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 January 7, 2026, wherein claim 1 is amended and claim 6 is canceled. This application is a national stage application of PCT/JP2021/019014, filed May 19, 2021, which claims priority to foreign application JP2020/090405, filed May 25, 2020.
Claims 1-5 and 8-11 are pending in this application.
Claims 1-5 and 8-11 as amended are examined on the merits herein.
The finality of the October 9, 2025 office action is withdrawn in view of the new grounds of rejection introduced herein.
Withdrawn Rejections
Applicant’s amendment, submitted January 7, 2025, with respect to the rejection of claim 6 under 35 USC 103 for being obvious over Callahan et al. in view of Srinivasan et al. in view of Chua et al., has been fully considered and found to be persuasive to remove the rejection as claim 6 has been canceled. Therefore the rejection is withdrawn.
The following rejections of record in the previous action are maintained:
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 1-5 and 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Callahan et al. (US pre-grant publication 2019/0071665, of record in previous action) in view of Srinivasan et al. (US pre-grant publication 2014/0087366, of record in previous action)
Independent claim 1 claims a process for purifying a nucleic acid comprising steps of combining the nucleic acid with a solution containing a metal cation, contacting the nucleic acid further with an anionic adsorbent, washing the adsorbent and bound nucleic acid with a solution having pH 5.0 or less, and then recovering the nucleic acid by contacting the bound nucleic acid with a solution having pH 6.0 or more. Furthermore the wash solution is defined as either water (i.e. unbuffered water adjusted to pH 5 or less by addition of an acid) potassium chloride, glycine, citrate, or phosphate. Dependent claims 2-5 further define elements of the recovery solution. Dependent claims 8-9 further define the composition of the extraction or binding solution. Claims 10 and 11 define the anionic adsorbent as silica.
Callahan et al. discloses methods for the isolation of RNA and protein from a sample comprising contacting the sample with a silica-containing surface, which binds RNA and proteins from the sample. (p. 1 paragraphs 6-7) In some embodiments the sample bound to the support has a pH of less than 4 and a chloride salt at a concentration of greater than 2M. (p. 1 paragraph 8) The RNA can then be eluted with RNAse free water or TE buffer, which is an elution buffer having a pH of greater than 6. (p. 1 paragraph 9) In some embodiments the chloride salt is selected from a number of different options including alkali metals such as sodium, potassium, or lithium, or alkaline earth metals having a valence of 2, for example magnesium or calcium. (p. 1 paragraph 13)
Regarding claim 2, RNAse-free water and TE buffer are both considered to be solutions that do not inhibit nucleic acid amplification. Regarding claim 3, TE buffer is a buffer. Regarding claim 5, in the absence of any further definition, the water and buffer used in the elution buffer can be considered to be amplification reagents. Regarding claims 10 and 11, p. 2 paragraph 20 describes the silica surface as glass fibers or silica-coated magnetic beads.
The disclosure of Callahan et al. differs from that of the present claims in that it does not disclose an acidic wash buffer. However, Srinivasan et al. discloses a process for extracting nucleic acids from biological samples using divalent ions, proteases, detergents, and low pH conditions. (p. 1 paragraph 6) The sample is prepared under conditions that can include adding either a transition metal or alkaline earth metal to inactivate nucleases in the sample, then adding an extraction solution and acidic buffer, separating the nucleic acids, and then possibly amplifying the nucleic acids by PCR. (p. 1 paragraphs 7-14) Regarding the wash solution, in some embodiments this solution comprises hydrochloric acid, or an acidic amino acid. (p. 6 paragraph 102) It would have been obvious to one of ordinary skill in the art at the time of the invention to use an acidic wash solution in a nucleic acid isolation method as described by Callahan et al. One of ordinary skill in the art would have seen the disclosure of Callahan as being fairly generic as to what wash steps can be used, and would have reasonably expected that the acidic wash steps described by Srinivasan et al. would have worked in the protocol of Callahan et al. as well.
In one embodiment the wash is trifluoroacetic or hydrochloric acid ad pH 1-5, and the elution is carried out in a solution of NaOH and 50 mM TRIS at pH 8.0, (p. 5 paragraph 85) which meets the limitations of present claim 1 and dependent claims 2-4. In particular, an aqueous solution of hydrochloric acid without a further buffer meets the limitation of “water” as recited in claim 1 for the wash solution. (See e.g. p. 34 lines 10-13 of the specification) Because the recovered nucleic acids can then be used for PCR, they are reasonably considered to be free of substances that interfere with PCR. Regarding claim 5, the term “nucleic acid amplification reagent” is not defined in the claims or specification, it is seen as including any reagent that could be present in an amplification reaction, including for example the base and buffer present in the extraction solution.
For these reasons the invention taken as a whole is prima facie obvious.
Response to Arguments: Applicant’s arguments, submitted January 7, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejection. Applicant argues that this rejection is moot in view of the incorporating of the limitations of claim 6 into claim 1. However, a review of the present specification and the disclosures of Callahan and Srinivasan indicates that the prior art would in fact render obvious an embodiment wherein the wash solution is unbuffered water with an acid added to adjust to pH 1-5, which falls within the scope of “water” as interpreted in view of the specification. Therefore this rejection is deemed proper and maintained.
The following new grounds of rejection are introduced:
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-5, 8, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Oommen et al. (US pre-grant publication 2018/0105908, cited in PTO-892)
Independent claim 1 claims a process for purifying a nucleic acid comprising steps of combining the nucleic acid with a solution containing a metal cation, contacting the nucleic acid further with an anionic adsorbent, washing the adsorbent and bound nucleic acid with a solution having pH 5.0 or less, and then recovering the nucleic acid by contacting the bound nucleic acid with a solution having pH 6.0 or more. Furthermore the wash solution is defined as either water (i.e. unbuffered water adjusted to pH 5 or less by addition of an acid) potassium chloride, glycine, citrate, or phosphate. Dependent claims 2-5 further define elements of the recovery solution. Dependent claims 8-9 further define the composition of the extraction or binding solution. Claims 10 and 11 define the anionic adsorbent as silica.
Oommen et al. discloses a method for extracting nucleic acids from a sample comprising adding a lysis buffer to a sample followed by a binding buffer, contacting the resulting solution with a portable nucleic acid extraction apparatus, washing the apparatus with a washing buffer, and eluting nucleic acids from the apparatus with an elution buffer. (p. 1 paragraphs 5-6) The tip of said apparatus is configured to bind nucleic acids. (p. 1 paragraph 19) The apparatus including the tip is preferably made of materials including polystyrene, glass, and silica. (p. 2 paragraphs 25-26) In a particular embodiment the nucleic acid binding portion of the apparatus is a fiber, such as a silica fiber, meeting the limitations of the adsorbent in claims 1 and 10. (p. 2 paragraphs 28-29) In a preferred embodiment the binding buffer contains sodium hypochlorite, which contains an alkali metal cation as recited in present claims 1 and 8, and glycine-HCl at pH 2-4, the wash buffer contains glycine-HCl, and the elution buffer contains TRIS-HCl at pH 8.8. (p. 2 paragraph 34) The wash buffer is further described as containing a salt that can include potassium chloride, as well as glycine-HCl as a buffer. (p. 5 paragraph 52) The elution buffer can contain TRIS-HCl at a concentration of 1 mM. (p. 5 paragraph 53) In a specific example (example 1
Regarding claim 2, TRIS buffer is considered to be a solution that does not inhibit nucleic acid amplification. Regarding claim 3, TE buffer is a buffer. Regarding claim 5, in the absence of any further definition, the water and buffer used in the elution buffer can be considered to be amplification reagents.
For these reasons Oommen et al. anticipates the present claims.
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 1-5, 8, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Oommen et al. (US pre-grant publication 2018/0105809, cited in PTO-892)
The disclosure of Oommen et al. is discussed above. While as discussed above, Oommen et al. is considered to anticipate the present claims, even assuming for the sake of argument that Oommen et al. does not specifically disclose that the Glycine-HCl wash buffer is acidic, it would have been obvious to one of ordinary skill in the art at the time of the invention to use a wash buffer having the claimed acidic pH. One of ordinary skill in the art would have seen the use of an acidic pH to bind the nucleic acids and an alkaline pH to release them as suggesting that the wash step, wherein nucleic acids are to be retained on the solid phase, should also be carried out at a pH similar to the binding step.
Therefore the invention taken as a whole is prima facie obvious.
Claims 1-5, 8, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Michelsen et al. (US patent 6355792, cited in PTO-892)
Independent claim 1 claims a process for purifying a nucleic acid comprising steps of combining the nucleic acid with a solution containing a metal cation, contacting the nucleic acid further with an anionic adsorbent, washing the adsorbent and bound nucleic acid with a solution having pH 5.0 or less, and then recovering the nucleic acid by contacting the bound nucleic acid with a solution having pH 6.0 or more. Furthermore the wash solution is defined as either water (i.e. unbuffered water adjusted to pH 5 or less by addition of an acid) potassium chloride, glycine, citrate, or phosphate. Dependent claims 2-5 further define elements of the recovery solution. Dependent claims 8-9 further define the composition of the extraction or binding solution. Claims 10 and 11 define the anionic adsorbent as silica.
Michelsen et al. discloses a method for isolating and purifying nucleic acids from a sample comprising diluting the sample with an acidic binding buffer, contacting the sample with a carrier material which is an inorganic hydroxide, separation, and elution in an alkaline solution. (column 2 lines 14-30) Furthermore in a preferred embodiment a wash buffer having a pH of between 3-6 and an elution buffer having a pH of 7.5-9 are used. (column 2 lines 31-36) In particular, the carrier material can be silica. (column 2 line 64 – column 3 line 4) The carrier can also be in the form of fibers or particles, as described in present claim 10. (column 3 lines 5-10) The binding buffer preferably contains a cation such as potassium, as well as a buffering ion which can be citrate. (col. 3 lines 11-28) Still further the wash buffer can use the same buffers (e.g. citrate) as the binding buffer. (column 3 lines 36-40)
Regarding claim 2, tris-EDTA buffer is considered to be a solution that does not inhibit nucleic acid amplification. Regarding claim 3, Tris buffer is a buffer. Regarding claim 5, in the absence of any further definition, the water and buffer used in the elution buffer can be considered to be amplification reagents.
The disclosure of Michelsen et al. differs from that of the present claims in that Michelsen et al. discloses a pH range of 4-7 for the wash buffer (column 3 lines 38-40) This range substantially overlaps with the claimed range of less than 5, and indicates that one of ordinary skill in the art would have regarded the pH of the wash buffer as a result-effective variable. In view of these factors it would have been obvious to one of ordinary skill in the art at the time of the invention to use a wash buffer having a pH of 5 or less in the method described by Michelsen et al.
Therefore the invention taken as a whole is prima facie obvious.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-5 and 8-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 12264311. (of record in previous action, herein referred to as ‘311) in view of Callahan et al. (US pre-grant publication 2019/0071665, of record in previous action) in view of Srinivasan et al. (US pre-grant publication 2014/0087366, of record in previous action)
Specifically, claims 1 and 3 of ‘311 claim methods for isolating nucleic acids comprising steps of contacting the specimen with an extraction solution, then bringing the solution into contact with an anionic adsorbent, contacting the adsorbent with a washing solution, and then contacting it with a collection solution. Furthermore the washing solution comprises a basic compound which is reasonably considered to be a buffer, and has a pH lower than the pKa value of the basic compound while the collection solution has a pH higher than the pKa value of the basic compound. Furthermore claim 2 of ‘311 requires that the extraction solution contains a metal cation having a valence of 2 or higher. Still further, claim 4 of ‘311 specifies that the pKa of the conjugate acid of the basic compound is between 4-6. While the method claimed by ‘311 does not specifically require that the wash solution has a pH of 5 or less or that the collection solution has a pH of 6 or more, it would have been obvious to one of ordinary skill in the art at the time of the invention to carry out the process defined by the claims of ‘311 having these pH values. Specifically, since the pKa value of the conjugate acid of the basic compound is between 4-6, the claims therefore define ranges of below and above this value that substantially overlap the ranges recited in present claim 1.
The claims of ‘311 do not specifically describe binding the nucleic acid to the solid phase using a concentration of 1M or more of the divalent metal as recited in claim 1 or using a silica solid phase as recited in claims 10 and 11. However, as discussed previously under 35 USC 103, Callahan et al. describes these elements for a similar method of purifying a nucleic acid. Furthermore regarding claims 2-5, Srinivasan et al. discloses as described above under 35 USC 102, including steps of extracting, binding, and collecting nucleic acids from a solid support similarly to the process claimed by ‘311. As discussed under 35 USC 103, Srinivasan et al. further describes the use of a collection solution that meets the requirements of present claims 2-4. It would have been obvious to one of ordinary skill in the art at the time of the invention to use the collection solutions described by Srinivasan et al. in the method claimed by ‘311. One of ordinary skill in the art would have seen these two processes to be similar enough that the collection solutions described in more detail by Srinivasan et al. would have performed the same function as those used in the method claimed by ‘311.
Conclusion
No claims are allowed in this 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 1/13/2026