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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/17/2025 has been entered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or
under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 of PCT/US2020/041777 filed 07/16/2020 which claims benefit of Application No. 62/874,643 filed 07/16/2019. Based on the filing receipt, the effective filing date of this application is July 16, 2019 which is the filing date of Application No. 62/874,643 from which the benefit of priority is claimed.
Status of Claims
Claims 5, 9-12, 16-17, and 19-21 are cancelled by the applicant.
Claims 1-4, 6-8, 13-15, 18, and 22-28 are pending and examined herein.
Withdrawn Rejections
The declaration is sufficient to overcome the rejection because the declaration incorporates an additional reduction to practice of the claimed invention and discloses that one of ordinary skill in the art is capable of using the claimed invention without undue experimentation. With the declaration’s disclosure added to the record, the Office understands that the claimed invention is properly enabled by the applicant’s specification. For these reasons, the enablement rejection of claims 1-4, 6-8, 13-15, 18, and 22-28 is withdrawn.
However, new issues are set forth below.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 13-14, 18, 22, 24, and 27-28 are rejected under 35 U.S.C. 102(a)(a) as being anticipated by The FYL Rapid Test Dipstick (urine) package insert by Hangzhou Alltest Biotech. Co., Ltd, REF DFY-101/111, published 3/17/2015 (referred to as Hangzhou henceforth).
With respect to claim 1, Hangzhou teaches a screening device for screening a sample for norfentanyl, comprising: a pervious medium, the pervious medium comprising a test region and a control region; the test region comprising the analyte immobilized to the test region of the pervious medium, the control region comprising a control binding partner immobilized to the control region of the pervious medium, the control binding partner being complementary to a detection complex that comprises (i) a nanoparticle and (ii) a detection antibody that is complementary to the analyte, and the test (a) being visually perceptible following contact with a testing sample formed from at least the detection complex and a sample originally comprising the analyte at less than a cutoff concentration of 10 ng/mL when the analyte is norfentanyl, and (b) being visually imperceptible following contact with a testing sample formed from at least the detection complex and a sample originally comprising the analyte at greater than the corresponding cutoff concentration (see, e.g., col. 1, under “PRINCIPLE”, and col. 1, under “REAGENTS, and col. 2, under “Analytical Sensitivity”). It is understood that the dipstick is comprised of a pervious medium because the urine sample flows upward through the dipstick by capillary action.
With respect to claim 13, Hangzhou teaches a screening device for screening a sample, comprising: a pervious medium, the pervious medium comprising a test region and optionally a control region; the test region comprising norfentanyl immobilized to the pervious medium, the control region comprising a control binding partner immobilized to the pervious medium, the control binding partner being complementary to a detection complex that comprises (i) a nanoparticle and (ii) a detection antibody complementary to the norfentanyl, and wherein the test region comprises a visually perceptible level of the detection complex following contact with a sample formed from at least the detection complex and a sample originally comprising less than 10 ng/mL of norfentanyl (see, e.g., col. 1, under “PRINCIPLE”, and col. 1, under “REAGENTS, and col. 2, under “Analytical Sensitivity”).
With respect to claim 14, Hangzhou teaches a screening method, comprising: contacting a sample with an amount of a detection complex, the detection complex comprising a (i) nanoparticle and (ii) a detection antibody complementary to norfentanyl, the contacting giving rise to a treated sample; introducing the treated sample to a pervious medium, the pervious medium comprising a test region and optionally a control region, the test region comprising norfentanyl immobilized to the test region of the pervious medium, the control region comprising a control binding partner immobilized to the control region of the pervious medium, wherein the amount of the detection complex is selected such that the test region is (a) visually perceptible following contact with a testing sample formed from at least the detection complex and a sample originally comprising the norfentanyl at less than a cutoff concentration of 10 ng/mL, and (b) visually imperceptible following contact with a testing sample formed from at least the detection complex and a sample originally comprising the norfentanyl at greater than the corresponding cutoff concentration (see, e.g., col. 1, under “PRINCIPLE”, and col. 1, under “REAGENTS, and col. 2, under “Analytical Sensitivity”). It is understood that pervious region of Hangzhou comprises a test region (called the test line region) and the sample with the detection complexes are introduced to the test region by capillary flow.
With respect to claim 18, Hangzhou teaches the samples comprises a body fluid sample (see, e.g., col. 1, under “SPECIMEN COLLECTION AND PREPARATION”).
With respect to claim 22, Hangzhou teaches a kit, comprising: (i) a screening device for screening a sample for norfentanyl, comprising: a pervious medium, the pervious medium comprising a test region and optionally a control region; the test region comprising norfentanyl immobilized to the test region of the pervious medium, the control region comprising a control binding partner immobilized to the control region of the pervious medium, the control binding partner being complementary to a detection complex that comprises (1) a nanoparticle and (2) a detection antibody that is complementary to the norfentanyl, and the test region (a) being visually perceptible following contact with a testing sample formed from at least the detection complex and a sample originally comprising the norfentanyl at less than a cutoff concentration of 10 ng/mL, and (b) being visually imperceptible following contact with a testing sample formed from at least the detection complex and a sample originally comprising the norfentanyl at greater than the corresponding cutoff concentration; and (ii) a supply of the detection complex (see, e.g., col. 1, under “PRINCIPLE”, and col. 1, under “REAGENTS, and col. 2, under “Analytical Sensitivity”). Hangzhou teaches everything after the word “comprising”. Thus, Hangzhou anticipates the kit even though it does not explicitly recite the word “kit”.
With respect to claim 24, Hangzhou teaches wherein the supply of the detection complex comprises the detection complex at a concentration selected such that the test region is (a) visually perceptible following contact with a sample that comprises the detection complex and an amount of norfentanyl that is less than the cutoff concentration, and (b) visually imperceptible following contact with a sample that comprises the detection complex and an amount of norfentanyl that is greater than the cutoff concentration (see, e.g., col. 1, under “PRINCIPLE”: “ A drug-positive urine specimen will not generate a colored line in the test line region, while a drug-negative urine specimen or a specimen containing a drug concentration less than the cut-off will generate a line in the test line region”).
With respect to claims 27 and 28, Hangzhou teaches the cutoff concentration when the analyte is norfentanyl is 10 ng/mL (see, e.g., col. 2, under “Analytical Sensitivity”).
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 to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 2-3, 23, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Hangzhou (cited above), as applied to claims 1, 13-14, 18, 22, 24, and 27-28 above, and further in view of Angelini, et al. (“Evaluation of a lateral flow immunoassay for the detection of the synthetic opioid fentanyl”, available online 2019-04-26) and Alexander-Scott, et al. (Abstract titled: “Detection of fentanyl on surfaces using multiplex immunoassay and lateral flow immunoassay methods to protect public safety workers”, published 2018-11).
Hangzhou teaches as set forth above, including the detection of fentanyl at 50 ng/mL, but fails to teach the cutoff concentration of fentanyl is 1 ng/mL, as in claims 2-3 and 26. Hangzhou fails to teach the kit comprises a diluent configured for addition to the supple of the detection complex, as in claim 23.
However, in a journal article evaluating, competitive lateral flow assays for measuring fentanyl, Angelini rectifies these deficiencies. Angelini teaches a screening device for screening a sample for fentanyl, comprising: a pervious medium with a test region and a control region; and the test is visually perceptible following contact with a test sample formed from at least the detection complex and a sample originally comprising the analyte at less than a cutoff concentration of 8 ng/mL while the test is visually imperceptible following contact with a testing sample formed from at least the detection complex and a sample originally comprising the analyte at a greater concentration than the corresponding cutoff concentration, as in claims 2-3 and 26 (see, e.g., p. 3, para. 2: “In competitive assays, the sample first encounters colored antibody-labeled competitive binding particles. As the sample and colored antibody- labeled competitive binding particles flow over the test line, any target analyte (i.e. fentanyl) present in the sample at a high enough concentration will block the binding site on the capture antibody bound to the test site; therefore, preventing any binding of the colored antibody-labeled competitive particle. Thus, a positive test is indicted by no colored band in the test area. In both assay types, there is a control line containing control antibodies that bind any free color-labeled detection antibodies. The appearance of this band indicates the assay was performed properly. It is interesting to note that the results of the competitive LFI are somewhat counterintuitive, since a positive result is indicated by one line (control line only) and a negative result is indicated by two lines (control line and test line)”, and “Liquid sample, typically in the form of a buffered solution containing a specific analyte, is placed on the absorbent sample pad (either by pipetting or by dipping the sample pad into the test liquid) which allows capillary action to move the liquid up the strip to the test and control lines containing the capture reagents (i.e. antibodies)”; 8 ng/mL fentanyl cutoff concentration – p. 15, under “Table 2:”).
Angelini teaches a kit comprising a diluent configured for addition to the supply of the detection complex, as in claim 23 (see, e.g., p. 4, under “Urine LFIs”: “Stocks of increasing concentrations of fentanyl analytical standards (or other experimental compounds) were added to either pooled normal human urine or PBS. Then, a 100 μL aliquot of each test concentration was placed in a well of a 96 well plate. The test strip was then submerged (up to the line marked “MAX”) into the dilutions for 10 s to 20 s”, and p. 3, para. 2: “In competitive assays, the sample first encounters colored antibody-labeled competitive binding particles”). It is understood that PBS is a diluent that is added to the supply of detection complex on the test strip when the strip is submerged in the spiked PBS.
While Angelini teaches the detection of fentanyl with a limit of detection of 8 ng/mL with a lateral flow assay (see, e.g., p. 15, under “Table 2:”), Angelini fails to teach the cutoff concentration for a fentanyl lateral flow assay is 1 ng/mL, as in claims 2-3 and 26.
However, in a journal abstract on the detection of fentanyl on surfaces, Alexander-Scott rectifies this deficiency. Alexander-Scott teaches “The lateral flow's cutoff values will recognize low ng/sample for fentanyl and will be designed in housing that will limit user’s exposure to the drug or reagents” (see p. 1, under “Results:”).
Hangzhou, Angelini, and Alexander-Scott are analogous to the field of the claimed invention because they are all in the field of lateral flow immunoassays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the disclosure of Alexander-Scott as motivation to increase the fentanyl cutoff concentration of Hangzhou and Angelini to 1 ng/mL. An artisan would have been motivated to do so because Alexander-Scott discloses, “Public safety workers throughout the country have reported exposure to fentanyl and its analogs such as carfentanil, furanyl fentanyl, and acryl fentanyl. However, there is a lack of data in the literature that quantifies how much of these substances are on environmental surfaces at crime scenes or during rescue. There are also no established federal or consensus occupational exposure limits these drugs. Currently, they are identified by sophisticated and expensive procedures such as liquid chromatography-mass spectrophotometry or gas chromatography-mass spectrophotometry (LC-MS and GC-MS), but the turn-around time for results can take weeks. The National Institute for Occupational Safety and Health (NIOSH) is developing methods to both semi-quantify and quantify fentanyl on these surfaces to reduce the lab time needed to make sound decisions regarding personal protective equipment necessary and cleanup”. Alexander-Scott clearly articulates a market need for methods to semi-quantify fentanyl using methods such as lateral flow immunoassays that can be executed on-site. An artisan would have understood that increasing the sensitivity of the lateral flow immunoassay of Hangzhou and Angelini to a 1 ng/mL cutoff concentration would fulfill the market need disclosed by Alexander-Scott. In addition, adding the diluent of Angelini to the assay of Hangzhou allows for greater sensitivity (see, e.g., Angelini, p. 80, under “4. Conclusions”, col. 1, para. 1). An artisan would have a reasonable expectation of success based on the given disclosures.
Claims 4 and 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Hangzhou (cited above), Angelini (cited above), and Alexander-Scott (cited above), as applied to claims 2-3, 23, and 26 above, and further in view of Liu, et al. ("A lateral flow strip based on gold nanoparticles to detect 6-monoacetylmorphine in oral fluid", published 2018-06-27, cited in PTO-892 dated 2025-01-13).
Hangzhou, Angelini, and Alexander-Scott teach as set forth above, but fail to teach the nanoparticles of the detection complex comprise gold with a diameter of 5 nm to 100 nm, as in claims 4 and 6-7.
However, in a journal article on a lateral flow assay to detect the opioid 6-monoacetylmorphine, Liu rectifies this deficiency.
Liu teaches the nanoparticle of the detection complex has a diameter of from 5 nm to 100 nm, as in claim 4 (see, e.g., p. 3, under “2.4. Preparation of gold nanoparticles–antibody conjugates”, para. 1).
Liu teaches the nanoparticle of the detection complex comprises a metal, as in claim 6 (see, e.g., p. 3, under “2.4. Preparation of gold nanoparticles–antibody conjugates”, para. 1).
Liu teaches the nanoparticle of the detection complex is gold, as in claim 7 (see, e.g., p. 3, under “2.4. Preparation of gold nanoparticles–antibody conjugates”, para. 1).
Hangzhou, Angelini, Alexander-Scott, and Liu are analogous to the field of the claimed invention because they are all in the field of opioid detection. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the nanoparticles of Liu into the assay of Hangzhou, Angelini, and Alexander-Scott. An artisan would have been motivated to do so because Liu discloses, “Of the methods for rapid detection, colloidal gold nanoparticle (AuNP)-based lateral flow strips (LFSs) have been widely adopted for rapid screening due to the size-dependent and distance-dependent optical property of AuNPs […] The principle of semi-quantitative lateral flow assays is that the red colour of the AuNPs can be viewed by the naked eye from the antigen–antibody combination in several minutes” (see p. 2, para. 3). An artisan would have a reasonable expectation of success based on the given disclosures.
Claims 8 and 15 is rejected under 35 U.S.C. 103 as being unpatentable over Hangzhou, Angelini, Alexander-Scott, and Liu as applied to claims 4 and 6-7 above, and further in view of Shin, et al. ("Multiplexed Detection of Foodborne Pathogens from Contaminated Lettuces Using a Handheld Multistep Lateral Flow Assay Device", published 2017, cited in PTO-892 dated 2025-01-13).
Hangzhou, Angelini, Alexander-Scott, and Liu teach as set forth above but fail to teach the detection complex is present in the sample at from 2.5 x 109/mL to 2.8 x 1011/mL, as in claim 15.
However, in a journal article on multiplex lateral flow assays, Shin rectifies this deficiency. Shin teaches the detection complex is present in the sample at 1.635 x 1011/mL, as in claims 8 and 15 (see, e.g., p. 292-293, col. 2 and 1, under “Optimization of Gold Nanoparticle Concentration and Duration”, para. 2).
Hangzhou, Angelini, Alexander-Scott, Liu, and Shin are considered analogous to the claimed invention because they are in the same field of lateral flow assays. Therefore, it would have been prima facie obvious to one skilled in the art before the effective filing date of the claimed invention to have modified Hangzhou, Angelini, Alexander-Scott, and Liu by incorporating the concentration of detection complex disclosed by Shin. The artisan would have been motivated to optimize the concentration of the detection complex in Hangzhou, Angelini, Alexander-Scott, and Liu and use Shin’s detection complex amount since Shin teaches both the duration of gold nanoparticle flow and the concentration of gold nanoparticle need to be optimized in order to reduce the total cost and time. Liu further teaches that to develop an economically efficient rapid detection system, their lateral flow device was optimized to use the lowest gold nanoparticle concentration that allows the signal to appear at the lowest analyte concentration as possible. (see, e.g., Shin, p. 292, col. 2, under “Optimization of Gold Nanoparticle Concentration and Duration”, para. 1). Optimizing the concentration of the detection complex in Hangzhou, Angelini, Alexander-Scott, and Liu would result in the best combination of cost and signal strength. An artisan would have a reasonable expectation of success based on the given disclosures.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Hangzhou (cited above), Angelini (cited above), and Alexander-Scott (cited above), as applied to claims 2-3, 23, and 26 above, and further in view of Hudson (US 20170307605 A1, published 2017-10-26, cited in PTO-892 dated 2025-01-13).
Hangzhou, Angelini, and Alexander-Scott teach as set forth above. In addition, Hangzhou identifies norfentanyl as “a metabolite of Fentanyl” (see col. 1, under “INTENDED USE”). However, the references fail to teach the kit comprises two test regions, a first of the test regions comprising fentanyl, and a second of the test regions comprising norfentanyl, and wherein the kit comprises two different detection complexes, a first of the different complexes comprising a detection antibody that is complementary to fentanyl, and a second of the different complexes comprising a detection antibody that is complementary to norfentanyl, as in claim 25.
However, in a patent application publication a sample analyzing device for low levels of narcotics, Hudson rectifies this deficiency (see, e.g., p. 9, col. 2, para. [0150]). Hudson teaches a kit using different antibodies with the same label to create different detection complexes that can bind to different analytes at different test sites, such as different drugs and/or their metabolites, as in claim 25 (see, e.g., p. 5, col. 1, para. [0073]).
Hangzhou, Angelini, Alexander-Scott, and Hudson are considered analogous to the claimed invention because they are in the same field of narcotics detection using lateral flow assays. Therefore, it would have been prima facie obvious to one skilled in the art before the effective filing date of the claimed invention to have modified Hangzhou, Angelini, and Alexander-Scott by incorporating the screening device into the kit capable multiplexing as disclosed by Hudson. The artisan would have been motivated to do so because Hudson discloses, “Providing two or more different antibody is therefore advantageous because more than one analyte, e.g. a drug or drug metabolite, can be detected in the sample, if present” (see para. [0073]). An artisan would have a reasonable expectation of success based on the given disclosures.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Brown (cited above) discloses, “While the physical components of the lateral flow test strip, construction techniques, and buffers and surfactants play a major role in optimizing the test, at the very heart of these processes are the antibodies themselves. If the antibodies are not meticulously selected for their ability to recognize the target antigen(s) in this format, no amount of optimization will be able to overcome this inherent defect. Often, assay developers may spend great deal of time struggling to ‘‘tweak’’ the assay to fit their specifications, but come away with an assay that just borders on having the right sensitivity and generally not very robust from a manufacturing standpoint. Instead, if they would spend more time in the creation and selection of optimized antibodies at the front end of the development process, it would make the rest of the development relatively easy”(see p. 59, under “4.1 Introduction”, para. 1). Innova Biosciences (cited above) highlighted the importance of antibody selection for lateral flow immunoassays, especially because “non-specific binding could lead to the misinterpretation of results” (see, e.g., p. 6-7, under “3.3.1 The antibody”).
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/MICHAEL CAMERON SVEIVEN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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