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 .
Status of Claims
Claims 1-19 are pending and have been examined.
Priority
This application 18/015,646 (PGPub: US2023/0251250) was filed 01/11/2023. This application is a 371 of PCT/CN2021/113725 filed 08/20/2021. This application claims priority to foreign application China 202010934760.5 filed 09/08/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)- (d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The Information Disclosure Statements filed 1/11/2023, 10/5/2023, 08/22/2024, 10/09/2024, 06/23/2025, 10/24/2025 have been considered by the Examiner.
Claim Rejections - 35 USC § 112
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 3 and 4 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.
Claim 3 is indefinite because it states the presence of a plurality of detection slots with the membrane strip correspondingly embedded in each of the plurality of slots and it is unclear if the single claimed membrane strip sits in each of the slots or if the claim is intended to state that there are a plurality of strips present in each of the plurality of slots.
Claim 4 is rejected by virtue of its dependence on claim 3.
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.
Claim(s) 1-4, 7 and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (US 2011/0189701, Pub Date: 08/04/2011).
Regarding claim 1, Kim teaches throughout the publication a microfluidic immunoassay chip (abstract and see Figure 1), comprising at least one detection unit and having a rotation center (paragraph 0009 and see Figure 2), wherein the detection unit comprises:
a loading cell provided with a loading hole (sample introduction inlet, 110, as seen in Figure 3);
a reaction and detection cell being in communication with the loading cell (analysis chamber 400), the reaction and detection cell being provided with a detection membrane strip coated with a capture antigen or a capture antibody (paragraphs 0067-0069, porous membrane with detection region 420 with a capture binder to assay analytes);
a washing cell configured to be pre-filled with a buffer solution, the washing cell being in communication with the reaction and detection cell (washer chamber 330, paragraph 0065);
an enzyme storing cell configured to be pre-filled with an enzyme labelled antibody, the enzyme storing cell being in communication with the reaction and detection cell (first buffer chamber 310, paragraphs 0055-0056);
a substrate cell configured to be pre-filled with a reaction substrate for the enzyme labelled antibody, the substrate cell being in communication with the reaction and detection cell (second buffer chamber 320, paragraph 0058);
a termination cell configured to be pre-filled with a reaction terminating liquid, the termination cell being in communication with the reaction and detection cell (stoppage chamber 460, paragraph 0071); and
a waste liquid cell configured to receive a waste liquid, the waste liquid cell being in communication with the reaction and detection cell (waste chamber 360);
wherein the reaction and detection cell is further away from the rotation center than the loading cell, the washing cell, the enzyme storing cell, the substrate cell, and is closer to the rotation center than the waste liquid cell (see cell placement of Figure 2).
While Kim teaches the presence of the termination cell (stoppage chamber 460), the reference does not teach that the reaction and detection cell is further away from the rotation center than the termination cell. However, one skilled in the art would have had motivation to move the termination cell of Kim to be closer to the rotation center than the reaction and detection cell since moving the position of the termination cell would not have significantly modified the operation of the device and since it would have been an obvious matter of design choice based on the overall desired device footprint or placement of the termination cell relative to the reaction/detection chamber (analysis chamber 400) of Kim. See MPEP 2144.04.
Regarding claim 2, Kim teaches the chip further comprising a valve disposed between the reaction and detection cell and each of the loading cell, the washing cell, the enzyme storing cell, the substrate cell, and the termination cell (see Figure 2 and valves 231, 311, 321, 331 and 461).
Regarding claim 3, Kim teaches that the analysis chamber can comprise a porous membrane and thus inherently teaches at least one slot through which the porous membrane is situated (claimed “embedded”) within the chamber (Figure 2 illustrating a membrane present within a rectangular chamber). Although Kim does not teach a plurality of detection slots spaced from each other to embed the porous membrane, it has been held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced (See MPEP 2144.04).
Regarding claim 4, while Kim does not specifically teach the chip wherein a height difference between a top surface of the detection membrane strip and a top edge of a side wall of the each of the plurality of detection slots is about 20 micrometer to about 200 micrometer, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 4 are for any particular purpose or solve any stated problem, and the prior art teaches that dimensions of the detection region may be varied based on the desired cross-section and range needed to complete the desired assays (for example, see paragraph 0073). Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the microfluidic immunoassay art.
Regarding claim 7, Kim teaches the chip wherein the detection unit further comprises a precipitation cell being in communication with the loading cell, and the precipitation cell is further away from the rotation center than the loading cell (see Figures 2 and 4, precipitation collector 220 and paragraph 0053).
Regarding claim 11, Kim teaches the chip comprising a washing cell in communication with the reaction and detection cell (paragraph 0065, washing chamber 330). Although Kim does not specifically teach that the washing cell is at least three washing cells, it has been held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced (See MPEP 2144.04).
Regarding claim 12, Kim teaches the chip wherein the detection unit further comprises an excess sample cell being in communication with the loading cell, and a distance between the excess sample cell and the rotation center is equal to a distance between the loading cell and the rotation center (Figure 2, chamber between 250 and 230 as described in paragraph 0054 to receive excess sample).
Regarding claim 13, Kim teaches the chip wherein the detection unit further comprises a venting hole and a gas channel (for example, see Figure 2, vent chamber 303 with gas channel downstream of chamber 303 but upstream of valve 314), the venting hole is closer to the rotation center than the washing cell, the enzyme storing cell, the substrate cell, and the termination cell; the washing cell, the enzyme storing cell, the substrate cell, and the termination cell each are in communication with the venting hole through the gas channel (see Figure 2).
Regarding claim 14, although Kim does not specifically teach the dimensions of the gas channel to have a width of the gas channel is about 50 micrometer to about 100 micrometer, and a height of the gas channel is about 50 micrometer to about 100 micrometer, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 14 are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the microfluidic immunoassay art.
Claim(s) 5-6 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (US 2011/0189701, Pub Date: 08/04/2011), as applied to claim 1 above, and further in view of Yoo (US 2009/0253130).
Regarding claims 5-6, Kim teaches the microfluidic chip as described above but fails to teach a dilution cell filled with a diluent.
Yoo teaches throughout the publication a lab on chip assay system (abstract). More specifically, as seen in Figure 9K, the chip includes a sample inlet (121) and a buffer chamber for diluting the sample with a diluting solution (131) as described in paragraph 0649. As seen in the figure, the dilution chamber (131) is further away from the rotation center (170) than the loading cell (121) and closer to the rotation center than the reaction and detection cell (132); the dilution cell is in communication with the loading cell through a siphonic channel (See preparation chamber 130); and the reaction and detection cell is in communication with the loading cell through the dilution cell (see Figure 9K). Additionally, Koo teaches that the siphonic channel from one end thereof being in communication with the loading cell extends in a direction towards the rotation center, bends at a position closer to the rotation center than the loading cell, and extends in a direction away from the rotation center, thereby being in communication with the dilution cell (see shape of chamber 130 extending from chamber 121 to 70a in Figure 9K).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to incorporate within the detection unit of Kim, a dilution chamber connecting to the loading chamber via a siphonic shaped channel as taught by Yoo because it would have been desirable to dilute the sample which is well-known to increase assay accuracy by reducing sample interferences.
Regarding claim 15, while Kim does not teach a bar code disposed on the detection unit, Yoo teaches that a cartridge is printed with a barcode pattern indicating product ID (paragraph 0206). It would have been obvious to one having ordinary skill in the art at the time the invention was filed to incorporate on the detection unit of Kim, a barcode as taught by Yoo because it would have been desirable to identify the unit being run and the assays being conducted (Yoo, paragraph 0214).
Claim(s) 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (US 2011/0189701, Pub Date: 08/04/2011), as applied to claim 1 above, and further in view of Bertozzi et al. (WO 2018/183779, Pub Date: 10/04/2018).
Regarding claims 8-10, Kim teaches the method as described above wherein the chip can be used in various applications such as for the detection of various environmentally harmful substances (paragraph 0046) wherein capture probes to assay desired analytes can include antigens, antibodies, enzymes, DNA, RNA and the like, depending on the subject analyte materials to be analyzed (paragraph 0072). However, Kim fails to teach that the capture antigen is an autoantibody target detection substance or an allergen.
Bertozzi teaches throughout the publication methods and reagents for multiplex detection of antibodies (abstract). More specifically, Bertozzi teaches the detection of allergen-specific antibodies, with target allergens including pollens, house dust, animal dander, cockroach allergy, to name a few (page 69, line 10 – page 70, line 6). Additionally, Bertozzi teaches that the sample can also be tested for autoantibodies such as dsDNA and ssDNA (page 84, line 22-32).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to incorporate within the membrane strip with immobilized capture antigen of Kim, autoantibody target detection or allergen detection as taught by Bertozzi because Kim is generic regarding the capture agents to be used and one skilled in the art would have been motivated to choose the appropriate capture agent based on the desired analyte to be analyzed.
Claim(s) 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (US 2011/0189701, Pub Date: 08/04/2011), as applied to claim 1 above, and further in view of Yoo (US 2009/0253130) and Watters et al. (US2018/0371058, Pub Date: 12/27/2018) .
Regarding claims 16-17, Kim teaches a method comprising: providing the microfluidic immunoassay chip of claim 1 (see rejection of claim 1 above); loading a sample liquid into the loading cell through the loading hole; centrifuging the microfluidic immunoassay chip, releasing the sample liquid from the loading cell into the reaction and detection cell, and incubating the sample liquid with the detection membrane strip; releasing the buffer solution from the washing cell into the reaction and detection cell to perform a first washing; releasing the enzyme from the enzyme storing cell into the reaction and detection cell, and incubating the enzyme with the detection membrane strip; releasing the buffer solution from the washing cell into the reaction and detection cell to perform a second washing; releasing the reaction substrate from the substrate cell into the reaction and detection cell, and incubating the reaction substrate with the detection membrane strip; releasing the buffer solution from the washing cell into the reaction and detection cell to perform a third washing; detecting a reaction result from the reaction and detection cell (paragraphs 0054-0074 and 0096-0101).
Although Kim does not explicitly teach an enzyme labeled antibody or releasing a reaction terminating liquid from the termination cell into the reaction and detection cell to terminate the reaction, in addition to a dilution cell for diluting the sample to provide to the reaction area, Yoo teaches that assay labels can include enzyme linked antibodies (paragraph 0112) and further teaches, as seen in Figure 9K, the chip includes a sample inlet (121) and a buffer chamber for diluting the sample with a diluting solution (131) as described in paragraph 0649. As seen in the figure and paragraph 0649, the sample travels from the inlet (121) to the dilution chamber (131) which releases the sample into the reaction and detection cell (132). Additionally, Watters teaches an assay kit that includes a stop buffer to stop reaction development (paragraph 0384).
It would have been prima facie obvious at the time the invention was filed to incorporate within the enzyme storing cell in the method of Kim, an enzyme linked antibody label as taught by Yoo because Kim is generic regarding the types of labels that can be incorporated and one skilled in the art would have been motivated to choose the appropriate label based on the desired type of assay to be conducted. Additionally, one skilled in the art would have been motivated to incorporate within the detection unit of Kim, a dilution chamber connecting to the loading chamber and storing dilution liquid as taught by Yoo because it would have been desirable to dilute the sample which is well-known to increase assay accuracy by reducing sample interferences. Finally, it would have been obvious to one skilled in the art to incorporate within the termination cell of Kim, a stop buffer as taught by Watters because it would have been desirable to have more control over the assay conditions in order to stop color development (Watters, paragraph 0384).
Regarding claim 18, Kim teaches the method wherein in the releasing the sample liquid from the loading cell into the reaction and detection cell, the sample liquid is stratified by centrifugation and an impurity in the sample liquid is precipitated into a precipitation cell, and the sample liquid after the precipitation is released from the loading cell into the reaction and detection cell (paragraphs 0050 and 0053, precipitate collector).
Regarding claim 19, Kim teaches the method wherein in the releasing the sample liquid from the loading cell into the reaction and detection cell, excess sample liquid is forced into an excess sample cell (paragraph 0054).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M GIERE whose telephone number is (571)272-5084. The examiner can normally be reached M-F 8:30-4:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy L Nguyen can be reached at 571-272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/REBECCA M GIERE/Primary Examiner, Art Unit 1677