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 10/03/2025 was filed before the mailing date of the FAOM. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 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, 5-14, 19, and 22-25 are rejected under 35 U.S.C. 103 as being unpatentable over Weber et al (US20190224673A1 published 07/25/2019; hereinafter Weber) in view of Shkolnikov et al (WO2021221629A1 published 11/04/2021; hereinafter Shkolnikov), as evidence by The Freeze-Drying of Foods NPL and Which plastics are suitable for welding NPL.
Regarding claim 1, Weber teaches a lyophilized reagent: substrate complex comprising:
a solid phase substrate (a porous element 21 applied to the surface of a carrier element 8 of a carrier tablet 24 – paragraph 44 and Figs. 6-7) having a first side and a second side opposite the first side (the porous element 21 having a first side with a dry reagent 5 and a second side connected to the carrier element 8 – Figs. 6-7), wherein the first side comprises comprising an enhanced surface having a reagent deposit zone (the porous element 21 can provide an enlarged surface area for holding the dry reagent 5 – paragraph 44), wherein the substrate is a flexible membrane, film, or mesh (the porous element 21 of the carrier tablet 24 is deemed to read on a mesh – paragraph 44); and
a lyophilized reagent (a dry reagent 5 from a freeze-drying process – Fig. 6a-e and paragraph 30) disposed on the reagent deposit zone of the enhanced surface (the upper surface of the porous element 21 holding the dry reagent 5 – Fig. 6a-e), wherein a maximum height of the lyophilized reagent is less than an outer diameter of the lyophilized reagent (a maximum height of the dry reagent 5 is less than an outer diameter of the dry reagent 5 because the dry reagent 5 is formed from a liquid droplet – Fig. 6a-e and paragraph 43) and the entire upper surface of the lyophilized reagent is convex (the entire upper surface of the dry reagent 5 is convex – Fig. 6a-e).
and an adhesive layer disposed on the second side of the solid phase substrate (the porous element 21 is applied to the carrier element 8 surface by adhesive bonding – Weber paragraph 44 and Figs. 6a-e).
However, Weber does not teach a solid phase substrate comprising a hydrophilicity-enhanced surface.
Shkolnikov teaches a PCR system with lyophilized reagent comprising a substrate complex (surface of the chamber particle 100 – paragraph 31) (reagent mixture may include some or all of the reagents used to perform a PCR amplification – paragraph 25), comprising: a solid phase substrate comprising a hydrophilicity-enhanced surface (surface of the chamber particle 100 is hydrophilic – paragraph 31) having a reagent deposit zone (introducing a reagent solution to the chamber 102 and lyophilizing the reagents within the chamber particle 100 – paragraph 24). Shkolnikov further teaches the particle chamber 100 can include two layers of reagents, the primer layer 302 and the additional reagent layer 304 (paragraph 37 and Fig. 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the surface of the porous element 21, as taught by Weber, with the hydrophobic chamber particle 100, taught by Shkolnikov, to gain the ability to hold two layers of reagents. One of ordinary skill would have expected that this modification could have been performed with a reasonable expectation of success because Weber and Shkolnikov teach systems for storing and rehydrating lyophilized reagents.
Regarding claim 3, Weber, modified by Shkolnikov, teaches the complex according to claim 1, wherein the lyophilized reagent comprises a substantially flat bottom surface (the dry reagent 5 comprises a substantially flat bottom surface – Weber Fig. 6a-e).
Regarding claim 5, Weber, modified by Shkolnikov, teaches the complex according to claim 1, wherein the complex is defined by a maximum height and an outer diameter (the porous element 21, carrier tablet 24, and dry reagent 5 defines a complex comprising a maximum height and an outer diameter – Weber Figs. 6-7), wherein the maximum height is equal to or less than about 50% of the outer diameter (the maximum height of the porous element 21, carrier tablet 24, and dry reagent 5 complex is equal to or less than about 50% of the outer diameter – Weber Fig. 6-7 and paragraph 43).
Regarding claim 6, Weber, modified by Shkolnikov, teaches the complex according to claim 1, wherein the complex has a disc shape (the porous element 21, carrier tablet 24, and dry reagent 5 defines a complex comprising the carrier element 8 that is disc shaped – Weber Figs. 6-7)
Regarding claim 7, Weber, modified by Shkolnikov, teaches the complex according to claim 1, wherein the lyophilized reagent (a dry reagent 5 from a freeze-drying process – Weber Fig. 6a-e and paragraph 30) comprises a moisture content of less than about 10% by weight (Weber teaches a moisture content of less than about 10% because lyophilization, as known as freeze drying, obtains dry matter content higher than 95% (moisture content of less than about 5%) is common as evidence by The Freeze-Drying of Foods NPL).
Regarding claim 8, Weber, modified by Shkolnikov, teaches the complex according to claim 1, wherein the lyophilized reagent is formed from a volume of liquid reagent of about 5000 µl or less prior to lyophilization (an area of 0.5×0.5 mm to 5×5 mm and thicknesses ranging from 0.1 to 1 mm to hold the liquid reagent before drying – Weber paragraphs 30 and 46).
Regarding claim 9, Weber, modified by Shkolnikov, teaches the complex according to claim 8, wherein at least the reagent deposit zone of the hydrophilicity-enhanced surface of the substrate is treated to stabilize the lyophilized reagent (the buffer is a chemical that, in solution, provides a suitable chemical environment for optimum activity and stability of the DNA polymerase – Weber paragraph 25).
Regarding claim 10, Weber, modified by Shkolnikov, teaches a substrate that comprises a plurality of lyophilized reagent: substrate complexes (the porous element 21, carrier tablet 24, and dry reagent 5 complexes – Weber Figs. 6-7) according to claim 1 (the porous element 21, carrier tablet 24, and dry reagent 5 complex comprising a plurality of porous elements 21 and the dry reagents 5 – Weber paragraph 47 and Fig. 6-7).
Regarding claim 11, Weber, modified by Shkolnikov, teaches the substrate according to claim 10, wherein some or all of the plurality of lyophilized reagent: substrate complexes (the porous element 21, carrier tablet 24, and dry reagent 5 complexes – Weber Fig. 6-7) comprise the same (a reagent liquid 7 is applied to form the dry substance 5 – Weber paragraph 47 and Fig. 6-7) or different dried reagents.
Regarding claim 12, Weber, modified by Shkolnikov, teaches the complex according to claim 8, further comprising a second lyophilized reagent layered on top of the lyophilized reagent disposed on the reagent deposit zone (two layers of reagents, the primer layer 302 and the additional reagent layer 304 – Shkolnikov paragraph 37 and Fig. 3), wherein the second lyophilized reagent comprises a formulation that differs from that of the lyophilized reagent disposed on the reagent deposit zone of the hydrophilicity-enhanced surface of the substrate (the primer layer 302 and the additional reagent layer 304 are different formulations – Shkolnikov paragraph 37 and Fig. 3).
Regarding claim 13, Weber, modified by Shkolnikov, teaches the complex according to claim 12.
However, Weber, modified by Shkolnikov, does not teach comprising at least one more lyophilized reagent layer on top of the second lyophilized reagent, wherein the at least one more lyophilized reagent layer has a different reagent formulation from the first and second lyophilized reagents.
Shkolnikov teaches a nucleic acid amplification method and device further comprising at least one more lyophilized reagent layer on top of the second lyophilized reagent (the delayed delivery film 400 may be formed by introducing a solution containing the film material to the chamber 102 and lyophilizing the solution – paragraph 41), wherein the at least one more lyophilized reagent layer has a different reagent formulation from the first and second lyophilized reagents (Suitable films include sucrose, dextrose, trehalose, or a mixture thereof – paragraph 41). Shkolnikov also teaches that the delayed delivery film 400 delays the solvation of the lyophilized reagent mixture into solution such that the reagents dissolve and will be trapped within the chamber particle to reduce risk of cross talk between chamber particles with different primer sets (paragraph 42).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the lyophilized reagents, as taught by Weber as modified by Shkolnikov, with the delayed delivery film 400, taught by Shkolnikov, to reduce risk of cross talk between chamber particles with different primer sets. One of ordinary skill would have expected that this modification could have been performed with a reasonable expectation of success because Weber and Shkolnikov teach systems for storing and rehydrating lyophilized reagents.
Regarding claim 14, Weber, modified by Shkolnikov, teaches an assay device comprising the complex according to claim 1, wherein the assay device is a microfluidic device (a microfluidic flow cell – Weber paragraph 2 and Fig. 5).
Regarding claim 19, Weber, modified by Shkolnikov, teaches the complex according to claim 1, wherein the flexible membrane or mesh is a polymer flexible membrane or mesh (carrier element 8 made of plastic such as PMMA, PC, PS, PEEK, PP, PE, COC, and COP – Weber paragraph 35) (the porous element 21 can be welded to the plastic carrier element 8 – Weber paragraph 32)(Welding plastics is only applicable to thermoplastics; therefore, the porous element 21 is deemed to be a thermoplastic polymer as evidence by Which plastics are suitable for welding NPL).
Regarding claim 22, Weber, modified by Shkolnikov, teaches the assay device according to claim 14, wherein the microfluidic device is a lateral flow diagnostic device (the microfluidic flow cell is capable of lateral flow – Weber paragraph 2 and Fig. 5).
Regarding claim 23, Weber, modified by Shkolnikov, the complex of claim 1, wherein the first side is a top side of the substrate (the first side is on the upper surface of the porous element 21 – Weber Fig. 6a-e).
Regarding claim 24, Weber, modified by Shkolnikov, the complex of claim 23, wherein the top side of the substrate comprises a planar surface (the top of the porous element 21 is a planar surface – Weber Fig. 6a-e).
Regarding claim 25, Weber, modified by Shkolnikov, the complex of claim 23, wherein the second side is a bottom side of the substrate (the second side is the bottom surface of the porous element 21 – Weber Fig. 6a-e).
Claims 15 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Weber, modified by Shkolnikov, in view of Ito (US20110014389A1 published 01/20/2011).
Regarding claim 15, Weber, modified by Shkolnikov, teaches the complex according to claim 1, wherein the reagent deposit zone has a periphery that is bounded by a perimeter region of the substrate (the top surface of the porous element 21 is bounded by a perimeter region of the porous element 21 – Weber Fig. 6a-e).
However, Weber, modified by Shkolnikov, does not teach wherein the perimeter region comprises one or more recessed portions that extend partially or entirely through the substrate so that the lyophilized reagent:substrate complex can be detached from the substrate.
Ito teaches a lyophilization device comprising a reagent deposit zone (a first member 2 – Fig. 1) with a perimeter region (a second member 7 – Fig. 1) comprises one or more recessed portions (a through hole 6 in the second member 7 – Fig. 1) that extend partially or entirely through the substrate so that the lyophilized reagent:substrate complex can be detached from the substrate (a film 11 formed by the liquid 10 is capable of being removed from the first member 2 – Fig. 1 and paragraph 48). Ito teaches to use a through hole 6 in the second member 7 to hold that an amount of liquid 10 larger than the capacity of the region enclosed by the second member 7 before drying the liquid into a film (paragraph 48).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the device, as taught by Weber as modified by Shkolnikov, with the through hole 6, taught by Ito, in order to hold a greater about of reagent. One of ordinary skill would have expected that this modification could have been performed with a reasonable expectation of success because the Weber, Shkolnikov, Ito teach devices for lyophilizing liquids samples.
Regarding claim 21, Weber, as modified by Shkolnikov modified by Ito, teaches the complex according to claim 15, wherein the one or more recessed portions extend at least about 50% or more through the substrate (through hole 6 goes all the way through the second member 7 – Ito Fig. 1).
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Weber, modified by Shkolnikov, in view of Azpiroz et al (US20200376485A1 published 12/03/2020; hereinafter Azpiroz).
Regarding claim 20, Weber, modified by Shkolnikov, teaches the complex according to claim 19.
However, Weber, modified by Shkolnikov, does not teach wherein the polymer flexible membrane or mesh is water soluble.
Azpiroz teaches an assay test wherein the polymer flexible membrane or mesh is water soluble (a blister 1075 with a water soluble polymer film, such as, for example, polyvinyl alcohol – paragraph 61). Azpiroz teaches to use a water soluble polymer film to control the release of reagent from a blister by the polymer dissolution time.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the device, as taught by Weber as modified by Shkolnikov, with the water soluble polymer film, taught by Azpiroz, to control the release of reagent from a blister by the polymer dissolution time. One of ordinary skill would have expected that this modification could have been performed with a reasonable expectation of success because Weber, Shkolnikov, and Azpiroz teaches microfluidic test kits with dried reagents.
Response to Arguments
Applicant’s addition arguments with respect to the 102/103 rejections of the claims have been considered, and the prior art rejection has been modified in order to address the amended claim language.
Point 1: The applicant’s argument that the references do not teach “a solid phase substrate having a first side and a second side opposite the first side”, “hydrophilicity-enhanced surface of the first side of the solid phase substrate”, and “an adhesive layer disposed on the second side of the solid phase substrate” is not persuasive.
The examiner points out that the limitations have been remapped and Weber, modified by Shkolnikov, now teaches “a solid phase substrate having a first side and a second side opposite the first side” (the porous element 21 having a first side with a dry reagent 5 and a second side connected to the carrier element 8 – Weber Figs. 6-7), “hydrophilicity-enhanced surface of the first side of the solid phase substrate” (surface of the chamber particle 100 is hydrophilic – Shkolnikov paragraph 31), and “an adhesive layer disposed on the second side of the solid phase substrate” (the porous element 21 is applied to the carrier element 8 surface by adhesive bonding – Weber paragraph 44 and Figs. 6a-e).
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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/T.C.S./Examiner, Art Unit 1796
/ELIZABETH A ROBINSON/Supervisory Patent Examiner, Art Unit 1796