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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-2, 8, 11-12, 23, 27, 31, 33, 35, 39, 48, 51, 53, 63, 65, 74, 76, and 85 in the reply filed on 03 October 2025 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 18 August 2023 and 03 October 2025 were filed. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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, 2, 8, 11, 12, 23, 27, 31, 33, 39, 48, 51, 53, 65, 74, and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 18/541,650 in view of Dohale et al (US 20170327867 A1).
With regards to claim 1, claim 63 of application 18/541,650 teaches a sample interface configured to receive a sample comprising nucleic acids, a detection region, a programmable nuclease probe, a guide nucleic acid, a target nucleic acid, and a reporter with a cleavable detection moiety. Claim 99 of application 18/541,650 teaches a heater and heating region.
Dohale et al additionally teaches the claimed capability regarding timing as well as the inclusion of a heater. The inclusion of a heat element would have been obvious to one of ordinary skill in the art, for the benefit of allowing amplification reactions and other temperature-driven reactions to occur. The claimed device timing is a results-dependent variable, and would be obvious in view of routine optimization of pump speed, binding affinities, etc. performed by one of ordinary skill in the art.
With regards to claim 2, claim 71 of application 18/541,650 teaches amplification reagents.
With regards to claim 8, claim 1 is obvious over claim 63 in view of Dohale et al. Dohale et al additionally teaches an isothermal temperature profile, which would have been obvious for the benefit of use with a single-use chemical heater that could not perform thermal cycling.
With regards to claims 11 and 12, claim 64 of application 18/541,650 teaches a swab and scraper.
With regards to claim 23, claim 100 of application 18/541,650 teaches fluidically connected chambers (which reads on channels). See also Dohale et al.
With regards to claim 27, Dohale et al teaches the additional movable mechanisms associated with chambers. It would have been obvious to one of ordinary skill in the art to include movable mechanisms such as valves, for the benefit of controlling fluid motion within the heating region.
With regards to claim 31, Dohale et al teaches the additional chemical heating element. It would have been obvious to include for the ability to heat the device in areas with limited or inconsistent power sources.
With regards to claim 33, Dohale et al teaches the use of chambers in the device. It would have been obvious to include a chamber for the benefit of a feature with a larger surface area for heating.
With regards to claim 39, Dohale et al teaches the use of a plurality of channels. According to MPEP 2144.04(VI)(B), duplication of parts may be prima facie obvious.
With regards to claims 48 and 51, Dohale et al teaches the inclusion of an actuator/pump for the movement of fluid. It would have been obvious to include an actuator for the benefit of pumping fluids through the device to allow for sequential processing of the sample.
With regards to claim 65, Dohale et al teaches the target nucleic acid being indicative of an infection related to a woman’s health. It would have been obvious to one of ordinary skill in the art, as the device of claim 1 in view of Dohale et al includes all the structural features required to perform the intended function recited in claim 65.
With regards to claim 74, Dohale et al teaches a physical filter. It would have been obvious to include a filter for the benefit of removing swab fibers or other debris to prevent clogs in the testing area.
With regards to claim 85, claim 72 of application 18/541,650 a sample interface configured to receive a sample comprising nucleic acids, a detection region, a programmable nuclease probe, a guide nucleic acid, a target nucleic acid, a reporter with a cleavable detection moiety, and a reagent mix including amplification reagents.
Dohale et al additionally teaches the claimed capability regarding timing, the inclusion of a manual actuator, as well as the inclusion of a heater. The inclusion of a heat element would have been obvious to one of ordinary skill in the art, for the benefit of allowing amplification reactions and other temperature-driven reactions to occur. The claimed device timing is a results-dependent variable, and would be obvious in view of routine optimization of pump speed, binding affinities, etc. performed by one of ordinary skill in the art. The inclusion of a manual actuator configured to transfer the sample from the heating region to the detection region would have been obvious for the benefit of allowing fluids to move through stages of processing even in situations with limited power.
Claim 35 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 18/541,650 in view of Dohale et al (US 20170327867 A1) and further in view of Bent et al (US 20190249226 A1).
With regards to claim 35, claim 1 is rejected for obvious double-patenting over claim 63 of application 18/541,650 in view of Dohale et al. Claim 69 of application 18/541,650 teaches magnetic silica beads, which feature both a bead and a coating. Bent et al teaches a polymer coating (see [0123]). It would have been obvious to include a polymer with the silica-coated beads, for the benefit of allowing different forms of functionalization and tuning overall particle size.
Claim 63 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 18/541,650 in view of Dohale et al (US 20170327867 A1) and further in view of Doudna et al (US 20190241954 A1, cited on the IDS filed 03 October 2025).
With regards to claim 63, claim 1 is rejected for obvious double-patenting over claim 63 of application 18/541,650 in view of Dohale et al. Dohale et al does not explicitly disclose wherein the programmable nuclease comprises a Cas enzyme. In the analogous art of programmable nuclease probes, Doudna et al teaches the use of a Cas enzyme programmable nuclease (see [0082]). It would have been obvious to one of ordinary skill in the art to combine the Cas enzyme as taught by Doudna et al with the device of claim 1/claim 63, and the heater as taught by Dohale et al, for the predictable result of detecting nucleic acids using a Cas enzyme, resulting in an improved system which allows for cleavage-activated detection moieties without requiring hydrolysis conditions.
Claim 76 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 18/541,650 in view of Dohale et al (US 20170327867 A1) and further in view of Spizz et al (US 20120129714 A1, cited on the IDS provided on 18 August 2023).
With regards to claim 76, claim 74 of application 18/541,650 teaches the immobilization of the claimed components to a device surface. Spizz et al teaches a covalent linkage to immobilize components (see [0067]). It would have been obvious to one of ordinary skill in the art to modify the device to include a covalent linkage as taught Spizz et al for the benefit of determining the identity of the guide nucleic acid based on its position on the surface (see Spizz et al [0068]).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, 8, 11, 23, 27, 31, 33, 39, 48, 51, 53, 63, 74, and 85 are rejected under 35 U.S.C. 103 as being unpatentable over Dohale et al (US 20170327867 A1) in view of Doudna et al (US 20190241954 A1, cited on the IDS filed 03 October 2025).
With regards to claim 1, Dohale et al teaches;
The claimed “a device for detecting a target nucleic acid” has been read on the taught ([0009], “The device simplifies and automates the processes required for Nucleic Acid Amplification Testing (NAAT)…”);
The claimed “a sample interface configured to receive a sample comprising a target nucleic acid” has been read on the taught ([0012], “…a system for analyzing a biological sample comprising a cartridge, the cartridge comprising a sample chamber…”);
The claimed “a heating region in fluid communication with the sample interface and configured to amplify the sample received via the sample interface” has been read on the taught ([0133], “… the sample is delivered to a reaction chamber 810. The sample will undergo a reaction, for instance an amplification reaction in reaction chamber 810…”; [0012], “…a reaction chamber heating system…”; The reaction chamber reads on the heating region.);
The claimed “a detection region in fluid communication with the heating region” has been read on the taught ([0012], “…a detection system…”; [0187], “…an excitation and/or detection port can be provided within the instrument at the defined height from the bottom of the reaction chamber which can detect the presence of an optically labelled fluid (for instance, fluorescently labelled)…”; The bottom of the reaction chamber aligned with a detection port reads on a detection region.);
The claimed “wherein the detection region is configured to detect a signal produced by the released detection moiety and corresponding to a presence of the target nucleic acid” has been read on the taught ([0247], “…there is provided a detection unit that can be used to detect the target of interest. […] In some embodiments, the target of interest will release DNA or nucleic acids upon lysing, which can be processed downstream for analysis, which analysis can be analyzed following detection of emissions, such as fluorescence.”; [0102] teaches that the device may use a polymerase to cleave a reporter dye.);
Dohale et al additionally teaches that detection reagents may be placed in the heating or detection region, as read on the taught ([0119], “In one embodiment, the reaction chamber contains dried reagents… The reaction performed in the reaction chamber may be an amplification reaction, including PCR.”). Dohale et al also teaches that cleavage-based probes may be used with the device, as read on the taught ([0102], “Hydrolysis probes (such as the TaqMan® probe) use the polymerase enzyme to cleave a reporter dye molecule from a quencher dye molecule attached to an oligonucleotide probe.”).
However, Dohale et al does not explicitly disclose wherein the device further comprises a programmable nuclease probe disposed within the sample interface, the heating region, or the detection region, wherein the programmable nuclease probe comprises a programmable nuclease and a guide nucleic acid; a reporter; and wherein the presence or absence of the target nucleic acid is determined within a time of less than 30 minutes after the sample is received at the sample interface.
In the analogous art of programmable nuclease probes, Doudna et al teaches;
The claimed “a programmable nuclease probe… wherein the programmable nuclease probe comprises a programmable nuclease and a guide nucleic acid” has been read on the taught ([0082], “Such methods can include (a) contacting the sample with: (i) a type V CRISPR/Cas effector protein (e.g., a Cas12 protein); (ii) a guide RNA comprising: a region that binds to the type V CRISPR/Cas effector protein, and a guide sequence that hybridizes with the target DNA.”; The effector protein reads on a programmable nuclease. The guide RNA reads on a guide nucleic acid.);
The claimed “a reporter” has been read on the taught ([0082], “Such methods can include… (iii) a detector DNA that is single stranded and does not hybridize with the guide sequence of the guide RNA.”);
The claimed “wherein the programmable nuclease is activated by selective binding between the guide nucleic acid and a target nucleic acid” has been read on the taught ([0082], “…once a subject Type V CRISPR/Cas effector protein […] is activated by a guide RNA, which occurs when the sample includes a target DNA to which the guide RNA hybridizes […] the Type V CRISPR/Cas effector protein […] is activated and functions as an endoribonuclease…”);
The claimed “wherein the reporter is configured to release a detection moiety upon cleavage by the activated programmable nuclease” has been read on the taught ([0007], “measuring a detectable signal produced by cleavage (by the type V CRISPR/Cas effector protein) of the single stranded detector DNA. In some cases, the single stranded detector DNA includes a fluorescence-emitting dye pair (e.g., a fluorescence-emitting dye pair is a fluorescence resonance energy transfer (FRET) pair, a quencher/fluor pair).”; The single stranded detector DNA reads on the reporter. The quencher/fluor pair, particularly the released fluor moiety, reads on a detection moiety released upon cleavage.);
The claimed “wherein the presence or absence of the target nucleic acid is determined within a time of less than 30 minutes after the sample is received at the sample interface” has been read on the taught ([0086], “In some cases the sample is contacted for 5 minutes or less prior to the measuring step. In some cases the sample is contacted for 1 minute or less prior to the measuring step.”).
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 device for detecting a target DNA sequence as taught by Dohale et al with the method of detecting DNA sequences as taught by Doudna et al. According to MPEP 2143(I)(D), applying a known technique to a known device ready for improvement to yield predictable results may be prima facie obvious. In the case of the instant invention, the prior art of Dohale et al contains a “base” device for detecting DNA using hydrolysis methods, upon which the claimed invention can be seen as an improvement. The prior art of Doudna et al contains a known technique of using a programmable nuclease with a guide probe, which is applicable to the device of Doudna et al. One of ordinary skill in the art would have recognized that applying the known method of using a programmable nuclease would have the predictable result of detecting target DNA, and would result in an improved system that makes use of a CRISPR/Cas endonuclease to generate a signal.
With regards to claim 2, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al additionally teaches;
The claimed device “further comprising a reagent mix comprising amplification reagents” has been read on the taught ([0119], “In one embodiment, the reaction chamber contains dried reagents… The reaction performed in the reaction chamber may be an amplification reaction, including PCR.”).
With regards to claim 8, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al additionally teaches;
The claimed “wherein the heating region is configured to maintain an isothermal, or non-cycled temperature profile” has been read on the taught ([0380], “…such a device can be used in other amplification reactions (e.g., isothermal amplification) consistent with the aim of DNA/RNA quantification.”; The device used in an isothermal amplification reads on the heating region being configured to maintain an isothermal temperature profile.).
With regards to claim 11, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al additionally teaches;
The claimed, “wherein the sample interface a) comprises a compartment configured to receive a swab containing the sample; b) is configured to receive the sample from a swab via pipetting; c) comprises a compartment configured to receive the sample from a container containing the sample; or d) is configured to receive the sample as a fluid” has been read on the taught ([0132], “In another embodiment, the sample tank allows for the input of a swab sample.”; The input of a swab sample into a sample tank reads on the sample interface comprising a compartment configured to receive a swab.).
With regards to claim 23, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al additionally teaches;
The claimed “wherein the heating region comprises one or more channels for fluid movement therethrough” has been read on the taught ([0122], “The aliquoter features draws the lysate through the main channel and dispenses a pre-determined reaction volume of lysate into the reaction chamber, which is mixed with reagents and undergoes the desired reaction.”; The main channel dispensing into the reaction chamber reads on one or more channels for fluid movement).
With regards to claim 27, the device of claim 23 is obvious over Dohale et al in view of Doudna et al.
Dohale et al additionally teaches;
The claimed “wherein each channel of the heating region comprises one or more movable mechanisms” has been read on the taught ([0366], “…channels having stop valves can be placed in main channel 512…”; Stop valves read on one or more movable mechanisms).
With regards to claim 31, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al additionally teaches;
The claimed device “further comprising a chemical heating element” has been read on the taught ([0317], “For PCR, a chemical heat pack could supply heat for isothermal PCR.”).
With regards to claim 33, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al additionally teaches;
The claimed “wherein the heating region comprises a chamber in fluid communication with the sample interface and the detection region” has been read on the taught ([0122], “The aliquoter feature draws the lysate through the main channel and dispenses a pre-determined reaction volume of lysate into the reaction chamber…”; [0012], “…a reaction chamber heating system…”; [0187], “…an excitation and/or detection port can be provided within the instrument at the defined height from the bottom of the reaction chamber…”; The reaction chamber reads on the heating region comprising a chamber. The main channel reads on the sample interface being in fluid communication with the heating region. The detection region being in the reaction chamber reads on the detection region being in fluid communication with the chamber.).
With regards to claim 39, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al additionally teaches;
The claimed device, “further comprising a plurality of channels to move the sample from the sample interface to the detection region, wherein the plurality of channels comprises at least one set of channels arranged in series or at least one set of channels arranged in parallel” has been read on the taught ([0124], “The lysis chamber 405 is connected to both a waste chamber 408 and one or more reaction chamber(s) 410 by means of a main channel 412 that is forked, Y-branched, T-branched or has other suitable configuration 413 to allow a fluid to be selectively moved to either of the waste 409 or reaction chamber(s) 410.”).
With regards to claim 48, the device of claim 1 is obvious over Dohale et al in view of Doudna et al..
Dohale et al additionally teaches;
The claimed device, “further comprising at least one actuator” has been read on the taught ([0234], “A pump (e.g., peristaltic, vacuum, piston, or syringe pump, etc.) can be used to drive fluid through the device.”).
With regards to claim 51, the device of claim 48 is obvious over Dohale et al in view of Doudna et al.
Dohale et al additionally teaches;
The claimed “wherein a first actuator of the at least one actuator is configured to move the sample from the sample interface to the heating region via manual actuation of the first actuator or wherein a second actuator of the at least one actuator is configured to move the detection moiety from the heating region to the detection region via manual actuation of the second actuator” has been read on the taught ([0234], “A pump (e.g., peristaltic, vacuum, piston, or syringe pump, etc.) can be used to drive fluid through the device.”; [0317], “In yet another embodiment of the present disclosure, the syringe displacement drives the fluidic function of the cartridge, and no pump is required.”).
With regards to claim 53, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al additionally teaches;
The claimed “wherein the device is configured to be operated manually without electrical power, or wherein the device further comprises a power source” has been read on the taught ([0317], “In yet another embodiment of the present disclosure, the syringe displacement drives the fluidic function of the cartridge, and no pump is required. A user can therefore load a sample and manually actuate all the fluidic sample processing steps required for testing. For PCR, a chemical heat pack could supply heat for isothermal PCR. This approach could be robust in dealing with low-resource settings and their inherent challenges, for example, intermittent power supply, by using primarily manual steps and an isolated heat source. A low-power, robust optical detection method could be added to create a complete sample-to-answer system.”).
With regards to claim 63, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al does not explicitly disclose wherein the programmable nuclease comprises a Cas enzyme, optionally wherein the Cas enzyme is selected from the group consisting of Cas12, Cas13, Cas 14a, Cas14a1, and CasPhi.
Doudna et al additionally teaches;
The claimed “wherein the programmable nuclease comprises a Cas enzyme, optionally wherein the Cas enzyme is selected from the group consisting of Cas12, Cas13, Cas 14a, Cas14a1, and CasPhi” has been read on the taught ([0082], “Such methods can include (a) contacting the sample with: (i) a type V CRISPR/Cas effector protein (e.g., a Cas12 protein)).
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 device for detecting a target DNA sequence as taught by Dohale et al with the method of detecting DNA sequences as taught by Doudna et al. According to MPEP 2143(I)(D), applying a known technique to a known device ready for improvement to yield predictable results may be prima facie obvious. In the case of the instant invention, the prior art of Dohale et al contains a “base” device for detecting DNA using hydrolysis methods, upon which the claimed invention can be seen as an improvement. The prior art of Doudna et al contains a known technique of using a programmable nuclease with a guide probe, which is applicable to the device of Doudna et al. One of ordinary skill in the art would have recognized that applying the known method of using a programmable nuclease would have the predictable result of detecting target DNA, and would result in an improved system that makes use of a CRISPR/Cas endonuclease to generate a signal.
With regards to claim 65, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al additionally teaches;
The claimed “wherein the target nucleic acid comprises a single nucleotide polymorphism (SNP); or wherein the target nucleic acid is indicative of a respiratory disorder, a respiratory pathogen, a sexually transmitted infection (STI), or an infection related to a woman's health” has been read on the taught ([0099], “…the sample may be one or more of the following types: bronchoalveolar lavage, […] endocervical, vaginal…”; [0100], “More specific applications and targets of interest within the scope of the present disclosure include, without limitation: Trichomonas vaginalis, Chlamydia trachomatis, and Neisseria gonorrhoeae, syphilis, antibiotic resistant strains, HIV, Zika, human papillomavirus, yeast, vaginal microbiome profiling, vaginosis panel, fungi, animal health targets, listeria, e. coli, sepsis, herpes, HCV, RSV, CMV, HSV, Group B strep, influenza, and others known to skill in the art.”; For instance, a vaginosis panel reads on an infection related to a woman’s health.).
With regards to claim 74, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al additionally teaches;
The claimed “further comprising a physical filter configured to filter one or more particles from the sample that do not comprise the target nucleic acid” has been read on the taught ([0101], “Enrichment may include separating the targets of interest from a portion of the sample by methods including filtering…”; [0109], “…The sample is released from the initial sample tank into the lysis chamber containing the filter. The sample is filtered through the filter…”).
With regards to claim 85, Dohale et al teaches;
The claimed “a device for detecting a target nucleic acid” has been read on the taught ([0009], “The device simplifies and automates the processes required for Nucleic Acid Amplification Testing (NAAT)…”);
The claimed “a sample interface for receiving the sample” has been read on the taught ([0012], “…a system for analyzing a biological sample comprising a cartridge, the cartridge comprising a sample chamber…”);
The claimed “a heating region in fluid communication with the sample interface” has been read on the taught ([0133], “… the sample is delivered to a reaction chamber 810. The sample will undergo a reaction, for instance an amplification reaction in reaction chamber 810…”; [0012], “…a reaction chamber heating system…”; The reaction chamber reads on the heating region.);
The claimed “a heating element configured to heat to the heating region” has been read on the taught ([0117], “At least one of the resistive heaters is attached to a heat block. The heat block is configured to have the same interior shape as the outer shape of the sample chamber.”);
The claimed “a detection region in fluid communication with the heating region” has been read on the taught ([0012], “…a detection system…”; [0187], “…an excitation and/or detection port can be provided within the instrument at the defined height from the bottom of the reaction chamber which can detect the presence of an optically labelled fluid (for instance, fluorescently labelled)…”; The bottom of the reaction chamber aligned with a detection port reads on a detection region.);
The claimed “wherein the detection region is configured to detect a signal produced by the released detection moiety” has been read on the taught ([0247], “…there is provided a detection unit that can be used to detect the target of interest. […] In some embodiments, the target of interest will release DNA or nucleic acids upon lysing, which can be processed downstream for analysis, which analysis can be analyzed following detection of emissions, such as fluorescence.”);
The claimed “a first manual actuator configured to transfer the sample from the heating region to the detection region” has been read on the taught ([0234], “A pump (e.g., peristaltic, vacuum, piston, or syringe pump, etc.) can be used to drive fluid through the device.”; [0317], “In yet another embodiment of the present disclosure, the syringe displacement drives the fluidic function of the cartridge, and no pump is required. A user can therefore load a sample and manually actuate all the fluidic sample processing steps required for testing.”);
The claimed “a reagent mix comprising amplification reagents” has been read on the taught ([0119], “In one embodiment, the reaction chamber contains dried reagents… The reaction performed in the reaction chamber may be an amplification reaction, including PCR.”);
The claimed “wherein the reagent mix is disposed within the sample interface, the heating region, the detection region, and/or between the sample interface and the heating region” has been read on the taught ([0119], “In one embodiment, the reaction chamber contains dried reagents… The reaction performed in the reaction chamber may be an amplification reaction, including PCR.”).
However, Dohale et al does not explicitly disclose wherein a programmable nuclease comprising a guide nucleic acid, a reporter, wherein the programmable nuclease is activated by selective binding between the guide nucleic acid and a target nucleic acid, wherein the reporter is configured to release a detection moiety upon cleavage by the activated programmable nuclease, and wherein the device is configured to determine the presence or absence of the target nucleic acid within a time of less than 30 minutes via the produced signal.
In the analogous art of programmable nuclease probes, Doudna et al teaches;
The claimed “a programmable nuclease probe… wherein the programmable nuclease probe comprises a programmable nuclease and a guide nucleic acid” has been read on the taught ([0082], “Such methods can include (a) contacting the sample with: (i) a type V CRISPR/Cas effector protein (e.g., a Cas12 protein); (ii) a guide RNA comprising: a region that binds to the type V CRISPR/Cas effector protein, and a guide sequence that hybridizes with the target DNA.”; The effector protein reads on a programmable nuclease. The guide RNA reads on a guide nucleic acid.);
The claimed “a reporter” has been read on the taught ([0082], “Such methods can include… (iii) a detector DNA that is single stranded and does not hybridize with the guide sequence of the guide RNA.”);
The claimed “wherein the programmable nuclease is activated by selective binding between the guide nucleic acid and a target nucleic acid” has been read on the taught ([0082], “…once a subject Type V CRISPR/Cas effector protein […] is activated by a guide RNA, which occurs when the sample includes a target DNA to which the guide RNA hybridizes […] the Type V CRISPR/Cas effector protein […] is activated and functions as an endoribonuclease…”);
The claimed “wherein the reporter is configured to release a detection moiety upon cleavage by the activated programmable nuclease” has been read on the taught ([0007], “measuring a detectable signal produced by cleavage (by the type V CRISPR/Cas effector protein) of the single stranded detector DNA. In some cases, the single stranded detector DNA includes a fluorescence-emitting dye pair (e.g., a fluorescence-emitting dye pair is a fluorescence resonance energy transfer (FRET) pair, a quencher/fluor pair).”; The single stranded detector DNA reads on the reporter. The quencher/fluor pair, particularly the released fluor moiety, reads on a detection moiety released upon cleavage.);
The claimed “wherein the presence or absence of the target nucleic acid is determined within a time of less than 30 minutes after the sample is received at the sample interface” has been read on the taught ([0086], “In some cases the sample is contacted for 5 minutes or less prior to the measuring step. In some cases the sample is contacted for 1 minute or less prior to the measuring step.”).
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 device for detecting a target DNA sequence as taught by Dohale et al with the method of detecting DNA sequences as taught by Doudna et al. According to MPEP 2143(I)(D), applying a known technique to a known device ready for improvement to yield predictable results may be prima facie obvious. In the case of the instant invention, the prior art of Dohale et al contains a “base” device for detecting DNA using hydrolysis methods, upon which the claimed invention can be seen as an improvement. The prior art of Doudna et al contains a known technique of using a programmable nuclease with a guide probe, which is applicable to the device of Doudna et al. One of ordinary skill in the art would have recognized that applying the known method of using a programmable nuclease would have the predictable result of detecting target DNA, and would result in an improved system that makes use of a CRISPR/Cas endonuclease to generate a signal.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Dohale et al (US 20170327867 A1) in view of Doudna et al (US 20190241954 A1, cited on the IDS filed 03 October 2025) as applied to claim 11 above, and further in view of Zappia et al (US 20110152720 A1).
With regards to claim 12, the device of claim 11 is obvious over Dohale et al in view of Doudna et al.
Dohale et al teaches that other known art for swab-based sample transport may be used with the taught disclosure (see [0133]).
However, Dohale et al in view of Doudna et al does not explicitly disclose wherein the compartment comprises a scraper configured to transfer the sample from the swab to the device.
In the analogous art of microfluidic sampling devices, Zappia et al teaches;
The claimed “wherein the compartment comprises a scraper configured to transfer the sample from the swab to the device” has been read on the taught ([0171], “…sample collection region 1902 may include […] a scraping device across which a swab map be provided to transfer a sample from the swab to the sample collection region.”).
It would have been obvious to one of ordinary skill in the art to modify the device including a sample interface as taught by Dohale et al with the swab scraper as taught by Zappia et al, for the benefit of using relatively small sample within the device ([0188], “Sample collection methods and systems as disclosed herein may be implemented to receive a relatively small sample, and to prepare, store and/or ship the prepared sample to a lab, which may otherwise require significantly more sample to compensate for the loss of sample during transportation.”).
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Dohale et al (US 20170327867 A1) in view of Doudna et al (US 20190241954 A1, cited on the IDS filed 03 October 2025) as applied to claim 1 above, and further in view of Bent et al (US 20190249226 A1).
With regards to claim 35, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al acknowledges the use of bead capture of analytes (see [0107]), but Dohale et al in view of Doudna et al does not explicitly disclose wherein the reporter is immobilized in the heating region via a support that is immobilized on a surface of the heating region, wherein the support comprises a bead, a coating, and an interspersed polymer.
In the analogous art of nucleic acid detection methods (see [0002]), Bent et al teaches;
The claimed “a support” and “wherein the support comprises a bead, a coating, and an interspersed polymer” has been read on the taught ([0123], “The bead may be a solid particle (e.g., a metal-based particle including but not limited to iron oxide, gold or silver) covered with a coating comprising one or more polymers.”; [0123] further discusses how the polymer matrix on a bead may be interspersed.);
The claimed “support that is immobilized on a surface” has been read on the taught ([0159], “In some cases, a combinatorial ligation method such as that described with reference to FIG. 9A may comprise immobilizing a plurality of beads to a plurality of supports…”);
Bent et al further teaches wherein a detectable molecule is attached to the bead by a cleavable linkage, and wherein cleavage activates the detectable molecule, as read on the taught ([0241], “…barcodes can be released or be releasable through cleavage of a linkage between the barcode molecule and the bead… In non-limiting examples, cleavage may be achieved through […] use of restriction enzymes […] or cleavage via other types of stimuli (e.g., […] enzymatic, etc.)... Releasable barcodes may sometimes be referred to as being activatable, in that they are available for reaction once released.”; [0152] teaches that nucleic acid molecules may be attached to the bead with a fluorophore.
It would have been obvious to one of ordinary skill in the art to modify the device including a heating region and a reporter molecule as taught by Dohale et al in view of Doudna et al with the bead support as taught by Bent et al, for the benefit of containing a pre-determined concentration of reagents within the heating region, as read on (Bent et al, [0245] “Any suitable number of molecular tag molecules (e.g., primer, barcoded oligonucleotide) can be associated with a bead such that, upon release from the bead, the molecular tag molecules (e.g., primer, e.g., barcoded oligonucleotide) are present in the partition at a pre-defined concentration. Such pre-defined concentration may be selected to facilitate certain reactions for generating a sequencing library, e.g., amplification, within the partition.”).
Claim 76 is rejected under 35 U.S.C. 103 as being unpatentable over Dohale et al (US 20170327867 A1) in view of Doudna et al (US 20190241954 A1, cited on the IDS filed 03 October 2025) as applied to claim 1 above, and further in view of Spizz et al (US 20120129714 A1, cited on the IDS provided on 18 August 2023).
With regards to claim 76, the device of claim 1 is obvious over Dohale et al in view of Doudna et al.
Dohale et al in view of Doudna et al does not explicitly disclose wherein the programmable nuclease, guide nucleic acid, or the reporter are immobilized to a device surface by a linkage, wherein the linkage comprises a covalent bond, a non-covalent bond, an electrostatic bond, a bond between streptavidin and biotin, an amide bond, or non-specific absorption.
In the analogous art of nucleic acid detection, Spizz et al teaches;
The claimed “wherein the programmable nuclease, guide nucleic acid, or the reporter are immobilized to a device surface by a linkage” has been read on the taught ([0070], “The system can be used in conjunction with a gene chip or biochip system comprising an array of oligonucleotides or nucleic acids immobilized on the substrate surface.”; The nucleic acids immobilized on the substrate surface read on guide nucleic acids—see also [0067].);
The claimed “wherein the linkage comprises a covalent bond, a non-covalent bond, an electrostatic bond, a bond between streptavidin and biotin, an amide bond, or non-specific absorption” has been read on the taught ([0067], “The TDR probes are immobilized on an untreated or treated surface of a substrate, preferably through covalent bonding…”).
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 device including a guide nucleic acid as taught by Dohale et al in view of Doudna et al with the immobilized guide nucleic acid as taught by Spizz et al, for the benefit of determining the identity of the guide nucleic acid based on its position on the surface ([0068], “The bound target generates a signal at each DNA spot where it is bound, and a signal detector can detect the signal while determining the identity of the probe and target based on their known location on the microarray.”).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kauppinen et al (US 20050053942 A1) teaches DNA capture probes bound to a surface of a device, and is of relevance to claim 76.
Abudayyeh et al (WO 2018170340 A1, cited on the IDS provided 03 October 2025) teaches the use of a programmable nuclease for molecular detection, and is of relevance to claim 1.
Adey et al (US 20180355348 A1) teaches the benefits of a nucleic acid array, wherein probes are bound to the surface of a device, and is of relevance to claim 76.
Gupta et al (US 20190024155 A1) teaches the use of fluorescent reporters and quencher molecules, and is of relevance to claim 1.
Walter et al (US 20190048415 A1, cited on the IDS provided 18 August 2023) teaches the use of a nuclease to detect target molecules, and is of relevance to claim 1.
Chen et al (WO 2020028729 A1, effectively filed August 01 2019 and cited on the IDS provided 18 August 2023) teaches the use of a programmable nuclease for target molecule detection, and is of relevance to claim 1.
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/ALISON CLAIRE GERHARD/Examiner, Art Unit 1797 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797