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 .
Status of claims / Response to Amendment
This office action is in response to an amendment filed on May 11, 2026.
Claims 31-50, 52-58, 60, 62-83 were previously pending. Applicant amended claim 79.
Claims 31-50, 52-58, 60, 62-83 are currently pending, with claims 35, 42-43, 47, 62-64, 66-68, 70 and 73 withdrawn from consideration.
Claims 31-34, 36-41, 44-46, 48-50, 52-58, 60, 65, 69, 71-72 and 74-83 are under consideration.
Applicant's claim amendments and arguments overcame the following rejections:
Rejections of Claims 31-34, 36-41, 44-46, 48-50, 52-58, 60, 65, 69, 71-72 and 74-83 under 35 U.S.C. 112(a) in independent claims 31 and 49;
Rejections of Claim 79 under 35 U.S.C. 112(a);
Rejections of Claims 31-34, 36-39, 44-45, 48-49, 52-58, 60, 65, 69, 71-72 and 74-83 under 35 U.S.C. 103 as being unpatentable over Thess , in view of Prazeres ; Scorza ; Bancel ; Azarani ; Shahrokh; as evidenced by Diogo; and Merten;
Rejections of Claims 40-41 under 35 U.S.C. 103 as being unpatentable over Thess, in view of Prazeres, Scorza, Bancel, Azarani and Shahrokh, as applied to claims 31 and 39 above and further in view of Hoerr as evidenced by Walker;
Rejections of Claims 46 and 50 under 35 U.S.C. 103 as being unpatentable over Thess, in view of Prazeres, Scorza, Bancel, Azarani and Shahrokh, as applied to claims 31, 45 and 49 above and further in view of Affymetrix.
The priority date for the instant claims has been updated in view of Applicant's remarks regarding written description support in the disclosure for the limitation "purifying the RNA by at least one step of chromatography and at least one step of filtration to obtain purified RNA," recited in independent claims 31 and 49. A detailed discussion is below in the "Response to Arguments" section.
Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
This office action contains new grounds for rejection NOT necessitated by amendment.
Accordingly, this office action is issued as a Non-Final Office Action.
Response to Arguments
Applicant's arguments filed on May 11, 2026 have been fully considered.
Priority/ Claim Rejections -35 USC§ 112(a)
Applicant's argument regarding whether the specification supports the limitation "purifying the RNA by at least one step of chromatography and at least one step of filtration to obtain purified RNA, " in the methods recited in claims 31 and 49, has been fully considered and found persuasive. Accordingly, the rejection of Claims 31-34, 36-41, 44-46, 48-50, 52-58, 60, 65, 69, 71-72 and 74-83 under 35 U.S.C. 112(a) in independent claims 31 and 49 has been withdrawn, and the priority date has been updated in this Office Action.
In the Remarks (page 9-12), Applicant points to descriptions in the specification, describing method embodiments comprising a step of purifying the in vitro transcribed RNA by preparative RP-HPLC (page 83) or size-selective HPLC (page 101-102, example 22). The purified, in vitro transcribed RNA are then lyophilized. Next, the RNA lyophilisate is re-suspended and sterile-filtered.
Here, although the embodiments above describe the chromatography and filtration steps as separate, nonconsecutive steps, they are nonetheless encompassed by the claims, which do not further limit whether those steps must be carried out in close temporal proximity. In other words, the claims permit additional steps to occur between the purification steps.
Therefore, upon reconsideration, the limitation "purifying the RNA by at least one step of chromatography and at least one step of filtration to obtain purified RNA" is found to be adequately supported by the written description in the specification.
Claim Rejections - 35 USC § 103
Applicant asserts that the previously set forth 103 rejections fail because there is lack of motivation to combine the teachings of Prazeres with Thess (Remarks, page 13-14). This argument has been considered and is found to be persuasive. Accordingly, the prior rejections have been withdrawn and new rejections have been made to address this issue (see in rejections below).
Priority -- Updated
The earliest priority date of the instant claims 31-34, 36-41, 44-46, 48-50, 52-58, 60, 65, 69, 71-72 and 74-83 is 05/08/2015, filling date of the PCT application NO. PCT/EP2015/000959.
Claim Interpretation
In evaluating the patentability of the claims presented in this application, claim terms have been given their broadest reasonable interpretation (BRI) consistent with the specification, as understood by one of ordinary skill in the art, as outlined in MPEP§ 2111.
For the purpose of applying prior art, independent claims 31 and 49 recite "the integrity of the linearized plasmid template DNA" and "the integrity of the RNA." The application's disclosure does not define the term "integrity" in the context of nucleic acids. Thus, it is interpreted under BRI to mean any state of nucleic acid molecules, encompassing degree of intactness of structure, level of degradation, purity and quality.
For the purpose of applying prior art, claims 69 and 72 recite "replicon RNA," which is not defined in the application's disclosure. The term "replicon RNA" does not have a well-established or universally accepted definition in the art, according to Merriam-Webster, "replicon" is defined as "a linear or circular section of DNA or RNA which replicates sequentially as a unit." (see www. merriam-webster.com/dictionary/replicon) Since any RNA can be replicated during transcription, under BRI, "replicon RNA" is interpreted to encompass any RNA.
New Grounds of Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 31-34, 36-39, 44-45, 48-49, 52-58, 60, 65, 69, 71-72, 74-78 and 80-83 are rejected under 35 U.S.C. 103 as being unpatentable over Thess (WO2013143699A1 - Artificial nucleic acid molecules for improved protein or peptide expression; Published 2013-10-03) , in view of
Prazeres (Prazeres, et al. "Design of flowsheets for the recovery and purification of plasmids for gene therapy and DNA vaccination." Chemical Engineering and Processing: Process Intensification 43.5 (2004): 609-624);
Scorza (WO2014140211A1- Rna purification methods; Published on: 2014-09-18);
Bancel (US20130259924A1 - Modified polynucleotides for the production of biologics and proteins associated with human disease ; Published 2013-10-03);
Azarani (Azarani et al., RNA analysis by ion-pair reversed-phase high performance liquid chromatography, Nucleic Acids Research, Volume 29, Issue 2, 15 January 2001, Page e7, https://doi.org/10.1093/nar/29.2.e7);
Shahrokh (WO2014144039A1 - Characterization of mrna molecules; 2014-09-18);
Artsimovitch (Artsimovitch et al., In vitro approaches to analysis of transcription termination. Methods. 2009 Jan;47(1):37-43. doi: 10.1016/j.ymeth.2008.10.006. Epub 2008 Oct 21. PMID: 18948199; PMCID: PMC2652710) ;
Edelmann (Edelmann et al. "Production of pure and functional RNA for in vitro reconstitution experiments." Methods 65.3 (2014): 333-341);
Sauer (Sauer, Marie-Laure, et al. "Sequential CaCl2, polyethylene glycol precipitation for RNase-free plasmid DNA isolation." Analytical biochemistry 380.2 (2008): 310-314));
Biosyn ("Template optimization for In Vitro Transcription" ; biosyn.com, 10/18/201);
as evidenced by
Diogo (Diogo et al.Chromatography of plasmid DNA. J Chromatogr A. 2005 Mar 25;1069(1):3-22. doi: 10.1016/j.chroma.2004.09.050. PMID: 15844479); and
Merten (Merten, et al. "Manufacturing of viral vectors: Part II. Downstream processing and safety aspects." Pharmaceutical Bioprocessing 2.3 (2014): 237-251.).
Regarding claims 31 and 49, while they are separate independent claims, they will be addressed together below as the claims' scopes largely overlap. Claim 49 is narrower in scope than claim 31 and further comprises determining the poly(A) length of the purified RNA in a sample, this feature is recited by claim 31's dependent claim 45.
The claims are generally directed to methods of producing RNA via in vitro transcription, comprising steps for:
preparing a plasmid DNA template for in vitro transcription;
performing quality control of the plasmid DNA template;
producing RNA transcripts by in vitro transcription using the plasmid DNA template;
purifying the in vitro transcribed RNA products;
performing quality control of the purified RNA products.
A) Thess teaches methods for producing RNA, specifically stable mRNA for applications in gene therapy and/or vaccination (entire document, pages 4 and 8 for example).
Regarding claims 31, 45 and 49, Thess teaches methods for producing purified RNA comprising the following steps:
providing a linearized plasmid template DNA comprising a nucleic acid sequence encoding an RNA (page 96, lines 11-26; page 98, lines 29-33 to page 99, lines 1-6, linearized vector; page 126, lines 4-9; page 1, lines 8-12; page 77, lines 9-11),
said RNA comprising a 5' untranslated region (UTR) (page 86, lines 1-6 ; page 96, line 13, 15), an open reading frame (page 86, lines 1-6; page 96, lines 11-13), a 3' UTR and a poly(A) sequence (page 86, lines 1-6; page 96, line 14),
in vitro transcribing the linearized plasmid template DNA to obtain a composition comprising the RNA (page 97, line 9-14, T7 RNA polymerase based in vitro transcription system.; page 126, lines 5-9; page 127, lines 21-26);
treating the composition with a DNase (page 127, line 23); and purifying the RNA (page 127, line 25).
While Thess teaches methods of producing and purifying RNA products using linearized plasmid DNA vectors as template for in vitro transcription, for the purpose of providing a pharmaceutical composition for use in gene therapy and/or vaccination (e.g., see page 8, lines 22-31 for object of Thess); it lacks details on the specific processes for purifying RNA, and performing quality control for the plasmid DNA and RNA.
It is noted that purification and quality control of nucleic acid products, such as plasmid DNA and RNA, are well-known and commonly practiced in the field of pharmaceutical manufacturing, particularly for gene therapy and vaccination applications. A detailed discussion with supporting references are provided below.
Furnishing known methods with well-known features in the same field and context, as would have been understood by a person of ordinary skill in the art, in this instance, cannot be considered nonobvious.
B) With respect to purification and quality control of plasmid DNA, Prazeres teaches methods for the recovery and purification of plasmids intended for pharmaceutical use, including gene therapy and vaccination (entire document).
Regarding claims 31, 45 and 49, Prazeres teaches purifying plasmid DNA by chromatography and filtration (Prazeres, Fig. 2). Prazeres teaches quality control of purified plasmid DNA comprising:
determining the concentration of the linearized plasmid template DNA in a sample (Prazeres, page 616, right-hand col, para 1 “Product specifications, quality control and monitoring”, Table 1) ;
determining the integrity of the linearized plasmid template DNA in a sample (Prazeres, page 616, right-hand col, para 1 “Product specifications, quality control and monitoring”, Table 1, “Appearance” “homogeneity,” etc.); and
determining the purity of the linearized plasmid template DNA by determining in a sample comprising the linearized plasmid template DNA the presence of endotoxin(Prazeres, page 616, right-hand col, para 1 “Product specifications, quality control and monitoring”, Table 1).
Furthermore, the use of chromatography combined with filtration to purify plasmid DNA, along with routine quality control measurements ꟷ such as assessing plasmid concentration, purity, and endotoxin levelsꟷ is well-known in the art, as evidenced by Diogo (entire document, see sec 2.1 and Table 4 for examples), a review paper titled "Chromatography of plasmid DNA."
A skilled artisan would have been motivated to purify and quality control the linearized plasmid DNA templates used for in vitro transcription, disclosed in Thess, because it is well-known in the art that the quality of template DNA is very important in in vitro transcription assays - low quality DNA template is the primary cause of sub-optimal results (see Artsimovitch at page 4, para 3, lines 1-2 ). Poor template quality or contaminations in the reaction could lead to poor quality of in vitro transcription (see Fig, 1A legend in Edelmann). In fact, it is common knowledge that the plasmid DNA for in vitro transcription need to be purified to be contamination free (see Sauer, Abstract; see also Biosyn, page 15).
Although Prazeres evaluates purified plasmid DNA as the final pharmaceutical product, whereas Thess uses plasmid DNA as an intermediate template for RNA production, the relevant principle remains the same: nucleic acid materials used for pharmaceutical applications should be high quality and free of contaminants.
A skilled artisan would therefore have understood that the plasmid DNA template used in the process of Thess should be purified with Prazeres ‘s DNA purification and quality control approach to ensure it is free of contaminants before used for in vitro transcription.
C) With respect to the purification and quality control of RNA products,
Scorza teaches methods for purifying RNA products following in vitro transcription for pharmaceutical applications (entire document, see [0002] for example).
Regarding claims 31, 45 and 49, Scorza teaches purifying RNA by at least one step of chromatography and at least one step of filtration to obtain purified RNA (Scorza, Abstract, [0008]; [00012] method comprises a step of tangential flow filtration and a step of hydroxyapatite chromatography). Scorza teaches assessing the quality of the purified RNA comprising:
determining the concentration of the purified RNA in a sample (000174], FIG. 7A shows recovery of RNA measured by direct quantification by RiboGreen® assay);
determining the integrity of the purified RNA in a sample ([0004] RNA stability; [000159]);
determining the purity of the purified RNA, by determining in a sample comprising the purified RNA the presence of linearized plasmid template DNA (Scorza, [000174] FIG. 7F shows plasmid DNA carryover, using qPCR assay on plasmid; [000202]),
determining the pH of a sample comprising the purified RNA ([000131], disclosing a specific pH range of pharmaceutical composition comprising purified RNA, thus requiring its pH to be measured).
Scorza specially teaches the application of its methods in the context of purifying in vitro transcribed RNA for pharmaceutical applications, which is directly relevant to the teachings of Thess, directed to methods for producing and purifying RNA products from in vitro transcription, for the purpose of providing a pharmaceutical composition.
It is further noted that the combined use of filtration and chromatography for the broader purpose of purifying nucleic acid products is well-known and routinely practiced in biomanufacturing, as evidenced by Merten, suggesting incorporation of a filtration step prior to any chromatography steps provides additional advantages, including efficient buffer exchange, reduced operation volume, and removal of larger cellular debris and other contaminants (page 244, left-hand col, para 1).
Scorza discloses that RNA to be purified can comprise poly(A) tails, but it does not specifically teach any quality control step for determining the length of the poly(A) tail. As suggested in Thess, the length of the poly(A) tail plays an important role in RNA stability and translational efficiency (page 7, lines 25-30). Accordingly, in view of Thess, a person of ordinary skill in the art would have been motivated to implement a quality control step to assess poly(A) tail length in order to ensure the stability and translational efficiency of the purified mRNA product.
Bancel fills this gap by specifically teaching a method for determining poly(A) tail length using poly(A)-binding proteins and further notes that poly(A) tails of approximately 80-160 nucleotides are functional ([0106]). The teachings of Bancel are directed to in vitro transcription of RNA from linearized plasmid DNA templates for applications such as vaccine formulation, which is highly relevant to the context of the references cited above, specifically Thess, Scorza and Prazeres, as evidenced by the overlap in subject matter and field of use.
In addition, Bancel teaches determining the identity of the purified RNA, by reverse transcription (RT)- PCR using the purified RNA as a template (Bancel, [0282]).
It is further noted that confirming RNA identity following purification by reverse transcription PCR is a well-known and routine practice in the field of life sciences art, as supported by Azarani (Azarani, page 5, the identity and integrity of purified RNA are confirmed by reverse-transcription PCR) and Shahrokh [0005]; [0131-0132]).
D) It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the detailed teachings of plasmid DNA purification and quality control as taught by Prazeres, and the detailed teachings of RNA purification and quality control as taught by Scorza, Bancel, Azarani and Shahrokh, to the method disclosed in Thess, which describes producing and purifying RNA products from in vitro transcription for use in pharmaceutical compositions.
All of the cited references are in the overlapping field of nucleic acid production and analysis, and provide complementary teachings. Thess discloses a general method for producing RNA products via in vitro transcription using linearized plasmid DNA and purifying the resulting RNA for pharmaceutical applications such as vaccination. While Thess does not provide specific details regarding purification and quality control steps for plasmid DNA intermediates or RNA products, a person of ordinary skill in the art would understand that stringent control and monitoring steps are necessary in pharmaceutical manufacturing (e.g., current good manufacturing practices for pharmaceutical products) to ensure a pharmaceutical-grade product that is free of contaminants and retains its intended function.
Indeed, Thess need not recite every such detail, as the methods for purification and quality control of nucleic acid products, including plasmid DNA for reverse transcription and RNA products, are well-known and commonly practiced in the life sciences art, as supported by Prazeres, Scorza, Bancel, Azarani, Shahrokh, Artsimovitch, Edelmann, Sauer and Biosyn, and further evidenced by Diogo and Merten.
Therefore, a skilled artisan ꟷ motivated by the inherent need in the biomanufacturing of RNA products (see, e.g., Scorza [0004]) for high yield, pharmaceutical-grade purity, and retention of RNA stability, potency, and functionality ꟷ would have naturally turned to common knowledge or routine practices in the field to supplement the general teachings of Thess. Applying established methods for plasmid DNA and RNA purification and quality control would have been a logical extension of teachings of Thess, guided by well-known practices in the life science and pharmaceutical manufacturing arts.
The person of ordinary skill would have had a reasonable expectation of success in combining these teachings because the references disclose technically compatible and overlapping teachings. A skilled artisan would have been able to combine these teachings, much like assembling pieces of a puzzle, to arrive at a predictable outcome ꟷ namely, a complete in vitro mRNA production workflow for generating pharmaceutical-grade RNA compositions.
This combination would also have been obvious as it represents the KSR principle of predictable use of prior art elements according to a known method to yield predictable results. (See MPEP §2143).
E) Regarding claim 32-34 and 52-54, Bancel teaches providing the linearized plasmid template DNA, comprises obtaining a plasmid template DNA([0260]); purifying the plasmid template DNA by chromatography and filtration([0260-0261]); and linearizing the plasmid template DNA with an endonuclease([0261] restriction enzyme).
Regarding claims 36 and 56, Bancel teaches determining the concentration of linearized plasmid template DNA by photometric measurement ([1260] line13, Nanodrop; [0521]).
Regarding claims 37 and 57, Thess teaches poly(A) sequence is 50 to 300 adenine nucleotides (page 19, line 7, “preferably from about 50 to about 300”).
Regarding claims 38 and 58, Bancel teaches DNase I ([0277]).
Regarding claim 39, Bancel teaches a reaction mixture that includes a cap analog for obtaining capped RNA([0225-0227]).
Regarding claim 44, Bancel teaches enzymatically capping the RNA ([1269-1270]).
Regarding claims 48 and 65, Bancel teaches capillary gel electrophoresis assay ([0283]lines15-16).
Regarding claim 55, Bancel teaches culturing bacteria comprising the plasmid template DNA under selective conditions ([0257]; [1247-1258], [1257] discloses culturing bacteria on a selection plate); isolating the plasmid template DNA from the bacteria ([1259]); and linearizing the plasmid template DNA with an endonuclease ([1260]).
Regarding claim 60, Thess teaches in vitro transcribing the linearized plasmid template DNA is in a reaction mixture that includes T7 polymerase (page 127, lines 21-23).
Regarding claims 69 and 72, Bancel teaches replicon RNA ([0232]; [0934] for example).
Regarding claim 71, Thess teaches mRNA (page 107, line 13) .
Regarding claims 74-76, Shahrokh teaches purifying RNA by at least one step of chromatography comprises at least one step of affinity chromatography, which is oligo-dT affinity chromatography for poly capture ([0162] oligodT affinity chromatography).
Regarding claim 77, Scorza teaches determining the presence of linearized plasmid template DNA comprises performing qPCR (Scorza, [000174] FIG. 7F shows plasmid DNA carryover, using qPCR assay on plasmid; [000202]).
Regarding claim 78, Shahrokh and Azarani both teach determining the integrity of the purified RNA comprises performing RP-HPLC (Azarani, Figure 6) ( Shahrokh , [0179]).
Regarding claim 80, Shahrokh teaches determining the identity of the purified RNA further comprises RT-PCR followed by Sanger sequencing (Shahrokh, [0130], [0132-[0133]).
Regarding claim 81, Bancel teaches in vitro transcribing the linearized plasmid template DNA is in a reaction mixture that includes a modified nucleotide (Bancel [0021]; [0924]; [1488]).
Regarding claim 82, Bancel teaches wherein the modified nucleotide is 1-methyl- pseudouridine1 (Bancel [0021]; [0924]; [1488]).
Regarding claim 83, Bancel teaches enzymatically capping the RNA (Bancel, [1269-1270]).
Claims 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over Thess, in view of Prazeres, Scorza, Bancel, Azarani, Shahrokh, Artsimovitch, Edelmann, Sauer and Biosyn as applied to claims 31 and 39 above and further in view of
Hoerr (US20110311472A1- Application of mrna for use as a therapeutic against tumour diseases; published 2011-12-22), as evidenced by Walker (Walker et al. General plasmids for producing RNA in vitro transcripts with homogeneous ends. Nucleic Acids Res. 2003 Aug 1;31(15):e82. doi: 10.1093/nar/gng082. PMID: 12888534; PMCID: PMC169970.).
A) The combined teachings of Thess, Prazeres, Scorza, Bancel, Azarani and Shahrokh
are recited above and applied as for base claims 31 and 39.
Thess teaches in vitro transcription but does not provide any detailed buffer composition; while Bancel teaches using a transcription buffer comprising Tris-HCL buffer, it does not specifically teach HEPES buffer.
Hoerr teaches a method of preparing a RNA vaccine via in vitro transcription from a linearized plasmid DNA (entire document, [0083] for example).
Regarding claim 40, Hoerr teaches HEPES buffer ([0083]line7). HEPES buffer is a buffer used in in vitro transcription reactions, as evidenced by Walker's teaching of using HEPES buffer instead of Tris-HCL in its in vitro transcription reaction (page 3, left-hand col, para 3).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the Tris-HCL buffer taught by the combined teaching of Thess, Prazeres, Scorza, Bancel, Azarani and Shahrokh with the HEPES buffer taught by Hoerr in the reaction mixture for in vitro transcription because the references are in the same field of nucleic acid product and analysis and share overlap in teachings.
Specifically, Thess, Bancel, and Hoerr all teach preparing RNA products in the field of biomanufacturing, specifically in vaccine production. All three references share the common focus of in vitro transcription reactions, and Walker explicitly demonstrates the use of HEPES buffer for this purpose.
This substitution aligns with the KSR principle as it represents a simple substitution of one known element (Tris-HCL) for another (HEPES) to obtain predictable results. Both buffers are well-known and commonly used in molecular biology for maintaining pH levels during in vitro transcription, as evidenced by the compatibility shown in Bancel and Hoerr. There is no indication that this substitution would result in any unexpected outcome; instead, it would have yielded the same predictable result of supporting the in vitro transcription reaction, as both buffers function similarly in maintaining the reaction environment.
Therefore, it would have been obvious to use HEPES buffer in the in vitro transcription reaction mixture of Bancel, representing a simple substitution of one known buffer for another to achieve predictable results, see MPEP 2141.
B) Regarding claim 41, Hoerr teaches a ratio of about 10:1 to 1:1 (cap analog : GTP) in reaction mixture ([0114] 8mM to 2mM is 4:1).
Claims 46, 50 and 79 are rejected under 35 U.S.C. 103 as being unpatentable over Thess, in view of Prazeres, Scorza, Bancel, Azarani, Shahrokh, Artsimovitch, Edelmann, Sauer and Biosyn as applied to claims 45/31, 49 and 78/77/75/74/60/49 above and further in view of
Affymetrix (Affymetrix (Poly(A) Tail-Length Assay Kit; 2010 Affymetrix, Inc; Published in 2010; cited as C66 in IDS filed 03/03/2023).
The combined teachings of Thess, Prazeres, Scorza, Bancel, Azarani and Shahrokh
are recited above and applied as for base claims 45, 49 and 78.
Regarding claims 46, 50 and 79, they recite determining the poly(A) length of the purified RNA comprises a PCR assay. While Bancel teaches determining the poly (A) length of purified RNA([0106]), it does not teach using a PCR assay but teaches using poly(A) binding proteins instead.
Affymetrix teaches a method of using a kit to determine poly (A) length of RNA samples (entire document).
Affymetrix teaches determining the poly(A) length of purified RNA comprises a PCR assay (entire document; page 5 for example).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the method of using poly(A) binding proteins taught by Bancel, in the combined teachings of Thess, Prazeres, Scorza, Bancel, Azarani and Shahrokh, with the PCR assay taught by Affymetrix for determining the poly(A) length of purified RNA, because both Bancel and Affymetrix are in the same or overlapping field of RNA analysis and processing and specifically address methods for determining poly(A) tail length.
This substitution represents a predictable use of a known technique within the same category -- determining poly(A) length -- within no unexpected change in function or result. Both methods aim to measure the poly (A) length, and using a PCR assay, as taught by Affymetrix, provides an equivalent result with the added benefit of using a commercially available and ready-to-use kit, thus simplifying the process. The skilled artisan in the art would have recognized the technical compatibility in the teachings, as both achieve the same outcome of measuring poly(A) length in RNA.
Therefore, it would have been obvious to apply the PCR assay method of Affymetrix in the method taught by the combined teachings of Thess, Prazeres, Scorza, Bancel, Azarani and Shahrokh for determining the poly(A) length, in place of poly(A) binding proteins, representing a simple substitution of one known element (PCR assay) for another (poly(A) binding proteins) to achieve the same predictable results, see MPEP 2141.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/TIAN NMN YU/Examiner , Art Unit 1681 /AARON A PRIEST/Primary Examiner, Art Unit 1681
1 "N1-methyl- pseudouridine" and "1-methyl- pseudouridine" are Synonyms, see pubchem.ncbi.nlm.nih.gov/compound/1-Methylpseudouridine
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