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 .
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.
Priority
This application is a U.S. National Stage (371) application of PCT/US2020/019840 filed on 02/26/2020 which claims priority to U.S. Provisional Application No. 62/813,297 filed on 03/04/2019.
Claim Status
Claims 1 and 10 are currently amended and the Applicant notes that no new matter is added. Claims 2, 4-5, and 24-28 are previously presented. Claims 7-10 are original. Claims 3, 6, 13-14, 17-18 and 22-23 are cancelled at the Applicant’s request. Claims 11-12, 15-16 and 19-21 are withdrawn for being drawn to a nonelected invention as noted in the Office action of 11/14/2024.
Thus, claims 1-2, 4-5, 7-10 and 24-28 are pending and are under examination.
Withdrawn Claim Rejections
The previous rejection of claims 1-2, 4-5 and 7-10 under 35 U.S.C. 112(b), regarding indefiniteness, is withdrawn in light of Applicant’s amendments of claims.
Maintained Rejection
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art (PHOSITA) to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 4-5, 7-9 and 24-28 are rejected under 35 U.S.C. 103 as being unpatentable over Ledden et al. (WO 2018/017332 A1) in view of Glezer et al. (US 2004/0189311 A1) and Falconnet et al. (WO 2018/069056 A1).
Regarding claims 1 and 24, the claims are still recited at high level of generality “wherein the at least one hydrophilic polysaccharide selected from the group consisting of cellulose, carboxymethylcellulose, FICOLL, starch, pullulan, maltodextrin, chitosan, chitin, dextran, arabinogalactan, and combinations” without further specifying the sugar to use, and thus according to the broadest reasonable interpretation (BRI), the claim reads on any hydrophilic sugar from the recited list of hydrophilic polysaccharides.
Regarding claims 1 and 24, Ledden teaches an analytical reaction kit (Abstract; page 3, [0013-0016]; page 14, [0046]).
Ledden teaches a housing or a setup for conducting at least one diagnostic assay (Page 1, [0003]).
Ledden teaches a reaction chamber and cassette for the conductance of one or more diagnostic assays (Page 19, [0053], “As shown in FIG. 10A, the first liquid reagent 24A contained within the first
cavity 24 is introduced into the reaction chamber”; page 24, [0072]).
Ledden teaches that the reaction chamber further comprises at least one solid reagent zone (Page 24, [0072]).
Ledden teaches that wherein at least one solid reagent zone comprises an antibody reagent zone for the detection of at least one analyte of interest present in a patient's liquid test sample (Page 16, [0048]).
Ledden teaches that the antibody reaction zone comprising at least one antibody (Page 16, [0048]).
Ledden teaches a liquid analytical reagent dispensing apparatus contained within the housing (Page 22, [0059]).
Ledden teaches that the apparatus comprises a container (Page 22, [0059]).
Ledden teaches that wherein the container contains at least one liquid analytical reagent (Page 22, [0059]).
Ledden teaches that the container being in fluid communication with the reaction chamber to thereby dispense the at least one liquid analytical reagent after sample is applied to the reaction chamber (Pages 23-24, [0071], “a reaction chamber in liquid communication with the inlet”; page 25, “thereby introducing the first liquid reagent from the first cavity into the reaction channel, whereby the first liquid reagent mixes with the liquid test sample to thereby form a first liquid reaction mixture in the reaction channel”).
Regarding claims 2 and 25, Ledden teaches that wherein the liquid test sample is whole blood (Page 6, [0027]).
Ledden teaches that wherein the volume of whole blood is in a range of from about 0.1 micro liter to about 100 microliters (Page 6, [0027]).
Regarding claims 4 and 26, Ledden teaches that wherein the one or more diagnostic assays is selected from a total hemoglobin detection assay, a glycated hemoglobin detection assay, and combinations thereof (Page 21, [0055] and [0057]).
Regarding claim 5 and 27, Ledden teaches that wherein the at least one analyte of interest is glycated hemoglobin (Page 21, [0055] and [0057]). Ledden teaches that at least one antibody comprises a glycated hemoglobin detection antibody (Page 16, [
0048]).
Regarding claim 1, Ledden does not teach that the at least one hydrophilic polysaccharide is selected from the group consisting of cellulose, carboxymethylcellulose, FICOLL, starch, pullulan, maltodextrin, chitosan, chitin, dextran, arabinogalactan, and combinations.
Regarding claims 1 and 24, Ledden does not teach that the antibody reaction zone comprises at least one monosaccharide, disaccharide, sugar alcohol, or combinations thereof.
Ledden does not teach that the antibody reaction zone comprises at least one hydrophilic polysaccharide.
Ledden does not teach combining at least one hydrophilic polysaccharide with at least one monosaccharide, disaccharide, sugar alcohol, or combination.
Ledden does not teach Increasing the stability or tensile strength of a surface area of a solid reagent zone.
Ledden does not teach that the solid reagent zone has a stabilized surface area with substantially no fracturing and no gritty surface after at least three weeks of storage at room temperature.
Regarding claims 7 and 28, Ledden does not teach that wherein the at least one monosaccharide is selected from the group consisting of fructose, galactose, glucose, and combinations thereof.
Regarding claims 8 and 28, Ledden does not teach that wherein the at least one disaccharide is selected from the group consisting of cellobiose, lactose, lactulose, maltose, sucrose, trehalose, and combinations thereof.
Regarding claims 9 and 28, Ledden does not teach that wherein the at least one sugar alcohol comprises mannitol.
Regarding claim 28, Ledden does not teach that wherein the at least one hydrophilic polysaccharide is selected from the group consisting of cellulose, carboxymethylcellulose, FICOLL, starch, pullulan, maltodextrin, chitosan, chitin, dextran, arabinogalactan, and combinations thereof.
Regarding claims 1 and 24, Glezer teaches how to add different sugars as stabilizers to a dry reagent such as sucrose (Page 25, [0201]) and teaches that wherein the at least one disaccharide is selected from the group consisting of sucrose or trehalose (Page 25, [201]). Glezer noted the ability of sugars to stabilize dry reagents to simplify mixing operations and reduce the volume and weight of a cartridge (Page 25, [201]).
Regarding claims 8 and 28, Glezer teaches that wherein the at least one disaccharide is selected from the group consisting of sucrose or trehalose (Page 25, [201]).
Regarding claims 1 and 24, Falconnet teaches using hydrophilic polysaccharide as lyoprotectant (Page 8, lines 1-2 and 11-13).
Regarding claims 1, Falconnet teaches that wherein the at least one hydrophilic polysaccharide is selected from the group consisting of cellulose, starch or dextran (Page 8, lines 10-13).
Falconnet teaches that the microfluidic cartridge of the invention is stable at a temperature of between -20°C and 37°C, yet preferably at a temperature of between -20°C and 37°C for 2 months, advantageously for 40 days. More preferably, the microfluidic cartridge of the invention is stable at a temperature of between -20°C and 25°C, yet preferably at a temperature of between -20°C and 25°C for 2 months, advantageously for 40 days (Page 11, lines 8-12). The microfluidic cartridges were functionalized with antibodies before storing the cartridges (Page 19, lines 3-9). Falconnet noted that part of maintaining the stability of a cartridge is to prevent loss of function during storage (Page 7, lines 22-25; page 10, lines 27-31; page 20, lines 23-25) and loss of function from drying out during storage could lead to cracking and loss of appearance.
Regarding claims 7 and 28, Falconnet teaches that wherein the at least one monosaccharide is selected from the group consisting of fructose, galactose, glucose, and combinations thereof (Page 8, lines 5-10).
Regarding claims 9 and 28, Falconnet teaches that wherein the at least one sugar alcohol comprises mannitol (Abstract; page 7-8: lines 20-33 of page 7 and lines 1-2 of page 8; page 8, lines 22-24).
Regarding claim 28, Falconnet teaches that wherein the at least one hydrophilic polysaccharide is selected from the group consisting of cellulose, starch or dextran (Page 8, lines 10-13).
Regarding claim 1, A skilled artisan would have been motivated to combine the teachings of Glezer with Falconnet by combining their sugars to further increase the stability of the solid reaction zone and resistance to stress because Falconnet mentioned that there is a need to simplify storage conditions of cartridges and their reagents (Page 2, lines 11-13), and Glezer noted the ability of sugars to stabilize dry reagents to simplify mixing operations and reduce the volume and weight of a cartridge (Page 25, [201]). A skilled artisan would have known that lack of stability could lead to visible changes in the solid reaction zone such as change in color, cracks, bends or crystal formation.
It would have been obvious for a PHOSITA before the effective filing date of the application to combine what Falconnet and Glezer taught over Ledden to improve the stability and performance of an analytical reaction kit because Glezer offered the use of sugars to stabilize the dry reagents of an assay (Page 25, [0201]) and noted substantially reducing if not eliminating the special handling and storage requirements. And Glezer further noted minimizing the complexity and cost of the system by using more stable dry, or dehydrated, forms of the assay reagents (Page 25, [0201]). Falconnet further teaches the use of different stabilizing sugars for dry storage of reagents (Page 7, lines 20-30). Falconnet notes the storage and transportation advantages of drying the reagents (Page 10, lines 4-7). Ledden teaches using an analytical reaction kit with housing for dispensing reagents and performing reactions (Abstract). A skilled artisan would be motivated to combine the above methods to produce an analyte assay reaction kit that has a longer shelf life and stability. A PHOSITA would have had a reasonable expectation of success in combining the methods of Falconnet, Glezer and Ledden because the methods are based on analytical methods that are aimed at manufacturing cartridges with solid zone areas and with high stability for long-term storage.
It would have been obvious for a PHOSITA to use different stabilizers in the method of Ledden to produce a diagnostic assay with highly stable reagents.
Regarding claim 24, Falconnet teaches that the microfluidic cartridge of the invention is stable at a temperature of between -20°C and 37°C as noted above. Falconnet noted that part of maintaining the stability of a cartridge is to prevent loss of function during storage (Page 7, lines 22-25; page 10, lines 27-31; page 20, lines 17-25) and loss of function from drying out during storage could lead to cracking and loss of appearance. A skilled artisan would know increased stability of a microfluidic cartridge would lead to functional improvements in the performance of a cartridge such as decreased reaction time and reduction in percent bias of the assay because these are inherent properties that are part of improving the stability of an assay.
MPEP 2112 clearly states that the express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. “The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness” In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) (affirmed a 35 U.S.C. 103 rejection based in part on inherent disclosure in one of the references). See also In re Grasselli, 713 F.2d 731, 739, 218 USPQ 769, 775 (Fed. Cir. 1983).
Furthermore, The Federal Circuit stated that while "inherency may support a missing claim limitation in an obviousness analysis", "the use of inherency, a doctrine originally rooted in anticipation, must be carefully circumscribed in the context of obviousness." Id. at 1194-95, 112 USPQ2d at 1952. "[I]n order to rely on inherency to establish the existence of a claim limitation in the prior art in an obviousness analysis – the limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art." Id. at 1195-96, 112 USPQ2d at 1952. But see, Persion Pharms. LLC v. Alvogen Malta Operations LTD., 945 F.3d 1184, 1191, 2019 USPQ2d 494084 (Fed. Cir. 2019), where the court stated that a proper finding of inherency does not require that all limitations are taught in a single reference, and that inherency may meet a missing claim limitation when the limitation is "the natural result of the combination of prior art elements." (emphasis in original). The court found that pharmacokinetic limitations of the asserted claims were inherently met by combining prior art references because the limitations were necessarily present in the prior art combination. Id. See also Hospira, Inc. v. Fresenius Kabi USA, LLC, 946 F.3d 1322, 1329-32, 2020 USPQ2d 6227 (Fed. Cir. 2020). In the instant case, the inherent properties of decreased reaction time and reduction in percent bias of the assay are also implicated by Falconnet that further teaches measuring the signal and comparing it between a microfluidic cartridge and a reference cartridge that is readily made as part of measuring the stability of the sensitivity of detection of a target molecule by the microfluidic cartridge (Page 11, lines 1-7).
Allowable Subject Matter
Claim 10 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Response to Arguments
Applicant's arguments filed 12/03/2025 have been fully considered but they are not persuasive.
The Applicant argued that Reference Ledden does not disclose anything about the formulation of the solid reaction zone. The Applicant further argued that Ledden does not teach or otherwise render obvious an antibody reagent zone that comprises at least one monosaccharide, disaccharide, and/or sugar alcohol and does not teach or otherwise render obvious the addition of at least one hydrophilic polysaccharide to the monosaccharide, disaccharide, and/or sugar alcohol to mitigate the fracturing caused by the presence of the monosaccharide, disaccharide, and/or sugar alcohol.
This argument is not persuasive because Ledden is not used in a 102 rejection. The Applicant is reminded to look at the teachings of references in combination as it has been noted in the MPEP. Regarding the rejection of claims under 35 U.S.C. 103 and in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, the references of Ledden, Glezer and Falconnet teaches the limitations of the claims of the instant application as discussed above. Specifically, Glezer teaches how to add different sugars as stabilizers to a dry reagent such as sucrose (Page 25, [0201]) and noted the ability of sugars to stabilize dry reagents to simplify mixing operations and reduce the volume and weight of a cartridge (Page 25, [201]). And Falconnet teaches using mixtures and sugars to stabilize functionalized cartridges (Page 7, lines 12-25; page 8, lines 3-20).
The Applicant argued that Glezer only provides a general notion about the invention that sugars may be pursued for dry reagent stability with just two examples of disaccharides. The Applicant further argued that Glezer does not teach concentrations nor ratios to use for sugars.
This argument is not persuasive because the claims do not provide such ratios or concentrations of sugars. Also, the general notion of using sugars to stabilize dry reagents is noted regardless of example number.
The Applicant argued that Falconnet does not teach combining hydrophilic polysaccharides with monosaccharides, disaccharides or sugar alcohols, and a skilled artisan is not motivated to combine Falconnet with the above references.
This argument is not persuasive because in response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Glezer teaches how to add different sugars as stabilizers to a dry reagent such as sucrose (Page 25, [0201]) and teaches that wherein the at least one disaccharide is selected from the group consisting of sucrose or trehalose (Page 25, [201]). Glezer further noted the ability of sugars to stabilize dry reagents to simplify mixing operations and reduce the volume and weight of a cartridge (Page 25, [201]). And Falconnet teaches that lyoprotectants include mixtures compounds acting as a lyoprotectant, where a first compound and a second compound have a protective effect when used in a mixture (Abstract; page 7, lines 28-30, “It should be understood that the definition also includes mixtures of compounds acting as a lyoprotectant, where a first compound and a second compound have a protective effect when used in a mixture.”). Thus, a skilled artisan would have been motivated from the teachings of Falconnet and Glezer to produce a mixture of one or more sugars and of different types.
The Applicant argued that impermissible hindsight reconstruction has been utilized to arrive at the presently claimed kits, as the prior art provides no articulated reasoning.
This argument is not persuasive because in response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, both Glezer and Falconnet teaches the advantages of including sugars in the preparation of functionalized cartridges regarding stability.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 OMAR RAMADAN whose telephone number is (571)270-0754. The examiner can normally be reached Monday-Friday 8:30 am - 5:00 pm.
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/OMAR RAMADAN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678