DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-3, 5, 6, 8-15, and 17 have been considered but are moot because the new ground of rejection does not rely on the combination of references applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
With respect to the rejection under 35 U.S.C. 101, Applicant has amended independent claim 1 to recite a microfluidic device having at least one inlet, a plurality of outlets, and a curvilinear fluid passageway having a widened portion that connects the curvilinear fluid passageway with the plurality of outlets, and argued that the claims are directed to eligible subject matter. The Examiner notes that the expression of cardiovascular disease associated biomarkers result from a subject’s disease state, thus the expression of cardiovascular disease associated biomarkers is a law of nature. The Examiner also notes that determining whether a subject has a cardiovascular disease is a mental process that only requires analyzing the expression of cardiovascular disease associated biomarkers, and making a determination of the subject’s health status based on the expressed biomarkers. As such, the Examiner contends that the claims recite both a law or nature and an abstract idea. The judicial exceptions are not integrated into a practical application as nothing occurs after making the determination with respect to cardiovascular disease in the subject. Also, the additional elements do not render the claim patent eligible as they are all directed to routine and conventional activity that are well known in the art. Specifically, the Examiner notes that the claimed microfluidic device having a curvilinear fluid passageway, and a widened channel portion connecting the curvilinear fluid passageway to a plurality of outlets are known in the art as evidenced by reference to Bhagat et al., (US 2016/0303565). Reference to Bhagat et al., teach a microfluidic device for cell sorting wherein the device comprises an inlet, a plurality of outlets, a curvilinear fluid passageway, and a widened channel portion for separating cells into different outlets (paragraph 0021, figure 1a, b). As such, the separating and collecting steps are known in the art, and do not provide significantly more to the judicial exceptions. Given these views, the Examiner maintains that the claims recite to a judicial exception without significantly more, and therefore are directed to ineligible subject matter.
With respect to the prior art rejections, the Examiner agrees that the combination of Tavassoli et al., in view of Malima et al., do not teach a microfluidic device as recited in amended claim 1. However, as detailed below, Independent claim 1 now stands rejected under 35 U.S.C. 103 as being unpatentable over the combination of Tavassoli et al., in view Bhagat et al., and further in view of Malima et al. Because reference to Bhagat et al., is newly cited, the Examiner will not argue the merits of its teachings here, but will instead rely on the rejection detailed below. Therefore, in light of the teachings of the prior art, and the arguments presented here, the Examiner contends that the limitations of the instant claims are taught by the references cited below, thus the claims are not in condition for allowance.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3, 5, 6, 8-15, and 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim(s) recite(s) both a law of nature and an abstract idea. Claim 1 is directed to a method of diagnosing a cardiovascular disease comprising obtaining a sample fluid from a subject, separating components of the sample fluid into a plurality of fluid fractions using a microfluidic device comprising a curvilinear fluid passageway having at least one inlet, a plurality of outlets and a widened channel portion connecting the inlet with the plurality of outlets, collecting one or more fluid fractions, detecting one or more cardiovascular disease associated biomarkers, and determining one or more cardiovascular diseases in the subject. The presence or amount of cardiovascular disease biomarkers present in a sample results from the subjects disease state, and therefore is a law of nature. Determining one or more cardiovascular diseases based on the presence or amount of cardiovascular disease biomarkers is an abstract idea in that it only requires the mental step of analyzing the biomarker data, and making a determination of whether a subject has a cardiovascular disease or not.
The judicial exceptions are not integrated into a practical application because nothing occurs after determining the presence of a cardiovascular disease. No practical steps to treat, or attenuate the cardiovascular disease are recited in the claim, thus no practical application of the law of nature or the abstract idea is recited by the claim.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional limitations are directed to well-understood, routine, and conventional activity. The Examiner notes that determining the level of a biomarker in blood by any means is well-understood, routine, and convention activity (MPEP 2106.05(d) II), thus the step of detecting one or more cardiovascular disease-associated biomarkers does amount to significantly more. With respect to the steps of obtaining a sample, separating components of the sample, and collecting one or more selected fluid fractions, the Examiner points to reference to Tavassoli et al., (Small, Vol 17, Issue 8, December 28, 2020) who teach label free isolation of cardiomyocytes wherein a sample is obtained from a subject, components of the sample are separated using inertial microfluidics in a microfluidic device having a spiral channel, collecting the separated fluid fractions, and detecting biomarkers within the sample. Additionally, utilizing a microfluidic device comprising a curvilinear fluid passageway having a widened channel portion connecting the inlet with the plurality of outlets is known in the art as evidenced by reference to Bhagat et al., (US 2016/0303565) (paragraph 0021, figure 1a, b) who teach sorting cells by size with a spiral microfluidic channel having a widened channel portion that connects the inlet with a plurality of outlets (paragraph 0021, figure 1a, b). Because these elements are known within the prior art, the Examiner contends that the obtaining, separating, collecting, and detecting steps are conventional and well known in the art.
Therefore, when considered as a whole, the Examiner contends that the limitations of claim 1 are directed to ineligible subject matter without significantly more, and therefore do not comply with 35 U.S.C. 101. For the sake of brevity, the Examiner has limited the discussion to claim 1, but notes that the rationale holds for claims 2, 3, 5, 6, 8-15, and 17.
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 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.
Claim(s) 1, 2, 5, 6, 8, 9, 11-15, and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tavassoli et al., (Small, Vol 17, Issue 8, December 28, 2021) in view of Bhagat et al., (US 2016/0303565), and further in view of Malima et al., (US 2016/0258945).
Regarding claims 1, 2, 6, 9, 14, and 15, Tavassoli et al., teach label-free isolation of cardiomyocytes comprising obtaining a sample fluid (Label-Free CM Fractionation, page 3), separating cells in the sample into different fractions (Label-Free CM Fractionation, page 3, figure 1B), and collecting fluid fractions from the sample outlets (Flow Rate Optimization Based on Biophysical Properties, page 4). Tavassoli et al., also teach a microfluidic device having an inlet, a plurality of outlets, and a curvilinear fluid passageway between the inlet and the outlets (figure 1B), but do not teach a widened channel portion connecting the fluid passageway with the plurality of outlets.
Bhagat et al., teach a microfluidic device for cell sorting and isolation comprising an inlet, a plurality of outlets, and a widened channel portion connecting the fluid passageway with the plurality of outlets (paragraph 0021, figures 1 and 2). Specifically, Bhagat et al., teach a fluid passageway having a width ranging from 100 to 500 µm and a widened portion having a width of 1mm wherein the inlet is at the center of the spiral channel (paragraph 0021, figure 1b). Bhagat et al., also teach the fluid passageway having a rectangular cross-section (figure 1B). The Examiner is reading this combination as combining prior art elements according to known methods to yield predictable results which would have been obvious to one of ordinary skill in the art. Reference to Bhagat et al., teach a fluid passageway having a widened portion connected to a plurality of outlets for sorting cells, thus one of ordinary skill in the art would have been motivated to utilize the widened channel portion connected to a plurality of outlets. Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Tavassoli et al., with the widened channel portion of Bhagat et al., as combining prior art elements according to known methods to yield predictable results requires only routine skill in the art. Tavassoli et al., in view of Bhagat et al., do not teach detecting cardiovascular disease associated biomarkers and determining a cardiovascular disease in the subject.
Malima et al., teach an immunosensing device for biomarker detection wherein troponin I and/or C-reactive protein are detected by immunofluorescence (paragraphs0119, 0143) in samples of serum, plasma, and urine (paragraph 0068). Malima et al., teach that it is advantageous to detect troponin I and/or C-reactive protein as a means of detecting biomarkers related to cardiovascular disease (paragraph 0143).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Tavassoli et al., in view of Bhagat et al., wherein troponin I and/or C-reactive protein are detected in order to detect biomarkers related to cardiovascular disease as taught by Malima et al.
Regarding claim 5, Tavassoli et al., teach a concentric spiral channel forming about 8 loops (Device Design and Fabrication, page 12, figure 1B).
Regarding claim 8, Tavassoli et al., teach two outlets (figure 1B).
Regarding claim 11, Tavassoli et al., teach flow rates of 1, 1.2, 1.4, and 1.6 ml/min (Flow Rate Optimization Based on Biophysical Properties, page 4).
Regarding claim 12, Tavassoli et al., teach separating and focusing cells based on size (Flow Rate Optimization Based on Biophysical Properties, page 3).
Regarding claim 13, Tavassoli et al., teach separating components by inertial migration (Introduction, page 2, right column).
Regarding claim 17, Tavassoli et al., teach detecting cardiomyocytes (Introduction, page 2, right column).
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tavassoli et al., (Small, Vol 17, Issue 8, December 28, 2021) in view of Bhagat et al., (US 2016/0303565) in view of Malima et al., (US 2016/0258945) as applied to claim 1 above, and further in view of Hou et al., (US 2018/0185846).
Regarding claim 3, Tavassoli et al., in view of Bhagat et al., in view of Malima et al., do not teach lysing blood cells prior to the separating step.
Hou et al., teach a method of fractioning a whole blood sample wherein the whole blood sample is lysed prior to separating fluids with a spiral microfluidic channel (paragraphs 0010, 0053). Hou et al., teach that it is advantageous to lyse cells in the sample as a means of releasing neutrophils and monocytes from the blood sample (paragraph 0058).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Tavassoli et al., in view of Bhagat et al., in view of Malima et al., wherein the whole blood cell sample is lysed prior to separating the fluid fractions in order to release neutrophils and monocytes from the whole blood sample as taught by Hou et al.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tavassoli et al., (Small, Vol 17, Issue 8, December 28, 2021) in view of Bhagat et al., (US 2016/0303565) in view of Malima et al., (US 2016/0258945) as applied to claim 9 above, and further in view of Voldman et al., (US 2016/0331297).
Regarding claim 10, Tavassoli et al., in view of Bhagat et al., in view of Malima et al., do not teach a plurality of outlets having a cross-sectional dimension of 300 µm in width and 200 µm in height.
Voldman et al., teach a system comprising a spiral microfluidic device wherein an outlet of the microfluidic channel has a width of about 300 µm and a height of about 100 µm (paragraph 0045). The Examiner is reading this combination as a change in size/proportion which would have been obvious to one of ordinary skill in the art (MPEP 2144.04 IV A). As set forth in the MPEP, where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device, and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device (MPEP 2144.04IV A). The Examiner contends that the cited prior art teach devices that would not function differently compared to the microfluidic channel and outlet of the instant claims, thus one of ordinary skill in the art would have found it obvious to form the channel and outlet at the claimed dimensions.
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Tavassoli et al., in view of Bhagat et al., in view of Malima et al., in view of Byun further in view of Voldman et al., wherein the channel has dimensions of about 500 µm width and 200 µm height, the outlet has dimensions of300 µm width and 200 µm height as changes in size or proportion requires only routine skill in the art.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DWAN A GERIDO whose telephone number is (571)270-3714. The examiner can normally be reached Mon-Fri 10-6.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DWAN A GERIDO/Examiner, Art Unit 1797 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797
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