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 .
This is a Non Final Rejection in response to applicant’s claim amendments and arguments filed December 16, 2025. Claims 14 and 15 are currently amended. Claims 1-20 are pending review in this correspondence.
Response to Amendment
Rejections of claims 1, 7-10, 17, and 18 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection) in view of Richmond et al (US 2009/0116714 A1) are withdrawn in view of applicant’s arguments to claims 1 and 10.
Rejection of claim 2 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection) and Richmond et al (US 2009/0116714 A1) in view of Voldman et al (US 2011/0045994 A1) to claim 1.
Rejection of claim 3 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection) and Richmond et al (US 2009/0116714 A1) in view of Zhou et al (US 2011/0143964 A1) is withdrawn in view of applicant’s arguments to claim 1.
Rejection of claim 4 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection) and Richmond et al (US 2009/0116714 A1) in view of Gerhardt et al (US 2006/0128006 A1) is withdrawn in view of applicant’s arguments to claim 1.
Rejections of claims 5, 6, 11, 12, and 19 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection) and Richmond et al (US 2009/0116714 A1) in view of Goldkorn et al (US 2011/0053152 A1) are withdrawn in view of applicant’s arguments to claims 1 and 10.
Rejections of claims 13 and 16 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection) and Richmond et al (US 2009/0116714 A1) in view of Makarova et al (WO 2011/139445 A1) are withdrawn in view of applicant’s arguments to claim 10.
Rejections of claims 14 and 15 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection) and Richmond et al (US 2009/0116714 A1) in view of Viovy et al (US 2011/0212440 A1) are withdrawn in view of applicant’s arguments to claim 10.
Rejection of claim 20 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection) and Richmond et al (US 2009/0116714 A1) in view of Voldman et al (US 2011/0045994 A1),further in view of Zhou et al (US 2011/0143964 A1), and further in view Gerhardt et al (US 2006/0128006 A1) are withdrawn in view of applicant’s arguments to claim 10.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 2, 4, 7, and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection) in view of Gong et al (US 2003/0138941 A1) (provided by applicant in IDS dated 10/13/2022).
With respect to claim 1 Tsutsui discloses a system (device A, See Fig. 1A and Para. 0023) comprising:
a substrate (body 1) comprising an inlet (inlet 3), an outlet (outlet 4), and a set of chambers (solid trapping portions 6) between the inlet and the outlet, wherein a chamber of the set of chambers is configured to retain a respective single cell of a set of cells of a sample (See Para. 0024 for discussion of how a fluid is introduced to the device and flowed through separation portion 5 which comprises a plurality of solid trapping portions 6 which are formed of wall bodies extending in the direction perpendicular to the bottom surface and having distal ends thereof brought into contact with the lower surface of a lid 100 are formed) and comprises:
a set of walls (partition walls 61, See Fig. 2 and Para. 0026) defining a chamber volume (See Para. 0024 for discussion of how the solid trapping portion which are formed of wall bodies extending in the direction perpendicular to the bottom surface and having distal ends thereof brought into contact with the lower surface of a lid 100 are formed; volume of each solid trapping member correlates to the space that would be occupied by a solid particle in each solid trapping portion, See Para. 0027),
an open surface (inlet portion 62, See Fig. 2) coupled to the inlet and permitting access of the respective single cell to the chamber volume (See Para. 0026), and
one or more pore channels (opening portion 64, See Fig. 2) at a downstream portion of the chamber volume and coupled to the outlet (See Para. 0026 for discussion of how the opening portion is formed on a downstream side of the accommodating portion),
wherein fluid received at the inlet enters each chamber only by way of the open surfaces of the set of chambers and arrives at the outlet only by way of the one or more pore channels of the set of chambers (See para. 0027 for description of how, when performing solid-liquid separation, the solid-liquid mixture moves as indicated by arrows, the solid 7 having a fixed size or larger is trapped in the accommodating portion 63, and liquid is allowed to flow downwardly from the opening portion 64. In other words, the solid-liquid mixture flows through a space formed in a sandwiched manner between opposedly facing faces from the upstream, solid particles having a fixed size or larger are trapped by the solid trapping portions arranged in the space (because the downward flow of the solid particle is prevented by the opening portion 64 smaller than the solid 7), and only the liquid flows downward in the gap); and
a cell removal tool (syringe, See para. 0038 for discussion of the incorporation of a syringe used to induce flow) configured to retrieve a target cell captured at one of the set of chambers. Applicant should further note the discussion of lid 100, which is discussed in Para. 0023; Para. 0038 discusses how the lid is formed of an optically transparent material such that a blood corpuscle trapping state can be optically observed and a value expressed in terms of hematocrit value can be optically measured.
Additionally, applicant should note the italicized limitations are directed to the function of the apparatus and/or the manner of operating the apparatus. All the structural limitations of the claim have been disclosed by Tsutsui and the apparatus of Tsutsui is capable of the recitation of claim 1. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of Tsutsui (see MPEP §2114) and the syringe disclosed in Tsutsui would be capable of performing the italicized recitation.
Tsutsui fails to disclose that the cell removal tool comprises a hollow needle, or that the lid is removable or pierceable.
Gong teaches a sample preparation integrated chip apparatus (100) having a sample fluid preparatory area shown as constructed on substrate (36). The substrate can be made of a suitable material such as glass, plastic, an elastomer such as poly-dimethylsiloxane (PDMS), metal, ceramic or a composite. To provide channels and assay stations, for example, various standard glass chemical etching techniques can be used on a glass substrate. Then the substrate may be sealed with a sealing layer (40; not shown in top view). If sealed, various configurations of sealing may be provided, such as sealing a portion of assay stations (26) only, or sealing the assay stations in combination with assay station channels (24, 28) and/or first and/or second multipurpose channel (30 and 22, respectively). The sealing layer is normally a plastic film that seals the channels and assay station or plurality of assay stations, except chamber (6) and all the inlets and outlets, by a bonding process including, but limited to, thermal bonding, electrostatic bonding, adhesive bonding. The sealing layer can also consist of other materials such as glass plate or plastic plate or an elastomer like polydimethylsiloxane (PDMS) (See Para. 0082). The sealing layer (40) may also be comprised of a self-healing/sealing type of material such as rubbers, elastomers, gels and/or a valve/lid which may be opened via mechanical, and/or electrical, and/or magnetic, and/or chemical means that would allow for introduction of a syringe, for example, into covered assay station 26, to provide for the application of a particular assay reaction component, for example, into assay station 26. Upon removal of the syringe, the sealing layer will self-seal (See Para. 0083).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the lid of Tsutsui with the self-sealing layer of Gong such that, upon introduction and removal of a syringe into a chamber of Tsutsui, the sealing layer will self-seal (See Para. 0083 of Gong). It should further be noted that Gong provides for the use of a syringe, which generally utilizes a needle for addition/removal of desired substances.
With respect to claim 2, as set forth in MPEP 2144.05, in the case where the claimed range “overlap or lie inside ranges disclosed by the prior art”, a prima facie case of obviousness exists, In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (See Para. 0122 of Gong for discussion of how the assay stations 26 can range in width or diameter typically from about 1 micrometer to about 10 mm, and typically from about 1 micrometer to about 1 mm in depth).
With respect to claim 4, as set forth in MPEP 2144.05, in the case where the claimed range “overlap or lie inside ranges disclosed by the prior art”, a prima facie case of obviousness exists, In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (See Para. 0122 of Gong for discussion of how channels 24 and 28 can range in width typically from about 1 micrometer to about 5 mm, while the channels can range in depth typically from about 1 micrometer to about 1 mm).
With respect to claim 7 the combination of Tsutsui and Gong teaches that the inlet is continuous with the open surfaces of each of the set of chambers, and the outlet is coupled to downstream portions of the one or more pore channels of each of the set of chambers (See Figs. 1A-2 and Paras. 0024-0028 of Tsutsui for discussion of how sample introduced into the inlet 3 moves in the direction of arrows 7, and liquid enters the accommodating portion 63 and flows towards the outlet 4 downwardly from the opening portion 64).
With respect to claim 9 the combination of Tsutsui and Gong teaches an imaging platform (stereoscopic microscope, See Paras. 0170-0172 of Tsutsui) configured to image the set of chambers for selective removal of the target cell from one of the set of chambers with the cell removal tool. Applicant should note the italicized limitations are directed to the function of the apparatus and/or the manner of operating the apparatus. All the structural limitations of the claim have been taught by the combination of Tsutsui and Richmond and the apparatus of combined Tsutsui and Richmond is capable of the italicized recitation of claim 9. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of combined Tsutsui and Richmond (see MPEP §2114).
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection) and Gong et al (US 2003/0138941 A1) (provided by applicant in IDS dated 10/13/2022) in view of Zhou et al (US 2011/0143964 A1).
Refer above for the combined teachings of Tsutsui and Gong.
With respect to claim 3, although Tsutsui discusses that a large number of solid trapping portions are formed (See Para. 0027), the combination of Tsutsui and Gong fails to teach that the set of chambers comprises from 10,000 to 1,000,000 chambers.
Zhou teaches that, depending on an application of the device, such as in the use of a
multiplexing bioassay, including but not limited to real-time PCR, hybridization, immunoassay, ELISA, and peptide or protein binding assay (See Para. 0135) a preferred number of chambers in each device can be above 10,000 (See Para. 0134).
It would have been obvious to one or ordinary skill in the art at the time of filing to incorporate a large number of trapping portions, such as 10,000, as taught by Zhou, into the device of combined Tsutsui and Gong that corresponds with the type of multiplexing bioassay that is to be performed (See Para. 0134 of Zhou).
Claim(s) 5 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection) and Gong et al (US 2003/0138941 A1) (provided by applicant in IDS dated 10/13/2022) in view of Goldkorn et al (US 2011/0053152 A1).
Refer above for the combined teachings of Tsutsui and Gong.
With respect to claim 5 the combination of Tsutsui and Gong fails to teach that the set of cells comprise circulating tumor cells (CTCs).
Goldkorn teaches a method for diagnosing cancer, predicting a disease outcome or response to therapy in a patient sample. The method involves isolating a circulating tumor cell (CTC), for example, a viable CTC, from a sample using a parylene microfilter device comprising a membrane filter having or consisting of a parylene substrate, which has an array of holes with a predetermined shape and size; and detecting and quantifying telomerase activity in blood circulating tumor cells (See abstract). The method is useful as a diagnostic, prognostic and predictive technique in cancer. For example, the system and method are capable of cell capture from 1 ml of whole blood in less than 5 minutes, achieving greater than 90% capture efficiency, greater than 90% cell viability and greater than 200-fold sample enrichment (See Para. 0005).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to enable to the device of combined Tsutsui and Gong to process circulating tumor cells, as taught by Goldkorn, such as the use is beneficial as a diagnostic, prognostic, and predictive technique in cancer detection (See Para. 0005 of Goldkorn).
With respect to claim 6, although the combination of Tsutsui and Gong teaches that the sample can be a blood sample (See Para. 0022 of Tsutsui), the combination fails to teach that the sample comprise a peripheral blood sample.
Goldkorn teaches a method for diagnosing cancer, predicting a disease outcome or response to therapy in a patient sample (See abstract). In one aspect, the present invention provides a highly sensitive yet specific method for diagnosing cancer and/or predicting disease outcome and response to therapy by (i) isolating circulating tumor cells from body fluids, such as blood samples including peripheral blood samples (See Para. 0034). The sample to be processed can be any body fluid containing tumor cells. For instance, the sample can be a blood sample from a mammal. In one embodiment, the sample is a peripheral blood sample obtained from a patient (See Para. 0043).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a peripheral blood sample, as taught by Goldkorn, into the sample of combined Tsutsui and Gong to source a bodily fluid that can contain tumors cells (See Paras. 0034 and 0043 of Goldkorn).
Claim(s) 8, 10, 17, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection) in view of Gong et al (US 2003/0138941 A1) (provided by applicant in IDS dated 10/13/2022), and further in view of Richmond et al (US 2009/0116714 A1).
Refer above for the combined teachings of Tsutsui and Gong.
With respect to claim 8, the combination of Tsutsui and Gong fails to teach that the hollow needle of the cell capture tool comprises a cannula structured to receive the target cell by capillary action.
Richmond teaches an apparatus for automated picking of animal cell colonies (See abstract), wherein the apparatus has a mammalian cell colony picking head (18) which is movable over the main bed of the apparatus by x- y- and z-positioners (20, 22 and 24) respectively. The head illustrated comprises an array of hollow pins (26), each connected to a fluid line (28) or aspiration (sucking) and dispensing (expulsion) of a cell colony to perform cell colony picking from a container followed by deposition of the cell colony sample into a well of a well plate (29) or other target location (See Para. 0035). Furthermore, Richmond teaches that the hollow needle of the cell capture tool comprises a cannula structured to receive the target cell by capillary action (See para. 0053 of Richmond for discussion of how, after a motor 60 is actuated to oscillate the end of inner pin 64, the forces induced by this motion have been found sufficient to detach the cell colony and allow aspiration of the detached cell colony into the hollow pin, which as mentioned above forms the end of a capillary 70).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the cannula and motor configuration taught by Richmond into the cell removal syringe taught by combined Tsutsui and Gong such that sufficient force is used to detach the selected cell and allow aspiration of said cell into the hollow pin (See Para. 0053 of Richmond).
With respect to claim 10 Tsutsui discloses a method comprising:
Providing a substrate (body 1) comprising an inlet (inlet 3), an outlet (outlet 4), and a set of chambers (solid trapping portions 6) between the inlet and the outlet, wherein a chamber of the set of chambers is configured to retain a respective single cell (See Paras. 0001, 0022, 0032-0033 for discussion of how blood corpuscles can be separated from a blood sample) of a set of cells of a sample (See Para. 0024 for discussion of how a fluid is introduced to the device and flowed through separation portion 5 which comprises a plurality of solid trapping portions 6 which are formed of wall bodies extending in the direction perpendicular to the bottom surface and having distal ends thereof brought into contact with the lower surface of a lid 100 are formed) and comprises:
a set of walls (partition walls 61, See Fig. 2 and Para. 0026) defining a chamber volume (See Para. 0024 for discussion of how the solid trapping portion which are formed of wall bodies extending in the direction perpendicular to the bottom surface and having distal ends thereof brought into contact with the lower surface of a lid 100 are formed; volume of each solid trapping member correlates to the space that would be occupied by a solid particle in each solid trapping portion, See Para. 0027),
an open surface (inlet portion 62, See Fig. 2) coupled to the inlet and permitting access of the respective single cell to the chamber volume (See Para. 0026), and
one or more pore channels (opening portion 64, See Fig. 2) at a downstream portion of the chamber volume and coupled to the outlet (See Para. 0026 for discussion of how the opening portion is formed on a downstream side of the accommodating portion),
wherein fluid received at the inlet enters each chamber only by way of the open surfaces of the set of chambers and arrives at the outlet only by way of the one or more pore channels of the set of chambers (See para. 0027 for description of how, when performing solid-liquid separation, the solid-liquid mixture moves as indicated by arrows, the solid 7 having a fixed size or larger is trapped in the accommodating portion 63, and liquid is allowed to flow downwardly from the opening portion 64. In other words, the solid-liquid mixture flows through a space formed in a sandwiched manner between opposedly facing faces from the upstream, solid particles having a fixed size or larger are trapped by the solid trapping portions arranged in the space (because the downward flow of the solid particle is prevented by the opening portion 64 smaller than the solid 7), and only the liquid flows downward in the gap); and
capturing and partitioning the set of cells of the sample individually within the set of chambers (See para. 0027 for discussion of how performing solid-liquid separation solid particles having a fixed size or larger are trapped by the solid trapping portions 6). Applicant should further note the discussion of lid 100, which is discussed in Para. 0023; Para. 0038 discusses how the lid is formed of an optically transparent material such that a blood corpuscle trapping state can be optically observed and a value expressed in terms of hematocrit value can be optically measured.
Tsutsui fails to disclose that the lid is removable or pierceable.
Gong teaches a sample preparation integrated chip apparatus (100) having a sample fluid preparatory area shown as constructed on substrate (36). The substrate can be made of a suitable material such as glass, plastic, an elastomer such as poly-dimethylsiloxane (PDMS), metal, ceramic or a composite. To provide channels and assay stations, for example, various standard glass chemical etching techniques can be used on a glass substrate. Then the substrate may be sealed with a sealing layer (40; not shown in top view). If sealed, various configurations of sealing may be provided, such as sealing a portion of assay stations (26) only, or sealing the assay stations in combination with assay station channels (24, 28) and/or first and/or second multipurpose channel (30 and 22, respectively). The sealing layer is normally a plastic film that seals the channels and assay station or plurality of assay stations, except chamber (6) and all the inlets and outlets, by a bonding process including, but limited to, thermal bonding, electrostatic bonding, adhesive bonding. The sealing layer can also consist of other materials such as glass plate or plastic plate or an elastomer like polydimethylsiloxane (PDMS) (See Para. 0082). The sealing layer (40) may also be comprised of a self-healing/sealing type of material such as rubbers, elastomers, gels and/or a valve/lid which may be opened via mechanical, and/or electrical, and/or magnetic, and/or chemical means that would allow for introduction of a syringe, for example, into covered assay station 26, to provide for the application of a particular assay reaction component, for example, into assay station 26. Upon removal of the syringe, the sealing layer will self-seal (See Para. 0083).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the lid of Tsutsui with the self-sealing layer of Gong such that, upon introduction and removal of a syringe into a chamber of Tsutsui, the sealing layer will self-seal (See Para. 0083 of Gong).
Tsutsui fails to specifically disclose the step of delivering a target cell of the set of cells from the set of chambers and into a cell removal tool.
Richmond teaches an apparatus for automated picking of animal cell colonies (See abstract), wherein the apparatus has a mammalian cell colony picking head (18) which is movable over the main bed of the apparatus by x- y- and z-positioners (20, 22 and 24) respectively. The head illustrated comprises an array of hollow pins (26), each connected to a fluid line (28) or aspiration (sucking) and dispensing (expulsion) of a cell colony to perform cell colony picking from a container followed by deposition of the cell colony sample into a well of a well plate (29) or other target location (See Para. 0035).
It would have been obvious to one of ordinary skill in the art before the effective filing date to incorporate the picker device of Richmond and process of isolating and removing desired cells of a cell colony to a target location into the method of combined Tsutsui and Gong to ensure sufficient picking and transfer of desired cells/solids from the solid trapping portions (See Para. 0035 of Richmond).
With respect to claim 17 the combination of Tsutsui, Gong, and Richmond teaches that delivering the target cell of the set of cells from the set of chambers and into the cell removal tool is performed using an imaging platform configured to image the set of chambers (See Paras. 0005 and 0035 of Richmond for discussion of the use of a high resolution camera for imaging each colony and performing cell colony picking; also See Paras. 0170-0172 of Tsutsui for discussion of a stereoscopic microscope).
With respect to claim 18 the combination of Tsutsui, Gong, and Richmond teaches performing fluorescent detection of contents of the set of chambers using the imaging platform (See Para. 0013 of Richmond for discussion of how the cell colonies may be detected optically with the aid of fluorescence stains; Para. 0081 discusses how the apparatus can be used with a variety of optical based methods. Simple contrast imaging can be used, or more sophisticated spectroscopic methods based on absorbance, luminescence or Raman scattering. If more sophisticated spectral analysis is needed, such as for resonant Raman scattering, the collection optics may include a spectrometer or continuously tunable bandpass filter placed in front of the detector. In order to achieve significant absorbance changes, very high concentrations of dyes must be used and many cells are needed to achieve significant changes in optical density. Preferably, the optical based methods rely on fluorescence and/or luminescence which are more sensitive assay methods compared to absorbance).
Claim(s) 11, 12, and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection), Gong et al (US 2003/0138941 A1) (provided by applicant in IDS dated 10/13/2022), and Richmond et al (US 2009/0116714 A1) in view of Goldkorn et al (US 2011/0053152 A1).
Refer above for the combined teachings of Tsutsui, Gong, and Richmond.
With respect to claim 11, although the combination of Tsutsui, Gong, and Richmond teaches that the sample can be a blood sample (See Para. 0022 of Tsutsui), the combination fails to teach that the sample comprise a peripheral blood sample.
Goldkorn teaches a method for diagnosing cancer, predicting a disease outcome or response to therapy in a patient sample (See abstract). In one aspect, the present invention provides a highly sensitive yet specific method for diagnosing cancer and/or predicting disease outcome and response to therapy by (i) isolating circulating tumor cells from body fluids, such as blood samples including peripheral blood samples (See Para. 0034). The sample to be processed can be any body fluid containing tumor cells. For instance, the sample can be a blood sample from a mammal. In one embodiment, the sample is a peripheral blood sample obtained from a patient (See Para. 0043).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a peripheral blood sample, as taught by Goldkorn, into the sample of combined Tsutsui, Gong, and Richmond to source a bodily fluid that can contain tumors cells (See Paras. 0034 and 0043 of Goldkorn).
With respect to claim 12 the combination of Tsutsui, Gong, and Richmond fails to teach that the set of cells comprise circulating tumor cells (CTCs).
Goldkorn teaches a method for diagnosing cancer, predicting a disease outcome or response to therapy in a patient sample. The method involves isolating a circulating tumor cell (CTC), for example, a viable CTC, from a sample using a parylene microfilter device comprising a membrane filter having or consisting of a parylene substrate, which has an array of holes with a predetermined shape and size; and detecting and quantifying telomerase activity in blood circulating tumor cells (See abstract). The method is useful as a diagnostic, prognostic and predictive technique in cancer. For example, the system and method are capable of cell capture from 1 ml of whole blood in less than 5 minutes, achieving greater than 90% capture efficiency, greater than 90% cell viability and greater than 200-fold sample enrichment (See Para. 0005).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to enable to the device of combined Tsutsui, Gong, and Richmond to process circulating tumor cells, as taught by Goldkorn, such as the use is beneficial as a diagnostic, prognostic, and predictive technique in cancer detection (See para. 0005 of Goldkorn).
With respect to claim 19 the combination of Tsutsui, Gong, and Richmond fails to teach that delivering the target cell comprises delivering the target cell into the cell removal tool in a viable state.
Goldkorn teaches a method for isolating a CTC, for example, a viable CTC, from a sample using a parylene microfilter device (See abstract). It is preferred that the isolated cells are alive because, compared to normal cells, most cancer cells have higher telomerase activity, which directly indicates their malignant/metastatic potential. Hence, the measurement of telomerase activity of CTCs is important for cancer metastasis study. Telomerase activity is preferably measured from viable cells. Although the telomerase activity of individual whole blood cell (WBC) is low, without an efficient enrichment, the telomerase activity from all the WBCs may still add high background noise to the telomerase activity of CTCs. The parylene filtration system of the present invention provides enrichment of CTCs and allows picking up a single cancer cell using micropipette from the enriched viable cancer cells on the filter and isolating the single cancer cell and obtaining its telomerase activity by sensitive quantitative PCR (qPCR) (See Para. 0060).
It would have been obvious to one of ordinary skill in the art before ethe effective filing date of the claimed invention to ensure that cells delivered in the cell removal tool of the device of claimed Tsutsui, Gong, and Richmond are in a viable state such that desirable characteristics, such as telomerase activity, can be measured, as taught by Goldkorn (See Para. 0006 of Goldkorn).
Claim(s) 13 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection), Gong et al (US 2003/0138941 A1) (provided by applicant in IDS dated 10/13/2022), and Richmond et al (US 2009/0116714 A1) in view of Makarova et al (WO 2011/139445 A1).
Refer above for the combined teachings of Tsutsui, Gong, and Richmond.
With respect to claim 13 the combination of Tsutsui, Gong, and Richmond fails to teach performing an immunocytochemistry assay upon the target cell of the set of cells.
Makarova teaches methods of manufacturing polymer microfilters (See abstract), wherein the microfilter can be held in a filter holder for medical diagnostics and/or prognostics. In some embodiments, the microfilter may be used to collect circulating tumor cells (CTCs) in blood. In such embodiments, a blood sample, typically in the range of 1-10 ml, is taken from a patient. The blood sample is then drawn through the microfilter by applying negative pressure, such as a sucking force (See Para. 0096). In certain embodiments, collected CTCs can be subjected to a variety of analyses and manipulations, such as immunofluorescence, cell counting, PCR, fluorescence in-situ hybridization (FISH), immunohistochemistry, flow cytometry, immunocytochemistry, image analysis, enzymatic assays, gene expression profiling analysis, efficacy tests of therapeutics, culturing of enriched cells, and therapeutic use of enriched rare cells (See Para. 0099).
It would have been obvious to one of ordinary skill in the at before the effective filing date of the claimed invention to incorporate the step of subjecting collected cells/CTCs to one or more of a variety of analysis and manipulations, to include immunocytochemistry, as taught by Makarova, into the method of combined Tsutsui, Gong, and Richmond to ensure that vital information can be collected for medical diagnostics and/or prognostics (See Paras. 0096 and 0099 of Makarova).
With respect to claim 16 the combination of Tsutsui, Gong, and Richmond fails to teach applying a negative pressure at the outlet in coordination with capturing the set of cells at the set of chambers.
Marakova teaches a filtration process (1701) using a microfilter, wherein the microfilter is positioned in a filter holder, wherein the filter holder includes an inlet, an outlet, and securely holds the microfilter around the edges of the filter. In some embodiments, a liquid may be input into the filter holder through the outlet. At block 1750, the liquid is passed through the microfilter. In certain embodiments, the liquid is a bodily fluid or a solution including a bodily fluid. In certain embodiments, the liquid is drawn through the microfilter by applying negative pressure at the outlet of the filter holder such that all or substantially all of the liquid is drawn through the pores of the microfilter. In other embodiments, the liquid is pushed through the microfilter. At block 1770, the microfilter is removed from the filter holder. In some embodiments, the filter may then be subject to processing and or analysis to analyze any cells or other materials, substances, etc. collected by the microfilter (See Para. 0094).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the application of negative pressure at the outlet, such as taught by Marakova, to the method of particle capture taught by combined Tsutsui, Gong, and Richmond to ensure that all or substantially all of the liquid is drawn through the particle trapping portions (See Para. 0094 of Marakova).
Claim(s) 14 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection), Gong et al (US 2003/0138941 A1) (provided by applicant in IDS dated 10/13/2022), and Richmond et al (US 2009/0116714 A1) in view of Viovy et al (US 2011/0212440 A1).
Refer above for the combined teachings of Tsutsui, Gong, and Richmond.
With respect to claim 14 the combination of Tsutsui, Gong, and Richmond fails to teach delivering a solution of conjugated antibodies into the set of chambers, the solution comprising one or more antibodies specific to the target cell.
Viovy teaches a cell sorting and capture device and method, wherein, in order to allow for high resolution microscopy observation, specific fluorescently labeled antibodies had to be prepared. Cell labelling of specific protein (Cytokeratine, CD45) is realized by conjugating a specific antibody with fluorescent anti-IgG antibody provided by Zenon Mouse IgG Labeling Units (Invitrogen): 1µg of antibody is diluted in phosphate-buffered saline (PBS) (=20µL, 5µL of the Zenon mouse IgG labeling reagent (Component A) is added to the antibody solution and incubated for 5 minutes at room temperature (See Para. 0407).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the step of adding conjugated antibodies that are specific to the target cell, as taught by Viovy, to the method of combined Tsutsui, Gong, and Richmond to allow for high resolution microscopy observation of the captured cells (See Para. 0407 0f Viovy).
With respect to claim 15 the combination of Tsutsui, Gong, Richmond, and Viovy teaches that the solution comprises a primary antibody cocktail comprising antibody specific for CD45 (See Para. 0407 of Viovy).
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsutsui (WO 2011/078115 A1) (English translation of the document is provided by US 2012/0261356 A1 and will be referenced for the rejection), Gong et al (US 2003/0138941 A1) (provided by applicant in IDS dated 10/13/2022), and Richmond et al (US 2009/0116714 A1) in view of Zhou et al (US 2011/0143964 A1).
Refer above for the combined teachings of Tsutsui and Richmond.
With respect to claim 20, while the combination of Tsutsui, Gong, and Richmond teaches that each chamber/solid trapping portion has a depth from 5 micrometers to 200 micrometers and the one or more pore channels of each of the set of pore channels have a width from 1 to 25 micrometers (See Para. 0122 of Gong for discussion of how the assay stations 26 can range in width or diameter typically from about 1 micrometer to about 10 mm, and typically from about 1 micrometer to about 1 mm in depth and how channels 24 and 28 can range in width typically from about 1 micrometer to about 5 mm, while the channels can range in depth typically from about 1 micrometer to about 1 mm) there is no teaching wherein the set of chambers comprises from 10,000 to 1,000,000 chambers,.
Zhou teaches that, depending on an application of the device, such as in the use of a
multiplexing bioassay, including but not limited to real-time PCR, hybridization, immunoassay, ELISA, and peptide or protein binding assay (See Para. 0135) a preferred number of chambers in each device can be above 10,000 (See Para. 0134).
It would have been obvious to one or ordinary skill in the art at the time of filing to incorporate a large number of trapping portions, such as 10,000, as taught by Zhou, into the device of combined device of Tsutsui, Gong, and Richmond, such that the number corresponds with the type of multiplexing bioassay that is to be performed (See Para. 0134 of Zhou).
Response to Arguments
Applicant’s arguments filed December 16, 2025, with respect to the combination of Tsutsui and Richmond, have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection was made above to incorporate Gong, which teaches penetrating a transparent lid/cover using a self-sealing cover, without disrupting fluid flow. The incorporation of Gong was implemented to more effectively address applicant’s arguments presented on pages 7-8 of applicant’s arguments/remarks.
Conclusion
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/BRITTANY I FISHER/Examiner, Art Unit 1796 March 21, 2026