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 .
DETAILED ACTION
Amendment Entry
1. Applicant's amendment / response filed January 27, 2026 is acknowledged and has been entered. Applicant’s amendment to the specification is also acknowledged and has been entered. Claims 1, 5, 6, and 8 have been amended. Claims 17, 24, 28, 29, and 34 have been cancelled. Claims 21, 24, 26, 31, 37, 38, 41, and 46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim.
Accordingly, claims 1-3, 5, 6, 8, 12-14, 18, 21, 24, 26, 31, 37, 38, 41, and 46 are pending. Claims 1-3, 5, 6, 8, 12-14, and 18 are under examination.
Withdrawn Rejections / Objections
2. Any objection or rejection not reiterated herein, has been withdrawn.
3. The rejections of claim 17 are moot in light of Applicant's cancellation of the claims.
Priority
4. Applicant’s claim for the benefit of a provisional application under 35 U.S.C. 111(a) and 37 C.F.R 1.53(b) is acknowledged. Based on the filing receipt, the effective filing date of this National Stage application, which is a 371 of PCT/US2021/023123 filed 03/19/2021, is March 19, 2020 which is the filing date of Provisional Application 62/992,061 from which the benefit of priority is claimed.
Claim Objections
5. Claim 1 is objected to in reciting “cell free sample” with open and close quotations in all occurrences in the claim. Appropriate correction is required.
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.
6. Claims 1-3, 5, 6, 8, 12-14, and 18 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 1 is vague and indefinite in reciting “to capture cells of said mammal from said biological sample via said one or more immobilized antibodies” and “cell free sample having a reduced number of the cells that were present in the biological sample” because it is unclear what is encompassed in all these recited “cells” that are captured by the immobilized antibodies so as to reduce their number in the cell free sample; given that the biological sample is heterogeneous and comprises blood having different cells as recited in claim 3. Does Applicant intend “to capture target cells of said mammal from said biological sample expressing cell surface antigen to which said one or more immobilized antibodies bind to” and “cell free sample having a reduced number of the target cells that were captured by the immobilized antibodies from the biological sample?” See paragraphs [0034, 0041]. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). See also claim 8.
Claim 1 is indefinite in reciting “wherein said second location is configured to receive … reagents for performing whole genome amplification (WGA)” because it is unclear how the microfluidic device is structured and configured so as to contain, and subsequently move, the recited different reagents for WGA through the microfluidic channels on the substrate. The microfluidic device does not appear to have incorporated therein, any reagent for WGA including DNA polymerase, DNA denaturing buffer and neutralizing buffer contained in a reagent container or dessicated in a location of the microfluidic device from which the reagents are received. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Claim 1 is indefinite in reciting “wherein said third location is configured to receive said amplified sample and reagents for performing library construction to form sequencing ready sample” because it is unclear how the microfluidic device is structured and configured so as to contain, and subsequently move, the recited different reagents for performing library construction through the microfluidic channels on the substrate. The microfluidic device does not appear to have incorporated therein, any reagent for performing library construction including a fragmentation reagent and an adapter contained in a reagent container or dessicated in a location of the microfluidic device from which the reagents are received. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
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.
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.
7. Claims 1-3, 5, 6, 8, 12-14, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Chia et al. (US 2020/0166509) in view of Tan et al. (US 20230219091).
Chia et al. teach a microfluidic device which is a digital microfluidic chip comprising A) a substrate (Figure 1) which comprises a planar surface having: a) a first location (first portion: immobilization electrode) comprising one or more immobilized antibodies that capture specific target cells of a mammalian subject blood sample to form a cell free sample having reduced number of the target cells, a second location, and a third location; and B) an array of electrodes defining microfluidic channels on the substrate between a) the first location, the second location, and the third location and configured to move the remaining cell free sample from the first location to the second location, and from the second location to the third location ([0006, 0013, 0024, 0025, 0027, 0028, 0031, 0037-0073]; Figure 1; Figure 2A; Figure 2B; Figure 7B). A coating of indium tin oxide (ITO electrodes) is disposed on the array of electrodes [0025]. The coating comprises an insulative material (to insulate the electrodes) or a hydrophobic material [0025].
Chia et al. teach that the one or more immobilized antibodies comprise anti-CD45 antibodies that are configured to capture and immobilize the specific target cells of the blood sample, being specifically white blood cells (WBCs) expressing CD45 surface antigen, so as to be separated and removed to a cell collection or waste reservoir [0006, 0009, 0029, 0032, 0037]. Chia et al. teach moving or flowing the cell free sample through the microfluidic channel to a separate (second) location and subjecting the cell free sample to polymerase chain reaction (PCR) wherein standard PCR reagents and techniques are used for genome wide RNA sequencing to form an amplified sample with amplified copies of specific DNA sequences [0006, 0009, 0029, 0037, 0068, 0069, 0072 ]. The third location is configured to receive the amplified sample wherein standard reagents and techniques are used to perform library construction to form sequencing ready sample for microarray analysis of targeted genes (i.e. DNA) [0068, 0069, 0072, 0073].
With respect to claim 8, since the DMF components taught by Chia et al. [0029, 0037] are consonant to components recited in Applicant’s claimed invention; absent evidence to the contrary, it is deemed that the one or more antibodies taught by Chia et al. can be configured to bind about 1,000 to 100,000 cells per each droplet of biological sample as recited in Applicant’s claimed invention [0029, 0037].
Chia et al. differ from the instant invention in failing to teach that the array of electrodes comprise chrome. Chia et al. further does not explicitly teach the reagents for performing WGA and reagents for performing library construction.
Tan et al. disclose a digital microfluidic (DMF) device for use in integrated nucleic acid analysis (Abstract). The DMF device as taught by Tan et al. comprises a substrate of electrode arrays that comprise chrome (chromium layer) as an alternative to ITO. Tan et al. teach that chrome provides advantage in promoting adhesion [0124]. Tan et al. specifically teach an array of electrodes configured to move a biological sample from a first location to a second location and from a second location to a third location; wherein the first location is functionalized with immobilized antibodies to capture target cells to form a cell-free sample, and the second location is configured to receive cell-free sample and standard PCR reagents such as DNA polymerase reagents, DNA denaturing buffers and neutralization buffers via electrokinesis to perform whole genome amplification (PCR amplification) to form an amplified sample ([0104, 0209]; Figure 14; claim 1). Tan et al. further teach that the third location is configured to receive the amplified sample and standard library construction reagents such as fragmentation reagents for denature, anneal, and extension steps and adapter and DNA templates via electrokinesis to perform library construction wherein the electrodes separate the processed nucleic acids to form sequencing ready sample ([0108, 0249]; claim 4).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have incorporated chrome as taught by Tan into the array of electrodes of Chia, as well as the WGA reagents and library construction reagents as taught by Tan into the DMF device of Chia because Tan taught that chrome is an obvious alternative equivalent of ITO that has the advantage of promoting adhesion in DMF device electrode arrays, and the WGA reagents and library construction reagents are shown by Tan to be standard reagents for use in amplification and library construction techniques conventionally known and used in the art for application in the DMF device of Chia. One of ordinary skill would have had reasonable expectation of success in substituting the ITO and reagents of Chia with the chrome, WGA reagents, and library construction reagents as taught by Tan because both Chia and Tan teach analogous art in fabrication and use of DMF devices.
It is proper for purposes of this obviousness rejection to interpret the teachings of Tan in Example 4 and Example 8 as encompassing the reagents and configurations set forth in the second location and third location recited in claim 5 because unpatented claims are given the broadest reasonable interpretation consistent with the specification. Additionally, it is deemed that "[T]he adaptation of an old idea or invention ... using newer technology that is commonly available and understood in the art" would be obvious to persons of ordinary skill in that art. Leapfrog Enters., Inc. v. Fisher-Price, Inc., 485 F.3d 1157, 1162 (Fed. Cir. 2007)."
Response to Arguments
8. Applicant’s arguments with respect to claims 1-3, 5, 6, 8, 12-14, and 18 have been considered but are moot in light of the new ground of rejection necessitated by Applicant’s amendment and because the new ground of rejection does not rely on the reference as applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
9. Applicant's arguments filed January 27, 2026 have been fully considered but they are not persuasive.
A) Applicant amended claim 1 and, nonetheless, argues in pages 9-11, items (2) and (5) that the indefiniteness, ambiguity, and/or lack of clarity issues leading to the 112(b) rejections were unfounded because a person skilled in the art, given the teachings of Applicant’s specification, would have understood the claim limitations such as relative locations and positions of the first, second, and third locations; and that they are comprised by the planar surface; and that the device is not recited to include the reagents for performing WGA or reagent for performing library construction.
In response to Applicant’s argument addressing the indefiniteness, ambiguity, and/or lack of clarity issues regarding the relative locations and positions of the first, second, and third locations and that they are comprised by the planar surface- that the claim recitations should have been clear to one skilled in the art given the teaching provided in the specification; Applicant is reminded that the statutory provision of 35 USC 112(b) is for the specification to “conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the Applicant regards as his invention.” As such, the recited claims are deemed to stand on their own merits.
In response to the reagents incorporated into the second location and the reagents incorporated into the third location; claim 5 is limited to each location being configured to receive reagents for WGA in the second location and to receive reagents for library construction in the third location; whereas there is no indication as to where these reagents would have been received from since they are not part of the first location and how they are positioned to be received with respect to the overall structure of the claimed microfluidic device.
10. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAILENE R. GABEL whose telephone number is (571)272-0820. The examiner can normally be reached Monday, Tuesday, and Thursday 5:30 AM to 4:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory S. Emch can be reached at (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GAILENE GABEL/Primary Examiner, Art Unit 1678
March 3, 2026