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 .
Drawings
The drawings were received on 29 December 2025. These drawings are acceptable.
Claim Interpretation
The specification (e.g., see “… the cleaning liquid and other reagent liquids may be used as they are as the observation liquid … all of the steps can be performed under a state in which some kind of liquid is constantly maintained on the spot …” in paragraph 85) serves as a glossary (MPEP § 2111.01) for the claim term “observation liquid”.
Claim Objections
Claim(s) 14 and 18 is/are objected to because of the following informalities:
(a) in claim 14, “the reagent liquid” on the last line should probably be --the at least any one reagent liquid--; and
(b) in claim 18, “a specimen” on the first line should probably be --a liquid specimen--.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 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.
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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-8, 11, 12, 15-20, 24, and 25 is/are rejected under 35 U.S.C. 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Handique et al. (US 2021/0370296).
In regard to claim 1, Handique et al. disclose an analysis method of analyzing a liquid specimen containing a target, using an array plate including, on one surface thereof, a plurality of spots each containing a biological substance, the analysis method comprising the steps of:
(a) a specimen introduction step of introducing the liquid specimen from a holder that holds the liquid specimen to the plurality of spots so as to bring the liquid specimen and the plurality of spots into contact with each other and cause a part of the plurality of spots and the target to react with each other (e.g., “… set of walls can include a set of channels that fluidly couple each well to at least one adjacent well in the array of wells … internal surfaces include a functional surface coating configured to bind to nucleic acid content that has been released from a captured solid support. The functional surface coating can be of synthetic, animal derived, human derived, or plant derived proteins … fluid reservoir can then be provided (e.g., glued or otherwise attached) around the active region containing the array of wells that allows a relatively large liquid sample to be placed during use (e.g., 0.5 mL to 5 mL) … solid support---containing sample, (e.g., up to 1 ml in volume), can be dispensed into the fluid reservoir formed by the recessed region of a first plate of a fluid delivery model surrounding the active region of the substrate …” in paragraphs 100, 102, and 105);
(b) a specimen amount reduction step of reducing an amount of the liquid specimen in contact with the plurality of spots and held in the holder (e.g., “… As noted above, in some embodiments, the wells in the array can include an affinity agent that binds to target molecules. This allows for elution of the target molecules from the capture molecules on the solid supports, allowing for additional manipulation of the target molecules as desired. For example, one can perform a wash of the well to remove components of the solution in the well while not displacing the target molecules, which remain bound by the affinity agent …” in paragraph 110);
(c) an observation liquid introduction step of bringing the one surface into contact with an observation liquid in the holder so that the plurality of spots are brought into contact with the observation liquid (e.g., see “prevent evaporation” in “… Following introduction of the solid supports into the wells of the array, the wells can be covered to prevent evaporation, diffusion into neighboring wells, and/or to retain the solid supports. Any sort of cover can be used. In some embodiments, the cover is solid, and in some embodiments translucent or clear to allow for detection of signal within the wells. In another embodiment, the cover is a layer of oil placed across the top of the wells …” in paragraph 111); and
(d) an acquisition step of acquiring optical information of the plurality of spots under a state in which the plurality of spots contact the observation liquid held in the holder (e.g., “… Detection of the target molecule, which may be amplified, can be performed in any way useful to generate a detectable signal. Preferably the signal can be detected optically, for example such that an automated scanner can detect the presence, absence or quantity of signal in each well. Signal can increase upon presence of the target molecule or in other embodiments signal can decrease (e.g., in the case of quenching of signal in the presence of the target molecule). In some embodiments, the wells comprise one or more optically detectable agents such as a fluorescent agent, phosphorescent agent, chemiluminescent agent, etc. …” in paragraphs 115 and 116),
the analysis method further comprising at least one of a first labeling step of labeling in the holder the target before the specimen introduction step, and a second labeling step of labeling the part of the plurality of spots reacted with the target in the holder, wherein the second labeling step is performed after the specimen amount reduction step (e.g., “… wells in the array can include an affinity agent that binds to target molecules …” in paragraph 110 or alternatively it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention that “an affinity agent that binds to target molecules” is before the specimen introduction step).
In regard to claim 2 which is dependent on claim 1, Handique et al. also disclose that the analysis method comprises the first labeling step, and the first labeling step comprises labeling using a fluorescent substance (e.g., “… Detection of the target molecule, which may be amplified, can be performed in any way useful to generate a detectable signal. Preferably the signal can be detected optically, for example such that an automated scanner can detect the presence, absence or quantity of signal in each well. Signal can increase upon presence of the target molecule or in other embodiments signal can decrease (e.g., in the case of quenching of signal in the presence of the target molecule). In some embodiments, the wells comprise one or more optically detectable agents such as a fluorescent agent, phosphorescent agent, chemiluminescent agent, etc. …” in paragraphs 115 and 116).
In regard to claim 3 which is dependent on claim 1, Handique et al. also disclose that the analysis method comprises the second labeling step, and the second labeling step comprises labeling using a fluorescent substance (e.g., “… wells comprise one or more optically detectable agents such as a fluorescent agent … washing probes away from the wells in between probing with different probes …” in paragraphs 116 and 123).
In regard to claim 4 which is dependent on claim 1, Handique et al. also disclose that the acquisition step comprises applying excitation light to the plurality of spots and acquiring, as the optical information, at least any one of light intensity information and spectral information of fluorescent light emitted from the plurality of spots (e.g., “… imaging system (e.g., fluorescence imaging system) can be operable in a mode for providing real-time or near real-time fluorescence imaging of samples processed according to an assay. The imaging subsystem is preferably positioned beneath the substrate and oriented to image the contents of the set of wells through the transparent (or translucent) material of the substrate … 4-color fluorescence detection system capable of uniform illumination of the microwell slide (array) and to detect fluorescence images of an area of the microwell slide with resolution of a fraction of the size of the microwells …” in paragraphs 124 and 132).
In regard to claim 5 which is dependent on claim 4, Handique et al. also disclose that the light intensity information and the spectral information are acquired in association with addresses of the plurality of spots in the array plate (e.g., “… imaging system (e.g., fluorescence imaging system) can be operable in a mode for providing real-time or near real-time fluorescence imaging of samples processed according to an assay. The imaging subsystem is preferably positioned beneath the substrate and oriented to image the contents of the set of wells through the transparent (or translucent) material of the substrate In some embodiments, the system comprises one or more computer processer configured to receive signal from the detection system. The signal from the detection subsystem can include, signal or signal intensity from detection of the target molecule, signal or signal intensity representing the distinguishable characteristic of the solid support, if present, and/or optionally the location (address) of the well in the array. The relative or absolute copy number of target molecule in the sample can be determined based on the number of wells having signal for the presence of the target molecule and optionally taking into consideration the intensity of the signal in embodiments in which more than one solid support can fit into a well. The total number of wells having a solid support from the sample can also be determined and used to calculate target molecule copy number in the sample … … 4-color fluorescence detection system capable of uniform illumination of the microwell slide (array) and to detect fluorescence images of an area of the microwell slide with resolution of a fraction of the size of the microwells …” in paragraphs 124, 125, and 132).
In regard to claim 6 which is dependent on claim 4, Handique et al. also disclose that the array plate has transmittance with respect to a wavelength of the excitation light (e.g., “… imaging system (e.g., fluorescence imaging system) can be operable in a mode for providing real-time or near real-time fluorescence imaging of samples processed according to an assay. The imaging subsystem is preferably positioned beneath the substrate and oriented to image the contents of the set of wells through the transparent (or translucent) material of the substrate … 4-color fluorescence detection system capable of uniform illumination of the microwell slide (array) and to detect fluorescence images of an area of the microwell slide with resolution of a fraction of the size of the microwells …” in paragraphs 124 and 132).
In regard to claim 7 which is dependent on claim 4, Handique et al. also disclose that the array plate has transmittance with respect to a wavelength of the fluorescent light (e.g., “… imaging system (e.g., fluorescence imaging system) can be operable in a mode for providing real-time or near real-time fluorescence imaging of samples processed according to an assay. The imaging subsystem is preferably positioned beneath the substrate and oriented to image the contents of the set of wells through the transparent (or translucent) material of the substrate … 4-color fluorescence detection system capable of uniform illumination of the microwell slide (array) and to detect fluorescence images of an area of the microwell slide with resolution of a fraction of the size of the microwells …” in paragraphs 124 and 132).
In regard to claim 8 which is dependent on claim 4, Handique et al. also disclose that the acquisition step comprises applying the excitation light to the plurality of spots through a backside surface in opposition the one surface in contact with the observation liquid; and detecting fluorescent light from the back surface side wherein the backside surface is noncontact with the observation liquid (e.g., “… imaging system (e.g., fluorescence imaging system) can be operable in a mode for providing real-time or near real-time fluorescence imaging of samples processed according to an assay. The imaging subsystem is preferably positioned beneath the substrate and oriented to image the contents of the set of wells through the transparent (or translucent) material of the substrate …” in paragraph 124).
In regard to claim 11 which is dependent on claim 1, Handique et al. also disclose that the second labeling step comprises bringing at least any one reagent liquid and the plurality of spots into contact with each other (e.g., “… wells comprise one or more optically detectable agents such as a fluorescent agent … washing probes away from the wells in between probing with different probes …” in paragraphs 116 and 123).
In regard to claim 12 which is dependent on claim 1, Handique et al. also disclose that the biological substance comprises at least one of a nucleic acid, a peptide or a protein (e.g., “… internal surfaces include a functional surface coating configured to bind to nucleic acid content that has been released from a captured solid support. The functional surface coating can be of synthetic, animal derived, human derived, or plant derived proteins …” in paragraph 102).
In regard to claim 15 which is dependent on claim 1, Handique et al. also disclose a specimen information acquisition step of acquiring information on the specimen based on the optical information (e.g., “… In some embodiments, the system comprises one or more computer processer configured to receive signal from the detection system. The signal from the detection subsystem can include, signal or signal intensity from detection of the target molecule, signal or signal intensity representing the distinguishable characteristic of the solid support, if present, and/or optionally the location (address) of the well in the array. The relative or absolute copy number of target molecule in the sample can be determined based on the number of wells having signal for the presence of the target molecule and optionally taking into consideration the intensity of the signal in embodiments in which more than one solid support can fit into a well. The total number of wells having a solid support from the sample can also be determined and used to calculate target molecule copy number in the sample …” in paragraph 125).
In regard to claim 16 which is dependent on claim 1, Handique et al. also disclose that the observation liquid introduction step also serves as a part of the specimen amount reduction step and the specimen introduction step, the specimen amount reduction step, the observation liquid introduction step and the acquisition step are continuously performed without undertaking a drying step (e.g., “… washing unbound sample components from the solid supports … Following introduction of the solid supports into the wells of the array, the wells can be covered to prevent evaporation, diffusion into neighboring wells, and/or to retain the solid supports. Any sort of cover can be used. In some embodiments, the cover is solid, and in some embodiments translucent or clear to allow for detection of signal within the wells. In another embodiment, the cover is a layer of oil placed across the top of the wells …” in paragraphs 26 and 111).
In regard to claim 17 which is dependent on claim 1, Handique et al. also disclose that the specimen in contact with the plurality of spots is replaced with the observation liquid in contact with the plurality of spots , and the specimen introduction step, the specimen amount reduction step, the observation liquid introduction step and the acquisition step are continuously performed without undertaking a drying step (e.g., “… Following introduction of the solid supports into the wells of the array, the wells can be covered to prevent evaporation, diffusion into neighboring wells, and/or to retain the solid supports. Any sort of cover can be used. In some embodiments, the cover is solid, and in some embodiments translucent or clear to allow for detection of signal within the wells. In another embodiment, the cover is a layer of oil placed across the top of the wells … where further manipulation of the contents of the wells is desired before detection, additional reagents for detection can be added to the wells (e.g., by flowing a solution comprising the reagents under or over the wells) after the cover is removed …” in paragraph 111 and 114).
In regard to claim 18, Handique et al. disclose an analysis apparatus for analyzing a liquid specimen containing a target, using an array plate including, on one surface thereof, a plurality of spots each containing a biological substance, the analysis apparatus comprising:
(a) a specimen introduction mechanism configured to introduce the liquid specimen from a holder that holds the liquid specimen to the plurality of spots so as to bring the liquid specimen and the plurality of spots into contact with each other (e.g., “… internal surfaces include a functional surface coating configured to bind to nucleic acid content that has been released from a captured solid support. The functional surface coating can be of synthetic, animal derived, human derived, or plant derived proteins … fluid reservoir can then be provided (e.g., glued or otherwise attached) around the active region containing the array of wells that allows a relatively large liquid sample to be placed during use (e.g., 0.5 mL to 5 mL) … solid support---containing sample, (e.g., up to 1 ml in volume), can be dispensed into the fluid reservoir formed by the recessed region of a first plate of a fluid delivery model surrounding the active region of the substrate … xyz gantry system that can move a z-head across the deck to various liquid handling operations … Sample racks allow strips of 8-well tubes containing samples to be loaded into the instrument …” in paragraphs 102, 105, 132, and 137);
(b) a specimen amount reduction mechanism configured to reduce an amount of the liquid specimen in contact with the plurality of spots and held in the holder (e.g., “… As noted above, in some embodiments, the wells in the array can include an affinity agent that binds to target molecules. This allows for elution of the target molecules from the capture molecules on the solid supports, allowing for additional manipulation of the target molecules as desired. For example, one can perform a wash of the well to remove components of the solution in the well while not displacing the target molecules, which remain bound by the affinity agent … xyz gantry system that can move a z-head across the deck to various liquid handling operations …” in paragraphs 110 and 132);
(c) an observation liquid introduction mechanism configured to bring the one surface into contact with an observation liquid held in the holder so that the plurality of spots are brought into contact with the observation liquid (e.g., see “prevent evaporation” in “… Following introduction of the solid supports into the wells of the array, the wells can be covered to prevent evaporation, diffusion into neighboring wells, and/or to retain the solid supports. Any sort of cover can be used. In some embodiments, the cover is solid, and in some embodiments translucent or clear to allow for detection of signal within the wells. In another embodiment, the cover is a layer of oil placed across the top of the wells … xyz gantry system that can move a z-head across the deck to various liquid handling operations …” in paragraphs 111 and 132); and
(d) an acquisition mechanism configured to acquire optical information of the plurality of spots under a state in which the plurality of spots contact the observation liquid held in the holder (e.g., “… Detection of the target molecule, which may be amplified, can be performed in any way useful to generate a detectable signal. Preferably the signal can be detected optically, for example such that an automated scanner can detect the presence, absence or quantity of signal in each well. Signal can increase upon presence of the target molecule or in other embodiments signal can decrease (e.g., in the case of quenching of signal in the presence of the target molecule). In some embodiments, the wells comprise one or more optically detectable agents such as a fluorescent agent, phosphorescent agent, chemiluminescent agent, etc. … 4-color fluorescence detection system capable of uniform illumination of the microwell slide (array) and to detect fluorescence images of an area of the microwell slide with resolution of a fraction of the size of the microwells …” in paragraphs 115, 116, and 132),
the analysis apparatus further comprising at least any of a first labeling mechanism and a second labeling mechanism, wherein the first labeling mechanism is configured to label the target in the holder and operate before the specimen introduction mechanism operates, and the second labeling mechanism is configured to label the part of the plurality of spots reacted with the target in the holder and operate after the specimen amount reduction mechanism operates (e.g., “… wells in the array can include an affinity agent that binds to target molecules … … xyz gantry system that can move a z-head across the deck to various liquid handling operations …” in paragraphs 110 and 132 or alternatively it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention that “an affinity agent that binds to target molecules” is before the specimen introduction step).
In regard to claim 19 which is dependent on claim 18, Handique et al. also disclose that the array plate is configured to transmit excitation light used in the acquisition mechanism, and the acquisition mechanism is configured to (i) apply the excitation light to the plurality of spots from a back surface side of the one surface of the array plate, and (ii) acquire, from the back surface side, the optical information of fluorescent light emitted from the plurality of spots (e.g., “… imaging system (e.g., fluorescence imaging system) can be operable in a mode for providing real-time or near real-time fluorescence imaging of samples processed according to an assay. The imaging subsystem is preferably positioned beneath the substrate and oriented to image the contents of the set of wells through the transparent (or translucent) material of the substrate … 4-color fluorescence detection system capable of uniform illumination of the microwell slide (array) and to detect fluorescence images of an area of the microwell slide with resolution of a fraction of the size of the microwells …” in paragraphs 124 and 132).
In regard to claim 20 which is dependent on claim 18, Handique et al. also disclose a holding mechanism configured to hold the observation liquid such that the plurality of spots are brought into contact with the observation liquid (e.g., “… fluid reservoir can then be provided (e.g., glued or otherwise attached) around the active region containing the array of wells that allows a relatively large liquid sample to be placed during use (e.g., 0.5 mL to 5 mL) … solid support---containing sample, (e.g., up to 1 ml in volume), can be dispensed into the fluid reservoir formed by the recessed region of a first plate of a fluid delivery model surrounding the active region of the substrate …” in paragraph 105).
In regard to claim 24 which is dependent on claim 18, Handique et al. also disclose a mechanism configured to acquire information on the specimen based on the optical information (e.g., “… In some embodiments, the system comprises one or more computer processer configured to receive signal from the detection system. The signal from the detection subsystem can include, signal or signal intensity from detection of the target molecule, signal or signal intensity representing the distinguishable characteristic of the solid support, if present, and/or optionally the location (address) of the well in the array. The relative or absolute copy number of target molecule in the sample can be determined based on the number of wells having signal for the presence of the target molecule and optionally taking into consideration the intensity of the signal in embodiments in which more than one solid support can fit into a well. The total number of wells having a solid support from the sample can also be determined and used to calculate target molecule copy number in the sample …” in paragraph 125).
In regard to claim 25, the cited prior art is applied as in claim 1 above. Handique et al. disclose a non-transitory storage medium storing a program for causing a computer to execute steps of the analysis method (e.g., “… programs incorporating various features of the present invention can be encoded on various computer readable media for storage …” in paragraph 130).
Claim(s) 9 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Handique et al. (US 2021/0370296) in view of Goodman et al. (US 2019/0113423).
In regard to claim 9 which is dependent on claim 1, the method of Handique et al. lacks an explicit description of details of the “… fluorescence detection system …” such as the observation liquid has a refractive index of 1.40 to 1.46. However, “… fluorescence detection system …” details are known to one of ordinary skill in the art (e.g., see “… refractive indices (RIs) of the various materials in the environment are matched, or are similar, such that a beam of light traveling through the optically homogenous environment will be insubstantially impacted by any changes in the RIs of the materials through which it travels … In some embodiments, the sample chamber of the optically homogenous sample manipulation component is filled with a solution. In some embodiments, the solution has an RI that matches the RI of the sample or the detection objective of the detection beam path. For example, in some embodiments, the solution used to fill the sample chamber is FocusClear or MountClear (both commercially available from CelExplorer Labs). In some embodiments, the solution used to fill the chamber is a liquid with a refractive index that ranges from about 1.42 up to about 1.46, such as about 1.45, including all values and sub ranges in between. In some embodiments, the solution used to fill the sample chamber is about 87% glycerol. Solutions having the desired range of refractive indices are commercially available from vendors, such as Cargille Labs …” in paragraphs 171 and 175 of Goodman et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional fluorescence detection system (e.g., comprising details such as “solution used to fill the chamber is a liquid with a refractive index that ranges from about 1.42 up to about 1.46, such as about 1.45, including all values and sub ranges in between. In some embodiments, the solution used to fill the sample chamber is about 87% glycerol”, in order to achieve “optically homogenous environment”) for the unspecified fluorescence detection system of Handique et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional fluorescence detection system (e.g., comprising details such as the observation liquid has a refractive index of 1.40 to 1.46) as the unspecified fluorescence detection system of Handique et al.
In regard to claim 10 which is dependent on claim 1, the method of Handique et al. lacks an explicit description of details of the “… fluorescence detection system …” such as the observation liquid contains glycerol of 40 vol % to 90 vol %. However, “… fluorescence detection system …” details are known to one of ordinary skill in the art (e.g., see “… refractive indices (RIs) of the various materials in the environment are matched, or are similar, such that a beam of light traveling through the optically homogenous environment will be insubstantially impacted by any changes in the RIs of the materials through which it travels … In some embodiments, the sample chamber of the optically homogenous sample manipulation component is filled with a solution. In some embodiments, the solution has an RI that matches the RI of the sample or the detection objective of the detection beam path. For example, in some embodiments, the solution used to fill the sample chamber is FocusClear or MountClear (both commercially available from CelExplorer Labs). In some embodiments, the solution used to fill the chamber is a liquid with a refractive index that ranges from about 1.42 up to about 1.46, such as about 1.45, including all values and sub ranges in between. In some embodiments, the solution used to fill the sample chamber is about 87% glycerol. Solutions having the desired range of refractive indices are commercially available from vendors, such as Cargille Labs …” in paragraphs 171 and 175 of Goodman et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional fluorescence detection system (e.g., comprising details such as “solution used to fill the chamber is a liquid with a refractive index that ranges from about 1.42 up to about 1.46, such as about 1.45, including all values and sub ranges in between. In some embodiments, the solution used to fill the sample chamber is about 87% glycerol”, in order to achieve “optically homogenous environment”) for the unspecified fluorescence detection system of Handique et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional fluorescence detection system (e.g., comprising details such as the observation liquid contains glycerol of 40 vol % to 90 vol %) as the unspecified fluorescence detection system of Handique et al.
Claim(s) 13 and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Handique et al. (US 2021/0370296) in view of Endo et al. (US 2007/0190579).
In regard to claim 13 which is dependent on claim 1, the method of Handique et al. lacks an explicit description of details of the “… functional surface coating permits biotinylated surface chemistry (e.g., biotin-streptavidin linkers) to bind to a probe including a functional linker …” such as the biological substance comprises a phosphorylated enzyme substrate. However, “… biotin-streptavidin …” details are known to one of ordinary skill in the art (e.g., see “… Amplified Luminescence Proximity Homogeneous Assay, comprising the steps of: 1) preparing a candidate autophosphorylated protein containing a biotin tag in a cell-free protein synthetic means, 2) activating the candidate autophosphorylated protein containing the biotin tag with a biotinylating enzyme and a biotin derivative to prepare a biotinylated candidate autophosphorylated protein, 3) bonding a phosphorylated detection antibody directly or indirectly to acceptor beads, and 4) contacting the biotinylated candidate autophosphorylated protein prepared in the step 2), the acceptor beads prepared in the step 3), and donor beads to which streptavidin is bonded to cause a signal change due to the proximity of the acceptor beads and the donor beads, thereby to detect a phosphorylation activity …” in paragraphs 31-41 of Endo et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional functional surface coating (e.g., comprising details such as “activating the candidate autophosphorylated protein containing the biotin tag with a biotinylating enzyme and a biotin derivative to prepare a biotinylated candidate autophosphorylated protein, 3) bonding a phosphorylated detection antibody directly or indirectly to acceptor beads, and 4) contacting the biotinylated candidate autophosphorylated protein prepared in the step 2), the acceptor beads prepared in the step 3), and donor beads to which streptavidin is bonded to cause a signal change due to the proximity of the acceptor beads and the donor beads”, in order to “detect a phosphorylation activity”) for the unspecified functional surface coating of Handique et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional functional surface coating (e.g., comprising details such as the biological substance comprises a phosphorylated enzyme substrate) as the unspecified functional surface coating of Handique et al.
In regard to claim 14 which is dependent on claim 11, the method of Handique et al. lacks an explicit description of details of the “… functional surface coating permits biotinylated surface chemistry (e.g., biotin-streptavidin linkers) to bind to a probe including a functional linker …” such as the reagent liquid includes a phosphorylation site recognition substance. However, “… biotin-streptavidin …” details are known to one of ordinary skill in the art (e.g., see “… Amplified Luminescence Proximity Homogeneous Assay, comprising the steps of: 1) preparing a candidate autophosphorylated protein containing a biotin tag in a cell-free protein synthetic means, 2) activating the candidate autophosphorylated protein containing the biotin tag with a biotinylating enzyme and a biotin derivative to prepare a biotinylated candidate autophosphorylated protein, 3) bonding a phosphorylated detection antibody directly or indirectly to acceptor beads, and 4) contacting the biotinylated candidate autophosphorylated protein prepared in the step 2), the acceptor beads prepared in the step 3), and donor beads to which streptavidin is bonded to cause a signal change due to the proximity of the acceptor beads and the donor beads, thereby to detect a phosphorylation activity …” in paragraphs 31-41 of Endo et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional functional surface coating (e.g., comprising details such as “activating the candidate autophosphorylated protein containing the biotin tag with a biotinylating enzyme and a biotin derivative to prepare a biotinylated candidate autophosphorylated protein, 3) bonding a phosphorylated detection antibody directly or indirectly to acceptor beads, and 4) contacting the biotinylated candidate autophosphorylated protein prepared in the step 2), the acceptor beads prepared in the step 3), and donor beads to which streptavidin is bonded to cause a signal change due to the proximity of the acceptor beads and the donor beads”, in order to “detect a phosphorylation activity”) for the unspecified functional surface coating of Handique et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional functional surface coating (e.g., comprising details such as the reagent liquid includes a phosphorylation site recognition substance) as the unspecified functional surface coating of Handique et al.
Claim(s) 21-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Handique et al. (US 2021/0370296) in view of Brum et al. (US 2020/0138764).
In regard to claims 21-23 which are dependent on claim 20, the apparatus of Handique et al. lacks an explicit description of details of the “… liquid handling …” such as a tilting mechanism configured to tilt at least one of the array plate and the holding mechanism with respect to a horizontal plane, wherein the tilting mechanism is configured to press at least one of the array plate and the holding mechanism vertically downward, and wherein the tilting mechanism comprises at least one of a pipette tip or a needle. However, “… liquid handling …” details are known to one of ordinary skill in the art (e.g., see “… Immediately after the initial measurements, AdipoRed containing cell media was gently aspirated by tilting the vessel so that the aspiration pipette does not damage any cells …” in paragraph 163 of Brum et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional liquid handling (e.g., comprising details such as “tilting the vessel”, in order that “the aspiration pipette does not damage any cells”) for the unspecified liquid handling of Handique et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional liquid handling (e.g., comprising details such as a tilting mechanism configured to tilt at least one of the array plate and the holding mechanism with respect to a horizontal plane, wherein the tilting mechanism is configured to press at least one of the array plate and the holding mechanism vertically downward, and wherein the tilting mechanism comprises at least one of a pipette tip or a needle) as the unspecified liquid handling of Handique et al.
Response to Arguments
Applicant’s arguments with respect to the amended claims have been fully considered but some are moot in view of the new ground(s) of rejection. Applicant's remaining arguments filed 29 December 2025 have been fully considered but they are not persuasive.
Applicant argues that each operation in the claimed apparatus or method is performed in the holder is not prima facie anticipated by Handique et al. because Handique et al. detect beads by housing them individually in an array of microwells, which differ in kind from the present invention wherein the specimen and observation liquid are held as a continuous liquid layer in a holder. In response to applicant's argument that the references fail to show certain features of applicant’s invention, it is noted that the features upon which applicant relies (i.e., the specimen and observation liquid are held as a continuous liquid layer in a holder) 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). Further it should be noted Handique et al. also teach a continuous liquid layer in a holder (e.g., see “… set of walls can include a set of channels that fluidly couple each well to at least one adjacent well in the array of wells …” in paragraph 100).
Applicant argues that each operation in the claimed apparatus or method is performed in the holder is not prima facie anticipated by Handique et al. because Handique et al.’s reagents and beads are at the bottom of the well and are observed from the back of the substrate. Examiner respectfully disagrees. Amended dependent claim 8 recites that “the acquisition step applying the excitation light to the plurality of spots through a backside surface in opposition the one surface in contact with the observation liquid; and detecting fluorescent light from the back surface side, wherein the backside surface is noncontact with the observation liquid”. Handique et al. state (paragraph 124) that “… imaging system (e.g., fluorescence imaging system) can be operable in a mode for providing real-time or near real-time fluorescence imaging of samples processed according to an assay. The imaging subsystem is preferably positioned beneath the substrate and oriented to image the contents of the set of wells through the transparent (or translucent) material of the substrate …”. Therefore, the cited prior art teaches or suggests all limitations as arranged in the claims.
Applicant argues that each operation in the claimed apparatus or method is performed in the holder is not prima facie anticipated by Handique et al. because each well of Handique et al. is an independent liquid phase. In response to applicant's argument that the references fail to show certain features of applicant’s invention, it is noted that the features upon which applicant relies (i.e., each well is an independent liquid phase) 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). Further it should be noted Handique et al. also teach fluidly couple each well to at least one adjacent well (e.g., see “… set of walls can include a set of channels that fluidly couple each well to at least one adjacent well in the array of wells …” in paragraph 100).
Applicant argues that the subject matter of the pending claims is not prima facie obvious over the prior art the deficiencies of Handique et al. Examiner respectfully disagrees for the reasons discussed above.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 2005/0239066 teaches a substrate having immobilized ligands.
US 2009/0218513 teaches imaging device.
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 Shun Lee whose telephone number is (571)272-2439. The examiner can normally be reached Monday-Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Uzma Alam can be reached at (571)272-3995. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SL/
Examiner, Art Unit 2884
/UZMA ALAM/Supervisory Patent Examiner, Art Unit 2884