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 .
Priority
The present application was filed on June 17,, 2021. The pending and examined claims have an effective filing date of June 17, 2021.
Status of the Claims
Claims 1-8, 12-21, 24-25, 35 and 32-33 are pending. Claims 9-11, 22-23, 26-31, 34, and 36 have been canceled. Claims 32 and 33 have been withdrawn. Claims 1-8, 12-21, 24-25, 35 are
examined herein.
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 1-6, 8, 13-18, 20-21, and 25 are rejected under 35 U.S.C 102(a)(1) as being unpatentable over Shultz et al., (US PG Pub No. 20170097337 A1, Pub. Date: 04/17/2017), in view of Pai et al., (U.S. Patent No. 9,599,591 B2, Date: 03/21/2017), as evidenced by Chen et al., (Yi-Ting Chen, et al., Biosensing Using Magnetic Particle Detection Techniques, 2017, Sensors (Basel), 17(10): 2300).
Throughout the disclosure, Shultz teaches methods and devices for detection and
quantitation of a small analyte suspected to be present in a fluid sample using a competitive
assay format in a magnetic biosensor. Shultz teaches that the magnetic biosensor may be a
magnetic tunnel junction sensor, Hall effect sensor, or magnetoresistive sensor. Furthermore,
the fluid sample is added to a biosensor detection chamber together with capture probes,
magnetic tags, and, in some embodiments, detection probes. A conformation-changing aptamer,
which binds specifically to an analyte and to magnetic tags, or labels, may be used as the
detection probe. In embodiments that use only one binding agent to simultaneously serve as the
capture and detection probe, it is understood that an aptamer, instead of an antibody, can be used
as the binding agent that has a specific affinity for an analyte and can detect if an analyte is
present in a sample. Shultz further teaches that the proximity or displacement of magnetic labels
to the biosensor surface allows for detection of the aptamer-analyte binding event and thus
presence and amount of analyte can be determined.
Regarding claim 1, Shultz teaches a method for determining an analyte suspected to be present in a sample comprising: (a) contacting said sample with at least one sensor element comprising:(i) at least one binding agent which is capable of specifically binding to the analyte and which comprises at least one magnetic label (Shultz et al., US 20170097337 A1: paras 0004, 0074); and in functional proximity thereto (ii) a magnetic tunnel junction generating a signal which is altered upon binding of the analyte to the binding agent for a time and under conditions which allow for specific binding of the analyte suspected to be present in the sample to the at least one binding agent (Shultz et al., US 20170097337 A1: paras 0004, 0008, 0070, 0074); (b) measuring an altered signal generated by the magnetic tunnel junction upon analyte binding to the at least one binding agent comprising the at least one magnetic label (Shultz et al., US 20170097337 A1: paras 0004, 0009, 00029, 0070); and (c) determining the analyte based on the altered signal which is generated by the magnetic tunnel junction (MTJ); wherein said at least one binding agent is an aptamer or fragment thereof, wherein said at least one binding agent is altered in its structure upon binding to the analyte such that the position of the at least one magnetic label becomes located closer (positive mode, when label is bound) or farther away (negative mode, when label is newly introduced) in respect to the sensitivity field of the magnetic tunnel junction (Shultz et al., US 20170097337 A1: paras 0004, 0008-0009, 0070, 0072, 0074). Further, in a separate embodiment, Shultz teaches an aptamer as a detection agent that can be pre-conjugated with a magnetic label via chemical reactions (Shultz et al., US 20170097337 A1: paras 0064, 0071-0072). Shultz does not explicitly teach wherein the at least one magnetic label is permanently bound to, or is a part of, the at least one binding agent.
Throughout the disclosure, Pai teaches an aptamer which is capable of specifically binding to an analyte (col 12, lines 13-14) and which comprises at least one magnetic label (col 19, lines 20-23 and lines 35-38), said aptamer being capable of altering its structure upon binding of the analyte (col 12, lines 14-17) such that the position of the at least one magnetic particle label is altered (col 19, lines 29-32). In detail, Pai discloses a probe attached to a surface of a sensor chip on one end and irreversibly and permanently attached to a magnetic bead on the other end (Fig 1A and col 6, lines 15-17 and 47-50). When the probe is unbound by analyte, it is in a bent configuration wherein the magnetic bead is separated from the sensor at a short distance (Fig 1A and col 6, lines 50-53). Upon binding to its analyte, the probe can change from the unbound configuration to a second configuration wherein the magnetic bead’s distance from the sensor is thus changed (Fig 1B and col 7, lines 1-16). Although the specific example described by Pai relates to a DNA probe, they make it clear that the probe can be another binding moiety capable of changing conformation, such as an aptamer (col 6, lines 38-45 and col 12, lines 13-17).
Pai, in the same field of endeavor and in an analogous method, teaches an aptamer (binding agent) that has a magnetic label covalently, or irreversibly and permanently, bound to one end (Pai et al., US 9,599,591 B2: col 6, lines 47-63 and col 7, lines 9-24; col 10, lines 5-11; col 12, lines 12-17; Figs. 1A-B).
It would have been prima facie obvious, at the time of filing, to combine the method comprising of a structuring switching capture probe (binding agent) for binding/detecting a specific analyte with the method comprising of an aptamer as a detection probe pre-conjugated with a magnetic label for detecting a target analyte, as taught by Shultz in different embodiments in the same reference, to arrive at a structure-switching aptamer as the capture probe (binding agent) pre-conjugated with a magnetic label. A skilled artisan would have recognized that a structure-switching capture probe has the same conformational property as the aptamer recited in the separate embodiment taught by Shultz and would have further reasonably recognized that this combination would result in a simpler detection system not requiring separate detection antibodies and labels. Further, Shultz teaches that an aptamer is more thermally stable alternative to an antibody approach and further teaches an aptamer-based approach would yield improved sensitivity, and specificity (see Shultz et al., para 0072). Thus a skilled artisan would have been motivated to combine the different embodiments of Shultz because it would result in a structure-switching aptamer (binding agent) with a pre-conjugated magnetic label enabling development of a simpler detection method with improved sensitivity and specificity. It would have been further prima facie obvious to combine the embodiments of Shultz with the teachings of an aptamer (binding agent) with a magnetic label permanently bound, as taught by Pai. Further, Pai discloses that a magnetic label that is not covalently and permanently bound to the aptamer (binding agent) is inadequate due to stability reasons (see Pai et al, col 6, lines 15-17). Thus, a skilled artisan would have been further motivated to combine these teachings because it would result in a stable structure-switching aptamer as a binding agent with a magnetic label that is stably and permanently attached resulting in a binding agent that is adequate for detecting a target analyte suspected to be present in a sample without the need for a detection antibody or separate labels. Combining the teachings of Shultz and Pai to arrive at a structure-switching aptamer (binding agent) immobilized on a sensor surface on one end and with a magnetic label covalently and permanently attached on the other end would necessarily and inevitable result in the magnetic label moving closer and farther away from a sensor’s sensing region upon conformational changes of the structure-switching aptamer induced by the binding of an analyte. A person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to combining known elements/ components, known to function the same separately as they would when combined, to yield expected and predictable results.
Regarding claim 2, Shultz and Pai teach all the limitations of claim 1. Shultz further teaches wherein said measuring the altered signal generated by the magnetic tunnel junction upon analyte binding to the at least one binding agent comprises measuring at least one of the strength of the generated signal and its duration (Shultz et al., US 20170097337 A1: paras 0008, 0074, and Figs 1H, 3B).
Regarding claim 3, Shultz and Pai teach all the limitations of claims 1. Shultz further teaches the method of claim 2, wherein said measuring comprises measuring a change in the altered signal over time and evaluating said change (Shultz et al., US 20170097337 A1: Figs. 1H, 3B; paras 0016; 0019; 0048; 0070).
Regarding claim 4, Shultz and Pai teach all the limitations of claim 1. Shultz further teaches wherein said altered signal is induced via the at least one magnetic label by application of an external magnetic field as external trigger (Shultz et al., US 20170097337 A1: paras 0008, 0048; claim 9).
Regarding claim 5, Shultz and Pai teach all the limitations of claim 1. Shultz further teaches wherein said analyte is selected from the group consisting of a protein, peptide, virus, bacterial cell or small molecule (Shultz et al., US 20170097337 A1: para 0005).
Regarding claim 6, Shultz and Pai teach all the limitations of claim 1. Shultz further teaches wherein said determining an analyte comprises determining the presence or absence of said analyte (Shultz et al., US 20170097337 A1: para 0029).
It would have been prima facie obvious, at the time of filing, to combine the method comprising of a structuring switching capture probe/binding agent (direct mode) for analyte detection and the method comprising of an aptamer probe pre-conjugated with a magnetic label for detecting a target analyte (competitive mode) for analyte detection taught by Shultz in separate embodiments in the same reference, with the method of an aptamer with a permanently attached magnetic label, as taught by Pai. Further, Shultz teaches that for the embodiments disclosed an MTJ sensor may be used as the magnetic sensor. the MTJ sensor taught by Shultz operates by detecting perturbations in local (stray) magnetic fields and converting these perturbations into measurable changes in electrical resistance. Further, binding of an analyte to the structure-switching binding agent with a pre-conjugated and permanently attached magnetic label, as taught by Shultz in view of Pai, would necessarily and inevitably result in the location of the attached magnetic label to change relative to the MTJ sensing region. This displacement of the magnetic label relative to the MTJ sensing region would be detected by the MTJ sensor, taught by Shultz, and generate a signal. Thus, a skilled artisan would have been motivated to combine these teaching because it would result in a sensitive and specific detection method capable of detecting a specific analyte suspected to be present in sample. A person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to combining known elements/ components, known to function the same separately as they would when combined, to yield expected and predictable results.
Regarding claim 8, Shultz and Pai teach all the limitations of claims 1. Shultz further teaches the method of claim 7, wherein said determining an analyte comprises determining the amount of said analyte (Shultz et al., US 20170097337 A1: paras 0029, 0036; claim 9).
Regarding claim 13, Shultz and Pai teach all the limitations of claim 1. Shultz further teaches wherein said sample is a biological sample (Shultz et al., US 20170097337 A1: paras 0016-0017, and 0073-0074).
Regarding claim 14, Shultz teaches a device for determining an analyte suspected to be present in a sample comprising at least one sensor element comprising: (i) at least one binding agent which is capable of specifically binding to the analyte and which comprises at least one magnetic label, and in functional proximity thereto (ii) a magnetic tunnel junction generating a signal which is altered upon binding of the analyte to the binding agent, wherein said at least one binding agent is an aptamer or fragment thereof, wherein said at least one binding agent is altered in its structure upon binding to the analyte such that the position of the at least one magnetic label becomes located closer (positive mode) or farther away (negative mode) in respect to the sensitivity field of the magnetic tunnel junction (Shultz et al., US 20170097337 A1: (Figs. 6A-B and paras 0064, 0074, 0070-0072). Further, in a separate embodiment, Shultz teaches an aptamer as a detection agent that can be pre-conjugate with a magnetic label via chemical reactions (Shultz et al., US 20170097337 A1: paras 0064, 0071-0072). Shultz does not explicitly teach wherein the at least one magnetic label is permanently bound to, or is a part of, the at least one binding agent.
However, Pai, in the same field of endeavor, teaches an immobilized aptamer (binding agent) that has a magnetic label covalently, or irreversibly and permanently, bound to one end (Pai et al., US 9,599,591 B2: col 6, lines 47-63 and col 7, lines 9-24; col 10, lines 5-11; col 12, lines 12-17; Figs. 1A-B).
It would have been prima facie obvious, at the time of filing, to combine the teachings of a device using a structure-switching capture probe (binding agent) for binding a specific analyte with another embodiment teaching and an aptamer as a detection probe pre-conjugated with a magnetic label for detecting a target analyte both taught by Shultz in the same reference to arrive at a structuring switching (aptamer) capture probe pre-conjugated with a magnetic label. A skilled artisan would have recognized that a structure-switching capture probe has the same conformational property as the aptamer recited in the separate embodiment taught by Shultz and would have further reasonably recognized that this combination would necessarily and inevitably result in a simpler detection system not requiring separate detection antibodies and labels. Thus, a skilled artisan would have been motivated to combine the different embodiments taught by Shultz to simplify the method so that it would be capable of integrating into a point-of-care (POC) device. It would have been further prima facie obvious to combine the embodiments of Shultz with the teachings of an aptamer (binding agent) with a magnetic label permanently attached, as taught by Pai. Further, Pai discloses that a magnetic label that is not covalently and permanently bound to the aptamer (binding agent) is inadequate due to stability reasons (see Pai et al, col 6, lines 15-17). Thus, a skilled artisan would have been further motivated to combine these teachings because it would result in a stable structure-switching aptamer as a binding agent with a magnetic label that is stably and permanently attached resulting in a binding agent that is adequate for detecting a target analyte suspected to be present in a sample without the need for a detection antibody or separate labels. Combining the teachings of Shultz and Pai to arrive at a structure-switching aptamer (binding agent) immobilized on a sensor surface on one end and with a magnetic label covalently and permanently attached on the other end would necessarily and inevitable result in the magnetic label moving closer and farther away from an MTJ sensor’s sensing region upon conformational changes of the structure-switching aptamer induced by the binding of an analyte. The MTJ sensor would generate a signal due to the displacement/repositioning of the covalently and permanently attached magnetic label relative to the MTJ’s sensing region. Thus a skilled artisan would have been motivated to combine the teachings of Shultz and Pai because it would enable development of a simplified, sensitive, and specific analyte detection device without the need of an additional energy source(s) and the high costs associates with the optical detection of an analyte. A person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to combining known elements/ components, known to function the same separately as they would when combined, to yield expected and predictable results.
Regarding claim 15, Shultz and Pai teach all the limitations of claim 14. Shultz further teaches wherein said device further comprises:(iii) a detector unit capable of measuring the altered signal generated by the magnetic tunnel junction of the sensor element upon analyte binding to the at least one binding agent; and (iv) an evaluation unit capable of determining the analyte based on the signal which is generated by the magnetic tunnel junction (Shultz et al., US 20170097337 A1: paras 0070; 0074; 0048; and Fig. 5).
Regarding claim 16, Shultz and Pai teach all the limitations of claim 14. Shultz further teaches wherein said measuring the altered signal generated by the magnetic tunnel junctions of the sensor element upon analyte binding to the at least one binding agent comprises measuring at least one of the strength of the generated signal and its duration (Shultz et al., US 20170097337 A1: paras 0008, 0070, 0048, 0074; Figs. 1H and 3C-E).
It would have been prima facie obvious, at the time of filing, to combine the method for determining an analyte suspected of being present in a sample comprising an MTJ-based sensor, as taught by Shultz in all embodiments in the same reference, in view of the method for detecting an analyte suspected to be present in sample comprising an aptamer with a permanently attached magnetic label, as taught by Pai. A skilled artisan would have recognized that a structure-switching capture probe has the same conformational property as the aptamer recited in a separate embodiment by Shultz in the same reference. A skilled artisan would have reasonably recognized that combining these embodiments to arrive at the claimed invention would necessarily and inevitable result in a simplified detection method, by eliminating the need for separate detection probes, agents, and washes. A skilled artisan would have been motivated to combine these embodiments because the simplified detection method would be capable of integrating into a point-of-care device. Further, the MTJ sensor taught by Shultz operates by detecting perturbations in local (stray) magnetic fields and converting these perturbations into measurable changes in electrical resistance. Further, binding of an analyte to the structure-switching binding agent with a pre-conjugated and permanently attached magnetic label, as taught by Shultz in view of Pai, would necessarily and inevitably result in the location of the attached magnetic label to change relative to the MTJ sensing region. This displacement of the magnetic label relative to the MTJ sensing region would be detected by the MTJ sensor taught by Shultz and generate a signal. Thus, a skilled artisan would have been further motivated to combine these teachings because it would yield a sensitive device capable of detecting a specific analyte. A person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to combining known elements/ components, known to function the same separately as they would when combined, to yield expected and predictable results.
Regarding claim 17, Shultz and Pai teach all the limitations of claim 14. Shultz further teaches wherein said analyte is selected from the group consisting of a protein, peptide, virus, bacterial cell or small molecule (Shultz et al., US 20170097337 A1: para 0073).
Regarding claim 18, Shultz and Pai teach all the limitations of claim 14. Shultz further teaches wherein said determining an analyte comprises determining the presence or absence of said analyte (Shultz et al., US 20170097337 A1: para 0074).
Regarding claim 20, Shultz and Pai teach all the limitations of claim 14. Shultz further teaches the device of claim 19, wherein said determining an analyte comprises determining the amount of said analyte (Shultz et al., US 20170097337 A1: para 0074).
Regarding claim 21, Shultz and Pai teach all the limitations of claim 14. Shultz further teaches the device of claim 20, wherein said determining the amount of said analyte comprises counting the individual measured altered signals generated by the magnetic tunnel junctions (Shultz et al., US 20170097337 A1: paras 0008, 0074 and claim 9).
Regarding claim 25, Shultz and Pai teach all the limitations of claim 14. Shultz further teaches wherein said sample is a biological sample (Shultz et al., US 20170097337 A1: paras 0073-0074).
It would have been prima facie obvious, at the time of filing, to combine the embodiments and teachings of a method for detecting an analyte comprising a structure-switching capture probe with a pre-conjugated and covalently/permanently bound magnetic label, as taught by Shultz in the same reference, in view of Pai. A skilled artisan would have been motivated to combine these teachings because it would yield a simple and sensitive device capable of detecting a specific analyte suspected to be present in a biological sample. A person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to combining known elements/ components, known to function the same separately as they would when combined, to yield expected and predictable results.
Claims 7, 12, 19, 24, and 35, are rejected under 35 U.S.C 102(a)(1) as being unpatentable over Shultz et al., (US PG Pub No. 20170097337 A1, Pub. Date: 04/17/2017), in view of Pai et al., (U.S. Patent No. 9,599,591 B2, Date: 03/21/2017), as applied to claims 1 and 14, further in view of Gaster et al., (U.S. Patent No. US 9,506,919 B2, Date: 11/29/2016), and as evidenced by Chen et al., (Yi-Ting Chen, et al., Biosensing Using Magnetic Particle Detection Techniques, 2017, Sensors (Basel), 17(10): 2300).
The teachings of Shultz and Pai are discussed herein above.
Regarding claims 7 and 19, Shultz and Pai teach all the limitations of claims 1. Shultz and Pai do not teach wherein a sample is contacted by 100 or more proximity sensors or sensor elements.
Throughout the disclosure, Gaster teaches methods, devices, and kits for the detection and quantification of an analyte in a sample, including a magnetic tunnel junction sensor in contact with a sample, a proximity label (e.g., a magnetic nanoparticle), and a capture probe capable of specifically binding to an analyte (e.g., a protein or peptide). The magnetic particle can be directly conjugated or bound to the capture probe and is in functional proximity to the magnetic tunnel junction sensor. Upon binding of the analyte to the capture probe associated with the proximity label, a signal is obtained from the sensor to detect the presence of the analyte in the sample which can be further processed and evaluated by a computer. It is understood from the disclosure that “each of the individual embodiments described and illustrated (therein) has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments” (Gaster et al., US 9,506,919 B2: col 4, lines 52-56).
Gaster teaches a method and device wherein a sample is contacted by 100 or more proximity sensors or sensor elements (Gaster et al., US 9,506,919 B2: col 25, lines 19-24 and lines 34-36).
It would have been prima facie obvious for one having ordinary skill in the art, before the effective filing date, to combine the method comprising an aptamer (binding agent) with a magnetic label covalently and permanently bound as taught by Shultz, in view of Pai, with the teachings of Gaster in order to modify the method and device of determining the presence of an analyte taught by Shultz, in view of Pai, using the method and device of contacting a sample with 100 or more proximity labels taught by Gaster. A skilled artisan would have been motivated to combine these methods and devices and make this modification because increasing the amount of sensor elements would increase sensitivity, lower detection limits, improve accuracy, and allow for multiplexing. One having ordinary skill in the art would have a reasonable expectation of success because Gaster teaches contacting a sample with a 100 or more sensor elements to detect an analyte using a magnetic tunnel junction and a skilled artisan would apply these teachings with predicable results.
Regarding claims 12 and 24, Shultz and Pai teach all the limitations of claims 1. Shultz and Pai do not teach superparamagnetic or ferromagnetic nanoparticles: iron-platinum nanoparticles, iron nanoparticles, nickel nanoparticles, and cobalt nanoparticles.
However, Gaster, the same field of endeavor, teaches wherein said at least one magnetic label is selected from the group consisting of: iron-platinum nanoparticles, iron nanoparticles, nickel nanoparticles, and cobalt nanoparticles (Gaster et al., US 9,506,919 B2: col 9, lines 21-26 and lines 56-57).
It would have been prima facie obvious for one having ordinary skill in the art, before the effective filing date, to apply the method and device wherein at least one magnetic label is either iron-platinum nanoparticles, iron nanoparticles, nickel nanoparticles, and cobalt nanoparticles as taught by Gaster with the method and device for detecting an analyte using detection labels and a magnetic tunnel junction sensor as taught by Shultz, in view of Pai. One skilled in the art would have been motivated to apply the method and device of Gaster to the method and device of Shultz, in view of Pai, because iron-platinum-, iron-, nickel-, and cobalt-based nanoparticles are part of a finite number of metals routinely used in the art due to their known magnetic properties and are routinely used with magnetic sensors (see Chen et al., 2017, Sensors (Basel), 17(10): 2300). One would have a reasonable expectation of success because a skilled artisan would have recognized that applying one of these known elements, from a finite number of identified potential solutions, would yield predicable results.
Regarding claim 35, Shultz and Pai teach the device of claim 14. Shultz and Pai do not teach a kit for determining an analyte suspected to be present in a sample comprising the device of claim 14.
Gaster teaches kit for determining an analyte suspected to be present in a sample comprising the device of claim 14 (Gaster et al., US 9,506,919 B2: col 33, lines 41-55).
It would have been prima facie obvious for one having ordinary skill in the art, before the effective filing date, to combine the device in claim 14 taught by Shultz, in view of Pai, with the kit taught by Gaster. A skilled artisan would have been motivated to combine the device taught by Shultz, in view of Pai, with the kit taught by Gaster because it would allow for the method and device of detecting the presence of an analyte in a biological sample to be a standardized, cost-effective, and straightforward test without requiring complex optimizations and ensuring reproducible results. One would have a reasonable expectation of success because Gaster teaches the use of a kit for detecting the presence or absence of analyte in a biological sample and a person having ordinary in the art would have recognized that combining this improvement to the teachings of Shultz, in view of Pai, would yield predicable results.
Response to Arguments
Claim Rejections Under 35 U.S.C. § 112(b)- Indefiniteness
Regarding rejection under 35 U.S.C. 112(b) of independent claims 1 and 14 and dependent claims 2-8, 12, 13 15-21, 24-25, and 35, Applicant traverses this rejection and presents arguments, filed on 04/29/2026. Applicant’s arguments have been fully considered and are persuasive. The 35 U.S.C. § 112(b) rejection of independent claims 1 and 14 and dependent claims 2-8, 12, 13 15-21, 24-25, and 35 is withdrawn.
Claim Rejections Under 35 U.S.C. § 102- Anticipation
Regarding rejection under 35 U.S.C. 102 of claims 1-6, 8, 13-21 and 25, Applicant traverses this rejection and presents arguments, filed on 04/29/2026. Applicant argues that (B1 and B2) the reference, Shultz, does not disclose a binding agent that comprises a magnetic label permanently bound or forming a part of the binding agent. Applicant’s arguments have been considered but are moot because amendments to claim 1 necessitated a new ground of rejection that does not rely solely on the reference applied in the prior rejection of record for the teaching or matter specifically challenged in the argument.
Applicant further argues (B3) that the base reference, Shultz, does not disclose the claimed detection principle comprising a signal generated by the repositioning of an attached magnetic field relative to the MTJ sensitivity field.
This is not persuasive. The detection principle recited in the instant claims and in the base reference, Shultz, is based on an MTJ sensing element. MTJ sensors operate by detecting perturbations in local (stray) magnetic fields and converting these perturbations into measurable changes in electrical resistance. The new introduction of a magnetic label into the sensing region of an MTJ sensor and the repositioning/ displacement of an existing magnetic label relative to the sensing region both alter/produce changes in the local (stray) magnetic field and are both detectable by an MTJ sensor. Thus, whether a magnetic label newly enters the sensing region or is already present and changes its position relative to the sensor, the fundamental detection principle remains the same: the MTJ sensor detects changes in the local (stray) magnetic field generated by the magnetic label.
Applicant further argues that (B4) Examiner’s anticipation reading §102 impermissibly combines distinct Shultz embodiments. Applicant’s arguments have been considered but are moot because amendments to claim 1 necessitated a new ground of rejection that does not rely solely on the reference applied in the prior rejection of record for the teaching or matter specifically challenged in the argument.
Applicant further argues (C) the rejection of the dependent claims 2-6, 8, 13, 15-21, and 25 as being dependent on amended claims 1 and 14, and thus argues the 102 rejection for dependent claims should be withdrawn. Applicant’s arguments have been considered but are moot because amendments to claims 1 and 14 necessitated a new ground of rejection that does not rely solely on the reference applied in the prior rejection of record for the teaching or matter specifically challenged in the argument.
Claim Rejections Under 35 U.S.C. § 103- Obviousness
Regarding rejection under 35 U.S.C. 103 of claims 7, 12, 19, 24, and 35, Applicant traverses this rejection and presents arguments, filed on 04/29/2026. Applicant argues (A) that the motivation and expectation of success for combining Shultz and Gaster is lacking and/or insufficient. Applicant’s arguments have been considered but are moot because amendments to claims 1 and 14 necessitated a new ground of rejection that does not rely solely on the references applied in the prior rejection of record for the teaching or matter specifically challenged in the argument.
Applicant further argues (B) that it is impermissible to select only those aspects of a reference that support a desired conclusion while ignoring aspects that contradict it; (C) amendments to claims 1 and 14 overcome the Office’s obviousness reasoning; and (D1) Shultz does not disclose the claimed detection principle comprising a permanently attached magnetic label and Gaster does not supply the missing limitation. Applicant’s arguments have been considered but are moot because amendments to claims 1 and 14 necessitated a new ground of rejection that does not rely solely on the references applied in the prior rejection of record for the teaching or matter specifically challenged in the argument.
Applicant further argues that (D2) (1) Chen does not disclose the claimed detection principle and supplies only evidence of known magnetic label compositions and (2) Chen does not address fundamental deficiencies in the Shultz-Gaster combination with respect to the claimed detection principle comprising the repositioning of an attached magnetic label relative to an MTJ sensitivity field upon analyte binding, and therefore, adds nothing to the obviousness analysis.
This is not persuasive. Chen, as an evidentiary reference, presents the current state of the art, at the time of filing, summarizing that, due to their known magnetic properties, iron-platinum, iron, nickel, and cobalt nanoparticles are well-known, routine, and conventional in biosensing applications including with GMR- and (TMR) MTJ-based sensors. Further, Chen suggests the combination of iron-platinum-, iron-, nickel-, and cobalt-based nanoparticles with GMR and MTJ sensors. Thus, it would have been obvious to a skilled artisan to combine Shultz and Gaster, in light of the evidence presented by Chen, and try the finite number of known solutions including iron-platinum-, iron-, nickel-, and cobalt-based nanoparticles with applications to an MTJ sensor to determine the optimal nanoparticle for the method and device recited in the instant claims to arrive at the claimed invention.
Further, GMR and MTJ sensors operate by detecting perturbations in local (stray) magnetic fields and converting these perturbations into measurable changes in electrical resistance. The disclosed embodiments in Shultz comprising the newly introduced and unbound magnetic label into the sensing region of an MTJ sensor (label is farther away) that then comes closer to the sensing region of an MTJ sensor when bound and the recited embodiment comprising the repositioning/displacement of an existing and bound magnetic label relative to the MTJ sensing region would necessarily and inevitably result in altering/producing changes in the local (stray) magnetic field that would be detectable by MTJ and GMR sensors for all aforementioned embodiments. Thus, whether a magnetic label is farther away as it newly enters and then is positioned closer to the sensing region when bound or is already present/bound and changes its position relative to the sensor due to conformational changes of the binding agent the label is attached to, the fundamental detection principle remains the same: MTJ and GMR sensors detect changes in the local (stray) magnetic field generated by the magnetic label when it first comes into the sensing region and/or moves its position within and relative to the sensing field.
Applicant further argues that (D3) the Office’s combination of Shultz and Gaster lacks sufficient motivation to arrive at the detection principle such that the magnetic label would be permanently bound to form a part of the binding agent and such that the signal would be generated by the repositioning of that attached label upon analyte-induced conformational change of the binding agent. Applicant’s arguments have been considered but are moot because amendments to claims 1 and 14 necessitated a new ground of rejection that does not rely solely on the references applied in the prior rejection of record for the teaching or matter specifically challenged in the argument.
Applicant also argues that (D3, second para) that the Office provides no motivation, grounded in cited references of Shultz, Gaster, or Chen, to modify any disclosed detection schemes such that the magnetic label would be permanently bound to or form part of the binding agent such that the signal would be generated by the repositioning of the attached label upon analyte-induced conformational change of the binding agent. Applicant’s arguments have been considered but are moot because amendments to claims 1 and 14 necessitated a new ground of rejection that does not rely solely on the references applied in the prior rejection of record for the teaching or matter specifically challenged in the argument.
Applicant further argues that (E) the Office’s reasoning for the obviousness rejection reflects impermissible hindsight reconstruction and a PHOSITA would have no basis, drawn from Shultz, Gaster, or Chen, to arrive at the amended limitation(s) of a single binding agent capable of both comprising the magnetic label as a permanently attached component and undergo an analyte-induced conformational change and repositioning of the label relative to the MTJ sensitivity field. Applicant’s arguments have been considered but are moot because of the aforementioned amendments to claims 1 and 14 necessitated a new ground of rejection that does not rely solely on the references applied in the prior rejection of record for the teaching or matter specifically challenged in the argument.
Conclusion
All examined claims are rejected. No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA L LIRIANO-NG whose telephone number is (571)272-0085. The examiner can normally be reached Monday-Friday, 7:30 am-3:30 pm (EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached at (571)272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MELISSA LIZETTE LIRIANO-NG/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 July 1, 2026
Prosecution Insights