Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-6 are pending in the application and are the subject of this office action.
Claim Interpretation
Claim 1 is directed to “a chemiluminescent lateral flow immunoassay method” (CL-LFIA), however, the majority of the method steps positively recited in the claim are steps for the preparation of a conjugate. Since applicant has affirmed in their response to previous office actions that the claims are directed to a CL-LFIA method, and since it is explicitly recited in the preamble of claim 1, claim 1 and its dependents are interpreted to be directed to a CL-LFIA method and not to a method of preparing a conjugate or a strip (i.e. the immunoassay method to which the claims are directed is understood to be the process of using the strip and not the process of manufacturing or making the strip or its components). Therefore, the only limitations of the claim which serve to distinguish over the prior art are limitations which limit the claimed CL-LFIA method. That is, the method of preparing the conjugate and the strip only limits the claim insofar as it imparts specific structural or functional features to the conjugate and strip used in the CL-LFIA method. As such, in order to read on the instant claim, the prior art needs only to teach the structures implied by the steps of making the conjugate and the strip, and not the exact manipulations of the recited steps of making.
Additionally, claim 1 recites a CL-LFIA method “for reducing cross reaction and false positives in a detection of protein analytes”. This is at best a functional limitation of the claimed method, which, from the context of the claims and the specification, appears to be provided by the claimed conjugate. Therefore, prior art which teaches all structural features of the claimed conjugate is understood to read on this limitation of the claim regardless of whether it is explicitly stated to reduce cross reaction and false positive in a detection of protein analytes.
Claims 3 and 6 depend from claim 1 and are directed to the CL-LFIA method, however, the only positively recited elements of the claim are directed to steps of a method of preparing the strip, which is not understood to be part of the immunoassay method itself (wherein the immunoassay method is understood to be the process of using the strip, not the process of manufacturing the strip). Since, as described above, claim 1 is directed to a CL-LFIA method, and since claims 3 and 6 depend from claim 1, claims 3 and 6 are interpreted to be directed to a CL-LFIA method, and not to a method of preparing the strip. Therefore, the only limitations of the claim which serve to distinguish over the prior art are limitation which limit the claimed CL-LFIA method. That is, the method of preparing the strip only limits the claims insofar as it imparts specific structural or functional features to the strip used in the CL-LFIA method to which the claims are directed.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-6 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is vague regarding “the reaction-site-blocked AuNP-Ab-HRP-PEG conjugate in line 6 of the claim. There is prior introduction of a “AuNP-Ab-HRP-PEG conjugate” but not of a “reaction-site-blocked AuNP-Ab-HRP-PEG conjugate”, as such there is insufficient antecedent basis for this limitation in the claim.
Dependent claims 2-6 are rejected as indefinite because they depend from an indefinite claim and fail to remedy its deficiencies.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Wan et al (US 2009/0111194 A1; previously cited) in view of Zhang et al (Combined Antibody Tagged HRP Gold Nanoparticle Probe for Effective PCV2 Screening in Pig Farms. Int J Nanomedicine. 2022 Jul 29;17:3361-3369.; previously cited), Kim et al (Highly sensitive rapid test with chemiluminescent signal bands. BioChip J 4, 155–160 (2010).; previously cited), hereinafter Kim 2010, Geng et al (Facile Preparation of Stable Antibody-Gold Conjugates and Application to Affinity-Capture Self-Interaction Nanoparticle Spectroscopy. Bioconjug Chem. 2016 Oct 19;27(10):2287-2300.. Epub 2016 Sep 16.; previously cited), Leopold et al (Assessment of PEG and BSA-PEG gold nanoparticles cellular interaction, Colloids and Surfaces A: Physicochemical and Engineering Aspects. Volume 532. 2017. Pages 70-76, ISSN 0927-7757; previously cited), Kim et al (US 2022/0099667 A1; previously cited), hereinafter Kim 2022, and Zangheri et al (A simple and compact smartphone accessory for quantitative chemiluminescence-based lateral flow immunoassay for salivary cortisol detection. Biosens Bioelectron. 2015 Feb 15;64:63-8.; previously cited).
Regarding claim 1, Wan teaches a lateral flow immunoassay for the detection of protein analytes (Par. 16: the detection of transferrin and hemoglobin is achieved using a lateral flow sandwich immunoassay device).
Wan teaches the immunoassay comprises use of a strip (Par. 17) and a conjugate, wherein the conjugate comprises gold nanoparticles conjugated to a detection antibody specific to a target analyte and coated with PEG and BSA (Par. 37: in the sandwich format immunoassay, the capture antibody is immobilized on a solid material, and the detection antibody is conjugated to a label or signal generator; Par. 38-41: the signal generator may comprise gold nanoparticles; Par. 55: in one embodiment, antibody-conjugated gold particles were chosen as the detection means. An antibody specific to the target analyte was used to coat gold nanoparticles. BSA and PEG were used to block leftover binding sites on the gold particles (thereby reducing nonspecific interactions)).
Wan teaches that the signal generator conjugated to the detection antibody may comprise enzyme labels (Par. 38), but Wan does not specifically teach that the detection antibody is conjugated to HRP, or that mPEG is covalently linked to the gold nanoparticles by an Au-S bond. Wan does not specifically teach that the lateral flow immunoassay is a chemiluminescent lateral flow immunoassay.
Regarding claim 1, Zhang teaches that conjugation of HRP-labeled detection antibodies to gold nanoparticle probes provides greatly increased sensitivity in the detection of a target analyte by a sandwich format immunoassay (Pg. 3362, Par. 2: Gold nanoparticles have large specific surface area and favorable biocompatibility. The use of gold nanoparticles allows the attachment of multiple enzyme molecules which can generate an amplified optical signal; Abstract: compared to conventional sandwich ELISA procedures, use of HRP-labeled detection antibodies conjugated to gold nanoparticles resulted in higher sensitivity (51-fold) and a shorter assay time; Pg. 3362, last Par.-Pg. 3362-first Par.: 10ul of freshly prepared Ab(HRP) solution was added to 200ul of AuNP solution under agitation, followed by gentle mixing and incubation. Then, 220ul of 2% BSA solution was added while stirring for 30 minutes at room temperature for blocking).
Regarding claim 1, Kim 2010 teaches a lateral flow immunoassay for the detection of a target analyte comprising the use of HRP-labeled antibodies applied in a chemiluminescence enzyme reaction. Kim 2010 further teaches that chemiluminescent detection with HRP is more sensitive than other detection methods (Abstract: A highly sensitive lateral flow immunoassay developed by applying a chemiluminescence enzyme reaction. Chemiluminescent signal was produced using HRP labeled antibodies and luminol as a chemiluminescence substrate. The sensitivity was determined to be improved as much as 100-fold compared to conventional lateral flow immunoassays based on gold colloids; Pg. 155, Col. 2, last Par.- Pg. 156, Col. 1, first Par.: Immunoassays based on chemiluminescence have been reported to be far more sensitive than immunoassays using chromogenic reactions and fluorescence labels).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the immunoassay method taught by Wan to specifically include an HRP-labeled detection antibody conjugated to the gold nanoparticle, as taught by Zhang. Wan teaches that a detection conjugate in a lateral flow immunoassay may comprise gold nanoparticles conjugated to detection antibodies (Par. 55), and further teaches that the signal generator used in the assay conjugate may comprise enzyme labels (Par. 38). Zhang teaches that Ab(HRP)-AuNP probes can be employed in sandwich format immunoassays for more sensitive detection of a target analyte as compared to conventional probes (Abstract). Thus, one of ordinary skill in the art would be motivated to apply a specifically HRP conjugated antibody to the Ab-AuNP conjugate taught by Wan for the purpose of lowering the limit of detection and achieving a more sensitive immunoassay. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Wan and Zhang are directed to sandwich immunoassays employing conjugates comprising detection antibodies conjugated to gold nanoparticles.
Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the immunoassay method of Wan in view of Zhang to specifically include the use of a chemiluminescent substrate for use with HRP, as taught by Kim 2010. Wan in view of Zhang teaches a lateral flow immunoassay method which employs an Ab(HRP)-AuNP conjugate. Though Zhang teaches the use of a TMB substrate with HRP, Kim 2010 teaches that HRP reacted with a chemiluminescent substrate can be used in a lateral flow immunoassay to achieve greater detection sensitivity as compared to colorimetric, fluorometric, and chromogenic detection methods. Thus, one of ordinary skill in the art would be motivated to use the chemiluminescent substrate with HRP as taught by Kim 2010 in order to improve the sensitivity of the lateral flow immunoassay. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Wan and Kim 2010 are directed to sandwich format lateral flow immunoassays comprising detectably labeled antibodies for the detection of a target analyte.
Regarding claim 1, Geng teaches methods for the improvement of protein-nanoparticle conjugates used in applications such as biomolecular detection (Abstract). Geng teaches that stable antibody-gold nanoparticle conjugates may be improved and stabilized by the addition of molecules such as PEG and BSA (Pg. 2287, Col. 1, Par. 1).
Specifically, Geng teaches methods for the synthesis of an antibody-functionalized PEG-AuNP which comprise conjugation of an antibody (i.e. detection antibody) to a gold nanoparticle by physisorption, followed by linking mPEG covalently to the AuNPs by an Au-S bond, and thereby resulting in covalent linkage of mPEG-SH to remaining exposed surface region of the AuNP-Ab-HRP conjugate via Au-S bonds (Abstract: an improved physisorption method for synthesis of antibody-gold conjugates; Pg. 2297, Col. 1, last Par.-Col. 2, first Par.: mPEG-SH acquired from Nanocs Inc; Pg. 2298, Col. 1, Par. 3-4: one part capture antibody mixed with nine parts AuNPs, mixed and incubated overnight to allow conjugation of antibody to AuNP. Next, thiolated mPEG is added to the conjugate solution and incubated under conditions which facilitate the formation of a covalent Au-S bond). Geng teaches that this method of particle synthesis will be useful for reproducibly preparing stable antibody-gold conjugates for diverse applications (Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Wan in view of Zhang and Kim 2010 such that the PEGylation of the conjugate taught by Wan specifically comprises linking mPEG covalently to the AuNPs by an Au-S bond, as taught by Geng. Wan teaches that antibodies are conjugated to the gold particle conjugate, and further teaches that this step is followed by blocking the conjugate with PEG and BSA, however, Wan is vague regarding the specific procedure used for the blocking and the specific species of PEG applied to the particle. As such, one would be motivated to use the proper reagents and procedures for blocking the conjugate with PEG, wherein Geng teaches that an antibody-gold conjugate used in biosensing may be stabilized and blocked by the addition of PEG which occurs after conjugation of the antibody to the gold particle, wherein the addition of PEG specifically comprises linking mPEG covalently to the AuNPs by an Au-S bond. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Wan and Geng disclose synthesis of gold nanoparticles which are conjugated to antibodies before the addition of PEG, and which may be used for biosensing applications.
Regarding blocking of the conjugate with BSA as recited in claim 1, Wan teaches a method which comprises blocking the conjugate with both PEG and BSA, but does not disclose the specific order or steps of BSA blocking.
Regarding claim 1, Leopold teaches methods for the synthesis of gold nanoparticles which are blocked and stabilized by both PEG and BSA (Abstract). Leopold teaches a procedure for applying both PEG and BSA to a gold nanoparticle, wherein BSA is applied after PEGylation of the particle in order to block reaction sites, increase stability, prevent aggregation, and improve biocompatibility (Pg. 71, Col. 1, last Par.: coating with PEG and BSA enhances biocompatibility. Coating with BSA increases particle stability and prevents particle aggregation; Pg. 71, Col. 2, Par. 2: first, PEG is conjugated to AuNPs. Then the PEG-AuNPs are mixed with a BSA solution for blocking with BSA). Leopold teaches that the addition of BSA in this way is advantageous because it prevents particle aggregation more effectively than PEGylation alone (Abstract; Fig. 3; Pg. 72, Col. 2, last Par.-Pg. 73, Col. 1, Par. 1: NP aggregation is strongly diminished by BSA coating of PEG-AuNPs. This is supported by DLS and zeta potential measurements for both types of synthesized nanoparticles. The size distribution profile shown by the DLS data proves that the PEG-AuNPs are polydisperesed in nature, wherein the data shows one peak at a smaller size, representing individual particles, and a second peak at a larger size, representing a population of aggregated particles. In contrast, the particles coated with PEG and then BSA are monodisperse, indicating a lack of aggregation).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Wan in view of Zhang, Kim, and Geng such that coating of the conjugate with BSA specifically occurs after coating of the conjugate with PEG, as taught by Leopold. Wan teaches an antibody-AuNP conjugate which is blocked by both PEG and BSA, but is generic regarding the order of blocking with PEG and BSA. As such, one would be motivated to use the proper procedure and proper order of steps to achieve the disclosed gold particle which is blocked with both PEG and BSA, wherein Leopold teaches a method for the synthesis of a gold nanoparticle blocked with both PEG and BSA, and teaches that BSA is added to the gold nanoparticle after the addition of PEG, wherein this allows for a BSA coating which is advantageous in preventing nanoparticle aggregation which is observed in particles with an outermost layer of PEG. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Wan and Leopold are directed to gold nanoparticles coated with both PEG and BSA.
Regarding claim 1, the combined references teach a CL-LFIA method comprising a step of mixing the conjugate and analytes on the strip (Wan, Par. 45-46: sample is applied to the sample pad and conjugate is contained in the conjugate pad). Kim 2010 further teaches that in a chemiluminescent LFIA, sample and then chemiluminescent substrate are applied to the strip sequentially, and a photo is taken of the results (Kim 2010, Pg. 157, Col. 1: sample is dropped on the test strip, then luminol solution is dropped on the test strip. Results are analyzed with a Chemi-doc XRS; Fig. 2b).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Wan in view of Zhang, Kim 2010, Geng, and Leopold to specifically use the photo detection method taught by Kim 2010. One of ordinary skill in the art would be motivated to make this modification because Wan is modified by Kim 2010 to comprise use of a chemiluminescent label and substrate for chemiluminescent detection of an analyte, and as such, one would be motivated to use the proper detection system for a chemiluminescent assay, as taught by Kim 2010. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because the modified invention of Wan is a CL-LFIA method, and Kim 2010 discloses proper and known methods of detecting results for a CL-LFIA.
Wan in view of Zhang, Kim 2010, Geng, and Leopold do not specifically teach how much time elapses between the addition of the sample to the strip and the addition of the chemiluminescent substrate.
Regarding claim 1, Kim 2022 further teaches a CL-LFIA method comprising the following steps: adding an analyte to a sample pad, waiting for 0.5-10 min (during which the sample mixes with conjugate in the conjugate pad), then adding a chemiluminescent substrate and taking a photo for recording after a luminescence (Par. 160-163: conjugate is lyophilized on the conjugate pad. Sample is loaded onto the sample pad, and reaction is allowed to proceed for 10 min. Following a wash, luminol reaction solution is loaded onto the membrane, after which the membrane is imaged using a ChemiDoc-MP imaging system).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the CL-LFIA method taught by Wan in view of Zhang, Kim 2010, Geng, and Leopold to include the specific wait time between adding the sample and adding the chemiluminescent substrate, as taught by Kim 2022. Kim 2010 teaches that it is standard in the art to sequentially apply the sample and then the chemiluminescent substrate, but is vague regarding the specific timing of the steps. One of ordinary skill would recognize that this sequential application allows for binding of the target analyte to the conjugate and binding of the target analyte-conjugate complex to the test line, and allows for a washing step to remove the unbound conjugate (thereby reducing background signal), as taught by Kim 2022. One would be motivated to modify the method as taught by Kim 2022 because one would be motivated to include the proper steps and incubation times for the chosen assay and reagents. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because Wan in view of Zhang, Kim 2010, Geng, and Leopold and Kim 2022 are both directed to lateral flow assays for chemiluminescent detection.
Regarding claim 1, the cited references teach a CL-LFIA method comprising the steps of mixing the conjugate and analytes, waiting 0.5-10 minutes, adding a chemiluminescent substrate, and taking a photo. The references do not specifically teach taking a photo by CMOS camera. Both Kim 2010 and Kim 2022 disclose the use of ChemiDoc imaging systems which employ CCD technology.
Zangheri discloses a simple and compact smartphone accessory for quantitative CL-LFIA (Abstract). Zangheri teaches that the CMOS used in a smartphone camera can be used for chemiluminescent detection and that the connectivity and data processing features of the smartphone can be exploited for at-home data analysis and quantitative results (Pg. 64, Col. 1, Par. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Wan in view of Zhang, Kim 2010, Geng, Leopold, and Kim 2022 to include taking a photo by CMOS camera, as taught by Zangheri. One of ordinary skill in the art would be motivated to use a smartphone CMOS camera in place of the ChemiDoc systems taught by Kim 2010 and Kim 2022, because a smartphone is cheaper, more portable, and more accessible than a ChemiDoc imaging system, and because the CMOS system does not require the cooling systems used in CCD imaging which further increase energy and cost of using CCD (Pg. 66, Col. 1, Par. 2; Abstract; Pg. 64, Col. 1, Par. 1). One of ordinary skill in the art would have a reasonable expectation of success in making this modification because the modified invention of Wan and the invention of Zangheri both disclose chemiluminescent lateral flow immunoassays wherein results are detected via an imaging device capable of detecting chemiluminescent signal.
Regarding claims 2 and 5, Wan further teaches the method wherein the strip comprises:
A backing plate, sample pad, conjugate pad, nitrocellulose membrane, and absorbent pad (Figs. 2-3; Par: 44-46; Par. 37);
The sample pad, conjugate pad, nitrocellulose membrane, and absorbent pad are arranged sequentially on the backing plate (Figs. 2-3; Par: 44-46; Par. 37);
A surface of the nitrocellulose membrane is equipped with a test line and a control line (Par. 44: a test area comprising immobilized capture antibodies, a control zone comprising immobilized control antibodies);
The test line is formed by immobilizing capture antibodies to the surface of the nitrocellulose membrane (Par. 44);
The control line is formed by immobilized IgG antibodies to the surface of the nitrocellulose membrane (Par. 50: the control zone comprising immobilized IgG); and
Regarding claim 2, Wan teaches that the conjugate pad contains the conjugate (Par. 46: the conjugate pad contains the conjugate).
Regarding claims 3 and 6, Wan teaches that capture antibodies of an analyte are immobilized on the nitrocellulose membrane to form the test line, and teaches that IgG antibodies are immobilized on the nitrocellulose membrane to form the control line (Par. 50).
Wan teaches that the sample pad, conjugate pad, nitrocellulose membrane and absorbent pad are disposed on the backing plate and teaches that all components are in contact, and that some components overlap (Figs. 2-3).
Regarding claim 3, Wan teaches that conjugate is disposed in the conjugate pad (Par. 46).
Wan does not specifically teach the claimed structure of overlapping the sample pad, conjugate pad, nitrocellulose membrane and the absorbent pad in turn. Wan does not specifically teach the dimensions of the lateral flow immunoassay.
Regarding claims 3 and 6, Kim 2010 teaches a lateral flow immunoassay comprising a sample pad, conjugate pad, nitrocellulose membrane, and absorbent pad, arranged in turn on a backing plate, wherein each of the sample pad, conjugate pad, nitrocellulose membrane, and absorbent pad are overlapped (Fig. 2a; Pg. 158, Col. 2, Par. 3). Kim 2010 further teaches the immunoassay strips are cut to have a width of 1-10mm (Pg. 158, Col. 2, Par. 3: strips are cut to a width of 6mm).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the strip used in the CL-LFIA method taught by Wan in view of Zhang, Kim 2010, Kim 2022, Geng, Leopold, and Zangheri to include the overlapping configuration and width of the strip taught by Kim 2010. Wan teaches all the claimed components of the strip and teaches that they should be in contact or overlapping one another (Par. 17) as this facilitates lateral flow through the device. One of ordinary skill in the art would be motivated to specifically overlap the components of the immunoassay because Kim 2010 teaches the overlap is advantageous in keeping consistent and intimate contact between the components in order to achieve an even flow of the sample fluid between the different components (Pg. 158, Col. 2, Par. 3). Additionally, one of ordinary skill in the art would be motivated to use the strip dimensions taught by Kim 2010 in the strip of Wan because Wan teaches a lateral flow device but is vague regarding the dimensions, while Kim 2010 teaches specific dimensions appropriate for a lateral flow device, and one of ordinary skill in the art would be motivated to use appropriately sized components. One of ordinary skill in the art would have a reasonable expectation of success in making these modifications because both Wan and Kim 2010 are directed to lateral flow strips comprising a sample pad, conjugate pad, nitrocellulose membrane, absorbent pad, and backing plate.
Regarding claims 4-5, Wan teaches an embodiment wherein conjugate is disposed in the conjugate pad, and does not teach the limitation of claim 5 wherein the conjugate pad does not contain the conjugate or the limitation of claim 4, wherein analyte is mixed with the conjugate prior to application to the strip.
Regarding claims 4-5, Kim 2022 teaches a CL-LFIA method wherein the conjugate pad does not contain the conjugate. Kim 2022 teaches that as an alternative to disposing the conjugate in the conjugate pad, one can mix the analyte with the conjugate particles to form a mixed solution before the sample is added to the strip (Par. 11: in one embodiment, sample is mixed with conjugate to allow specific binding of conjugate to target analyte),
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Wan in view of Zhang, Kim 2010, Kim 2022, Geng, Leopold, and Zangheri such that the conjugate is not contained in the conjugate pad, and is instead mixed with the sample prior to application of the sample to the strip. One would be motivated to mix the sample and the conjugate before addition of the sample to the strip, because one of ordinary skill would recognize that this allows for control over how much time is allowed for the conjugate to specifically bind to the analyte, wherein the more precise control of binding time in addition to more direct contact between the conjugate and the analyte (provided by mixing in solution rather than within the test strip) will allow for more complete binding of the conjugate to the analyte and greater assay accuracy. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because Wan and Kim 2022 are both directed to similarly structured and conducted lateral flow immunoassay methods.
Response to Arguments
Applicant’s arguments filed 9 March 2026 have been fully considered.
Previous 112(b) rejections are overcome by amendment and are withdrawn. New grounds of 112(b) rejection necessitated by amendment are presented above.
Regarding the 103 rejection, many of applicant’s arguments address individual references used in the rejection without addressing the combination of references in the rejection as a whole; that is, the arguments indicate that no single reference teaches every feature of the claimed invention. These arguments are not persuasive because no single reference is relied upon to teach every features of the claimed invention.
Regarding the combination of references, applicant argues that the cited references do not disclose or suggest the ordered surface engineering strategy or the resulting surface architecture of the conjugate of the claim. This argument is not persuasive because the cited references are used to address a specific combination of order of steps that would result in the proper surface configuration in which : antibodies first occupy portions of the AuNP surface; PEG is covalently attached to remaining exposed gold surface regions; and BSA blocking occurs after PEG conjugation.
Applicant further argues that the rejection reconstructs the invention by selectively extracting unrelated teachings from multiple references across different technical fields, and that the rejection relies on improper hindsight. This argument is not persuasive. Regarding improper hindsight, MPEP 2145(X)(A) provides: Any judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant's disclosure, such a reconstruction is proper. All the references used in the rejection contain teachings and motivations of the prior art which are specifically relevant to the way they are combined in the rejection (i.e. the rejection does not include knowledge gleaned only from applicant’s disclosure). For example, teachings regarding nanoparticle stabilization and synthesis are relevant to the rejection which concerns the synthesis and use of nanoparticle conjugates; teachings regarding the types of labels and detection methods used in immunoassays are relevant to the rejection which concerns an immunoassay method. One of ordinary skill in the art who is employing nanoparticle conjugates and labels in an LFIA method such as the one taught by the primary reference Wan would be motivated to seek out teachings relevant to the synthesis and optimization of such nanoparticles, and teachings relevant to the types of labels and detection which may be advantageously used in an LFIA method. While Applicant argues that there is insufficient motivation to combine these teachings without improper hindsight, Applicant’s arguments do not specifically address or rebut the particular motivations to combine and expectations of success presented in the rejection above.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/ELLIS FOLLETT LUSI/Examiner, Art Unit 1677
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677