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 .
DETAILED ACTION
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 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.
Status of the claims
Claims 1-20 are pending and examined on merits in this office action to the extant it encompasses the elected species.
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.
Claims 11-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e. a product of nature) without significantly more.
Is the claim to a process, machine or composition of matter”? the invention of claim 11 is directed to a method of detecting a urinary tract infection (UTI) using a lateral flow immunoassay system capable of detecting at least two biomarkers selected from the group consisting of NGAL, IL-1β and IL-8, wherein detection of at least two biomarker proteins above a reference level is indicative of a UTI (Step 1: YES).
ELIGIBILITY STEP 2A; WHETHER A CALIM IS DIRECTED TO A JUDICIAL EXCEPTION. First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A Prong 1
In claim 11, the following limitations fall under the laws of nature/natural phenomena: In claim 11, the following limitation fall under the laws of nature/natural phenomena:
Claim 1 is directed to detection of urinary tract infection (UTI) in a subject by detection of at least two biomarkers selected from of NGAL, IL-1β and IL-8, comparing with a reference level of the biomarkers and detecting UTI when at least two biomarkers are above the reference level. The claim thereby recites the laws of nature/natural phenomena. The natural relationship to which the claims are directed (i.e., the naturally occurring correlation between the UTI infection and biomarker proteins in a urine sample) exists in principle apart from any human action. Similar concepts have been held by the courts to constitute laws of nature/ natural phenomena, as in the identification of a correlation between the presence of a marker in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017); see also Univ. of Utah Research Found. v. Ambry Genetics Corp., 774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014) and In re Grams, 888 F.2d 835, 12 U.S.P.Q.2d 1824 (Fed. Cir. 1989)).
Dependent claims 12-13 recites limitations directed to law of nature and natural phenomena, as the claims are directed to the subjects for detecting with the detection of biomarker and correlation to UTI.
Step 2A Prong 2:
The Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception.
Besides the abstract ideas and natural phenomena, claims 14-20 discloses additional element of using LFA system (claims 11-16 and 19-20) and automated LFA system (claims 17-18) for detection of the biomarkers and data gathering for analyses. When so evaluated, these additional limitations represent mere utilization of known system and data gathering. Data gathering and outputting seps are not sufficient to integrate judicial exception into a practical exception (MPEP 2106.05 (g)). Such limitations in the claims are thus insignificant extra-solution activity, which is required to measure the levels of the target biomarkers utilizing known systems. Therefore, the judicial exceptions are not integrated into a practical application.
Step 2B:
In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP 2106.05. The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception. As such, the claims simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (MPEP2106.05(d)). The data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
The additional element of LFA systems is well-understood, routine, and conventional. This position is supported by Chen et al (Food Chemistry 2016) and Park et al (Sensors, 2022). Chen teaches lateral flow immunoassay system for multiplexing utilizing multiple test lines for detection of multiple target analytes. Park teaches LFA reader technologies for quantitative point-of-care testing (Title). Park teaches colorimetric readers wherein image sensor mounted on the reader acquires an image of the test line, which is a combination of labeled particles, antigens, and antibodies. The pixel intensity of the test line is then converted to the concentration of the target analyte. Park teaches automated process by applying a fuzzy cellular neural network with adaptive threshold (FCNN-AT) algorithm was developed for noise reduction of the obtained assay image and image segmentation of ROI regions (i.e., test line and Sensors 2022, 22, 7398 4 of 21 control line regions) (Fig.2, 3 and 6).
Therefore, taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself. (Step 2B: NO)
Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea without significantly more. For additional guidance, applicant is directed generally to applicant is directed generally to the MPEP § 2106.
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 of this title, 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 1-7, 9-16 and 19-20 are rejected under 35 U.S.C. 103 as obvious over Santos et al. (J. of Pharmaceutical and Biomedical Analysis 2022) in view of Gadalla et al (Scientific Reports 2019, 9:19694, pp. 1-11) and Chen et al. (Food Chemistry, 2016).
Claim 1 is a detection system comprising a) sample receiving zone and b) at least two detection zone for detecting at least two proteins selected from the groups consisting of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-1β (IL-1β) and IL-8.
The recitation “for detecting a urinary tract infection (UTI) in a subject having or suspected of having a urinary tract infection” and the recitation “wherein detection of at least two biomarker proteins above a reference level is indicative of a UTI” and considered an intended process utilizing the detection system. However, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In a claim drawn to a process of making, the intended use must result in a manipulative difference as compared to the prior art. See In re Casey, 152 USPQ 235 (CCPA 1967) and In re Otto, 136 USPQ 458, 459 (CCPA 1963).
In regards to claims 1, 4-6 and 11, Santos teaches a point-of-care system for diagnosis of urinary tract infection (Title). Santos teaches that there are different immunoassays based on the specific interaction between an antigen and an antibody in order to measure its concentration in a solution. The Enzyme-Linked Immunosorbent Assay (ELISA) is a biochemical assay that use antibodies and enzyme-mediated color change to detect the presence of antigens, antibodies and proteins in a sample (section 4.1, page 2). Santos teaches that the lateral flow assays (LFA) are the most common POC tests and are based on the migration of a liquid sample through different membranes placed in a backing card: sample pad (usually made of cellulose acetate or glass fiber), conjugate pad, reaction membrane (usually made of nitrocellulose (NC)), and absorption pad (Fig. 3(A)). Santos teaches that when a sample is dropped in the sample pad, it flows by capillary force to the conjugation pad, where labeled biorecognition elements bond to the analyte, then, depending on the presence or absence of the target pathogen, the control and test lines composed by biorecognition elements fixed on the reaction membrane, produce a detectable signal and the absorption pad is responsible for stopping the flow of the remaining fluid. The label elements used in this type of devices to obtain direct or indirect detectable signals can be gold nanoparticles (GNPs), polymeric latex, selenium nanoparticles, silver nanoparticles, magnetic particles, quantum dots (QD), carbon-based materials, electrochemical active tags, fluorescent and luminescent materials, textile dyes, liposomes, enzymes amongst others.
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Therefore, Santos clearly discloses a system for detection urinary tract infection comprising: a) sample receiving zone to receive a portion of urine sample and at least a detection zones having biorecognition element (e.g. antibody) bound to the detection zone for binding to analyte.
Santos does not teach two detection zones for detecting at least two biomarker proteins selected from the group consisting of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-1β (IL-1β) and IL-8.
Gadalla teaches detection of urinary tract infection by detecting urine biomarkers (Title). Gadalla teaches that UTI diagnosis has been based on serum and urinary biomarkers (page 1). Gadalla teaches that the diagnostic relevance of IL-1β and MMP9 was corroborated in an independent analysis and teaches urinary biomarkers alongside NGAL and IL-8/CXCL8 (page 2). Gadalla identified a set of four urinary immunological markers (MMP9, NGAL, IL-8/CXCL8 and IL-1β) (Discussion, page 5). Gadalla also teaches that the immunological markers MMP9, IL-1β and NGAL continued to be important predictors, thereby confirming their relevance in UTI diagnosis (Discussion, page 5). Gadalla also teaches that the most promising immunological biomarkers identified were MMP9, NGAL, IL-8/CXCL8 and IL-1β (page 7). Gadalla teaches that MMP9, NGAL, IL-8/CXCL8 and IL-1β in urine may be useful predictors of UTI and these biomarkers could be used to develop a new point of care test for UTI (page 7).
Chen teaches lateral flow immunoassay system for multiplexing utilizing multiple test lines for detection of multiple target analytes:
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Therefore, given the fact that MMP9, NGAL, IL-8 and IL-1β are useful biomarker for detection of urinary tract infection using urine sample (Gadalla) and given the fact that a point-of-care lateral flow immunoassay system using immobilized antibodies at test lines recognizing specific analytes can be utilized for diagnosis of urinary tract infection and given the fact that Lateral flow test strips with multiple test lines can be utilized for multiplexing (Chen et al), it would be obvious to one of ordinary skilled in the art to easily envisage providing lateral flow immunoassay strip having two or more detection zones with immobilized antibodies specific for the biomarkers, as for example, MMP9, NGAL, IL-8 and IL-1β, as disclosed by Gadalla, on the lateral flow immunoassay strip with the expectation of detection of urinary tract infection with a reasonable expectation of success.
In regards to claims 2-3, the subject and the urine samples are for intended process steps and are not included in the test strip.
In regards to claims 7 and 9, the reference level and the detection with change in color are for intended use and are considered not a part of the system.
In regards to claim 10, both Santos and Chen disclose lateral flow immunoassay test strips having control zone.
In regards to claims 12 and 13, Santos and Gadalla teach detection of urinary tract infection in a subject in urine sample and different subject having different symptoms would be obvious to one of ordinary skilled in the art.
In regards to claims 14 and 15, as described above, Santos teaches lateral flow assay (LFA).
In regards to claim 16, Gadalla teaches detection of urinary levels of MMP9, NGAL, CXCL8 and IL-1β and teaches a stringent determination of cut-off levels for the individual biomarkers for detection of urinary tract infection and thus establishing reference levels of NGAL, IL-8 and IL-1β would be obvious and would be within the purview of one of ordinary skilled in the art.
In regards to claim 19, as described above, Santos and Chen disclose lateral flow immunoassay test strips having control zone.
In regards to claim 20, Santos teaches detection of bacterium and the combination of the references, as described above teach detection of urinary tract infection.
Claims 1-20 are rejected under 35 U.S.C. 103 as obvious over Santos et al. (J. of Pharmaceutical and Biomedical Analysis 2022) in view of Gadalla et al (Scientific Reports 2019, 9:19694, pp. 1-11) and Chen et al. (Food Chemistry, 2016) as describe above for claims 1-7, 9-16 and 19-20 above, and further in view of Park, Jongwon (Sensors 2022).
Santos in view of Gadalla and Chen has been described above that provides obviousness of the detection system and the method of claims 1-7, 9-16 and 19-20. Santos in view of Gadalla and Chen, however, do not teach LFA with automated system wherein sensors operatively coupled to detection zones and generate signal based on the change in the detection zones and transmit the signal to a computing device.
In regards to claims 8 and 17-18, Park teaches LFA reader technologies for quantitative point-of-care testing (Title). Park teaches colorimetric readers wherein image sensor mounted on the reader acquires an image of the test line, which is a combination of labeled particles, antigens, and antibodies. The pixel intensity of the test line is then converted to the concentration of the target analyte. Park teaches automated process by applying a fuzzy cellular neural network with adaptive threshold (FCNN-AT) algorithm was developed for noise reduction of the obtained assay image and image segmentation of ROI regions (i.e., test line and Sensors 2022, 22, 7398 4 of 21 control line regions) (Fig.2, 3 and 6).
Therefore, since the basic concept of detection of urinary tract infection by detection of two or more biomarkers have been found to be obvious in view of Santos, Gadalla and Chen and since automation of LFA point of care testing has been taught by Park, one of ordinary skilled in the art would easily envisage adopting automation as taught by Park for the detection of urinary tract biomarker which have found to be obvious in view of Santos, Gadalla and Chen with a reasonable expectation of success.
Conclusion
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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