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 .
Election/Restrictions
Newly submitted claims 23-24 and 32-34 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
Claims 23-24 and 32-34 are directed to Group II as they depend from claim 13 and are directed to the method of manufacturing. The applicant elected Group I in the Remarks 5/27/2025, and the election was made final in the Office Action 7/02/2025.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 23-24 and 32-34 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Status of Claims
Applicant's amendment filed 10/02/2025 is acknowledged. Claims 1, 7, 9, 11, and 13 have been amended. Claims 23-34 have been added. Claims 2-3 have been cancelled. Claims 13-24 and 32-34 are withdrawn. Claims 1 and 4-34 are pending in the instant application and claims 1, 4-12, and 25-31 are the subject of this final office action.
All of the amendments and arguments have been reviewed and considered. Any rejections or objections not reiterated herein have been withdrawn in light of amendments to the claims or as discussed in this office action.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Previous Rejections/Objections
Status of Prior Rejections/Objections:
The objection to the drawing is withdrawn in view of the color petition granted 01/26/2026 and amended specification.
The objections to the specification regarding trademarks and to claims 9 and 10 are withdrawn in view of the amendments.
The 112(b) rejection of claim(s) claims 1, 2, 7, and 11 and corresponding rejections of dependent claims are withdrawn in view of the amendments to or cancellation of the claims. The 112(b) rejection of claim 6 is maintained and clarified.
The prior art rejection(s) under 35 USC 102 directed to claim(s) 1-3, 5, and 8-10 as being anticipated by Seok and claims 1-8 and 12 as being anticipated by Dou are withdrawn in view of the amendments to the claims.
All prior art rejection(s) under 35 USC 103 are withdrawn in view of the amendments to the claims. See new 103 rejections as necessitated by amendments.
All double patenting rejections over copending applications 17/576,971; 17/576,974; 17/576,975; and 17/576,976 are withdrawn in view of the amendments; see new double patenting rejections as necessitated by amendments and the Terminal Disclaimer section.
New Ground(s) of Rejections
The new ground(s) of rejections were necessitated by applicant’s amendment of the claims.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Information Disclosure Statement
The information disclosure statements filed 12/15/2025 and 04/09/2026 fail to comply with the provisions of 37 CFR 1.97(a) because they lack the appropriate size fee set forth in 37 CFR 1.17(v).
The Applicant noted that the size fee has been submitted in the IDS dated 12/15/2025; however, the Office has indicated that the size fee has not been paid. Applicant may consider calling the Receipts Accounting Division (571-272-6500).
The information disclosure statement filed 08/18/2026 fails to fully comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. It has been placed in the application file, but the information referred to therein has not been considered.
Applicant is requested to submit a translation of the Taiwanese search reports and/or a list of the documents cited therein and the US applications the TW Applications correspond to.
Terminal Disclaimer
The terminal disclaimers filed 10/02/2025 are disapproved because the person who signed each terminal disclaimer is not the applicant, the patentee or an attorney or agent of record. See 37 CFR 1.321(a) and (b).
It is noted that a power of attorney has since been filed on 10/17/2025 and resubmission of a terminal disclaimer for copending applications 17/576,971; 17/576,974; 17/576,975; and 17/576,976 is required for approval. No additional fee is required.
Claim Notes
While claim 1 recites both “solid-phase reaction medium” and “solid phase reaction medium” such there is an antecedent basis is for both a hyphenated and non-hyphenated forms of “solid-phase ... medium”, Applicant is encouraged to choose one form of the term for consistency throughout the claims.
Claim Objections
Claims 25-31 are objected to because of the following informalities:
Claims 25-27 and 29-31 lack a comma after the claim number of the preamble.
Claim 28 had an extra space after “spacer” in line 6 of the claim.
Claim 29 recites “lamp”; this should be “LAMP”.
Claim 30 has an extra space after “2 years”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
Claims 6 and 25-31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 6, as discussed previously, the claim recites “a surface area to thickness ratios between about 30 and about 600”. Surface area is in squared distance measurement units, whereas thickness units are unsquared.
The inputs to the surface area and thickness may be of any unit, and even if they are of the same unit or are converted, they leave behind an uncancelled linear distance unit after performing such a calculation. Because of this, the physical structures required of the assembly may vary widely despite having a same “about 30” surface area to thickness ratio, e.g., if the “about 30” is 30 m, 30 uM, 30 ft^2/in, etc. Without a unit to guide the artisan, there is not reasonable certainty whether such structures would fall within the bounds of the claim.
Therefore, the metes and bounds are not clear to one of ordinary skill in the art.
Regarding claim 25, the new claim recites “the results of the ... LAMP ... reaction are analyzed by color”. A single claim that claims both a product and the method steps of using the product is indefinite. See MPEP 2173.05(p).
Applicant may consider a limitation which focuses on the capabilities of the product or a structural requirement, not specific actions or functions performed by a user, e.g., “wherein the solid-phase reaction medium is capable of colorimetric characterization” or “wherein the LAMP reagent mixture of the solid-phase reaction medium further comprises a colorimetric indicator”.
Claim 26-31 are indefinite for depending on claim 25 and not rectifying the deficiency.
Regarding claim 26, the new claim recites “the solid phase reaction medium has a buffering capacity from about 0.01 mM to about 5 mM”. This limitation is unclear because the buffering capacity does not provide the artisan sufficient information to understand the metes and bounds of the claim.
First, where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “buffering capacity” the claim is used by the claim to mean “an amount of something the medium can buffer,” while the accepted meaning is “the reciprocal of the slope of a titration curve.” The term is indefinite because the specification does not clearly redefine the term.
Second, as the buffering capacity of a system is directly related to the pH of a system (e.g., may be defined as the reciprocal of the slope of a titration). It is not clear what pH/pH range relative to which the buffering capacity is intended to be calculated (e.g., neutral pH, pH of the reagent mixture prior to drying or lyophilization into a solid phase, pH of an anticipated sample, etc.). Thus, despite having the same structures (e.g., X amount of a buffer), a product may have a buffer capacity within the range given a one rehydration solution but not another, for example.
Third, the boundaries of the claim scope are unclear because it merely describes the result achieved by the invention, wherein it would be unclear to the artisan which structures or materials that accomplish the function or achieve the result (i.e., are encompassed by the claim) and how, if at all, these limitations further limit the claim. See MPEP 2173.05(g).
Regarding claim 27, the new claim recites that “the solid phase reaction medium has an Amax ranging from about 443 nm to about 570 nm”.
It is unclear if the limitation is intending to claim a range of Amax states the solid phase reaction medium is capable of transitioning between or if the limitation is directed to a single Amax within the range.
Regarding claim 29-31, the new claim 29 recites “further comprising: a combination of a solid phase reaction medium and lamp reagents when stored ... maintain a coloration of the solid phase reaction medium”.
It is not clear if the claim intends to recite an additional “a solid phase reaction medium” combined with “lamp reagents” to impose additional restrictions on the “solid phase reaction medium compris[ing]: ... a LAMP reagent mixture” of claim 1.
If an additional combination was intended, each “the solid phase reaction medium” lacks sufficient antecedent basis.
Claims 30-31 are indefinite for depending on claim 29 and not rectifying the deficiency.
In addition, the references to “the combination” of claims 30-31 lack sufficient antecedent basis given that it is unclear whether “the combination” is the “a combination” claim 29 or “a LAMP reagent mixture combined with the reaction layer” of claim 1.
Further, the limitations of claims 29-31 are unclear for reciting a result achieved by the invention, wherein it would be unclear to the artisan which structures or materials that accomplish the function or achieve the results (i.e., are encompassed by the claim) and how, if at all, these limitations further limit the claim. See MPEP 2173.05(g).
Claim Rejections - 35 USC § 103
Claim(s) 1, 4, 8-10, 12, and 25-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tanner (US 10968493 B1; effectively filed 07/24/2020; as cited in the IDS dated 06/12/2025) in view of Engelhard (AU 621236 B2; granted 03/05/1992).
Regarding claim 1, Tanner teaches a LAMP reaction assembly comprising:
a solid-phase reaction medium comprising:
a LAMP reagent mixture combined with a reaction layer (col 5, para 5; col 17, j).
Tanner teaches that the LAMP master mix comprises KCl (col 39, Example 6, para 1; Fig. 17B and C; col 17, m) and does not disclose any of glycerol, ethanol, methanol, CaCl2, or CaSO4 (col 39, Example 6, para 1; Example 5), wherein the WarmStart RTx is explicitly taught to be glycerol-free in the lyophilized master mix condition (col 39, line 4).
It is also noted that the exemplary “final device” of the instant disclosure (instant Example 29, para [00285]) uses the same WarmStart Bst 2.0 and WarmStart RTx as Tanner and the other components are not known in the art to potentially comprise glycerol (see Examples 5 and 6). See MPEP 2112.01(I).
Regarding claim 8, Tanner teaches that the master mix may be immobilized on paper (col 3, para 2; col 3, para 5; col 5, para 5; col 11, line 52; col 17, j; col 25, para 5; claim 18;).
Regarding claim 25, Tanner teaches that its indicators are encompass colorimetric and/or fluorescent dyes (entire document, e.g., col 2, para 1-2;).
Regarding claim 26, Tanner teaches that its master mix, following reconstitution should be in a weakly buffered solution, wherein the pH of the master mix may be buffered in the range of pH 7.5-9.0 or pH 8.1-8.5 (col 3, para 3).
Tanner teaches that the master mix for use in a pH colorimetric LAMP may have a low buffer concentration of 1.5 mM Tris or less and that the master mix may be prepared in any suitable concentration including 2x to 10x such that when diluted by the sample it will result in 1x concentration; Tanner also teaches that the low buffer concentration is not required if a metallochromic or fluorescent dye is used (col 18, lines, 19-26).
Tanner teaches testing various pH options for a master mix for a given pH sensitive dye to determine the maximum pH for retaining a visually detectable signal change for a positive signal if amplification has occurred and testing reducing below a standard pH of the master mix to provide a particular color change that was desirable (col 23, para 3). Tanner teaches that different pH sensitive dyes have different ranges of pH optima (col 23, para 3). Tanner teaches that lyophilization may reduce the pH of the master mix when reconstituted (col 11, para 1).
Regarding claim 27, Tanner teaches use of PAR and various metals in a paper-based spot-test showing metal-PAR reactivity for a number of metals, wherein the color [i.e., absorbance of light] produced depends on the metal chosen (Fig. 12), wherein PAR is used as a metallochromic indicator of LAMP (Example 6) and may be lyophilized on a paper device (col 17, j).
Tanner teaches that PAR may have an Amax of about 500 nM (Fig. 11B).
Tanner also teaches pH indicator phenol red, which transitions between an Amax of 560 nm and an Amax of 432 nm [i.e., about 443] and that the precise peaks depend at least in part on pH (Fig. 26). Tanner teaches phenol red in the lyophilization system (Example 5).
Tanner also teaches that the microfluidic device may alternatively be lab on chip device or a matrix such as paper, plastic, or glass (col 21, para 8, spanning col 22).
Tanner teaches that a desirable format for measuring a color change is a strip test (col 22, para 2; see also col 17, j) and that an easy detection process provides portable, field detection in addition to rapid screening for point-of-need testing applications (col 17, lines 44-46).
Tanner teaches that the sample may be a body fluid, including blood or urine (e.g., col 4, para 1)
Tanner fails to explicitly teach:
that the solid-phase medium of Tanner is disposed on a substrate (claim 1) or specific characteristics of the medium (claim 4); and
that the solid-phase medium comprises glass fiber (claim 9) or the materials of claim 10.
Regarding claim 1, Engelhard teaches a strip test (entire document, e.g., pg. 1A, Field of the Invention) comprising a reagent matrix (12) attached with its active separating layer (reagent layer) onto a transparent (see also pg. 19, line 3) polymer film (11) by means of double-sided adhesive tape (13) (pg. 19, lines 20-25; Fig. 3) [i.e., a substrate; an adhesive layer disposed on the substrate; and a reaction layer disposed on the substrate via the adhesive layer].
Regarding claim 4, Engelhard teaches that the test strip is porous (entire document, e.g., claim 1); that nylon is hydrophilic (pg. 5, line 21); that previous systems cannot be employed directly because their surfaces wet nonuniformly and absorb liquid too slowly (pg. 21, para 3); and adjusting materials to fulfill a particular task, including adjusting the absorptive capacity of the materials based on the application, such that absorption is capable of absorbing a defined liquid (pg. 24, para 2; pg. 24, para 3, spanning pg. 25 through para 1). See also nylon as a preferred carrier material below.
Regarding claims 9 and 10, Engelhard teaches that color-based detection elements have a sensitivity that is dependent on the filler content of the membrane (pg. 18, lines 7-12) and that the finished membrane is a composite of semipermeable membrane with a carrier material, wherein preferred carrier materials for the detection elements are a glass fiber fabric (instant claim 9) or a nylon fabric (instant claim 10) for improved homogeneity (pg. 18, para 1; see also pg. 18, para 2, spanning pg. 19 on the advantages of using carrier materials). Engelhard also teaches that reagents may be applied with a polymer such as polysulfone or cellulose acetate (pg. 12, para 1-2; instant claim 10).
Regarding claim 12, Engelhard teaches attaching a permeable layer to the top side of the reagent matrix to improve distribution and adsorption of the sample and covering these with a film (pg. 20, para 1), wherein the particular material may be adjusted to fulfil the particular task (pg. 24, para 2). Engelhard teaches that hydrophobic or hydrophobized films are preferred for dip-and-read tests (pg. 27, para 1).
Engelhard is directed to test strips or test devices for analyzing substances from biological fluids (pg. 1A, Field of the Invention), particularly for chromogenic detection systems using a detection reaction (pg. 9, para 4) with detection reagents incorporated in the membrane systems (entire document, e.g., pg. 8, para 6). Engelhard is taught to be applicable to biological fluids (e.g., claim 1), but particularly advantageous for blood and urine by removing interfering components (throughout, e.g., pg. 6, Summary of the Invention, para 1).
Engelhard teaches that the reagent matrix may consist of paper (pg. 23, para 1).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the multi-layer test strip structure of Engelhard in the solid-phase LAMP assembly of Tanner, motivated by the desire to remove interfering components from biological samples in the chromogenic detection of Tanner, as taught by Engelhard. Further, as Tanner teaches glycerol-free enzyme in the lyophilization condition, if the master mix were not already fully glycerol-free, it also would have been obvious to the POSITA before the EFD of the claimed invention to use at least broadly glycerol-free conditions in the master mix to further enable effective lyophilization, as suggested by Tanner (instant claim 1).
It further would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select a species of carrier fabric material from the particular glass fiber and nylon (instant claims 9 and 10) taught by Engelhard as both are taught as preferred and equivalent options for improved homogeneity, wherein they are both art recognized as suitable for an intended purpose. See MPEP 2144.07.
In recommending nylon and teaching that it is hydrophilic, it further would have been obvious to the ordinary artisan before the EFD of the claimed invention, combined with the teachings that the test strip be porous and to choose an absorptive capacity of the materials based on the application, to make the solid-phase medium hydrophilic, absorbent, and porous, wherein the degree of which would be subject to routine optimization based on the needs of the application, as taught by Engelhard (instant claim 4). See MPEP 2144.05(II).
Accordingly, it would have been obvious to the ordinary artisan before the EFD of the claimed invention that if the solid-phase reaction medium is hydrophilic, given the teachings of a combined permeable layer for improve distribution and hydrophobic/hydrophobized film [i.e., “spreading layer”], such a layer would be less hydrophilic than the solid-phase reaction medium (instant claim 12).
Given Tanner’s teaching of pH-based colorimetric dye detection systems and low buffer concentrations, a “buffering capacity from about 0.01 mM to about 5 mM” would be understood to be a results effective variable obtainable through routine experimentation for a particular sample/pH range, and further would depend on the volume used for reconstitution [i.e., given variability of the chosen concentration], size of device, amount of master mix applied, etc. Tanner teaches any of the classes of indicator dyes, wherein the selection thereof would be obvious to the POSITA before the EFD of the claimed invention to substitute as equivalents known for the same purpose. See MPEP 2144.06. Based on that decision, it further would have been obvious to the ordinary artisan before the EFD of the claimed invention to optimize according to the directions of Tanner, which include 1.5 mM or less Tris, which would be expected to overlap with a buffering capacity of about 0.01 mM as that range overlaps with about 0 mM Tris (instant claim 26). See MPEP 2144.05(II).
Further, as the structures of the claimed invention are substantially similar to those of the disclosure, the amount of buffering capacity is understood to be a property inherent to the buffers of product and/or materials chosen. See MPEP 2112.01(I).
It is also noted that “an Amax ranging from about 443 to about 570 nm” would be understood to be a results effective variable dependent on at least the choice of a species of indicator dye, the metal used if a metallochromic indicator, and/or the pH of the medium once rehydrated, and therefore obvious to the ordinary artisan before the EFD of the claimed invention to have routinely optimized the Amax (instant claim 27). See MPEP 2144.05(II) and 2144.08. Engelhard teaches utilizing a transparent substrate (e.g., claim 5), using transparent polymer fabrics, and limiting auxiliary reagents to colorless products (pg. 24, para 1), such that the Amax of the solid-phase medium of the combined product would be expected to be that of the chosen dye of Tanner and there would be a high expectation of success in the combination.
There would have been a strong expectation of success both are directed to colorimetric detection products with reagents in a matrix for use with biological samples, and each element represents the application of a known technique/element to a known product.
Claim(s) 5-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tanner (US 10968493 B1; effectively filed 07/24/2020; as cited in the IDS dated 06/12/2025) in view of Engelhard (AU 621236 B2; granted 03/05/1992) as applied to claims 1, 4, 8-10, 12, and 25-27 above, and further in view of Li (US 2016/0008809 A1; as cited in the IDS dated 04/24/2025).
Regarding claims 5-7, in the LAMP assembly of Tanner in view of Engelhard, Tanner and Engelhard teach that the matrix may be a paper matrix, as discussed and cited above. Tanner teaches providing portability for point-of-need testing applications (col 17, line 44). Engelhard teaches an approximate rectangular prism (e.g., Fig. 4-5) and that filter papers are suitable for permeable layers (pg. 24, para 2).
Tanner and Engelhard fail to specify that the paper is cellulose-based.
Li teaches paper devices integrated with nucleic amplification especially for use in low-resource settings (e.g., Abstract; Fig. 11). Li teaches that low-cost point of care devices for rapid detection of pathogens may be all-paper, as paper is inexpensive and easy to obtain (para [0041]).
Li teaches that paper is typically made from cellulose pulp and teaches using chromatography [cellulose-based] paper having pores with a diameter of 5-15 um (para [0009]; instant claim 7). Li teaches preloading LAMP primers on chromatography paper disks (e.g., para [0028]) and suggests performing such detection on a paper-based device (para [0041]). Li teaches that paper has a high surface-to-volume ratio provided by the macroporous structure in the paper material, and that this improves DNA hybridization kinetics allowing for faster pathogen detection (para [0091]; [0041]). Li teaches that [chromatography] paper provided more stable testing results than their comparison (para [0044]).
Li teaches that the chromatography paper has a thickness of 0.05 to 0.25 mm (para [0009]). Li teaches microwells of 0.5 to 3 mm in diameter and cutting a microwell into paper layers or sublayers of paper layers (para [0011]).
While noted that figures are not to be understood as necessarily to scale, for purposes of estimation, it is noted that Li represents “packing tape” as approximately one equivalent thickness to the paper layers (Fig. 11) and Engelhard portrays adhesive as approximately equivalent to the thickness of substrate and less thick than the reaction layer (e.g., Fig. 4). Accordingly, it is estimated that the height/thickness of the rectangular prism of the combined solid-phase reaction medium (e.g., Fig. 3) is between 2 and 3 paper thicknesses, e.g., 0.25 mm * 2 = 0.5 mm or, for 3, 0.75 mm. Given that the surface area may be calculated as A = 2(w*l+h*l+h*w), this results in a ratios of 24 mm^2 / .5 mm [50 mm] to 27 mm^2 / 0.75 mm [36 mm] (instant claim 6)
It is noted that the first value converted to inches produces 0.037 in^2 / 0.0295 in, i.e., a ratio of 1.254 in, despite being directed to identical underlying structures.
The choice of particular sizes of the reaction medium would be a results effective variable subject to optimization, based on a desire to provide portability, as suggested by Tanner, with sufficient space for visualization and volume for the reaction/sample absorption, suggested by Engelhard, as previously discussed.
It is noted that the choice of shape may be considered a matter of aesthetic design choices, which further would impact the surface area calculation (e.g., rectangular prism vs. cube prism vs. cylinder).
Li teaches storage of LAMP reagents on paper and performing LAMP on paper in one embodiment (para [0091-99]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the macroporous chromatography paper of Li for at least the reaction layer to make a “cellulose-based” medium, motivated by the teachings of Li that the structure of paper improves DNA hybridization kinetics and stable testing and/or as a cost reduction. There would have been a strong expectation of success as Li teaches storing LAMP reagents on paper and represents the application of a known technique to a known product, where all are directed to reagent storage on matrices of analysis of biological samples.
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tanner (US 10968493 B1; effectively filed 07/24/2020; as cited in the IDS dated 06/12/2025) in view of Engelhard (AU 621236 B2; granted 03/05/1992) as applied to claims 1, 4, 8-10, 12, and 25-27 above, and further in view of Kumari (Kumari S, et al. On-site detection of tissues of Buffalo origin by loop-mediated isothermal amplification (LAMP) assay targeting mitochondrial gene sequences. Food Analytical Methods. 2020 Feb 12;13(5):1060–8) and Schroff (Schroff S. 100% solids: A compelling solution to the challenges of medical adhesive coating [Internet]. SAE Media Group; 2015 [accessed 2025 Jan 13]. Available from: https://www.medicaldesignbriefs.com/component/content/article/23535-100-solids-a-compelling-solution-to-the-challenges-of-medical-adhesive-coating; as cited in the IDS dated 04/24/2025).
Regarding claim 11, in the LAMP assembly of Tanner in view of Engelhard, Engelhard teaches alternative adhesives and tailoring to the particular polymer network (pg. 21, para 2). Engelhard teaches that auxiliary reagents in contact with the reagent layer are easily carried into the reaction zone upon application of the sample and teaches incorporating only those reagents which cannot undergo any undesirable secondary reactions with the reagent system in the reagent matrix (pg. 23, para 3).
As discussed and cited above, Engelhard teaches optimizing absorptive capacity of the device to fulfill a particular task and that the adhesive layer bons the reaction layer to the substrate.
Tanner and Engelhard fail to explicitly teach that the adhesive is free of magnesium-interfering agents and hygroscopic agents.
Kumari teaches that Mg2+ is a key cofactor for Bst DNA polymerase activity and that Mg2+ concentration can greatly affect the amplification efficiency of LAMP assays because low Mg+ concentration may result in extremely low amplification efficiency, while excessive magnesium would decrease the specificity of the LAMP reaction due to binding of primers with incorrect template (Discussion, para 1).
Schroff teaches that in a sensitive in vitro diagnostic assay device, chemical migration from a pressure-sensitive adhesive could be enough to throw off precise measurements used to make important healthcare decisions (pg. 2, para 3). Schroff teaches an adhesive that is “ultra-clean” (pg. 4, line 7) with chemical inertia that prevents their interference with assay chemistries or reactions (pg. 4, para 2).
Schroff teaches tailoring the adhesive to exhibit desired levels of hydrophilic/hydrophobic properties (pg. 3, bullet point 2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized an adhesive, such as that of Schroff, that is free of magnesium-interfering agents, motivated by the teachings of Kumari that Mg2+ is critical for controlling efficiency and specificity of LAMP, and that is free of hygroscopic agents, motivated by the desire to optimize the absorption of the device, as suggested by Engelhard, wherein the chemical affinity for water [which would be understood to be underly hygroscopic interactions] is further determined to be a results effective variable, as taught by Schroff. There would have been a strong expectation of success as Schroff teaches its adhesive to be applicable for in vitro diagnostics, chemically “ultra-clean”/[inert] such that it does not interfere with assay chemistries/reactions, and such represents the application of known technique to a known device.
Claim(s) 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tanner (US 10968493 B1; effectively filed 07/24/2020; as cited in the IDS dated 06/12/2025) in view of Engelhard (AU 621236 B2; granted 03/05/1992) as applied to claim 25 above, and further in view of Azpiroz (US 2020/0378957 A1; published 12/03/2020) and Acros Organics (Acros Organics. Phenol Red Safety Data Sheet [Internet]. 2014 [accessed 2026 May 04] Available from: https://westliberty.edu/health-and-safety/files/2010/02/Phenol-Red.pdf).
Regarding claim 28, in the LAMP assembly of Tanner in view of Engelhard, as discussed and cited in claims 1 and 27, Tanner teaches using colorimetric indicators including the pH-sensitive indicator phenol red in the lyophilized reagents.
As discussed previously in claims 1 and 11, Engelhard teaches an adhesive. Engelhard teaches that the test strip supports may be polystyrene film [i.e., a plastic carrier] in a preferred embodiment (pg. 27, para 1).
As discussed and cited in claim 12, Engelhard teaches a distribution layer.
Engelhard teaches a test strip with multiple reagent matrices to which the biological fluid can be applied via an opening (Fig. 4b; pg. 20, para 1).
As discussed and cited in claim 11, Engelhard teaches that auxiliary reagents in a layer in contact with the reagent layer may be carried into the reaction zone upon application of the sample.
Tanner and Engelhard fail to explicitly teach a spacer and that the element is free of oxidizing agents and pH-interfering agents.
Azpiroz teaches a multiplexed assay device with an opening to receive a sample deposition, wherein the housing element houses a spacer element arranged between the top and bottom covers and provides a cap between the assays (Abstract).
Azpiroz teaches that the spacer element isolates the plurality of assays housed in the multiplexed assay (para [0010-12]) and functions as an intermediate support layer (para [0039]). Azpiroz teaches that the material may be pre-treated to make the material impermeable to liquid (para [0039]) and may prevent contamination (para [0040]).
Acros Organics teaches that phenol red is incompatible with strong oxidizing agents (10. Stability and reactivity).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention first to have utilized the spacer of Azpiroz in the combined device, motivated by the desire to reduce potential contamination and improve physical support in multiplexed embodiments, as taught by Azpiroz. Further, it would have been obvious to the POSITA before the EFD of the claimed invention, in choosing a pH indicator [which is inherently sensitive to pH] of phenol red as the LAMP read out as taught by Tanner, to have avoided pH interfering agents and oxidizing agents in the surrounding structures given the teachings of Engelhard that auxiliary reagents can travel upon deposition of the sample, motivated by the desire to avoid agents that are incompatible with that indicator, as taught by Acros Organics and suggested by Tanner. There would have been a strong expectation of success at least because multiple alternative materials are suggested by Engelhard and Azpiroz and such are directed to devices for assaying biological samples or indicators for such assays, wherein the application of which represents a known technique applied to a known device.
Claim(s) 29-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tanner (US 10968493 B1; effectively filed 07/24/2020; as cited in the IDS dated 06/12/2025) in view of Engelhard (AU 621236 B2; granted 03/05/1992) as applied to claim 25 above, and further in view of Precision Labs (Why don’t pH test strips require special packaging? [Internet]. Precision Laboratories; 2015 [cited 2026 May 2]. Available from: https://www.preclaboratories.com/faq-items/why-dont-ph-test-strips-require-special-packaging/), evidenced by Air and Me (Dry Air [Internet]. Air and Me; 2024 [cited 2026 May 5]. Available from: https://airandme.fr/en/glossary1/dry-air).
Regarding claims 29-31, in the LAMP assembly of Tanner in view of Engelhard, Engelhard describes optimizing for color stability in a reagent mixture for one colorimetric detection embodiment by using detergents (pg. 17, para 2). As discussed and cited previously in at least claim 4, Engelhard teaches optimizing the absorptive capacity of the reaction medium.
As cited and discussed in at least claims 1 and 27, Tanner teaches a variety of indicators including pH indicators. Tanner further teaches the colorimetric indicators may be additional pH sensitive dyes (col 2, para 1).
Tanner and Engelhard do not explicitly teach maintaining a particular coloration shade, a coloration for a length of time, or that is maintained in particular a relative humidity.
Precision Labs teaches that pH test trips are based on acidobasic indicators [pH sensitive dyes], which are generally very stable compounds (para 1). Precision Labs teaches choosing the “best” indicators based on properties such that they do not require air-tight packaging or a desiccant (para 1).
Precision Labs teaches that a minimum expiration date for pH test strips and papers is 3 years when stored at 10-30 C in a dry place away from chemical fumes in laboratories (para 4; instant claims 30-31).
Precision Labs suggests that the pH indicators have stable coloration [interpreted to be within 10% of an initial shade] at about 40% relative humidity by teaching the stability of the compounds without the need for desiccants (para 1) and storage in a dry place at 10-30 C (para 4), evidenced by Air and Me. While Precision Labs does not explicitly teach about 40% humidity at 25 C, it is inherently taught because Air and Me recites that air is considered dry when relative humidity is below 40% (para 1) [i.e., encompassing “about” 40%].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have optimized the choice of pH indicator and absorptive capacity of the materials, given the teachings of Precision Labs and Engelhard, wherein the ability to maintain a particular coloration/shade in storage, including at a relative humidity of about 40%, is determined to be a results effective variable based on at least that choice.
There would be a strong expectation for success as Tanner teaches a variety of pH indicators and Precision Labs is directed to pH indicator strips, wherein such represents the application of a known technique to a known product.
Further, the structures of the claimed device are rendered obvious by Tanner in view of Engelhard and features of embodiments of described in the disclosure are substantially taught. Tanner also teaches that if the reagents in the master mix are stored in a dried or lyophilized form, then the pH and buffer concentration of the master mix is not relevant until the dried master mix interacts with the sample or is rehydrated (col 22, para 1). The specification discusses the coloration in the context of the claimed hydroscopic agents in para [00113-114], which are not disclosed by Tanner and are further suggested to be entirely free of at least glycerol, as discussed previously in the rejection of claim 1.
Accordingly, the claimed properties of maintaining coloration of the claimed combination are believed to be inherent given the evidence of record. See MPEP 2112.01(I).
Double Patenting
Claims 1, 4-12, and 25-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 17/576,971 in view of Tanner (US 10968493 B1), Engelhard (AU 621236 B2), Li (US 2016/0008809 A1), Kumari (Kumari, 2020), Schroff (Schroff, 2015), Azpiroz (US 2020/0378957 A1), Acros Organics (Acros Organics, 2014), Precision Labs (Precision Labs, 2015), as evidenced by Air and Me (Air and Me, 2024), all as cited in further detail above. This is a provisional nonstatutory double patenting rejection.
The system of claim 22 recites the composition of claim 1 and a solid phase medium on to which the composition is dried, where in the composition of claim 1 comprises LAMP reagents comprising a colorimetric indicator wherein the colorimetric indicator does not undergo a color change when the composition is applied and dried.
The claims of ‘971 recite that the composition may be substantially free of glycerol, ethanol, methanol, calcium chloride, and calcium sulfate (claim 6) and that the composition may further comprise a non-discoloration additive (claim 14-15).
The claims of ‘971 teach compositions that are substantially free of volatile agents (claim 3) and hygroscopic agents (claim 4); substantially free of agents that absorb more than about 10% wt% when stored between about 40% and about 90% RH at 25 C (claim 5); and comprise an antioxidant (claim 2).
The claims of ‘971 fail to recite:
reagent mixture comprises KCl (instant claim 1);
reagent mixture is combined with the reaction layer disposed on a substrate (instant claim 1);
solid-phase medium is hydrophilic, adsorbent, and porous (instant claim 4);
solid-phase medium is cellulose-based (instant claim 5), has a particular surface area to thickness ratio (instant claim 6), or has a particular pore size (instant claim 7);
solid-phase medium comprises paper (instant claim 8), glass fiber (instant claim 9), or the materials of instant claim 10 (instant claim 10);
the solid-phase medium is bonded to the substrate by an adhesive that is free of magnesium-interfering agents and hygroscopic agents (instant claim 11);
a spreading layer or the relative level of its hydrophilic nature (instant claim 12);
a particular buffering capacity (instant claim 26);
a particular absorbance maximum (instant claim 27);
that the system/assembly further comprises adhesive, spacer, spreading layer, and wherein the substrate is a plastic carrier and wherein each of these additional elements are free of oxidizing agents and pH-interfering agents (instant claim 28);
that the combination of solid phase medium and reagents maintain a coloration shade within 10% of the initial shade when stored at 25 C (instant claim 25) for either a particular length of time (claim 30) or at a relative humidity between about 40-90% at 25 C (claim 31)
As discussed and cited in the corresponding 103 rejections above, Tanner teaches:
a LAMP reagent composition comprising KCl and combining with a solid-phase medium;
that the solid-phase medium may be paper;
an amount of buffer in the solid-phase LAMP reagents that provides such a low buffered to no buffer state; and
pH-dependent colorimetric indicator phenol red and a corresponding absorbance maximum.
As discussed and cited in the corresponding 103 rejections above, Engelhard teaches or suggests:
the configuration of a reaction layer comprising reagents disposed on a substrate, wherein the substrate may be a “plastic carrier”;
that the solid-phase medium is porous, the use of hydrophilic materials, and selecting materials optimizing materials to suit desired absorptive capacity;
a rectangular prism substrate (instant claim 6);
that the solid-phase medium may comprise glass fiber and/or at least nylon of the materials of claim 10;
using a layer to improve distribution above the reagent matrix combined with a film that is preferably hydrophobic/hydrophobized for a particular application; and
embodiments with multiple reagent matrices and that auxiliary reagents can travel upon application of a sample.
As discussed and cited in the corresponding 103 rejections above, Li teaches or suggests:
a cellulose-based/paper medium with a particular dimension (such that given the approximate shape taught by Engelhard, a surface area to thickness ratio is suggested) and pore size less than 100 microns.
As discussed and cited in the corresponding 103 rejections above, Kumari and Schroff teach:
that Mg2+ levels are essential for optimal LAMP reactions; and
that chemical migration from a pressure-sensitive adhesive may throw off precise measurements in vitro diagnostic assays and that Schroff’s adhesive is “ultra-clean”, has “chemical inertia” that prevents interference with assay chemistries/reactions, and can be tailored for desired hydrophilicity/hydrophobicity.
As discussed and cited in the corresponding 103 rejections above, Azpiroz and Acros Organics teach:
a spacer for multiplexed embodiments; and
that pH indicator phenol red is sensitive to strong oxidizing agents
As discussed and cited in the corresponding 103 rejections above, Precision Labs, as evidenced by Air and Me, teaches or suggests:
pH indicators are very stable compounds and the “best” indicators do not require air-tight packaging or a desiccant and such test strips/papers have a minimum expiration date of 3 years when stored at 10-30 C in a dry place away from chemical fumes.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized KCl in the composition, as the LAMP reagents of Tanner are taught as an equivalent for the same purpose, wherein a combination of compositions for the same purpose is obvious. See MPEP 2144.06. There would have been a strong expectation of success as both are directed to LAMP including that in the solid phase and Tanner teaches optimization of the KCl concentration compared to at least another component (e.g., Fig. 17).
Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the configuration of the solid phase medium and materials of Engelhard, motivated by the desire to remove interfering components from biological samples in chromogenic detection systems, as previously cited and discussed, and because the materials are taught as species that are art recognized as suitable for an intended purpose and/or because they improved homogeneity. See MPEP 2144.07. Additionally, it would have been obvious to remove each of the undesired constituents, as taught by ‘971 (e.g., claim 6), from each of the layers, motivated by the desire to prevent interference given teachings of Engelhard about the ability of auxiliary reagents to travel layers, wherein omission of an element is obvious if the function is not desired, as discussed in MPEP 2144.04(II)(A).
In recommending the nylon material and teaching that it is hydrophilic, it further it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, combined with the teachings that the test strip of Engelhard be porous and to choose an absorptive capacity of the materials based on the application, to make the solid-phase medium hydrophilic, absorbent, and porous, wherein the degree of which would be subject to routine optimization based on the needs of the application, as taught by Engelhard. See MPEP 2144.05(II).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that if the solid-phase reaction medium is hydrophilic, given the teachings of a combined permeable layer for improve distribution and hydrophobic/hydrophobized film [i.e., “spreading layer”], such a layer would be less hydrophilic than the solid-phase reaction medium.
Likewise, in view of Tanner’s teaching of a particular range of buffer in the reagents in the species of a pH dependent detection system, the buffering capacity is understood to be a results effective variable dependent on a particular sample/pH range and further dependent on at least the volume of master mix, size of device (absorbency), amount of master mix applied, etc. and/or a property inherent to the chosen amounts of the buffer of the reagent mixture and/or the materials of the assembly/medium.
It further would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the cellulose-based paper of Li in the combined system with the claimed pore size, such that the surface area to thickness ratio may be achieved under certain units, motivated by the teachings of Li of the decreased cost and improved DNA hybridization kinetics of paper and stability of chromatography paper, as previously discussed and cited.
In addition to the motivations above regarding the removal of undesired elements, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, motivated by at least the teachings of Engelhard regarding auxiliary reagents and optimizing absorbency and Kumari about the essentialness of Mg2+ concentration, to have utilized the “ultra pure” chemically inert adhesives of Schroff in the combined device such that the adhesive may be free of magnesium-interfering and hygroscopic agents, wherein the affinity for water is further understood to be a results effective variable as described by Engelhard and Schroff.
In multiplexed embodiments, such as those taught by Engelhard which would have been obvious to the POSITA before the EFD of the claimed invention to improve the throughput of analysis and/or to allow for additional assays, it further would have been obvious to the POSITA before the EFD of the claimed invention to utilize the spacer of Azpiroz, motivated by the desire to reduce contamination and/or to improve physical support. It further would have been obvious to the POSITA before the EFD of the claimed invention in the embodiments utilizing a pH-sensitive dye such as phenol red, which would have been an obvious choice for indicator to the POSITA before the EFD of the claimed invention as it was taught by Tanner in the lyophilized embodiments (see MPEP 2144.08), motivated by the teachings of Engelhard about the ability of auxiliary reagents to travel layers and those of Arcos Organics that oxidizing agents are incompatible with the indicator, to have designed a device that avoids such auxiliary reagents in the further structures of the assembly.
Finally, it would have been obvious to the POSITA before the EFD of the claimed invention, motivated by the teachings of Precision Labs, evidenced by Air and Me, to preferentially choose indicators that can be stored in pH strips/papers for 3 years at 10-30C in a dry [i.e., about 40% RH at 25 C] location as they are considered the “best”, wherein such a choice of dye would further be understood to be optimizable for such conditions based on these teachings. Further, as acidobasic indicators are considered “very stable compounds” and the combined structures of system are free of hygroscopic agents, the claimed properties are understood to be inherent to the system. See MPEP 2112.01(I).
The further combinations not already discussed here would have had the same expectations for success for the same reasons as in the 103 rejections above.
Any additional limitations of the ‘971 claims are encompassed by the open claim language “comprising” found in the instant claims.
Claims 1, 4-12, and 25-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 17/576,974 in view of Tanner (US 10968493 B1), Engelhard (AU 621236 B2), Li (US 2016/0008809 A1), Kumari (Kumari, 2020), and Schroff (Schroff, 2015), as cited in further detail above. This is a provisional nonstatutory double patenting rejection.
The system of ‘974 claim 1 recites a system for chromatic [i.e., analyzed by color; instant claim 25] LAMP analysis comprising a substantially non-reactive solid phase reaction medium and a non-interfering reagent mixture, wherein the reaction medium is hydrophilic, absorbent, and porous (claim 5; instant claim 4); is cellulose or glass fiber (claim 4; instant claims 5 and 9); has claimed buffering capacity (claim 2; instant claim 26); the claimed Amax (claim 3; instant claim 27); and the components of instant claim 28 (claim 7).
The system of ‘974 claim 16 recites a system for chromatic LAMP analysis comprising solid phase reaction medium and LAMP reaction, which when stored at 25 C maintain coloration of the solid phrase reaction medium that is within 10% of an initial shade of the medium, wherein in the combination maintains that when stored for the claimed periods (claim 17; instant claim 30) or the claimed relative humidity ranges (claim 18; instant claim 31).
The method of manufacturing a chromatic LAMP system as recited in claim 1 of ‘974 claim 19 comprises combining the non-interfering reagent mixture with a substantially non-reactive solid-phase reaction medium such that the mixture is held in contact with the medium, wherein the reagent mixture is combined with the medium using a reel-to-reel process (claim 22), which the artisan would understand to be the deposition of a flexible substrate [i.e., a reaction layer].
The claims of ‘974 fail to explicitly recite:
that the LAMP reagent mixture comprises KCL (claim 1);
that the LAMP reagent mixture does not comprise glycerol, methanol, CaCl, or CaSO4 (claim 1);
the dimensions or pore size or the cellulose-based medium (claims 6 and 7);
that the medium comprises paper (claim 8);
that the medium comprises any of the materials of claim 10;
that the reaction layer is bonded by the adhesive or that it is free of magnesium interfering agents and hygroscopic agents (claim 11); and
that the spacer is less hydrophilic than the solid-phase reaction medium (claim 12).
As discussed and cited in the corresponding 103 rejections above, Tanner teaches or suggests that:
a LAMP reagent composition comprising KCl and combining with a solid-phase medium;
that the reagents may be glycerol-free; and
that the solid-phase medium may be paper.
As discussed and cited in the corresponding 103 rejections above, Engelhard teaches or suggests:
that the solid-phase medium may comprise at least nylon of the materials of claim 10;
selecting materials optimizing materials to suit desired absorptive capacity;
using a layer to improve distribution above the reagent matrix combined with a film that is preferably hydrophobic/hydrophobized for a particular application; and
embodiments with multiple reagent matrices and that auxiliary reagents can travel upon application of a sample.
As discussed and cited in the corresponding 103 rejections above, Li teaches or suggests:
a cellulose-based/paper medium with a particular dimension (such that given the approximate shape taught by Engelhard, a surface area to thickness ratio is suggested) and pore size less than 100 microns.
As discussed and cited in the corresponding 103 rejections above, Kumari and Schroff teach:
that Mg2+ levels are essential for optimal LAMP reactions; and
that chemical migration from a pressure-sensitive adhesive may throw off precise measurements in vitro diagnostic assays and that Schroff’s adhesive is “ultra-clean”, has “chemical inertia” that prevents interference with assay chemistries/reactions, and can be tailored for desired hydrophilicity/hydrophobicity.
First, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the systems of ‘974 and the method of manufacturing for the system of claim 1 that recites R2R manufacturing and inherently the product produced by such a method as they were equivalents known for the same purpose, namely chromatic LAMP. See MPEP 2144.06(I). The artisan would have had had a high expectation for success as all were addressed to the same purpose.
Second, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized KCl in the composition and to have avoided at least glycerol, as the LAMP reagents of Tanner are taught as an equivalent for the same purpose, wherein a combination of compositions for the same purpose is likewise obvious, as discussed in MPEP 2144.06. There would have been a strong expectation of success as both are directed to LAMP including that in the solid phase and Tanner teaches optimization of the KCl concentration compared to at least another component (e.g., Fig. 17) and the removal of glycerol was known in the art (see Conclusion).
Third, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the configuration of the solid phase medium and materials of Engelhard, motivated by the desire to remove interfering components from biological samples in chromogenic detection systems, as previously cited and discussed, and because the materials are taught as species that are art recognized as suitable for an intended purpose and/or because they improved homogeneity. See MPEP 2144.07. Additionally, it would have been obvious to remove undesired constituents, as taught by ‘974, from each of the layers, motivated by the desire to prevent interference given teachings of Engelhard about the ability of auxiliary reagents to travel layers and ‘974 about being substantially non-reactive and free of oxidizing and pH-interfering, wherein omission of an element is obvious if the function is not desired, as discussed in MPEP 2144.04(II)(A).
In recommending the nylon material and teaching that it is hydrophilic, it further it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, combined with the teachings that the test strip of Engelhard to choose an absorptive capacity of the materials based on the application, to routinely optimize the degree of the hydrophilicity of the medium, as taught by Engelhard. See MPEP 2144.05(II).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that if the solid-phase reaction medium is hydrophilic, given the teachings of a combined permeable layer for improve distribution and hydrophobic/hydrophobized film [i.e., “spreading layer”], such a layer would be less hydrophilic than the solid-phase reaction medium.
Fourth, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the cellulose-based paper of Li in the combined system with the claimed pore size, such that the surface area to thickness ratio may be achieved under certain units, motivated by the teachings of Li of the decreased cost and improved DNA hybridization kinetics of paper and stability of chromatography paper, as previously discussed and cited.
Fifth, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, motivated by at least the teachings of Engelhard regarding auxiliary reagents and absorbency and Kumari about the essentialness of Mg2+ concentration, to have utilized the “ultra pure” chemically inert adhesives of Schroff in the combined device, wherein the affinity for water is further understood to be a results effective variable as described by Engelhard and Schroff.
The further combinations not already discussed here would have had the same expectations for success for the same reasons as in the 103 rejections above.
Any additional limitations of the ‘974 claims are encompassed by the open claim language “comprising” found in the instant claims.
Claims 1, 4-12, and 25-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of copending Application No. 17/576,975 in view of Tanner (US 10968493 B1), Engelhard (AU 621236 B2), Li (US 2016/0008809 A1), Kumari (Kumari, 2020), Schroff (Schroff, 2015), Acros Organics (Acros Organics, 2014), Precision Labs (Precision Labs, 2015), as evidenced by Air and Me (Air and Me, 2024), all as cited in further detail above. This is a provisional nonstatutory double patenting rejection.
The claims of ‘975 recite a solid phase LAMP reaction medium comprising:
a substrate; and
a reaction layer containing a substantially hygroscopic agent free LAMP reagent mixture disposed on the substrate [via an adhesive layer; instant claim 28] (claim 1; instant claim 1).
‘975 claim 1 recites that at least a spreading layer of the medium is porous (instant claim 4) and claim 16 recites that the reaction layer may have a surface area to thickness ratio from about 30 to about 600 (claim 16; instant claim 6).
The claims of ‘975 recite that the medium comprises a spacer (claim 13; instant claim 28) and the spreading layer (claim 1; instant claim 28) and that either may be cellulose, glass fiber, or at least nylon (claims 11 and 14; instant claims 5 and 9-10).
The claims of ‘975 recite that the reaction layer is disposed on the substrate by an adhesive (claim 1) and a method of maximizing accuracy of a positive test result from a solid phase LAMP reaction comprising providing a solid phase reaction medium including a pH sensitive dye and a combination of LAMP reagents (claim 34), wherein the LAMP reagents are substantially free of magnesium-containing reagents (claim 36) and the pH sensitive dye produces a positive result by changing colors (claim 34; instant claim 25).
‘975 claim 35 recites that the pH sensitive dye may be phenol red (instant claim 27).
‘975 claim 21 recites that the substrate may be a plastic carrier (instant claim 28).
The claims of ‘975 fail to recite:
that the reagent mixture comprises KCl (claim 1);
that the reagent mixture is entirely free of glycerol, ethanol, methanol, CaCl, or CaSO4 (claim 1);
that the medium is hydrophilic and absorbent (claim 4);
that a cellulose-based medium has the surface area to thickness ratio of the recited reaction layer (instant claim 6);
that a cellulose-based medium has particular pore size (claim 7);
that the adhesive is free of magnesium interfering agents and hygroscopic agents (claim 11);
that the spreading layer is less hydrophilic than the reaction medium (claim 12);
that the medium has a particular buffering capacity (claim 26);
explicitly that the dyes result in a particular Amax (claim 27);
that the adhesive, spreading layer, spacer, and plastic carriers are each free of oxidizing agents and pH-interfering agents (claim 28); and
that the medium and LAMP reagents are able to be stored, including for a particular time or at a particular humidity, and maintain a particular shade (claims 29-31).
As discussed and cited in the corresponding 103 rejections above, Tanner teaches:
a LAMP reagent composition comprising KCl and combining with a solid-phase medium;
that the solid-phase medium may be paper;
an amount of buffer in the solid-phase LAMP reagents that provides such a low buffered to no buffer state; and
pH-dependent colorimetric indicator phenol red and a corresponding absorbance maximum (Amax).
As discussed and cited in the corresponding 103 rejections above, Engelhard teaches or suggests:
that the solid-phase medium is porous, the use of hydrophilic materials, and selecting materials optimizing materials to suit desired absorptive capacity;
a rectangular prism substrate (instant claim 6);
using a layer to improve distribution above the reagent matrix combined with a film that is preferably hydrophobic/hydrophobized for a particular application; and
embodiments with multiple reagent matrices and that auxiliary reagents can travel upon application of a sample.
As discussed and cited in the corresponding 103 rejections above, Li teaches or suggests:
a cellulose-based/paper medium with a particular dimension (such that given the approximate shape taught by Engelhard, a surface area to thickness ratio is suggested) and pore size less than 100 microns.
As discussed and cited in the corresponding 103 rejections above, Kumari and Schroff teach:
that Mg2+ levels are essential for optimal LAMP reactions; and
that chemical migration from a pressure-sensitive adhesive may throw off precise measurements in vitro diagnostic assays and that Schroff’s adhesive is “ultra-clean”, has “chemical inertia” that prevents interference with assay chemistries/reactions, and can be tailored for desired hydrophilicity/hydrophobicity.
As discussed and cited in the corresponding 103 rejections above, Acros Organics teaches:
that pH indicator phenol red is sensitive to strong oxidizing agents
As discussed and cited in the corresponding 103 rejections above, Precision Labs, as evidenced by Air and Me, teaches or suggests:
pH indicators are very stable compounds and the “best” indicators do not require air-tight packaging or a desiccant, and such test strips/papers have a minimum expiration date of 3 years when stored at 10-30 C in a dry place away from chemical fumes.
First, it would have been obvious to one of ordinary skill in the art before the effective filing date to have avoided at least the “substantially free from” reagents of ‘975 claim 36 and to have utilized the pH sensitive dye in a colorimetric test with the solid phase LAMP reaction medium of claim 1 and dependents, motivated by the desire to maximize the accuracy of a positive test result, as taught by ‘975 claim 34. There would have been a strong expectation of success, and both the system and methods are directed to LAMP, and such represents the application of a known method to a known device.
Second, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized KCl in the composition and to have avoided at least glycerol, as the LAMP reagents of Tanner are taught as an equivalent for the same purpose and the ‘975 reagent mixture is recited to be substantially hygroscopic agent free, wherein a combination of compositions for the same purpose is likewise obvious, as discussed in MPEP 2144.06. There would have been a strong expectation of success as both are directed to LAMP including that in the solid phase and Tanner teaches optimization of the KCl concentration compared to at least another component (e.g., Fig. 17) and the removal of glycerol was known in the art and glycerol is known to be hygroscopic (see Conclusion).
Third, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the configuration of the solid phase medium and materials of Engelhard, motivated by the desire to remove interfering components from biological samples in chromogenic detection systems, as previously cited and discussed, and because the materials are taught as species that are art recognized as suitable for an intended purpose and/or because they improved homogeneity. See MPEP 2144.07. Additionally, it would have been obvious to remove each of the undesired constituents, as taught by ‘975, from each of the layers, motivated by the desire to prevent interference given teachings of Engelhard about the ability of auxiliary reagents to travel layers, wherein omission of an element is obvious if the function is not desired, as discussed in MPEP 2144.04(II)(A).
In recommending the nylon material and teaching that it is hydrophilic, it further it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, combined with the teachings that the test strip of Engelhard to choose an absorptive capacity of the materials based on the application, to routinely optimize the degree of the hydrophilicity of the medium, as taught by Engelhard, and as discussed in MPEP 2144.05(II).
Additionally, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that if the solid-phase reaction medium is hydrophilic, given the teachings of a combined permeable layer for improve distribution and hydrophobic/hydrophobized film [i.e., “spreading layer”], such a layer would be less hydrophilic than the solid-phase reaction medium.
Fourth, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the cellulose-based paper of Li in the combined system with the claimed pore size, such that the surface area to thickness ratio may be achieved under certain units, motivated by the teachings of Li of the decreased cost and improved DNA hybridization kinetics of paper and stability of chromatography paper, as previously discussed and cited.
Fifth, additional to the motivations above regarding omission of undesired elements, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, motivated by at least the teachings of Engelhard regarding auxiliary reagents and optimizing absorbency and Kumari about the essentialness of Mg2+ concentration, to have utilized the “ultra pure” chemically inert adhesives of Schroff in the combined device such that the adhesive may be free of magnesium-interfering and hygroscopic agents, wherein the affinity for water is further understood to be a results effective variable as described by Engelhard and Schroff.
Sixth, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrive at the claimed buffering capacity in the combined assembly as buffering capacity is determined to be a results effective variable given the teachings of Tanner dependent on a particular sample/pH range and further dependent on at least the volume of master mix, size of device (absorbency), amount of master mix applied, etc. and/or a property inherent to the chosen amounts of the buffer of the reagent mixture and/or the materials of the assembly/medium. As such, it would have been obvious to the POSITA before the EFD of the claimed invention to optimize the buffering capacity, as discussed in MPEP 2144.05.
Seventh, it would have been obvious in the embodiments utilizing a pH-sensitive dye such as phenol red, wherein such is at least an obvious species of ‘975 claim 35, which also would have been an obvious choice to the POSITA before the EFD of the claimed invention for indicator is it was taught by Tanner in the lyophilized embodiments (see MPEP 2144.08). In choosing such an indicator, it would have been obvious to the POSITA before the EFD of the claimed invention that assembly would have had Amax that overlaps the range claimed, wherein such is further recognized as a results effective variable subject to routine optimization, as previously discussed, as Tanner teaches such is dependent at least on the pH.
Finally, it would have been obvious to the POSITA before the EFD of the claimed invention, motivated by the teachings of Precision Labs, evidenced by Air and Me, to preferentially choose indicators that can be stored in pH strips/papers for 3 years at 10-30C in a dry [i.e., about 40% RH at 25 C] location as they are considered the “best”, wherein such a choice of dye would further be understood to be optimizable for such conditions based on these teachings. Further, as acidobasic indicators are considered “very stable compounds” and the combined structures of system are free of hygroscopic agents, the claimed properties are understood to be inherent to the system. See MPEP 2112.01(I).
The further combinations not already discussed here would have had the same expectations for success for the same reasons as in the 103 rejections above.
Response to Arguments
Applicant's arguments filed 10/02/2025 have been fully considered but they are not persuasive.
Regarding the 112(b) rejection, Applicant argues that the ratios are known to the artisan as demonstrated by the Office and that supplying any particular units needlessly restricts the claim as surface area or thickness can be measured in many different units. Applicant argues that the rules of geometry and algebra are more than adequate to supply the required metes and bounds to the artisan.
This argument is not persuasive. The ratio divides surface area by thickness, i.e., a squared linear measurement divided by a linear measurement, which results in a linear measurement if they cancel (which they may not as the same units are not required) not a unitless ratio. The specification does not define the linear measurements to be used, and as Applicant argues on pg. 11 of the Remarks, the “surface-area or thickness may be measured in many different units”. As described in the clarified 112(b) above, the same “about 30” ratio may therefore refer to about 30 m, 30 uM, 30 ft^2/in, etc. Without a unit to guide the artisan, there cannot be reasonable certainty about whether a particular structure falls within the metes and bounds of the claim.
In applying the prior art, the Office interpreted the limitation in mm (mm^2/mm), consistent with the units used in Dou. This interpretation is not compelled by the claim language or the specification, and a different unit assumption would yield a different scope, as has been demonstrated in the art rejections necessitated by claim amendments. That the Office was able to proceed under one interpretation does not establish that the claim boundary is definite; it merely demonstrates that the claim requires such an external assumption regarding units to be applied.
Applicant’s arguments, see pg. 11-12, filed 10/02/2025, with respect to the rejection(s) under 102 and 103 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 Tanner and Engelhard.
Applicant notes that terminal disclaimers have been submitted.
As above, the terminal disclaimers have not been approved. Resubmission will be required for their approval. As such, the double patenting rejections have been modified in view the amendments.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
De Rosier (US 6,294,365 B1; granted 09/25/2001) teaches formulations to enhance stability of biologically active materials, particularly enzymes during and after lyophilization, including by adding stabilizing agents to improve stability at room temperature over extended periods of time (Field of the Invention). De Rosier teaches a stabilized water-free mixture of one or more enzymes comprising: a carrier protein, which may be BSA (claim 55); a disaccharide, which may be trehalose (claim 58-59); and a buffer, which may be a Tris buffer (claim 65-66).
De Rosier teaches that enzymes stored in 50% glycerol storage buffers will not lyophilize as glycerol lowers the freezing point and acts as a hygroscopic agent (I. Preparation of the Enzymes for Lyophilization, para 1). De Rosier teaches that glycerol may be removed by ultrafiltration into an appropriate storage buffer (I. Preparation of the Enzymes for Lyophilization, para 1).
De Rosier teaches deglycerolized enzyme in a nucleic amplification procedure (II. Testing of Deglycerolized Enzymes in NASBA).
De Rosier teaches the effect of long term storage at temperatures from -20 C to 65 C in the stabilized compositions of the invention (VI. Stability Study on Lyophilized Enzymes; Examples 3 and 4).
Carter (Carter, 2017 as previously cited and in the IDS dated 04/09/2026) also teaches that removal of highly hygroscopic glycerol from the reagents allowed for effective water removal during lyophilization (Discussion, para 3) and that cold storage is a barrier for the use of LAMP in resource limited setting and that the reaction mixes can be lyophilized and maintain excellent activity with room temperature storage (Discussion, para 3).
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 Emma R Hoppe whose telephone number is (703)756-5550. The examiner can normally be reached Mon - Fri 11:00 am - 7:00 pm.
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/EMMA R HOPPE/Examiner, Art Unit 1683
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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