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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/14/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Amendment
The amendments and remarks, filed on 7/14/2025, has been entered. The claim amendments overcome the previous prior art rejection, and a new prior art rejection is applied to address the claim amendments.
The amendments and remarks, filed on 7/14/2025, has been entered. The claim amendments overcome the previous claim objections of claims 14-16.
Claim Status
Claims 1 and 4-43 are pending with claims 1 and 4-24 being examined and claims 25-43 are withdrawn.
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.
Claim 14 is 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 14 recites the limitation "the upper edge are fluorophilic" in line 2. There is insufficient antecedent basis for this limitation in the claim, thus the limitation is unclear. Further, the limitation is unclear as to which upper edge the applicant is referring to. For purpose of prosecution, the applicant interprets to be the upper edge/surface of the substrate.
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 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, 4-8, and 13-24 are rejected under 35 U.S.C. 103 as being unpatentable over Handique et al (US 20190064168 A1; hereinafter “Handique”; already of record) in view of Saez et al (US 20120231517 A1; hereinafter “Saez”; already of record).
Regarding claim 1, Handique teaches a microwell array comprising a plurality of wells (Handique; Abstract; the system includes an array of wells), wherein at least one well of the plurality of wells comprises:
a glass bottom surface (Handique; para [50]; the substrate 110 can be composed of any one or more of: glass) configured to receive a vacuum pressure and configured to transmit the vacuum pressure to an interior volume of the well1 (Handique; para [47]; Actuation pressure is preferably provided by the flow control subsystem 180 e.g., a vacuum pressure system), wherein the interior volume of the well is comprised of a side wall and the bottom surface (Handique; Fig. 1); and
the side wall is hydrophilic, wherein the glass bottom surface is either hydrophobic or hydrophilic (Handique; para [59]; the open surfaces of each well can optionally include a coating (e.g., hydrophobic, hydrophilic).
1 The limitations are directed to the function and/or the manner of operating the glass bottom surface, all the structural limitations of the claim has been disclosed Handique and the glass bottom surface of Handique is capable of being “configured to receive a vacuum pressure and configured to transmit the vacuum pressure to an interior volume of the well”. As such, it is deemed that the claimed apparatus is not differentiated from the glass bottom surface of Handique (see MPEP §2114).
Handique does not teach wherein the plurality of wells are etched into a porous glass and said bottom surface comprises porous glass.
However, Saez teaches an analogous art of a microwell array (Saez; Abstract) comprising a plurality of wells (Saez; para [34]; microwells can be created on all types of substrates), wherein the plurality of wells is etched into a porous glass (Saez; para [34, 48]; microwells can be created on all types of substrates…porous glass are contemplated for substrate base use… the walled portion is created using molding techniques with thermo-setting plastics, followed by etching (dry or wet) to expose the substrate surface) and said bottom surface comprises porous glass (Saez; para [34]; microwells can be created on all types of substrates…porous glass are contemplated for substrate base use). Examiner further finds that the prior art contained a substrate (i.e., glass) which differed from the claimed device by the substitution of component(s) (i.e., porous glass), and the substitution and their functions were known in the art as above set forth. An ordinarily skilled artisan at the time of invention could have substituted one known element with another (i.e., porous glass), and the results of the substitution (i.e., porous glass substrate) would have been predictable. Therefore, pursuant to MPEP §2143 (I), Examiner concludes that it would have been obvious to an ordinarily skilled artisan at the time of invention to substitute the glass substrate of Handique with the porous glass substrate of Saez, since the result would have been predictable.
Regarding claim 4, modified Handique teaches the microwell array of claim 1, wherein the side wall is non-porous (Handique; para [50, 62]; The walls of the array of wells are preferably constructed from the same material as that of the substrate…The walls of the array of wells are preferably constructed from the same material as that of the substrate (as described in a previous section), but can alternatively be constructed of any other suitable material to confer desired physical or chemical properties to the well cavities of the array of wells. For example, the walls can be configured to be non-permeable or semipermeable to various particles or fluids in solution).
Regarding claim 5, modified Handique teaches the microwell array of claim 1, wherein the side wall is porous (Handique; para [50, 62]; The walls of the array of wells are preferably constructed from the same material as that of the substrate…The walls of the array of wells are preferably constructed from the same material as that of the substrate (as described in a previous section), but can alternatively be constructed of any other suitable material to confer desired physical or chemical properties to the well cavities of the array of wells. For example, the walls can be configured to be non-permeable or semipermeable to various particles or fluids in solution).
Regarding claim 6, modified Handique teaches the microwell array of claim 1, wherein the plurality of wells is deposited on an upper surface of the glass bottom surface (Handique; para [51]; the etched elements of the silicon mold are then transferred polymethylmethacrylate (PMMA) sheets as a substrate 110 using a hot embossing process).
Regarding claim 7, modified Handique teaches the microwell array of claim 6, wherein the side wall comprises a deposited metal (Handique; para [62, 91]; The walls of the array of wells are preferably constructed from the same material as that of the substrate…the heat-conductive substrate can be composed of a conductive material, e.g., silicon, aluminum, copper, gold, silver).
Regarding claim 8, modified Handique teaches the microwell array of claim 1, wherein portions of the side wall of adjacent wells are hydrophobic (Handique; para [59]; To enhance fluid flow across the open surfaces of the array of wells, the open surfaces of each well can optionally include a coating (e.g., hydrophobic)).
Regarding claim 13, modified Handique teaches the microwell array of claim 1, further comprising a plurality of beads in each of the plurality of wells (Handique; para [133]; the population of particles (e.g., microspheres, beads, etc.) received into the array of wells), wherein the plurality of beads is configured to fill a plurality of pores in the glass bottom surface (Saez; para [34, 48]; microwells can be created on all types of substrates…porous glass are contemplated for substrate base use… the walled portion is created using molding techniques with thermo-setting plastics, followed by etching (dry or wet) to expose the substrate surface). The modification of Handique in view of Saez is capable of having plurality of beads is configured to fill a plurality of pores in the glass bottom surface. The limitation is directed to the function and/or the manner of operating the plurality of beads, all the structural limitations of the claim has been disclosed Handique in view of Saez. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Handique (see MPEP §2114).
Regarding claim 14, modified Handique teaches the microwell array of claim 1, wherein at least one of the glass bottoms surfaces and the upper edge are fluorophilic (Handique; para [63]; the internal surfaces of the well are configured to add a chemical agent (e.g., a drug interacting with the cell, an agent that controls pH of the solution within the well, an agent that controls density of fluid within the well, etc.), biochemical agent (e.g., a fluorescent marker)).
Regarding claim 15, modified Handique teaches the microwell array of claim 1, further comprising a plurality of first barcodes, wherein the plurality of first barcodes is printed on at least one of the side walls and the bottom surface (Handique; para [98]; The tag identifying system is preferably fixed in location, but can alternatively be configured to move relative to other system elements… a mechanism that can identify a unique identifier located on the an imaging substrate or other aspect of the system 100 (e.g., glass slide, cartridge, array of wells, etc.). The tag identifying system can alternatively or additionally be configured to parse and interpret non-encoded information (e.g., text) on an identifying tag).
Regarding claim 16, modified Handique teaches the microwell array of claim 15, further comprising a plurality of second barcodes, wherein the plurality of second barcodes is printed on at least one of the side walls and the bottom surface (Handique; para [44, 98]; clusters of cells (e.g., doublets, triplets)…tag identifying system functions to read barcodes… a mechanism that can identify a unique identifier located on the an imaging substrate or other aspect of the system 100 (e.g., glass slide, cartridge, array of wells, etc.). The tag identifying system can alternatively or additionally be configured to parse and interpret non-encoded information (e.g., text) on an identifying tag). The examiner notes that the “plurality of second barcodes” that the microwells are not limited to a single cell and a cluster of cells would comprise individual “tags” as each cell is tagged with a fluorescence signal (Handique; para [106]).
Regarding claim 17, modified Handique teaches the microwell array of claim 15, wherein the plurality of first barcodes is attached to a first particle (Handique; para [137]; a cell barcode used to identify the cell from which the nucleic acid content originated (e.g., a unit identifier)).
Regarding claim 18, modified Handique teaches the microwell array of claim 17, wherein the plurality of first barcodes is attached by grafting, printing or synthesizing of the first barcodes directly onto a surface of the first particle (Handique; para [138]; the outer shell of each particle can be modified to tailor the linker density of barcoded oligonucleotides to a specific number in order to maximize the number of biomolecules captured from the single cell lysate).
Regarding claim 19, modified Handique teaches the microwell array of claim 17, wherein the interior volume of the well comprises the first particle (Handique; Fig. 19).
Regarding claim 20, modified Handique teaches the microwell array of claim 16, wherein the plurality of first barcodes is attached to a second particle (Handique; Fig. 19; para [138]; the outer shell of each particle can be modified to tailor the linker density of barcoded oligonucleotides to a specific number in order to maximize the number of biomolecules captured from the single cell lysate). Examiner notes that the barcodes are specific to the particles, thus as seen in Fig. 19 the second particle would have the barcode.
Regarding claim 21, modified Handique teaches the microwell array of claim 20, wherein the plurality of first barcodes is attached by grafting, printing or synthesizing of the first barcodes directly onto a surface of the second particle (Handique; para [137]; a cell barcode used to identify the cell from which the nucleic acid content originated (e.g., a unit identifier)).
Regarding claim 22, modified Handique teaches the microwell array of claim 20, wherein the interior volume of the well comprises the second particle (Handique; Fig. 19).
Regarding claim 23, modified Handique teaches the microwell array of claim 1, wherein a space between the upper edge of two adjacent wells of the plurality of wells forms an upper surface, wherein the upper surface is hydrophobic (Handique; para [59]; To enhance fluid flow across the open surfaces of the array of wells, the open surfaces of each well can optionally include a coating (e.g., hydrophobic)).
Regarding claim 24, modified Handique teaches the microwell array of claim 1, wherein the at least one well of the plurality of wells further comprises an upper edge of the side wall, wherein the upper edge of the side wall is hydrophobic (Handique; para [59]; To enhance fluid flow across the open surfaces of the array of wells, the open surfaces of each well can optionally include a coating (e.g., hydrophobic)).
Claims 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over Handique in view of Saez, and in further view of Liu et al (Chapter Five – Fabricating Porous Ceramics, Porous Materials Processing and Applications, 2014, pp 221-302; hereinafter “Liu”; already of record).
Regarding claim 9, modified Handique teaches the microwell array of claim 1, with the glass bottom.
Modified Handique does not teach wherein the glass bottom surface has a pore size of about 4 microns to about 8 microns.
However, Liu teaches an analogous art of fabricating porous glass products (Liu; pp 269) wherein the glass bottom surface has a pore size of about 4 microns to about 8 microns (Liu; pp 269; the pore sizes can be 10 nm–20 μm with an increased surface area). It would have been obvious to one of ordinary skill in the art by the effective filing date to have modified the glass bottom of Handique to comprise a pore size of about 4 microns to about 8 microns as taught by Liu, because Liu teaches that porous glass prepared by this method can be made into different geometric shapes like spheres, fibers, and membranes (Liu; pp 269). Examiner notes that the base/bottom substrate of modified Handique is a membrane that would be shaped to match the wells that are deposited on top (Handique; para [49]). Further, the claimed range overlaps or falls within the prior art range; in cases where the claimed range overlaps or falls within the prior art range, a prima facie case of obviousness of the range exists. It would have been obvious to one having ordinary skill in the art to have selected the portion of 4 microns to about 8 microns in the range that corresponds to the claimed range. See MPEP 2144.05(I).
Regarding claim 10, modified Handique teaches the microwell array of claim 1, with the glass bottom.
Modified Handique does not teach wherein the glass bottom surface has a pore size of about 2 microns to about 2.5 microns.
However, Liu teaches an analogous art of fabricating porous glass products (Liu; pp 269) wherein the glass bottom surface has a pore size of about 2 microns to about 2.5 microns (Liu; pp 269; the pore sizes can be 10 nm–20 μm with an increased surface area). It would have been obvious to one of ordinary skill in the art by the effective filing date to have modified the glass bottom of Handique to comprise a pore size of about 2 microns to about 2.5 microns as taught by Liu, because Liu teaches that porous glass prepared by this method can be made into different geometric shapes like spheres, fibers, and membranes (Liu; pp 269). Examiner notes that the base/bottom substrate of modified Handique is a membrane that would be shaped to match the wells that are deposited on top (Handique; para [49]). Further, the claimed range overlaps or falls within the prior art range; in cases where the claimed range overlaps or falls within the prior art range, a prima facie case of obviousness of the range exists. It would have been obvious to one having ordinary skill in the art to have selected the portion of 2 microns to about 2.5 microns in the range that corresponds to the claimed range. See MPEP 2144.05(I).
Regarding claim 11, modified Handique teaches the microwell array of claim 1, with the glass bottom.
Modified Handique does not teach wherein the glass bottom surface has a pore size of about 0.9 microns to about 1.4 microns.
However, Liu teaches an analogous art of fabricating porous glass products (Liu; pp 269) wherein the glass bottom surface has a pore size of about 0.9 microns to about 1.4 microns (Liu; pp 269; the pore sizes can be 10 nm–20 μm with an increased surface area). It would have been obvious to one of ordinary skill in the art by the effective filing date to have modified the glass bottom of Handique to comprise a pore size of about 0.9 microns to about 1.4 microns as taught by Liu, because Liu teaches that porous glass prepared by this method can be made into different geometric shapes like spheres, fibers, and membranes (Liu; pp 269). Examiner notes that the base/bottom substrate of modified Handique is a membrane that would be shaped to match the wells that are deposited on top (Handique; para [49]). Further, the claimed range overlaps or falls within the prior art range; in cases where the claimed range overlaps or falls within the prior art range, a prima facie case of obviousness of the range exists. It would have been obvious to one having ordinary skill in the art to have selected the portion of 0.9 microns to about 1.4 microns in the range that corresponds to the claimed range. See MPEP 2144.05(I).
Regarding claim 12, modified Handique teaches the microwell array of claim 1, with the glass bottom.
Modified Handique does not teach wherein the glass bottom surface has a pore size of about 10 microns to about 20 microns.
However, Liu teaches an analogous art of fabricating porous glass products (Liu; pp 269) wherein the glass bottom surface has a pore size of about 10 microns to about 20 microns (Liu; pp 269; the pore sizes can be 10 nm–20 μm with an increased surface area). It would have been obvious to one of ordinary skill in the art by the effective filing date to have modified the glass bottom of Handique to comprise a pore size of about 10 microns to about 20 microns as taught by Liu, because Liu teaches that porous glass prepared by this method can be made into different geometric shapes like spheres, fibers, and membranes (Liu; pp 269). Examiner notes that the base/bottom substrate of modified Handique is a membrane that would be shaped to match the wells that are deposited on top (Handique; para [49]). Further, the claimed range overlaps or falls within the prior art range; in cases where the claimed range overlaps or falls within the prior art range, a prima facie case of obviousness of the range exists. It would have been obvious to one having ordinary skill in the art to have selected the portion of 10 microns to about 20 microns in the range that corresponds to the claimed range. See MPEP 2144.05(I).
Response to Arguments
In the applicant’s arguments, on pp 8, the applicant notes that the examiner does not address the side wall as being “non-porous” and admits that Handique does not address the glass bottom surfaces and upper edge as being fluorophilic. The examiner notes modified Handique still teaches the same claimed material of the bottom and upper edge being glass. Further, Handique teaches the internal surfaces of the well are configured to add a chemical agent (e.g., a drug interacting with the cell, an agent that controls pH of the solution within the well, an agent that controls density of fluid within the well, etc.), biochemical agent (e.g., a fluorescent marker) (para [63]).
In the applicant’s arguments, on pp 9, the applicant argues that Handique, Saez, and/or Liu fail to teach the etched glass and porous bottom surface. The examiner respectfully disagrees. As stated by the applicant, on page 9, the examiner relies on Saez to teach the claimed limitation as one element is substituted for another. The applicant fails to provide persuasive evidence that the substitution would have not been predictable.
In response to applicant's argument, on pp 9-10, that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., allows the use of vacuum actuation to flow liquids through the microwells) are not recited in the rejected claim(s). 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). Further, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
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 Austin Q Le whose telephone number is (571)272-7556. The examiner can normally be reached Monday - Friday 9am - 5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Elizabeth Robinson can be reached at (571)272-7129. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A.Q.L./Examiner, Art Unit 1796
/ELIZABETH A ROBINSON/Supervisory Patent Examiner, Art Unit 1796
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