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 .
Claims 1-56 are cancelled.
Claims 57-76 are pending.
Applicant’s election without traverse of Group I, claims 57-57 and 74-76, as well as the species of claim 57 and its dependent claims 58-67 in the reply filed on 10/17/2025 is re-acknowledged.
Claims 68-76 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected groups/species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on10/17/2025.
Claim 57 is amended.
Claims 57-67 are under examination on the merits.
Priority
This application is a 371 of PCT/US2020/060500, filed 11/13/2020, which claims benefit of priority to US Provisional Application No. 63/016,758, filed 04/28/2020, and claims benefit of priority to US Provisional Application No. 62/936,147, filed 11/15/2019.
Maintained-Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Maintained-Claim Interpretation
Recitations of one or more “particle(s)” are being interpreted to include a magnetic bead as is consistent with paragraphs 0081 and 0113 of the instant specification.
Regarding the recitations of “determining a fraction of locations comprising both the capture agent and the detection agent,” this limitation is being interpreted as determining the number of locations comprising both the capture agent and the detection agent relative to the total number or some other number of the individual locations (see for example, paragraphs 0111-0112 of the instant specification at page 23 which are deemed to inform and support this interpretation).
Recitations of “quantifying the concentration….based on the fraction of locations…to locations comprising only capture agent,” are being interpreted as requiring quantification of the concentration of the molecule of interest based upon the number of locations found to comprise both the capture agent and the detection agent relative to the number of locations found to comprise only the capture agent (locations comprising both agents: locations comprising only capture agent) (paragraphs 011-0112 and 0159 at pages 23 and 32 are deemed to inform and support this interpretation).
Withdrawn Objections/Rejections
The objection to claim 57 is withdrawn in light of the corrective claim amendments dated 04/13/2026. The rejections under 35 USC §112(b) of claims 57-67 are withdrawn as addressed by the corrective claim amendments dated 04/13/2026. The claim rejections under 35 USC §103 presented in the previous office action dated 01/12/2026 are withdrawn and replaced with the claim rejections as presented in this Office Action under 35 USC §103 to better account for the new and altered claim scope resulting from the 04/13/2026 claim amendments.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 57-59 and 63-67 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sheehan et al (US 20140127719 A1; citation 1 under US Published Patent Applications in the IDS dated 11/29/2023) in view of Dong et al (WIREs Nanomed Nanobiotechnol 2017, 9:e1457. doi: 10.1002/wnan.1457; citation 1 under Non-Patent Literature in the IDS dated 05/06/2024) and Xiao et al (Comb Chem High Throughput Screen. 2013 Jul;16(6):441-448. doi: 10.2174/1386207311316060004).
Regarding claim 57, the claim recites a method for detecting one or more molecules of interest in a sample, the method comprising:
1. providing a solid support
a. comprising a plurality of spatially identifiable individual locations
b. each spatially identifiable individual location comprising a capture agent from one or more capture agent pools, wherein each capture agent pool comprises at least one type of capture agent each configured to bind a single molecule of interest and be separately detected, and wherein the plurality of spatially identifiable locations are pre-patterned into two or more subsets of locations, each subset associated with a single capture agent pool and comprising two or more individual locations such that the identity of the molecule of interest bound by a capture agent at a given location is encoded by position of the given location within the array;
2. loading one or more samples comprising one or more of the molecules of interest onto the solid support, wherein each sample is loaded into one or more of the individual locations;
3. incubating to form capture agent-molecule of interest complexes;
4. detecting the presence or absence of a capture agent-molecule of interest complex at each location; and
5. assigning a binary readout state to each individual location based on the presence or absence of the capture agent-molecule of interest complex at each individual location.
It is noted that the drafting of “the plurality of spatially identifiable locations are pre-patterned into two or more subsets of locations” is not deemed to require any structure different than a typical microarray or femtoliter well plate as the wells (rows and columns) are pre-patterned, where subsets of locations may be grouped together by selective loading of one or both of the sample and/or immobilized bead capture agent in subsets of the wells or even a mental grouping of subsections of the well plate. Furthermore, the drafting of “assigning a binary readout state to each individual location based on the presence or absence of the capture agent-molecule of interest complex at each individual location” does not require more than a mental understanding of a presence or absence, such that noting the presence/absence of a detectable signal indicative of binding of the molecule of interest (such as enzymatic activity or fluorescence) may be understood as assigning a binary readout state to each individual location based on the presence or absence of the capture agent-molecule of interest complex at each individual location.
Sheehan et al teach a method for detecting a non-nucleic acid analyte in a sample, the method comprising:
providing a reaction vessel (solid support) comprising a solid substrate (such as a particle or bead) comprising a bound immobilization agent, wherein the immobilization agent comprises an anti-peptide tag antibody;
providing an antibody capture agent in solution which can bind the analyte, wherein the antibody capture agent comprises a peptide tag ligand for the anti-peptide tag antibody;
providing an antibody detectable agent in solution which can bind to the analyte;
contacting the sample, the capture agent, the detectable agent and the solid substrate in the reaction vessel (held to read upon and make obvious the recited steps of loading and incubating) to allow the formation of a sandwich immunocomplex comprising the analyte, the antibody capture agent and the antibody detectable agent; and
detecting the analyte by detecting the presence of the antibody detectable agent bound to the solid substrate in the reaction vessel (held to read upon assigning a binary readout state based on the presence or absence of the capture agent-molecule of interest complex)
(see for example, Sheehan’s claims 48 and 59-61). Sheehan et al further teach that a reaction vessel (reading on the solid support as recited in the instant claims), being for example a physical container that allows the contacting of the sample, the capture agent, the detectable agent and the solid substrate to occur in the container. Examples of reaction vessels include a test tube, a micro centrifuge tube, a well, or a flask. In some embodiments, the reaction vessel comprises a well of a multi-well plate, such as a microtitre plate, or a well or surface of a microfluidic device (see for example, paragraph 0120-0124). Sheehan et al further explain that in certain embodiments, the solid substrate is separate to the reaction vessel. In these embodiments, the solid substrate may be mobilizable and may be added to the reaction vessel. For example, the solid substrate may be a bead, such as an art-known/conventional, commercially available magnetic bead to which the immobilization agent (such as a capture antibody binding analyte) may be covalently attached (see for example, paragraphs 0129-131). Microfluidics are discussed in further detail at paragraphs 0417-0429 of Sheehan et al.
Sheehan et al do not explicitly teach the use of the bead attached to the capture agent.
However, Dong et al teach successful adaptation of ELISA to incorporate magnetic beads and microfluidic devices/microchips (see for example, column 2 of page 2-column 1 of page 8) and digital ELISA (see for example, column 2 of page 8-column 2 of page 14; paying particular attention to Figures 7-9 and their captions). Dong et al further discuss the work of Rissin et al, through which a PSA digital ELISA was developed using magnetic beads coated in capture antibody yielding a linear relationship between the concentration of analyte (PSA) and the average number of enzyme labels per bead), extending the dynamic range of the ELISA down to a subfentomolar level in a single measurement (see for example, column 2 of page 14 at the End-Point Protein Measurement with Large Dynamic Range heading at the end of the first paragraph of the 1st column of page 15). Dong et al teach that multichannel microELISA systems are reasonably suitable for ubiquitous assays, including point-of-care testing (POCT) (see for example, column 1 of page 2 and column 2 of page 5). Dong et al are deemed to make obvious the isolation of the capture agent to a portion of the individual locations as well as detection.
With respect to the recitation that “each location comprising a capture agent from one or more capture agent pools, wherein each capture agent pool comprises at least one type of capture agent each configured to bind a single molecule of interest and be separately detected,” the only requirement with any bearing upon the instant method is that the location comprises a capture agent (singular). Therefore, a prepared stock of capture agent would suffice to meet the limitation of a capture agent pool, defined as comprising at least one-four capture agents (see for example, paragraph 0145 at page 30 of the instant specification). Though, with regard to a larger capture agent pool (comprising more than 1 capture agent), Sheehan et al teach that in certain embodiments, more than 1 analyte is detected (see for example, paragraph 0362). In certain embodiments the detection of more than one analyte may be achieved by providing several target-specific antibody capture agents to the reaction vessel, in combination with providing their respective detection agents (see for example, paragraph 0364).
Sheehan et al and Dong et al do not explicitly teach that the beads are immobilized into the well (so as to be pre-patterned).
However, Xiao et al teach that one-bead-one-compound (OBOC) combinatorial library screening has been broadly utilized for the last two decades to identify small molecules, peptides or peptidomimetics targeting variable screening probes such as cell surface receptors, bacteria, protein kinases, phosphatases, proteases etc. Xiao et al teach a bead immobilization method such that a bead library array can be conveniently prepared and screened in its entirety, sequentially many times with a series of distinct probes (capture agents). This method not only allowed Xiao et al to increase the screening efficiency but also allowed for determination of the binding profile of each and every library bead against a large number of target receptors. As proof of concept, Xiao et al serially screened a random OBOC disulfide containing cyclic heptapeptide library with three water soluble dyes as model probes: malachite green, bromocresol purple and indigo carmine. This multiplicative screening approach resulted in a rapid determination of the binding profile of each and every bead respective to each of the three dyes. Beads that interacted with malachite green only, bromocresol purple only, or both indigo carmine and bromocresol purple were isolated, and their peptide sequences were determined with microsequencer. Ultimately, the novel OBOC multiplicative screening approach could play a key role in the enhancement of existing on-bead assays such as whole cell binding, bacteria binding, protein binding, post-translational modifications etc. with increased efficiency, capacity, and specificity (see for example, the abstract at page 1; for greater details on the process and benefits of Xiao et al’s PDMS bead immobilization, see the reference in its entirety with page 7, teaching the process, being an exemplary citation).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Sheehan et al and Dong et al. The artisan would have been motivated to make and use the invention as claimed because both references teach devices compatible with methods for performing ELISA where Dong et al teach ways to modify/optimize ELISA for POCT and further teach the state of the art regarding ELISA. The loading of sample and the loading of the beads into the individual wells of the microarray, well plate, femtoliter well plate, etc. so as to create subsets of individual locations within the prepatterned array/plate is a matter of obvious choice yielding no more that predictable results allowing the artisan to visualize presence or absence of the molecule of interest (analyte) complexed with the bead coated in capture agent in the well(s) (see MPEP §2141.I). The artisan could and would have, with high predictability as no structure is altered, arranged any number of subsets by loading of a single bead coated in a capture agent into a given well and loading of one or more samples accordingly (such as creating rows of wells each holding a bead coated in a different capture agent and columns corresponding to a single sample, allowing for spatial encoding of capture-agent molecule of interest complex that would allow for binary present/absent readouts based upon the pre-patterned individual location (well). This is particularly true, with respect to pre-patterning the subsets of locations, where the beads are immobilized by a process such as that of Xiao et al, which the artisan would have been motivated to do in order to achieve the significant and varied advantages taught by Xiao et al. This would enable easy analysis of data such that the artisan would have found it an obvious matter of choice yielding highly predictable results. Detection of the antibody binding of Sheehan, the fluorescence well signal of Dong et al, or the dye signal of Xiao et al would allow for detection of the presence or absence of the bound molecule of interest in one or more given subsets of wells, therefore reading on the assignment of a binary readout state step as instantly claimed. The artisan would have so modified the references to allow for the use of multiple capture agents (one capture agent on a single bead) as discussed in Sheehan et al and Xiao et al) for enhanced, rapid screening for multiple analytes in a sample with the expectation of predictable results for successful screening/assaying. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references and would have been motivated prior to the effective filing date.
Regarding claim 58, as defined at paragraph 0069 of the specification (see page 14 of the instant specification), a probe refers to a molecule that binds specifically or selectively to a molecule [of interest such as the analyte]. 'The probe may be a nucleic acid, an aptamer, an avimer, receptor-binding ligands, binding peptides, protein, small organic molecules, or a metal ligand. The probe may be an antibody, antibody fragment, a bispecific antibody or other antibody-based molecule or compound designed to bind to a specific biomolecule. The probe may be the same type of molecule as the biomolecule, for example, a protein biomolecule may be bound by a peptide-based probe.
Dong et al teach the use of a capture antibody immobilized on a magnetic bead in an immunoassay (see for example, column 2 of page 3 and Figure 2 and its caption at page 4).
The method of claim 58 is obvious for the same reasons that the method of claim 57 is obvious.
Regarding claim 59, as noted in the Claim Interpretation section of this Office Action above, a particle is being interpreted to encompass/include a magnetic bead. This is taught and made obvious by the combination of Sheehan et al and Dong et al (see the rejections of claims 57 and 58 above).
The method of claim 59 is obvious for the same reasons that the method of claim 57 is obvious.
Regarding claim 63, as noted above, Sheehan et al, in view of Dong et al, teach a method comprising contacting the sample, the capture agent, the detectable agent and the solid substrate in the reaction vessel to allow the formation of a sandwich immunocomplex comprising the analyte, the antibody capture agent and the antibody detectable agent and then detecting the analyte by detecting the presence of the antibody detectable agent bound to the solid substrate in the reaction vessel (see for example, claims 48, 59, and 60). Dong et al further teach that such contacting to form a capture-agent-molecule of interest-detection agent complex is well known in the art (see for example, figure 1 and its caption at page 3, figure 2 and its caption at page 4, figure 3 and its caption at page 5, and column 1 and figure 4(a) of page 6).
The method of claim 63 is obvious for the same reasons that the method of claim 57 is obvious.
Regarding claim 64, Dong et al teach that a common ELISA format comprises an enzyme-linked secondary antibody (detection agent which is a probe) configured to bind the molecule of interest and a detection moiety (where the detection moiety may be substrate for the enzyme) (see for example, column 1 of page 2, Figure 1 and its caption at page 3, and the discussion of Kim et al at column 2 of page 3-page 4 including Figure 2 and its caption).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Sheehan et al and Dong et al. The artisan would have been motivated to make and use the invention as claimed because Dong et al teach that contacting the solid support, capture agent, molecule of interest, and detection agent, to form a capture agent-molecule of interest-detection agent complex where the detection agent (a probe (a secondary antibody that is linked to an enzyme) is capable of binding the same molecule of interest as the capture agent as well as binding a detection moiety (substrate) (see paragraph 0010 at page 2 of the instant specification which supports this understanding of the scope of the claim). The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Regarding claim 65, the recited step of using software configured to spatially identify the individual locations of the solid support to correlate the presence of capture agent and detection agent with the presence of the molecule of interest is being interpreted to encompass using software capable of measuring the various locations of the solid support to measure the detected signal from the capture agent-molecule of interest-detection agent complex which has reacted with substrate, thereby producing a detectable product/reaction. Note further that the recitation of “using software configured to spatially identify the individual locations” is being interpreted as using any software capable of performing spatial-spectral encoding (the term Applicant used repeatedly throughout the disclosure as encompassing the analysis performed. The instant specification provides descriptive definition of the term “spatial-spectral encoding” at paragraph 0138 of page 28. The Examiner believes that this section supports the Examiner’s interpretation of this limitation in light of the high-level of generality in the claim language.
Dong et al appear to teach an ELISA for analyzing testosterone concentration where the chemiluminescent images were captured using a house-made instrument, and the images were analyzed by Image J software to calculate the testosterone concentration in samples (see for example, the first paragraph of column 2 of page 6; see also figure 10 and its caption at page 14). Dong et al further teach that Chang et al, using a digital ELISA platform, detected fluorescence of each well on a CCD camera, where the fraction of beads associated with at least one enzyme, the average fluorescent intensity of the beads, and the average number of enzyme associated with the beads in an assay were analyzed by the software (which is held to read on the recitation of using software to spatially identify the individual locations) (see for example, column 2 of page 11 of Dong et al). Dong et al appear to further show that analysis by spatially identifying individual locations on the solid support is well known in the art, whether by using software or not (see for example, Figures 7, 9, and 10 at respective pages 10, 13, and 14).
The method of claim 65 is obvious for the same reasons that the method of claims 57, 63, and 64 are obvious.
Regarding claims 66 and 67, Dong et al teach that a microfluidic system for generation and analysis of water-in-oil droplets was developed by Shim et al and was used for digital counting of enzyme molecules. This digital fluidic ELISA used PSA bound to antibody-coated beads which was then sandwiched by a biotinylated detection antibody and a streptavidin-β-galactosidase conjugate. After incubation, three types of femtodroplets, droplets containing no bead, those containing a bead without immunocomplexes, and those containing a bead with an immunocomplex were observed. The droplets exhibited a positive fluorescence signal derived of the activity of a single-enzyme molecule. The numerical ratio of wells with fluorescence signal to wells containing beads yields the concentration of the target analyte (see for example, column 2 of page 13 through column 2 of page 14, including Figure 10 and its caption at page 14). This teaches detection of the fraction (number) of wells with only capture agent and the detection of the fraction (number) of wells with capture agent-molecule of interest-detection agent complexes was known in the art and understood to be relevant for determining the concentration of analyte in the sample (for this example in Dong et al, the concentration of PSA). Where Dong et al, at the caption of figure 10 (see page 14), teach that the numerical ratio of wells containing capture agent-molecule of interest-detection agent complexes to well with only beads coated in capture agent and wells containing capture agent-molecule of interest-detection agent complexes yields the concentration of the target analyte, this is deemed to read upon the claim limitation(s) of instant claim 67 as presently drafted.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Sheehan et al, Dong et al, and Xiao et al. The artisan would have been motivated to make and use the invention as claimed because Dong et al teach that quantification of the concentration of the molecule of interest based upon the fraction of locations having an immunocomplex (complex of capture agent-molecule of interest-detection agent) is known in the art to be successful, with or without software. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Claim(s) 60-62 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sheehan et al, Dong et al and Xiao et al, as applied to claims 57-59 and 63-67 above, in further view of Rissin et al (Lab Chip, 2013,13, 2902-2911; citation 51 under Non-Patent Literature in the IDS dated 11/29/2023).
Regarding claim 60, the instant specification is deemed to best describe a detectable label at paragraph 0081 (noting that this specific term is not mentioned throughout this instant specification).
Sheehan et al, Dong et al, and Xiao et al do not appear to explicitly teach labeling the beads (capture agent).
However, Rissin et al teach that they developed a method that enables the multiplexed detection of proteins based on counting single molecules. Paramagnetic beads were labeled with fluorescent dyes to create optically distinct subpopulations of beads, and antibodies to specific proteins were then immobilized to individual subpopulations. Mixtures of subpopulations of beads were then incubated with a sample, and specific proteins were captured on their specific beads; these proteins were then labeled with enzymes via immunocomplex formation. The beads were suspended in enzyme substrate, loaded into arrays of femtoliter wells—or Single Molecule Arrays (Simoa)—that were integrated into a microfluidic device (the Simoa disc). The wells were then sealed with oil, and imaged fluorescently to determine: a) the location and subpopulation identity of individual beads in the femtoliter wells, and b) the presence or absence of a single enzyme associated with each bead. The images were analyzed to determine the average enzyme per bead (AEB) for each bead subpopulation that provide a quantitative parameter for determining the concentration of each protein. Rissin et al used this approach to simultaneously detect TNF-α, IL-6, IL-1α, and IL-1β in human plasma with single molecule resolution at subfemtomolar concentrations, i.e., 200- to 1000-fold more sensitive than current multiplexed immunoassays. Rissin et al teach that the simultaneous, specific, and sensitive measurement of several proteins using multiplexed digital ELISA could enable more reliable diagnoses of disease (see for example, the abstract at page 2902).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Sheehan et al, Dong et al, and Rissin et al. The artisan would have been motivated to make and use the invention as claimed because Sheehan et al, Dong et al, Xiao et al, and Rissin et al all pertain to the adaptation and use of ELISA where Rissin et al teach that the use of dyed beads create optically distinct subpopulations of beads for later analysis of the localized subpopulations in a multiplexed immunoassay. This would, for example, make distinction of beads comprising only capture agent (not detection agent) more readily visualized for background control/quality control. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Regarding claim 61, Rissin et al teach that 7-μm-diameter, carboxyl-functionalized paramagnetic beads were obtained from Agilent Technologies. Alexa Fluor 488 hydrazide was obtained from Life Technologies. Cyanine-5 (cy5) hydrazide was obtained from GE Healthcare. Hilyte 750 hydrazide was obtained from Anaspec (see for example, the Materials section at column 1 of page 2903). Note that Alexa Fluor 488 hydrazide, Cyanine-5 (cy5) hydrazide, and Hilyte 750 hydrazide are known in the art as fluorophores, any one or more of which would have been obvious to include in the method of Sheehan et al, Dong et al, Xiao et al, and Rissin et al as a detectable label on the capture agent (such as a dye on the bead to which the capture antibody is attached) which is deemed to make obvious the limitations of instant claim 61.
Claim 61 is obvious for the same reasons that claim 60 is obvious.
Regarding claim 62, Sheehan et al teach that in certain embodiments, more than 1 analyte is detected (see for example, paragraph 0362). In certain embodiments the detection of more than one analyte may be achieved by providing several target-specific antibody capture agents to the reaction vessel, in combination with providing their respective detection agents (see for example, paragraph 0364).
While the Examiner believes that the teachings of Sheehan et al in view of Dong et al and Xiao et al would sufficiently teach and make obvious the limitations of instant claim 62, the teachings of Rissin et al more explicitly teach the limitation of loading one or more capture agent pools into the solid support.
Rissin et al teach that a Single Molecule Array (Simoa) disc composed of 24, 3 × 4 mm arrays of ∼216 000 femtoliter wells and individually addressable microfluidic manifolds was placed on the platen of a customized system developed by Stratec Biomedical for the load, seal, and imaging of the arrays. For each sample analyzed, 15 μL of the solution containing the mixture of bead subpopulations (held to read upon one or more capture pool) and RGP was pipetted manually into the inlet port of the disc (held to read upon the limitation of loading the one or more capture pools into the solid support) (see for example, column 2 of page 2903-column 1 of page 2904).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references. The artisan would have been motivated to make and use the invention as claimed because the combined references teach multiplexed assays where the artisan would have understood the need to have multiple capture agents in order to have an agent specific for each molecule of interest. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Applicant’s Arguments and Responses
A. Applicant argues that the drawings are in black and white as a basis for withdrawal of the objections to the drawings.
Response: Applicant submitted black and white drawings which appear to have been initially rendered using color noting that the figures and the descriptions of the figures discuss color (see for example, the description of figure 1J (paragraph 0017at page 3 of the specification) and Fig. 12B at page 29/62. The descriptions referring to color where no color can be observed creates unnecessary confusion. Either the drawings should be accompanied by a petition to permit color figures to correspond to the descriptions or the descriptions of the figures should be amended to avoid reference to color which is absent in the black and white figures.
B. Applicant argues that the rejections of the claims under 35 USC §103 did not account for pre-patterned subsets of individual locations.
Response: The rejections presented in this Office action, replacing the rejections presented prior to Applicant’s 04/13/2026 claim amendments, account for the newly claimed features. It is noted that certain feature which Applicant discusses in the arguments/remarks dated 04/13/2026 are not required by the claims as drafted, but reflect an unclaimed, perhaps preferred embodiment. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., loading the sample across all subsets, the requirement for more than one capture agent (as a pool may be a single agent per Applicant’s own definition as referenced above), perpendicular loading relative to the patterning channels, etc.) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Additionally, Applicant discusses the references in isolation, but does not address the combined teachings and rationale as articulated in the claim rejections. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The rejections under 35 USC §103 as presented in this Office Action are deemed to make obvious, before the effective filing date, the claimed invention, with a reasonable expectation of success, and are therefore maintained at this time.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Ekins et al (US 5516635A; citation 1 under US Patents in the IDS dated 11/29/2023) is deemed relevant and discusses pre-equilibrium quenching and measurements.
Duffy et al (US9310360B2) is deemed relevant.
Link et al (US11187702B2) is deemed relevant.
Kimoto et al (Nucleic Acids Res. 2019 Sep 19;47(16):8362-8374. doi: 10.1093/nar/gkz688), Waritani et al (MethodsX. 2017 Mar 30;4:153-165. doi: 10.1016/j.mex.2017.03.002), Swanson et al (Curr Opin Microbiol. 2012 Jun;15(3):337-47. doi: 10.1016/j.mib.2012.05.015), Drummond, J. (Common ELISA Problems and Solutions, My Assays, available from: https://www.myassays.com/common-elisa-problems-and-solutions.html#:~:text=The%20B%20control%20consists%20of,the%20wash%20process%20is%20needed.; available as of 2015 as evidenced by Wayback Machine), and Mitsuno et al (Biosens Bioelectron. 2015 Mar 15; 65: 287-94) are deemed relevant to the use of a kinetic/non-saturated (preequilibrium) measurement and calculations therefrom.
WO2015109020 A1 (citation 1 under foreign patent literature on the IDS dated 10/29/2024) and Wilson et al (citation 2 under Non-Patent Literature on the IDS dated 05/06/2024) are deemed relevant.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ASHLEY GAO whose telephone number is (571) 272-5695. The examiner can normally be reached on Monday- Friday 8-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
supervisor, Gregory Emch can be reached on (571) 272-8149. The fax phone number for the
organization where this application or proceeding is assigned is 571-273-8300.
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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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