DETAILED ACTION
The present Office Action is responsive to the Amendment received on November 3, 2025.
Preliminary Remark
Claims 1, 4 and 5 are canceled.
Claims 21-27 are new.
Claims 11-13 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 May 17, 2022.
Claim Objections
The objection to claim 8 for the informality noted in the Office Action mailed on August 4, 2025 is withdrawn in view of the Amendment received on November 3, 2025.
Claim Rejections - 35 USC § 112 – 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.
Claims 2, 3, 6-10, and 14-27 are 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.
Claims 17 and 18 recite the phrase, “the sample port”. There is an insufficient antecedent basis for this limitation in the claim. The phrase should be amended to, “the liquid sample inlet port”.
Claim 21 recites the phrase, “electric circuitry comprising first, second and thermal elements.” It would appear that the phrase is missing a word. For the purpose of prosecution, the phrase has been construed to mean, “electric circuitry comprising first, second, and third thermal elements”. Relatedly, the phrase, “wherein the first, second, and third thermal elements are spatially separated” do not have a proper antecedent basis for the term, “third” as currently recited.
Claims 23, 24, and 25 recites the phrase, “the inlet port”. It is unclear what this is as the term has no proper antecedent basis. For the purpose of prosecution, the phrase has been assumed to mean, “the liquid sample inlet port”.
Claim 27 is indefinite because the claim term appears to be redundant to claim 26. Claim 27 depends from claim 26, to claim 21. Claim 21 already recites that the reaction channel includes “a cyclic fluidic path having a triangular shape”. While claim 26 (dependent from claim 21) further defines this reaction channel as comprising a capillary, claim 27 which recites that the capillary comprises a continuous triangular loop is redundant as the claim already required that the reaction is “cyclic” in a triangular form. There is no another embodiment contemplated by Applicants and therefore, claim 27 does appear to further limit the parent claim 26.
Claims 2, 3, 6-10, 14-20, and 22-27 are indefinite by way of their dependency on claim 21.
Claim Rejections - 35 USC § 103
The rejection of claims 1-3, 6-10, and 14-20 under 35 U.S.C. 103 as being unpatentable over Chen et al. (Analytical Chemistry, 2004, vol. 76, pages 3707-3715) in view of Agrawal et al. (Angew. Chem. Int. Ed., 2007, vol. 46, pages 4316-4319), Priye et al. (Microfluidic Methods for Molecular Biology, 2016, Chapter 3, pages 55-69) and Wang et al. (International Journal of Nanomedicine, 2012, vol. 7, pages 5019-5028), as evidenced by Chung et al. (US 2008/0131956 A1, published June 5, 2008), made in the Office Action mailed on August 4, 2025 is withdrawn in view of the Amendment received on November 3, 2025.
The rejection has been withdrawn based on formality as Applicants have canceled the sole independent claim (claim 1) from which the dependent claims were established and submitted new claim 21 with new limitations.
Rejection – New Grounds, Necessitated by Amendment
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 2, 3, 9, 10, 14, 15, 17-19, and 21-24 are rejected under 35 U.S.C. 103 as being unpatentable over Abrams et al. (Annals of the New York Academy of Sciences, 2007, vol. 1098, pages 375-388) in view of Priye et al. (Microfluidic Methods for Molecular Biology, 2016, Chapter 3, pages 55-69) and LaBarre et al. (US 2009/0004732 A1, published January 2009).
With regard to claim 21, Abrams et al. teach a thermocycling unit comprising the below configuration (from Fig. 4):
PNG
media_image1.png
485
511
media_image1.png
Greyscale
As seen, the thermocycling unit comprises:
A reaction channel (or conduit) including cyclic fluid path having a triangular shape (see shape); and
First, second, and third thermal elements spatially separated and are configured to be set to different pre-determined temperature values to establish distinct temperature zones and a temperature gradient along the reaction channel for inducing a stable and cyclic flow within the reaction channel following the thermal gradient (see the three distinct heaters which are configured to heat to three separate temperature conditions of a PCR reaction1).
With regard to claim 22, the first thermal element defines a denaturing zone, the second thermal element defines an annealing zone having a second temperature that is lower than the first temperature (i.e., annealing is lower than denaturation), and the third thermal element defines an elongation zone having a third temperature that is higher than the second temperature and lower than the first temperature (i.e., extension is higher than annealing, but lower than the denaturation).
While Abrams et al. teach a closed, triangular-looped thermocycler with three separate heaters on each of the three sides (see above), the artisans do not incorporate the thermocycler into a device that can be utilized to receive a sample and analyzed in an integrated system.
Consequently, Abrams et al. do not teach: a) a housing comprising an optical interface being connected to an optical path within the thermocycling unit for guiding light source through the reaction channel via an optic window in the reaction channel to the camera of a smartphone; b) a data transfer port and an energy transfer port; c) a liquid sample inlet port having a gate connected to the reaction channel, wherein the sample inlet port is arranged to inject into the reaction channel in a flow direction aligned with and following the temperature gradient, thereby providing movement with minimized turbulence of the reaction mixture; and d) a docking mechanism for reversibly docking the thermocycling unit to the smartphone.
Abrams et al. do not explicitly teach a sample inlet port being disposed between the denaturing zone and the elongation zone (claim 23) or into the denaturing zone (claim 24), or that the sample port is configured to accept a lancet (claim 17), or a capillary tube (claim 18), or that the sample inlet port is in the same direction as the flow through the triangular cyclic fluidic path (claim 19), or that the data transfer port and energy port are combined in a USB port (claim 2).
Abrams et al. do not explicitly teach that the PCR reagents are prefill-ed (claim 3).
LaBarre et al. teach a closed-loop thermocycler, wherein the artisans teach a well-known and common-sense approach of adding a sample inlet to the closed-loop thermocycler path (see Fig. 10, element 1020; also “a closed-loop reaction channel 1012 … sample inlet tape 1020 is first removed … 50 mL (for example) of sample is then pipetted into the channel 1012 at inlet 1021 and fills the entire closed loop volume … sample will reconstitute with a PCR master mix 1024 of primers, uNTPs, and TAQ polymerase which is prestaged [or pre-filled] in the denaturation zone 1018.”, section [0068]).
Priye et al. teach a well-known practice of adopting a diagnostic assays into a housing which means to provide power, imaging, and data collection in a portable PCR device:
“[t]hermal convention-driven to drive a microliter-scale convective flow that transports reagents through the denaturing, annealing, and extension temperature zones without the need for external mechanical pumping, offering the advantages of isothermal operation in a greatly simplified format” (page 56, 3rd paragraph),
Priye et al. also explicitly suggest that the triangular shaped convection means as discussed by Agrawal et al. (see page 57, Figure 3.1(e)).
PNG
media_image2.png
656
464
media_image2.png
Greyscale
Priye et al. also teach that such convective PCR thermocyclers, because of their low power consumption, can be configured to work together with a smart phone such as iPhone 4S (which comprises a CPU, a camera, a power source (its own battery, see below-reproduced figure 3.3):
As shown, the artisans teach that a thermocycling unit with a PCR reactor and its heater unit encased in a 3D printed housing, wherein the unit also comprise a docking mechanism for reversibly docking the thermal cycling unit to the smartphone (also, see the assembled structure on Figure 3.5 on page 62).
With regard to claim 9, the docking mech for docking the smartphone unit to the smart phone comprises a snap fit (see Figure 3.3, where the smartphone housing comprises a molded depression that molds to the shape of the iPhone).
With regard to claim 10, the optical path from the PCR reactor to the camera of the iPhone is via lens (see 60X mini microscope, Fig. 3.3).
With regard to claim 14, the system comprising the smartphone and PCR reactor is disclosed in Figure 3.3 and 3.5).
With regard to claim 15, the system performs quantitative/qualitative real time PCR (see Figure 3.5 where amplification intensity is mapped in real time).
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 Abrams et al. with the teachings of Priye et al. and LaBarre et al., thereby arriving at the invention as claimed for the following reasons.
As discussed above, Abrams et al. teach a miniaturized convective thermocycling device that performs a PCR reaction in a closed-loop, triangular shaped format, wherein each of the three triangular shaped regions are configured to heat in each of the conventional PCR temperature condition (i.e., denaturation, annealing, and elongation).
While Abrams et al. did not explicitly teach this thermocycler in an integrated system that allows sample introduction, detection, and data transfer, doing so would have been obvious given the advancement of the portable, on-site diagnostic technology in the area of molecular diagnostics.
This is plainly evidenced by Priye et al.:
“[w]e sought to apply these newfound physical insights to design a low-cost convective PCR thermocycling system suitable for portable operation” (page 60)
As well, Priye et al. also motivate the combination of utilizing smartphones for providing the necessary components for operation and detection of such convective thermocyclers:
“Smartphones have become an ubiquitous devices that are not only an essential part of daily communication but also provide state-of-art imaging, computation, and data analysis capabilities” (page 63)
And as demonstrated by Priye et al. in Fig. 3.5, as well as in Fig. 3.6, fabrication of a housing that integrate the smartphone with the thermocycler has been demonstrated.
Therefore, the integration of the thermocycler of Abrams et al. into a system comprising a housing configured to operate with a smartphone would have been obvious for the benefit of producing a low-cost, portable device for molecular diagnostics.
As to configuring the thermocycler to accept a sample into for analysis, doing so would have been an obvious modification to utilize the thermocycler of Abrams et al. for the purpose of analyzing samples via means known in the art, as explicitly demonstrated by LaBarre et al. who teach pipetting the sample into a sample inlet port (section [0067]).
As to the well-known means of delivering the sample via a lancet or a capillary, the Office asserts that such means of sample delivery into a microfluidic device are well-known and recognized in the art as functional equivalents and therefore render them obvious, well within the purview of an ordinarily artisan.
As to injecting the sample into a region of the flow path which is between the denaturing zone and an elongation zone, or into the denaturing zone in the directional flow of the triangular path, the Office contends that such a placement simply would have involved common sense.
This is because the thermocycling device of Abrams et al. operated via a closed-loop cycling of the sample mixture through the three temperature conditions of a PCR profile, that involves denaturation, annealing, and elongation (or extension) conditions.
Therefore, one of ordinary skill in the art would have had the common sense to inject the sample into a region of the path at the point or slightly before (i.e., between elongation/denaturation) the denaturation conditions, into a flow path that goes from denaturation, annealing, and elongation conditions of a PCR cycle.
In KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007), the Supreme Court held that “obvious to try” was a valid rationale for an obviousness finding, for example, when there is a “design need” or “market demand” and there are a “finite number” of solutions. 550 U.S. at 421, 82 USPQ2d at 1397 (“The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.”).
With regard to the energy and data being provided through the same USB, it is a well-established means known in the art to utilize USB ports, such as USB-C port for providing power as well as data transmittal and its integration with smartphones such as an iPhone, thus obvious.
Lastly, with regard to the term, “gate,” the term is not distinctive over the teachings of LaBarre et al. wherein an opening through which the sample is injected could be considered a “gate” that is permanently open.
For these reasons, the invention as claimed is deemed prima facie obvious over the cited references.
Claim 8, 26, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Abrams et al. (Annals of the New York Academy of Sciences, 2007, vol. 1098, pages 375-388) in view of Priye et al. (Microfluidic Methods for Molecular Biology, 2016, Chapter 3, pages 55-69) and LaBarre et al. (US 2009/0004732 A1, published January 2009), as applied to claims 2, 3, 9, 10, 14, 15, 17-19, and 21-24 above, and further in view of Agrawal et al. (Angew. Chem. Int. Ed., 2007, vol. 46, pages 4316-4319) and Chen et al. (Analytical Chemistry, 2004, vol. 76, pages 3707-3715).
The teachings of Abrams et al., Priye et al. and LaBarre et al. have already been discussed above.
Abrams et al., Priye et al., and LaBarre et al. do not explicitly teach every possible heating means for their thermocycler. Abrams et al. do not teach that channel is capillary (claims 26 and 27).
Agrawal et al. teach a thermocycling unit for carrying our PCR (polymerase chain reaction) comprising the below structure (from Supplementary Fig.: 4(a)):
PNG
media_image3.png
312
406
media_image3.png
Greyscale
As seen, unit comprises a looped triangular PCR reactor similar to that disclosed by Abrams et al., wherein the unit is integrated into a device which comprises: a) a removable reaction channel providing a single triangular cyclic fluidic path (FEP tubing, also, “[l]oops were constructed from three different tubing diameters: inside diameter 320, 400, and 510 mm … corresponding to reactor volumes of 10, 16, and 25 mL, respectively. Lengths of tubing were filled with PCR reagents and then the two open ends were joined together by using a short sleeve tygon tubing”, page 4318, 2nd column; tubing is removably placed upon the aluminum scaffold), the single triangular cyclic fluidic path comprising a single denaturing zone, a single annealing zone, and a single elongation zone (see Figure 1, where the tubing is exposed to three different temperature regions of denaturing, annealing, and extension reactions), wherein the denaturation, anneal, and extension temperatures are explicitly taught as being 95oC, 50-60 oC, and 72 oC, respectively (see Figure 1(a)), wherein the three separate temperature conditions are provided by their respective thermal elements (aluminum heating blocks, “heaters are independently adjusted to maintain denaturation … extension … across the two inclined legs while the horizontal leg passively attains annealing conditions”, page 4316, 2nd column), wherein the electric circuitry is disposed on a reusable scaffold of the thermocycling unit that is separate from the removable reaction channel (see aluminum scaffolding above, and electronic circuitry which provides the temperature conditions from power source (Supplementary Figure 5).
The reaction channel is prefilled with PCR reagents (see above).
The thermal element is Peltier heater (see page 4318, 2nd column).
Chen et al. teach a closed-loop triangular shaped PCR device (see page 3708, Figure 2).
Chen et al. suggest that while the tubes of the closed-loop carrying the amplification reagents had an inner diameter of 764 mm), the artisans teach that smaller diameter tube could have been used without sacrificing performance (“the fluid velocity depends on sensitivity on the tube’s diameter, we could have used a smaller diameter tube without sacrificing performance”, page 3709, 2nd column, 2nd paragraph).
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 Abrams et al., Priye et al., and LaBarre et al., with the teachings of Agrawal et al. and Chen 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.”
Utilizing heating means which are known in the art to be useful in a thermocycling reaction, such as Peltier elements, would have yielded no more than a predictable outcome, that is, providing heating means known in the art to that of Abrams et al.
As well, given that the thermocycling device of Agrawal et al. is in the same configuration as that of Abrams et al., that is, a closed-looped, triangle, the integration of Peltier element for the heaters of Abrams et al. would have yielded a reasonable expectation of success.
With regard to the closed-loop being made of capillary based on the suggestion made by Chen et al., one of ordinary skill in the art would have had a reasonable expectation of success at utilizing any material, such as a capillary tubing of smaller diameter as the closed-loop triangular path means.
For these reasons, the invention as claimed is deemed prima facie obvious over the cited references.
Claims 6, 7, 20, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Abrams et al. (Annals of the New York Academy of Sciences, 2007, vol. 1098, pages 375-388) in view of Priye et al. (Microfluidic Methods for Molecular Biology, 2016, Chapter 3, pages 55-69) and LaBarre et al. (US 2009/0004732 A1, published January 2009), as applied to claims 2, 3, 9, 10, 14, 15, 17-19, and 21-24 above, and further in view of Van Den Boom et al. (WO 2019/067567 A1, published April 2019).
The teachings of Abrams et al., Priye et al. and LaBarre et al. have already been discussed above.
Abrams et al., Priye et al., and LaBarre et al. do not explicitly teach a gate connected to a reaction channel and a liquid sample inlet port, which is a separation unit for a biological sample (claim 6), which is a blood plasma separation filter (claim 7), or that the liquid sample inlet port comprises a filter to capture red blood cells (claim 20), or that the gate comprises a check valve disposed between the inlet port and the reaction channel (claim 25).
Van Den Boom et al. teach a well-known means of collecting a sample through a filtering means that separate the blood particles to analyze plasma:
“devices that comprise a sample purifier for removing a cell from a biological fluid sample to produce a cell-depleted sample; and at least one of a detection reagent and a signal detector detecting a plurality of biomarkers in the cell-depleted samples.” (section [0006])
“In some instances, the sample purifier comprises a filter. In some instances, the sample purifier comprises a wicking material or capillary device for pushing the biological fluid through the filter” (section [0006])
“In some instances, the sample purifier removes cells from blood, and the cell-depleted sample is plasma. In some instances, the device is contained in a single housing” (section [0006])
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 Abrams et al., Priye et al. and LaBarre et al. with the teachings of Van Den Boom et al. and features well-known in the art, 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.”
Adding features known in the art, such as providing a filtering means to an analytical device, or check valves that manipulate the sample flow into a diagnostic device would have been well-within the purview of the ordinarily artisan. For example, molecular diagnostic devices have long been recognized in the art for analyzing samples of all types, with means to filter out undesired elements prior to their detection (as evidenced by Van Den Boom et al.), as well as utilizing valves to control the entry of the sample.
Therefore, addition of such features would have been known in the art, as well as the advantages of doing so, yielding no more than a predictable outcome recognized in the art.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Conclusion
No claims are allowed.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YOUNG J KIM/Primary Examiner
Art Unit 1637 January 28, 2026
/YJK/
1 Absent evidence to the contrary, the temperature gradient would necessarily form as the configuration is identical to that of Applicants’ own, see Fig. 3A.