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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/23/2026 has been entered.
New claim 67 has been added. Claims 6-7, 18-40, and 61-62 remain withdrawn. Claims 1, 3-5, 8-17, 54-59, and 63-67 are pending and are examined on the merits herein.
Response to Applicant’s Amendments and Arguments
Regarding the 35 USC 103 Rejections, Applicant argues that Dong, the primary reference, relies on direct liquid extraction for DNA/RNA isolation, while the instant invention involves the absorption of biomolecules into the microneedle tips (Remarks, page 13).
While the instant claims do recite the absorption of analyte onto the microneedle generally, the claimed invention is not limited to such absorption only. The claimed method comprises the listed steps, and so while absorption is required, microneedle extraction is also not prohibited. Additionally, Applicant argues that the claim requires absorption onto the microneedle tip, but in reality, the claim requires the absorbed analyte to be generally present on the removed microneedle (“wherein the removed microneedle comprises absorbed analyte extracted from the plant tissue”) and the analyte to be absorbed/deposited onto the surface of the microneedle, and not necessarily the tip. As Applicant does not provide a specific definition for “surface of the microneedle” in their instant specification, the surface of the microneedle can be anywhere on the inner or outer surface of said microneedle.
In Dong, hydrophilic microneedles are described – Figures 21A and 21B note that the microneedle has a hydrophilic coating to promote analyte uptake (explained in column 9, para. 6), column 11, para. 6 notes that hydrophilic material attracts fluid for sensing, and column 18, para. 2 states, “The needle is treated hydrophilic…to enable automatic extraction of fluids from the plant to the sensing element.” In Figure 21A in particular, the hydrophilic coating extends to the tip of the needle, which would allow for the absorption and uptake of fluids containing the analyte. Dong also states that polymers generally may be used in microneedle construction (column 26, paras. 2-3). Silicon is specifically mentioned in column 26, para. 2, and is also cited as a microneedle construction element in columns 16 (see step 6) and 17 (para. 2, which references Figure 12A) and is noted as a specific needle tip element (column 15, para. para. 6). Thus, even though Dong does not itself teach that the silicon structure of the microneedle is capable of automatic fluid extraction, Dong does teach coatings which serve this purpose, and would naturally lead to the claimed absorption as extracted fluid is drawn to said coating.
In combining Dong and Khanna, the actual materials of the microneedles of Dong are not being changed - see para. 26 of the Final Rejection, which recites, “Prior to the effective filing date, it would have been prima facie obvious for one of ordinary skill in the art to use the teachings of Khanna to modify the sensor of Dong. In particular, the ordinary artisan would have been motivated to take the array format of the microneedles of Khanna, with its force and length measurements, and use it in the sensor with a plurality of silicon microneedles of Dong.” Additionally, earlier in the rejection, the hydrophilic nature of the microneedles of Dong are recited (see para. 20 of the Final Rejection for example). Thus, Dong in view of Khanna has an array of silicon microneedles with particular force and length measurements, where the microneedles can contain an additional hydrophilic element to absorb analytes.
Thus, Applicant’s arguments against the existing 35 USC 103 Rejections are not considered persuasive. These rejections have been maintained. See also new grounds of rejection below for newly added claim 67
Claim Rejections - 35 USC § 112(b)
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 16-17 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 16 recites the limitation "the biological sample" in line 1. There is insufficient antecedent basis for this limitation in the claim, as “a biological sample” is not recited earlier in the claim or in claim 1, from which this claim depends. It will be interpreted as though “the biological sample” is referring to the “plant tissue” of claim 1.
Claim 17 is rejected due to its dependence on rejected claim 16. It is noted that claim 17 recites the limitation “said plant tissue” in line 1. As “plant tissue” is recited in claim 1, this phrase is not considered to lack antecedent basis. This phrase will be interpreted as referring to the same tissue/sample as presented in claim 16.
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 1, 3-5, 8-10, 13-17, 54-59, 63, and 65-66 are rejected under 35 U.S.C. 103 as being unpatentable over Dong et al. (U.S. Patent 10,921,303 B1), in view of Khanna et al. (Microsyst Technol, 2010).
Dong teaches apparatuses, methods, and systems for taking measurements from plants using microneedles (Abstract). One embodiment of this invention involves inserting a sensor device with said microneedle into a plant leaf (Figure 3, column 11, para. 5; instant claim 16). Once inserted, the microneedle can extract liquid from the plant. Dong teaches this in the context of analyzing nitrogen levels in the plant (column 6, paras. 2-5 and column 17, final paragraph through column 18, para. 1; instant claims 15 and 66). The microneedle itself has a base and a tip, and can be conical and hollow, where the base has a wider diameter than the tip (column 25, final paragraph, Figure 18B, column 5, para. 1 after listed steps, and column 6, para. 2). Once a measurement has been taken, the sensor can then be removed (column 13, para. 7).
The body of the microneedle can be a polymer (column 26, para. 2), specifically silicon (column 16, step 6), and at least part of the microneedle may be hydrophilic (Figure 21A and B and column 20, step 3). Figures 21A and 21B note that the microneedle can have a hydrophilic coating to promote analyte uptake (explained in column 9, para. 6), column 11, para. 6 notes that hydrophilic material attracts fluid for sensing, and column 18, para. 2 states, “The needle is treated hydrophilic…to enable automatic extraction of fluids from the plant to the sensing element.” In Figure 21A in particular, the hydrophilic coating extends to the tip of the needle, which would allow for the absorption and uptake of fluids containing the analyte (instant claim 5). The extraction of fluids from the plant can involve microfluidic channels and check values within the sensor, and the hydrophilic needle can enable automatic extraction of fluids from plants (column 17, final paragraph through column 18, para. 1, column 18, para. 2, and Figure 21; instant claim 8). As Dong teaches that the hydrophilic material will attract fluid such as water (e.g. column 11, para. 6) and teaches that plants contain water-based solution (column 15, para. 3), as the microneedle is at least partially composed of hydrophilic and/or swellable material, upon insertion into plant tissue, the water-based solution inside the plant would be attracted to said microneedle, absorbing and/or depositing analyte onto the surface of the microneedle as described in the “Response to Applicant’s Arguments” section above.
The microneedle is designed to puncture the outer surface of the plant tissue (i.e. the epidermis) and make contact with the cells beneath (Figure 7, column 10, para. 4, and column 11, para. 3; instant claims 10 and 63). The measurements taken with the sensor can be very short, lasting fractions of seconds (column 13, para. 4; instant claim 14). The tip of the microneedle can be less than the width of a typical cell (i.e. less than or equal to 5 µm, column 5, para. 1 after the listed steps). Dong also teaches that the microneedle can exist on a probe with a plurality of microneedles (Figure 17B and D and column 26, para. 5; instant claim 13)
Dong specifically mentions that the plants used in their method can be crops with agricultural uses (column 3, para. 5, column 23, para. 4, Figure 15C), and mentions nitrogen measurements are useful for farmers (column 2, para. 3; instant claim 17).
In addition to plant leaves, the device of Dong can also can used for stems and seeds (Figure 3, column 11, para. 5 and claim 4; instant claim 54). Once the plant fluid has been taken up by the sensor, it can be collected via collecting mat (Figure 13C and column 20, para. 5 not including the listed steps; instant claim 55).
However, though Dong teaches that the microneedle tip can be less than or equal to 5 µm (column 5, para. 1 after the listed steps) and teaches a plurality of microneedles (Figure 17B and D and column 26, para. 5), this reference does not teach specific fracture forces, that the body of the needle has the length requirements stated in instant claim 3, or that microneedles can specifically be provided in an array. As stated above, note that Dong also teaches that the body of the microneedle can contain silicon (column 16, step 6).
Khanna teaches the fracture strength evaluation of silicon microneedles (Abstract). Using a silicon microneedle array (Figure 2) and various sized needles (Table 1), axial and shear fracture strength were measured. The arrays contained microneedles that were all 200 µm tall (page 974, column 2, para. 1). Figure 9 plots a graph of shear force variation for various needle parameters. For outer diameter, once the needle outer diameter dimension reaches slightly less than 130 µm, shear force is below 100 gf. This is slightly lower than 1 N force per needle.
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the teachings of Khanna to modify the sensor of Dong. In particular, the ordinary artisan would have been motivated to take the array format of the microneedles of Khanna, with its force and length measurements, and use it in the sensor with a plurality of silicon microneedles of Dong (instant claims 1, 3 and 65). Using an array of microneedles appropriately spaced apart would allow the array to reach multiple plant cells at one time, increasing the number of measurements that can be made and/or analytes collected. Dong teaches that the needle tip can be a fraction of the total length of the needle, and does not put particular size restrictions on the needles (column 25, para. 5). Therefore, using an array of 200 µm microneedles with tips of 5 µm or less would be encompassed by the teachings of Dong, and this array would result in fracture forces below 1 N for each needle, as shown by Khanna. A needle depth of 200 µm would allow for sampling of both shallower and deeper cells within the plant leaves depending on how much of the needle body was pushed into the plant leaf. This would allow for data comparisons between different cell layers, potentially revealing trends about analyte movement through the leaves. There would be a reasonable expectation of success with this modification because Khanna teaches that their array can be mounted onto a device (page 974, column 2, para. 1), and so could be mounted onto the device of Dong. Given that Dong already teaches a plurality of microneedles, the ordinary artisan would simply need to construct said plurality with the array specifications provided by Khanna.
Therefore, claims 1, 3, 5, 8, 10, 13-17, 54-55, 63, and 65-66 is obvious over Dong in view of Khanna.
Regarding claim 4, Dong in view of Khanna teaches the method of claim 3, and wherein the microneedles themselves have a base and a tip, and can be conical and hollow, where the base has a wider diameter than the tip (Dong column 25, final paragraph, Figure 18B, column 5, para. 1, and column 6, para. 2).
Therefore, claim 4 is prima facie obvious over Dong in view of Khanna.
Regarding claim 9, Dong in view of Khanna teaches the method of claim 1, as described above. Dong also teaches that the sensor can detect DNA, proteins, and other biomolecules (column 10, para. 5 and column 31, list elements and para. 1 after list element m). Though these analytes are not specifically taught with regard to plants and the embodiment of Dong described above, it would be prima facie obvious for one of ordinary skill in the art to analyze extracted plant DNA with the sensor of Dong in view of Khanna. Given that this sensor is designed to puncture plant cells and extract fluid, DNA will already be present in the microneedle and sensor device (Figure 7 and column 17, final paragraph through column 18, para. 1). The method for sensing these elements is also explained by Dong, further motivating the ordinary artisan (column 31, list elements and para. 1 after list element m).
Therefore, claim 9 is obvious over Dong in view of Khanna.
Regarding claim 56, as stated above, Dong in view of Khanna teaches fracture forces of less than 1 N per microneedle on an array for silicon microneedles with particular dimensions. Regarding appropriate amounts of force in the instant invention, the instant specification notes that said force must be “sufficient to puncture the outer surface of the plant tissue or the animal tissue with the tip of the microneedle, thereby bringing at least a portion of the body of the microneedle into contact with inner cells of the plant tissue or the animal tissue,” (page 4, para. 1) and that “Plant soft tissues can include, but are not limited to, immature plant tissue, a flower, a seedling, a plant leaf, a tuber, a fruit, a stem or any other plant tissue that whose outer surface can be punctured by the tip of a microneedle having a fracture force of about 1 newton (N) or less,” (page 32, para. 2). Applicant also notes that, “The type of polymer and amount of polymer crosslinking can affect the fracture force of the microneedle. In addition, the dimensions of the microneedle can affect the fracture force,” (page 34, para. 2). These comments from the specification do not demonstrate that the specific range of 0.1 N to 1 N cited in claim 56 is critical to the function of the invention – in fact, for the instant invention involving plant soft tissues, only a force equal to or less than 1 N seems to be required. Determining a desired fracture force based on the precise polymer components and microneedle measurements used that meets this force requirement would therefore be considered routine optimization. Routine optimization is not considered inventive and no evidence has been presented that the selection of specific fracture forces was other than routine, that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. See MPEP 2144.05 II.
Therefore, claim 56 is prima facie obvious over Dong in view of Khanna.
Regarding claims 57-59, the limitations recited discuss different microneedle parameters for total length, tip diameter, and base diameter. In the instant specification, a microneedle in general is defined as “a structure having at least one region with a dimension of less than about 1,000 microns,” (page 21, para. 2). No size limiting definitions for diameter or length are provided. Microneedle dimensions are noted to affect fracture force (as noted in the para. above, page 34, para. 2 of the instant specification). The lack of specific teachings in the specification regarding the measurement parameters taught in claims 57-59 fail to show that these parameters are critical to the invention. Thus, creating a microneedle with the described parameters is considered routine optimization. Routine optimization is not considered inventive and no evidence has been presented that the selection of specific microneedle lengths, tip diameters, and body diameters was other than routine, that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. See MPEP 2144.05 II.
Therefore, claims 57-59 are prima facie obvious over Dong in view of Khanna.
Claims 11-12 and 64 are rejected under 35 U.S.C. 103 as being unpatentable over Dong et al. (U.S. Patent 10,921,303 B1), Khanna et al. (Microsyst Technol, 2010), and in view of Mahmood et al. (U.S. Patent Application Publication No. 2014/0287942 A1).
Regarding claims 11-12 and 64, Dong in view of Khanna teaches the methods of claims 1, 3-5, 8-10, 13-17, 54-59, 63, and 65-66, as described above, as described above. Though Dong does teach collecting an analyte, and particularly nucleic acids (Figure 13C and column 20, para. 5 not including the listed steps and column 10, para. 5 and column 31, list elements), this reference does not teach contacting the microneedle with a liquid in which the analyte is soluble.
Mahmood teaches an array of microneedles for detecting and capturing molecular biomarkers (Abstract). Mahmood also teaches that “each microneedle can be inserted into its own cavity (e.g., pinprick cavity), containing unique PCR reagents (e.g., unique probes or primers). PCR reactions can be conducted and the samples can be analyzed for various biomarkers,” (paras. 106 and 122). Mahmood also teaches an embodiment where DNA is immersed in sterile water and heated, and then DNA in the water is collected before undergoing PCR (para. 170).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the teachings of Mahmood to perform PCR on the nucleic acids collected in the microneedle array of Dong in view of Khanna. Specifically, this would involve contacting the microneedle with sterile water, allowing the nucleic acids in the needle to dissolve in said water, and then collecting that water to perform PCR. PCR can allow the nucleic acids collected to be amplified and quantified, and can be used to identify particular biomarkers (Mahmood paras. 29 and 70). In this manner, it can be determined if the plant samples have particular mutations or genes that that may be informative to farmers, such as those that determine pathogen resistance, response to environmental stimuli, and overall growth pattern. There would be a reasonable expectation of success with this addition to the method of Dong in view of Khanna because PCR is well known in the art, as evidenced by Mahmood, and performing PCR on nucleic acids already present in the microneedle would not change the sensing or sampling protocols of Dong.
Therefore, claims 11-12 and 64 are prima facie obvious over Dong, in view of Khanna, and in view of Mahmood.
Claim 67 is rejected under 35 U.S.C. 103 as being unpatentable over Dong et al. (U.S. Patent 10,921,303 B1), in view of Khanna et al. (Microsyst Technol, 2010), and further in view of Demir et al. (PLoS ONE, 2013), Davis et al. (Journal of Biomechanics, 2004), and Ramchandani et al. (Journal of Controlled Release, 1997).
Dong in view of Khanna teaches the methods of claims 1, 3-5, 8-10, 13-17, 54-59, 63, and 65-66, as described above. And though Dong does not require that their microneedles contain silicon, the combination of Dong in view of Khanna does utilize microneedles that contain silicon.
Demir teaches the microfabrication and physical characterization of various array types (Abstract). One such array type is an array made with PLGA, a biodegradable polymer (page 2, column 1, paras. 3-4). The PLGA array was made with 50:50 pellets (page 4, column 2, para. 1). Both axial and transverse fracture force were measured (pages 4-5). The fracture force per needle on the array varied depending on specific needle measurements, but Demir states, “Needle failure was rose from 0.10 to 0.22 N/needle as the needle length increased from 700 to 1500 mm with constant tip (25 mm) and base (200 mm) diameters,” (page 6, column 2, para. 6). Figure 5B and 5D also note needle failure below 1 N/needle. Transverse fractures in Table 2 were also noted to occur at below 1 N/needle.
Davis teaches forces associated with microneedle array insertion (Abstract). In Figure 6A, a general trend is shown where fracture force of a needle increases with increased tip radius (and therefore would decrease with decreased tip radius), and a similar trend is shown in Figure 7A. It is noted that the solid line in Figure 6A and the data in Figure 7 are based on analytical data that is shown to be slightly more accurate than the finite element analysis, which is shown by the dashed line in Figure 6A (see pages 1161, para. 2 through page 1162, para. 4).
Ramchandani provides details on PLGA as a biodegradable polymer, specifically noting that it is capable of water uptake and that degradation for a 50:50 composition occurs in 6-8 weeks (Abstract, and see page 170, column 1, para. 1 and “Conclusions”).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to utilize the teachings of Demir, Davis, and Ramchandani with Dong in view of Khanna to arrive at the method of claim 67 by utilizing a PLGA microarray rather than a silicon microarray. Specifically, Dong in view of Khanna renders obvious the use of an array of microneedles to collect more analyte than a single microneedle can for a given length of time. Dong does not require a particular width for the needle tip, but does note that tips with a width less than that of a typical cell (less than or equal to 5 µm) are used (column 5, first para. under the steps). Dong also provides no requirements for the length of their microneedles, though column 16, in the first para. under the list, states that a needle body may be “micro-sized.” Similar wording is used in column 23, para. 1 under (c). Additionally, Dong teaches that polymers generally may be used in their microneedles (column 26, para. 2) without being particularly limiting as to which polymers may be used (and so, PLGA would be encompassed by said general polymers). Demir teaches that PLGA microarrays have resistance and mechanical stability, which can make them generally useful and appealing to the ordinary artisan (page 8, column 1, para. 2). Such microarrays are taught by Demir as being biodegradable, which can generally make them less wasteful, and Ramchandani provides guidance that this degradation occurs on long time scales that would not affect the immediate use of a microarray with a plant leaf. Thus, the ordinary artisan would be motivated to use a PLGA microarray as a substitute for a silicon microarray as recited in Dong in view of Khanna. MPEP 2143 I (B) states, “The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art.” As PLGA is also taught by Ramchandani to be swellable with water, utilizing PLGA with the needles with hydrophilic coatings as taught in Dong in view of Khanna would lead to similar or better performance compared to the silicon needles taught above in that analyte would be successfully absorbed onto the surface of the microneedles. Furthermore, Demir provides evidence that their fracture forces are generally under 1 N, with trends of decreasing fracture force for PLGA as needle length decreased (page 6, column 2, para. 6). The microneedle tip diameters used in Demir are larger than those of Dong in view of Khanna (25 µm vs ~5 µm), but the guidance of decreasing fracture force with decreasing tip diameter provided by Davis would give evidence to the ordinary artisan that the fracture force would remain below 1 N if a PLGA microarray with the microneedle tip and body dimensions of Dong in view of Khanna were used. This would further the expectation of predictable and successful results.
Thus, claim 67 is prima facie obvious over Dong, in view of Khanna, and further in view of Demir, Davis, and Ramchandani
Conclusion
No claims are currently allowable.
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/FRANCESCA FILIPPA GIAMMONA/Examiner, Art Unit 1681