DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Applicant' s amendment filed 03/16/2026 is acknowledged. Claims 1, 3, 5-6, 8-9, and 11-16 have been amended. Claim 7 has been cancelled. Claims 1-27 are pending in the instant application, claims 18-27 remain withdrawn, and claims 1-6 and 8-17 are subject of this final office action.
All of the amendments and arguments have been reviewed and considered. Any rejections or objections not reiterated herein have been withdrawn in light of amendments to the claims or as discussed in this office action.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Previous Action
Status of Prior Rejections/Objections:
The objections to the specification and drawings are withdrawn in view of the respective amendments.
The objections of claims 1, 7-8, and 13-14 are withdrawn in view of the amendments to or cancellation of the claims.
The 112(b) rejections directed to claims 1, 11-14, and 16 have been withdrawn in view of the amendments. The 112(b) rejection directed to claim 3 is withdrawn in part and clarified in view of amendments. The 112(b) rejection directed to claim 6 is modified in view of the amendments.
The 112(d) rejection of claim 10 is withdrawn in view of the amendments. The 112(d) rejection of claim 3 is maintained and clarified in view of the amendments.
The prior art rejection(s) under 35 USC 103 over Steinmetzer in view of Martin are maintained and modified in view of the amendments.
Each of the double patenting rejections is maintained and modified in view of the amendments.
New Ground(s) of Rejections
The new ground(s) of rejections were necessitated by applicant’s amendment of the claims.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Interpretation
In evaluating the patentability of the claims presented in this application, claim terms have been given their broadest reasonable interpretation (BRI) consistent with the specification, as understood by one of ordinary skill in the art, as outlined in MPEP 2111.
Regarding claims 1-6 and 8-17, the specification lacks a limiting definition of “porous”. Merriam Webster (Merriam-Webster [Internet]. Springfield (MA): Merriam-Webster; 2025. Porous; [cited 2025 Sep 6]. Available from: https://www.merriam-webster.com/dictionary/porous) defines the term as “possessing or full of pores”, “permeable to fluids”, and/or “capable of being penetrated”. The claims were interpreted broadly to encompass any of these definitions.
Claim Rejections - 35 USC § 112(b)
Claims 3-6 and 15-16 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.
Regarding claim 3, as discussed previously, the claim recites “A method…according to claim 1, said method comprising the following steps…”, wherein the steps comprise overlapping steps to those of claim 1 and the elements appear to have been replaced with new recitations of the same concepts under new terminology, but each claim has unique limitations. The nexus to claim 1 and the terminology thereof is therefore unclear.
Specifically, it is not clear whether the claim intends replace the steps of claim 1, wherein it would be unclear how the additional limitations of claim 1 map to the newly recited elements, or to recite an additional set of steps.
Given this lack of nexus between the claim terms of claims 1 and 3, where there are definite articles used, the terms lack antecedent basis in claim 3 and each of the dependent claims thereof (e.g., “said sample” in claim 3, b where claim 3 recites “a plurality of separate biological samples” and claim 1 recites “a plurality of different biological samples”).
Claims 4-6 and 15-16 are indefinite for depending from claim 3 and not rectifying the deficiency.
Regarding claims 4-5 and 16, as newly amended, claim 3 recites “a plurality of porous microparticles” and “subsets of prefabricated porous microparticles”. Claim 1 recites “a plurality of differently labelled subsets of porous microparticles ... wherein each of said porous microparticles has a porous matrix that allows said ... microparticle to accumulate an analyte ... through: ... (i) – (iii)” and “subsets of porous microparticles”.
Claim 4 recites “subset(s) of microparticles”. Claim 5 recites “subset of microparticles”. Claim 16 recites “said microparticles”.
It is unclear which microparticle(s) is being referred to in each of the identified claims, as amended. This is an antecedent basis issue.
Regarding claim 6, the amended claim recites “The method according to claim 5, wherein step e)”. Under the new claim dependency, there is no antecedent basis for “step e” which is recited in claim 4.
For the sake of compact prosecution, Applicant is reminded of the “said first and second records of correlation” which are introduced in claim 5.
Claim Rejections - 35 USC § 112(d)
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Regarding claim 3, the claim recites “A method…according to claim 1” but fails to incorporate all the limitations of claim 1. In particular, it re-recites “a plurality of…samples”; “a plurality…of porous microparticles”; etc. and recites steps that seemingly overlap with and replace those of claim 1. Namely, it fails to incorporate all the limitations of claim 1.
As newly amended, claim 3 also recites “a plurality of prefabricated porous microparticles” and then recites “plurality of prefabricated porous microparticles” throughout. Newly amended claim 1 now recites “wherein each of said porous microparticles has a porous matrix that allows said porous microparticles to accumulate an analyte of interest through: (i) ... (ii) ... (iii) ...; or (iv) any combination of (i) – (iii).” As the terminology of claim 3 for the prefabricated microparticles is distinct from that of claim 1, the microparticles of claim 3 would also not be required to accumulate the analyte of interest by any of (i) – (iii) or a combo thereof.
For these reasons, claim 3 is not in proper dependent form and therefore fails to comply with the requirements of 112(d).
Claim Rejections - 35 USC § 103
Claim(s) 1-6 and 8-17 are rejected under 35 U.S.C. 103 as being unpatentable over Steinmetzer (WO 2018/122162 A1; published 05/07/2018; as cited in the IDS dated 05/07/2018) in view of Martin (WO 2009/048530 A2; published 04/16/2009; as cited in the IDS dated 05/18/2023), as evidenced by Thermo Fisher (Thermo Fisher Scientific. Invitrogen Platinum Hot Start PCR 2X Master Mix [Internet]. Thermo Fisher Scientific; 2015 Jul 14 [cited 2025 Sep 6]. Available from: https://documents.thermofisher.com/TFS-Assets/LSG/manuals/Platinum_Hot_Start_PCR_Master_Mix_UG.pdf).
Regarding claim 1, Steinmetzer teaches a method of detection of an analyte in a sample (pg. 6, lines 22-23) comprising:
Providing a porous microparticle (pg. 6, lines 24-pg. 7, line 2; pg. 9, line 22) and an aqueous [i.e., liquid] sample suspected of containing an analyte (pg. 7, line 3), wherein the microparticles are specifically labelled (pg. 10, line 12) and part of a collection [i.e., subsets of microparticles] (pg. 10, lines 14-15; see also pg. 10, lines 32-pg. 11, line 20), wherein a collection comprises different types of microparticles [i.e., subsets] (pg. 19, lines 12-18) and may be spatially separated from each other (pg. 19, lines 20-24)
Exposing said microparticle to an aqueous [i.e., liquid] sample, allowing the microparticle to bind/immobilize/receive the analyte to be detected if present [i.e., take up the sample] (pg. 7, line 3-5)
Transferring the microparticle into a non-aqueous phase (pg. 7, lines, 6-9), wherein if the microparticles are spatially separated in the previous step such an act of transferring likewise would be separate
Generating a suspension in the non-aqueous phase (pg. 11, line 31-32; see also the embodiment of the gel microparticles: pg. 15, lines 9-14, lines 26-28)
Performing a detection reaction (pg. 11, lines 16-19)
Detecting the signal from the reaction indicative of the analyte (pg. 11, line 19), wherein the microparticles are suspended (Fig. 2)
Steinmetzer teaches that the method may also be used for quantitation (entire work, e.g., Abstract; pg. 1, line 8; pg. 21, line 24; and pg. 32, line 6). Steinmetzer teaches further performing digital PCR (e.g., pg. 28, line 7) and digital ELISA (pg. 28, lines 26-pg. 29, line 4 and pg. 32, lines 1-14) [i.e., quantification of said analyte; see instant claim 17]).
Steinmetzer teaches that collections of microparticles comprising different types [i.e., subsets of microparticles] particularly useful for detection of analytes in one or several samples [i.e., a plurality] (pg. 19, lines 12-18).
Steinmetzer teaches that in a collection of microparticles, the corresponding analytes can be distinguished by specific labels (pg. 5, lines 12-16). See also pg. 19, para 1.
Steinmetzer teaches an example with an HIV-1 RNA liquid sample [i.e., a biological liquid sample] (pg. 26, lines 24-30).
Steinmetzer teaches that the microparticles bind the analyte(s) (pg. 7, lines 3-6) and that porous microparticle that allows the uptake of liquid and of an analyte present in said liquid in the space provided for by the pores of said microparticle (pg. 7, lines 20-34, spanning pg. 8, lines 1-2), wherein the microparticle may be made of a gel-forming agent that forms a porous matrix (pg. 9, para 6) and the gel-forming agent is selected from a group comprising polymers (pg. 9, para 7) [i.e., each of said porous microparticles has a porous matrix that allows the microparticles to accumulate an analyte of interest by binding to an analyte through a polymer that forms a porous matrix]. Steinmetzer teaches ultra-low gelling agarose-based “DAB” matrix microparticles (pg. 24-26, Embodiment 1).
In teaching microparticles that have the porous matrix, ability to accumulate analyte, and overlapping polymers of the instant application (see, e.g., instant pg. 13, para 2), the capability of microparticles of Steinmetzer to bind to the analyte through the polymer or polymer mixture that forms the porous matrix is understood to be an inherent characteristic. See MPEP 2112.01(I).
Steinmetzer also teaches that the polymers may comprise polypeptides including gelatin or polynucleotides [i.e., at least one charged group and/or at least one ionizable group on the polymer of the matrix] (pg. 4, para 4).
However, Steinmetzer fails to explicitly teach in such an embodiment with a plurality of samples that the microparticles have a label corresponding to a sample subset and that the differently labeled subsets are mixed after the transferring step.
Martin rectifies this by teaching a method of detecting and optionally quantitating analytes (Abstract; Fig. 2) comprising:
Separately providing a first and a second sample and a first and a second set of microparticles (para [0027]; see also para [0105]), wherein the subsets of microparticles are distinguishable [i.e., labeled] (para [0076] and [0105]; see also para [0094] for distinguishing features, i.e., instant labels) and the liquid sample may be a biological liquid sample (para [0091])
Separately exposing both sets of microparticles to their corresponding sample (para [0027]
Mixing together the subsets of microparticles (para [0028])
Martin teaches that in the methods of the invention, different populations of particles are contacted with each sample separately, combined before processing steps for detection of the analyte, and then read together, enabling analytes from different samples to be detected simultaneously with concomitant savings in both processing and read times (para [0075]).
Therefore, it would have been obvious to one of ordinary skill in the art at the time of filing to utilize the multiplexing method of Martin wherein the populations of microparticles corresponding to samples are distinctly labeled to improve the detection method using porous microparticles of Steinmetzer in order to save on processing and read time, as taught by Martin. There would have been a strong expectation for success as both are directed to using microparticles to detect analytes in one or more samples and the combination represents a known technique applied to a known method.
Regarding claim 2, in the method of Steinmetzer in view of Martin, Steinmetzer teaches that a detection agent [i.e., a detection composition] is included in an aqueous solution in which it microparticles are reconstituted (pg. 9, lines 13-15), wherein a detection agent may comprise a mixture of reagents capable of starting a chemical reaction (pg. 10, lines 5-10). Steinmetzer teaches that the microparticles take up the liquid (pg. 7, lines 28-30).
Both the methods of Martin and Steinmetzer teach exposing (sub)sets of microparticles to one biological sample each, as cited in the rejection of claim 1.
Regarding claim 8, in the method of Steinmetzer in view of Martin, Steinmetzer teaches microparticles made of a gel-forming agent, wherein the gel-forming agent forms a porous matrix and wherein the gel-forming agent is a polymer (pg. 9, lines 17-34; pg. 4, lines 15-16).
Steinmetzer teaches the matrix defines the surface and the void volume of the microparticle (pg. 15, lines 16-17).
Steinmetzer teaches microparticles with capture agent molecule [i.e., an instant analyte-specific reagent] immobilized on [i.e., attached to] the surface and void volume [i.e., contained in] (pg. 21, lines 9-24; Fig. 1), wherein the capture agent [instant ASR] is capable of specifically binding the analyte of interest (pg. 21, line 33-pg. 22 line 1; pg. 8, line 29) and allowing enrichment of an analyte (pg. 9, lines 1-3).
Steinmetzer teaches that the capture agent [instant ASR] is selected from antibodies/fragments thereof, nucleic acids, and non-antibody proteins capable of specifically binding an analyte or analyte complex (pg. 10, lines 1-5).
Regarding claim 9, in the method of Steinmetzer in view of Martin, Steinmetzer further teaches that all microparticles may be specific for the detection of one analyte [i.e., wherein the ASR that specifically binds to the analyte would be the same] (pg. 19, line 14).
Regarding claim 10, in the method of Steinmetzer in view of Martin, Martin further teaches its differently labeled microparticles, as cited in the rejection of claim 1 above, and an embodiment in which the capture molecules on each of the subsets of particles of the second population [corresponding to the second sample] is substantially identical to the capture molecules on the subsets of the capture molecules on each of the subsets of the first population [corresponding to the first sample] (para [0031]).
Martin teaches that the particles of the first and second populations are distinguishable [i.e., labeled and defined by said label] (para [0030] and para [0098]). Steinmetzer and Martin both teach the use of microparticles with dyes in the microparticles [i.e., contained in the microparticles] (Steinmetzer: pg. 23 line 10; Fig. 4; Martin: para [0158]).
Martin teaches that the number of particle populations [corresponding to sample(s)], subsets of particles in each population, etc. can be varied as desired for the particular application of interest (para [0013]).
Thus, as Steinmetzer teaches that all microparticles [i.e., in a subset] may be specific for an analyte and Martin teaches that the samples may comprise substantially identical populations of subsets, in the combined method, it follows that each sample may be exposed to microparticles that share the same ASR but differ by the label of Martin.
Further, such an arrangement of subsets represents mere routine optimization of the number of labels and ASRs, not least because Martin discusses optimizing for a particular application.
It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed range merely represents routine optimization of the vales of the cited prior art.
Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel's arguments in place of evidence in the record.
Regarding claim 11, in the method of Steinmetzer in view of Martin, as cited in the rejection of claim 9, Steinmetzer teaches that the microparticles may be specific for the detection of one analyte. As cited in the rejection of claim 10, Martin teaches a first and a second population of microparticles exposed to a first and second sample, respectively.
Thus, it follows that the number of subsets would equal the number of samples.
Martin teaches that the number of particle populations [corresponding to sample(s)], subsets of particles in each population, etc. can be varied as desired for the particular application of interest (para [0013]).
Further, such an arrangement of subsets represents mere routine optimization of the number of subsets, not least because Martin discusses optimizing for the particular application.
The notes and advice regarding routine optimization in the rejection of claim 10 above are reiterated here.
Regarding claim 12, in the method of Steinmetzer in view of Martin, Steinmetzer teaches that there may be different types of microparticles with each type being specific for the detection of a different analyte [i.e., wherein the ASR that specifically binds to the analyte would be different] (pg. 19, lines 15-18).
Regarding claim 13, in the method of Steinmetzer in view of Martin, as in the rejection of claim 8, Steinmetzer teaches that the ASRs may be attached to the porous matrix.
Martin further teaches an embodiment with different panels [instant classes, corresponding to, e.g., samples] consisting of eight different color coded beads [instant subsets having a distinct label component contained in said microparticle], wherein each panel contains the same eight “zip code oligos” [instant ASRs] on the beads, wherein each of the 64 different beads subsets is distinguishable [i.e., defined and identifiable by the label and respective ASR] (para [0191]; Fig. 4B).
Martin teaches that the different classes differ by the respective ASR (Fig. 4B), wherein each class comprises eight subsets, wherein each of said subsets have the same ASR but a different label (Fig. 4B; para [0191]).
Regarding claim 14, in the method of Steinmetzer in view of Martin, as cited in the rejection of claim 13, Martin teaches an 8x8 embodiment in which eight analytes of interest are detected and/or quantitated. Martin teaches that a sample of RNAs was added to each well containing the number 1, 2, 3, 4, 5, 6 ,7 or 8 microparticle class set (para [0191]).
In this embodiment, Martin does not explicitly teach that the sample is a biological liquid sample.
Martin rectifies this by teaching various biological liquid samples as cited in the rejection of claim 1. Martin teaches that the samples may be different, e.g., from different or differently treated cell lines, cell types, tissues, or organisms (para [0091]).
Martin further teaches that since later processing steps for the beads across the eight panels are performed in the same wells, the inter-panel [i.e., instant inter-class] precision is improved relative to that typically observed for samples processed in different wells (para [0192]).
Martin teaches that the number of particle populations [corresponding to sample(s)], subsets of particles in each population, etc. can be varied as desired for the particular application of interest (para [0013]).
Therefore, in the method of Steinmetzer in view of Martin, it would have been obvious to one of ordinary skill in the art at the time of filing to utilize the method on different samples in the 8x8 format of Steinmetzer in view of Martin, motivated by the desire to obtain improved precision relative to what may be obtained by processing such samples in different wells, as taught by Martin. There would have been a strong expectation of success as this is a known technique applied to a known method directed to analyte detection with microparticles.
In such a method with different, e.g., cell types utilized in each well with each of the eight classes capable of detecting the eight analytes, there would 64 total subsets for 8 samples times 8 analytes.
Further, such an arrangement of subsets represents mere routine optimization of the number of subsets and analytes chosen, not least because Martin discusses optimizing for the particular application.
It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed range merely represents routine optimization of the vales of the cited prior art.
Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel's arguments in place of evidence in the record.
Regarding claim 17, in the method of Steinmetzer in view of Martin, Steinmetzer teaches that the detection comprises amplification of nucleic acids (pg. 7, d2-d3) and performing digital detection (pg. 8, line 5).
Regarding claim 3, Steinmetzer teaches a method of detection of an analyte in a sample (pg. 6, lines 22-23) comprising:
Providing a porous microparticle (pg. 6, lines 24-pg. 7, line 2; pg. 9, line 22) and an aqueous [i.e., liquid] sample suspected of containing an analyte (pg. 7, line 3), wherein the microparticles are specifically labelled (pg. 10, line 12) and part of a collection [i.e., subsets of microparticles] (pg. 10, lines 14-15; see also pg. 10, lines 32-pg. 11, line 20), wherein a collection comprises different types of microparticles [i.e., subsets] (pg. 19, lines 12-18), may be spatially separated from each other (pg. 19, lines 20-24), and may have a porous matrix (pg. 9, lines 17-34), wherein the matrix further defines the void volume (pg. 15, lines 16-17) which receives the aqueous solution (entire document, e.g., pg. 8, lines 5-6) [i.e., is configured to receive a volume of liquid in the matrix]
Steinmetzer teaches a detection agent [i.e., a detection composition] is included in an aqueous solution in which microparticles are reconstituted (pg. 9, lines 13-15), wherein a detection agent may comprise a mixture of reagents capable of starting a chemical reaction (pg. 10, lines 5-10) and the detection agent is contained in the microparticles (pg. 22, lines 14-15).
Exposing said microparticle to an aqueous [i.e., liquid] sample, allowing the microparticle to bind/immobilize/receive the analyte to be detected if present [i.e., take up the sample] (pg. 7, line 3-5), wherein Steinmetzer teaches agarose particles with embedded regents for carrying out a PCR amplification (pg. 28, line 30, spanning pg. 29, line 1)
Transferring the microparticle into a non-aqueous phase (pg. 7, lines, 6-9), wherein if the microparticles are spatially separated in the previous step such an act of transferring likewise would be separate
Steinmetzer further teaches removing any aqueous liquid not embedded in a particle from the non-aqueous phase (pg. 22, lines 33-34), which generates a reaction space comprising a detection reaction [i.e., the sample and reagents for performing said reaction, which are inherently required for said reaction; see also pg. 26, lines 27-28, where DABs are equivalent to the instant microparticles and the streptavidin is a reagent] (pg. 23, lines 5-7), wherein said reaction space is defined by the “void volume” [i.e., confined to said volume] of the prefabricated microparticle (pg. 6, lines 17-20).
Generating a suspension in the non-aqueous phase (pg. 11, line 31-32; see also the embodiment of the gel microparticles: pg. 15, lines 9-14, lines 26-28)
Subjecting said microparticle to conditions required for performing a detection reaction (pg. 11, d2; pg. 28, lines 10-25) and performing a detection reaction (pg. 11, lines 16-19)
Detecting the signal from the reaction indicative of the analyte (pg. 11, line 19), wherein the microparticles are suspended (Fig. 2)
Steinmetzer teaches that the method may also be used for quantitation (entire work, e.g., Abstract, pg. 1, line 8, and pg. 32, line 6). Steinmetzer teaches further performing digital PCR (e.g., pg. 28, line 7) and digital ELISA (pg. 28, lines 26-pg. 29, line 4 and pg. 32, lines 1-14) [i.e., quantification of said analyte; see instant claim 17]).
Steinmetzer teaches that collections of microparticles comprising different types [i.e., subsets of microparticles] particularly useful for detection of analytes in one or several samples [i.e., a plurality] (pg. 19, lines 12-18).
Steinmetzer teaches that in a collection of microparticles, the corresponding analytes can be distinguished by specific labels (pg. 5, lines 12-16).
Steinmetzer teaches an example with an HIV-1 RNA liquid sample [i.e., a biological liquid sample] (pg. 26, lines 24-30).
However, Steinmetzer fails to explicitly teach that in such an embodiment with a plurality of samples that each subset of microparticles is characterized by a specific label component corresponding to a sample subset and that the step of providing includes at least as many different subsets of microparticles as the number of separate biological liquid samples.
Martin rectifies this by teaching a method of detecting and optionally quantitating analytes (Abstract; Fig. 2) comprising:
Separately providing a first and a second sample and a first and a second set of microparticles (para [0027]; see also para [0105]), wherein the subsets of microparticles are distinguishable [i.e., labeled] (para [0076] and [0105]; see also para [0094] for distinguishing features, i.e., instant labels) and the liquid sample may be a biological liquid sample (para [0091])
Separately exposing both sets of microparticles to their corresponding sample (para [0027]
Mixing together the subsets of microparticles (para [0028])
Martin teaches that in the methods of the invention, different populations of particles are contacted with each sample separately, combined before processing steps for detection of the analyte, and then read together, enabling analytes from different samples to be detected simultaneously with concomitant savings in both processing and read times (para [0075]).
Martin teaches that the method include contacting each sample with a population of microparticles comprising one or more subsets of particles distinguishable from each other and from those of the other populations and comprising capture molecules to capture analytes of the respective group, wherein the samples and particle populations are contacted separately and then combined prior to detection [i.e., the number of different subsets provided is at least as big as the number of separate samples provided] (para [0013]).
Therefore, it would have been obvious to one of ordinary skill in the art at the time of filing to utilize the multiplexing method of Martin wherein the populations of microparticles corresponding to samples are distinctly labeled and comprise at least as many populations of subsets as samples to improve the detection method using porous microparticles of Steinmetzer in order to save on processing and read time, as taught by Martin. There would have been a strong expectation for success as both are directed to using microparticles to detect analytes in one or more samples and the combination represents a known technique applied to a known method.
Regarding claim 4, in the method of Steinmetzer in view of Martin, Martin teaches further determining which population/panel of microparticles provided contains the analytes of interest (Fig. 2 and 7-9), wherein the identity of the subsets of microparticles is determined by the distinguishing feature [i.e., instant specific label] that is, e.g., contained in the microparticles (Fig. 2I; para [0121] and [0134]; see also para [0121]).
Regarding claim 5, in the method of Steinmetzer in view of Martin, Martin teaches that a correlation exists between a particular subset of particle and a particular analyte from a particular sample such that which subsets bear captured analytes indicates which analytes were present in each sample (para [0012]). Martin teaches having a record of which panel corresponds to which well [i.e., exposed to a given sample] (Fig. 4B-E; see also para [0129]) and with which analyte (Fig. 9).
Thus, it follows that the first and second records of correlation were generated at steps b) and d).
Regarding claim 6, in the method of Steinmetzer in view of Martin, as discussed and cited in the rejection of claim 5, Martin teaches that a correlation exists and having a record of which panel corresponds to a sample/well and with which analyte. Martin teaches utilizing the label and distinguishing feature information to determine which sample correlates with the present of the analyte(s) of interest in a particular original sample (para [0121]; Fig. 2I; see also Fig. 9; para [0192]).
Regarding claim 15, in the method of Steinmetzer in view of Martin, Steinmetzer teaches microparticles made of a gel-forming agent, wherein the gel-forming agent forms a porous matrix and wherein the gel-forming agent is a polymer (pg. 9, lines 17-34).
Steinmetzer teaches avoiding cross-linking of the microparticles (pg. 26, line 13). Steinmetzer teaches that the microparticles are composed of agarose (pg. 28, line 13; pg. 9, line 30).
Regarding claim 16, in the method of Steinmetzer in view of Martin, Steinmetzer teaches an embodiment wherein the analyte of interest is a nucleic acid and the reaction is a nucleic acid amplification (pg. 28, Amplification reaction in DAB micro-compartments), wherein a detection composition comprising Platinum™ Hot Start PCR Master Mix (Invitrogen, # 13000012) and SYBR Green I nucleic acid gel stain or EvaGreen Fluorescent DNA stain [nucleic acid dyes] (pg. 27, lines 7-15).
Steinmetzer teaches a buffer, nucleoside triphosphates, and an amplification enzyme by teaching the Invitrogen PCR Master Mix # 13000012, evidenced by Thermo Fisher. While Steinmetzer does not explicitly teach a composition with these components, it is inherently taught because the Invitrogen PCR Master Mix # 13000012 contains Taq DNA polymerase in an optimized buffer with dNTPs (Thermo Fisher: Product description).
Steinmetzer teaches use of fluorescent probes in a nucleic acid amplification embodiment (pg. 24, lines 1-3) and primers (pg. 27, Component 3). As described and cited above in claim 1, Steinmetzer teaches that the porous matrix may comprise polynucleotides. Steinmetzer also teaches that detection agents [attached to the microparticles] may be nucleic acids labelled with a suitable reporter molecule such as a dye (pg. 10, para 1).
It is further noted that while other detection compositions have previously been discussed, Steinmetzer teaches multiple embodiments (e.g., the detection agent discussed in the rejection of claim 3 added in the step of providing and the composition discussed here added at the step of exposing).
Martin teaches that the particles are optionally combined prior to addition of a detection reagent and any processing required to detect the analytes before the read step (para [0006]), i.e., that they may be maintained as separate for any processing required to detect the analytes including the addition of the detection reagent(s).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have either provided the primers and probe separately in view of Martin or to have already attached the reagents to the microparticles in view of Steinmetzer. Adding separately represents a change in the order of adding ingredients (MPEP 2144.04(IV)(C)) and having already attached the reagents represents making the polynucleotides integral (MPEP 2144.04(V)(B)). There would have been a strong expectation of success as both are directed to microparticles for detecting analytes, Steinmetzer teaches such integrations of nucleic acids into microparticles, and Martin teaches maintaining the separation of the microparticles when performing steps needed to detect analytes.
With respect to the order of steps, it is likewise noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Double Patenting
Claims 1-6 and 8-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,073,518 B2 in view of Steinmetzer (WO 2018/122162 A1; published 05/07/2018; as cited in the IDS dated 05/07/2018) in view of Martin (WO 2009/048530 A2; published 04/16/2009; as cited in the IDS dated 05/18/2023), as evidenced by Thermo Fisher (Thermo Fisher Scientific. Invitrogen Platinum Hot Start PCR 2X Master Mix [Internet]. Thermo Fisher Scientific; 2015 Jul 14 [cited 2025 Sep 6]. Available from: https://documents.thermofisher.com/TFS-Assets/LSG/manuals/Platinum_Hot_Start_PCR_Master_Mix_UG.pdf).
Both sets of claims are directed to a method of detecting an analyte in a sample comprising providing microparticles with a void volume capable of receiving an aqueous solution [i.e., porous], exposing the microparticles to an aqueous sample suspected of containing an analyte, transferring to a non-aqueous phase, performing a detection reaction, and detecting, wherein the microparticles may be specifically labelled.
The claims of ‘518 are directed to microparticles with a capture agent [instant ASR].
Claim 9 of ‘518 recites polymer-based microparticles with a gel-forming agent selected from polynucleotides and polypeptides [i.e., a polymer is capable of binding an analyte and/or at least one charged group ionizable and/or at least one ionizable group].
Any additional limitations of the ‘518 claims are encompassed by the open claim language “comprising” found in the instant claims.
‘518 fails to teach that: a plurality of samples that each subset of microparticles is characterized by a specific label component corresponding to a sample subset; particular numbers/combinations of analyte-specific reagents and samples; removing some or all of the aqueous phase; a record of correlation is generated; specific detection compositions; the microparticles are agarose or agarose + gelatin; and specific detection methods(s).
Steinmetzer and Martin, in view of Thermo Fisher rectify these. The teachings of Steinmetzer and Martin, in view of Thermo Fisher as cited in the rejections of 1-6 and 8-17 are incorporated from above. Any additional motivations and expectations of success from the rejections of said claims are also incorporated.
Steinmetzer further teaches that its methods for detection of an analyte are easy to handle and can be performed without extensive efforts on the part of apparatuses used, is universally employable, and allows for the enrichment of analytes from different volume of liquid without having to adjust the final volume of the detection reaction (pg. 2, lines 6-14).
Martin teaches that in the methods of the invention, different populations of particles are contacted with each sample separately, combined before processing steps for detection of the analyte, and then read together, enabling analytes from different samples to be detected simultaneously with concomitant savings in both processing and read times (para [0075]).
Therefore, it would have been obvious to combine ‘518 with Steinmetzer evidenced by Thermo Fisher, motivated by the desire for a universally employable and simpler enrichment of analyte detection scheme, as taught by Steinmetzer. It further would have been obvious to combine ‘518 and Steinmetzer evidenced by Thermo Fisher with Martin, motivated by the desire to enable analytes from different samples to be detected simultaneously, thereby saving in processing and reading times, as taught by Martin. There would have been a strong expectation of success as all are directed to microparticle detection techniques of analytes and represent the application of known techniques/products to known methods.
Claims 1-6 and 15-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,007,390 B2 in view of Steinmetzer (WO 2018/122162 A1; published 05/07/2018; as cited in the IDS dated 05/07/2018) in view of Martin (WO 2009/048530 A2; published 04/16/2009; as cited in the IDS dated 05/18/2023), as evidenced by Thermo Fisher (Thermo Fisher Scientific. Invitrogen Platinum Hot Start PCR 2X Master Mix [Internet]. Thermo Fisher Scientific; 2015 Jul 14 [cited 2025 Sep 6]. Available from: https://documents.thermofisher.com/TFS-Assets/LSG/manuals/Platinum_Hot_Start_PCR_Master_Mix_UG.pdf).
Both sets of claims are directed to a method of detecting an analyte in a sample comprising providing microparticles with a void volume capable of receiving an aqueous solution [i.e., porous], exposing the microparticles to an aqueous sample suspected of containing an analyte, transferring to a non-aqueous phase, performing a detection reaction, and detecting, wherein the microparticles may be specifically labelled.
Claim 8 of ‘390 teaches a gel-forming agent that forma matrix using polymers selected from polypeptides and polynucleotides [i.e., a polymer capable of binding to an analyte and/or a polymer with at least one charged group and/or a polymer with at least one ionizable group].
The claims of ‘390 are directed to microparticles that do not have a capture agent [instant ASR].
Any additional limitations of the ‘390 claims are encompassed by the open claim language “comprising” found in the instant claims.
‘390 fails to teach that: a plurality of samples that each subset of microparticles is characterized by a specific label component corresponding to a sample subset; particular numbers/combinations of analyte-specific reagents and samples; removing some or all of the aqueous phase; a record of correlation is generated; specific detection compositions; the microparticles are agarose or agarose + gelatin; and specific detection methods(s).
Steinmetzer and Martin, in view of Thermo Fisher rectify these. The teachings of Steinmetzer and Martin, in view of Thermo Fisher as cited in the rejections of 1-7 and 15-17 are incorporated from above. Any additional motivations and expectations of success from the rejections of said claims are also incorporated.
Steinmetzer further teaches that its methods for detection of an analyte are easy to handle and can be performed without extensive efforts on the part of apparatuses used, is universally employable, and allows for the enrichment of analytes from different volume of liquid without having to adjust the final volume of the detection reaction (pg. 2, lines 6-14).
Martin teaches that in the methods of the invention, different populations of particles are contacted with each sample separately, combined before processing steps for detection of the analyte, and then read together, enabling analytes from different samples to be detected simultaneously with concomitant savings in both processing and read times (para [0075]).
Therefore, it would have been obvious to combine ‘390 with Steinmetzer evidenced by Thermo Fisher, motivated by the desire for a universally employable and simpler enrichment of analyte detection scheme, as taught by Steinmetzer. It further would have been obvious to combine ‘390 and Steinmetzer evidenced by Thermo Fisher with Martin, motivated by the desire to enable analytes from different samples to be detected simultaneously, thereby saving in processing and reading times, as taught by Martin. There would have been a strong expectation of success as all are directed to microparticle detection techniques of analytes and represent the application of known techniques/products to known methods.
Claims 1-6 and 8-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 26-36 and 38-50 of copending Application No. 17/786,012 in view of Steinmetzer (WO 2018/122162 A1; published 05/07/2018; as cited in the IDS dated 05/07/2018) in view of Martin (WO 2009/048530 A2; published 04/16/2009; as cited in the IDS dated 05/18/2023), as evidenced by Thermo Fisher (Thermo Fisher Scientific. Invitrogen Platinum Hot Start PCR 2X Master Mix [Internet]. Thermo Fisher Scientific; 2015 Jul 14 [cited 2025 Sep 6]. Available from: https://documents.thermofisher.com/TFS-Assets/LSG/manuals/Platinum_Hot_Start_PCR_Master_Mix_UG.pdf). This is a provisional nonstatutory double patenting rejection.
Both sets of claims are directed to a method of detecting at least one analyte in a sample comprising providing a library of microparticles with a porous matrix and an ASR, exposing the microparticles to an aqueous sample suspected of containing said analyte(s), transferring to a non-aqueous phase, performing a detection reaction, and detecting and/or quantitating, wherein the microparticles may be specifically labelled and wherein there are as many or at least as many different classes of separate subsets of microparticles as different analytes and samples to be tested. Both sets of claims encompass microparticles with subsets distinctly labeled for performing detection of a single analyte in several samples or of multiple analytes in several samples.
Claim 29 of ‘012 recites a library of prefabricated microparticles configured for performing specific detection of analytes of interest in a sample that has a polymer or polymer mixture, wherein an analyte specific reagent is attached to said microparticles through a reagent binding component by direct binding of an analyte specific reagent to the polymer or polymer mixture, direct binding of the ASR to charged groups on said polymer which has at least one ionizable group, or direct binding of the ASR or said ionizable group. See also claims 30-31.
Any additional limitations of the ‘012 claims are encompassed by the open claim language “comprising” found in the instant claims.
It would be obvious to substitute any of the product claims comprising a library of the microparticles into the method as the detection method claims depend from method of making claims, which depend from a product claim, motivated by a desire to gain the additional functionality discussed in the corresponding claims with a high expectation of success as they are taught as compatible and directed to microparticles for the same purpose.
‘012 fails to teach or explicitly that: all of the particular numbers/combinations of analyte-specific reagents and samples; a record of correlation is generated and specific detection methods(s).
Steinmetzer and Martin, in view of Thermo Fisher rectify these. The teachings of Steinmetzer and Martin, in view of Thermo Fisher as cited in the rejections of 1-17 are incorporated from above. Any additional motivations and expectations of success from the rejections of said claims are also incorporated.
Steinmetzer further teaches that its methods for detection of an analyte are easy to handle and can be performed without extensive efforts on the part of apparatuses used, is universally employable, and allows for the enrichment of analytes from different volume of liquid without having to adjust the final volume of the detection reaction (pg. 2, lines 6-14).
Martin teaches that in the methods of the invention, different populations of particles are contacted with each sample separately, combined before processing steps for detection of the analyte, and then read together, enabling analytes from different samples to be detected simultaneously with concomitant savings in both processing and read times (para [0075]).
Therefore, it would have been obvious to combine ‘012 with Steinmetzer evidenced by Thermo Fisher, motivated by the desire for a universally employable and simpler enrichment of analyte detection scheme, as taught by Steinmetzer. It further would have been obvious to combine ‘518 and Steinmetzer evidenced by Thermo Fisher with Martin, motivated by the desire to enable analytes from different samples to be detected simultaneously, thereby saving in processing and reading times, as taught by Martin. There would have been a strong expectation of success as all are directed to microparticle detection techniques of analytes and represent the application of known techniques/products to known methods.
Response to Arguments
Applicant's arguments filed 03/16/2026 have been fully considered but they are not persuasive.
Regarding the 112(b) and 112(d) rejections, Applicant argues on pgs. 20 and 21 of the Remarks that claim 3 translates the “sample-specific process part” and the “generic process part” of claim 1 into a specific order of steps a)-d) and thus represents a further limitation of claim 1, from which it depends.
This argument is not persuasive because the indefiniteness and dependency issues have not been resolved. Indeed, the amendments exacerbate the nexus and the lack of incorporation of all limitations issues. For example, the amendments adding limitations to the “a plurality of differently labelled subsets of porous microparticles” of claim 1 and establishing that the microparticles of claim 3 are “a plurality of prefabricated porous microparticles” clearly separate the groups of microparticles under US claim limitation practice. The artisan would not know, for example, in claim 16 which of “said microparticles” the ASR is intended to be attached to. The rejections have been further clarified.
Applicant may consider making claim 3 an independent claim.
Regarding the 103 rejections, Applicant argues on pgs. 22-23 of the Remarks that the teachings of Steinmetzer are directed to detection of analytes in a sample not to the simultaneous processing and detection of analytes in a plurality of samples. Applicant acknowledges that Steinmetzer “briefly refers” to “several samples” but argues that the statement represent the only mention in the entire reference, and the Steinmetzer lacks further discussion or examples of processing of multiple samples. Applicant argues that, accordingly, Steinmetzer is not directed to the same purpose or objective as the present invention.
Applicant further argues on pgs. 23-24 that Steinmetzer requires the presence of a “capture agent” and provides no teaching or suggestion that such capture agents could be omitted and replaced with the structural features as recited in the Applicant’s claims, such that the artisan would not have been motivated to omit or replace the capture agents of Steinmetzer with the Applicant’s structural features nor the artisan have a reasonable success in doing so. Applicant argues on pgs. 24-25 that the microparticles of Martin differ fundamentally from the porous microparticles of the present invention, as they are directed to non-porous solid particles that also have capture molecules.
Applicant also argues on pg. 25 that Steinmetzer and Martin disclose fundamentally different particle structures where Steinmetzer teaches microparticles with a void volume and Marin described solid non-porous particles, such that the artisan would face conflicting teachings regarding the particle structure. Applicant argues that to arrive at the claimed invention, the artisan would need to remove the capture agents required by Steinmetzer and Martin and redesign the particle to include the porous matrix with the mechanisms of amended claim 1, which represents a change of the principle of operation. Applicant argues that there is no suggestion or motivation for such modifications.
First, in response to applicant's argument that Steinmetzer is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Steinmetzer describes labelled, porous microparticles for the analysis of analytes in biological liquids (entire document, e.g., pg. 1, para 1; pg. 4; pg. 7; Embodiments 1-3). Further, Martin described particle-based assays for detecting analytes that can be multiplexed (entire document, e.g., Abstract.). Both Steinmetzer and Martin are in the field of the inventors’ endeavor.
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).
It is further noted that Steinmetzer also recites “different samples” on pg. 14, lines 31-33 and pg. 18, para 1.
Second, contrary to the alleged lack of teaching of embodiments that lack a “capture agent” or the allegations that such “capture agent” is incompatible with a porous matrix, Steinmetzer recites on pg. 7, lines 20-34:
“the presence of a capture agent on the prefabricated microparticle is not necessary, as long as the prefabricated microparticle is capable of taking up liquid from the surroundings to which it is exposed. For example, such microparticle may be a porous microparticle, thus allowing the uptake of liquid and of an analyte present in said liquid in the porous microparticle, i.e. in the space provided for by the pores of said microparticle. Thus, according to this aspect of the present invention, the method even works if the prefabricated microparticle does not have a capture agent. ... The presence of a capture agent increases the specificity and/or selectivity of the prefabricated microparticles for said analyte but is, however, not absolutely required or essential for the prefabricated microparticles according to the present invention to function.”
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., lack of “capture agent”) is 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).
Applicant is also directed to US 12,007,390 B2, which claims priority to Steinmetzer (PCT/EP2017/084370, i.e., WO 2018/12216) and claims substantially similar subject matter without the purportedly critical capture agent (‘390 claim 1). See also the double patenting rejection over said patent.
Further, the claims recite “comprising” and Applicant themselves recites “analyte-specific reagent” that is attached to or contained by the porous matrix in at least claims 8-10, 12-13, and 16. As taught by Steinmetzer, the artisan would not find the porous nature of a microparticle and “capture agent” incompatible.
Accordingly, there is no need to further modify the microparticles of Steinmetzer; the further limitations of claim 1 are taught as discussed in more detail in the updated rejection.
Third, regarding the arguments that the combination represents or would be required to fundamentally change the mode of operation of either/both Steinmetz or Martin, the method of Marin repeatedly recite “subset of particles (microspheres, microbeads, etc.)” (e.g., para [0006], [0008], [0076]). Martin further recites that “any particle-based assay can be multiplexed ... using the method of the present invention” (para [0099]). Martin teaches the multiplexing and, as discussed above, removal of a capture agent is not required by the claims, nor would it fundamentally represent a teaching away as Martin is relatively particle agnostic. Further, as previously discussed, Steinmetzer also suggests several/different samples, such that multiplexing its assay also would not represent a teaching away, nor, again, would removal of the capture agent should the claims be so amended, given the teachings of pg. 7 above.
As the combination of Steinmetz and Martin does not require a redesign of the microparticle, no further suggestion or motivation to redesign it is necessary.
Accordingly, the arguments regarding the 103 rejection(s) are not persuasive.
Applicant argues that the double patenting rejections are sufficient because of the same reasons as in the 103.
These arguments are not persuasive for the same reasons as in the 103 rejection(s).
Conclusion
No claims are allowed.
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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/EMMA R HOPPE/ Examiner, Art Unit 1683
/WU CHENG W SHEN/ Supervisory Patent Examiner, Art Unit 1682
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