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 .
Drawings
The drawings were received on April 7, 2023. These drawings are acceptable.
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 recites the limitation "the same" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 4 recites the limitation "the same" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-3, 6-11, and 13-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Haun et al (US 2019/0070605 A1) (hereinafter referred to as “Haun-605” and provided by applicant in IDS filed January 18, 2025) in view of Haun et al (US 2020/0283723 A1) (hereinafter referred to as “Haun-723” and provided by applicant in IDS filed January 18, 2025).
With respect to claim 1 Haun-605 discloses a microfluidic system for processing a tissue sample comprising:
a microfluidic digestion device (microfluidic device 10, See Fig. 1 and Para. 0042) comprising an inlet (inlet 22, See Fig. 1 and Para. 0050) and an outlet (outlet 28, See Fig. 1 and Para. 0050) and a flow path defined between the inlet and the outlet (inlet channel 20 to outlet channel 26, See Fig. 1 and Para. 0050), the flow path comprising a tissue chamber (sample chamber 14, See Fig. 1 and Para. 0042) configured to hold the tissue sample (See Para. 0042 for discussion of how the sample chamber 14 holds a sample 16 in place) and a plurality of upstream fluidic channels communicating with the tissue chamber on the inlet side of the flow path (hydro-mincing microfluidic channels 18, See Fig. 1 and Para. 0044) and a plurality of downstream fluidic channels communicating with the tissue chamber on the outlet side of the flow path (downstream sieve microfluidic channels 24, See Fig. 1 and Para. 0046);
a first pump (pump 32, See Fig. 2 and Para. 0049) configured to pump a buffer-containing fluid and/or an enzyme containing fluid into the inlet of the microfluidic digestion device (See Fig. 2 and Para [0048] - ‘pumper 32 is illustrated....flow may pass directly through the devices without any recirculation’ - see arrow from pump 32 going to inlet 22); and
a microfluidic dissociation/filter device (tissue dissociation device 100, See Fig. 2 and Para. 0048),
wherein the outlet of the microfluidic digestion device (outlet 28, See Fig. 1 and Para. 0050) is fluidically coupled to the inlet of the microfluidic dissociation/filter device (See Para. 0049 for discussion of ‘output of the first microfluidic device 10 may be coupled to the input of the second microfluidic device 100’).
Haun-605 fails to disclose a microfluidic dissociation/filter device comprising an inlet, a first outlet, a second outlet, and a flow path defined between the inlet and the outlet, the flow path comprising a plurality of furcating dissociation channels having a plurality of expansion and constriction regions disposed along a length thereof, wherein one or more filters are disposed In the flow path downstream of the plurality of furcating dissociation channels; a second pump configured to pump a buffer—containing or other fluid into the Inlet of the microfluidic dissociation filter device.
Haun-723 teaches a microfluidic dissociation filter device (tissue dissociation device 10, See Fig. 1 and Paras. 0034,0038) comprising an inlet (inlet 12, See Fig. 1 and Para. 0034), a first outlet (outlet 52, Fig. 8; See Para. 0044), a second outlet (outlet 14, See Fig. 1 and Para. 0039), and a flow path defined between the inlet and the outlet (serially connected stages 16A, 16B, 16C, 16D, 16E, 18, 35, See Fig. 1 and Para. 0034 - ‘inlet 12 and an outlet 14 as well as plurality of serially connected stages 16A, 16B, 16C, 16D, 16E formed within tissue dissociation device 10'...single channel 18...downstream channel 35), the flow path comprising a plurality of furcating dissociation channels having a plurality of expansion and constriction regions disposed along a length thereof (plurality of expansion and constriction regions 20, See Fig. 1 and Para. 0036 - 'second stage 16B includes a plurality of channels 24 with each channel 24 having a plurality of expansion and constriction regions 20'), wherein one or more filters are disposed in the flow path downstream of the plurality of furcating dissociation channels (filter 50, See Fig. 8 ad Para. 0042); a second pump (on-chip pump(s) 60, See Fig. 8 and Para. 0049) configured to pump a buffer containing or other fluid into the inlet of the microfluidic dissociation/filter device (See Para. 0049 for discussion of how ‘on-chip pump 60 is used to pump the tissue containing fluid 70 through the tissue dissociation device 10). The device significantly improves single cell recovery following enzymatic treatment because small clusters of cells can be dissociated more effectively (See Para. 0051).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the microfluidic dissociation/filter device of the system of Haun-605 with Haun-723’s tissue dissociation device, and its associated components, in order to provide a platform that can shorten processing time and enhance single cell recovery for all tissue types (See Para. 0051 of Huan-723).
With respect to claim 2, the combination of Haun-605 and Haun-723 teaches the microfluidic system of claim 1, further wherein Haun-605 discloses one or more valves interposed between the outlet of the microfluidic digestion device and the inlet of the microfluidic dissociation/filter device 30 (See Fig. 2 and Para. 0049 for discussion of how “valve 30 may be located between the two devices (10,100) to allow selective flow through the second tissue dissociation device 100’).
With respect to claim 3, the combination of Haun-605 and Haun-723 teaches the microfluidic system of claim 1, further wherein Haun-723 teaches that the first outlet (outlet 52, See Fig. 89 and Para. 0044) comprises a valve or cap to close the same (valve 54, See Fig. 8 and Para. 0044), and wherein when the first outlet of the microfluidic dissociation/filter device is closed, fluid causes fluid to flow through a flow path containing the one or more filters (See Fig. 8 and Para. 0048 for discussion of how “valve 54 to the outlet 52 is closed…pulled into the tissue dissociation device 10’).
With respect to claim 6, the combination of Haun-605 and Haun-723 teaches the microfluidic system of claim 1, wherein Haun-805 discloses upstream fluidic channels (18, Fig. 1; para [0044] - 'hydro-mincing microfluidic channels 18') and downstream fluidic channels (24, Fig. 1; para [0046] - "downstream sieve microfluidic channels 24’).
However, the combination of Haun-605 and Haun-723 fails to teach wherein the number of upstream fluidic channels equals the number of downstream fluidic channels.
Fig. 10 of Haun-605 illustrates one alternative embodiment of a microfluidic device 10 where one or more of the hydro-mincing microfluidic channels 18 can be selectively turned on or off by way of individual valves 54. The direction of fluid flow is indicated by arrow A in FIG. 10. In this regard, the option is provided to mince a large area of the sample 16 by sequentially using a small number of hydro-mincing microfluidic channels 18. For example, one or few of the hydro-mincing microfluidic channels 18 may be opened at any particular time so that high jetting or shearing forces are imparted on the sample 16. The valve(s) 54 may then be closed and another valve 54 or set of valves 54 that are aimed at a different region of sample 16 can then be turned on. The valves 54 may include microfluidic valves 54 that are known in the art (See Para. 0056). Fig. 10 depicts wherein the number of upstream fluidic channels equals the number of downstream fluidic channels (Fig. 10 - see 7 upstream and downstream channels).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the even number of channels in the separate embodiment of Haun-605 with the device of combined Haun-605 and Haun-723 in order to optimize the strength of the fluidic jets while also reducing device backpressures (See Para. 0056 of Haun-605).
With respect to claim 7, the combination of Haun-605 and Haun-723 teaches the microfluidic system of claim 6, further wherein Haun-605 discloses wherein the upstream and downstream fluidic channels have a width within the range between about 250 microns and 750 microns (See Paras. 0044-0046 for discussion of how the ‘width of hydro-mincing microfluidic channels 18...range of about 50 microns to about 1 mm... width of the downstream sieve microfluidic channels 24...within the range of about 10 micron and 1 mm’).
With respect to claim 8, the combination of Haun-605 and Haun-723 teaches the microfluidic system of claim 1 but fails to teach that the system further comprises a port disposed on the microfluidic digestion device and in communication with the tissue chamber.
Fig. 9A and Para. 0055 of Haun-605 teaches an alternative embodiment, wherein the system further comprises a port disposed on the microfluidic digestion device and in communication with the tissue chamber (sample port 46, See Fig. 9A and Para. 0055 for discussion of how ‘sample port 46 located in the side of the microfluidic device 10 that can be used to load a sample 16 into the sample chamber 14').
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have incorporated the sample port in the alternative embodiment described by Haun-605 into the device of combined Haun-605 and Haun-723 to allow the user to preload samples into the microfluidic digestion device (See Fig. 9A and Para. 0055 of Haun-605).
With respect to claim 9, the combination of Haun-605 and Haun-723 disclose a method of using the microfluidic system of claim 1, specifically wherein Haun-605 teaches the method comprising:
loading the tissue sample (sample 16, See Fig. 1 and Para. 0042) into the tissue chamber (sample chamber 14, See Fig. 1 and Para. 0042) of the microfluidic digestion device (microfluidic device 10, See Fig. 1 and Para. 0042);
pumping the buffer-containing fluid and/or an enzyme-containing fluid (See Para. 0042 for discussion of how ‘fluid containing proteolytic enzyme or other digestive agents is passed into the sample chamber 14 and onto the surface of the sample 16") into the inlet of the microfluidic digestion device (inlet 22, See Fig. 1 and Para. 0050) with the first pump (pump 32, See Fig. 2 and Para. 0049); and
transferring fluid containing processed tissue sample to the microfluidic dissociation/filter device (See Fig. 2 and Para. 0049 for discussion of how ‘microfluidic device 10 may be coupled to the input of the second microfluidic device 100 that is used for further tissue dissociation’).
Haun-605 fails to teach the step of pumping a buffer-containing or other fluid into the inlet of the microfluidic dissociation/filter device along with the processed tissue from the microfluidic digestion device with the second pump and collecting effluent from the second outlet of the microfluidic dissociation/filter device.
Haun-723 teaches pumping a buffer-containing or other fluid into the inlet of the microfluidic dissociation/filter device along with the processed tissue from the microfluidic digestion device with the second pump (See Para. 0049 for discussion of how ‘on-chip pump 60 is used to pump the tissue containing fluid 70 through the tissue dissociation device 10); and effluent is collected from the second outlet of the microfluidic dissociation/filter device (See Para. 0055). It should further be noted that the device of Haun-605 in view of Haun-723 is implicitly used to perform the claimed method - Haun-605 in view of Haun-723 teach how the microfluidic system functions and how to operate it.
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have utilized the system and teachings of Haun-605 in view of Haun-723 as a whole, effectively providing a method of use through enabling a user to operate the microfluidic system and process samples (See Paras. 0049 and 0055 of Haun-723).
With respect to claim 10, the combination of Haun-605 and Haun-723 teaches the method of claim 9, wherein Haun-605 further teaches pumping the buffer-containing fluid and/or an enzyme-containing fluid (See Para. 0042 for discussion of how "fluid containing proteolytic enzyme or other digestive agents Is passed into the sample chamber 14 and onto the surface of the sample 16") into the inlet of the microfluidic digestion device with the first pump comprises recirculating fluid into the microfluidic digestion device with the first pump (See Para. 0049 for discussion of how ‘pump 32...is used to recirculate flow between one or both of the microfluidic devices 10, 100’).
With respect to claim 11, the combination of Haun-605 and Haun-723 teaches the method of claim 9, wherein Haun-605 further teaches the enzyme-containing fluid (See Para. 0042 for discussion of how ‘fluid containing proteolytic enzyme or other digestive agents is passed into the sample chamber 14 and onto the surface of the sample 16') comprises a fluid containing collagenase (See Para. 0061 for discussion of how ‘device where then primed with PBS bugger containing collagenase’).
With respect to claim 13, the combination of Haun-605 and Haun-723 teaches the method of claim 9, further wherein Haun-605 teaches that the total processing time in the microfluidic digestion device and the microfluidic dissociation/filter device is 1 minute or more (See Para. 0032 for discussion of how ‘total of processing 15, 30, or time 60 min’).
With respect to claim 14, the combination of Haun-605 and Haun-723 teaches the method of claim 9, further wherein Haun-605 teaches that the total processing time in the microfluidic digestion device and the microfluidic dissociation/filter device is 15 minutes or more (See Para. 0032 for discussion of how ‘total of processing 15, 30, or time 60 min’).
With respect to claim 15, the combination of Haun-605 and Haun-723 teaches the method of claim 9, further wherein Haun-605 teaches that the processed tissue from the microfluidic digestion device is recirculated through the plurality of furcating dissociation channels in the microfluidic dissociation/filter device a plurality of times (See Para. 0045 for discussion of how ‘sample Is run through the tissue dissociation device 10 in multiple passes’) prior to exit from the second outlet (outlet 14, See Fig. 1 and Para. 0039).
With respect to claim 16, the combination of Haun-605 and Haun-723 teaches the method of claim 9, further wherein the combination of Haun-605 and Haun-723 teaches that the microfluidic dissociation/filter device contains a single filter (See Para. 0058 of Haun-605 for discussion of the outlet channels 26 including a filtering capability that restrict the passage of larger pieces of sample from flowing downstream; Haun-723 teaches the incorporation of filters 50, See Fig. 8 and Para. 0042).
With respect to claim 17, the combination of Haun-605 and Haun-723 teaches the method of claim 9, and the combination teaches that the microfluidic dissociation/filter device contains a single filter (See Para. 0058 of Haun-605 for discussion of the outlet channels 26 including a filtering capability that restrict the passage of larger pieces of sample from flowing downstream; Haun-723 teaches the incorporation of filters 50, See Fig. 8 and Para. 0042). The combination does not teach that the microfluidic dissociation/filter device contains a plurality of filters. However, it has been held that the mere duplication of parts, without any new or unexpected results, is within the ambit of one of ordinary skill in the art.
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Haun et al (US 2019/0070605 A1) and Haun et al (US 2020/0283723 A1) in view of Qiu et al (“Microfluidic filter device with nylon mesh membranes efficiently dissociates cell aggregates and digested tissue into single cells, Lab Chip. 2018 September 11, 18(18): 2776-2786, doi:10.1039/c8ic00507a) (submitted by applicant in IDS dated 4/25/2023).
With respect to claim 5, the combination of Haun-605 and Haun-723 teaches the microfluidic system of claim 1 but fails to teach that the one or more filters comprises a first filter having a pore size within the range of about 50-100µm and a second filter having a pore size within the range of about 15-50µm.
Qiu teaches multiple filters, wherein the filters comprise a first filter having a pore size within the range of about 50-100 microns (See Introduction for discussion of how ‘coupling two filter devices in series...50 micron pore size') and a second filter having a pore size within the range of about 15-50 micron (See Introduction for discussion of ‘coupling two filter devices in series...15 micron pore size').
It would have been obvious to a person having ordinary skill in the art to have utilized Qiu's multi-filter design in the combined device of Haun-605 and Haun723 to increase single cell yield while maintaining cell viability and reducing aggregates (See introduction of Qui).
Allowable Subject Matter
Claim 12 is objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: The closest cited prior art of reference fails to disclose, suggest, or fairly teach that pumping the buffer-containing fluid and/or an enzyme-containing fluid into the inlet of the microfluidic digestion device is performed in intervals where effluent is removed from the microfluidic digestion device at the end of each interval and replacement enzyme-containing fluid is pumped into the microfluidic digestion device.
Claim 4 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The closest cited prior art of reference fails to disclose, suggest, or fairly teach that the second outlet comprises a valve or cap to close said second outlet and wherein when the second outlet of the microfluidic dissociation/filter device is closed, fluid is caused to exit the microfluidic dissociation/filter device via the first outlet without passing the one or more filters.
Conclusion
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/BRITTANY I FISHER/Examiner, Art Unit 1796 December 10, 2025