DETAILED ACTION
The present Office Action is responsive to the Amendment received on February 2, 2026.
Preliminary Remark
Claims 1-19 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 6, 2025. Applicants’ request for rejoinder is noted. As the elected invention is not allowable, Applicants are advised to follow the guidelines based on In re Ochiai.
Claim 38 is canceled.
Information Disclosure Statement
The IDS received on February 3, 2026 is proper and are being considered by the Examiner.
Claim Rejections - 35 USC § 112
The rejection of claim 20 and 23-39 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter, made in the Office Action mailed on October 31, 2025 is withdrawn in view of the Amendment received on February 2, 2026.
Rejection – Maintained & New Grounds, Necessitated by Amendment
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
The rejection of claims 21 and 22 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter, made in the Office Action mailed on October 31, 2025 is maintained for the reasons of record.
Applicants’ claim amendment/argument presented in the Amendment received on February 2, 2026 have been carefully considered but they have not been found persuasive for the reasons discussed in the, “Response to Arguments” section.
The Rejection:
Claims 21 and 22 are indefinite because the claims nor the parent claim (20) actively require that a plurality of chambers are comprised by the system, and it is unclear how the processor(s) or detection unit is further limited or distinguished by defining the chambers’ volume.
Response to Arguments:
Applicants state that the amendment made to claim 20 addresses the rejection (page 9, Response).
The Office respectfully disagrees.
While claim 20 has been amended to effectively further recite the phrase, “a thermal unit configured to be in thermal communication with a plurality of chambers of a plate”, the claimed system does not actively comprise the plate which comprises the plurality of chamber. As amended, claim, at best requires the presence of a thermal unit and this unit has an intended usage of being in contact with the plate. Therefore, claims 21 and 22 which further define these chamber volumes do not further define the system as the plate which comprises the chamber are not required by the system.
The rejection is maintained therefore.
Rejection – New Grounds
Claim 33 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 33 is now indefinite based on the amendment which took place on parent claim 20. Claim 20 has been amended to recite that the plurality of chambers are found on a plate1. Claim 33 recites that the system comprises a “substrate” on which a plurality of chamber arrays are found. It is unclear whether the substrate is referring to the plate of claim 30.
Claim Rejections - 35 USC § 102
The rejection of claim 38 under 35 U.S.C. 102(a)(1) as being anticipated by Zayac et al. (WO 2018/094091 A1, published May 2018), made in the Office Action mailed on October 31, 2025 is withdrawn in view of the Amendment received on February 2, 2026, canceling the rejected claim.
Rejection - Maintained
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.
The rejection of claims 20-28, 31-, 37, and 39 under 35 U.S.C. 102(a)(1) as being anticipated by Zayac et al. (WO 2018/094091 A1, published May 2018), made in the Office Action mailed on October 31, 2025 is maintained for the reasons of record.
Applicants’ claim amendment/arguments presented in the Amendment received on February 2, 2026 have been carefully considered but they have not been found persuasive for the reasons discussed in the, “Response to Arguments” section.
The Rejection:
With regard to claim 20, Zayac et al. teach a system comprising:
a detection unit configured to collect and process signals for identification of nucleic acids (“system that may be useful for amplifying and quantifying nucleic acids and detecting the presence or absence of targets (e.g., actual or suspected targets)”, section [0007]; “digital HRM analysis platform that integrates absolute quantification in digital PCR (dPCR) with HRM analysis”, section [0011]; “imaging is performed using a detector that detects fluorescence emission at two or more wavelengths … processing signals to determine a number of nucleic acid molecules in the at least a subset of the plurality of partitions …”, section [0026]); and
one or more processors operatively coupled to said detection unit, wherein said one or more processors are individually or collectively programmed or otherwise configured to (“computer processor operatively coupled to the detector … programmed to … process the signals to determine a number of nucleic acid molecules”, section [0032]):
use a plurality of nucleic acid molecules to generate, in a plurality of chambers a plurality of double-stranded nucleic acid molecules (“device comprising a plurality of partitions”, section [0032]; “one or more processors are individually or collectively programmed to direct the fluid flow unit to load the plurality of nucleic acid molecules into the plurality of partitions”, section [0033]), wherein (i) a first subset of said plurality of double-stranded molecules comprises a first double-stranded nucleic acid molecules comprising a first sequence corresponding to a first nucleic acid molecule of said plurality of nucleic acid molecules and an added sequence; and (ii) a second subset of said plurality of double-stranded nucleic acid molecules comprises a second double-stranded nucleic acid molecule comprising a second sequence corresponding to a second nucleic acid molecule of said plurality of nucleic acid molecules and does not comprise said added sequence2);
denature double-stranded nucleic acid molecules of said plurality of double-stranded nucleic acid molecules (“[c]ontrolled heating of a subset of the plurality of partitions of a device may be performed at any useful rate and over any useful temperature range … controlled heating may be performed to an upper temperature of at least about … 100oC or more”, section [00155]);
detect signal indicated of said denaturing to generate a plurality of denaturation profiles (“HRM methods of the present disclosure can create sequence-dependent melting curves [or profiles] with single nucleotide resolution”, section [0008]), wherein
a first denaturation profile of said plurality of denaturation profiles is derived from denaturation of said first double-stranded nucleic acid molecule;
a second denaturation profile of said plurality of denaturation profiles is derived from denaturation of said second double-stranded nucleic acid molecules; and
said first denaturation profile and said second denaturation profiles are different (“device comprising a plurality of partitions, wherein at least a subset of the plurality of partitions comprises the plurality of nucleic acid molecules … subjecting the at least the subset of the plurality of partitions to controlled heating, collecting signals from the at least the subset of the plurality of partitions; and processing the collected signals to yield data indicative of a melting point of at least a subset of the plurality of nucleic acid molecules in the at least the subset of the plurality of partitions”, section [0012]; “method further comprises using the data indicative of a melting point to determine the presence or absence of the pathogen in each partition of the at least the subset of the plurality of partitions” section [0017]; “temperature may be increased by about 0.1oC over a range where significant melting of a nucleic acid molecule is expected …”, section [00155]; “[c]ollecting signal may comprise imaging … Processing collected signals may comprise using the signals to generate signal versus temperature data … [or profile] for the subset of the plurality of nucleic acid molecules in the subset of the plurality of partitions”, section [00156]; see Fig. 22A for multiple different double-stranded nucleic acid profiles being capable being generated, “FIG. 22A illustrates the difference between digital and bulk HRM analyses … the top panel, in digital HRM analysis, each partition includes at most 1 target DNA molecule and melt curves of different bacteria are resolved”, section [0161]);
processing said plurality of denaturation profiles to identify a nucleic acid molecule of said plurality of nucleic acid molecules.
With regard to claims 21 and 22, the claimed device does not actively require that the device comprise any surface/substrates, nor any chambers/partitions, and therefore, does not require the volumes of the chambers/partitions3.
With regard to claims 23 and 24, the plurality of chambers are not actively required in the claims. However, Zayac et al. explicitly teach that their device comprises additional elements wherein the device comprises 1,000 to about 20,000 partitions (“the plurality of partitions comprises from about 1,000 to about 20,000 partitions”, section [0022]).
With regard to claims 25 and 26, the detection unit is configured to image at least a portion of said plurality of chambers (“[s]ignals may be collected (e.g., image taken) from the microfluidic device [all partitions] or a subset of the plurality of partitions (e.g., microchambers) thereof.”, section [00123]).
With regard to claims 27, 28, and 31, the optical unit comprise a field of view of 25 mm to 25 mm (“optical unit has a 25 mm by 25 mm field of view and a Numerical Aperture (NA) of 0.14”, section [00205], also see above for optical unit collecting optical signals).
With regard to claim 32, the optical unit comprises greater than or equal to four channels, each channel configured to collect a different wavelength of light (“detector may be configured to collect signals from all or a subset of the plurality of partitions of the device … detector may collect optical … configured to emit and detect multiple wavelengths of light … optical unit may be configured to detect one, two, three, four, or more wavelengths of light … may correspond to the excitation wavelength of indicator molecule”, section [00171]).
With regard to claims 33, the microfluidic device may comprise multiple arrays of microchambers (“microfluidic device may comprise a single array of microchambers. Alternatively, the microfluidic device may comprise multiple arrays of microchambers, each array of microchambers isolated from the others”, section [0085]).
With regard to claims 33-35, the substrate (i.e., microfluidic device) comprises a plurality of chamber arrays, and a chamber array of said plurality of chamber arrays comprises said plurality of chambers (“microfluidic device may comprise multiple arrays of microchamber, each array of microchambers isolated from the others … The microfluidic device may have at least about 1, at least about 2, at least about 3, … about 4 … 5 … or more arrays of microchambers”, section [0085]; “each array of microchambers isolated from the others”, section [0085]).
With regard to claim 36, the system comprises a configuration to receive the microfluidic device (“system may comprise a support unit such as a transfer stage, platform, slot, or groove configured to hold one or more microfluidic devices”, section [00167]).
With regard to claims 37 and 38, the system further comprises a thermal unit coupled to the one or more processors to control the temperature (“a thermal unit configured to subject the at least the subset of the plurality of partitions to controlled heating …”, section [0034]; “one or more computer processors operatively coupled to the thermal unit and the detector”, section [0034], the controlled heating refers to both the processes involving dPCR and dHRMA which involve denaturation temperatures).
With regard to claim 39, the thermal unit comprises a thermoelectric temperature control unit (“thermal control unit may perform … thermal programs with different arrays of microchambers”, section [00170]; “[h]eating … methods may include resistive heating [involves electric] … conductive heating … convective heating …”, section [00130]).
Therefore, Zayac et al. anticipate the invention as claimed.
Response to Arguments:
Applicants traverse the rejection.
Applicants state that independent claim 20 has been amended to recite a system for nucleic acid identification inter alia, a) one or more processors operatively coupled to a detection unit and a thermal unit, wherein said one of more processors are individually or collectively programmed or configured to: i) instruct the thermal unit to perform thermal cycling whereby a plurality of nucleic acid molecules are amplified to generate, in a plurality of chambers, a plurality of double-stranded nucleic acid molecules, wherein a) a first subset of said plurality of ds nucleic acid molecules comprises a first double-stranded molecule of said plurality of nucleic acid molecules and an added sequence, the added sequence being non-complementary to the first nucleic acid molecule” (page 10, Response).
This argument has been carefully considered but has not been found persuasive.
The rejection is maintained based on the broadest reasonable interpretation of the claim that the system as presently claimed do not actively require the presence of the “plate” on which a plurality of chambers are found. Since the amplification reaction comprising the plurality of the nucleic acids, including those with “added sequence that are non-complementary to the first nucleic acid molecule,” are to be present in the chambers of the plate which is not required, this feature is simply not required by the claims.
As to the actual thermal unit that has been amended to be actually required by the system, Zayac et al. teach, “a therma unit configured to subject the at least a subset of plurality of partitions to controlled heatin” that is controlled by “one or more computer processors operatively coupled to the thermal unit and the detector” (section [0034]).
Therefore, in as much as the actively required components of the claimed system, Zayac et al. anticipate the claims.
The rejection is maintained therefore.
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.
The rejection of claims 21 and 22 under 35 U.S.C. 103 as being unpatentable over Zayac et al. (WO 2018/094091 A1, published May 2018) in view of Makrigiorgos et al. (WO 2012/135664 A2, published October 4, 2012), made in the Office Action mailed on October 31, 2025 is maintained for the reasons of record.
Applicants do not present any arguments for the present rejection but rely solely on their argument presented for the anticipation rejection over Zayac et al. which have been fully responded to above.
Therefore, instant rejection is maintained for the reasons of record.
The Rejection:
The present rejection contains claims 21 and 22 based on the alternative interpretation that the device comprises the plurality of chambers having a volume of less than or equal to about 500 picoliters (claim 21) or 250 picoliters (claim 22).
Zayac et al. do not explicitly teach the device comprises a plurality of chabmers having a volume of less than or equal to about 500 picoliters or 250 picoliters.
Makrigiorgos et al. teach that microfluidic devices comprising a plurality of wells/partitions, wherein the number of wells are greater than 10,000, greater than 50,000, greater than 500,000, wherein the volume of wells is 100 pL or less:
“device (e.g., a titer plate, or a microfluidic device) can include any suitable number of wells … device can include greater than … 10,000, greater than 50,000, greater than 100,000 …” (page 41, lines 19-22)
“wells may have any suitable size, volume, shape, and/or configuration … well can have a volume of less than … 100 pL …” (page 41, lines 25-30)
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 combine the teachings of Zayac et al. with the teachings of Makrigiorgos et al., thereby arriving at the invention as claimed for the following reasons.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
As evidenced above, one of ordinary skill in the art would have been well aware of diagnostics devices comprising wells of varying sizes of partitions. Given that the assay discussed by Zayac et al. is directed to a digital PCR and digital HRMA, one of ordinary skill in the art would have been motivated to arrive at smaller sized chambers in which to perform the assays so as to allow a large number of chambers onto the limited real estate of the microfluidic device to achieve the required averaged zero to one template molecule in each of the partitioned chambers. And doing so would have been within the purview of the ordinarily skilled artisans as evidenced by Makrigiorgos et al. who already suggest for a microfluidic device comprising wells/partitions of claimed volume.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
The rejection of claims 29 and 30 under 35 U.S.C. 103 as being unpatentable over Zayac et al. (WO 2018/094091 A1, published May 2018) in view of Cao et al. (Journal of Laboratory Automation, 2016, vol. 21, no. 3, pages 402-411) and Sreejith et al. (Lab Chip, 2019, vol. 19, pages 3220-3227), made in the Office Action mailed on October 31, 2025 is maintained for the reasons of record.
Applicants do not present any arguments for the present rejection but rely solely on their argument presented for the anticipation rejection over Zayac et al. which have been fully responded to above.
Therefore, instant rejection is maintained for the reasons of record.
The Rejection:
Zayac et al. do not explicitly teach the detection unit comprises a camera comprising CMOS sensor (claim 29), or that telecentric lens is disposed between the camera and the plurality of chambers (claim 30).
Cao et al. teach that camera comprising CMOS sensor is also used in detection of fluorescence signals from a microfluidic device (“instrument uses a CMOS sensor in a Canon EOS 5D Mark II camera for fluorescence imaging of the liquids in the cartridge”, page 403, 2nd column) for an HRMA (High Resolution Melting Analysis) (“we present an integrated microfluidic based rapid PCR-HRMA system …”, page 403, 1st column, bottom para).
Sreejith et al. evidence that a telecentric lens is known in the art to be coupled with camera comprising a CMOS sensor:
“PCR microreactor was captured using a vertically mounted CMOS camera … attached with 0.5 x telecentric lens” (page 3223, 1st column, 2nd full para)
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 combine the teachings of Zayac et al. with the teachings of Cao et al. and Sreejith et al., thereby arriving at the invention as claimed for the following reasons.
The reasons to combine the teachings of Cao et al. and Sreejith et al. is one based on a combination of teachings yielding no more than a predictable outcome, as discussed by the Supreme Court.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
As evidenced by Cao et al. and Sreejith et al. the art evidences that a camera comprising a CMOS sensor is an alternative means of detecting fluorescence image produced in HRMA, with telecentric lens being employed.
Therefore, their combination into the optical detection system of Zayac et al. would have yielded no more than a predictable outcome of a system which comprises means of optical detection which are employed in the art and therefore, would have been an obvious consideration for the one of ordinary skill in the art.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Conclusion
No claims are allowed.
Applicants are advised that Zhang et al. (Scientific Reports, November 2017, pages 1-8) teach a method of multiplex HRM assay, wherein the method performs an amplification reaction to generate at least two amplification products, one of which containing a non-complementary 5’ region of the primer (GC-rich tail) therein and another which does not (see page 2, Results; also Fig. 4, “a GC tail was added … to increase the melting temperature separation”, page 5). Therefore, Zhang et al. would render obvious the generation of two amplification products, one of which containing an added sequence of the GC region from an allele-specific forward primer and another allele-specific forward primer without said added sequence for the advantage of producing better separation during an HRM.
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.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 April 7, 2026
/YJK/
1 “a plurality of chambers of a plate”, see claim 1.
2 The detection unit and processor(s) are recited as being “configured to use a plurality of nucleic acid molecules to generate”, which does not actively require that the system comprise the recited double-stranded nucleic acid. Because the system is disclosed as having detection means and processor(s) that is capable to delivering nucleic acids into the partitions, the system of Zayac et al. is fully capable of delivering any reagents (such as primers, substrates, and samples) to the partitions of the their device.
3 An alternative interpretation of the device comprising the partitions/chambers will be addressed in a subsequent obvious rejection below.