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 .
Response to Amendments
This Office Action is in reply to Applicant’s response of 1 May 2026. Applicant’s remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance.
Note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is made FINAL.
Withdrawn Objections and Rejections
The objections to the specification in the Office Action mailed 5 February 2026 are withdrawn in view of Applicant’s amendments to the specification filed 1 May 2026
The objections to claims 1 and 10 in the Office Action mailed 5 February 2026 are withdrawn in view of Applicant’s amendments to the claims filed 1 May 2026.
All objections and rejections of claims 2-3, 5, and 11-12 in the Office Action mailed 5 February 2026 are withdrawn in view of Applicant’s amendments to the claims filed 1 May 2026 canceling claims 2-3, 5, and 11-12; rejections that recited any of claims 2-3, 5, and 11-12 are modified as necessitated by their cancelation.
Applicant’s arguments, see remarks pages 10-11, filed 1 May 2026, with respect to the rejections of claims 10 and 14 under 35 U.S.C. 103 and for non-statutory double patenting have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, new grounds of rejection are made and are necessitated by the amendments to the claims filed 1 May 2026. See 35 U.S.C. 103 rejection of claims 10 and 14 below and non-statutory double patenting rejection of claims 10 and 14 below.
Applicant’s arguments, see remarks pages 10-11, filed 1 May 2026, with respect to claims 1, 4, and 7-9 have been fully considered and are persuasive. The rejections of claims 1, 4, and 7-9 under 35 U.S.C. 103 and for non-statutory double patenting have been withdrawn. See Allowable Subject Matter section below.
Claim Status
Claims 1, 4, 6, 10, and 13 have been amended.
Claims 2-3, 5, and 11-12 are canceled.
Claims 1, 4, 6-10, and 13-14 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) filed 28 April 2026 is considered, initialed, and attached hereto.
Claim Objections
New - Necessitated by Amendment
The claims are objected to because the lines are crowded too closely together, making reading difficult. Substitute claims with lines one and one-half or double spaced on good quality paper are required. See 37 CFR 1.52(b).
Claim 1 is objected to because claim 1 lines 33-37 recite “thereby dehydrating a content of the wells, reducing a volume, causing accumulation of the content inside the second well, forming the three-part complex in the presence of the target nucleic acid fragment in the content, cleaving the substrate nucleic acid fragment, and separating the fluorescent substance from the quencher” immediately following the recitation “(a3’) replacing the sealing liquid with a water-absorbing organic solvent”. The clause “forming the three-part complex in the presence of the target nucleic acid fragment in the well, cleaving the substrate nucleic acid fragment, and separating the fluorescent substance from the quencher” appears to be stating a condition that may arise when step (a) has been performed, which is how it will be interpreted for the purpose of examination, but the placement in line with the replacement step suggests that it is specific to and caused by the step of replacing the sealing liquid with a water-absorbing organic solvent.
Appropriate correction is required.
Claim Interpretation
Maintained - Modified as Necessitated by Amendment
Claim 1 lines 10-12 and claim 6 lines 14-16 recite the conditional limitation “when the fluorescent substance is separated from the quencher due to a cleavage caused by nuclease activity of the three-part complex, fluorescent light is emitted by irradiation with excitation light”. It is noted that the broadest reasonable interpretation of a method requires only those steps that must be performed and does not include steps that are not required (see MPEP §2111.04 II.). Given that the recitation “when” is clearly conditional in nature and the recited “target nucleic acid fragment” is not required to be present for the method to be done, this claim language is not given patentable weight when comparing the claim 1 and the claims that depend from it with the prior art. This same rationale applies to the recitation in claim 1 lines 14-16 and claim 6 lines 18-20 of “thereby forming the three-part complex in a case where the target nucleic acid fragment is present in the sample, cleaving the substrate nucleic acid fragment, and separating the fluorescent substance from the quencher”, as the use of the phrase “in a case where” and lack of requirement for the presence of the target nucleic acid fragment renders this claim limitation conditional such that it is not given patentable weight. This same rationale applies to the recitation in claim 1 lines 35-37 of “forming the three-part complex in the presence of the target nucleic acid fragment in the content, cleaving the substrate nucleic acid fragment, and separating the fluorescent substance from the quencher”, as the use of the phrase “in the presence of” creates a condition for the forming, cleaving, and separating limitation, which along with the lack of requirement for the presence of the target nucleic acid fragment renders the claim limitation conditional such that it is not given patentable weight.
Response to Arguments
Applicant did not present arguments regarding the above claim interpretation. The claim interpretation has been modified to maintain references to claim and line numbers consistent with the amended claims.
Claim Rejections - 35 USC § 103
Maintained - Modified as Necessitated by Amendment
Claims 6 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Ching et al. (US PG PUB 2024/0294970, 102(a)(2) effectively filed date of 17 December 2020, cited in previous office action), herein Ching, in view of Makino and Kunitomi (EP 3101115, published 7 December 2016, cited in IDS), herein Makino.
Regarding claim 6, Ching teaches a method for detecting a target nucleic acid fragment in a sample (“a method of assaying for a plurality of different target nucleic acids in a sample” [0013]) comprising mixing the sample, a gRNA complementary to the target nucleic acid fragment, and a CRISPR/Cas family protein which is immobilized on a surface of a particle in a container (“The method can comprise receiving the plurality of sub-samples in a detection chamber and contacting the plurality of sub-samples with at least one programmable nuclease probe disposed on a surface of said detection chamber. The at least one programmable nuclease probe can comprise a guide nucleic acid complexed with a programmable nuclease” [0265], “the guide nucleic acid is complementary to the target nucleic acid” [0199], and “Several programmable nucleases are consistent with the systems and methods of the present disclosure. For example, CRISPR/Cas enzymes are programmable nucleases that can be used to implement the methods and systems disclosed herein” [0083] teaching mixing the components of the three-part complex; “a surface at a known location” [0006], “programmable nucleases immobilized at the known locations” [0009], and “the surface can comprise a surface of a fluidic chamber or a bead” [0010] teaching that the programmable nuclease may be immobilized to a surface that is a bead/particle) and forming the three-part complex including the CRISPR/Cas family protein, the gRNA, and the target nucleic acid fragment on the particle (“forming activated complexes at one or more of the known locations, wherein the activated complexes comprise (i) one of the different non-naturally occurring guide nucleic acids, (ii) a programmable nuclease, and (iii) one of the different target nucleic acids” [0013]; and the known locations are on a surface that can comprise a bead/particle as described above). Ching also teaches contacting the three-part complex with a substrate nucleic acid fragment (“contacting a surface with the sample” [0013]; “wherein the surface comprises: (i) […] non-naturally occurring guide nucleic acids” [0013]; “forming activated complexes […], wherein the activated complexes comprise (i) one of the […] guide nucleic acids, (ii) a programmable nuclease, and (iii) one of the different target nucleic acids” [0013]; “in some embodiments, the programmable nuclease is immobilized to the device surface” [0197]; Fig. 1A-B wherein the surface is a bead as discussed above; “the surface comprises […] (ii) a plurality of reporters” [0013]) wherein the substrate nucleic acid fragment is labeled with a fluorescent substance and a quencher (“the reporter may comprise a fluorescent label joined to a quencher by a short polynucleotide sequence” [0081]). Ching also teaches that in a case where the target nucleic acid fragment is present the three-part complex is formed (“the trans cleavage activity of the CRISPR enzyme can be activated when the guide nucleic acid comprising a tracrRNA and crRNA are complexed with the target nucleic acid” [0087]), the substrate nucleic acid is cleaved by nuclease activity (a programmable nuclease as disclosed herein can, in some cases, bind to a target sequence or target nucleic acid to initiate trans cleavage of a reporter molecule” [0081]), and the fluorescent substance is separated from the quencher (“upon cleavage of the polynucleotide, the fluorescent label is separated from the quencher” [0081]). Ching also teaches that this separation of the fluorescent label from the quencher leads to a detectable indication of the presence of the target nucleic acid fragment based on fluorescent light emitted by the fluorescent substance in response to irradiation with excitation light (“cleavage of the polynucleotide results in a change in a signal […] little to no fluorescence is detectable from the fluorescent label when joined to the quencher. However, upon cleavage of the polynucleotide, the fluorescent label is separated from the quencher, resulting in a significant and detectable increase in fluorescent signal upon excitation of the label” [0081]).
However, Ching does not teach the contacting step being performed in a reaction space having a volume of 10 aL to 100 pL. This deficiency is made up for in the teachings of Makino.
Regarding claim 6, Makino teaches a “biomolecule analysis method” ([0018]) applicable to detection of target nucleic acids (“as a biomolecule to be analyzed, any of DNA, RNA, miRNA, mRNA […], and a protein is selected” [0042]) by fluorescence (“may generate a signal by any one of fluorescence” [0028]; “detects […] fluorescence […] as a signal” [0082]. Makino teaches that this method is performed so that the reaction occurs in microspaces (“as a result, each of the microspaces 11 becomes an independent reaction chamber”) that have a volume that is exemplified as being less than or equal to 100 pL (“for example, the volume of the microspace 11 is equal to or less than 100 picoliters” [0048]). Makino also teaches that the same biomolecules can be analyze using a second embodiment ([0074-0075]), wherein the reaction space (“the amount of liquid that fills the wells 26 may be appropriately set according to the number of through holes 25a” [0119]; “the plurality of well 26 becomes a plurality of independent reaction chambers 36 (reaction containers for nucleic acid detection) [0120]; FIGs 6-8) may have a volume of about 60 fL (“the volume of the through hole 25a is about 60 femtoliters” [0079]). Because the 60 fL embodiment falls within the claimed range of 10aL to 100 pL, the claimed range is anticipated (MPEP §2131.03 I.). Additionally, the claimed range, a reaction space having a volume of 10 aL to 100 pL, overlaps with the disclosed reaction space volumes of less than or equal to 100pL, so a prima facie case of obviousness exists (MPEP §2144.05 I.).
Regarding claim 13, Makino teaches a kit for detecting a target nucleic acid fragment comprising a substrate having a surface (“a biomolecule analysis kit according to a first aspect of the present invention includes a reaction container configured to perform an enzymatic reaction” [0019]; also see [0024, 0035]) on which a well having a volume of 10 aL to 100 pL is formed (see discussion of claim 6 above). Ching teaches one such enzymatic reaction comprising a gRNA complementary to the target nucleic acid fragment; a CRISPR/Cas family protein immobilized on a surface of a particle; and a substrate nucleic acid fragment, wherein the CRISPR/Cas family protein expresses nuclease activity after forming a three-part complex with the gRNA and the target nucleic acid fragment, the substate nucleic acid fragment is labeled with a fluorescent substance and a quencher, and in a case where the nuclease activity of the three-part complex separates the fluorescent substance from the quencher, fluorescent light is emitted by irradiation with excitation light as discussed for claim 6 above.
In view of the teachings of Makino, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the methods of Ching so as to have reduced the quantities and volumes taught by Makino and to employ the methods of Ching in kits utilizing reduced quantities and volumes taught by Makino. One of ordinary skill in the art would have been motivated to have made such a modification for advantages as taught by Makino of the use of such smaller volumes, such as the teaching that smaller reaction spaces facilitate shorter reaction times (Makino [0048, 0080]). One of ordinary skill in the art would have a reasonable expectation of success in combining the teachings of Ching and Makino because both teach methods and structures for performing enzymatic detection of nucleic acids that are detected by fluorescence. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Arguments
Applicant's arguments filed 1 May 2026 have been fully considered but they are not persuasive. Applicant argues that claims 6 and 13 are distinguishable over the prior art because Ching does not describe or suggest a CRISPR/Cas family protein immobilized on a surface of a particle and that the immobilization on a particle is significant because the instant specification finds that it significantly improves detection sensitivity. However, Ching does teach an embodiment where a CRISPR/Cas family protein is immobilized on a surface of a particle. Ching teaches in [0006] that each guide nucleic acid is immobilized to a surface at a known location and in [0009] that guide nucleic acids may be immobilized to a surface by being releasably bound to Cas nucleases that are immobilized at the known location by a linkage. From this, one of ordinary skill in the arts understands that there are embodiments where the Cas nucleases are immobilized to known locations on the surface. Since Ching teaches in [0010] that the surface can be a surface of a bead, which is interpreted to fall within the broadest reasonable interpretation of a particle, this combination of teachings in Ching when read together teach a Cas nuclease immobilized at a known location on a surface of a particle. Therefore, Applicant’s argument that claims 6 and 13 are non-obvious over the cited prior art is not persuasive.
New - Necessitated by Amendment
Claims 10 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Ching et al. (US PG PUB 2024/0294970, 102(a)(2) effectively filed date of 17 December 2020, cited in previous office action), herein Ching, in view of Makino and Kunitomi (EP 3101115, published 7 December 2016, cited in IDS), herein Makino, as applied to claims 6 and 13 above, and further in view of Simon et al. (US PG PUB 2014/0004539, published 2 January 2014 with effectively filed date 15 June 2012, cited in previous office action), herein Simon, and European Union Reference Laboratory for GM Food and Feed (“Report on the In-house Validation of a DNA Extraction Method from Oilseed rape Grains and Validated Method” JRC publication JRC85313, 18 October 2013), herein EU.
Regarding claim 10, Ching and Makino teach a kit for detecting a target nucleic acid fragment as discussed for claim 13 above. Ching also teaches that, instead of the CRISPR/Cas family protein being immobilized on a surface of a particle as in claim 13, it may instead be immobilized on the inner surface of a well (“the programmable nuclease probe (e.g., a CRISPR probe) can be immobilized to an immobilization matrix. In some cases, the interior side of the immobilization matrix may be exposed to an inside wall” [0194]; see Example 4 in its entirety, particularly: “96-well streptavidin coated plate” [0353] and “results of this experiment (See FIGS. 10A-10F) […] FIGS. 10A and 10D show results where […] a complex of biotinylated RNA and CAS protein were immobilized” [0368]). However, Ching and Makino do not teach a well having a first well and a second well arranged at a bottom of the first well and having a smaller capacity than the first well, the CRISPR/Cas family protein being immobilized on an inner surface of the second well, and the kit further comprising a water-absorbing organic solvent wherein the water-absorbing organic solvent is 1-heptanol, 1-octanol, or 1-nonanol. These deficiencies are made up for in the teachings of Simon and EU.
Regarding claim 10, Simon teaches a well that has a first well (Figure 1(A) “Large Sample Well”) and a second well arranged at a bottom of the first well and having a smaller capacity than the first well (Figure 1(A) “Smaller Wells”; “FIG. 1 […] (a) A side view of the plate shows that each of the 96 large wells contains 4 smaller wells” [0010]), effectively creating a separate reaction space in each second smaller well (“acceptor beads and biotinylated detection antibodies against 4 different antigens […] were dispensed into each of the four DEX wells per larger PEG well” [0110]). Because Ching teaches the CRISPR/Cas family protein being immobilized on an inner surface of a well that makes up the reaction space (see discussion of claim 2 above) and the reaction space of Simon is the second smaller well, the combination of Ching, Makino, and Simon teach that the CRISPR/Cas family protein is immobilized on an inner surface of the second well. Additionally, Ching teaches that their method can by multiplexed by “spatial multiplexing wherein multiple different target nucleic acids are detected at the same time, but the reactions are spatially separated” ([0238]) and Simon teaches that having smaller wells inside the larger wells allows for spatial multiplexing by allowing “for the simultaneous detection of four antigens (4-plex assays)” ([0010]).
Regarding claim 10, EU teaches a process of extracting DNA for downstream analyses (“The method for DNA extraction described below is suitable for the isolation of high quality genomic DNA” page 8) using 1-octanol (“Add 10 mL Chloroform/1-Octanol (24:1) per tube” page 9).
Regarding claim 14, Ching teaches that the CRISPR/Cas family protein is a Cas12 protein or a Cas13 protein (“In some embodiments, the type V CRISPR/Cas effector protein is a Cas12 protein” [0018]; “In some embodiments, the type VI CRISPR/Cas effector protein is a Cas13 protein” [0018]).
In view of the teachings of Simon and Ching, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the spatial multiplexing described in Ching in view Makino with the spatial multiplexing using the wells taught by Simon. One of ordinary skill in the art would recognize that both provide the function of spatial multiplexing. One of ordinary skill in the art would find that the results of the substitution would have been predictable since both methods of multiplexing spatially separate individual reactions.
One of ordinary skill in the art would be motivated by EU’s teaching that their method extracts high quality genomic DNA to combine its materials, including 1-octanol, as part of the kit taught by the combination of Ching, Makino, and Simon, so that the kit can be used for extracting a DNA sample from which the target nucleic acid can be detected. One of ordinary skill in the art would have a reasonable expectation of success in this combination because the extraction with 1-octanol taught by EU simply provides an input for the detection accomplished by the other components of the kit and therefore would not prevent it from being used for the detection of target nucleic acids. Therefore, the invention as a whole of claims 10 and 14 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Arguments
Applicant’s arguments, see pages 10-12 of the remarks, filed 1 May 2026, with respect to the rejection of claims 10 and 14 under 35 U.S.C. 103 have been fully considered and are persuasive, as none of the references cited teach a water-absorbing organic solvent that is 1-heptanol, 1-octanol, or 1-nonanol. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the combination of the teachings of Ching, Makino, Simon, and EU. This new rejection is necessitated by the amendment of claim 10 (on which claim 14 depends) because the previous listing of claims did not claim a kit comprising a water-absorbing organic solvent.
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.
Maintained - Modified as Necessitated by Amendment
Claims 6 and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3 and 5 of U.S. Patent No. 12,522,859 and further in view of Ching et al. (US PG PUB 2024/0294970, 102(a)(2) effectively filed date of 17 December 2020, cited in previous office action), herein Ching.
Regarding instant claim 6, claim 3 of ‘859 depends on claim 1, which together recite a method for detecting a target nucleic acid fragment in a sample comprising steps with language identical or equivalent to the language of instant claim 6. Via its dependency on claim 1, claim 3 of ‘859 differs from the instant claim 6 in that it requires that the CRISPR/Cas family protein is a Cas12 protein or a Cas13 protein, the reaction space is a well formed in a baseplate, the opening of the well is sealed by a lipid membrane, and the method is performed without amplifying the target nucleic acid fragment. Nothing in the language of the instant claims exclude embodiments in which these requirements take place. However, ‘859 does not claim a method wherein the CRISPR/Cas family protein is immobilized on a surface of a particle, as required by instant claim 6. This deficiency is made up for in the teachings of Ching.
Regarding instant claim 6, Ching teaches a method wherein the CRISPR/Cas family protein is immobilized on a surface of a particle (e.g. a bead) (“a surface at a known location” [0006]; “programmable nucleases immobilized at the known locations” [0009]; and “the surface can comprise a surface of a fluidic chamber or a bead” [0010]). Ching also teaches a method wherein the sample, the gRNA, and the CRISPR/Cas family protein are mixed in a container (e.g. detection chamber) (“The method can comprise receiving the plurality of sub-samples in a detection chamber and contacting the plurality of sub-samples with at least one programmable nuclease probe disposed on a surface of said detection chamber. The at least one programmable nuclease probe can comprise a guide nucleic acid complexed with a programmable nuclease” [0265]) and form the three-part complex including the CRISPR/Cas family protein, the gRNA, and the target nucleic acid fragment on the particle (“forming activated complexes at one or more of the known locations, wherein the activated complexes comprise (i) one of the different non-naturally occurring guide nucleic acids, (ii) a programmable nuclease, and (iii) one of the different target nucleic acids” [0013] and the known locations are on a surface that can comprise a bead as described above).
Regarding instant claim 13, claim 5 of ‘859 depends on claim 4, which together recite a kit for detecting a target nucleic acid fragment in a sample comprising components with language identical or equivalent to the language of instant claim 13. Via its dependency on claim 4, claim 5 of ‘859 differs from instant claim 13 in that it requires that the CRISPR/Cas family protein is a Cas12 protein or a Cas13 protein and that the opening of the well is sealed by a lipid membrane. Nothing in the language of the instant claims exclude embodiments in which these requirements take place. However, ‘859 does not claim a kit wherein the CRISPR/Cas family protein is immobilized on a surface of a particle, as required by instant claim 13. This deficiency is made up for in the teachings of Ching.
Regarding instant claim 13, Ching teaches the CRISPR/Cas family protein being immobilized on a surface of a particle as discussed for instant claim 6 above.
In view of the teachings of ‘859 and Ching, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the methods of ‘859 with the methods of Ching so as to immobilize the CRISPR/Cas family protein to the surface of a particle and to perform the method without purifying the target nucleic acid fragment from the biological sample. Both ‘859 and Ching are in the same field of endeavor, using CRISPR/Cas family proteins to detect target nucleic acids, and the combined elements of the method of Ching would merely perform the same function in the combination of ‘859 and Ching as they do in Ching alone. Due to being in the same field of endeavor and the elements of Ching performing the same function they are disclosed as performing, one of ordinary skill in the art would recognize that the results of the combination of ‘859 and Ching are predictable. Therefore, instant claims 6 and 13 are obvious variations of claims 3 and 5 in ‘859 in view of Ching.
New - Necessitated by Amendment
Claim 10 and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 5 of U.S. Patent No. 12,522,859 and further in view of Simon et al. (US PG PUB 2014/0004539, published 2 January 2014 with effectively filed date 15 June 2012, cited in previous office action), herein Simon, and European Union Reference Laboratory for GM Food and Feed (“Report on the In-house Validation of a DNA Extraction Method from Oilseed rape Grains and Validated Method” JRC publication JRC85313, 18 October 2013), herein EU.
Regarding instant claim 10, claim 5 of ‘859 depends on claim 4, which together recite a kit for detecting a target nucleic acid fragment in a sample comprising components with language identical or equivalent to the language of instant claim 10. Via its dependency on claim 4, claim 5 of ‘859 differs from instant claim 10 in that it requires that the CRISPR/Cas family protein is a Cas12 protein or a Cas13 protein and that the opening of the well is sealed by a lipid membrane. Nothing in the language of the instant claims exclude embodiments in which these requirements take place, and in fact instant claim 14 requires that the CRISPR/Cas family protein is a Cas12 protein or a Cas13 protein. However, ‘859 does not claim a kit wherein the well has a first well and a second well arranged at a bottom of the first well and having a smaller capacity than the first well, the CRISPR/Cas family protein is immobilized on the inner surface of the second well, and the kit further comprising a water-absorbing organic solvent wherein the water-absorbing organic solvent is 1-heptanol, 1-octanol, or 1-nonanol. These deficiencies are made up for in the teachings of Simon and EU.
Regarding instant claim 12, Simon teaches a well that has a first well (Figure 1(A) “Large Sample Well”) and a second well arranged at a bottom of the first well and having a smaller capacity than the first well (Figure 1(A) “Smaller Wells”; “FIG. 1 […] (a) A side view of the plate shows that each of the 96 large wells contains 4 smaller wells” [0010]), effectively creating a separate reaction space in each second smaller well (“acceptor beads and biotinylated detection antibodies against 4 different antigens […] were dispensed into each of the four DEX wells per larger PEG well” [0110]). Because claim 5 of ‘859 recites the CRISPR/Cas family protein being immobilized on an inner surface of a well where the reaction occurs and the reaction space of Simon is the second smaller well, the combination of ‘859 and Simon is a kit wherein the CRISPR/Cas family protein is immobilized on an inner surface of the second well. Additionally, Simon teaches that having smaller wells inside the larger wells is advantageous because it allows for spatial multiplexing by allowing “for the simultaneous detection of four antigens (4-plex assays)” ([0010]).
Regarding instant claim 12, EU teaches a process of extracting DNA for downstream analyses (“The method for DNA extraction described below is suitable for the isolation of high quality genomic DNA” page 8) using 1-octanol (“Add 10 mL Chloroform/1-Octanol (24:1) per tube” page 9).
Regarding instant claim 14, claim 5 of ‘859 via its dependency on claim 4 recites that the CRISPR/Cas family protein is a Cas12 protein or a Cas13 protein.
In view of Simon’s teaching that their system of having a first well and a second well arranged at a bottom of the first well has the advantage in that it allows for spatial multiplexing, one of ordinary skill in the art would be motivated to combine Simon with the kit of ‘859. One of ordinary skill in the art would have a reasonable expectation of success because both Simon and ‘859 are reciting kits in which the reaction space is the interior of a well. One of ordinary skill in the art would further be motivated by EU’s teaching that their method extracts high quality genomic DNA to combine its materials, including 1-octanol, as part of the kit of claim 5 of ‘859, so that the kit can be used for extracting a DNA sample from which the target nucleic acid can be detected. One of ordinary skill in the art would have a reasonable expectation of success in this combination because the extraction with 1-octanol taught by EU simply provides an input for the detection accomplished by the other components of the kit and therefore would not prevent it from being used for the detection of target nucleic acids. Therefore, instant claims 10 and 14 are obvious variations of claim 5 of ‘859 in view of Simon and EU.
Response to Arguments
Applicant's arguments filed 1 May 2026 have been fully considered and are persuasive in-part. Regarding double patenting rejections, Applicant argues: “Claims 1 and 3-5 are rejected on obviousness-type double patenting grounds as being obvious over claim 3 of U.S. Patent No. 12,522,859 in view of Ching, Makino, Simon and Aygan (NPL). Applicant submits that this double patenting rejection is obviated by the foregoing amendments for the reasons set forth above.”
Examiner first notes that, in the Office Action mailed 5 February 2026, claims 1-2, 7-8, 10-11, and 14 were rejected for non-statutory double patenting over U.S. Patent No. 12,522,859 (herein ‘859), claims 1, 6, 9-10, and 13 were rejected for non-statutory double patenting over ‘859 in view of Ching, claims 10-12 were rejected for non-statutory double patenting over ‘859 in view of Simon, and claims 1 and 3-5 were rejected for non-statutory double patenting over ‘859 in view of Ching, Makino, Simon, and Aygan. It appears that Applicant has only directly argued the last of these rejections, but their argument is interpreted to apply to all double patenting rejections of the Office Action mailed 5 February 2026.
The non-statutory double patenting rejections of claims 2-3, 5, and 11-12 have been withdrawn due to the cancelation of the rejected claims.
Regarding the non-statutory double patenting rejection of claims 6 and 13 over ‘859 in view of Ching, Applicant’s arguments are not persuasive. As discussed in the Response to Arguments section above regarding the rejection of claims 6 and 13 under 35 U.S.C. 103 as being obvious over Ching in view of Makino, Ching teaches a CRISPR/Cas family protein immobilized on a surface of a particle.
Regarding the non-statutory double patenting rejections of claims 10 and 14 over ‘859 alone or in view of either Ching or Simon, Applicant’s arguments are persuasive as neither ‘859 nor either of Ching or Simon teach a water-absorbing organic solvent that is 1-heptanol, 1-octanol, or 1-nonanol. Therefore, the rejections have been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the combination of the ‘859 with the teachings of Simon, and EU. This new rejection is necessitated by the amendment of claim 10 (on which claim 14 depends) because the previous listing of claims did not claim a kit comprising a water-absorbing organic solvent.
Allowable Subject Matter
Claims 1, 4, and 7-9 are allowed. The following is a statement of reasons for the indication of allowable subject matter.
Claim 1 is free of the prior art because the art does not teach “replacing the sealing liquid with a water-absorbing organic solvent, thereby dehydrating a content of the wells, reducing a volume, causing accumulation of the content inside the second well […] wherein the water-absorbing organic solvent is 1-heptanol, 1-octanol, or 1-nonanol. The nearest prior art is the combination of Ching et al. (US PG PUB 2024/0294970, 102(a)(2) effectively filed date of 17 December 2020), herein Ching, in view of Makino and Kunitomi (EP 3101115, published 7 December 2016, cited in IDS), herein Makino, and in view of Simon et al. (US PG PUB 2014/0004539, published 2 January 2014 with effectively filed date 15 June 2012), herein Simon as applied to claim 12 above, and further in view of Aygan ("Nucleic Acid Extraction from Clinical Specimens for PCR Applications", Turk J Biol 30, 107-120 (2006)), which teaches the entirety of claim 1 except that the water-absorbing organic solvent, taught by Aygan, is 2-butanol and not one of 1-heptanol, 1-octanol, or 1-nonanol as claimed in claim 1 (see 35 U.S.C. 103 rejection of claim 3 in the Office Action mailed 5 February 2026 for mapping of all other limitations). While the art of European Union Reference Laboratory for GM Food and Feed (“Report on the In-house Validation of a DNA Extraction Method from Oilseed rape Grains and Validated Method” JRC publication JRC85313, 18 October 2013), herein EU, teaches a method of extracting DNA using 1-octanol, such that one of ordinary skill in the art may use it to obtain a sample for using in the method of detecting a target nucleic acid taught by the combination of Ching, Makino, Simon, and Aygan, there is no rationale for why the 1-octanol solution taught by EU would be used to replace the sealing liquid in a step after the sample has been contacted with the CRISPR/Cas family protein, gRNA, and substrate nucleic acid fragment. Furthermore, the prior art of Amidon et al. (“Solubility of Nonelectrolytes in Polar Solvents II: Solubility of Aliphatic Alcohols in Water” J Pharm Sci 63(12), pages 1858-1866 (1974)), herein Amidon, teaches that 2-butanol has a solubility in water of 1.068, whereas 1-heptanol (under the synonym n-heptanol) has a solubility in water of 1.55 × 10-2, 1-octanol has a solubility in water of 4.51 × 10-3, and 1-nonanol has a solubility in water of 1.0 × 10-3 (Table I, page 1860-1861). Because Amidon teaches that 1-heptanol, 1-octanol, and 1-nonanol have a solubility in water multiple magnitudes below that of 2-butanol, one of ordinary skill in the art would expect that water would not be able to partition into the significantly more hydrophobic 1-heptanol, 1-octanol, and 1-nonanol to a sufficient degree to substitute for 2-butanol’s use in decreasing the volume of an aqueous phase by having water partition into the butanol phase as taught by Aygan (Aygan page 7 right column paragraph 5). Therefore, the method of claim 1 including a water-absorbing organic solvent wherein the water-absorbing organic solvent is 1-heptanol, 1-octanol, or 1-nonanol is neither anticipated nor obvious in view of the prior art. Claims 4 and 7-9 are free of the prior art by virtue of being dependent on claim 1.
Conclusion
Claims 1, 4, and 7-9 are allowed. Claims 6, 13, 10, and 14 are rejected. Claims 2-3, 5, and 11-12 are canceled.
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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/JEFFREY BELLAH/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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