DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This appln claims benefit of 63/420,827 filed 10/31/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/24/2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings were received on 10/31/2023 is acknowledged. These drawings are found acceptable by the Examiner.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Beverly et al (US 20200325532, October 15, 2020) in view of Marquardt et al (20180274009, September 2018, effective filing date October 2016)
Regarding claim 1, Beverly et al teach a method of determining a mRNA poly(A) tail size comprising: digesting an mRNA molecule to liberate a poly(A) tail; preparing a chromatographic sample comprising the mRNA poly(A) tails; preparing a second chromatographic sample comprising a reference sequence with a predetermined length; separating the first and second samples by a chromatography method, which result in one or more chromatograms; and determining a sequence length of the mRNA poly(A) tails by comparing the chromatograms of the first and second samples (see entire document, especially paragraphs [0008] – [0013], [0017] – [0019], [0024] –[0025], [0043], [00113] – [0114], [0123], [0125] – [0126], [0152] – [0171]; see also paragraphs [0174] – [0177] which teaches mass spectrometry techniques performed to carry out the method).
Regarding claims 2 and 11, Beverly teaches wherein the reference sequence comprises 30-150 nt in length ([0125]-[0126] and [0152] – [0171]).
Regarding claims 3 and 5, Beverly teaches further comprising selecting a length of the reference sequence by calibrating with a DNA or RNA reference sequence standard (see [0040] – [0043], [0125] –[0173]).
Regarding claim 4, Beverly teaches that the mRNAs can be produced synthetically through in vitro transcription. In vitro, MRNAs gain their polyA tails either by encoding the polyA sequence into the template DNA or by having he polyAs added post-synthesis using a polyadenylase ([0054]).
Regarding claim 6, Beverly teaches wherein the mRNA poly(A) tails range between about 80 to about 120 oligonucleotides ([0100], [0109]).
Regarding Claim 7, Beverly teaches wherein the mRNA poly(A) tails have a length distribution that is observable from chromatogram having high resolution ([0047] – [0048], [0057]. [0099], [0208], [0210], Table 1).
Regarding claim 8, Beverly teaches wherein the method further comprises calculating the dispersity of the mRNA poly(A) tails based on one or more poly(A) tail peak widths of the chromatograms ([0044], [0046] – [0048], [0201], Table 1 and [0215]).
Regarding claim 9, Beverly teaches wherein the chromatography method is performed with mass spectrometry (MS) compatible mobile phases ([0068], [0071], [0200]).
Regarding claim 10, Beverly teaches wherein the digesting step comprises liberating the 3' poly(A) tail of the mRNA molecule by enzymatic cleavage [0108].
Regarding claims 12-17, Beverly teaches wherein the chromatography method may comprise of ultraviolet ion-pair reversed- phase liquid chromatography (IP RP LC UV) ([0208]).
Beverly differs from the instant invention in that Beverly does not expressly teach the order of method steps recited therein. However, MPEP2144.04 states that the selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930).
Beverly does not expressly teach the use of a combination of different chromatograph assay as recited by the instant claims.
Regarding claims 1-17, Marquardt et al teach a method comprising: (a) digesting a test mRNA with an RNase enzyme to produce a plurality of mRNA fragments; (b) physically separating the plurality of mRNA fragments; (c) determining the masses of the fragments; (d) identifying the test mRNA by comparing the signature to the predicted mass pattern (e.g., a theoretical pattern) and/or an empirically-derived chromatographic pattern, and (e) confirming the identity of the test mRNA if the observed masses and/or chromatogram [0009].
At paragraph [0013] and [0014]. Marquardt et al teach in some embodiments, the physical separation and/or the detecting is achieved by one or more methods selected from the group consisting of: gel electrophoresis, liquid chromatograph, high pressure liquid chromatography (HPLC), and mass spectrometry. In some embodiments, the HPLC is HPLC-UV. In some embodiments, the mass spectrometry is Electrospray Ionization mass spectrometry (ESI-MS) or Matrix-assisted Laser Desorption/Ionization mass spectrometry (MALDI).
[0014] In some embodiments, the signature assigned to the test mRNA is an absorbance spectrum, a mass spectrum, a UV chromatogram, a total ion chromatogram, an extracted ion chromatogram, a combination of extracted ion chromatograms, or any combination of the foregoing.
Marquardt et al teach at paragraph [0055], [0078], [0083], that the Figures 13, 37, and 42, respectively, depict data for mRNA tail length determination by reverse-phased ion paired chromatography with UV detection or by liquid chromatography-mass spectrometry (LC-MS). See also paragraphs [0183], [0184], [0189], [0203] and [0208] – [0210] which further discuss determining polyA tail length identification and quantification using chromatographic techniques.
Marquardt further teaches that test mRNA can be physically separate by chromatography or mass spectrometry. The reference teaches examples of chromatography within the scope of the invention comprise size exclusion chromatography, high performance liquid chromatography ad mass spectrometry techniques comprise electrospray ionization mass-spectrometry, matriz-assiost laser desorption ionization mass spectrometry and further may encompass various combinations thereof ([0157]). Marquardt teaches that coupling various techniques allow for second dimension of separation as well as detection [0157].
It would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date of the claimed invention to have been motivated to have combined the teachings of Beverly with the teachings of Marquardt since they are of similar scope and both are directed to method steps involved in measuring mRNA polyA tail lengths using chromatogram data. The ordinary artisan would have been motivated to utilized and/or combined different types of chromatography techniques in the method of Beverly and Marquardt for the benefit of providing multiple dimensions of separations thereby increasing specificity and sensitivity of determining mRNA poly(a) tail lengths as suggested by Marquardt. The combination of the cited prior art is prima facie obvious in the absence of secondary consideration.
Conclusion
9. No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CYNTHIA B WILDER whose telephone number is (571)272-0791. The examiner can normally be reached Flexible.
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/CYNTHIA B WILDER/Primary Examiner, Art Unit 1681