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 .
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.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-4, 8-11, 14, 16-18, 20, 22, 25, 29 and 33-35, and the species of reporter binding moieties associated with reagent species as recited at claim 35 (each reporter binding moiety having a corresponding tag, the tag comprising desthiobiotin, binding partner to the tag comprising streptavidin, the reporter binding moiety having a first oligonucleotide bound thereto, the reporter having a second oligonucleotide bound thereto, wherein the second oligonucleotide is configured to hybridize to the first when the tag (desthiobiotin) interacts with the tag binding partner (streptavidin), in the reply filed on 01/06/2026 is acknowledged.
Applicant’s election of Group I in the reply filed on 01/06/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
No claims appear to be withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species of invention (not the elected reporter binding moiety associated reagent species), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/06/2026.
Priority
Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT Application No. PCT/IB2021/057294, filed 08/06/2021, which claims benefit under 35 U.S.C. 119(e) to provisional application No. 63/063,028, filed 08/07/2020.
Information Disclosure Statement
The information disclosure statements (IDS) filed 02/03/2023, 06/14/2023 and 08/08/2025 are considered, initialed and are attached hereto.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4, 8-11, 14, 16-18, 20, 22, 25, 29 and 33-35 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 35 each recite “each reporter configured to generate a corresponding different signal” at step (c), the claim later recites at (e), “based on detection of a signal generated by each of the reporters”. The claim language at step e is indefinite because the language “a signal generated” does not clearly refer back to the different signals corresponding to each of the reporters. It is suggested that Applicant amend the claims to improve clarity, and recite something such as “based on detection of the different signals corresponding to each of the plurality of reporters”.
Claim 2 references the trademark/trade names “SNAP”, “CLIP”, “Myc” and “FLAG” (referring to SNAP™-tag, CLIP™-tag, Myc™-tag, and FLAG™-tag). Where a trademark or trade name is used in a claim as a limitation to identity or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b). See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. In the instant case, the trademark/trade names are being used to identify/describe specific amino acid tags.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 20 recites the broad recitation “at least six analytes”, and the claim also recites “at least four analytes” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. For example, “at least 4 analytes” is already encompassed in “at least 6 analytes”.
Claim 22 recites the limitation "the magnetic particle" in lines 6 and 7. There is insufficient antecedent basis for this limitation in the claim. The claim encompasses two instances of magnetic particles, namely the magnetic particle of the magnetic conjugate of claim 1 and the additional “magnetic particle conjugate” introduced by the pretreatment step, recited as a distinct particle separate from the particle of the magnetic conjugate of claim 1. As such, the language “the magnetic particle” is indefinite because it is not clear which particle the claim is in reference to.
Claim 25 recites “wherein the method is suitable for point-of-care usage, field usage, home usage, and/or wherein the method is compatible with the World Health Organization’s ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable) criteria. The claim is indefinite because the limitations impart a functional characteristic/result to the claimed method, but does not clearly impart any specific or particular step or reagent in addition to those already recited at independent claim 1. Given that there is no additional step/element recited or clearly tied to limitations of claim 25, the claim is indefinite because it is not clear if those methods limited to those steps/elements at claim 1 would necessarily be considered to meet the claimed characteristics, or rather if the recited language is intended as imposing some additional limitation in terms of structure or method steps performed as part of the claimed invention, which results in the method being considered suitable for those purposes as claimed.
Even further the claim recites parenthesis in the claims. The parenthesis raises question as to what is actually required by the claim. It is not readily clear if the terms inside the parenthesis are required by the claim, for example if combability with WHO’s ASSURED requires that the claimed method be/meet each of “affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable”, and even further what is meant by each of these (for example, equipment-free, it is not clear what is and is not encompassed by “equipment free”, for example, as all assays, to some extent, require some form of equipment/structural components).
Similarly, claim 29 recites “wherein the method is substantially free of false positives; substantially free of false negatives; provides better sensitivity and specificity than a method using a solid phase immunoassay; and/or provides better sensitivity and specificity than a method using a bead-based flow cytometry-based assays, optionally bead-based, flow cytometry- based assays and/or wherein the method provides better sensitivity and specificity than a method using a lateral flow immunochromatographic assay”, however, the claimed limitations appear to be a direct result of the method steps/reagents as recited at claim 1. The claim is indefinite because the claim does not clearly impart any additional claimed steps/elements (the claimed limitations do not appear to be a result of any further implied limitations to the claimed method in addition to claim 1), as a result, it is unclear methods limited to those steps/elements at claim 1 would necessarily be considered to meet the claimed characteristics, or rather if the recited language is intended as imposing some additional limitation in terms of structure or method steps performed as part of the claimed invention,
Claim 34 is indefinite because while it appears that “portions” is recited in terms of referring to different locations in terms of different epitopes of the same antigen/analyte, the term portions could be interpreted as referring to amounts/volume. As such, the recited language is indefinite and it is suggested that “portions” be amended in order to recite something such as “different epitopes”, consistent with language as shown in the PG Publication of the instant application at para [0065] (see for example, at least at para [0116] of the PG publication of the instant application, the term “portions” is also used by applicant to reference volume).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-2, 4, 8-11, 17-18, 20, 25, 29, 33 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Carron et al., US PG Pub No. 2006/0240572A1 (referred to as Carron et al. (2006)) in view of Carron et al., WO2012030870A1 (referring to as Carron et al. (2012)), Neely et al., US PG Pub No. 2013/0196341A1 (IDS entered 06/14/2023) and Molecular Probes™ Handbook Chapter 4 Biotin and Hapten Derivatives. ThermoFisher Scientific, 2010, (21 pages), https://www.thermofisher.com/content/dam/LifeTech/global/technical-reference-library/Molecular%20Probes%20Handbook/chapter-pdfs/Ch-4-Biotin-Hapten-Derivatives.pdf?icid=WE216841.
Carron et al. (2006) teach a method for detecting a plurality of analytes in a biological sample (para [0018], samples such as e.g., blood, paras [0061] and [0076]). The method of Carron et al. comprises bringing into contact a sample with at least one magnetic conjugate comprising a magnetic particle and a plurality of capture moieties coupled to the magnetic particle, each configured to bind corresponding analytes of a plurality of analytes (paras [0033] and [0076]-[0077], particle 22 coated with antibodies 26a, see figure 9), and a plurality of reporter moieties that bind a corresponding plurality of the analytes (each reporter has a binding agent specific for a particular analyte, see Figure 9), each reporter moiety having thereon a reporter that is spectrally distinct (each configured to generate a corresponding different signal). Carron et al. further teach, following binding of the analyte, magnetic conjugate and reporter moieties, magnetically localizing (applying a magnetic field to separate the magnetic conjugate bound complex), for detection of each analyte based on the detection of signal generated by each of the reporters (paras [0018]-[0019] and [0023].
Carron (2006) does teach each of the components brought into contact to cause formation of the complex, see at for example para [0092] and Figure 23, one embodiment describes Carron et al. performed in the order of, adding together sample and paramagnetic particles (scene 2), adding spectral enhancement particles (reporter moieties, see scene 4), localizing complex with the applied magnetic field (scene 4), detecting (scene 5).
Carron et al. (2006) teaches one type of antibody (26a) that binds multiple different antigens (see Figure 9) provided on the capture particle, and as such does not clearly teach “a plurality of capture moieties…configured to bind a corresponding analyte of the plurality of analytes” (this language suggests a plurality of different antibody species on the sample magnetic particle).
Carron et al. (2006) teaches reporter moieties bound to the reporter, and as such fails to teach a step of contacting with a plurality of reporter binding moieties having a corresponding tag bound thereto, followed by contacting with a plurality of reporters each having a corresponding tag binding partner configured to bind a corresponding tag.
Carron et al. (2012) is similar to Carron (2006), in that the reference similarly describes multiplex particle based immunoassay for detection of a plurality of target analytes simultaneously (e.g., see paras [0015], [0017] and [0048]). See at para [0048], Carron (2012) describes figure 16B, unlike Carron et al. (2006) teaching a capture particle with an antibody that binds a plurality of targeted analytes, Carron (2012) demonstrate a motive particle (capture particle) having thereon a plurality of different receptors specific to corresponding plurality of different analytes.
Neely et al., also similarly to Carron (2006), demonstrate particle-based assay format for the detection of an analyte, see for Example Neely at figure 4, and described at para [0137]. Regarding the detectable label component of Neely, see Neely describe a component (referred to by Neely as target probe), comprising a second binding group, 423 (binding group specific for a different part of the targeted analyte different from that on the capture particle), the binding group attached to a reporter particle, 430, by way of a target probe, 420 bound to the reporter particle at a binding/active site on the target probe. Neely describe a target probe (comprising for example two or more binding groups, see para [0021], via specific binding interaction). See for example para [0029], Neely describe a reporter particle comprising biotin binding groups capable of binding a target probe via biotin-avidin binding interaction, or a detector moiety comprising a plurality of avidin functionalized biding groups capable of binding a reporter particle via biotin-avidin binding (see also paras [0033] and [0083]).See also para [0090], Neely describe a reporter particle can be bound to an analyte or analyte-target probe complex during the binding with a detector moiety, or alternatively can be disassociated and then contacted with the detector moiety.
ThermoFisher Scientific teach biotin and desthiobiotin conjugates, ThermoFisher Scientific teach the use of biotin-streptavidin binding/bridge in order to amplify detection of biotinylated targets (see starting on page 164, see page 166, col. 1, para 2, page 167, col. 2, para 2).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the capture particle in the method of Carron (2006) (the particle comprising one antibody (binding moiety) that binds a plurality of targeted analytes) to instead provide a plurality of target analyte specific antibodies (binding moieties) as a simple substitution of one known capture particle binding format for another. In particular, the prior art contained the particle binding assay as taught by Carron et al. (2006), which differed from the claimed binding format by the substitution of the capture moieties (antibody). In particular, Carron (2006) teach binding a plurality of targeted analytes using a plurality of capture antibody on a carrier particle (magnetic particle), however Carron only shows one type of capture antibody. The prior art demonstrates that alternative to a single plurality of antibodies to bind a plurality of different target analytes, it is known in the art (Carron et al. (2012)) to alternatively rely on a plurality of distinct antibodies on a single particle to capture the plurality of different analytes. The prior art supports that the substituted techniques (one antibody for a plurality of targeted analytes, or a plurality of antibodies for a plurality of target analytes) and their functions were known in the art. One having ordinary skill in the art would have found it obvious to have substituted one known binding format for the other and the results of the substitution would have been predictably been the same.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the reporter moieties of Carron et al. (2006) in order to provide the binding moiety for analyte bound/linked to the reporter via biotin/streptavidin binding system, as in Neely et al. or ThermoFisher Scientific as an obvious matter of applying a known technique to a known method, one further motivated to apply this technique in order to achieve signal amplification (the biotin/avidin system bridging the binding moiety for analyte to the reporter resulting in amplified detection, as taught by ThermoFisher Scientific). In particular, the prior art contained the base method as taught by Carron et al. (2006) (see as described in detail previously above), further the technique of linking binding moiety for analyte and reporter particle by way of linking system, such as a biotin/avidin system (biotinylated conjugate and avidin labeled reporter) was a technique known to those of ordinary skill in the art (see for example Neely), and was known to result in amplification of signal (ThermoFisher Scientific). One having ordinary skill in the art would have recognized that applying the technique would have yielded a predictable result, namely would not be expected to interfere with detection, and rather would be expected to improve detection (by amplifying signal, report and binding moiety still would be linked, linked through the biotin-avidin binding system).
Further, see as cited above, Neely describe a reporter particle can be bound to an analyte or analyte-target probe complex during the binding with a detector moiety, or alternatively can be disassociated and then contacted with the detector moiety, as such, it would have been further obvious to have modified the method to include an additional step, following binding with reporter binding moiety (biotin tagged antibody), to contact complex with avidin linked reporter to achieve binding/association of reporter and antibody for detection, as a further obvious matter of applying a known technique to a known method, in view of Neely which teach either binding already associated, or dissociated components. One having ordinary skill would have had a reasonable expectation of success because the modification would be expected to achieve the same outcome (either order, already associated or disassociated), namely reporter would still conclude bound to target analyte through the linked system.
Although Neely is teaching biotin/avidin binding/bridge system, see further as cited above ThermoFisher teach biotin or desthiobiotin conjugates as alternatives usable for the same purpose. One having ordinary skill in the art would have found it prima facie obvious to one of ordinary skill in the art to substitute desthiobiotin for biotin based on ThermoFisher since the reference refers to each for the same purpose. Further, it would have been considered prima facie obvious to try, namely, to try desthiobiotin in place of biotin for this same reason (considering ThermoFisher indicates both biotin and desthiobiotin conjugates as known and available to those of ordinary skill in the art). As such, one having ordinary skill would have a reasonable expectation of success using one in place of the other.
Regarding claims 2 and 4, see the combination of the cited art teaches tag comprises a biotin or desthiobiotin (see the combination of the cited art detailed above, it would have been obvious to have used either, one in place of the other) and the tag partner is streptavidin.
Regarding claim 8, see figure 9, Carron et al. (2006) is teaching capture moieties and reporter binding moieties as first and second antibodies (see figure 9, and e.g., paras [0065], [0069]).
Regarding claim 9, see Carron et al. (2006) teach antibodies used to detect an analyte that is a protein antigen.
Regarding claims 9-11, see further Carron (2012) teach target analyte can be an antigen or antibody of interest (para [0020]). It would have been further obvious to have modified the method of Carron et al. (2006) to detect either protein or antibody, detecting antibody an obvious matter of a simple substitution of one targeted analyte for another, both known detectable with a system as taught by the cited art (both Carron 2006 and 2012 teaching particle based capture and detection of an analyte), further the combination teaching detecting presence/quantity of the target.
Regarding claim 10, see Carron et al. (2006) and the combined cited prior art is teaching an antibody on the capture molecule and a second antibody associated with the reporter (reads on “secondary antibody”, as is secondary to the first antibody that binds associated with the magnetic particle).
Regarding claim 17, see the combination of the cited art is teaching reporters that produce different spectral signals (differentially detectable).
Regarding claim 18, Carron et al. teach, for example, sample such as blood.
Regarding claim 20, although the example of Carron et al. cited above demonstrates detection of 3 analytes, see at para [0076] Carron teach the concept lends itself to multiplex assay for a large number of analytes in a single sample; see further para [0065], tens, hundreds, thousands or more analytes may bind, thereby addressing at least 4 or at least 6 analytes (the method as taught by the combination of the cited art is expected to bind at least 4 or 6 as claimed, and more).
Claim 25 of the present application recites “the method is suitable for point of care usage, field usage, home usage, and/or wherein the method is compatible with the World Health Organization’s ASSURED…criteria”; however, it is not clear what specific method steps or structure the claimed functional language “suitable for” implies or imposes to the claimed methods or reagents included in the claimed methods. In particular, given broadest reasonable interpretation, it appears the method as taught by Carron and the cited art could be performed/used in “field” or “home”.
Claim 29, see as discussed in detail above, the multiplex detection taught by the combination of Carron et al. (2006) in view of the cited art would be expected to result in “better sensitivity and specificity” than other methods such as those claimed (see paras [0097], [0098] significant increase in sensitivity observed, see also paras [0025], [0026], [0054], [0064] compared to lateral flow immunoassay).
Nonetheless, it is also noted that other than the functional limitations regarding false results and specificity/sensitivity recited at claim 29, claim 29 recites no additional specific method steps or specific reagents/components attributed to the claimed functional results. The combination of the cited prior art teaches a method as claimed (comprising the same method steps/reagents), as a result it would be expected capable of the same functional results specific to sensitivity/specificity and false results.
Regarding claim 33, see for example para [0092] and Figure 23, Carron describe applying a reducing the magnetic field between steps, the method separating analyte from sample by applying the magnetic field, reducing the magnetic field before contacting with reporter moieties.
Regarding claim 34, see as cited in detail previously above, Carron’s citation describe antibodies that bind analyte at different portions (positions) of the analyte.
Claim(s) 14 is rejected under 35 U.S.C. 103 as being unpatentable over Carron et al. (2006), in view of Carron et al. (2012), Neely et al. and ThermoFisher Scientific, as applied to claim 1 above, and further in view of Lambert et al., US PG Pub No. 2008/0032420A1.
Carron et al. (2006) is teaching reporter particles that are active SERS metal particles (abstract), see for example, para [0018], report is spectral enhancement particle comprised of an active SERS metal coated with a material that provides a unique spectrum signature (Raman spectroscopy reporters).
Carron et al. fail to teach reporter comprises a plurality of quantum dots (claim 14).
See Lambert et al., Lambert teach multiplex detection employing species of SERS nanoparticles having a unique Raman shift (abstract). In particular, Lambert teach Quantum dots as suitable labels, see para [0007], Lambert teach quantum dots allow multiplex detection, that they have high quantum efficiency, resist photobleaching, and can be produced in colloidal suspensions with a narrow emission spectrum, they can be selected to achieve emission in a variety of colors. Lambert (para [0007]) recognize quantum dots and SERS nanoparticles each as desirable reporters (referred in Lambert as tags). See throughout Lambert, the references teaches either of quantum dots or SERS nanoparticles for spectral multiplex detection (see e.g., para [0011], [0024], [0028]. See also para [0098], biotinylated antibodies, avidin coated quantum dots, when incubated together, the antibodies bind the quantum dots at the biotin-avidin connection.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to have modified the method of Carron et al. (2006), in order to use quantum dots for spectral multiplex detection in place of the SERS active nanoparticles of Carron et al. (2006) because both were recognized in the art suitable for the same purpose (spectral multiplex detection of a plurality of analytes in a sample), the modification a simple substitution of one known label for another, both usable and available to those of ordinary skill for the same purpose. Even further, one having ordinary skill would have been motivated considering the benefits/advantages afforded by quantum dot labels, as recognized by Lambert (namely, as having high quantum efficiency, resist photobleaching, and can be produced in colloidal suspensions with a narrow emission spectrum, they can be selected to achieve emission in a variety of colors).
Because of their advantages, and because they are recognized as both suitable for the same purpose, one having ordinary skill in the art would have a reasonable expectation of success using one in place of the other. Even further, Lambert et al. teach quantum dots can be linked to antibody reagent via biotin/avidin linkage, and as such one having ordinary skill would further have a reasonable expectation of success modifying the combination of the cited art with Lambert (see the combination detail previously above relative to claim 1, it would have been obvious to have linked via a biotin/avidin system for the reasons discussed previously above).
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Carron et al. (2006), in view of Carron et al. (2012), Neely et al. and ThermoFisher Scientific, as applied to claim 1 above, and further in view of Glass et al., A combination of labeled an unlabeled antibody enables self-calibration and reduction of sample matrix effects in immunoassay, Analytical Biochemistry, 331, (2004), p. 68-76.
Carron et al. (2006) and the cited prior art teach a method substantially as claimed, however fails to teach wherein a concentration of the reporter binding moiety is greater than a concentration of the reporter, optionally at least 5 times greater, or at least 10 times greater, or at least 100 times greater, or at least 1000 times greater, optionally about 1000 times greater.
Glass et al. teach sample matrix is considered to be everything else in a sample, other than the analyte itself (see page 68, col. 1, para 1). Glass teach matrix effects in immunoassay are well known, if not always well understood (also para 1). Glass teach a technique comprising adding excess unlabeled antibody (the same antibody used for detection, but unlabeled) to bind analyte without changing detection antibodies’ response to the matrix component (page 69, col. 1, para 2). Glass teaching (page 69, col. 1, para 3), for optimum sensitivity, the labeled detection concentration will be approximately equal to the Kd of the antibody, and this concentration will also be a near the midpoint of the assay working range for analyte; see further teaching adding unlabeled antibody in significant excess (approximately 100 fold above the labeled antibody concentration) results in binding of essentially all the specific analyte, while simultaneously reducing to near zero the amount of labeled antibody bound to analyte.
It would have been prima facie obvious to one having ordinary skill before the effective filing date of the claimed invention, to have modified the method as taught by Carron et al. and the cited art, in order to provide reporter binding moiety at a greater concentration than the amount of reporter (for example, 100X), such that upon binding there will be both labeled and unlabeled antibody for detection in order to address any potential matrix effects which may affect results(Glass et al.). One having ordinary skill in the art would have had a reasonable expectation of success because glass teach it is recognized in the art that matrix is considered everything other than analyte in a sample, and the effects caused by matrix are well known and understood in the prior art. Considering Carron et al. and the cited art teach an assay involving detection antibody for binding/detection analyte in a sample, it would be expected that the method would similarly be subject to potential matrix effects and that applying the technique of Glass would improve sensitivity by neutralizing any such matrix effects.
Claim(s) 22 is rejected under 35 U.S.C. 103 as being unpatentable over Carron et al., (2006) in view of Carron et al. (2012), Neely et al. and ThermoFisher Scientific, as applied to claim 9 above, and further in view of Safarik et al., Magnetic techniques for the isolation and purification of proteins and peptides, BioMagnetic Research and Technology, 2(7), (2004), 17 pages.
Carron et al. (2006) and the cited prior art teach a method substantially as claimed (see above), however fails to teach the method comprising a step of pre-treating the sample with a magnetic conjugate comprising a magnetic particle and a moiety configured to bind contaminant antibodies and/or non-antibody moieties, wherein the pre-treating reduces or eliminates one or more of a-c as claimed (claim 22). Safarik et al. teach, regarding magnetic separation techniques utilizing small magnetic particles, that magnetic beads in many cases exhibit low non-specific binding of non-target molecules present in different samples (see page 5, col. 1, para 3). Safarik teach certain samples may require preclearing to removed molecules which have high non-specific binding activity, that if pre-clearing is needed, the sample can be mixed with magnetic beads not coated with affinity ligand, or with secondary antibody or irrelevant antibody (see at para 3).
It would have been prima facie obvious to one having ordinary skill in the art to have modified Carron et al. in view of the cited art, to further perform a pre-treatment step comprising contacting sample with magnetic particle comprising antibody/irrelevant antibody in order to remove interfering substances in samples, one having ordinary skill in the art would have been motivated to introduce such a pre-treatment step because small magnetic beads were known/recognized in the prior art as exhibiting non-specific binding so this is an expected issue when performing assays utilizing such particles/beads, the modification is an art recognized technique known to reduce interference (Safarik). One having ordinary skill would have a reasonable expectation of success because the assay of Carron et al. involves magnetic separation/concentration, and since such particles are known to be subject to low non-specific interference, it would be expected that the assay would benefit from the technique as in Safarik.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
16/479,827
Claims 1, 2, 8-11, 14, 18, 20, 25, 29, 33 and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13, 35-38, 41-42, 44-47 and 50 of copending Application No. 16/479,827 in view of Carron et al. (2012).
Copending ‘872 recites a method substantially as claimed at claim 1, comprising steps (a)-(e) (see copending ‘872 at claims 13 and 42), comprising the same steps of contacting with at least one magnetic conjugate comprising an antibody for analyte, contacting with a plurality of reporter binding moiety (plurality of quantum dots), reporter binding moiety comprising tag and reporter having binding partner that binds the tag (see copending, refers to biotin/streptavidin, thereby also addressing present claim 2), applying a magnetic field to separate, and detecting presence, absence or level of analyte.
The copending application recites a method substantially as claimed, however fails to teach the magnetic particle comprising a plurality of capture moieties configured to bind corresponding analyte (claim 1).
Carron et al. (2012) similarly describes multiplex particle based immunoassay for detection of a plurality of target analytes simultaneously (e.g., see paras [0015], [0017] and [0048]). See at para [0048], Carron (2012) describes figure 16B, unlike Carron et al. (2006) teaching a capture particle with an antibody that binds a plurality of targeted analytes, Carron (2012) demonstrate a motive particle (capture particle) having thereon a plurality of different receptors specific to corresponding plurality of different analytes.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the capture particle of the copending application in order to instead provide a plurality of target analyte specific antibodies (binding moieties) as a simple substitution of one known capture particle binding format for another. In particular, the prior art contained the particle binding assay as taught by the copending application, which differed from the claimed binding format by the substitution of the capture particle comprising plurality of capture moieties (antibody). In particular, the copending application recites binding targeted analytes using a capture antibody on a carrier particle (magnetic particle) and a plurality of detection particles (quantum dots), however only shows one type of capture antibody. The prior art demonstrates that alternative to a single plurality of antibodies to bind a plurality of different target analytes, it is known in the art (Carron et al. (2012)) to alternatively rely on a plurality of distinct antibodies on a single particle to capture the plurality of different analytes. The prior art supports that the substituted techniques (one antibody for a plurality of targeted analytes, or a plurality of antibodies for a plurality of target analytes) and their functions were known in the art. One having ordinary skill in the art would have found it obvious to have substituted one known binding format for the other and the results of the substitution would have been predictable, and as such (because it would have been predictable), one having ordinary skill in the art would have a reasonable expectation of success.
Regarding claim 8, the copending application and the cited art address the claim, teaching first antibody, and second antibody that bind the analytes.
Regarding claim 9, see the copending recites antibodies used to detect an analyte that is a protein antigen.
Regarding claims 9-11, see further Carron (2012) teach target analyte can be an antigen or antibody of interest (para [0020]). It would have been further obvious to have modified the method of the copending application in order to detect either protein or antibody, detecting antibody an obvious matter of a simple substitution of one targeted analyte for another, both known detectable with a system as taught by the cited art (both the copending and 2012 teaching particle based capture and detection of an analyte), further the combination teaching detecting presence/quantity of the target. Regarding 11, the combination of the cited art addresses “providing an amount of antibodies”, as claimed”.
Regarding claim 14, see copending as cited above, teaching a plurality of quantum dots.
Regarding claim 18, the copending application recites sample, but fails to specify the type of sample (teaching examples of protein biomarkers detected in a sample).
However, Carron et al. (2012) teach the assay applicable to detect protein targets in samples such as blood (para [0024]) for example.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have applied the method for detection of protein target analytes in samples such as blood as an obvious matter of applying a known method to detect target in a known sample. In particular, Carron et al. is a magnetic particle assay similar to that of the copending application, Carron et al. supporting detection in samples including blood, as a result one of ordinary skill would have a reasonable expectation of success. Further one would have an expectation of success considering the copending does not limit to a particular sample type.
Regarding claim 20, the copending application teaches 4 analytes, the copending in light of the prior art addresses multiplex detection for at least 4 analytes.
Claim 25 of the present application recites “the method is suitable for point of care usage, field usage, home usage, and/or wherein the method is compatible with the World Health Organization’s ASSURED…criteria”; however, it is not clear what specific method steps or structure the claimed functional language “suitable for” implies or imposes to the claimed methods or reagents included in the claimed methods. In particular, given broadest reasonable interpretation, it appears the method as taught by Carron and the cited art could be performed/used in “field” or “home”.
Regarding claim 29, the claim recites the method is “substantially free of false positives, … negatives, provides better sensitivity and specificity…etc.”, however, claim 29 recites no additional specific method steps or specific reagents/components attributed to the claimed functional results. The combination of the copending and the cited prior art teaches a method as claimed (comprising the same method steps/reagents), as a result it would be expected capable of the same functional results specific to sensitivity/specificity and false results.
Regarding claim 33, see copending claim 41.
Regarding claim 34, see the copending claims are silent as to whether the antibodies bind at different locations.
However, see Carron et al. (2012), at for example para [0026], Carron teach antibodies that bind different sites on an antigen.
It would have been further prima facie obvious to one having ordinary skill in the art to have modified the copending application such that the antibodies bind different sites on an antigen (different locations), as an obvious matter of applying a known technique for performing a two antibody binding assay (two antibodies that bind for detection of same antigen). One having ordinary skill having a reasonable expectation of success applying a known technique.
Claim 4 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13, 35-38, 41-42, 44-47 and 50 of copending Application No. 16/479,827 in view of Carron et al. (2012), as applied to claim 1 above, and further in view of ThermoFisher Scientific.
The copending application and the cited art teach a method substantially as claimed (biotin/streptavidin), however fails to recite tag is desthiobiotin and the tag binding partner comprises streptavidin (claim 4).
ThermoFisher Scientific teach biotin and desthiobiotin conjugates, ThermoFisher Scientific teach the use of biotin-streptavidin binding/bridge in order to amplify detection of biotinylated targets (see starting on page 164, see page 166, col. 1, para 2, page 167, col. 2, para 2).
One having ordinary skill in the art would have found it prima facie obvious to one of ordinary skill in the art to substitute desthiobiotin for biotin based on ThermoFisher since the reference refers to each for the same purpose. Further, it would have been considered prima facie obvious to try, namely, to try desthiobiotin in place of biotin for this same reason (considering ThermoFisher indicates both biotin and desthiobiotin conjugates as known and available to those of ordinary skill in the art). As such, one having ordinary skill would have a reasonable expectation of success using one in place of the other.
Claim 16 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13, 35-38, 41-42, 44-47 and 50 of copending Application No. 16/479,827 in view of Carron et al. (2012), as applied to claim 1, and further in view of Glass et al.
The copending application and the cited prior art teach a method substantially as claimed.
However, fails to teach wherein a concentration of the reporter binding moiety is greater than a concentration of the reporter, optionally at least 5 times greater, or at least 10 times greater, or at least 100 times greater, or at least 1000 times greater, optionally about 1000 times greater.
Glass et al. teach sample matrix is considered to be everything else in a sample, other than the analyte itself (see page 68, col. 1, para 1). Glass teach matrix effects in immunoassay are well known, if not always well understood (also para 1). Glass teach a technique comprising adding excess unlabeled antibody (the same antibody used for detection, but unlabeled) to bind analyte without changing detection antibodies’ response to the matrix component (page 69, col. 1, para 2). Glass teaching (page 69, col. 1, para 3), for optimum sensitivity, the labeled detection concentration will be approximately equal to the Kd of the antibody, and this concentration will also be a near the midpoint of the assay working range for analyte; see further teaching adding unlabeled antibody in significant excess (approximately 100 fold above the labeled antibody concentration) results in binding of essentially all the specific analyte, while simultaneously reducing to near zero the amount of labeled antibody bound to analyte.
It would have been prima facie obvious to one having ordinary skill before the effective filing date of the claimed invention, to have modified the method as taught by the copending application and the cited art, in order to provide reporter binding moiety at a greater concentration than the amount of reporter (for example, 100X), such that upon binding there will be both labeled and unlabeled antibody for detection in order to address any potential matrix effects which may affect results(Glass et al.). One having ordinary skill in the art would have had a reasonable expectation of success because glass teach it is recognized in the art that matrix is considered everything other than analyte in a sample, and the effects caused by matrix are well known and understood in the prior art. Considering Carron et al. and the cited art teach an assay involving detection antibody for binding/detection analyte in a sample, it would be expected that the method would similarly be subject to potential matrix effects and that applying the technique of Glass would improve sensitivity by neutralizing any such matrix effects.
Claim 17 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13, 35-38, 41-42, 44-47 and 50 of copending Application No. 16/479,827 in view of Carron et al. (2012), as applied to claim 1 above, and futher in view of Lambert et al.
Regarding claim 17, the combination of the copending application and Carron (2012), is teaching multiplex detection of a plurality of analytes, the combination of the art teaches a method substantially as claimed.
However, fails to teach each of the plurality of reporters (quantum dots of the copending) produces a different property of a signal (claim 17).
See Lambert et al., Lambert teach multiplex detection employing species of SERS nanoparticles having a unique Raman shift (abstract). In particular, Lambert teach Quantum dots as suitable labels, see para [0007], Lambert teach quantum dots allow multiplex detection, that they have high quantum efficiency, resist photobleaching, and can be produced in colloidal suspensions with a narrow emission spectrum, they can be selected to achieve emission in a variety of colors. Lambert (para [0007]) recognize quantum dots and SERS nanoparticles each as desirable reporters (referred in Lambert as tags). See throughout Lambert, the references teaches either of quantum dots or SERS nanoparticles for spectral multiplex detection (see e.g., para [0011], [0024], [0028]. See also para [0098], biotinylated antibodies, avidin coated quantum dots, when incubated together, the antibodies bind the quantum dots at the biotin-avidin connection.
Although silent as to whether the different quantum dots produce different signals, it would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention that each of the plurality of quantum dots have a different spectra signal (as in Lambert) to facilitate the multiplex detection (so that each of the distinct analytes is a distinctly detectable, as in Lambert). One having ordinary skill int eh art would have a reasonable expectation of success because the copending application is already teaching a plurality of quantum dots, as such one would expect success applying ones that are detectably distinct.
Claim 22 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13, 35-38, 41-42, 44-47 and 50 of copending Application No. 16/479,827 in view of Carron et al. (2012), as applied to claim 9 above, and further in view of Safarik et al.
Regarding claim 22, the copending application and the cited prior art teach a method substantially as claimed, however, fails to teach the method comprising a step of pre-treating the sample with a magnetic conjugate comprising a magnetic particle and a moiety configured to bind contaminant antibodies and/or non-antibody moieties, wherein the pre-treating reduces or eliminates one or more of a-c as claimed (claim 22).
Safarik et al. teach, regarding magnetic separation techniques utilizing small magnetic particles, that magnetic beads in many cases exhibit low non-specific binding of non-target molecules present in different samples (see page 5, col. 1, para 3). Safarik teach certain samples may require preclearing to removed molecules which have high non-specific binding activity, that if pre-clearing is needed, the sample can be mixed with magnetic beads not coated with affinity ligand, or with secondary antibody or irrelevant antibody (see at para 3).
It would have been prima facie obvious to one having ordinary skill in the art to have modified the copending application in view of the cited art, to further perform a pre-treatment step comprising contacting sample with magnetic particle comprising antibody/irrelevant antibody in order to remove interfering substances in samples, one having ordinary skill in the art would have been motivated to introduce such a pre-treatment step because small magnetic beads were known/recognized in the prior art as exhibiting non-specific binding so this is an expected issue when performing assays utilizing such particles/beads, the modification is an art recognized technique known to reduce interference (Safarik). One having ordinary skill would have a reasonable expectation of success because the assay of the copending application similarly involves magnetic separation/concentration, and since such particles are known to be subject to low non-specific interference, it would be expected that the assay would benefit from the technique as in Safarik.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
18/019,677
Claims 1, 2, 8-11, 14, 16-18, 20, 25, 29, 33 and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44-57 of copending Application No. 18/019,677 (reference application) in view of Carron et al. (2006) and Carron et al. (2012).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending ‘677 similarly recites a method substantially as claimed, comprising steps (a)-(e) (see copending claim 44).
The copending application differs from that presently claimed in that the copending teach detection of analyte (singular), and as such fails to teach detection “a plurality of analytes”, that the magnetic conjugate comprises a plurality of capture moieties, a plurality of reporter moieties, each to bind corresponding analyte, each reporter configured to generate a different signal.
Carron et al. (2006) is extremely similar to the copending however the method is applied for detection of multiple targeted analytes at onces, Carron (2006) teach a method for detecting a plurality of analytes (multiplex detection) in a biological sample (para [0018], samples such as e.g., blood, paras [0061] and [0076]). The method of Carron et al. comprises bringing into contact a sample with at least one magnetic conjugate comprising a magnetic particle and a plurality of capture moieties coupled to the magnetic particle, each configured to bind corresponding analytes of a plurality of analytes (paras [0033] and [0076]-[0077], particle 22 coated with antibodies 26a, see figure 9), and a plurality of reporter moieties that bind a corresponding plurality of the analytes (each reporter has a binding agent specific for a particular analyte, see Figure 9), each reporter moiety having thereon a reporter that is spectrally distinct (each configured to generate a corresponding different signal). Carron et al. further teach, following binding of the analyte, magnetic conjugate and reporter moieties, magnetically localizing (applying a magnetic field to separate the magnetic conjugate bound complex), for detection of each analyte based on the detection of signal generated by each of the reporters (paras [0018]-[0019] and [0023].
Carron et al. (2012) similarly describes multiplex particle based immunoassay for detection of a plurality of target analytes simultaneously (e.g., see paras [0015], [0017] and [0048]). See at para [0048], Carron (2012) describes figure 16B teaching a capture particle with an antibody that binds a plurality of targeted analytes, Carron (2012) demonstrate a motive particle (capture particle) having thereon a plurality of different receptors specific to corresponding plurality of different analytes.
It would have been prima facie obvious to have modified the copending to apply the method for a plurality of target analytes simultaneously as an obvious matter of applying a known technique (multiplex detection) to a known method (the particle based assay), the advantage being detection of a plurality of analytes at once time. One having ordinary skill would have a reasonable expectation of success because Carron (2006) support the feasibility of such a modification, Carron similar to the copending in that both comprise a magnetic capture particle and a plurality of detectable reporter particles.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the capture particle in the method of the copending in view of Carron (2006) (the particle comprising one antibody (binding moiety) that binds a plurality of targeted analytes) to instead provide a plurality of target analyte specific antibodies (binding moieties) as a simple substitution of one known capture particle binding format for another. In particular, the prior art contained the particle binding assay as taught by copending and Carron et al. (2006), which differed from the claimed binding format by the substitution of the capture moieties (antibody). In particular, Carron (2006) teach binding a plurality of targeted analytes using a plurality of capture antibody on a carrier particle (magnetic particle), however Carron only shows one type of capture antibody. The prior art demonstrates that alternative to a single plurality of antibodies to bind a plurality of different target analytes, it is known in the art (Carron et al. (2012)) to alternatively rely on a plurality of distinct antibodies on a single particle to capture the plurality of different analytes. The prior art supports that the substituted techniques (one antibody for a plurality of targeted analytes, or a plurality of antibodies for a plurality of target analytes) and their functions were known in the art. One having ordinary skill in the art could have substituted one known binding format for the other and the results of the substitution would have been predictable.
Regarding claim 2, see the copending teach biotin/streptavidin (cited in detail above, copending claim 44).
Regarding claim 8, see the copending and the cited prior art cited above, addresses the claim (first and second antibodies to the corresponding analyte).
Regarding claim 9, see the copending recites antibodies used to detect an analyte that is a protein antigen.
Regarding claims 9-11, see further Carron (2012) teach target analyte can be an antigen or antibody of interest (para [0020]). It would have been further obvious to have modified the method of the copending application in order to detect either protein or antibody, detecting antibody an obvious matter of a simple substitution of one targeted analyte for another, both known detectable with a system as taught by the cited art (both the copending and 2012 teaching particle based capture and detection of an analyte), further the combination teaching detecting presence/quantity of the target. Regarding 11, the combination of the cited art addresses “providing an amount of antibodies”, as claimed”.
Regarding claim 14, see copending claim 49 (quantum dots).
Regarding claim 16, see copending claim 44, more binding moiety than reporter (consistent with claims, at least 5X greater, 1000X greater.).
Regarding claim 17, see the combination of the copending and the cited art addresses different signal (property signal) generated for each reporter.
Regarding claim 18, see copending claim 52.
Regarding claim 20, Carron et al.(2006) cited above demonstrates detection of 3 analytes, see at para [0076] Carron teach the concept lends itself to multiplex assay for a large number of analytes in a single sample; see further para [0065], tens, hundreds, thousands or more analytes may bind, thereby addressing at least 4 or at least 6 analytes (the method as taught by the combination of the cited art is expected to bind at least 4 or 6 as claimed, and more). As such, the combination of the cited art addresses the claims.
Claim 25 of the present application recites “the method is suitable for point of care usage, field usage, home usage, and/or wherein the method is compatible with the World Health Organization’s ASSURED…criteria”; however, it is not clear what specific method steps or structure the claimed functional language “suitable for” implies or imposes to the claimed methods or reagents included in the claimed methods. In particular, given broadest reasonable interpretation, it appears the method as taught by Carron and the cited art could be performed/used in “field” or “home”.
Claim 29, it is noted that other than the functional limitations regarding false results and specificity/sensitivity recited at claim 29, claim 29 recites no additional specific method steps or specific reagents/components attributed to the claimed functional results. The combination of the cited prior art teaches a method as claimed (comprising the same method steps/reagents), as a result it would be expected capable of the same functional results specific to sensitivity/specificity and false results.
Regarding claim 33, see copending claim 44.
Regarding claim 34, see the copending claims are silent as to whether the antibodies bind at different locations.
However, see Carron et al. (2012), at for example para [0026], Carron teach antibodies that bind different sites on an antigen.
It would have been further prima facie obvious to one having ordinary skill in the art to have modified the copending application such that the antibodies bind different sites on an antigen (different locations), as an obvious matter of applying a known technique for performing a two antibody binding assay (two antibodies that bind for detection of same antigen). One having ordinary skill having a reasonable expectation of success applying a known technique.
Claim 4 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44-57 of copending Application No. 18/019,677 (reference application) in view of Carron et al. (2012), as applied to claim 1 above, and further in view of ThermoFisher Scientific.
The copending application and the cited art teach a method substantially as claimed (biotin/streptavidin), however fails to recite tag is desthiobiotin and the tag binding partner comprises streptavidin (claim 4).
ThermoFisher Scientific teach biotin and desthiobiotin conjugates, ThermoFisher Scientific teach the use of biotin-streptavidin binding/bridge in order to amplify detection of biotinylated targets (see starting on page 164, see page 166, col. 1, para 2, page 167, col. 2, para 2).
One having ordinary skill in the art would have found it prima facie obvious to one of ordinary skill in the art to substitute desthiobiotin for biotin based on ThermoFisher since the reference refers to each for the same purpose. Further, it would have been considered prima facie obvious to try, namely, to try desthiobiotin in place of biotin for this same reason (considering ThermoFisher indicates both biotin and desthiobiotin conjugates as known and available to those of ordinary skill in the art). As such, one having ordinary skill would have a reasonable expectation of success using one in place of the other.
Claim 22 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44-57 of copending Application No. 18/019,677 in view of Carron et al., (2006) and Carron et al. (2012), as applied to claim 9 above, and further in view of Safarik et al.
Regarding claim 22, the copending application and the cited prior art teach a method substantially as claimed, however, fails to teach the method comprising a step of pre-treating the sample with a magnetic conjugate comprising a magnetic particle and a moiety configured to bind contaminant antibodies and/or non-antibody moieties, wherein the pre-treating reduces or eliminates one or more of a-c as claimed (claim 22).
Safarik et al. teach, regarding magnetic separation techniques utilizing small magnetic particles, that magnetic beads in many cases exhibit low non-specific binding of non-target molecules present in different samples (see page 5, col. 1, para 3). Safarik teach certain samples may require preclearing to removed molecules which have high non-specific binding activity, that if pre-clearing is needed, the sample can be mixed with magnetic beads not coated with affinity ligand, or with secondary antibody or irrelevant antibody (see at para 3).
It would have been prima facie obvious to one having ordinary skill in the art to have modified the copending application in view of the cited art, to further perform a pre-treatment step comprising contacting sample with magnetic particle comprising antibody/irrelevant antibody in order to remove interfering substances in samples, one having ordinary skill in the art would have been motivated to introduce such a pre-treatment step because small magnetic beads were known/recognized in the prior art as exhibiting non-specific binding so this is an expected issue when performing assays utilizing such particles/beads, the modification is an art recognized technique known to reduce interference (Safarik). One having ordinary skill would have a reasonable expectation of success because the assay of the copending application similarly involves magnetic separation/concentration, and since such particles are known to be subject to low non-specific interference, it would be expected that the assay would benefit from the technique as in Safarik.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
19/053,713
Claims 1, 2, 4, 8-11, 14, 17-18, 20, 25, 29, 33 and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35-54 of copending Application No. 19/053,713 (reference application) in view of Carron et al. (2006) and Carron et al. (2012).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending ‘713 similarly recites a method substantially as claimed, comprising steps (a)-(e) (see copending claim 35).
The copending application differs from that presently claimed in that the copending teach detection of analyte (singular), and as such fails to teach detection “a plurality of analytes”, that the magnetic conjugate comprises a plurality of capture moieties, a plurality of reporter moieties, each to bind corresponding analyte, each reporter configured to generate a different signal.
Carron et al. (2006) is extremely similar to the copending however the method is applied for detection of multiple targeted analytes at onces, Carron (2006) teach a method for detecting a plurality of analytes (multiplex detection) in a biological sample (para [0018], samples such as e.g., blood, paras [0061] and [0076]). The method of Carron et al. comprises bringing into contact a sample with at least one magnetic conjugate comprising a magnetic particle and a plurality of capture moieties coupled to the magnetic particle, each configured to bind corresponding analytes of a plurality of analytes (paras [0033] and [0076]-[0077], particle 22 coated with antibodies 26a, see figure 9), and a plurality of reporter moieties that bind a corresponding plurality of the analytes (each reporter has a binding agent specific for a particular analyte, see Figure 9), each reporter moiety having thereon a reporter that is spectrally distinct (each configured to generate a corresponding different signal). Carron et al. further teach, following binding of the analyte, magnetic conjugate and reporter moieties, magnetically localizing (applying a magnetic field to separate the magnetic conjugate bound complex), for detection of each analyte based on the detection of signal generated by each of the reporters (paras [0018]-[0019] and [0023].
Carron et al. (2012) similarly describes multiplex particle based immunoassay for detection of a plurality of target analytes simultaneously (e.g., see paras [0015], [0017] and [0048]). See at para [0048], Carron (2012) describes figure 16B teaching a capture particle with an antibody that binds a plurality of targeted analytes, Carron (2012) demonstrate a motive particle (capture particle) having thereon a plurality of different receptors specific to corresponding plurality of different analytes.
It would have been prima facie obvious to have modified the copending to apply the method for a plurality of target analytes simultaneously as an obvious matter of applying a known technique (multiplex detection) to a known method (the particle based assay), the advantage being detection of a plurality of analytes at once time. One having ordinary skill would have a reasonable expectation of success because Carron (2006) support the feasibility of such a modification, Carron similar to the copending in that both comprise a magnetic capture particle and a plurality of detectable reporter particles.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the capture particle in the method of the copending in view of Carron (2006) (the particle comprising one antibody (binding moiety) that binds a plurality of targeted analytes) to instead provide a plurality of target analyte specific antibodies (binding moieties) as a simple substitution of one known capture particle binding format for another. In particular, the prior art contained the particle binding assay as taught by copending and Carron et al. (2006), which differed from the claimed binding format by the substitution of the capture moieties (antibody). In particular, Carron (2006) teach binding a plurality of targeted analytes using a plurality of capture antibody on a carrier particle (magnetic particle), however Carron only shows one type of capture antibody. The prior art demonstrates that alternative to a single plurality of antibodies to bind a plurality of different target analytes, it is known in the art (Carron et al. (2012)) to alternatively rely on a plurality of distinct antibodies on a single particle to capture the plurality of different analytes. The prior art supports that the substituted techniques (one antibody for a plurality of targeted analytes, or a plurality of antibodies for a plurality of target analytes) and their functions were known in the art. One having ordinary skill in the art could have substituted one known binding format for the other and the results of the substitution would have been predictable.
Regarding claim 2, see the copending teach biotin/streptavidin (cited in detail above, copending claim 35).
Regarding claim 4, see copending claim 35.
Regarding claim 8, see the copending and the cited prior art cited above, addresses the claim (first and second antibodies to the corresponding analyte).
Regarding claim 9, see the copending recites antibodies used to detect an analyte that is a protein antigen.
Regarding claims 9-11, see further Carron (2012) teach target analyte can be an antigen or antibody of interest (para [0020]). It would have been further obvious to have modified the method of the copending application in order to detect either protein or antibody, detecting antibody an obvious matter of a simple substitution of one targeted analyte for another, both known detectable with a system as taught by the cited art (both the copending and 2012 teaching particle based capture and detection of an analyte), further the combination teaching detecting presence/quantity of the target. Regarding 11, the combination of the cited art addresses “providing an amount of antibodies”, as claimed”.
Regarding claim 14, see copending claims 35, 42 and 43.
Regarding claim 17, see the combination of the copending and the cited art addresses different signal (property signal) generated for each reporter.
Regarding claim 18, see copending claims 35 and 45 (blood, serum, urine).
Regarding claim 20, Carron et al.(2006) cited above demonstrates detection of 3 analytes, see at para [0076] Carron teach the concept lends itself to multiplex assay for a large number of analytes in a single sample; see further para [0065], tens, hundreds, thousands or more analytes may bind, thereby addressing at least 4 or at least 6 analytes (the method as taught by the combination of the cited art is expected to bind at least 4 or 6 as claimed, and more). As such, the combination of the cited art addresses the claims.
Claim 25 of the present application recites “the method is suitable for point of care usage, field usage, home usage, and/or wherein the method is compatible with the World Health Organization’s ASSURED…criteria”; however, it is not clear what specific method steps or structure the claimed functional language “suitable for” implies or imposes to the claimed methods or reagents included in the claimed methods. In particular, given broadest reasonable interpretation, it appears the method as taught by Carron and the cited art could be performed/used in “field” or “home”.
Claim 29, it is noted that other than the functional limitations regarding false results and specificity/sensitivity recited at claim 29, claim 29 recites no additional specific method steps or specific reagents/components attributed to the claimed functional results. The combination of the cited prior art teaches a method as claimed (comprising the same method steps/reagents), as a result it would be expected capable of the same functional results specific to sensitivity/specificity and false results.
Regarding claim 33, see copending claim 35 similarly recites the step of separating.
Regarding claim 34, see copending claim 35, the first and second antibodies bind different portions.
Claim 16 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35-54 of copending Application No. 18/040,559 in view of Carron et al. (2012), as applied to claim 1, and further in view of Glass et al.
The copending application and the cited prior art teach a method substantially as claimed.
However, fails to teach wherein a concentration of the reporter binding moiety is greater than a concentration of the reporter, optionally at least 5 times greater, or at least 10 times greater, or at least 100 times greater, or at least 1000 times greater, optionally about 1000 times greater.
Glass et al. teach sample matrix is considered to be everything else in a sample, other than the analyte itself (see page 68, col. 1, para 1). Glass teach matrix effects in immunoassay are well known, if not always well understood (also para 1). Glass teach a technique comprising adding excess unlabeled antibody (the same antibody used for detection, but unlabeled) to bind analyte without changing detection antibodies’ response to the matrix component (page 69, col. 1, para 2). Glass teaching (page 69, col. 1, para 3), for optimum sensitivity, the labeled detection concentration will be approximately equal to the Kd of the antibody, and this concentration will also be a near the midpoint of the assay working range for analyte; see further teaching adding unlabeled antibody in significant excess (approximately 100 fold above the labeled antibody concentration) results in binding of essentially all the specific analyte, while simultaneously reducing to near zero the amount of labeled antibody bound to analyte.
It would have been prima facie obvious to one having ordinary skill before the effective filing date of the claimed invention, to have modified the method as taught by the copending application and the cited art, in order to provide reporter binding moiety at a greater concentration than the amount of reporter (for example, 100X), such that upon binding there will be both labeled and unlabeled antibody for detection in order to address any potential matrix effects which may affect results(Glass et al.). One having ordinary skill in the art would have had a reasonable expectation of success because glass teach it is recognized in the art that matrix is considered everything other than analyte in a sample, and the effects caused by matrix are well known and understood in the prior art. Considering Carron et al. and the cited art teach an assay involving detection antibody for binding/detection analyte in a sample, it would be expected that the method would similarly be subject to potential matrix effects and that applying the technique of Glass would improve sensitivity by neutralizing any such matrix effects.
Allowable Subject Matter
The limitations of claim 3 (in combination with those of claim 1), further which are recited at claim 35, appear to free of the prior art and so may form the basis for allowable subject matter if the other outstanding rejections are addressed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLEN J MARCSISIN whose telephone number is (571)272-6001. The examiner can normally be reached M-F 8:00am-4:30pm.
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/ELLEN J MARCSISIN/Primary Examiner, Art Unit 1677