DETAILED ACTION
Claims 1-5 and 9-15 are pending.
The following is a second non-final action.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 08/19/2026 has been considered by the examiner.
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.
1.Claims 1-5 and 9-15 are rejected under 35 U.S.C. 103 as being unpatentable over
Eglen et al., “The use of AlphaScreen technology in HTS: current status.” Current chemical
genomics vol. 1 2-10. 25 Feb. 2008, doi:10.2174/1875397300801010002 (IDS filed on
07/03/2024), in view of Macevicz et al., (US 20060281104) (IDS filed on 12/17/2021), and in
further view of Bosse (WO 2017091609 A1) (IDS filed on 12/05/2025).
Eglen teaches a method for detecting an analyte in a sample, the method comprising the steps of:(i) providing a mixture comprising a sample and a reporter reagent to a device (see figure 2, See page 2 “In all AlphaScreen assays, the Acceptor beads contain three chemical dyes; thioxene, anthracene and rubrene (hence the designation, ‘TAR’ beads)”);
(ii) allowing a portion of the reporter reagent to bind to the surface of the substrate via
the binding component (see figure 1, See page 2 “In both AlphaScreen and AlphaLISA
assays, the bead surface are coated with latex-based hydrogels containing reactive aldehydes.
This coating both reduces nonspecific binding but additionally provides a functionalized surface
to which a variety of different ligand or receptor binding partners may be affixed.”) (instant
claim 13);
(iii) irradiating the device with electromagnetic radiation absorbed by a photosensitiser of
the bound portion of the reporter reagent, wherein the photosensitiser induces a change in the
optical component from a first optical state to a second optical state, thereby forming a set of
local regions of the optical component having the second optical state on the substrate (see
page 2 “Donor beads contain a photosensitizing agent (phthalocyanine) that, when irradiated at
680 nm, excites ambient oxygen to a singlet state. Excitation of each Donor beads generates
approximately 60,000 oxygen singlets per second [8], resulting in a highly amplified response
upon interaction with Acceptor beads”, see figure 1) (instant claim 1, instant claim 13,
instant claim 15). Eglen teaches the sample being unprocessed (see page 7) (instant claim
11) and the steps (i) to (iii) take place in the absence of wash steps (see abstract “Collectively,
AlphaScreen and AlphaLISA technologies provide a facile assay platform with which one can
quantitate complex cellular processes using simple no-wash microtiter plate-based assays.”,
see figure 2 showing that AlphaLISA assays do not contain a washing step.) (instant claim 10).
Eglen wherein the photosensitiser interacts with a pre-activator reagent present in the
mixture thereby to generate an activator reagent (see page 2 “Donor beads contain a
photosensitizing agent (phthalocyanine) that, when irradiated at 680 nm, excites ambient
oxygen to a singlet state. Excitation of each Donor beads generates approximately 60,000 oxygen singlets per second [8], resulting in a highly amplified response upon interaction with
Acceptor beads.”), and
the activator reagent interacts with the optical component to change from the first optical
state to the second optical state (see figure 1, see page 2 “Donor beads contain a
photosensitizing agent (phthalocyanine) that, when irradiated at 680 nm, excites ambient
oxygen to a singlet state. Excitation of each Donor beads generates approximately 60,000
oxygen singlets per second [8], resulting in a highly amplified response upon interaction with
Acceptor beads.”) (instant claim 2).
Eglen teaches the activator reagent is a reactive oxygen species that is a singlet oxygen
(see abstract “Here, singlet oxygen molecules, generated by high energy irradiation of Donor
beads, travel over a constrained distance (approx. 200 nm) to Acceptor beads.”, see page 2
“Donor beads contain a photosensitizing agent (phthalocyanine) that, when irradiated at 680
nm, excites ambient oxygen to a singlet state. Excitation of each Donor beads generates
approximately 60,000 oxygen singlets per second [8], resulting in a highly amplified response
upon interaction with Acceptor beads.”, see page 4 “Singlet oxygen then transfers, resulting in a
chemiluminescent signal (Fig 2).”) (instant claims 3-4).
Eglen does not teach detecting a set of local regions, a substrate that forms one of the
interior surfaces of a chamber configured to hold the sample in contact with the substrate,
wherein the amount of the bound portion is proportional to the concentration of the analyte in
the sample, and wherein the substrate forms at least one interior surface of the chamber, and
wherein each local region is counted as a discrete binding event, and wherein the first optical
state is fluorescent and the second optical state is non-fluorescent.
Macevicz teaches detecting the set of local regions having the second optical state on
the substrate and each local region is counted as a discrete binding event (see figure 1, see [0045]). Macevicz teaches wherein the first optical state is fluorescent and the second optical state is nonfluorescent (see [0047] teaching linking together a fluorescer and a quencher by a cleavable linkage. It is known in the art that combining a fluorophore with a quencher will result in a nonfluorescent state) (instant claim 1).
Macevicz teaches wherein the device is irradiated with electromagnetic radiation for
more than 1 second (see [0066] “In general, the period for irradiation may be less than about a
microsecond to as long as about 10 minutes, usually in the range of about one millisecond to
about 60 seconds”) (instant claim 12).
Macevicz teaches that the first optical state can be changed to a second optical state
when the first optical state interacts with a singlet oxygen (an activator) (see [0031], see [0048]). While Macevicz does not explicitly state that the change from the first optical state to the second optical state is irreversible. One of ordinary skill in the art would know that introducing an activator such as a singlet oxygen to the first optical state is irreversible, as once the activator is introduced, it changes to the second optical state (instant claim 9). Macevicz teaches comprising a cartridge, wherein the substrate is within the cartridge, and wherein the device further comprises a detector for detecting the set of local regions having the second optical state on the substrate using optical microscopy (see figure 1D, see figure 1E, see [0011] “In another aspect, the invention provides compositions comprising a plurality of nanoparticles each having a surface and each having attached to Such surface (i) leuco dyes capable of being converted into detection moieties by a reactive species, the detection moieties being capable of generating a first optical signal and (ii) one or more binding compounds each having a specificity for an antigen, such that the specificity of the one or more binding compounds on the same nanoparticle is for the same antigen, and such that the specificity of the one or more binding compounds on each different nanoparticle of the plurality is for a different antigen. In still another aspect, the above nanoparticles each have attached to their surface an indicator molecule. In one embodiment, such indicator molecules are non-reactive with at least one reactive species. In another embodiment, each different indicator molecule is capable of producing a different spectrally resolvable fluorescent signal.”, see [0049]) (instant claims 5 and 14).
Bosse teaches a substrate that forms one of the interior surfaces of a chamber
configured to hold the sample in contact with the substrate (see [0015], see [0074] – [0075],
the substrate being a bead), and wherein the substrate forms at least one interior surface of the
chamber (see [0074] – [0075]). Bosse teaches the amount of the bound portion is proportional
to the concentration of the analyte in the sample (see [0023], see [00214], see claim 71 of
Bosse) Bosse teaches detecting a set of local regions and a detection signal for the presence
and/or mount of the analyte in the sample (see [00256] teaching the use of computers and
mobile computing devices for user interface, see [00132], see [00214], see figure 8D) (instant
claim 1, instant claim 13).
It would have been obvious to one of ordinary skill in the art at the time of the instant
application to modify the method of detecting an analyte in a sample as taught by Eglen with
the set of local regions having an optical substrate (leuco dye) as taught by Macevicz, with
the methods of chemiluminescence taught by Bosse. Macevicz teaches that methods of quenching fluorescent probes are widely known and used in the art (see [0047]), thus it would have been obvious to one of ordinary skill in the art to use that technique. Macevicz further teaches that reagent pairs that are provided can comprise a reactive species generator that specifically binds to a first region of a molecular target and one or more signaling reagents that each specifically bind to one or more second regions that do not overlap with the first regions (see [0006]). Bosse teaches that the use of a digital readout allows for interaction with the user (see [0265]). Bosse further teaches that first and second binding partners conjugated to its
interior surface can achieve a variety of levels of sensitivity (see [0074]). The artisan would
have reasonable expectation of success based on the cumulative disclosure of these prior art
references at the time the instant application was filed.
Response to Arguments
Applicant's arguments filed 06/23/2026 have been fully considered but they are not persuasive.
Applicant pointed to the fact that the previous 103 rejection did not point out fluorescent to non-fluorescent. While Macevicz does teach fluorescent to non-fluorescent, since it was not explicitly pointed out in the previous non-final action and to maintain customer service, this action is a non-final.
On pp. 6-7 applicant argues that each cited reference detects by generating an optical signal, which is the opposite of the instant invention.
While it is understood that Macevicz teaches methods of detection where the first optical state is non-fluorescent and the second optical state is fluorescent, that is only one aspect of the methods of Macevicz. Macevicz does explicitly teach the use of a quencher (see [0047]). It is known in the art that a quencher is used to make a fluorescent molecule convert into a non-fluorescent molecule.
Elgen teaches a method for detecting an analyte in a sample, the method comprising the steps of: (i) providing a mixture comprising a sample and a reporter reagent to a device; (ii) allowing a portion of the reporter reagent to bind to the surface of the substrate via the binding component; (iii) irradiating the device with electromagnetic radiation absorbed by a photosensitiser of the bound portion of the reporter reagent, wherein the photosensitiser induces a change in the optical component from a first optical state to a second optical state, thereby forming a set of local regions of the optical component having the second optical state on the substrate, the sample being unprocessed, and the steps (i) to (iii) take place in the absence of wash steps. Eglen further teaches the photosensitiser interacts with a pre-activator reagent present in the mixture thereby to generate an activator reagent, the activator reagent interacts with the optical component to change from the first optical state to the second optical state, the activator reagent is a reactive oxygen species that is a singlet oxygen.
Bosse teaches a substrate that forms one of the interior surfaces of a chamber configured to hold the sample in contact with the substrate, the amount of the bound portion is proportional to the concentration of the analyte in the sample, detecting a set of local regions and a detection signal for the presence and/or mount of the analyte in the sample.
On p. 8 applicant argues that Macevicz is relied upon for teaching a singlet-oxygen driven change in the fluorescent state of an optical component.
However, in the non-final action filed on 03/23/2026, Eglen is cited as teaching a singlet oxygen.
Macevicz does however mention the use of a singlet oxygen as well (see [0031], see [0048]).
On p. 9 applicant argues that Bosse does not cure the deficiency of fluorescent to non-fluorescent conversion and discrete-event counting.
However, Macevicz teaches the conversion of a fluorescent molecule into a non-fluorescent molecule. Macevicz also teaches counting discrete binding events.
Bosse teaches a substrate that forms one of the interior surfaces of a chamber configured to hold the sample in contact with the substrate, the amount of the bound portion is proportional to the concentration of the analyte in the sample, detecting a set of local regions and a detection signal for the presence and/or mount of the analyte in the sample.
On pp. 9-10 applicant argues that there is no proper motivation to combine and reflects hindsight reasoning.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Macevicz.
Macevicz teaches that the use of a quencher on a fluorescent molecule is a known technique in the art (see [0047]), thus converting a fluorescent probe into a non-fluorescent probe by adding a quencher is not a new technique in the art. Macevicz further teaches that reagent pairs can that are provided can comprise a reactive species generator that specifically binds to a first region of a molecular target and one or more signaling reagents that each specifically bind to one or more second regions that do not overlap with the first regions (see [0006]). Bosse teaches the use of a digital readout allows for interaction with the user (see [00265]). Bosse further teaches that first and second binding partners conjugated to its interior surface can achieve a variety of levels of sensitivity (see [0074]).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
2.Claims 1-5 and 9-15 are provisionally rejected on the ground of nonstatutory double
patenting as being unpatentable over claims 1 and 5-15 of copending Application No. 18267726
in view of Bosse (WO 2017091609 A1) (IDS filed on 12/05/2025).
Regarding claim 1 of the instant application, ‘726 teaches a method for detecting an analyte in a sample, the method comprising the steps of: (i) providing a mixture comprising a
sample and a reporter reagent to a device, the device comprising a substrate having an optical
component and a binding component attached to a surface of the substrate; (ii) allowing a
proportion of the reporter reagent to bind to the surface of the substrate in proportion to the
concentration of the analyte, by means of the binding component; (iii) irradiating the device with
electromagnetic radiation for absorption by a photosensitiser of the reporter reagent, such that
the photosensitiser of the bound reporter reagent portion interacts with the optical component to
cause the optical component to change from a first optical state to a second optical state,
thereby forming a set of local regions of the optical component having the second optical state
on the substrate; and (iv) detecting the set of local regions having the second optical state on
the substrate (claim 1 of ‘726), and the first optical state being fluorescent and the second
optical state being non-fluorescent (see claim 8 of ‘726).
‘726 is does not teach a substrate that forms one of the interior surfaces of a chamber
configured to hold the sample in contact with the substrate, and wherein the substrate forms at
least one interior surface of the chamber, wherein the amount of the bound portion is
proportional to the concentration of the analyte in the sample, and detecting a set of local
regions and providing a digital readout of the presence and/or amount of the analyte in the
sample.
Bosse teaches a substrate that forms one of the interior surfaces of a chamber
configured to hold the sample in contact with the substrate (see [0015], see [0074] – [0075],
the substrate being a bead), and wherein the substrate forms at least one interior surface of the
chamber (see [0074] – [0075]). Bosse teaches the amount of the bound portion is proportional
to the concentration of the analyte in the sample (see [0023], see [00214], see claim 71 of
Bosse) Bosse teaches detecting a set of local regions and providing a digital readout of the
presence and/or mount of the analyte in the sample (see [00256] teaching the use of computers and mobile computing devices for user interface, see [00132], see [00214], see figure 8D
showing the digital readout).
Regarding claim 13 of the instant application, ‘726 teaches a device for detecting an
analyte in a sample, the device comprising: a substrate having an optical component and a
binding component attached to a surface of the substrate, the optical component being capable
of changing from a first optical state to a second optical state, in response to interaction with
irradiated photosensitisers of reporter reagents bound to the surface of the substrate in
proportion to the concentration of analyte in the sample, thereby to form a set of local regions of
the optical component having the second optical state on the substrate (claims 1 and 13 of
‘726), and the first optical state being fluorescent and the second optical state being non-
fluorescent (see claim 8 of ‘726).
‘726 is does not teach a substrate that forms one of the interior surfaces of a chamber
configured to hold the sample in contact with the substrate, and wherein the substrate forms at
least one interior surface of the chamber, and detecting a set of local regions and providing a
digital readout of the presence and/or amount of the analyte in the sample.
Bosse teaches a substrate that forms one of the interior surfaces of a chamber
configured to hold the sample in contact with the substrate (see [0015], see [0074] – [0075],
the substrate being a bead), and wherein the substrate forms at least one interior surface of the
chamber (see [0074] – [0075]). Bosse teaches the amount of the bound portion is proportional
to the concentration of the analyte in the sample (see [0023], see [00214], see claim 71 of
Bosse) Bosse teaches detecting a set of local regions and providing a digital readout of the
presence and/or mount of the analyte in the sample (see [00256] teaching the use of computers
and mobile computing devices for user interface, see [00132], see [00214], see figure 8D
showing the digital readout).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to modify the method of detecting an analyte in a sample as taught by ‘725 with the
method of chemiluminescence taught by Bosse. Bosse provides motivation by teaching that
the use of a digital readout allows for interaction with the user (see [00265]). Bosse provides
further motivation by teaching that first and second binding partners conjugated to its interior
surface can achieve a variety of levels of sensitivity (see [0074]). The artisan would have
reasonable expectation of success based on the cumulative disclosure of these prior art
references at the time the instant application was filed.
Regarding claim 2 of the instant application, ‘726 teaches wherein the photosensitiser interacts with a pre-activator reagent present in the mixture thereby to generate
an activator reagent, and the activator reagent interacts with the optical component to change
from the first optical state to the second optical state (claim 1 of ‘726).
Regarding claim 3 of the instant application, ‘726 teaches wherein the activator
reagent is a reactive oxygen species (claim 1 of ‘726).
Regarding claim 4 of the instant application, ‘726 teaches wherein the reactive
oxygen species is singlet oxygen (claim 5 of ‘726).
Regarding claim 5 of the instant application, ‘726 teaches wherein the set of local
regions having the second optical state on the substrate is detected using optical microscopy
(claim 6 of ‘726).
Regarding claim 9 of the instant application, ‘726 teaches wherein the change from
the first optical state to the second optical state is irreversible (claim 9 of ‘726).
Regarding claim 10 of the instant application, ‘726 teaches wherein steps (i) and (ii)
take place in the absence of wash steps (claim 10 of ‘726).
Regarding claim 11 of the instant application, ‘726 teaches wherein the sample is
unprocessed (claim 11 of ‘726).
Regarding claim 12 of the instant application, ‘726 teaches wherein the device is
irradiated with electromagnetic radiation for more than 1 second (claim 12 of ‘726).
Regarding claim 14 of the instant application, ‘726 teaches a cartridge, wherein the
substrate is within the cartridge, and wherein the device further comprises a detector for
detecting the set of local regions having the second optical state on the substrate (claim 14 of
‘726).
Regarding claim 15 of the instant application, ‘726 teaches a system for detecting an
analyte in a sample, comprising: the device as claimed in claim 13; and the reporter reagent for
forming a mixture comprising the sample, the reporter reagent comprising the photosensitiser,
wherein the photosensitiser is capable of absorbing electromagnetic radiation to interact with
the optical component to change the optical component from the first optical state to the second
optical state (claim 15 of ‘726).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 06/23/2026 have been fully considered but they are not persuasive.
On p. 11 applicant argues that if a provisional nonstatutory double patenting rejection is the only rejection remaining in the application having the earlier patent term filing date, then the examiner should withdraw the rejection in the application having the earlier filing date. That is true, however, the instant application has 103 rejections. The instant application does not only have a nonstatutory double patenting rejection remaining, thus the provisional nonstatutory
double patenting rejection remains.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MCKENZIE A DUNN whose telephone number is (571)270-0490. The examiner can normally be reached Monday-Tuesday 730 am -530pm, Wednesday-Friday 730 am-430 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached at (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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/MCKENZIE A DUNN/ Examiner, Art Unit 1678
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678
Prosecution Insights