Detailed Action
This is a 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 1-10 and 21-30 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 .
Status of the Rejection
The §102 rejection of claim 1 is withdrawn in view of Applicant’s amendment.
New §103 grounds are applied.
Claim Interpretation
During patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." (Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005)). The words of the claim must be interpreted in accordance with their plain meaning, unless such meaning is inconsistent with the specification (MPEP §2111-2111.01)
Particularly we are concerned with the phrase “cylindrical nanopillars”, appearing in claims 26-28. The prefix “nano-“, when applied in the naming of a structure or shape (e.g. nanostructure, nanoparticle, nanotube, nanopillar, etc), conventionally means that the structure so named has a characteristic dimension in the range of from 1 nm to 100 nm. The plain meaning of “cylindrical nanopillar”, as understood by one of ordinary skill in the art, would be a cylindrical pillar structure with one or more characteristic dimensions in the 1 nm to 100 nm length scale. However, this plain meaning interpretation is not consistent with the instant disclosure, because claim 27 requires that the cylindrical nanopillar is 10 to 100 microns tall, and claim 28 requires that the cylindrical nanopillar is 500 nm to 10 microns in diameter. Therefore for the purpose of examination and treatment against the art, Examiner interprets that a pillar structure that is taller and wider than 100 nm can read on claimed “nanopillar”, so long as its size is no larger than the maximum of the size ranges disclosed by the instant specification. Particularly, a “nanopillar” can have a height of up to 2 mm and a width of up to 100 microns consistent with instant para [0043].
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 1-9, 21-22, 25, 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). 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 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]).
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]).
Regarding claim 2, Egeland modified to incorporate the structure of Nguyen ‘967, renders obvious the device of claim 1, and Nguyen ‘967 further teaches the structure comprises a plurality of protrusions (figure 6, coating 604 comprises a plurality of protrusions from substrate 102).
Regarding claims 3 and 4, Egeland, modified to incorporate the structure of Nguyen ‘967, 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, modified to incorporate the structure of Nguyen ‘967, 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 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 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, modified to incorporate the structure of Nguyen ‘967, 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, modified to incorporate the structure of Nguyen ‘967, 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 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 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 29, Egeland and Nguyen ‘967 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 and Nguyen ‘967 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 and Nguyen ‘967 as applied to claim 1 above, in further view of “Goldberg” (US 5,959,098 A to Goldberg et al).
Regarding claim 10, Egeland, modified to incorporate the structure of Nguyen ‘967, 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).
Claims 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Egeland and Nguyen ‘967 as applied to claim 1 above, in further view of “Berthold” (Berthold et al, “Glass-to-glass anodic bonding with standard IC technology thin films as intermediate layers”, Sensors and Actuators, 82, 224-228 (2000)).
Regarding claim 23-24, Egeland in view of Nguyen ‘967 renders obvious the device of claim 1. Egeland further teaches the first substrate is made of glass (para [0159]-[0161]) and the second substrate is also made of glass (para [0103]-[0107], [0162], [0167]).
Egeland does not teach the first substrate and second substrate are coupled by fusion bonding or anodic bonding. Egeland does not teach the first substrate and second substrate are coupled by a layer of SiN.
Berthold teaches that an effective way to couple a first glass substrate to a second glass substrate is by anodic bonding with a silicon nitride interlayer (pg 225-227, “Results ...”).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to couple Egeland’s first substrate to the second substrate using anodic bonding with a layer of SiN between the two substrates, because Egeland teaches that their substrate surfaces are glass, and the prior art as disclosed in Berthold teaches that an effective way to attach a first glass substrate to a second glass substrate is by anodic bonding with a SiN interlayer. The use of a known material based on its art-recognized suitability for the intended purpose is within the ambit of one of ordinary skill in the art (MPEP 2144.07).
Claims 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Egeland and Nguyen ‘967 as applied to claim 1 above, in further view of “Petralia” (Petralia et al, “A novel miniaturized biofilter based on silicon micropillars for nucleic acid extraction”, Analyst, 142, 140-146 (2017)).
Regarding claim 26, Egeland in view of Nguyen ‘967 renders obvious the device of claim 2 wherein the structure that is incorporated from Nguyen ‘967 into the second substrate of Egeland comprises a plurality of protrusions on which the surface is disposed (Nguyen ‘967 figure 6, coating 604 comprises a plurality of protrusions from substrate 102). Note that one 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]).
Egeland and Nguyen ‘967 do not teach that the plurality of protrusions form an array of cylindrical nanopillars on which the surface is disposed.
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”).
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 protrusions which form an array of nanocylinders, based on Petralia’s disclosure that such a structure is effective for adsorption of nucleic acids.
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.
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).
Response to Arguments
Applicant’s arguments, see Remarks filed 13 November 2025, with respect to the rejection(s) of claim 1 under §102, have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Egeland.
Applicant argues that the amendments to claim 1 overcome the previously applied §102 ground of rejection. Particularly, Applicant amends claim 1 to recite that the electrodes are disposed on a first substrate, the structure is disposed on a second substrate which faces the first substrate to define a cavity therebetween. Applicant argues that the device disclosed in Nguyen ‘467 does not anticipate the amended claim because Nguyen ‘467 positions the structure and the electrode on a shared substrate, rather than on two distinct substrates.
Applicant’s argument is persuasive and the §102 rejection of record is withdrawn. However on further review Examiner finds that the claimed device structure, in which the molecules are synthesized on one substrate while the electrodes are positioned on a separate substrate, is known in the art as disclosed e.g. in Egeland. New §103 grounds are applied based on the combination of Egeland with Nguyen ‘467.
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.
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/ANDREW KOLTONOW/Examiner, Art Unit 1795
/LUAN V VAN/Supervisory Patent Examiner, Art Unit 1795