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 the Claims
The amendment filed 12/17/2025 has been entered. Claims 1 and 5 have been amended and claim 14 is new. Claims 1-14 are currently pending, and claims 1-9 and 14 are examined herein.
Status of the Rejection
Applicant’s amendments to the claims have overcome various objections and rejections previously set forth in the Non-Final Rejection mailed 9/25/2025.
The claim objections have been overcome by the applicant's amendments.
All 35 U.S.C. § 103 rejections from the previous office action are withdrawn in view of the Applicant’s amendment.
New grounds of rejection under 35 U.S.C. § 103 are necessitated by the amendments as outlined below.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-9 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Yann et al. (WO 2019092269 A1, referencing previously furnished copy) in view of Marshall et al. (US 20190071661 A1) and Schneider et al. (US 20220033322 A1).
Regarding claim 1, Yann teaches a method of isolating nucleic acids from a sample (a method of performing epitachophoresis on nucleic acids in a sample [005-006, 0094]), wherein said method comprises:
i. providing a device for effecting epitachophoresis (ETP) (the device for effecting epitachophoresis in Figs. 1-2 [009-0011]) comprising a circular outer electrode (outer circular electrode 1 in Fig. 2A [00318]) encircling a gel comprising a leading electrolyte (LE) (leading electrolyte 3 in Fig. 2A is stabilized by a gel [00318]), a central electrode (electrode 5 in Fig. 2A [00319]) and a collection well (reservoir 4 in Fig. 2A [00319]);
ii. preparing, from the sample, a sample solution in a trailing electrolyte (TE) (before loading, the sample may be mixed with trailing/terminating electrolyte 2 in Fig. 2A [0079, 00318]);
iii. performing an epitachophoresis run by applying constant power to said device (the device is operated at constant power [0081]); and
iv. collecting said one or more focused zones from the collection well (sample is concentrated in reservoir 4 in Fig. 2A and then removed via pipetting [0037, 00319]).
Yann is silent to the following limitations: (1) the sample comprises a formalin-fixed paraffin-embedded tissue (FFPET) sample and (2) a centrifugation-based cleanup on the solution of isolated nucleic acids using a centrifugal filter after step iv.
Marshall teaches a method of isolating nucleic acids from a FFPET sample using an electrophoresis device (processing FFPE tissue samples and extracting nucleic acids via isotachophoresis [Abstract, 0005]), as FFPET samples are important resources for developing therapeutics [0004]. Marshall further teaches how to prepare FFPET samples prior to electrophoresis [0072, 0105, 0290].
Yann and Marshall are considered analogous to the claimed invention because they are in the same field of electrophoresis. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method in Liu by using FFPET as a sample, since this would provide information for developing therapeutics [0004 in Marshall]. Furthermore, Marshall teaches the claimed improvement as a known technique that is applicable to the base method in Yann. One skilled in the art could have applied the modifications from Marshall in the same way to the base method in Yann, yielding predictable results (MPEP 2143(I)(D)).
Schneider teaches a method of purifying nucleic acid samples after electrophoretic separation [0108], wherein the nucleic acid extracted from the gel is subjected to a centrifugation-based cleanup using a centrifugal filter (the DNA suspension was filtered using 3 kDa cut off centrifugal filter columns [0108]). Schneider further teaches that this centrifugation filtering step desalts the DNA sample [0108, 0120].
Modified Yann and Schneider are both considered analogous to the claimed invention because they are in the same field of nucleic acid separation using electrophoresis. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method in modified Yann by purifying the solution of isolated nucleic acids with a centrifugation-based cleanup step using a 3 kDa cut off centrifugal filter, as taught in Schneider, since this would desalt the DNA sample [0108, 0120]. Furthermore, Schneider teaches the claimed improvement as a known technique that is applicable to the base device in modified Yann. One skilled in the art could have applied the centrifugation-based cleanup step in Schneider in the same way to the base device in modified Yann, yielding predictable results (MPEP 2143(I)(D)).
The limitations “to focus the nucleic acids into one or more focused zones” and “thereby obtaining a solution of isolated nucleic acids” are intended results of positively recited steps. The court noted that a “'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
Regarding claim 2, modified Yann teaches the method of claim 1, and further teaches wherein preparing the FFPET sample comprises deparaffinization and lysis (for FFPET samples, deparaffinization and cell lysis occur prior to sample loading and electrophoretic separation [0424 in Marshall]).
Regarding claim 3, modified Yann teaches the method of claim 1, and further teaches wherein the FFPET sample solution further comprises a dye (the sample can be pretreated with a dye for imparting color [00131 in Yann]) and the method further comprises monitoring the migration of the dye and collecting the focused zones when the dye reaches the collection well (in Fig. 11, dyed samples are used to generate two differently colored focused zones, such that each sample can be separately monitored and collected as each dyed ring reaches the center of the device [00391 in Yann]).
Regarding claim 4, modified Yann teaches the method of claim 1, and further teaches wherein the nucleic acids are a combination of DNA and RNA (FFPET samples contain both DNA and RNA [0288 in Marshall], such that the isolated nucleic acids are a mixture of DNA and RNA).
Regarding claim 5, modified Yann teaches the method of claim 1, and Yann further teaches wherein the solution of isolated nucleic acids includes nucleic acids of a predetermined size (the target nucleic acid can have a known sequence, and the collected target nucleic acid can be of a predetermined desired size [0051, 0083]).
Regarding claim 6, modified Yann teaches the method of claim 1, but is silent to the method further comprising isolating DNA by treating the solution of isolated nucleic acids with RNase.
Marshall further teaches that performing nuclease digestion by adding RNase to the FFPET sample before electrophoresis results in RNA-free DNA extractions [0422].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method in modified Yann by adding RNase to the FFPET sample before electrophoresis, as taught in Marshall, such that RNA is digested in the equivalent of step ii of the instant claim 1, since this would result in RNA-free DNA extractions [0422 in Marshall]. Furthermore, Marshall teaches the improvement as a known technique that is applicable to the base method in modified Liu. One skilled in the art could have applied the addition of RNase in Marshall in the same way to the base method in modified Yann, yielding predictable results (MPEP 2143(I)(D)).
Modified Yann is silent to the limitation wherein the RNase is added to the solution of isolated nucleic acids after the equivalent of step iv of the instant claim 1.
In general, the transposition of process steps or the splitting of one step into two, where the processes are substantially identical or equivalent in terms of function, manner and result, was held to not patentably distinguish the processes (e.g., Ex parte Rubin, 128 USPQ 440 (Bd. Pat. App. 1959); In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930)). See MPEP § 2144.04 (IV)(C). In the instant case, adding RNase to the sample in step ii, instead of after step iv, still results in the isolation of DNA (adding RNase to the FFPET sample before electrophoresis results in RNA-free DNA extractions [0422 in Marshall]).
Regarding claim 7, modified Yann teaches the method of claim 1, but is silent to the method further comprising isolating RNA by treating the solution of isolated nucleic acids with DNase.
Marshall further teaches that performing nuclease digestion by adding DNase to the FFPET sample before electrophoresis results in DNA-free RNA extractions [0422].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method in modified Yann by adding DNase to the FFPET sample before electrophoresis, as taught in Marshall, such that DNA is digested in the equivalent of step ii of the instant claim 1, since this would result in DNA-free RNA extractions [0422 in Marshall]. Furthermore, Marshall teaches the improvement as a known technique that is applicable to the base method in modified Yann. One skilled in the art could have applied the addition of DNase in Marshall in the same way to the base method in modified Yann, yielding predictable results (MPEP 2143(I)(D)).
Modified Yann is silent to the limitation wherein the DNase is added to the solution of isolated nucleic acids after the equivalent of step iv of the instant claim 1.
In general, the transposition of process steps or the splitting of one step into two, where the processes are substantially identical or equivalent in terms of function, manner and result, was held to not patentably distinguish the processes (e.g., Ex parte Rubin, 128 USPQ 440 (Bd. Pat. App. 1959); In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930)). See MPEP § 2144.04 (IV)(C). In the instant case, adding DNase to the sample in step ii, instead of after step iv, still results in the isolation of RNA (adding DNase to the FFPET sample before electrophoresis results in DNA-free RNA extractions [0422 in Marshall]).
Regarding claim 8, modified Yann teaches the method of claim 1, and Yann further teaches wherein the leading electrolyte comprises HCl-histidine (HCl-histidine may be used as a leading electrolyte [0076]).
Regarding claim 9, modified Yann teaches the method of claim 1, and Yann further teaches wherein the trailing electrolyte comprises MES (the terminating ions include MES [0073]).
Regarding claim 14, modified Yann teaches the method of claim 1, and further teaches wherein the centrifugal filter is a 3 kDa cut off filter (as stated in the rejection of claim 1 above, the centrifugal filter is a 3 kDa cut off filter [0108 in Schneider]).
Response to Arguments
Applicant’s arguments, see Remarks Pg. 4-5, filed 12/17/2025, with respect to the 35 U.S.C. § 103 rejections have been fully considered. All 35 U.S.C. § 103 rejections from the previous office action are withdrawn in view of the Applicant’s amendment. However, applicant’s arguments are moot in view of the new grounds of rejection.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/K.T./Examiner, Art Unit 1795
/LUAN V VAN/Supervisory Patent Examiner, Art Unit 1795