Detailed Action
This is a Non-Final Office action based on application 18/392,362 filed on December 21, 2023. The application is a 111(a) with priority to EP22216633.2 filed December 23, 2022.
Claims 1, 3-10, 21-31 are pending and have been fully considered.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 June, 2026 has been entered.
Status of the Rejection
The §103 rejection of claim is substantially maintained, but updated to reflect changes in the claim.
The rejection of claim 23 is withdrawn. Claims 23 and 31 define allowable subject matter.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3-9, 21-22, 25-27, and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over “Egeland” (US 2008/0070803 A1 to Egeland) in view of “Nguyen ‘967” (US 2021/0106967 A1 to Nguyen et al) and “Petralia” (Petralia et al, “A novel miniaturized biofilter based on silicon micropillars for nucleic acid extraction”, Analyst, 142, 140-146 (2017)). Evidentiary support in the rejection of claim 1 is provided by “Nguyen ‘434” (US 2020/0384434 A1 to Nguyen et al).
Regarding claim 1, Egeland teaches a device for electrochemically synthesizing a plurality of molecules (figure 7 and para [0153], device for synthesizing a plurality of polymer molecules), comprising:
a first substrate comprising one or more electrodes configured to generate reaction conditions to mediate the synthesis of the molecules (figure 7, substrate 12 with electrode(s) 14 on it; para [0153], the electrode is operable to generate a redox product which removes protecting group 28 from polymer precursors 26, thereby mediating a synthesis reaction) and
a second substrate comprising a structure having a surface configured to attach thereon precursors of the molecules and having a footprint (figure 7, second substrate 40 has polymer precursors 26 attached to its surface and protected by protecting groups 28),
wherein the first substrate and the second substrate are coupled such that the first substrate and the second substrate define a cavity disposed therebetween (figure 7, a space for electrolyte 22 is defined between the first substrate 12 and second substrate 40).
Egeland does not disclose that the surface configured to attach molecular precursors thereon has a surface area which is at least 5 times larger than its footprint area.
Nguyen ‘967, similarly directed to a device for electrochemically synthesizing a plurality of molecules (para [0005], “‘stacks’ for use in solid-phase synthesis of polymers”; para [0058]-[0066], figure 6-7), teaches that the device comprises:
one or more electrodes configured to generate reaction conditions to mediate the synthesis of the molecules (figure 7, electrodes 606; para [0062], “polymer synthesis may be regulated using the electrodes 606. ... Examples of using microelectrode arrays in solid-phase synthesis of polymers are described in U.S. patent application Ser. No. 16/435,363”; Nguyen ‘434, which is the pre-grant publication corresponding to the cited application, describes ways in which the electrodes can generate reaction conditions to mediate the synthesis of the molecules, particularly at paragraphs [0034]-[0047]), and
a structure having a surface configured to attach thereon precursors of the molecules and having a footprint (figure 6, coating 604 having functional groups 108 on its surface to attach thereon monomers of polymer 110; para [0061]-[0062]; figure 7, coatings 702 and 704 are similarly configured with functional groups on their surfaces which provide points of attachment for polymer 110; para [0064]-[0066]) ;
wherein the surface comprises a plurality of protrusions or indentations (Nguyen ‘967 discloses various 3D structured surfaces that read on protrusions or indentations including a surface roughened with projecting asperities (i.e. protrusions, see figure 1), an micropatterned hole array (i.e. indentations, see figure 2), and an array of microwells (i.e. indentations, see figures 4 and 6)), and has an area that is at least 5 times larger than the footprint (para [0023], “available surface area may be increased by... 5x, 10x, 25x, 50x, 100x, or more”).
Nguyen ‘967 teaches that “[p]roviding additional surface area without increasing the size of the solid substrate increases the quantity of polymers synthesized thereby increasing polymer density which can increase throughput and decrease cost” (para [0005]).
Note that a particular synthesis reaction which both Egeland and Nguyen ‘967 are directed to carrying out on the surface is the synthesis of polynucleotide chains by stepwise deprotection and addition of nucleic acids (Egeland [0112]-[0115], [0131]-[0137]; Nguyen ‘967 at para [0025]-[0027], [0146]-[0147]).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the polymer synthesis device of Egeland, by using, as the structure on the second substrate, a structure having a surface area at least fivefold greater than its footprint area, based on Nguyen’s ‘967’s teaching that the incorporation of such a feature into a similar polymer synthesis device improves the device (Nguyen ‘967 at para [0005]-[0006]).
Egeland and Nguyen do not teach that the protrusions and/or indentations are between 2 and 200 microns in height.
Petralia is directed to an on-chip biofilter for purification of DNA samples, which operates by selectively adsorbing DNA from a mixed sample onto silica surfaces, then releasing and eluting the separated DNA (pg 140-141, “Introduction ...”). Petralia teaches that extraction efficiency can be improved by providing a microstructure with high specific surface area for the DNA to adsorb to (pg 143 §3.1-3.2, “One of the key parameters for effectively capturing the DNA in SPE using the pillar approach is the surface-to-volume ratio (SVR): ... It can be clearly noticed that the DNA binding capacity increases with the SVR of the device”). The structure Petralia provides for nucleic acid adsorption comprises a plurality of protrusions which form an array of cylindrical nanopillars on which the capture surface is disposed (pg 141 left column para 2, “microfabricated silicon pillars”; pg 142 figure 2; note that Petralia’s cylinders have a diameter of 12-15 µm and a height of 100 µm, and therefore would conventionally be called microstructures rather than nanostructures. However, the instant application, in claims 27-28 and para [0043], says that the claimed nanocylinders can have similar dimensions to Petralia’s cylinders. Therefore, in light of the disclosure of the instant application, it is understood that Petralia’s cylinders read on the claimed “nanocylinders”). Petralia’s protrusions have a height of about 100 microns (pg 142 figure 2) which falls within the claimed range of from 2 to 200 microns.
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify Egeland and Nguyen ‘967 by providing, as the structure on which nucleic acids are adsorbed and polynucleotides are grown, a structure comprising cylindrical protrusions having a height of about 100 microns, based on Petralia’s disclosure that such a structure is effective for adsorption of nucleic acids. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results [MPEP 2143(A)].
Regarding claims 3 and 4, Egeland in view of Nguyen ‘967 and Petralia renders obvious the device of claim 1, and Nguyen ‘967 further teaches, in an example, that the footprint of the structure has an area of 137 mm2 (para [0099]-[0100]), which falls in the claimed ranges of between 5 mm2 and 5000 mm2 (from claim 3) and between 50 mm2 and 1000 mm2 (from claim 4).
Regarding claim 5, Egeland in view of Nguyen ‘967 and Petralia renders obvious the device of claim 1, and Nguyen ‘967 teaches the structure comprises a dielectric (para [0038], “coating 104 may be comprised of a metal oxide, a high-κ dielectric, a low-κ dielectric”; para [0051], “one example ... a coating 202 of porous anodic aluminum oxide (AAO); para [0096], “Example 2 ... coating is ... colloidal silica nanoparticles”).
Regarding claim 6, Egeland in view of Nguyen ‘967 and Petralia renders obvious the device of claim 1 and Egeland further teaches the electrodes comprise a noble metal (para [0047], “selected from indium tin oxide (ITO), iridium, platinum, palladium, gold, ... Preferably ... iridium”).
Regarding claim 7, Egeland in view of Nguyen ‘967 and Petralia renders obvious the device of claim 1 and Egeland further teaches one or more further electrodes operable to counter the reaction conditions to mediate the synthesis of the molecules (para [0153], “the second electrode (14) is able to generate a second redox product (34) which can remove the protecting group (28) from the substrate (40) facing the particular second electrode (14). The common first electrode (16) generates a first redox product (36) which is able to quench the second redox product (34)”).
Regarding claim 8, Egeland in view of Nguyen ‘967 and Petralia renders obvious the device of claim 1, and Nguyen ‘967 further teaches the structure is porous (per figure 2 and para [0051] and [0095], in one example the structure is porous anodic aluminum oxide; per figure 7 and para [0065] and [0096]-[0097], in another example the structure comprises a porous coat of colloidal silica or silica aerogel).
Regarding claim 9, Egeland in view of Nguyen ‘967 and Petralia renders obvious the device of claim 1, and Nguyen ‘967 further teaches the surface has an area that is at least 50 times larger than the footprint (para [0023], “available surface area may be increased by... 50x, 100x, or more”).
Regarding claims 21 and 22, Egeland in view of Nguyen ‘967 and Petralia renders obvious the device of claim 1.
Egeland further teaches wherein the one or more electrodes are a first set of one or more electrodes, and the device comprises a second set of one or more electrodes configured to generate reaction conditions to mediate the synthesis of the molecules (as seen figure 1 and 7, each cell 18 comprising an electrode pair 14, 16 is one pixel in a pixel array of a plurality of such cells; para [0147], [0153]), and one or more fluidic channels configured to direct a fluid through the device (figure 7, the space between first substrate 12 on which are disposed the plurality of electrode sets, and second substrate 40 on which the molecules are synthesized, is a fluidic channel through which flows electrolyte 22; para [0135], [0153]), such that (i) the first set of one or more electrodes and the structure on which the molecules are synthesized and (ii) the second set of one or more electrodes and the second structure are fluidically coupled, by the one or more fluidic channels, in parallel or series (figure 7, first set of electrodes 14, 16, and second set of electrodes 14, 16 in fluidic series with the first, are both coupled to molecule growth substrate 40 by the channel).
Egeland does not teach that there is a distinct first structure associated with the first electrode set, and second structure associated with the second electrode set, where the second structure has its own footprint, and a surface area that is at least 5 times greater than its footprint area.
Nguyen ‘967, in addition to teaching a set of electrodes and a structure as discussed above with respect to claim 1, further teaches the one or more electrodes are a first set of one or more electrodes, wherein the structure is a first structure, and wherein the device further comprises:
a second set of one or more electrodes configured to generate reaction conditions to mediate the synthesis of the molecules (figure 6 and 7, and para [0061]-[0062], there is an array of a plurality of electrode sets 606 which may be actuated independently of one another);
a second structure having a second surface configured to attach thereon precursors of the molecules and having a second footprint (figure 6 and 7, each electrode set 606 has a corresponding coating structure 604 and/or 704 configured to attach thereon precursors of the molecules, having respective footprint), wherein the second surface has an area that is at least 5 times larger than the second footprint (para [0023], “available surface area may be increased by... 5x, 10x, 25x, 50x, 100x, or more”).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention, when modifying Egeland by incorporating a high area structure on which the molecules are grown, as taught in Nguyen ‘967, to furthermore incorporate a first such structure at a position on the second substrate facing Egeland’s first set of electrodes, a second such structure at a position on the second substrate facing Egeland’s second set of electrodes, and so on, because Egeland and Nguyen ‘967 are both directed to using a planar array of electrode sets to carry out a plurality of localized polymer synthesis reactions on a substrate in parallel, and Nguyen ‘967, who professes the advantages of adding a surface-area-enhancing structure (para [0005]-[0006]), discloses placing a surface-area-enhancing structure at each of the synthesis locations of the array.
Regarding claim 25, Egeland in view of Nguyen ‘967 and Petralia renders obvious the device of claim 1, wherein Nguyen ‘967 teaches the surface area of the structure is at least 10 times greater than the area of its own footprint (para [0023], “such as ... 10x, 25x, 50x, 100x, or more”).
In Egeland’s device the electrode sets are arranged as pixels in a planar array (figure 1, 7, electrodes 14 and 16), and the substrate on whose surface on which the molecules are synthesized (figure 7 #40) is arranged as a plane facing the electrode array, such that the area on which the molecule is synthesized corresponds to the area of the electrode set that is actuated (para [0153], “In this way, the second redox product (34) generated by the second electrode (14), is substantially confined to the cell (18) in which that second electrode is positioned, thereby increasing resolution of the patterned substrate by preventing the second redox product from removing the protecting group (28) in the region of the substrate (40) facing neighbouring cells”). It follows that the footprint area of the electrodes approximately corresponds to the footprint area of the structure.
Since the structure from Nguyen ‘967 provides a surface area that “10x, 25x, 50x, 100x, or more” than the footprint area of the structure (para [0023]), and the area of the electrode is about the same as the footprint area of the structure, it naturally follows that, when the teachings of Nguyen ‘967 are incorporated into the device of Egeland, the area of the structure will be at least 10 times the area of the one or more electrodes.
Regarding claim 26, Egeland in view of Nguyen ‘967 and Petralia renders obvious the device of claim 1, wherein the structure that is incorporated from Petralia into the second substrate of Egeland comprises a plurality of cylindrical nanopillars protrusions on which the surface is disposed (pg 141 left column para 2, “microfabricated silicon pillars”; pg 142 figure 2; note that Petralia’s cylinders have a diameter of 12-15 µm and a height of 100 µm, and therefore would conventionally be called microstructures rather than nanostructures. However, the instant application, in claims 27-28 and para [0043], says that the claimed nanocylinders can have similar dimensions to Petralia’s cylinders. Therefore, in light of the disclosure of the instant application, it is understood that Petralia’s cylinders read on the claimed “nanocylinders”).
Regarding claim 27, Egeland, Nguyen ‘967, and Petralia render obvious the device of claim 26, and Petralia teaches each cylindrical nanopillar within the array of cylindrical nanopillars has a height of 100 µm (pg 141 right column para 1; pg 141 table 1), which falls in the claimed range of from 10 µm to 100 µm.
Regarding claim 29, Egeland in view of Nguyen ‘967 and Petralia render obvious the device of claim 5, and Nguyen ‘967 teaches that the dielectric comprises a coating or functionalized surface (para [0029], “coating 104 is covered with functional groups 108”).
Regarding claim 30, Egeland in view of Nguyen ‘967 and Petralia render obvious the device of claim 22. Egeland further teaches one or more further electrodes operable to counter the reaction conditions to mediate the synthesis of the molecules (figures 1 and 7, counter electrode 16, para [0153], electrode 16 is operable to counter reaction conditions created by electrodes 14), wherein at least one of the one or more further electrodes is arranged along the one or more fluidic channels between the first structure and the second structure to decouple reaction conditions in the first structure from reaction conditions in the second structure (figure 7, electrode 16 is arranged along the fluidic channel between the first and second substrates; figure 1, electrodes 14 define a pixel array of electrochemical cells 18, and the counter electrode 16 is disposed as a grid that surrounds the pixels and demarcates each pixel from its neighbors; para [0153], “The common first electrode (16) generates a first redox product (36) which is able to quench the second redox product (34). In this way, the second redox product (34) generated by the second electrode (14), is substantially confined to the cell (18) in which that second electrode is positioned, thereby increasing resolution of the patterned substrate by preventing the second redox product from removing the protecting group (28) in the region of the substrate (40) facing neighbouring cells”).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Egeland, Nguyen ‘967, and Petralia as applied to claim 1 above, in further view of “Goldberg” (US 5,959,098 A to Goldberg et al).
Regarding claim 10, Egeland in view of Nguyen ‘967 and Petralia renders obvious the device of claim 1, and Nguyen ‘967 further teaches the surface has an area that 100 or more times larger than the footprint (para [0023], “available surface area may be increased by... 100x, or more”). Nguyen ‘967 also teaches that the increased surface area may be attained by forming at least a portion of the surface from an aerogel (para [0012], [0065], “second coating 704 may be formed from any of microparticles, aerogels, and organic polymers”). However Nguyen ‘967 does not specifically teach the surface area may be at least 200 times larger than the footprint.
Goldberg is similarly directed to an array of structures for conducting many solid phase polymer synthesis reactions in parallel (col 1 ln 50 - col 2 ln 62). Goldberg teaches that the corresponding structure having a surface configured to attach thereon precursors of the molecules (col 5 ln 50 – col 9 ln 50, “solid substrates”) may be made of a silica aerogel material for the purpose of increasing the available surface area for reaction, and that such aerogel has an available surface area that is 100 to 1000 times larger than its footprint (col 6 ln 39-49, “Silica aerogels may also be used as substrates. ... Aerogel substrates provide the advantage of large surface area for polymer synthesis, e.g., ... a total useful surface area of 100 to 1000 cm2 for a 1 cm2 piece of aerogel substrate”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to implement the aerogel substrate disclosed in Nguyen ‘967 using an aerogel which has a ratio of surface area to footprint area that is within the disclosed range of Goldberg (i.e., surface area of from 100x to 1000x the footprint area per Goldberg at col 6 ln 39-49), including those amounts that are within the claimed range (i.e., at least 200x), based on the teachings from both Nguyen ‘467 and Goldberg that it is desirable to provide the solid phase synthesis substrate with a higher surface area, so that a greater amount of the molecules can be synthesized on a given amount of footprint. (Nguyen ‘467 at para [0006]; Goldberg at col 6 ln 39-49). It has been held that obviousness exists where the claimed ranges overlap or lie inside ranges disclosed by the prior art. See MPEP 2144.05 (I).
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Egeland, Nguyen ‘967, and Petralia as applied to claim 1 above, in further view of Kalhor et al (US 10,745,814 B2) and Luo et al (US 2014/0147989 A1).
Regarding claim 24, modified Egeland renders claim 1 obvious. However, Egeland is silent as to whether the first and second substrates are coupled together by a layer of silicon nitride (SiN).
Kalhor discloses a first glass substrate comprising ITO electrodes, a second glass substrate facing the first onto which oligonucleotide sequences can attach and grow (figure 6-7). The two substrates are temporarily adhered together using plastic frame spacers with layers of pressure sensitive adhesive (col 7 ln 18-41), a reaction is carried out, and then the substrates are separated to collect the synthesized product (col 17 ln 45 – col 18 ln 28).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to temporarily fix the first and second substrates in relative position to one another, in light of Kalhor’s teaching that, when growing molecules on a second substrate using electrodes on a first substrate to mediate reaction conditions, it is appropriate to temporarily attach the two substrates together with temporary adhesive layers, so that they can be held in fixed position during synthesis and then separated afterward (col 17-18; figure 6-7).
Kalhor does not teach the adhesive coating comprises silicon nitride (SiN).
Luo teaches an adhesive composition suitable for temporarily bonding substrates together in the course of electronic wafer processing (para [0030]). The adhesive composition comprises, in addition to thermoplastic, a particulate filler which serves the purpose of improving the adhesive’s mechanical stability (para [0030], [0036]-[0044]). The filler is selected from a group of ceramic materials that includes silicon nitride (para [0036], claims 3 and 10).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention, when adhering the first and second substrates together with a temporary adhesive as suggested by Egeland in view of Kalhor, to select an adhesive composition that is disclosed in the art as being suitable for temporarily adhering wafer substrates together for processing, such the adhesive composition of Luo comprising ceramic particle filler, in particle the variation of Luo that uses silicon nitride as the filer. The selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art [MPEP § 2144.07]. The court has held that if an anticipated success is attained by a person pursuing one of a finite number of known options within their technical grasp, the outcome likely reflects ordinary skill and common sense, rather than inventiveness (see KSR Int'l Co. v. Teleflex Inc., 550 U.S. at 421, 82 USPQ2d at 1397 (2007); also see MPEP 2143(E) and case law discussed therein).
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Egeland, Nguyen ‘967, and Petralia as applied to claim 26 above, in further view of “Soper” (US 2018/0074039 A1 to Soper et al).
Regarding claim 28, Egeland, Nguyen ‘967, and Petralia render obvious the device of claim 26, and Petralia teaches each cylindrical nanopillar within the array of cylindrical nanopillars has a diameter of 12 µm or 15 µm (pg 141 right column para 1; pg 141 table 1), a range which is near, but not within, the claimed range of from 0.5 µm to 10 µm. Petralia also teaches that the efficiency of nucleic acid adsorption increases as the surface-area-to-volume ratio (SVR) of the cylinder array structure is increased, and SVR in turn depends on the diameter of the nanocylinders, with smaller-diameter cylinders and smaller-pitched arrays having higher SVR values (pg 143 §3.1-3.2).
Soper is similarly directed to an on-chip DNA purification device which comprises a plurality of structures for binding a target nucleic acid sequence (“spaced support structures” as described in para [0007]), wherein the structures are an array of nanocylinders (figure 2B, array of cylindrical pillars 4; para [0071]-[0073], “spaced support structures 4”). Soper teaches that a suitable diameter for the nanocylinders is from 0.1 to 10 µm (para [0074] “each support structure is 0.1, 0.5, 1, ..., or 10 μm in diameter”).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to reduce the nanocylinder diameter, from the diameter of 12 to 15 µm as used in Petralia, to a smaller diameter based on Petralia’s teaching that such a modification is expected to improve the SVR of the nanocylinder array and thereby improve the efficiency of nucleic acid binding to the nanocylinder surface. In so doing it would have been obvious to select a diameter from the range 0.1 µm to 10 µm (including values within the claimed range of from 0.5 µm to 10 µm) based on Soper’s teaching that cylinders with diameters in this range are suitable for the intended purpose of absorbing nucleic acids. It has been held that obviousness exists where the claimed ranges overlap or lie inside ranges disclosed by the prior art. See MPEP 2144.05 (I).
Allowable Subject Matter
Claim 31 is allowed. Claims 23 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Claims 23 and 31 each require the combination of:
wherein the electrodes configured to generate reaction conditions are on a first substrate, and the substrate onto which molecular precursors are attached is a second substrate positioned opposite the first substrate to define a cavity therebetween, and
wherein the first and second substrates are coupled together by anodic bonding or fusion bonding.
The use of anodic or fusion bonding to attach substrates together is known in the art of microfluidic lab-on-a-chip devices, as a way of securely bonding one glass substrate to another. See e.g. Ulmer (US 5,674,743 A) at column 16, ln 36-61. Substrates bonded together this way are permanently fixed to each other and cannot be separated without fracturing the glass.
The feature of an electrochemical synthesis device, which employs electrodes on one substrate to modulate reaction conditions for synthesis of a molecule on a second substrate, the two substrates defining a cavity therebetween, is also known to the art. However, in each of the most pertinent prior art disclosures, the substrates are not permanently fixed to one another.
Egeland, discussed above with respect to claim 1, discloses a first substrate comprising a wafer with a patterned an electrode array, and a second substrate onto which molecules can be attached and grown. However, Egeland contemplates that the two substrates are to be separated from one another after growth of the molecules is complete (para [0102]). In an embodiment, Egeland is preparing glass slides functionalized with biomolecules, which may be used for combinatorial chemistry applications ([0114]-[0117], [0124]-[0125]). In another embodiment, Egeland is depositing a luminescent pixel array on glass substrate, to be incorporated into a display screen (para [0118]-[0122]). Each of these applications necessitates that the second substrate must be removable from the first substrate after synthesis is complete. It therefore would not have been obvious to modify Egeland by permanently attaching the first and second substrates together because this would undermine Egeland’s principle of operation.
Kalhor, discussed above with respect to claim 24, discloses a first glass substrate comprising ITO electrodes, a second glass substrate facing the first onto which oligonucleotide sequences can attach and grow (figure 6-7). The two substrates are temporarily adhered together using a polymer adhesive; a reaction is carried out; and then the substrates are separated to collect the synthesized product (col 17-18). It would not have been obvious to modify Kalhor by permanently attaching the first and second substrates together via anodic bonding or fusion bonding, because this would undermine Kalhor’s principle of operation by preventing the user from separating the substrates to collect the synthesized product.
Merriman et al (US 2022/0280906 A1) discloses a system which uses an acid-generating electrode and an acid-neutralizing electrode to generate a localized region of high pH, which creates a reaction condition by removing an acid-labile protecting group from a substrate-bound polynucleotide molecule (para [0004]). In an embodiment, the electrodes are disposed on a first substrate, and the surface the molecules grow on is a second substrate, and the first and second substrates define a cavity therebetween (figure 32B-32G, para [0195]-[0200]). Merriman also teaches that the second substrate may be structured such that it has a surface area greater than its footprint area (para [0198], “with pegs, protrusions, or the like”; para [0172]-[0179], “10 fold, 100 fold, or even more increase in area available for the DNA synthesis”; figure 23-24). However Merriman also specifies that the second substrate is attached to a motor allowing it to move relative to the first substrate, so that the two can be brought together for a synthesis step, and then separated afterwards (para [0197]-[0200], figure 32C, 32F). It therefore would not have been obvious to modify Merriman by permanently attaching the first and second substrates together via anodic bonding or fusion bonding, because this would undermine Merriman’s principle of operation by preventing the second substrate from moving relative to the first substrate.
Of the pertinent works of art that suggest locating the reaction-condition-generating electrodes on a first substrate and locating the solid-state molecular synthesis on a second substrate that opposes the first substrate so as to define a cavity therebetween, none suggest that the first and second substrate should be rigidly and permanently affixed to one another. Applicant’s claimed device is therefore distinguished from the prior art by the claimed feature of wherein the first substrate and second substrate are coupled by anodic bonding or fusion bonding.
Response to Arguments
Applicant’s arguments, see Remarks filed June 1, 2026, are unpersuasive with respect to claim 1, and persuasive with respect to claims 23 and 31. The rejection of claim 1 is substantially maintained and edited only to reflect changes in the claim text. The rejection of claim 23 is withdrawn.
With respect to claim 1, Applicant argues that the modification of Egeland’s second substrate by addition of surface-area-increasing structures with a height of 2 to 200 microns, would not have been obvious in light of Nguyen’s ‘967 because it does not carry a reasonable expectation of success. Applicant notes that Nguyen’s ‘967 discloses surface features on the order of 0.5 µm to 1 µm tall. Applicant argues that the purported benefit of texturing the second substrate to give it a larger surface area (to increase the amount of surface sites available for reaction, thereby increasing the amount of polymer that can be synthesized, per Nguyen ‘967 at para [0005]) would not have carried over into Egeland’s device if the surface were given protrusions or indentations as large as from 2 to 200 µm, because if the surface featured protrusions as large as those claimed, the distance from the electrodes to the closest portion of the second surface would be far smaller than the distance from the electrodes to the deepest recesses of the second surface.
Examiner respectfully disagrees. While Nguyen ‘967 does disclose surface coating structures 0.5 µm to 1 µm tall, shorter than the claimed range, there is nothing in the reference to suggest that this feature height is important to device operation or that a surface with larger features would be ineffective for the intended purpose of solid phase polynucleotide synthesis. Meanwhile Petralia (previously cited in the rejection of claim 26; now cited in the rejection of claim 1) discloses that a suitable surface for polynucleotide synthesis is an array of cylinders that are 100 µm tall. Examiner sees no indication in the art that Petralia’s structure, disclosed as being a suitable substrate for synthesizing polymers upon, would cease to be suitable in the context of Egeland’s electrochemical synthesis device. Therefore applicant’s argument, that one skilled in the art would be dissuaded from making this combination due to lack of a reasonable expectation of success, is found unpersuasive.
With respect to claims 23 and 31, Applicant argues that one would not have used anodic bonding or fusion bonding to attach Egeland’s first and second substrates together, even though these glass bonding techniques are known in the pertinent art, because Egeland teaches the second substrate is meant to be separated from the first substrate after the synthesis of molecules on the second substrate is finished. If the substrates were anodically bonded or fusion bonded together, they would not be separable.
Applicant’s argument is persuasive. Note that the court has held it is prima facie obvious to rigidly secure separate components together or to make inseparable components separable if there is an obvious reason to do so (see In re Larson, 340 F.2d 965, 968, 144 USPQ 347, 349 (CCPA 1965); see In re Dulberg, 289 F.2d 522, 523, 129 USPQ 348, 349 (CCPA 1961)). In this case, since Egeland intends for the second substrate to be removed and incorporated into a different device after synthesis is finished, the incorporation of anodic bonding into the device (making the second substrate inseparable from the first) would apparently render the prior art device unsatisfactory for its intended purpose.
The rejection of claim 23 is withdrawn.
Conclusion
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/ANDREW KOLTONOW/Examiner, Art Unit 1795
/LUAN V VAN/Supervisory Patent Examiner, Art Unit 1795
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