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 .
Detailed Action
This office action is a response to applicant’s communication submitted April 22, 2026, wherein claims 8 and 16 are amended. This application is a national stage application of PCT/KR2021/014744, filed October 20, 2021, which claims benefit of foreign application 10-2021-0005968, file d January 15, 2021.
Claims 8, 11, 13, 14, and 16 are pending in this application.
Claims 8, 11, 13, 14, and 16 as amended are examined on the merits herein.
Withdrawn Rejections
Applicant’s amendment, submitted April 22, 2026, with respect to the rejection of claims 8, 11, 13, 14, and 16 under 35 USC 103 for being obvious over Hillebrand et al., has been fully considered and found to be persuasive to remove the rejection as the claims have been amended to require a specific binding matrix which is not the same ones described by Gerdes et al. Therefore the rejection is withdrawn.
Applicant’s amendment necessitates the following new grounds of rejection:
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.
Claims 8, 11, 13, 14, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Hillebrand et al. (US pre-grant publication 2001/0041332, of record in previous action) in view of Lai et al. (US pre-grant publication 2016/0108393, of record in previous action) in view of Kelso et al. (US pre-grant publication 2012/0231466, cited in PTO-892) in view of Kenrick et al. (US pre-grant publication 2016/0017315, cited in PTO-892) in view of Schrader et al. (Reference of record in previous action)
Independent claim 8 claims a method for isolating and amplifying nucleic acids from a sample comprising immersing the sample in a buffer defined as containing a number of specific components, incubating the solution at room temperature, transferring the solution to a column containing a membrane filter, immobilizing the nucleic acids on the filter and removing the buffer compositions, and subjecting the filter to a nucleic acid amplification reaction without performing any further washing or elution step.
Hillebrand et al. discloses a method for isolating nucleic acids such as DNA from complex starting materials comprising binding to a solid support using solutions comprising antichaotropic salts and not including chaotropic agents. (p. 2 paragraphs 18-20) In addition to the antichaotropic salt, the lysis buffer can contain Tris-HCl, EDTA, and sodium dodecylsulfate, and preferably an alcohol such as ethanol. (p. 2 paragraph 21) The solid phase can preferably be a conventional solid phase such as glass or silica, including glass fibers or membranes. (p. 2 paragraph 23, p. 3 paragraph 39) Starting materials can include biological materials such as blood and tissues. (p. 2 paragraph 25) The antichaotropic salt can include sodium salts, and can have a preferred concentration of less than 1M. (p. 3 paragraphs 43-44) A specific lysis buffer is described containing 3M potassium chloride, 2% CTAB, 18.2 mM TRIS-HCl, 12.5 mM EDTA, and 2.8% polyvinyl pyrrolidone, to which 500 µL whole blood and 200 µL isopropanol (about 40%) is added before transfer to a centrifugation column. (p. 9 paragraphs 161-169) Hillebrand et al. specifically discloses a method comprising steps of lysis of the starting material using the lysis buffer, binding to a solid phase such as a spin column, washing, and elution. (p. 3 paragraphs 31-35) Elution is preferably carried out by Tris-HCl, or TE buffer. (pp. 3-4 paragraph 50)
While Hillebrand et al. does not specifically disclose an embodiment wherein sodium chloride is used as the antichaotropic salt, as discussed previously the reference exemplifies compositions comprising potassium chloride, and further suggests that the antichaotropic ions can include sodium ions. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use sodium chloride as the antichaotropic salt, in view of the teaching that these two ions are equivalents usable for the same purpose.
While Hillebrand et al. does not specifically disclose a buffer comprising all of the specific components ethanol, SDS, EDTA, and Tris-HCl, the reference does disclose all of these components as preferred additives for the lysis buffer, thereby motivating one of ordinary skill in the art to use them together. Regarding the specific concentrations recited in present claim 8, the concentrations described by Hillebrand et al. substantially overlap those in the claims, thereby rendering them obvious.
Furthermore while Hillebrand et al. describes adding the lysis buffer comprising the antichaotropic salt and other additives besides ethanol to the sample first, followed by adding the ethanol after the lysis is complete, after the step of adding ethanol the composition can include Tris-HCl, NaCl, SDS, and ethanol. Therefore at this step of the process the buffer would infringe the present claims. Furthermore as discussed in MPEP 2144(IV)(C), changes in the sequence of adding ingredients is considered to be prima facie obvious, so it would also have been obvious to one of ordinary skill in the art to combine the ethanol and the other lysis buffer components before adding the sample, in the absence of evidence that the sequence of adding ingredients is critical.
While Hillebrand does not disclose a method wherein the column is a syringe and the application of the sample to the column is performed by applying pressure to the column, Lai et al. discloses a device for rapid extraction of nucleic acids comprising a syringe comprising a filter membrane. (p. 1 paragraphs 6-10) A sample to be extracted is applied to the syringe and the plunger is activated to apply pressure and force the sample through the membrane, in accordance with the steps recited in present claim 8.
It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use a syringe comprising a filter membrane as described by Lai et al. as the column in the method described by Hillebrand et al. One of ordinary skill in the art would have seen the disclosure of Lai et al. as describing these syringe columns as an improvement over prior art spin columns and therefore would have found it to be obvious to substitute them for spin columns, for example to produce a kit for DNA extraction that was fast and portable.
The method of claim 8 as presently amended further differs from the disclosure of Hillebrand and Lai in that it requires directly subjecting the membrane filter to a nucleic acid amplification reaction without performing a washing or elution step. However, Kelso et al. discloses compositions for isolating and purifying nucleic acids, utilizing a device wherein blood cells are lysed and retained on a membrane. (p. 1 paragraph 10 – p. 2 paragraph 13) The solid phase can be any suitable material. (p. 3 paragraph 47) In some embodiments the membrane itself is placed directly into a PCR reaction without a further elution step, and is itself used as the PCR template. (p. 5 paragraph 71, also figs. 1 and 10)
Kenrick et al. discloses a method for amplifying nucleic acids by contacting a solid support with a nucleic acid and amplifying the nucleic acid in the presence of said support. (p. 2 paragraph 23) In some embodiments neither washing nor elution steps are used. (p. 3 paragraph 45) In particular, these methods reduce the number of steps involved, reduce the amount of time required, and avoid the loss of target material. (p. 3 paragraph 46) Furthermore the use of washing steps to remove denaturants can lead to the loss of smaller nucleic acid species from the sample, such as viral nucleic acids. (p. 5 paragraph 98)
It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to directly use a filter (e.g. a glass or silica membrane) to which nucleic acids have been bound by the method of Hillebrand et al. in view of Lai, as the template in a PCR reaction without further elution. One of ordinary skill in the art would have been motivated to do so as Kelso et al. and Kenrick et al. disclose that a separate elution step is not in fact necessary and a membrane containing a bound nucleic acid can in fact be used in a subsequent amplification reaction.
It would additionally have been obvious to one of ordinary skill in the art at the time of the invention to optimize the purification scheme in such a way as to not require washing steps. One of ordinary skill in the art would have expected this to be beneficial because Kenrick discloses that certain nucleic acids are lost from the sample during washing, and that avoiding this step would be beneficial.
Still further, regarding the specific concentrations of SDS and ethanol in the lysis buffer, Schrader et al. discloses that these compounds are known to inhibit PCR reactions, and are furthermore known to be introduced during sample processing. (p. 1018right column second paragraph) Therefore one of ordinary skill in the art at the time of the invention would have been aware that these substances can inhibit PCR and would have found it to be obvious to use lower concentrations in order to minimize the amount of inhibitors ultimately introduced into the PCR reaction.
Regarding claim 11, Hillebrand et al. discloses that the lysis step can involve incubating for e.g. 5 minutes (p. 5 paragraph 73) or 10 minutes. (p. 8 paragraph 125)
Regarding claim 13, Hillebrand et al. notes a number of different biological materials from which nucleic acids can be extracted including for example whole blood. (p. 3 paragraph 42)
Regarding claim 14, Hillebrand et al. does not specifically disclose using this method to purify peptide nucleic acid. (PNA) However, Lai et al. discloses extraction of PNA on a membrane filter. (p. 3 claim 3) It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use the method described by Hillebrand to isolate PNA. One of ordinary skill in the art would have found this to be obvious in view of the fact that it is known that there is a need in the art to isolate PNA and furthermore that binding to a filter membrane can be used to accomplish this.
Regarding claim 16, Hillebrand et al. describes using the bound nucleic acids in a PCR reaction. (p. 5 paragraph 78)
Therefore the invention taken as a whole is prima facie obvious.
Response to Arguments
Applicant’s arguments, submitted April 22, 2026, have been fully considered as they apply to the newly introduced ground of rejection above.
Firstly, all arguments based on the fact that the method described by Gerdes et al. using a solid phase that differs from those presently claimed are not relevant to the presently pending rejection, because Gerdes et al. is no longer cited in the present rejection and the references discussing direct amplification from a solid phase, Kelso et al. and Kenrick et al., allow for a wide variety of solid phases and would accommodate the glass or silica solid phases used by Hillebrand.
Applicant further argues that the specific use of sodium chloride in the presently claimed method has technical significance because sodium chloride occupies a specific position in the spectrum of antichaotropic ions leading to the salting out and precipitation of nucleic acids while solubilizing proteins. By this reasoning one of ordinary skill in the art would not have regarded substitution of sodium for potassium as simply substituting one equivalent for another.
Firstly, it is noted that none of this reasoning is provided in the original disclosure of this application. It does not appear to have been part of the original reasoning behind the choice of NaCl as the salt used in the isolation buffer as opposed to some other salt. Secondly, attorney argumentation cannot be taken as a statement of fact. The argument that one of ordinary skill in the art would not have regarded sodium and potassium as equivalents must be taken alongside the fact that the disclosure of Hillebrand et al. lists ammonium, cesium, potassium, and sodium ions as different options that can be used interchangeably, suggesting that they are in fact interchangeable. Hillebrand et al. further discloses that the optimal concentration of salt is less than 1M. (p. 3 paragraph 44) Overall, the arguments presented are not persuasive to establish that there somehow would not be a prima facie case of obviousness for selecting sodium as the cation.
Still further, Applicant argues that Hillebrand’s method could not function if ethanol were included in the composition from the beginning rather than added after the sample is already lysed. This is contradicted by p. 2 paragraph 21 of Hillebrand, which describes a lysis/binding buffer preferably containing ethanol.
Regarding the disclosure of Lai et al. and the use of a syringe to apply pressure to the sample, Applicant argues that this substitution goes beyond the scope of a mere structural substitution. However, the proper standard to use in this case is the substitution of equivalents usable for the same purpose. In the present case a centrifuge and a syringe perform the same function of exerting a force on a sample to move it through a membrane. One of ordinary skill in the art would have seen that both of these methods have been used in the art for this purpose and would have regarded it as prima facie obvious to substitute one for the other.
Finally, Applicant argues that because Schrader discloses that SDS and ethanol inhibit amplification reactions, one of ordinary skill in the art would have omitted them entirely rather than simply minimizing the amount used. However, this would only be the case if these elements were seen to be unnecessary. If, as in the present case, they were seen to perform a necessary function then the obvious course of action would be to determine the optimal or minimum necessary amount to include, rather than eliminate them entirely.
For these reasons the rejection is deemed proper and maintained.
Conclusion
No claims are allowed in this action. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Y Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ANDREA OLSON/ Primary Examiner, Art Unit 1693 6/5/2026
Prosecution Insights