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 Amendment
The Amendment filed November 03, 2025 has been entered. Claims 1-9 and 11-19 remain pending in the application.
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-9, 11-16 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz et al. (US 10034625 B1) ("Schwartz") in view of Polsky et al. (US 2019/0274599 A1) ("Polsky").
Regarding claim 1, Schwartz discloses A continuous sensing device for at least one analyte in an invasive biofluid, comprising (Figures 3A, 3B, 3C; column 22, line 65-column 23, line 28; column 4, line 48: "receive measurements continuously");
at least one affinity-based sensor with a plurality of probes with binding that is specific to the at least one analyte (column 1, line 34-40: "sensor comprising aptamer conjugates... configured to obtain one or more measurements related to at least one analyte in... interstitial fluid");
wherein there is at least one diffusion pathway between the at least one affinity-based sensor and the source of the invasive biofluid (FIG. 3, “372” and column 23, line 19-22: "the substrate includes a microneedle array protruding into through the epidermis of the skin to enable the assay component to interact with an analyte in the interstitial fluid of the dermis"); and
Schwartz fails to disclose including at least one sample volume adjacent to the affinity-based sensor, wherein the sample volume is less than one of 10 µL/cm2, 5 µL/cm2, 2 µL/cm2, 1 µL/cm2, 0.5 µL/cm2, or 0.2 µL/cm2.
However, in the same field of endeavor, Polsky teaches including at least one sample volume adjacent to the affinity-based sensor, wherein the sample volume is less than one of 10 µL/cm2, 5 µL/cm2, 2 µL/cm2, 1 µL/cm2, 0.5 µL/cm2, or 0.2 µL/cm2 (FIG. 3a and [0022] discussing volume of microneedles and [0029], if each microneedle can allow 1 µL of fluid it follows that the dimensions are within range to allow for such limitation).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to modify the device as taught by Schwartz to include a including at least one sample volume adjacent to the affinity-based sensor, wherein the sample volume is less than one of 10 µL/cm2, 5 µL/cm2, 2 µL/cm2, 1 µL/cm2, 0.5 µL/cm2, or 0.2 µL/cm2 as taught by Polsky to fulfil spacing requirements ([0024], “The extracted fluid 18 can be collected in a microfluidic sample reservoir 19 on the chip 13. Flow rates can be adjusted to minimize bore occlusion in the microneedles due to suction of tissue. While the negative pressure method has shown some success, alternative IF extraction techniques can be more amenable to an on-body diagnostic platform due to power and spacing requirements of such a device.”).
Regarding claim 2, Schwartz as modified discloses The device of claim 1, wherein the affinity-based sensor is ex-vivo (FIG. 3A).
Regarding claim 3, Schwartz as modified discloses The device of claim 1, wherein the at least one affinity-based sensor can sense a change in analyte concentration, and wherein the majority of the change in analyte concentration that is sensed by the at least one affinity-based sensor is transported to and from the at least one affinity-based sensor by a diffusion of analyte, and if the analyte concentration in the invasive biofluid decreases the diffusion of analyte is in the direction back towards the source of the invasive biofluid (Col. 3 lines 35-38, diffusion implies high concentration to low concentration, backwards diffusion implies decreasing concentration.).
Regarding claim 4, Schwartz as modified discloses The device of claim 1, wherein the at least one affinity-based sensor is an aptamer sensor (Col. 12 lines 21-24).
Regarding claim 5, Schwartz as modified discloses The device of claim 4, wherein the at least one affinity-based sensor is an electrochemical aptamer sensor (Col. 10 line 44).
Regarding claim 6, Schwartz as modified discloses The device of claim 4, wherein the at least one affinity-based sensor is an optical aptamer sensor (Col. 3 lines 31-32).
Regarding claim 7, Schwartz as modified discloses The device of claim 1, wherein the at least one diffusion pathway includes at least one microneedle that provides a pathway for diffusion of the at least one analyte through the dermis (Col. 3 lines 19-21).
Regarding claim 8, Schwartz as modified discloses The device of claim 7, wherein the microneedle is hollow (FIG. 3, “372” and column 23, line 19-22: "the substrate includes a microneedle array protruding into through the epidermis of the skin to enable the assay component to interact with an analyte in the interstitial fluid of the dermis" Needle implies hollow).
Regarding claim 9, Schwartz as modified discloses The device of claim 1, wherein the at least one affinity-based sensor is outside of the body and outside the stratum-corneum of the skin (FIG. 3A).
Regarding claim 14, Schwartz as modified discloses The device of claim 1, wherein the at least one affinity-based sensor is in fluidic communication with a plurality of microneedles, and in further fluidic communication with the dermis, even if at least one, but not all, microneedle is not in fluidic communication with the dermis (FIG. 3, “372” and column 23, line 19-22: "the substrate includes a microneedle array protruding into through the epidermis of the skin to enable the assay component to interact with an analyte in the interstitial fluid of the dermis" only one microneedle needs to technically contact the dermis to be in contact).
Regarding claim 15, Schwartz as modified discloses The device of claim 7, Schwartz as modified further discloses wherein the at least one microneedle is a plurality of microneedles, and number of microneedles in the plurality of microneedles is at least one of >3, >10, >20, >50, >100, >200 microneedles (Polsky FIG. 3a).
Regarding claim 16, Schwartz as modified discloses The device of claim 1, wherein said affinity-based sensor probes have an attached redox couple which generates the signal change (Col. 11 lines 49-52).
Regarding claim 18, Schwartz discloses A continuous sensing device for at least one analyte in an invasive biofluid, comprising (Figures 3A, 3B, 3C; column 22, line 65-column 23, line 28; column 4, line 48: "receive measurements continuously"):
at least one affinity-based sensor with a plurality of probes with binding that is specific to the at least one analyte (column 1, line 34-40: "sensor comprising aptamer conjugates... configured to obtain one or more measurements related to at least one analyte in... interstitial fluid");
wherein the at least one affinity-based sensor is in fluidic communication with a plurality of microneedles (FIG. 3, “372” and column 23, line 19-22: "the substrate includes a microneedle array protruding into through the epidermis of the skin to enable the assay component to interact with an analyte in the interstitial fluid of the dermis"), and
in further fluidic communication with a dermis, even if at least one, but not all, microneedle is not in fluidic communication with the dermis (FIG. 3, “372” and column 23, line 19-22: "the substrate includes a microneedle array protruding into through the epidermis of the skin to enable the assay component to interact with an analyte in the interstitial fluid of the dermis" only one microneedle needs to technically contact the dermis to be in contact),
wherein there is at least one diffusion pathway between the at least one affinity-based sensor and the source of the invasive biofluid (FIG. 3, “372” and column 23, line 19-22: "the substrate includes a microneedle array protruding into through the epidermis of the skin to enable the assay component to interact with an analyte in the interstitial fluid of the dermis"); and
Schwartz fails to disclose including at least one sample volume adjacent to the affinity-based sensor, wherein the sample volume is less than one of 10 µL/cm2, 5 µL/cm2, 2 µL/cm2, 1 µL/cm2, 0.5 µL/cm2, or 0.2 µL/cm2.
However, in the same field of endeavor, Polsky teaches including at least one sample volume adjacent to the affinity-based sensor, wherein the sample volume is less than one of 10 µL/cm2, 5 µL/cm2, 2 µL/cm2, 1 µL/cm2, 0.5 µL/cm2, or 0.2 µL/cm2 (FIG. 3a and [0022] discussing volume of microneedles and [0029], if each microneedle can allow 1 µL of fluid it follows that the dimensions are within range to allow for such limitation).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to modify the device as taught by Schwartz to include a including at least one sample volume adjacent to the affinity-based sensor, wherein the sample volume is less than one of 10 µL/cm2, 5 µL/cm2, 2 µL/cm2, 1 µL/cm2, 0.5 µL/cm2, or 0.2 µL/cm2 as taught by Polsky to fulfil spacing requirements ([0024], “The extracted fluid 18 can be collected in a microfluidic sample reservoir 19 on the chip 13. Flow rates can be adjusted to minimize bore occlusion in the microneedles due to suction of tissue. While the negative pressure method has shown some success, alternative IF extraction techniques can be more amenable to an on-body diagnostic platform due to power and spacing requirements of such a device.”).
Regarding claim 19, Schwartz as modified discloses The device of claim 18, Schwartz as modified further discloses wherein the plurality of microneedles includes a number of microneedles that is at least one of >3, >10, >20, >50, >100, or >200 microneedles. (Polsky FIG. 3a).
Claims 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz et al. (US 10034625 B1) ("Schwartz") in view of Polsky et al. (US 2019/0274599 A1) ("Polsky") in further view of Liepmann et al. (US 2016/0166185 A1) ("Liepmann").
Regarding claim 11, Schwartz as modified discloses The device of claim 1, Schwartz as modified fails to disclose wherein the at least one analyte has a diffusion coefficient greater than 1.2E-6 cm2/s, and wherein the device has a diffusion lag time that is less than at least one of 250 min, 125 min, 50 min, 25 min, 12.5min, or 5 min.
However, in the same field of endeavor, Liepmann teaches wherein the at least one analyte has a diffusion coefficient greater than 1.2E-6 cm2/s, and wherein the device has a diffusion lag time that is less than at least one of 250 min, 125 min, 50 min, 25 min, 12.5min, or 5 min (Para. [0073] – [0078]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to modify the device as taught by Schwartz as modified to include wherein the at least one analyte has a diffusion coefficient greater than 1.2E-6 cm2/s, and wherein the device has a diffusion lag time that is less than at least one of 250 min, 125 min, 50 min, 25 min, 12.5min, or 5 min as taught by Liepmann in order to have reliable measurements over time (Para. [0109], “The subject blood analyte collection device finds use as a complete and reliable clinical assessment of a total 24 hr blood glucose level for a patient, regardless of their blood glucose variability over time.”).
Regarding claim 12, Schwartz as modified discloses The device of claim 1, Schwartz as modified fails to disclose wherein the at least one analyte has a diffusion coefficient greater than 6E-7 cm2/s, and wherein the device has a diffusion lag time that is less than at least one of 500 min, 250 min, 100 min, 50 min, 25 min, or 10 min.
However, in the same field of endeavor, Liepmann teaches wherein the at least one analyte has a diffusion coefficient greater than 6E-7 cm2/s, and wherein the device has a diffusion lag time that is less than at least one of 500 min, 250 min, 100 min, 50 min, 25 min, or 10 min (Para. [0073] – [0078]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to modify the device as taught by Schwartz as modified to include a including wherein the at least one analyte has a diffusion coefficient greater than 6E-7 cm2/s, and wherein the device has a diffusion lag time that is less than at least one of 500 min, 250 min, 100 min, 50 min, 25 min, or 10 min as taught by Liepmann in order to have reliable measurements over time (Para. [0109], “The subject blood analyte collection device finds use as a complete and reliable clinical assessment of a total 24 hr blood glucose level for a patient, regardless of their blood glucose variability over time.”).
Regarding claim 13, Schwartz as modified discloses The device of claim 1, Schwartz as modified fails to disclose wherein the at least one analyte has a having a molecular weight less than 1000 Da in molecular weight, and wherein the device has a diffusion lag time that is less than at least one of 150 min, 60, 30, 15, 10, 5, 2.5, or 1 min.
However, in the same field of endeavor, Liepmann teaches wherein the at least one analyte has a having a molecular weight less than 1000 Da in molecular weight, and wherein the device has a diffusion lag time that is less than at least one of 150 min, 60, 30, 15, 10, 5, 2.5, or 1 min (Para. [0073] – [0078]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to modify the device as taught by Schwartz as modified to include wherein the at least one analyte has a having a molecular weight less than 1000 Da in molecular weight, and wherein the device has a diffusion lag time that is less than at least one of 150 min, 60, 30, 15, 10, 5, 2.5, or 1 min as taught by Liepmann in order to have reliable measurements over time (Para. [0109], “The subject blood analyte collection device finds use as a complete and reliable clinical assessment of a total 24 hr blood glucose level for a patient, regardless of their blood glucose variability over time.”).
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Schwartz et al. (US 10034625 B1) ("Schwartz") in view of Polsky et al. (US 2019/0274599 A1) ("Polsky") in further view of Bigelow (US 2017/0020422 A1) (“Bigelow”).
Regarding claim 17, Schwartz as modified discloses The device of claim 3 Schwartz as modified fails to disclose wherein the at least one affinity-based sensor is in-dwelling.
However, in the same field of endeavor, Bigelow teaches wherein the at least one affinity-based sensor is in-dwelling (FIG. 1B).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to modify the device as taught by Schwartz as modified to include wherein the at least one affinity-based sensor is in-dwelling as taught by Bigelow in order to continuously sense and avoid biofouling (Para. [0013], “Also described herein is a tool that may be used to continuously monitor the concentrations of various drugs or biomarkers (e.g., chemotherapeutic levels) in the blood using catheter or needle bearing at least one aptamer biosensor as described herein. The catheter or needle is specifically designed to permit prolonged monitoring in blood while avoiding biofouling of the sensor through a boundary layer of buffer flowing past the sensor.”).
Response to Arguments
Applicant's arguments filed November 03, 2025 have been fully considered but they are not persuasive. With respect to the arguments regarding the 103 rejections under Schwartz in view of Polsky. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant argues that there is an issue of lag time to be solved and the secondary reference Polsky fails to address the issue of lag time. Firstly, there is no lag time claimed. There is a sensing device having an affinity based sensor…at least one diffusion pathway and a sample volume. Polsky is used to teach the specific sizing of the device since the primary reference Schwartz does not discuss the sizing of the probes, Polsky teaches the benefits of power and spacing techniques. Polsky does not have to teach the same motivation from the application, that is not claimed. The primary reference Schwartz does disclose the aptamer based affinity based sensor and thus the combination of Schwartz and Polsky is an affinity based sensor. Thus, the arguments are not persuasive.
With respect to the arguments further regarding Liepmann, the arguments are moot.
With respect to the arguments further regarding Bigelow, the arguments are moot. The reference assumed by Applicant was correct, it is the Bigelow reference from the IDS submitted and thus was not submitted in the 892. The arguments do not argue about the teachings on Bigelow but rather that it does not cure the deficiencies and thus the arguments are moot.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Heikenfeld et al. (US 2018/0353748 A1) (“Heikenfeld”). Heikenfeld additionally discloses small sample size affinity based sensors.
THIS ACTION IS MADE FINAL. 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.
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/J.A.T./Examiner, Art Unit 3791
/TSE W CHEN/Supervisory Patent Examiner, Art Unit 3791