DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. This action is in response to the amendment filed on 15 December 2025. Applicant's arguments and amendments to the claims have been fully considered but do not place the application in condition for allowance. All rejections and objections not reiterated herein are hereby withdrawn.
Claim Status
3. Claims 26 and 28-54 are pending.
Claims 35-53 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 26, 28-34 and 54 read on the elected invention and have been examined herein.
Drawings
4. The replacement drawings filed on 15 December 2025 have been received and are accepted.
New Claim Rejections - 35 USC § 112(b)
5. 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 26, 28-34 and 54 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.
Claims 26, 28-34 and 54 are indefinite and unclear over the recitation “the support substrate having a support substrate depth greater than a distance between the front surface and the back surface of the microneedle base substrate, thereby forming a recess in the microneedle device.” The claims include devices in which a single support substrate is present adjacent to the microneedle base substrate. It is unclear as to how this configuration permits the formation of a recess. Figure 1 shows a recess that is formed when a support substrate is present at each end of the microneedle base substrate and overlaps / is on top of a portion of the microneedle base substrate. It is unclear as to how the generally recited arrangement of the microneedle base substrate and support substrate form a recess when the support substrate is adjacent to one end / side of the microneedle base substrate.
New / Modified Claim Rejections - 35 USC § 103
6. 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.
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) 26, 28-30, 33-34 and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Mahmood et al (U.S. 20140287942) in view of Simmers et al (U.S. 20180001071; cited in the IDS).
Mahmood teaches a microneedle device for capturing and detecting RNA biomarkers in situ (e.g., [0005-0006] and [0071]), wherein the microneedle device is injection molded (para [0087]) and comprises: (a) a microneedle base substrate comprising a front surface having a plurality of microneedles protruding therefrom and a back surface and (b) a support substrate adjacent to the microneedle substrate (e.g., para [0071] and [0086-0087]); and the microneedles in the microneedle device are attached to probes for capturing and detecting mRNA (e.g., para [0067-0068] and [0094]). Also, Mahmood does teach that the first base substrate that is the surface to which the microneedles are attached can be attached to a second base substrate surface that is a compartment configured so that a PCR assay can be performed (e.g., para [0123]).
Mahmood exemplifies devices wherein the microneedles are of the same length (see Figure 4). See para [0071] “FIG. 4 is a diagram of a surface of a device of the invention comprising a plurality of microneedles’ and Figure 4 (in part) below:
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Thereby, in the microneedle device of Mahmood, the needles do not deviate in length, which meets the limitation of the claims of “wherein the lengths of no more than 3% of the microneedles in the plurality of microneedles deviate by more than about 50 um from an average length of the plurality of microneedles.”
Mahmood does not teach that the support substrate has a depth greater than a distance between the front surface and the back surface of the microneedle base substrate, thereby forming a recess in the microneedle device, wherein the distance between the front surface and the back surface of the microneedle base substrate is between 150 m to 350 um, and wherein a ratio between (i) the distance between the front surface and the back surface of the microneedle base substrate and (ii) the support substrate depth is between 1:2 and 1:10.
However, Mahmood (para [0086]) does teach:
“the microneedle devices of the invention can additionally contain an applicator unit that can be used to apply the device to a subject. The applicator unit can control various application parameters, such as the speed with which the array is applied, the force with which the array is applied, and/or the angle with which the array impacts a tissue of the subject (e.g., the skin). In addition, the applicator may aid in handling or otherwise transferring the array from a storage unit to the subject… The physical insertion of microneedle probes can disrupt cell membranes to release genetic material, including biomarkers, that are available for binding to probes on the inserted microneedles.”
Further, Simmers teaches a microneedle device comprising: (a) a microneedle base substrate having a front substrate surface and a back substrate surface and (b) an applicator (i.e. support substrate) that is connected to and adjacent to the microneedle base substrate (e.g., Figure 5A and para [0158]). As shown in Figure 5A, the applicator / support substrate has a depth that is greater than the distance between the front surface and the back surface of the microneedle base substrate (i.e., greater than the depth of the microneedle base substrate), and this forms a recess in the microneedle device (e.g., [0158-161], [0201], and Figures 4 and 5). Pressing the applicator / support substrate applicator into the microneedle base substrate results in pressing the microneedle device into a subject’s skin (e.g., para [0157-0161] and Figure 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the microneedle device of Mahmood so as to have included a support substrate (applicator substrate) having a depth greater than a distance between the front surface and the back surface of the microneedle base substrate, so that a recess area would be formed in the microneedle device. One would have been motivated to have done so because Simmers teaches that this design allows for the support substrate / applicator to be pressed in a manner that results in the microneedles pressing into and penetrating the skin of a subject. Accordingly, one would have been motivated to have made this modification in order to have facilitated the use of the microneedle device when contacting a subject’s skin with the device and capturing biomarkers of interest from the subject in situ.
The combined references do not specifically teach that the distance between the front surface and the back surface of the microneedle base substrate is between 150 m to 350 um, and wherein a ratio between (i) the distance between the front surface and the back surface of the microneedle base substrate and (ii) the support substrate depth is between 1:2 and 1:10.
However, to have determined the optimum distance between the front and back surfaces of the microneedle base substrate including distances between 150um and 350um, and to have determined the optimum ratio between (i) the distance between the front surface and the back surface of the microneedle base substrate and (ii) the support substrate depth of between 1:2 and 1:10 would have been obvious to one of ordinary skill in the art and well within the skill of the art. Simmers teaches the parameters that are important in the use of the microneedle device to ensure that applicator / support base is pressed into the recessed area and the needles are then pressed into the skin of a subject at an optimum level and at an optimum pressure / force (e.g., para [0148], [0154], [0159-0160] and [0164]). Thus, the ordinary artisan would have recognized the result-effective variables of the depth between the front and back surfaces of the base substrate and the ratio between (i) the distance between the front surface and the back surface of the microneedle base substrate and (ii) the support substrate depth and would have selected the optimum depths and ratio so as to have accomplished the objective set forth by Mahmood and Simmers of properly applying the microneedle device to a subject’s skin so as to penetrate the skin at an appropriate depth.
Regarding claim 28, Mahmood teaches wherein the microneedle device comprises 50 microneedles (para [0075]) or comprises at least 100 microneedles (e.g., para [0074] and [0076]), which constitutes at least 50 microneedles.
Regarding claim 29, Mahmood teaches that the base width of the microneedles is in “the range of 10 μm to 500 μm, preferably in the range of 20 μm to 200 μm” (para [0072]), which is a base width of no greater than 500 μm.
Regarding claim 30, Mahmood teaches that the center-to-center distance between two microneedles is less than 1000 μm (e.g., para [0082]).
Regarding claim 33, Mahmood does not specifically teach that the “probes for mRNA” are probes for intact mRNA. However, this recitation in the claim does not distinguish the probes in the claimed microneedle device over the probes attached to the microneedle device of Mahmood since the claims do not recite any particular structure of the probes. Further, Mahmood (e.g., para [0182-0185]) teaches the use of the microneedles having probes for the detection of target mRNA from skin samples attached thereto and the ability to amplify by RT-PCR the mRNA bound to the probes of the microneedle. Since the mRNA could be amplified and detected, the mRNA is considered to be intact (as opposed to being degraded into individual nucleotides).
Regarding claim 34, Mahmood teaches that the mRNA detected by / complementary to the probe is associated with psoriasis (e.g., para [0134]).
Regarding claim 54, the combined references do not teach that the back surface of the microneedle substrate and the support substrate form an angle of 110°. Rather, Simmers (Figure 5A) shows that the back surface of the microneedle substrate and the support substrate form an angle of 90°. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have selected alternative angles at whish the back surface of the microneedle substrate and the support substrate meet, including an angle of 110° since this would be a design choice to permit the optimum pressing of the applicator into the recess / cavity to ensure proper control and pressure at which the microneedles are inserted into the skin of the subject.
6. Claim(s) 31 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Mahmood et al (U.S. 20140287942) in view of Simmers et al (U.S. 20180001071; cited in the IDS), as applied to claims 26, 28-30, and 33-34 above, and further in view of Ibrahim et al (2017. J Invest Dermatology. “Non-invasive transcriptome extraction from the skin using MINDERA microneedle technology” available via URL <wp-content/uploads/201 9/03/MiINDERA-SID-201 7-Poster-.pdf>; cited in the IDS) and Frisen et al (U.S. 20140066318).
The teachings of Mahmood and Simmers are presented above.
The combined references do not teach that the probes comprise a polynucleotide with a homopolymeric sequence (claim 31), particularly wherein the homopolymeric sequence comprises two or more consecutive thymine residues (claim 32).
However, Ibrahim et al discloses methods for isolating RNA samples from the skin using a microneedle device in which needles are conjugated to probes for capturing mRNA from skin. It is stated in the Introduction that MINDERA “has developed a minimally invasive microneedle device that extracts the whole transcriptome from the skin of patients, eliminating the need for clinical researchers to source skin biopsies, a major pain point in dermatology research.” It is reported that there was “excellent correlation’ between the mRNA extracted by the MiINDERA device and mRNA extracted from biopsy samples. Ibrahim teaches using the methods disclosed therein to “(r)eplace biopsies and visual observation to monitor response to treatment.”
Further, Frisen teaches methods of performing whole transcriptome analysis using probes comprising poly-T sequences (i.e., a homopolymeric sequence comprising two or more consecutive thymine residues) to capture mRNA from a tissue sample (e.g., para [0002-0003] [0091], [0325], and [0404]). Frisen teaches that whole transcriptome capture permits the analysis of gene expression patterns in different tissue samples (e.g., para [0011] and [0013]).
In view of the teachings of Ibrahim of using a microneedle device to extract the whole transcriptome from the skin of patients and the teachings of Frisen that the whole transcriptome can be captured using probes comprising poly-T sequences (complementary to the polyA tail of mRNA), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Mahmood so as to have attached polyT probe sequences to the microneedles in order to have permitted the isolation of all mRNA from skin samples. One would have been motivated to have done so because Ibrahim teaches using the microneedle device to capture the complete transcriptome from skin samples, for example to monitor mRNA expression changes following therapy, and Frisen teaches that probes comprising polyT sequences can be effectively used to capture all mRNA in a sample for whole transcriptome analysis.
Response to Remarks:
The response traverses the previous grounds of rejection over Mahmood in view of Trautman and argues that the combined references do not teach each of the limitations in the amended claims.
In response to the amendments to the claims, the rejection has been modified and the rejection is over the combined teachings of Mahmood and Simmers. The amendments to the claims have been addressed in the above rejections.
The response asserts that the claimed microneedle device provides improved results. However, it has not been established that the asserted improvements are obtained over the full breadth of the claims or that the newly recited structural features would not have been obvious.. The response points to Figure 1 and states:
“having a narrow microneedle base substrate, 120, improves the flow and/or penetration of a polymer/resin used to fabricate the device into a mold resembling the structure of the device during manufacturing. Original specification at [0064]. As the heat material is injected through the mold, the smaller width of the interior section (as compared to the peripheral section(s)) facilitates the heated materials movement to the one or more cavities to generate the plurality of microneedles prior to generating the interior section and the peripheral section(s), which facilitates generation of uniform, sharp microneedles.”
However, the claims are not directed to a method of manufacture and do not necessarily require that the complete microneedle device is made of a resin, and particularly a polyolefin resin, as discussed in the specification at para [0072]. Further, in the absence of evidence to the contrary or cogent arguments to the contrary, it appears that the asserted attributes of the microneedle device are in reference to Figure 1, which requires that the microneedle device has a support substrate adjacent to each side of the microneedle base substate. However, the claims include devices in which the support substrate is adjacent to just one side of the microneedle base substrate.
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 CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng (Winston) Shen can be reached on 571-272-0731. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682