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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 18 August 2025 has been entered.
Status of the Claims
Claims 1-3, 8, 14, 26, 31-33, 35-37, 43, 59, 64-77, 82-83, and 86-90 are pending in the application.
Claims 31-33, 35-37, 43, 59, and 64-76 are withdrawn.
Claims 1-3, 8, 14, 26, 77, 82-83, and 86-90 are the subject of this office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 16 May 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 8, 14, 26, 77, 82-83, and 86-90 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.
Claim 1 is rejected as indefinite over the recitation of “the conjugate” in lines 14-15. There is previous introduction of both “a conjugate” and “a first antibody conjugate” in the claim, such that it is unclear which of these two conjugates lines 14-15 are intended to refer to. Clarification is required.
Dependent claims 2-3, 8, 14, 26, 77, 82-83, and 86-90 are rejected as indefinite because they depend from an indefinite claim and fail to remedy its deficiencies.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 77 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 77 depends from claim 1, but does not further limit the immunoassay test strip of claim 1. Claim 77 presents limitations of a test system which do not further limit the immunoassay test strip of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 77 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim recites that a test result is determined by a software application comprising computer-executable instruction stored in a non-transitory memory and is determined to be valid or invalid based at least in part on the software application determining that an intensity of an optical signal from the sample adequacy line is above or below a predetermined threshold. The step of comparing a test value to a predetermined threshold or control value and thereby determining the validity of a result is an abstract idea, namely a mental step (concepts performed in the human mind including an observation, evaluation, judgment, or opinion). It is noted that the courts do not distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer (see MPEP 2106.04(a)(2)(III)).
Step 2a) prong one: is the claim directed to a law of nature, natural phenomenon (product of nature) or an abstract idea? Yes. The claim is drawn to an abstract idea, namely the mental step of comparing sample data to a control value or predetermined threshold in order to judge the validity of the data. In the instant claim, this mental process is performed by computer-executable instruction stored in a non-transitory memory, however, MPEP 2106.04(a)(2)(III)(C) indicates that a claim that requires a computer may still recite a mental process. In the instant case, a computer (i.e. computer executable instructions stored in a non-transitory memory that, when executed, cause one or more processors of a mobile device to perform a specific function) is used as a tool to perform a mental process which could be performed by humans without a computer. For example, in Berkheimer v. HP, Inc., 881 F.3d 1360, 125 USPQ2d 1649 (Fed. Cir. 2018), in which the patentee claimed methods for parsing and evaluating data using a computer processing system. The Federal Circuit determined that
these claims were directed to mental processes of parsing and comparing data, because the steps were
recited at a high level of generality and merely used computers as a tool to perform the processes. 881
F.3d at 1366, 125 USPQ2d at 1652-53. In the instant case, although a computer may be required to provide a quantitative test result from an assay strip, a human would be capable of performing the mental step of comparing that value to a predetermined threshold and thereby judging the validity of the test result, as recited in claim 77.
Although the claim recites a system which comprises components in addition to the judicial exception (i.e. test strip and software application), the claim is nevertheless understood to be directed to the judicial exception because the additional components are used only to gather data to support the judicial exception (i.e. test strip and software application), and in the case of the software application, are recited at a high level of generality such that the software application is primarily defined by its function of performing the judicial exception. This is discussed in further detail below.
Step 2a) prong two: Do the claims recite additional elements that integrate the exception into a practical application of the judicial exception? No. MPEP 2106.04(d)(I) discusses relevant considerations for evaluating whether additional elements integrate a judicial exception into a practical application. Beyond the judicial exception, the claim recites the additional elements of the test strip of claim 1, and a software application installed on a mobile device.
In the context of claim 77 and its recited judicial exception, the test strip is used only to gather data which is necessary to support the judicial exception (i.e. the test strip provides the signal at the test line, control line, and sample adequacy line which is evaluated in the performance of the judicial exception). Mere data gathering has been identified by the courts as insignificant extra solution activity to the judicial exception, which the courts have specifically identified as not integrating a judicial exception into a practical application (see MPEP 2106.04(d)(I), and 2106.05(g)).
Regarding the software application installed on a mobile device, of the limitations the courts have found indicative that an additional element may have integrated an exception into a practical application, the closest consideration to the instant claim would be “implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim”. MPEP 2106.05(b)(I) discusses criteria used to determine whether a machine is suitably particular to integrate a judicial exception into a practical application, and explicitly states “it is important to not that a general purpose computer that applies a judicial exception, such as an abstract idea, by use of convention computer functions does not qualify as a particular machine”. As it applies to the instant case, the software application is recited at a high level of generality (i.e. a software application comprising computer-executable instructions and a mobile device comprising one or more processors) and is primarily defined by the particular computer-executable instructions which prompt it to perform the judicial exception. As such, this is understood to be essentially a general purpose computer which is used simply to apply the judicial exception, and therefore is not sufficient to integrate the judicial exception into a practical application.
Step 2b: does the claim as a whole amount to significantly more than the judicial exception? The claim elements have been considered individually and in combination, and the claims as a whole do not amount to significantly more than the judicial exception. The claim recites the judicial exception, the test strip of claim 1, and a software application installed on a mobile device, as described above. The software application installed on a mobile device is recited at a high level of generality and is used only to apply the judicial exception itself, while the test strip itself is used only to gather data to support the execution of the judicial exception (i.e. the judicial exception cannot be performed without the data gathered by the test strip. Steps which amount to data gathering in conjunction with a judicial exception such as an abstract idea are considered to be adding insignificant extra-solution activity to the judicial exception, and are not considered enough to qualify as “significantly more” when recited in a claim with a judicial exception. See MPEP 2106.05(g). Additionally, both the software application installed on a mobile device and the test strip of claim 1 are insufficient to amount to significantly more than the judicial exception because these elements are all routine and conventional in the art, as taught by Deirmengian et al (WO 2013/112216; previously cited) and Sommera et al (US 2019/0302028 A1) (which teach a test strip such as the one disclosed in claim 1, as described at length in the 102 and 103 rejections below) and Rowe et al (US 2022/0084659; previously cited) which teaches a software application installed on a mobile device which may used computer-executable instructions stored on non-transitory memory to analyze an image of a test strip and determine test results. Use of these components together is not sufficient to amount to significantly more than the judicial exception, as the use of a test strip in conjunction with a detection system comprising a software application, computer executable instructions, non-transitory memory, and one or more processors is specifically contemplated in the references which teach test strips such as the ones claimed and is itself considered routine and conventional in the art.
Therefore, claim 77 as a whole does not amount to significantly more than the judicial exceptions when the claim elements are considered individually or in combination. Claim 77 is rejected under 35 U.S.C. 101 for lack of subject matter eligibility.
Claim Rejections - 35 USC § 102
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.
(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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3-4, 8, 14, and 89 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Deirmengian et al (WO 2013/112216; previously cited).
Regarding claims 1, 8, and 14, Deirmengian teaches an immunoassay test strip (Abstract), comprising:
A flow path configured to receive a sample (Fig. 1);
A sample receiving zone coupled to the flow path and comprising at least a conjugate and a first antibody conjugate (i.e. the sample pad and conjugate pad shown in Fig. 1 are interpreted to collectively comprise a sample receiving zone and are coupled to the flow path; Pg. 49, Ln. 17-26: a detector may be integrated into an assay device (for example included in a conjugate pad). A detector may be a single reagent or a series of reagents that collectively serve the detection purpose. In some instances, a detector reagent is a labeled binding partner specific for the analyte (such as a gold-conjugated antibody for a particular protein of interest; Pg. 53, Ln. 31-Pg. 54, Ln. 7: in an embodiment of the lateral flow device there may be a second (or third, fourth, or more) test line for detection of additional biomarkers. In such a multiplexed embodiment, the test strip will comprise additional detector reagents specific for additional analyte disposed in the conjugate pad, and will comprise additional test lines with immobilized specific binding partners of the additional biomarkers). That is, Derimengian teaches multiple detector reagents disposed in the conjugate pad of the sample receiving zone, wherein these multiple detector reagents are understood to read on the conjugate and the first antibody conjugate of the instant claim;
A sample adequacy line comprising a first capture agent for a sample adequacy marker, wherein an immunoassay conducted in the sample adequacy line is a sandwich type lateral flow assay configured to emit an optical signal when the sample comprises the sample adequacy marker and when the sample adequacy marker is bound to the first antibody conjugate and the first capture agent, wherein the sample adequacy marker is HSA and/or lactotransferrin (Pg. 2, Ln. 19-26: biomarkers detected by the test strip may include lactoferrin (i.e. lactotransferrin); Pg. 53, Ln. 4-21: the test strip comprises a detector reagent (i.e. first antibody conjugate) disposed in the conjugate pad which specifically binds to the biomarker to be detected (for example, the detector reagent may be a gold-conjugated antibody, wherein the antibody binds specifically to the biomarker (i.e. lactotransferrin)). An analyte specific binding partner (such as an antibody which binds specifically to the biomarker lactotransferrin) is immobilized at a test line, such that in the process of using the device, lactotransferrin is bound and labeled by the detector reagent in the conjugate pad, and the detector-reagent-lactotransferrin complex then flows downstream and is bound by anti-lactotransferrin antibodies at the test line, such that a detectable optical signal is produced at the test line when lactotransferrin is present in the sample; Pg. 57, Ln. 30-32).
It is noted that Deirmengian teaches all physical and structural features of the claimed sample adequacy line, as described above, but does not explicitly teach that lactotransferrin is a “sample adequacy marker”. The matter of what distinguishes a sample adequacy marker from any other analyte of interest in a sample is a matter of intended use which does not distinguish over the prior art in an apparatus claim such as claim 1, since an apparatus claim is defined by what an apparatus is and not what it does (see MPEP 2114 and 2115). Therefore, as long as Deirmengian teaches all physical and structural features required by the “sample adequacy line” it is understood to be sufficient to meet this limitation of the claim, regardless of whether or not it teaches that the line is used to evaluate the adequacy of the sample.
A PC line comprising a second capture agent for the conjugate, wherein when the conjugate is bound to the second capture agent, the PC line forms a visible line that validates an integrity of the immunoassay and/or ensures proper reagent function (Pg. 53, Ln. 18-21: a control line may contain an immobilized, detector-reagent-specific binding partner, which can bind the detector reagent in the presence or absence of the analyte. Such binding at the control line indicates proper performance of the test, even in the absence of analyte of interest; Pg. 51, Ln. 20-23);
An analyte capture line configured to bind to an analyte of interest in the sample, wherein the presence and/or abundancy of the analyte of interest in the sample is dependent on a disease state of a donor of the sample, wherein the analyte of interest comprises a marker of an infectious respiratory disease (Deirmengian indicates that the test strip may be multiplexed for the detection of multiple biomarkers on a single test strip. For each biomarker to be detected, the conjugate pad comprises a detector reagent specific for that biomarker (i.e. a labeled antibody), and the test strip comprises a distinct capture line for each biomarker, wherein the capture line comprises a reagent which binds specifically to its target biomarker (i.e. an antibody) (Pg. 53, Ln. 5-Pg. 54, Ln. 7; Fig. 2); Deirmengian further teaches that the biomarkers detected may comprise lactotransferrin in combination with any one or more of: HNPI-3, ELA-2, BPI, resistin, thrombospondin, IL-1B, IL-8, CRP, TNFa, IL-6, HNE, a2M, VEGF, FGF2, SKALP, IP-10, LMP, orsomucoid (Pg. 2, Ln. 19-22)). These teachings read on the instant limitation in that they indicate that the test strip of Deirmengian may comprise a detector reagent (i.e. first antibody conjugate) and capture reagent for the detection of lactotransferrin, and may further comprise additional detector reagents (i.e. conjugates) and capture reagents (i.e. antibodies immobilized at an analyte capture line) for the detection of additional biomarkers which may be considered markers of infectious respiratory disease. For example, from the list of biomarkers taught by Deirmengian, at least IL-1B, IL-6, CRP, and IP-10 may be considered markers of infectious respiratory disease because they are known in the art to be markers associated with influenza (such as influenza A), SARS-CoV-2, and/or acute respiratory infection, as evidenced by Chiaretti et al (IL-1 β and IL-6 upregulation in children with H1N1 influenza virus infection. Mediators Inflamm. 2013;2013:495848.), Vasileva et al (C-reactive protein as a biomarker of severe H1N1 influenza. Inflamm Res. 2019 Jan;68(1):39-46.), Hayney et al (Serum IFN-γ-induced protein 10 (IP-10) as a biomarker for severity of acute respiratory infection in healthy adults. J Clin Virol. 2017 May;90:32-37.), and Kong et al (VEGF-D: a novel biomarker for detection of COVID-19 progression. Crit Care 24, 373 (2020)). Whether or not the biomarker is detected in Deirmengian for the purpose of serving as a marker of infectious respiratory disease does not prevent Deirmengian from reading on the instant limitation, since this is a matter of intended use which does not distinguish the claimed device over the prior art.
Wherein an immunoassay conducted in the analyte capture line is a sandwich-type lateral flow assay configured to emit an optical signal when the sample comprises the analyte of interest (Pg. 53, Ln. 5-Pg. 54, Ln. 7; Pg. 57, Ln. 30-32).
Wherein assignment of an invalid test result to the sample based on a PC line intensity is unrelated to an intensity of the optical signal emitted at the sample adequacy line when the sample comprises the sample adequacy marker, and when the sample adequacy marker is bound to the first antibody conjugate and the first capture agent (Pg. 53, Ln. 18-21: the control line may contain an immobilized detector-reagent specific binding partner which can bind the detector reagent in the presence or absence of the analyte. Such binding at the control line indicates proper performance of the test, even in the absence of the analyte of interest; Pg. 51, Ln. 20-23).
Regarding the limitations “wherein the optical signal emitted at the sample adequacy line indicates whether the sample present in the immunoassay is of sufficient quantity and integrity to elicit detection of the analyte of interest at the analyte capture line when the sample comprises the analyte of interest”, this is noted as a recitation of intended use. The only structural limitation provided by the recited sample adequacy line is a region on the claimed test strip comprising an immobilized capture agent which participates in a sandwich-type lateral flow assay configured to emit an optical signal when the sample comprises the at least one sample adequacy marker, wherein the sample adequacy marker is HSA and/or lactotransferrin. Whether or not “the at least one sample adequacy line indicates whether the sample present in the immunoassay is of sufficient quantity and integrity to elicit detection of the at analyte of interest at the analyte capture line when the sample comprises the analyte of interest” is an issue/limitation of the sample itself and the intended use of the device and does not provide any further structural limitation of the device (i.e. immunoassay test strip) to which the claim is directed. Since recitations of intended use do not distinguish over the prior art in an apparatus claim such as claim 1, and since Deirmengian teaches all structural and physical features of the claimed device, Deirmengian is understood to read on the instant claim, regardless of whether it recites the same intended use.
Similarly, regarding the limitation “wherein the sample is a nasal swab sample”, this is noted as a recitation of intended use which does not distinguish over the prior art in a device claim such as claim 1. The limitation is relevant to the sample used with the device during the process of using the device, and does not impose any further structural or physical limitation on the claimed device. Since Deirmengian teaches all physical components and structural features of the claimed device, it is understood to meet the instant claim regardless of whether or not it teaches that the device is used with the same particular sample type.
Regarding claim 3, Deirmengian further teaches the immunoassay test strip wherein the sample adequacy marker comprises lactotransferrin and the first capture agent comprises an anti-lactotransferrin antibody (Pg. 53, Ln. 4-21: the test line comprises an analyte-specific binding partner such as an antibody that binds a particular protein; Pg. 2, Ln. 20: the particular protein detected may be lactotransferrin).
Regarding claim 89, Deirmengian further teaches the immunoassay test strip wherein the sample adequacy line indicates the presence of lactotransferrin in the sample when lactotransferrin is present at a concentration of at least 10 ng/mL (Pg. 29, Ln. 17-26). It is noted that the recitation “at least 10 ng/mL” creates an open-ended range which has a lower limit of 10 ng/mL but no upper limit. As such, a test strip with a sample adequacy line that indicates the presence of lactotransferrin when it is present in the sample at any concentration higher than 10 ng/mL is understood to read on this limitation of the claim.
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 1-2, 8, 14, 26, 83, and 87-88 are rejected under 35 U.S.C. 103 as being unpatentable over Sommera et al (US 2019/0302028 A1) in view of Deirmengian et al (WO 2013/112216; previously cited) and Hagan et al (Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine. EPMA J. 2016 Jul 13;7(1):15.).
Regarding claims 1-2, Sommera teaches an immunoassay test strip (Fig. 2), comprising:
A flow path configured to receive a sample (Fig. 2);
A sample receiving zone coupled to the flow path and comprising at least a conjugate and a first antibody conjugate (Fig. 2: the sample pad and conjugate pad are interpreted to collectively comprise a sample receiving zone; Par. 67, 114, 102, 135: for each analyte to be detected, the test strip comprises an analyte specific conjugate disposed in the conjugate pad (e.g. a labeled detection antibody that binds specifically to its target analyte) and a test line which comprises an immobilized capture agent for that analyte (i.e. an antibody which binds specifically to its target analyte); Abstract: the strip is used to detect two or more of the following markers: HSA, lactoferrin, lysozyme, mucin; wherein a strip configured for detection of two or more analytes will necessarily comprise two or more conjugates disposed in the conjugate pad, thereby reading on the instantly recited conjugate and first antibody conjugate);
A sample adequacy line comprising a first capture agent for a sample adequacy marker, wherein an immunoassay conducted in the sample adequacy line is a sandwich type lateral flow assay configured to emit an optical signal when the sample comprises the sample adequacy marker and when the sample adequacy marker is bound to the first antibody conjugate and the first capture agent, wherein the sample adequacy marker is HSA and/or lactotransferrin (Fig. 2, Abstract: a test strip may be used to quantify an amount of at least two markers in a tear sample collected from a subject, wherein the at least two markers are selected from the group consisting of HSA, mucin, lactoferrin, (i.e. lactotransferrin) and lysozyme; Par. 102: in an embodiment which comprises detection of HSA, the test strip contains an amount of at least one anti-HSA antibody, where the amount of the at least one anti-HSA antibody is conjugated to colloidal gold; Par. 135: in an exemplary test strip for detection of HSA, a sample comes into contact with anti-HSA antibodies conjugated to gold particles which bind any HSA in the sample to create a conjugate-HSA complex. The complex flows downstream to reach a test zone on the nitrocellulose membrane, wherein the test zone comprises an immobilized anti-HSA monoclonal antibody which binds to the conjugate-HSA complex to produce a detectable signal at the test line which indicates the presence and concentration of HSA in the sample);
It is noted that Sommera teaches all physical and structural features of the claimed sample adequacy line, as described above, but does not explicitly teach that HSA is a “sample adequacy marker”. The matter of what distinguishes a sample adequacy marker from any other analyte of interest in a sample is a matter of intended use which does not distinguish over the prior art in an apparatus claim such as claim 1, since an apparatus claim is defined by what an apparatus is and not what it does (see MPEP 2114 and 2115). Therefore, as long as Sommera teaches all physical and structural features required by the “sample adequacy line” it is understood to be sufficient to meet this limitation of the claim, regardless of whether or not it teaches that the line is used to evaluate the adequacy of the sample.
A PC line comprising a second capture agent for the conjugate, wherein when the conjugate is bound to the second capture agent, the PC line forms a visible line that validates an integrity of the immunoassay and/or ensures proper reagent function (Par. 135, 227, 319, 408: a control line comprising a capture agent which specifically binds to a conjugate of the test strip may be used to capture excess conjugate and produce detectable signal at a control line which indicates test validity and function, independent of whether the target analyte is present in the sample);
An analyte capture line configured to bind to an analyte of interest in the sample wherein an immunoassay conducted in the analyte capture line is a sandwich-type lateral flow assay configured to emit an optical signal when the sample comprises the analyte of interest (Abstract, Par. 67, 114, 102, 135: the test strip is configured for the detection of at least two biomarkers, wherein for each biomarker intended to be detected, the test strip comprises a conjugate (e.g. a detectably labeled anti-analyte antibody) and a test line which comprises an immobilized capture agent for the analyte (i.e. an antibody which binds specifically to the analyte);
Wherein assignment of an invalid test result to the sample based on a PC line intensity is unrelated to an intensity of the optical signal emitted at the sample adequacy line when the sample comprises the sample adequacy marker, and when the sample adequacy marker is bound to the first antibody conjugate and the first capture agent (Par. 135: an excess amount of the anti-HSA conjugate flows downstream past the test zone to a second zone where anti-mouse IgG are impregnated and bind the monoclonal anti-HSA gold conjugate. A second line is formed (a control line) which indicates test validity, independent of whether the target analyte is present in the sample).
Regarding the limitation “wherein the optical signal emitted at the sample adequacy line indicates whether the sample present in the immunoassay is of sufficient quantity and integrity to elicit detection of the analyte of interest at the analyte capture line when the sample comprises the analyte of interest”, this is noted as a recitation of intended use. The only structural limitation provided by the recited sample adequacy line is a region on the claimed test strip comprising an immobilized capture agent which participates in a sandwich-type lateral flow assay configured to emit an optical signal when the sample comprises the at least one sample adequacy marker, wherein the sample adequacy marker is HSA and/or lactotransferrin. Whether or not “the at least one sample adequacy line indicates whether the sample present in the immunoassay is of sufficient quantity and integrity to elicit detection of the at analyte of interest at the analyte capture line when the sample comprises the analyte of interest” is an issue/limitation of the sample itself and the intended use of the device and does not provide any further structural limitation of the device (i.e. immunoassay test strip) to which the claim is directed. Since recitations of intended use do not distinguish over the prior art in an apparatus claim such as claim 1, and since Sommera teaches all structural and physical features of the claimed device, Sommera is understood to read on the instant claim, regardless of whether it recites the same intended use.
Similarly, regarding the limitation “wherein the sample is a nasal swab sample”, this is noted as a recitation of intended use which does not distinguish over the prior art in a device claim such as claim 1. The limitation is relevant to the sample used with the device during the process of using the device, and does not impose any further structural or physical limitation on the claimed device. Since Sommera teaches all physical components and structural features of the claimed device, it is understood to meet the instant claim regardless of whether or not it teaches that the device is used with the same particular sample type.
While Sommera teaches detection of HSA (i.e. the sample adequacy marker) and additional biomarkers, Sommera differs from the instant claim in that it does not specifically teach that the biomarker(s) detected in addition to HSA are markers of an infectious respiratory disease, wherein the presence and/or abundancy of the biomarker in a sample is dependent on a disease state of a donor of the sample.
Regarding claim 1, Hagan that IL-6 is a biomarker of dry eye syndrome (Pg. 4, Col. 1, Par. 2: IL-6 has been found to be significantly increased in tears from DED patients as compared to controls).
Regarding claim 1, Deirmengian teaches that IL-6 can be detected by a sandwich format assay on a lateral flow test strip, wherein a conjugate comprising an anti-IL-6 antibody and a detectable label is disposed in a sample receiving zone, and a test line for IL-6 comprises immobilized anti-IL-6 antibody (Fig. 1; Pg. 2, Ln. 19-22; Pg. 57, Ln. 30-32).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the test strip of Sommera to further comprise detection of IL-6 as an analyte of interest, wherein IL-6 can be detected by a sandwich format assay on the test strip, as taught by Derimengian. One of ordinary skill in the art would be motivated to make this modification because Sommera is directed to methods and devices for the diagnosis of dry eye syndrome, and Hagan teaches that IL-6 is a biomarker of dry eye syndrome. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because Sommera and Deirmengian disclose similar lateral flow test strips comprising sandwich format immunoassays for the detection of analytes of interest.
Regarding claims 1, 8 and 14, the modified test strip of Sommera in view of Deirmengian and Hagan is understood to meet instant claim 1 and the limitation that the analyte of interest is a marker of infectious respiratory disease influenza A in that IL-6 is known in the art to be a marker of H1N1 influenza, as evidenced by Chiaretti et al (IL-1 β and IL-6 upregulation in children with H1N1 influenza virus infection. Mediators Inflamm. 2013;2013:495848.).
Regarding claims 26 and 83, Sommera teaches the test strip comprising a positive control line, a sample adequacy line, and an analyte capture lines, as described in the rejection of claim 1 above, wherein the positive control line comprises a capture agent which binds to at least one species of conjugate. Sommera does not explicitly limit the order of lines on the disclosed test strip, though one of ordinary skill in the art would recognize from the function of the control line as described in Par. 135, 227, 319, and 408 that it would be preferable for the control line to be disposed downstream of the test line that is specific for an analyte which is bound by the same conjugate as the control line (such that binding of conjugate to the control line does not interfere with production or quantity of signal produced at the test line). Sommera does not provide specific limitation on the disposition of the control line relative to other test lines which may be present on the device. Additionally, because the instant specification provides no specific reasoning or advantage for the claimed orders of lines on the test strip, and because Sommera does not explicitly limit the order of the lines, one of ordinary skill in the art could be expected to arrive at the other claimed orders of lines on the strip as a result of routine optimization (i.e. the positive control line comprising a capture agent which specifically binds the conjugate of the analyte of interest is located on the test strip between the analyte capture line and the sample adequacy line. See MPEP 2144.05).
Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arranged the control, test, and sample adequacy lines such that the PC line is located on the test strip between the analyte capture line and the sample adequacy line (for example, in the order of analyte capture line, positive control line, sample adequacy line) because Sommera is not explicitly limiting regarding the order of analyte capture, sample adequacy, and control lines (beyond the limitation that the control line should presumably be disposed downstream of any analyte capture lines which bind to conjugates that are cross reactive with the capture reagent of the control line), and arriving at any particular order of a finite number of test and control lines on the test strip is obvious to try because one is choosing from a finite number of identified, predictable solution with a reasonable expectation of success. Since the order of test lines does not affect the functioning of the test strip disclosed by Sommera (as long as the control line is downstream of any test line that binds the same conjugate), arranging the lines in any of the possible orders would have a similar and reasonable expectation of success with no unexpected results.
Regarding claims 87-88, Sommera further teaches the test strip wherein the sample adequacy line indicates the presence of HSA in the sample when the HSA is present at a concentration of at least 100ng/mL (or at least 1.5 pg/ml) (Par. 136). It is noted that the recitation “at least 100 ng/ml” (or at least 1.5 pg/ml) creates an open-ended range with a lower limit at 100ng/ml (or 1.5 pg/ml) and no upper limit, such that if the sample adequacy line indicates the presence of HSA when it is present at any concentration of 100 ng/ml or higher (or 1.5 pg/ml or higher), this is understood to read on the instant claim.
Claims 26 and 83 are rejected under 35 U.S.C. 103 as being unpatentable over Deirmengian et al (WO 2013/112216; previously cited).
Regarding claims 26 and 83, Deirmengian teaches the test strip comprising a positive control line, a sample adequacy line, and an analyte capture lines, as described in the rejection of claim 1 above, wherein the positive control line comprises a capture agent which binds to at least one species of conjugate. Deimengian does not explicitly limit the order of lines on the disclosed test strip, though one of ordinary skill in the art would recognize from the function of the control line as described in the reference that it would be preferable for the control line to be disposed downstream of the test line that is specific for an analyte which is bound by the same conjugate as the control line (such that binding of conjugate to the control line does not interfere with production or quantity of signal produced at the test line). Deirmengian does not explicitly limit the disposition of the control line relative to other test lines which may be present on the device. Additionally, because the instant specification provides no specific reasoning or advantage for the claimed orders of lines on the test strip, and because Deirmengian does not explicitly limit the order of the lines, one of ordinary skill in the art could be expected to arrive at the other claimed orders of lines on the strip as a result of routine optimization (i.e. the positive control line comprising a capture agent which specifically binds the conjugate of the analyte of interest is located on the test strip between the analyte capture line and the sample adequacy line. See MPEP 2144.05).
Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arranged the control, test, and sample adequacy lines such that the PC line is located on the test strip between the analyte capture line and the sample adequacy line (for example, in the order of analyte capture line, positive control line, sample adequacy line) because Deirmengian is not explicitly limiting regarding the order of analyte capture, sample adequacy, and control lines (beyond the limitation that the control line should presumably be disposed downstream of any analyte capture lines which bind to conjugates that are cross reactive with the capture reagent of the control line), and arriving at any particular order of a finite number of test and control lines on the test strip is obvious to try because one is choosing from a finite number of identified, predictable solution with a reasonable expectation of success. Since the order of test lines does not affect the functioning of the test strip disclosed by Deirmengian (as long as the control line is downstream of any test line that binds the same conjugate), arranging the lines in any of the possible orders would have a similar and reasonable expectation of success with no unexpected results.
Claim 77 is rejected under 35 U.S.C. 103 as being unpatentable over Deirmengian et al (WO 2013/112216; previously cited) as applied to claim 1 above, and further in view of Rowe et al (US 2022/0084659; previously cited).
ADDITIONALLY, claim 77 is rejected under 35 U.S.C. 103 as being unpatentable over Sommera et al (US 2019/0302028 A1) in view of Deirmengian et al (WO 2013/112216; previously cited) and Hagan et al (Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine. EPMA J. 2016 Jul 13;7(1):15.) as applied to claim 1 above, and further in view of Rowe et al (US 2022/0084659; previously cited).
Regarding claim 77, it is noted that the software limitations of claim 77 are largely related to intended use and/or functional limitations. That is, for example, whether the “computer-executable instructions…cause one or more processors of the mobile device to analyze an image of the immunoassay test strip to determine a test result based at least in part on the sample adequacy line” and “computer-executable instruction, when executed, further cause the one or more processors to indicate an invalid test result based at least in part on determining that the intensity of the optical signal from the sample adequacy line is below a predetermined threshold” and “the computer-executable instruction, when executed, further cause the one or more processors to indicate a valid test result based at least in part on determining that the intensity of the optical signal from the sample adequacy line is above a predetermined threshold” is at best a functional limitation. Regarding a functional limitation in a system claim, prior art must teach all of the claimed structural features of the system and must be understood to be capable of performing the recited function, but does not necessarily have to teach the specific recited use. Structurally, the claims require that the system comprises a software application installed on a mobile device comprising computer-executable instructions stored in non-transitory memory. In terms of functional capability, the claim requires that the software application is capable of analyzing an image of an immunoassay test strip and indicating results based on that analysis.
Regarding claim 77, Deirmengian teaches the test strip of claim 1, as described above, and further teaches that optical signals emitted from each of the multiple test lines (i.e. the sample adequacy line and the analyte capture line) and the control line are used to determine assay results, and that an electronic reader can be used to obtain assay results (Pg. 7, Ln. 30-32: the control line may be a reference line that insures the test has been run correctly. The control line may be used as a reference when the reader determines if the result is positive or negative; Pg. 53, Ln. 27-30: the test results may be visualized directly, or may be measured using a reader (such as a scanner). The readout device may detect color, fluorescence, luminescence, radioactivity, or any other detectable marker derived from the labeled reagent from the readout area (for example the test line and/or control line; Pg. 55, Ln. 21-27: the system includes a reader for reading patient data, a test device designed for use with the reader, and software designed for analysis of the data generated from the test strip).
Deirmengian teaches that the system may comprise a number of different readers/detection systems known in the art, but does not specifically teaches the system comprising a software application installed on a mobile device.
Similarly, Sommera in view of Deirmengian and Hagan teaches the test strip of claim 1, as described above, and further teaches that optical signal emitted from each of the multiple test lines (i.e. the sample adequacy line and the analyte capture line) and the control line are used to determine assay results, and that an electronic reader can be used to obtain assay results, but is generic regarding the type of reader used (Par. 68: the test strip may provide qualitative, quantitative, or semi-quantitative results and may be read by a reader). Sommera differs from the instant claim in that it does not teach the detection system comprising a software application installed on a mobile device.
Rowe is directed to methods of analyzing diagnostic tests such as immunoassay test strips (Abstract).
Regarding claim 77, Rowe discloses a software application installed on a mobile device comprising computer-executable instruction that, when executed, cause one or more processors of the mobile device to analyze an image of an immunoassay test strip (Fig. 3B, 7A; Par. 75: one or more processors receiving an image depicting a diagnostic test; Par. 77: method includes receiving an image of a diagnostic test and one or more control markings. Control markings may include suitable markings that are representative of one or more predetermined test results for the diagnostic test. Computer vision techniques may assess whether all (or a sufficient portion) of the control markings may be detected in the image. If not all of the control markings are detected in the image, then the used may be notified of the error; Par. 85: the method may be performed locally such as on a mobile computing device (e.g. a mobile application executed on a mobile computing device)). The method performed by the processor of Rowe which uses computer vision to assess the presence of control markings and notifies that user of an error if control markings are not detected, inherently implies that the processor utilizes threshold values to determine the presence or absence of signal at a control line and deems the result valid if control signal above a threshold is detected, or invalid if control signal below the threshold is detected. Thus, the software application of Rowe is understood to read on all required structural components and functional capabilities of the software application of claim 77.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the detection system and software disclosed by Rowe to analyze results of the test strip disclosed by Deirmengian (or the test strip taught by Sommera in view of Deirmengian and Hagan) because the software and analysis taught by Rowe provides a portable test reading device which provides accurate evaluation of test results without the need for specialized instrumentation and training (Rowe, Par. 3-4). One of ordinary skill in the art would have a reasonable expectation of success in making this modification because Deirmengian and Sommera disclose immunoassay test strips with visually observable test results which may be read either by eye or with an electronic reader, while Rowe provides an analysis system that uses computer vision techniques to provide analysis of results for diagnostic tests including immunoassay test strips.
Claims 82 and 90 are rejected under 35 U.S.C. 103 as being unpatentable over Deirmengian et al (WO 2013/112216; previously cited) as applied to claim 1 above, and further in view of Soh et al (("Strategies for Developing Sensitive and Specific Nanoparticle-Based Lateral Flow Assays as Point-of-Care Diagnostic Device." Nano today 30(2020): 100831-.; previously cited).
ADDITIONALLY, Claims 82, 86, and 90 are rejected under 35 U.S.C. 103 as being unpatentable over Sommera et al (US 2019/0302028 A1) in view of Deirmengian et al (WO 2013/112216; previously ci