowed.
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/FRANK W LU/Primary Examiner, Art Unit 1683 June 29 , 2026
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