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 .
Status of the Claims
Claims 1-33 are pending and examined on the merits.
Claims 1-33 are rejected.
Priority
The application filed 10/07/2021 claims priority to US Provisional 62/832,129 filed 04/10/2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/07/2021 and 08/15/2022 are acknowledged. A signed copy of the corresponding 1449 form has been included with this Office action.
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 1-33 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Claim Analysis
In accordance with MPEP § 2106, claims found to recite statutory subject matter are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1).
Framework with which to Evaluate Subject Matter Eligibility:
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application; and
Step 2B: If the claims do not integrate the judicial exceptions, do the claims provide an inventive concept?
Framework Analysis on the Instant Claims:
Step 1:
With respect to Step 1: claims 1-33 are directed to a system, i.e., a process, machine, or manufacture within the above 35 U.S.C. 101 categories [Step 1: YES; See MPEP § 2106.03]
Step 2A, Prong One:
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas [see MPEP § 2106.04(a)(2)]. Under the Step 2A, Prong One evaluation, the claims found to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing, and organizing information) and mathematical concepts (in particular mathematical relationships and formulas) are as follows:
Independent claim 1:
Mental step:
determine a relaxation time
correlate the relaxation time with a species of the biomarker
Independent claim 20:
Mental step:
correlate the relaxation time period
Dependent claims 2-19, and 21-33 recite further steps that limit the judicial exceptions in independent claims 1 and 20 and, as such, are also directed to those abstract ideas. For example, claims 5 and 22 further limit the parameters of claims 1 and 20 by further specifying the limitations of the relaxation threshold.
These recitations are similar to the concepts of collecting information, analyzing it and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind or mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI). When read in light of and consistent with the specification, the claims are determined to be directed to mental processes that in the simplest embodiments are not too complex to practically perform in the human mind. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind. The instant claims must therefore be examined further to determine whether they integrate the abstract idea into a practical application. [Step 2A, Prong 1: YES; See MPEP § 2106.04].Step 2A, Prong Two:
In determining whether a claim is directed to a judicial exception, further examination is performed that analyzes if the claim recites additional elements that when examined as a whole integrates the judicial exception(s) into a practical application (MPEP § 2106.04(d)). A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements are analyzed to determine if the abstract idea is integrated into a practical application (MPEP § 2106.04(d)(I)). If the claim contains no additional elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP § 2106.04(d)(III)). With respect to Step 2A, Prong Two,
receive a data signal
output configured to output one or both of the relaxation time and the species
Further steps directed to additional non-abstract elements of data analysis should describe any specific computational steps by which the “computer software product” or “interface,” perform or carry out the judicial exceptions, or provide any details of how specific structures of the computer, such as the computer-readable recording media, are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, and therefore the claim does not integrate the judicial exceptions into a practical application. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc.… are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (MPEP 2106.05(f)). Thus, none of the claims recite additional elements which would integrate a judicial exception into a practical application, and the claims are directed to one or more judicial exceptions [Step 2A, Prong 2: NO; See MPEP § 2106.04(d)].
Step 2B
According to analysis so far, the additional elements described above do not provide
significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional.
Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s) (WURC).
With respect to the instant claims, the courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at
1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information),
buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014)
(computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, as discussed in MPEP 2106.05(d)(II)(i)).
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)).
With respect to claims 1 and 20 and those claims dependent therefrom, the computer-related elements or the general-purpose computer do not rise to the level of significantly more than the judicial exception. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions when using a computer, which the courts have found to not provide significantly more when recited in a claim with a judicial exception (see MPEP 2106.06(A)).
The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself [Step 2B: NO; See MPEP § 2106.05].
As such, claims 1-33 are not patent eligible.
Claim Rejections - 35 USC § 102
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.
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 20, 21, 25, 27-29, 31, and 32 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US 2015/0177348 A1 (hereinafter Peng).
Regarding Claim 20, Peng discloses a disease species differentiation system (In accordance with one aspect of this disclosure, there is provided a device for performing magnetic resonance relaxometry, Abstract; The biological sample may comprise a biomarker of a disease, the biomarker being detectable by magnetic resonance, Para. [0008]; we expect the MRR in accordance with one aspect of this disclosure to also work on less infectious and less common human infecting parasites such as P. malariae, P. vivax, and P. ovale, since hemozoin is a common signature among hemoglobin-feeding parasites, Para. [0112]), comprising: a reader configured to receive a biological sample having a biomarker, the reader having: a magnetic field source configured to apply a magnetic field to the biological sample and remove or lower the magnetic field from the biological sample (The method comprises concentrating at least a portion of a blood sample comprising the blood from the animal body thereby producing concentrated red blood cells; inserting the concentrated red blood cells within a detection coil of a magnetic resonance relaxometry device, Para. [0009]); a timer configured to measure a relaxation time period that begins when the magnetic field is removed or lowered from the biological sample (In accordance with one aspect of this disclosure, the whole system may cost less than $2500; in which the majority of the cost lies on the... external GHz-clock ..., Para. [0043]; determining an infection level of the cells in the blood based at least in part on a transverse relaxation rate of the concentrated red blood cells in the magnetic resonance relaxometry device, Para. [0009]); a reader processor configured to output the relaxation time period (By measuring the fluctuation AR2 over a period of time, MRR can give a quick assessment of the patient's condition based on the severity index, Para. [0106]); and a species differentiation processor configured to receive the relaxation time period and correlate the relaxation time period with a species of the biomarker (in the experiment in accordance with one aspect of this disclosure, by calculating the magnitude of the transverse relaxation rate enhanced, AR2=R2(iRBC)-R2(RBC), thus a correlation (R2>0.98) between AR2 versus parasitemia levels can be established, Para. [0083]; An embodiment according to one aspect of this disclosure exploits the relatively large paramagnetic susceptibility of these hemozoin particles, which induce substantial changes in the transverse relaxation rate of proton nuclear magnetic resonance of RBCs, to infer the “infection severity” of an infected patient, Para. [0064]), and an output configured to output one or both of the relaxation time period and the species of the biomarker (In accordance with one aspect of this disclosure, in order to facilitate processing of information to and from the MRR system 100, the FPGA-based rf spectrometer 102 is couplable to at least one external electronic device which may, for example, include a personal computer, mobile phone and/or a portable electronic tablet, Para. [0042]).
Regarding Claim 21, Peng discloses the system of claim 20, wherein the magnetic-field sensitive biomarker is hemozoin and the biological sample is a patient blood sample (In accordance with another aspect of this disclosure, there is provided a method of determining an infection level of cells in blood from an animal body using magnetic resonance relaxometry, Para. [0009]; An embodiment according to one aspect of this disclosure exploits the relatively large paramagnetic susceptibility of these hemozoin particles, which induce substantial changes in the transverse relaxation rate of proton nuclear magnetic resonance of RBCs, to infer the “infection severity” of an infected patient, Para. [0064]).
Regarding Claim 25, Peng discloses the system of claim 20, wherein the biomarker is hemozoin and the species of the biomarker is one or more type of malaria parasite (One aspect of this disclosure exploits the presence of the hemozoin crystallites formed within the erythrocyte as early as in the ring stage itself as a natural magnetic label for MRR detection of P. falciparum iRBCs, Para. [0071]; An embodiment according to one aspect of this disclosure exploits the relatively large paramagnetic susceptibility of these hemozoin particles, which induce substantial changes in the transverse relaxation rate of proton nuclear magnetic resonance of RBCs, to infer the “infection severity” of an infected patient, Para. [0064]).
Regarding Claim 27, Peng discloses the system of claim 20, wherein the output includes an external device having a display (In accordance with one aspect of this disclosure, in order to facilitate processing of information to and from the MRR system 100, the FPGA-based rf spectrometer 102 is couplable to at least one external electronic device which may, for example, include a personal computer, mobile phone and/or a portable electronic tablet, Para. [0042]).
Regarding Claim 28, Peng discloses the system of claim 20, wherein the processor and the output are integrated into a medical device configured to diagnose a patient (According a further aspect of this disclosure, methods and devices discussed herein may also be used for the diagnosis of any disease (provided that the biomarkers can be uncovered by means of magnetic resonance), or immuno-labeling, | within a single portable system, Para. [0097]; It was demonstrated that the MRR biosensor can be a portable platform for medical diagnosis by measuring the transverse relaxation rate, R2 of actual biological cells, Para. [0061]).
Regarding Claim 29, Peng discloses the system of claim 28, wherein the output includes one or more of a screen, a speaker, and a tactile output (In accordance with one aspect of this disclosure, in order to facilitate processing of information to and from the MRR system 100, the FPGA-based rf spectrometer 102 is couplable to at least one external electronic device which may, for example, include a personal computer, mobile phone and/or a portable electronic tablet, Para. (0042]).
Regarding Claim 31, Peng discloses the system of claim 20, wherein the data signal is an average of 2 or more cycles of a high/low magnetic field or an on/off magnet (The transverse relaxation rates, R2 were measured by standard Carr-Purcell-Meiboom-Gill train pulses (60 ps of inter-echo time) consisting of 5000 echoes. A total of 48 scans were typically acquired for signal averaging unless mentioned otherwise, Para. [0120]).
Regarding Claim 32, Peng discloses the system of claim 31, wherein each cycle has the same speed of magnetic field change (The transverse relaxation rates, R2 were measured by standard Carr-Purcell-Meiboom-Gill train pulses (60 ps of inter-echo time) consisting of 5000 echoes. A total of 48 scans were typically acquired for signal averaging unless mentioned otherwise. All samples were measured at room-temperature. Al! data were acquired five times and reported as (meanststandard error measurement (s.e.m)). The transmitter power output is maintained at 1.56 W for a single 90°-pulse of pulse length 14 us, which correspond to nutation frequency of 17.9 kHz. A recycle delay of 1 s which was set between each pulse is sufficiently long enough to allow all the spins to return to thermal equilibrium, Para. [0120]).
Claim Rejections - 35 USC § 103
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.
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.
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 1-3, 9, 11-14, and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over US 2015/0177348 A1 (hereinafter Peng) in view of US 2018/0203080 A1 (hereinafter Acosta).
Regarding Claim 1, Peng discloses a species differentiation system (In accordance with one aspect of this disclosure, there is provided a device for performing magnetic resonance relaxometry, Abstract; The biological sample may comprise a biomarker of a disease, the biomarker being detectable by magnetic resonance, Para. [0008]; we expect the MRR in accordance with one aspect of this disclosure to also work on less infectious and less common human infecting parasites such as P. malariae, P. vivax, and P. ovale, since hemozoin is a common signature among hemoglobin-feeding parasites, Para. [0112}), comprising: a processor configured to: receive a data signal having a feature or parameter that represents a property, a value of the property, or a range of values of the property of a magnetic-field sensitive biomarker in a biological sample, the feature or parameter that represents the property including a time measurement measured from a time a magnetic field applied to the biological sample is removed or lowered to a time a relaxation transmittance value reaches a relaxation threshold (As can be seen, one aspect of this disclosure is able to use a re-programmable FPGA processor, Para. [0060}; In further, related embodiments, the determining of the infection level of the cells may be based at least in part on a change in a transverse relaxation rate of the concentrated red blood cells relative to a predetermined standard for transverse relaxation rate for blood that is not infected with a disease, Para. [0010]; In an experiment in accordance with one aspect of this disclosure, the transverse relaxation rate of proton NMR of uninfected RBCs, R2(RBC) were measured to establish the baseline to compare the amount of R2 shifted due to the presence of iRBCs, Para. [0078]; An embodiment according to one aspect of this disclosure exploits the relatively large paramagnetic susceptibility of these hemozoin particles, which induce substantial changes in the transverse relaxation rate of proton nuclear magnetic resonance of RBCs, to infer the “infection severity” of an infected patient, Para. [0064]); determine a relaxation time for the species sample based on the time measurement (By measuring the fluctuation AR2 over a period of time, MRR can give a quick assessment of the patient's condition based on the severity index, Para. [0106]); correlate the relaxation time with a species of the biomarker (In the experiment in accordance with one aspect of this disclosure, by calculating the magnitude of the transverse relaxation rate enhanced, AR2=R2(iRBC)-R2(RBC), thus a correlation (R2>0.98) between AR2 versus parasitemia levels can be established, Para. [0083]; An embodiment according to one aspect of this disclosure exploits the relatively large paramagnetic susceptibility of these hemozoin particles, which induce substantial changes in the transverse relaxation rate of proton nuclear magnetic resonance of RBCs, to infer the “infection severity” of an infected patient, Para. [0064]); and an output configured to output one or both of the relaxation time and the species correlated with the relaxation time (In accordance with an aspect of this disclosure, in order to facilitate processing of information to and from the MRR system 100, the FPGA-based rf spectrometer 102 is couplable to at least one external electronic device which may, for example, include a personal computer, mobile phone and/or a portable electronic tablet, Para. [0042]).
Peng fails to explicitly disclose relaxation transmittance value is a relaxation light transmittance value.
Acosta teaches using relaxation light transmittance values (Some example magnetic resonance spectrometers may include a doped nanostructured crystal, a light source, and a photodetector. An analyte may be positioned in the doped nanostructured crystal for measurement. The light source may generate one or more light pulses directed at the doped nanostructured crystal. The photodetector may detect a fluorescence signal emitted from the doped nanostructured crystal, wherein the fluorescence signal is influenced by magnetic resonance processes in the analyte, Para. [0005]; In some embodiments, analytes may be tested for the presence of the malarial byproduct hemozoin, Para. (0010); At the “Apply Light/Microwave Pulse Sequences” operation 702 and the “Apply Light/Microwave Pulse Sequences or Croco Relaxation Spectroscopy” operation 802. one or more laser beam pulses 124 and/or one or more microwave pulses may be directed at the doped nanostructured crystal 101 in order to interrogate the paramagnetic color centers therein, Para. [0005]. In some embodiments of operation 802, cross-relaxation spectroscopy may be employed as an alternative method to stimulate an EPR response in the analyte 104, Para. [0066)).
Regarding Claim 2, modified Peng discloses the system of claim 1. Peng further discloses wherein the magnetic-field sensitive biomarker is hemozoin and the biological sample is a patient blood sample (In accordance with another aspect of this disclosure, there is provided a method of determining an infection level of cells in blood from an animal body using magnetic resonance relaxometry, Para. [0009]; An embodiment according to one aspect of this disclosure exploits the relatively large paramagnetic susceptibility of these hemozoin particles, which induce substantial changes in the transverse relaxation rate of proton nuclear magnetic resonance of RBCs, to infer the “infection severity” of an infected patient, Para. [0064]).
Regarding Claim 3, modified Peng discloses the system of claim 1. Peng fails to explicitly disclose wherein the data signal includes an optical signal. Acosta teaches an optical signal (In some embodiments, analytes may be tested for the presence of the malarial byproduct hemozoin, e.g., by comparing the EPR influenced fluorescence signal to EPR influenced fluorescence signal produced by the malarial byproduct hemozoin, Para. [0010]; The doped nanostructured crystal 101 contains large numbers of paramagnetic color sensors 103, e.g., the doped nanostructured crystal 101 may contain one billion or more paramagnetic color sensors 103.Each paramagnetic color sensor 103 serves as a tiny magnetic field sensor by optically detecting changes in energy levels, Para. [0028)). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Peng with the teaching of Acosta for the purpose of generating a signal that can be detected optically for increased efficiency in detection and observation.
Regarding Claim 9, modified Peng discloses the system of claim 1. Peng further discloses wherein the biomarker is hemozoin and the species of the biomarker is one or more type of malaria parasite (One aspect of this disclosure exploits the presence of the hemozoin crystallites formed within the erythrocyte as early as in the ring stage itself as a natural magnetic label for MRR detection of P. falciparum iRBCs, Para. [0071]; An embodiment according to one aspect of this disclosure exploits the relatively large paramagnetic susceptibility of these hemozoin particles, which induce substantial changes in the transverse relaxation rate of proton nuclear magnetic resonance of RBCs, to infer the “infection severity” of an infected patient, Para. [0064)].
Regarding Claim 11, modified Peng discloses the system of claim 1. Peng further discloses wherein the output includes an external device having a display (In accordance with one aspect of this disclosure, in order to facilitate processing of information to and from the MRR system 100, the FPGA-based rf spectrometer 102 is couplable to at least one external electronic device which may, for example, include a personal computer, mobile phone and/or a portable electronic tablet, Para. [0042)).
Regarding Claim 12, modified Peng discloses the system of claim 1. Peng further discloses wherein the output is further configured to output the species correlated with the relaxation time (A magnetic susceptibility index could be determined, corresponding to the measured change in transverse relaxation rate, each level of which magnetic susceptibility index could be associated with likelihoods of the patient having certain parasitemia levels and certain stages of infection, Para. [0091]; The method may comprise determining infection level of red blood cells infected with hemoglobin-feeding parasites in blood from a human body; such as determining infection level for at least one of red blood cells infected with plasmodium falciparum, Para. [0010)).
Regarding Claim 13, modified Peng discloses the system of claim 1. Peng further discloses wherein the processor and the output are integrated into a medical device configured to diagnose a patient (According a further aspect of this disclosure, methods and devices discussed herein may also be used for the diagnosis of any disease (provided that the biomarkers can be uncovered by means of magnetic resonance), or immuno-labeling, within a single portable system, Para. [0097]; It was demonstrated that the MRR biosensor can be a portable platform for medical diagnosis by measuring the transverse relaxation rate, R2 of actual biological cells, Para. [0061)).
Regarding Claim 14, modified Peng discloses the system of claim 13. Peng further discloses wherein the output includes one or more of a screen, a speaker, and a tactile output (In accordance with one aspect of this disclosure, in order to facilitate processing of information to and from the MRR system 100, the FPGA-based rf spectrometer 102 is couplable to at least one external electronic device which may, for example, include a personal computer, mobile phone and/or a portable electronic tablet, Para. {0042)).
Regarding Claim 16, modified Peng discloses the system of claim 1. Peng further discloses wherein the data signal is an average of 20 or more cycles of a high/low magnetic field or an on/off magnet (The transverse relaxation rates, R2 were measured by standard Carr-Purcell-Meiboom-Gill train pulses (60 µs of inter-echo time) consisting of 5000 echoes. A total of 48 scans were typically acquired for signal averaging unless mentioned otherwise, Para. [0120)).
Regarding Claim 17, modified Peng discloses the system of claim 16. Peng further discloses wherein each cycle has the same speed of magnetic field change (The transverse relaxation rates, R2 were measured by standard Carr-Purcell-Meiboom-Gill train pulses (60 Ys of inter-echo time) consisting of 5000 echoes. A total of 48 scans were typically acquired for signal averaging unless mentioned otherwise. All samples were measured at room-temperature. All data were acquired five times and reported as (means±standard error measurement). The transmitter power output is maintained at 1.56 W for a single 90°-pulse of pulse length 14 us, which correspond to nutation frequency of 17.9 kHz. A recycle delay of 1 s which was set between each pulse is sufficiently long enough to allow all the spins to return to thermal equilibrium, Para. [0120]).
Case for prima facie obviousness:
The claims are directed to a species differentiation system that measures a relaxation time of a magnetic-field-sensitive biomarker in a biological sample which receives data, measures the time it takes for a light transmittance to return to a relaxation threshold after an external magnetic field is removed/lowered, correlate the relaxation time with a specific species of malaria parasite, and output the correlated species and relaxation time.
In KSR Int 'l v. Teleflex, the Supreme Court, in rejecting the rigid application of the teaching, suggestion, and motivation test by the Federal Circuit, indicated that “The principles underlying [earlier] cases are instructive when the question is whether a patent claiming the combination of elements of prior art is obvious. When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR Int'l v. Teleflex lnc., 127 S. Ct. 1727, 1740 (2007).
Applying the KSR standard of obviousness to Peng in view of Acosta represents combining prior art elements according to known methods to yield predictable results. It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Peng with the teaching of Acosta for the purpose of generating a signal that can be detected optically for increased efficiency in detection and observation to determine the presence and type of species in a biological sample.
There would be an expectation of success in combining Peng et al. and Acosta et al., as both teach devices for performing magnetic resonance relaxometry on biological samples.
Regarding Claim 18, modified Peng discloses the system of claim 16, Peng fails to explicitly disclose wherein at least two cycles have different speeds of magnetic field change. It would have been obvious to one of ordinary skill in the art at the time of the invention to use at least two cycles having different speeds of magnetic field change, since the provision of adjustability, where needed, involves only routine skill in the art. The motivation for doing so would be to monitor relaxation rates using different speeds of magnetic field change to differentiate a species-specific biomarker to detect a pathogen in a sample derived from a subject.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Peng in view of Acosta as applied to claims 1-3, 9, 11-14, and 16-18 above, and further in view of Donolato et al. US 2016/0146798 A1.
Peng in view of Acosta are applied to claims 1-3, 9, 11-14, and 16-18.
Peng fails to explicitly disclose wherein the relaxation threshold represents a starting light transmittance value or range of values that is measured before the magnetic field is applied to the biological sample.
Donolato teaches using pre-magnetic field light transmittance values as a threshold (The invention relates to a novel two-pass biosensor adapted for rapid and sensitive detection of target analytes utilizing magnetic nanoparticles, Para. [0001]; Disclosed herein is a biosensor comprising at least one optical reservoir containing a suspension of magnetic particles. The biosensor further comprises a light source emitting light at a wavelength λ, with an intensity I, the light source being directed at the optical reservoir and being adapted for interacting with the suspension of magnetic particles, wherein the light source is an optical pickup head and wherein the light entering the optical reservoir has an intensity lin, and light transmitted through the optical reservoir has an intensity ltrans, Para. [0007]; In FIG. 3a, the signal level fur the measurements obtained with no magnetic field excitation, line 206, is the same before and after an experiment. The signal with the field excitation, line 204, is dominated by a component at 2f, and shows sharp minima when the applied field Intensity Is close to zero and maxima when the field is numerically large. The signal level of the minima is close to that obtained when no magnetic field excitation is applied, Para. [0091]).
Case for prima facie obviousness:
Applying the KSR standard of obviousness to modified Peng in view of Donolato represents combining prior art elements according to known methods to yield predictable results. It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Peng with the teaching of Donolato for the purpose of using a pre-magnetic field light transmittance value as a threshold for determining if a target biomarker is present based on changes in light transmittance resulting from changes in relaxation times.
Claims 5 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Peng in view of Acosta as applied to claims 1 and 20 above, and further in view of US 2013/0289383 A1 (hereinafter Flynn).
Peng in view of Acosta are applied to claims 1 and 20 as above.
Regarding Claim 5, Peng fails to explicitly disclose wherein the relaxation threshold represents a Brownian relaxation threshold or range of values that indicates that the biomarker is wholly randomized or partially randomized within the biological sample.
Flynn teaches Brownian relaxation values for determining if a biomarker is present in a sample (This invention relates to the in vivo detection and measurement of cells or substances using nanoparticles and magnetic relaxation measurements, Para. [0002]; An example method according to the present invention can comprise: (a) introducing into the first region a plurality of superparamagnetic nanoparticles, having properties such that they undergo Brownian motion that randomizes the orientation of the nanoparticles according to a predetermined characteristic time; (b) after a time sufficient to allow transport of nanoparticles from the first region to the second region, subjecting the second region to an applied magnetic field of sufficient strength to induce magnetization of individual nanoparticles, and having a substantially uniform direction throughout the second region; (c) measuring the magnetic field of the second region at a plurality of times after ceasing application of the magnetic field; (d) analyzing the measured magnetic field to detect signals that correspond to decay of the magnetic field due to randomization of the nanoparticles’ orientation by Brownian motion; (e) determining the presence of nanoparticles in the second region from the signals detected in step (d), Abstract).
Regarding Claim 22, Peng fails to explicitly disclose wherein the relaxation time period represents a Brownian relaxation threshold are range of values that indicates that the biomarker is wholly randomized or partially randomized within the biological sample.
Flynn teaches Brownian relaxation values for determining if a biomarker is present in a sample (This invention relates to the in vivo detection and measurement of cells or substances using nanoparticles and magnetic relaxation measurements, Para. [0002]; An example method according to the present invention can comprise: (a) introducing into the first region a plurality of superparamagnetic nanoparticles, having properties such that they undergo Brownian motion that randomizes the orientation of the nanoparticles according to a predetermined characteristic time; (b) after a time sufficient to allow transport of nanoparticles from the first region to the second region, subjecting the second region to an applied magnetic field of sufficient strength to induce magnetization of individual nanoparticles, and having a substantially uniform direction throughout the second region; (c) measuring the magnetic field of the second region at a plurality of times after ceasing application of the magnetic field; (d) analyzing the measured magnetic field to detect signals that correspond to decay of the magnetic field due to randomization of the nanoparticles’ orientation by Brownian motion; (e) determining the presence of nanoparticles in the second region from the signals detected in step (d), Abstract).
Case for prima facie obviousness:
Applying the KSR standard of obviousness to modified Peng in view of Flynn represents combining prior art elements according to known methods to yield predictable results. It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Peng with the teaching of Flynn for the purpose of using properties of particles sensitive to magnetic fields to determine the presence and/or quantity of a target biomarker in a sample.
Claims 6-7, and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Peng in view of Acosta as applied to claims 1 and 20 above, and further in view of US 2018/0252709 A1 (hereinafter Dryga).
Peng et al. is applied to claims 1 and 20 above.
Regarding Claim 6, Peng fails to explicitly disclose further comprising a viscosity agent that increases a viscosity of a processed biological sample, wherein the processed biological is formed by processing the biological sample.
Dryga teaches processing a biological sample using viscosity-modifying agents to increase viscosity (In particular embodiments, methods of the invention isolate a pathogen from body fluid, Para. [0054]; Another approach may be to use a secondary fluid component that constitutes only a small fraction of the total fluid mixture.... The fluid components employed may act in concert to produce the desired fluid flow characteristics, such as high-viscosity and/or plug flow. The fluid components may be useful for providing fluid characteristics that are advantageous for the performance of the NMR detector, for example by providing NMR relaxation times that allow faster operation or higher signal intensities, Para. [0093]).
Regarding Claim 7, Peng fails to explicitly disclose wherein the biological sample includes a viscosity agent that increases the viscosity of the biological sample from a viscosity value of the biological sample without the viscosity agent. Dryga teaches processing a biological sample using viscosity-modifying agents to increase viscosity (In particular embodiments, methods ‘of the invention isolate a pathogen from body fluid, Para. [0054]; Another approach may be to use a secondary fluid component that constitutes only a small fraction of the total fluid mixture.... The fluid components employed may act in concert to produce the desired fluid flow characteristics, such as high-viscosity and/or plug flow. The fluid components may be useful for providing fluid characteristics that are advantageous for the performance of the NMR detector, for example by providing NMR relaxation times that allow faster operation or higher signal intensities, Para. [0093]).
Regarding Claim 23, Peng fails to explicitly disclose further comprising a viscosity agent that increases a viscosity of a processed biological sample, wherein the processed biological is formed by processing the biological sample. Dryga teaches processing a biological sample using viscosity-modifying agents to increase viscosity (In particular embodiments, methods of the invention isolate a pathogen from body fluid, Para. [0054]; Another approach may be to use a secondary fluid component that constitutes only a small fraction of the total fluid mixture... The fluid components employed may act in concert to produce the desired fluid flow characteristics, such as high-viscosity and/or plug flow. The fluid components may be useful for providing fluid characteristics that are advantageous for the performance of the NMR detector, for example by providing NMR relaxation times that allow faster operation or higher signal intensities, Para. [0093]).
Regarding Claim 24, Peng fails to explicitly disclose further comprising a viscosity agent that decreases a viscosity of the biological sample from a viscosity value of the biological sample without the viscosity agent. Dryga teaches processing a biological sample using viscosity-modifying agents to decrease viscosity (In particular embodiments, methods of the invention isolate a pathogen from body fluid, Para. [0054]; An alternative approach to achieve high binding efficiency while reducing time required for the binding step is to use static mixer, or other mixing devices that provide efficient mixing of viscous samples at high flow rates, such as at or around 5 mL/min. In one embodiment, the sample is mixed with binding buffer in ratio of, or about, 1:1, using a mixing interface connector. The diluted sample then flows through a mixing interface connector where it is mixed with target-specific nanoparticles. Additional mixing interface connectors providing mixing of sample and antigen-specific nanoparticles can be attached downstream to improve binding efficiency. The combined flow rate of the labeled sample is selected such that it is compatible with downstream processing, Para. [0061]; Another approach may be to use a secondary fluid component that constitutes only a small fraction of the total fluid mixture... The fluid components may be useful for providing fluid characteristics that are advantageous for the performance of the NMR detector, for example by providing NMR relaxation times that allow faster operation or higher signal intensities, Para. [0093]).
Case for prima facie obviousness:
Applying the KSR standard of obviousness to modified Peng in view of Dryga represents combining prior art elements according to known methods to yield predictable results. It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Peng with the teaching of Dryga for the purpose of modifying a biological sample to optimize its properties such as increasing viscosity for optimal operation and signal intensity.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Peng in view of Acosta as applied to claim 1 above, and further in view of US 2014/0103924 A1 (hereinafter Griswold).
Peng in view of Acosta is applied to claim 1 above.
Peng fails to explicitly disclose wherein the processor is further configured to determine the relaxation time for the species based on a comparison of the determined relaxation time to a known value or range of values of a known species-specific relaxation time. Griswold teaches comparing relaxation time for a test species to relaxation times of known species for characterization of a sample (NMRfp applies radio frequency (RF) energy in a series of varied sequence blocks that cause both R1 and R2 to simultaneously produce different NMR signals. A signal evolution can be produced from these simultaneously produced different NMR signals. Relaxation... can be determined from the signal evolution through comparison with other signal evolutions tor which relaxation or other NMR parameters are known. The resonant species R1 and R2 can then be characterized by the relaxation or other NMR parameters. Since different tissues have different known relaxation or other NMR parameters, different tissues can be identified using the relaxation or other NMR parameter characterization, Para [0027]).
Case for prima facie obviousness:
Applying the KSR standard of obviousness to modified Peng in view of Griswold represents combining prior art elements according to known methods to yield predictable results. It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Peng with the teaching of Griswold for the purpose of identifying a test species by comparing relaxation rates of biomarkers to known values of biomarkers specific to each species for determining the presence and/or identity of a species.
Claims 10 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Peng in view of Acosta as applied to claim 1 above, and further in view of Pershina et al., Hemozoin "knobs" in Opisthorchis felineus infected liver. Parasit Vectors. 2015 Sep 17;8:459.
Peng et al. is applied to claims 1 and 20 above.
Regarding Claim 10, modified Peng discloses the system of claim 1. Peng fails to explicitly disclose wherein the biomarker has one or more species-specific characteristics, and wherein the processor is further configured to correlate the relaxation time with the species of the biomarker based on the one or more species-specific characteristics of the biomarker. Pershina teaches hemozoin has species-specific characteristics such as length that can be used to correlate relaxation time with species (Several diagnostic methods, such as... magnetic resonance relaxometry [...] have been developed on the basis of magnetic properties of hemozoin crystal, Pg. 2, left column, first partial paragraph; T1 and T2 relaxation maps of water hemozoin suspension phantoms were recorded in order to investigate the MRI-contrast properties of hemozoin, Pg. 3, right column, first partial paragraph; Hemozoin crystals produced by the O. felineus were lath shaped with lengths about 100-600 nm and average length-to-width ratio about 2.0.... Parameters of external size of extracted hemozoin crystals produced by O. felineus and produced by P. falciparum hemozoin are slightly different. The hemozoin crystals produced by P. falciparum have average length 500 nm (from 180 to 1400 nm) and length-to-width ratio 3.4. By no surprise since hemozoin crystals extracted from various species such as P. falciparum, S. mansoni and H. columbae also have different morphology, Pg. 5, left column, final partial paragraph - Pg. 5, right column, first partial paragraph).
Regarding Claim 26, Peng fails to explicitly disclose wherein the biomarker has a species-specific length, and wherein the processor is further configured to correlate the relaxation time with the species of the biomarker based on the species-specific length of the biomarker. Pershina teaches a biomarker such as hemozoin has a species-specific length and relaxation time can be correlated with biomarker length (Several diagnostic methods, such as... magnetic resonance relaxometry [...] have been developed on the basis of magnetic properties of hemozoin crystal, Pg. 2, left column, first partial paragraph; T1 and T2 relaxation maps of water hemozoin suspension ph