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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 16th, 2026 has been entered.
Claims 1-2, 5, 9, 11, 14-15, 19, 23-24, 27-30, 37-38, 40, 43, 46-47 and 51 remain pending in the application. Claim 26 has been cancelled and claim 52 has been added.
Response to Arguments
Applicant’s arguments with respect to claims 1-2, 5, 9, 11, 14-15, 19, 23-24, 27-30, 37-38, 40, 43, 46-47 and 51, filed January 16th, 2026, have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Examiner note: A 101 analysis was performed on the claims but concluded it was not necessary because the claimed system/structures are not well understood, routine, and conventional.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 27-29, 37-38, 40, 43, 46, 47, and 51 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 27 (Claims 28-29, 37-38, 40, 43, 46, 47, and 51 by virtue of dependency) recites the limitation “sending, to the cutting apparatus, a command to cut through the one or more sample collectors and the substrate along the delineation overlay, the cells of interest separated from the surrounding portion by the cutting apparatus and analyzed to detect expression levels of one or more target genes associated with a skin condition”. It is unclear which structural component (cutting apparatus or computing device/application) is performing the analyzing to detect expression levels. The limitation is suggested to recite
“sending, to the cutting apparatus, a command to cut through the one or more sample collectors and the substrate along the delineation overlay, the cells of interest separated from the surrounding portion by the cutting apparatus; and
analyzing the cells of interest separated from the surrounding portion to detect expression levels of one or more target genes associated with a skin condition”.
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.
Claims 1-2, 9, 19, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Routamaa (US 20180333884 A1 – previously cited) in view of Chung (WO 2005026811 A1 – previously cited), and further in view of Palmer (US 20180110500 A1).
Regarding claim 1, Routamaa discloses a method for isolating cells of interest from a tissue sample collection kit (Abstract, method in fig. 2), the method (fig. 2) comprising: receiving at least one image (image 104, fig. 1, para. [0031]) at a computing device (processor 102 & display screen 108, fig. 1, para. [0031]) via an imaging apparatus (optical imaging unit 101, fig. 1, para. [0031]) (step 201, fig. 2), the at least one image generated based on image data captured by the imaging apparatus of one or more sample collectors (sample carrier 109, fig. 1) (“image of at least portion of the sample carrier 109”, para. [0031], fig. 1), each of the one or more sample collectors comprising a sample (“sample material … blood”, para. [0029]); processing the at least one image using the computing device (“102 … image analyzing algorithm”, para. [0032, 0045]), the processing comprising identifying a delineation between the cells of interest and a surrounding portion of each of the one or more sample collectors (finding, … a region which is distinguished from its surroundings … determine the location of … sample regions to be cut, para. [0032, 0045]) (step 202, fig. 2) and overlaying the delineation with a delineation overlay (“display one or more indicators 105,105’ … location of sample region to be cut”; “displaying, on top of the image, one or more indicators”, fig. 1, para. [0031, 0042]) (step 203, fig. 2), sending a command from the computing device to a cutting apparatus (cutting unit 103, fig. 1) (“computer program … instructions … control a cutting unit to cut”, para. [0052], as seen in fig. 1), the command (“instructions … control”, para. [0052]) causing the cutting apparatus to cut along the delineation overlay to separate the cells of interest from the surrounding portion (“cutting unit … cutting impact produced by the cutting instrument is moved along the outer periphery of each sample region so as to cut off the sample region from the sample carrier”; “indicators … expressing the location … cutting off the one or more sample regions”, para. [0030, 0042-0043], step 204, fig. 2).
Routamaa does not expressly disclose each of the one or more sample collectors comprising a tissue sample having cells of interest; the one or more sample collectors positioned on a substrate; and the command causing the cutting apparatus to cut through the one or more sample collectors and the substrate along the delineation overlay to separate the cells of interest from the surrounding portion.
However, Chung directed to a microdissection system discloses one or more sample collectors (186, fig. 21) comprising a tissue sample (tissue sample 184, fig. 21) having cells of interest (“tissue sample … cell specimen”, pages 1-2); the one or more sample collectors (186, fig. 21) positioned on a substrate (182, fig. 21) (tissue sample 184 is seated into an upper center of the high molecular film 182 … and surrounded by a liquid phase cover slip 186, page 24 lines 20-26); the command (“dissection command”, page 31 lines 9-13) causing the cutting apparatus to cut through the one or more sample collectors and the substrate along a selected dissected region (dissected region is selected, a laser beam is illuminated … to dissect the high molecular film 182, the tissue sample 184, and the liquid phase cover slip 186 within the selected region … the dissected tissue slices freely drop; cutting a drawing path … using a laser beam from a laser device … under the control of the control unit, page 26 lines 3-11 & page 31 lines 19-21, figs. 21-22) to separate the cells of interest from the surrounding portion (“microdissection … separating normal cells and tumor cells”; “tissue slices … dissected from the cell tissue”, page 8 lines 14-21 & page 32 lines 10-19, fig. 22). Chung further discloses providing a microdissection method in which optical definition of a tissue slice when observing the tissue slice using a microscope can be sufficiently improved, and a tissue slice of a cell having a thick tissue can be dissected rapidly and exactly while keeping high optical definition and providing an increased rate of regions for a dissected cell or a tissue gathered (Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa to further comprise each of the one or more sample collectors comprising a tissue sample having cells of interest, the one or more sample collectors positioned on a substrate and the command causing the cutting apparatus to cut through the one or more sample collectors and the substrate along the delineation overlay, in view of the teachings of Chung, as this would aid in rapidly and exactly dissecting tissue while keeping high optical definition and providing an increased rate of regions for a dissected cell or tissue gathered.
Routamaa further discloses that the one or more detached sample regions can be conveyed for further analysis (para. [0029, 0044]) and Chung further discloses that the microdissection method can be mainly employed in researches into cancer (page 8 lines 14-21).
Routamaa, as modified by Chung hereinabove, does not disclose analyzing expression levels of one or more target genes associated with a skin condition in the cells of interest that are separated from the surrounding portion.
However, Palmer directed to non-invasive tape stripping methods for the collection of a skin sample and isolating cellular material from the skin sample (para. [0034]) discloses analyzing expression levels of one or more target genes associated with a skin condition in the cells of interest that are separated from the surrounding portion (“histopathologic diagnosis”; “isolated RNA … expression levels of these target genes are quantified … gene expression signature … associated with a disease such as melanoma”; “identification of a disease state, para. [0036-0038, 0040, 0062, 0075-0076]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Chung hereinabove, to further comprise analyzing expression levels of one or more target genes associated with a skin condition in the cells of interest that are separated from the surrounding portion, in view of the teachings of Palmer, as this would aid in histopathologic diagnosis and identifying a disease state, likelihood of treatment success for a given disease state, identification of progression of a disease state (e.g., invasiveness of melanoma), and identification of a disease stage (Palmer, para. [0036, 0076]).
Regarding claim 2, Routamaa, as modified by Chung and Palmer hereinabove, discloses the method of claim 1. Routamaa, as modified by Chung and Palmer hereinabove, does not disclose wherein the one or more sample collectors comprises one or more non-invasive, adhesive sample collectors.
However, Palmer directed to non-invasive tape stripping methods for the collection of a skin sample discloses wherein the one or more sample collectors comprises one or more non-invasive, adhesive sample collectors (“adhesive skin sample collection kit”, para. [0033-0034, 0037]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Chung and Palmer hereinabove, such that the one or more sample collectors comprises one or more non-invasive, adhesive sample collectors, in view of the teachings of Palmer, as this would aid in collecting and adhering an effective amount of a skin sample containing cellular material with minimal discomfort and without scarring.
Regarding claim 9, Routamaa, as modified by Chung and Palmer hereinabove, discloses method of claim 1, wherein the imaging apparatus includes an optical scanning system (optical imaging unit 101, fig. 1, “scanner”, para. [0039]).
Regarding claim 19, Routamaa, as modified by Chung and Palmer hereinabove, discloses the method of claim 1, wherein the cutting is performed with a mechanical cutting system, a plasma cutting system, or a laser cutting system (“punch 107 and a die … laser beam cutter or a liquid jet cutter”, para. [0030]).
Regarding claim 23, Routamaa, as modified by Chung and Palmer hereinabove, discloses the method of claim 1, wherein identifying the delineation and sending the command are performed by an automated, computer-controlled apparatus (“computer program … software modules for controlling”, para. [0052-0055]).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Routamaa in view of Chung and Palmer, as applied to claim 1 above, and further in view of Bonner (US 6251516 B1- previously cited).
Regarding claim 5, Routamaa, as modified by Chung and Palmer hereinabove, discloses the method of claim 1. Routamaa, as modified by Chung and Palmer hereinabove, does not disclose wherein the one or more sample collectors comprises a plurality of sample collectors arranged in an array of sample collectors.
However, Bonner discloses wherein the one or more sample collectors comprises a plurality of sample collectors arranged in an array of sample collectors (col. 18 lines 3-13 & lines 41-48, one can ensure that the target sites are at known positions on the transfer substrate; multiple small pieces of adhesive transfer film can be selectively applied to those locations on the tissue which correspond to sites to be extracted; linear array of separately activatable target sites; size of the adhesive film spot determines the size of the target zone within which selection of the objects/cells are made for that one transfer (array number); target zone size is determined by the selection of the particular film (i.e., the geometry of ordered arrays)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Chung and Palmer hereinabove, such that the one or more sample collectors comprises a plurality of sample collectors arranged in an array of sample collectors, in view of the teachings of Bonner, as this would aid in determining the size and positions of the target zones/sites by providing a linear array of separately activatable target sites selectively applied to those locations on the tissue which correspond to sites to be extracted such that the size of the adhesive film spot determines the size of the target zone within which selection of the objects/cells are made for that one transfer (array number) and ensures that the target sites are at known positions on the transfer substrate (Bonner, col. 18 lines 3-13 & lines 41-48).
Claims 11 and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Routamaa in view of Chung and Palmer, as applied to claim 1 above, and further in view of Venkataramani (US 20180000462 A1 – previously cited).
Regarding claim 11, Routamaa, as modified by Chung and Palmer hereinabove, discloses the method of claim 1. Routamaa, as modified by Chung and Palmer hereinabove, does not disclose wherein the delineation overlay comprises digital information comprising a plurality of points and at least one of one or more lines or one or more curves connecting the plurality of points to form a polygon.
However, Venkataramani discloses wherein the delineation overlay comprises digital information (“thermographic image”, para. [0022]) comprising a plurality of points (N points, as seen in fig. 5, para. [0022]) and at least one of one or more lines or one or more curves connecting the plurality of points to form a polygon (as seen in fig. 5, “points are connected to form a N≧5 sided polygon which defines a boundary contour … in the image … boundary lines”, para. [0022]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Chung and Palmer hereinabove, such that the delineation overlay comprises digital information comprising a plurality of points and at least one of one or more lines or one or more curves connecting the plurality of points to form a polygon, in view of the teachings of Venkataramani, as this would aid in defining a boundary contour to identify the region of interest.
Regarding claim 52, Routamaa, as modified by Chung and Palmer hereinabove, discloses the method of claim 1. Routamaa further discloses a region which is distinguished from its surroundings with respect to e.g. color and/or brightness in order to determine the location of such a part of the sample carrier which has been impregnated with the sample material (para. [0032, 0033]).
Routamaa, as modified by Chung and Palmer hereinabove, does not disclose wherein the delineation is a demarcation provided on the one or more sample collectors.
However, Palmer directed to non-invasive tape stripping methods for the collection of a skin sample discloses a delineation (“demarcation”, para. [0077]), wherein the delineation is a demarcation provided on the one or more sample collectors (“demarcating the sampled skin region on … adhesive tape … demarcation indicates the sample region to be processed”, para. [0077, 0096], fig. 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Chung and Palmer hereinabove, such that the delineation is a demarcation provided on the one or more sample collectors, in view of the teachings of Palmer, as this would aid in indicating/distinguishing the sample region to be processed.
Routamaa further discloses indicator 105 expressing the sample region to be cut off (para. [0032, 0033]).
Routamaa, as modified by Chung and Palmer hereinabove, does not disclose wherein the delineation overlay is a polygon and includes one or more manipulation points.
However, Venkataramani discloses wherein the delineation overlay is a polygon (as seen in fig. 5, “points are connected to form a N≧5 sided polygon which defines a boundary contour … in the image … boundary lines”, para. [0022]) and includes one or more manipulation points (N points, as seen in fig. 5, “points is a vertex … selectively manipulate … adjusting the vertices”, para. [0022], fig. 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Chung and Palmer hereinabove, such that the delineation overlay is a polygon and includes one or more manipulation points, in view of the teachings of Venkataramani, as this would aid in defining a boundary contour to identify the region of interest and enable manipulation of the shape of the polygon defining the boundary of the region of interest/express to indicate the sample region to be cut off.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Routamaa in view of Chung and Palmer, as applied to claim 1 above, and further in view of Krizman (US 20180112277 A1 – previously cited).
Regarding claim 14, Routamaa, as modified by Chung and Palmer hereinabove, discloses the method of claim 1. Routamaa, as modified by Chung and Palmer hereinabove, does not disclose wherein identifying the delineation between the cells of interest and a surrounding portion of a sample collector comprises delineating the cells of interest obtained from a lesion area from other cells obtained from a non-lesion surrounding area.
However, Krizman discloses wherein identifying the delineation between the cells of interest and a surrounding portion of a sample collector comprises delineating the cells of interest obtained from a lesion area from other cells obtained from a non-lesion surrounding area (para. [0004, 0042], specified and desired cells to be excised for molecular analysis, such as tumor cells, are identified; non-desirable cells … that should not be analyzed; imperative that non-tumor cells be excluded from analysis of patient tumor tissue; an exclusion signal to prevent benign, non-malignant cells such as normal cells from contaminating analysis of tumor cells, which creates an optimized sample).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Chung and Palmer hereinabove, such that identifying the delineation between the cells of interest and a surrounding portion of a sample collector comprises delineating the cells of interest obtained from a lesion area from other cells obtained from a non-lesion surrounding area, in view of the teachings of Krizman, as this would aid in providing an optimized sample by excluding non-tumor cells in analysis of patient tumor tissue.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Routamaa in view of Chung and Palmer, as applied to claim 1 above, and further in view of Fauver (US 11541386 B2 – previously cited).
Regarding claim 15, Routamaa, as modified by Chung and Palmer hereinabove, discloses the method of claim 1. Routamaa, as modified by Chung and Palmer hereinabove, does not disclose wherein the at least one image is processed using a computer vision algorithm.
However, Fauver discloses wherein the at least one image is processed using a computer vision algorithm (col. 11 lines 49-56, “computer vision algorithm”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Chung and Palmer hereinabove, such that the at least one image is processed using a computer vision algorithm, in view of the teachings of Fauver, as this would aid in detecting and describing local features in images and detecting the presence of the biological specimen (Fauver, col. 11 lines 49-56).
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Routamaa in view of Chung and Palmer, as applied to claim 23 above, and further in view of Kelso (US 20200270560 A1 - previously cited).
Regarding claim 24, Routamaa, as modified by Chung and Palmer hereinabove, discloses the method of claim 23. Routamaa, as modified by Chung and Palmer hereinabove, does not disclose wherein the automated, computer- controlled apparatus has a throughput of at least 16, at least 32, or at least 48 sample collectors per minute.
However, Kelso discloses wherein the automated, computer- controlled apparatus has a throughput of at least 16, at least 32, or at least 48 sample collectors per minute (para. [0058, 0095-0096], methods for then efficiently removing the unwanted cells can provide for a much higher throughput and less costly clone production process; culture plate wells may be processed at a rate of at least 16, … or at least 20 wells per minute; larger numbers of discrete regions or wells on a substrate may be advantageous in terms of increasing the processing throughput of the disclosed methods)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Chung and Palmer hereinabove, such that the automated, computer- controlled apparatus has a throughput of at least 16, at least 32, or at least 48 sample collectors per minute, in view of the teachings of Kelso, as this would aid in increasing the processing throughput by incorporating the substrate having a larger number of discrete regions such that the methods for efficiently removing the unwanted cells can provide for a much higher throughput.
Claims 27-30 and 37-38 are rejected under 35 U.S.C. 103 as being unpatentable over Routamaa in view of Morris (US 20110194749 A1 – previously cited), further in view of Chung, and further in view of Palmer.
Regarding claim 27, Routamaa discloses a system for isolating cells of interest from a tissue sample collection kit (fig. 1, Abstract), the system (fig. 1) comprising: an imaging apparatus (optical imaging unit 101, fig. 1); a cutting apparatus (cutting unit 103, fig. 1); and a computing device (processor 102 & display screen 108, fig. 1) comprising at least one processor (processor 102, fig. 1), and instructions executable by the at least one processor to provide an application (“computer program … software modules … instructions”, para. [0052, 0056-0057]); wherein the computing device (102 & 108, fig. 1) is communicatively coupled to the imaging apparatus (101, fig. 1) and the cutting apparatus (103, fig. 1) (as seen in fig. 1, para. [0052]); wherein the application is configured to perform operations (“functions”, para. [0052-0056]) comprising: instructing the imaging apparatus to image (optical imaging unit 101, fig. 1, para. [0031]) (step 201, fig. 2) one or more sample collectors (sample carrier 109, fig. 1) to generate at least one image (“image of at least portion of the sample carrier 109”, para. [0031], fig. 1), each of the one or more sample collectors comprising a sample (“sample material … blood”, para. [0029]); processing the at least one image (“102 … image analyzing algorithm”, para. [0032, 0045]), the processing comprising identifying a delineation between cells of interest of the tissue sample and a surrounding portion of each of the one or more sample collectors (finding, … a region which is distinguished from its surroundings … determine the location of … sample regions to be cut, para. [0032, 0045]) (step 202, fig. 2) and overlaying the delineation with a delineation overlay (“display one or more indicators 105,105’ … location of sample region to be cut”; “displaying, on top of the image, one or more indicators”, fig. 1, para. [0031, 0042]) (step 203, fig. 2); and sending, to the cutting apparatus, a command to cut (“computer program … instructions … control a cutting unit to cut”, para. [0052], as seen in fig. 1) along the delineation overlay (“cutting unit … cutting impact produced by the cutting instrument is moved along the outer periphery of each sample region so as to cut off the sample region from the sample carrier”; “indicators … expressing the location … cutting off the one or more sample regions”, para. [0030, 0042-0043], step 204, fig. 2).
Routamaa does not disclose the computing device comprising a communications interface; wherein the computing device is communicatively coupled to the imaging apparatus and the cutting apparatus through the communications interface.
However, Morris discloses a computing device (control 810, para. [0054]) comprising at least one processor (“computer”, para. [0054]), a communications interface (network 130; antennas and/or transceivers to communicate, para. [0054, 0080], fig. 1), and instructions executable by the at least one processor to provide an application (para. [0082], implemented in software … as one or more instructions or code on a tangible, non-transitory computer-readable medium; computer program); wherein the computing device (controller 810, fig. 8) is communicatively coupled to the imaging apparatus (digital imaging system 110, para. [0054]) and the cutting apparatus (laser cutting apparatus 800, para. [0054]) through the communications interface (para. [0054, 0080, 0082], laser cutting system includes a laser cutting apparatus 800 coupled to a controller 810; coupled to a network 130 and a digital imaging system 110; antennas and/or transceivers to communicate with various components within the network or within the device).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa such that the system further comprises the computing device comprising at least one processor, a communications interface, and instructions executable by the at least one processor to provide an application; wherein the computing device is communicatively coupled to the imaging apparatus and the cutting apparatus through the communications interface, in view of the teachings of Morris, as such a modification would have been merely a substitution of the processor of Routamaa for the controller and computer program of Morris that is coupled to the laser cutting system, the network, and the digital imaging system such that the laser movement and cutting properties can be wirelessly programmed and/or controlled by controller.
Routamaa, as modified by Morris hereinabove, does not disclose each of the one or more sample collectors comprising a tissue sample and positioned on a substrate; and sending, to the cutting apparatus, a command to cut through the one or more sample collectors and the substrate along the delineation overlay, the cells of interest separated from the surrounding portion by the cutting apparatus and analyzed to detect expression levels of one or more target genes associated with a skin condition.
However, Chung directed to a microdissection system discloses each of the one or more sample collectors (186, fig. 21) comprising a tissue sample (tissue sample 184, fig. 21) and positioned on a substrate (182, fig. 21) (tissue sample 184 is seated into an upper center of the high molecular film 182 … and surrounded by a liquid phase cover slip 186, page 24 lines 20-26); and sending, to the cutting apparatus (laser device 22, fig. 1), the command (“dissection command”, page 31 lines 9-13) to cut through the one or more sample collectors and the substrate along a selected dissected region (dissected region is selected, a laser beam is illuminated … to dissect the high molecular film 182, the tissue sample 184, and the liquid phase cover slip 186 within the selected region … the dissected tissue slices freely drop; cutting a drawing path … using a laser beam from a laser device … under the control of the control unit, page 26 lines 3-11 & page 31 lines 19-21, figs. 21-22), the cells of interest separated from the surrounding portion by the cutting apparatus (“microdissection … separating normal cells and tumor cells”; “tissue slices … dissected from the cell tissue”, page 8 lines 14-21 & page 32 lines 10-19, fig. 22). Chung further discloses providing a microdissection method in which optical definition of a tissue slice when observing the tissue slice using a microscope can be sufficiently improved, and a tissue slice of a cell having a thick tissue can be dissected rapidly and exactly while keeping high optical definition and providing an increased rate of regions for a dissected cell or a tissue gathered (Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Morris hereinabove, to further comprise each of the one or more sample collectors comprising a tissue sample and positioned on a substrate; and sending, to the cutting apparatus, the command to cut through the one or more sample collectors and the substrate along the delineation overlay, the cells of interest separated from the surrounding portion by the cutting apparatus, in view of the teachings of Chung, as this would aid in rapidly and exactly dissecting tissue while keeping high optical definition and providing an increased rate of regions for a dissected cell or tissue gathered.
Routamaa further discloses that the one or more detached sample regions can be conveyed for further analysis (para. [0029, 0044]) and Chung further discloses that the microdissection method can be mainly employed in researches into cancer (page 8 lines 14-21).
Routamaa, as modified by Morris and Chung hereinabove, does not disclose that the cells of interest separated from the surrounding portion by the cutting apparatus are analyzed to detect expression levels of one or more target genes associated with a skin condition.
However, Palmer directed to non-invasive tape stripping methods for the collection of a skin sample and isolating cellular material from the skin sample (para. [0034]) discloses the cells of interest separated from the surrounding portion (“at least a portion of the skin sample cellular material can be harvested from a used tape … cellular material is isolated from the skin sample … isolated RNA”, para. [0033-0035, 0062]) are analyzed to detect expression levels of one or more target genes associated with a skin condition (“histopathologic diagnosis”; “isolated RNA … expression levels of these target genes are quantified … gene expression signature … associated with a disease such as melanoma”; “identification of a disease state, para. [0036-0038, 0040, 0062, 0075-0076]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Morris and Chung hereinabove, such that the cells of interest separated from the surrounding portion by the cutting apparatus and analyzed to detect expression levels of one or more target genes associated with a skin condition, in view of the teachings of Palmer, as this would aid in histopathologic diagnosis and identifying a disease state, likelihood of treatment success for a given disease state, identification of progression of a disease state (e.g., invasiveness of melanoma), and identification of a disease stage (Palmer, para. [0036, 0076]).
Regarding claim 28, Routamaa, as modified by Morris, Chung, and Palmer hereinabove, discloses system of claim 27, wherein the imaging apparatus comprises an optical scanner (optical imaging unit 101, fig. 1, “scanner”, para. [0031]).
Regarding claim 29, Routamaa, as modified by Morris, Chung, and Palmer hereinabove, discloses the system of claim 27, wherein the cutting apparatus comprises a mechanical cutting system, a plasma cutting system, or a laser cutting system (“punch 107 and a die … laser beam cutter or a liquid jet cutter”, para. [0030]).
Regarding claim 30, Routamaa, as modified by Morris, Chung, and Palmer hereinabove, discloses the system of claim 27, wherein the cutting apparatus comprises a laser cutting system (“laser beam cutter”, para. [0030]).
Regarding claim 37, Routamaa, as modified by Morris, Chung and Palmer hereinabove, discloses the system of claim 27. Routamaa, as modified by Morris, Chung and Palmer hereinabove, does not disclose wherein the one or more sample collectors comprises one or more non-invasive, adhesive sample collectors.
However, Palmer directed to non-invasive tape stripping methods for the collection of a skin sample discloses wherein the one or more sample collectors comprises one or more non-invasive, adhesive sample collectors (“adhesive skin sample collection kit”, para. [0033-0034, 0037]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Morris, Chung and Palmer hereinabove, such that the one or more sample collectors comprises one or more non-invasive, adhesive sample collectors, in view of the teachings of Palmer, as this would aid in collecting and adhering an effective amount of a skin sample containing cellular material with minimal discomfort and without scarring.
Regarding claim 38, Routamaa, as modified by Morris, Chung, and Palmer hereinabove, discloses the system of claim 37. Routamaa, as modified by Morris, Chung, and Palmer hereinabove, does not disclose wherein the tissue sample comprises skin tissue, and wherein the cells of interest comprise skin cells.
However, Palmer directed to directed to non-invasive tape stripping methods for the collection of a skin sample discloses wherein the tissue comprises skin tissue, and wherein the cells of interest comprise skin cells (para. [0021, 0057, 0076], an effective amount of a skin sample is an amount sufficient to isolate and identify the cellular material; adhered skin sample, in certain embodiments, comprises cellular material including nucleic acids and proteins. In some instances, the nucleic acid is RNA or DNA; the diagnostic assay is performed on the cellular material adhered to the used adhesive tape).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Morris, Chung, and Palmer hereinabove, such that the tissue comprises skin tissue, and such that the cells of interest comprise skin cells, in view of the teachings of Palmer, as this would aid in histopathologic diagnosis and identifying a disease state, likelihood of treatment success for a given disease state, identification of progression of a disease state (e.g., invasiveness of melanoma), and identification of a disease stage, by performing diagnostic assays (Palmer, para. [0036, 0076]).
Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over Routamaa in view of Morris, Chung, and Palmer, as applied to claim 27 above, and further in view of Bonner.
Regarding claim 40, Routamaa, as modified by Morris, Chung, and Palmer hereinabove, discloses the system of claim 27. Routamaa, as modified by Morris, Chung, and Palmer hereinabove, does not expressly disclose wherein the one or more sample collectors comprises a plurality of sample collectors arranged in an array of sample collectors.
However, Bonner discloses wherein the one or more sample collectors comprises a plurality of sample collectors arranged in an array of sample collectors (col. 18 lines 3-13 & lines 41-48, one can ensure that the target sites are at known positions on the transfer substrate; multiple small pieces of adhesive transfer film can be selectively applied to those locations on the tissue which correspond to sites to be extracted; linear array of separately activatable target sites; size of the adhesive film spot determines the size of the target zone within which selection of the objects/cells are made for that one transfer (array number); target zone size is determined by the selection of the particular film (i.e., the geometry of ordered arrays)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Morris, Chung, and Palmer hereinabove, such that the one or more sample collectors comprises a plurality of sample collectors arranged in an array of sample collectors, in view of the teachings of Bonner, as this would aid in determining the size and positions of the target zones/sites by providing a linear array of separately activatable target sites selectively applied to those locations on the tissue which correspond to sites to be extracted such that the size of the adhesive film spot determines the size of the target zone within which selection of the objects/cells are made for that one transfer (array number) and ensures that the target sites are at known positions on the transfer substrate (Bonner, col. 18 lines 3-13 & lines 41-48).
Claim 43 is rejected under 35 U.S.C. 103 as being unpatentable over Routamaa in view of Morris, Chung, and Palmer, as applied to claim 27 above, and further in view of Venkataramani.
Regarding claim 43, Routamaa, as modified by Morris, Chung, and Palmer hereinabove, discloses the system of claim 27. Routamaa, as modified by Morris, Chung, and Palmer hereinabove, does not expressly disclose wherein the delineation overlay comprises digital information comprising a plurality of points and at least one of one or more lines or one or more curves connecting the plurality of points to form a polygon.
However, Venkataramani discloses wherein the delineation overlay comprises digital information (“thermographic image”, para. [0022]) comprising a plurality of points (N points, as seen in fig. 5, para. [0022]) and at least one of one or more lines or one or more curves connecting the plurality of points to form a polygon (as seen in fig. 5, “points are connected to form a N≧5 sided polygon which defines a boundary contour … in the image … boundary lines”, para. [0022]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Morris, Chung, and Palmer hereinabove, such that the delineation overlay comprises digital information comprising a plurality of points and at least one of one or more lines or one or more curves connecting the plurality of points to form a polygon, in view of the teachings of Venkataramani, as this would aid in defining a boundary contour to identify the region of interest.
Claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over Routamaa in view of Morris, Chung, and Palmer, as applied to claim 27 above, and further in view of Krizman.
Regarding claim 46, Routamaa, as modified by Morris, Chung, and Palmer hereinabove, discloses the system of claim 27. Routamaa, as modified by Morris, Chung, and Palmer hereinabove, does not disclose wherein identifying the delineation between the cells of interest and a surrounding portion of a sample collector comprises delineating the cells of interest obtained from a lesion area from other cells obtained from a non-lesion surrounding area.
However, Krizman discloses wherein identifying the delineation between the cells of interest and a surrounding portion of a sample collector comprises delineating the cells of interest obtained from a lesion area from other cells obtained from a non-lesion surrounding area (para. [0004, 0042], specified and desired cells to be excised for molecular analysis, such as tumor cells, are identified; non-desirable cells … that should not be analyzed; imperative that non-tumor cells be excluded from analysis of patient tumor tissue; an exclusion signal to prevent benign, non-malignant cells such as normal cells from contaminating analysis of tumor cells, which creates an optimized sample).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Morris, Chung, and Palmer hereinabove, such that identifying the delineation between the cells of interest and a surrounding portion of a sample collector comprises delineating the cells of interest obtained from a lesion area from other cells obtained from a non-lesion surrounding area, in view of the teachings of Krizman, as this would aid in providing an optimized sample by excluding non-tumor cells in analysis of patient tumor tissue.
Claim 47 is rejected under 35 U.S.C. 103 as being unpatentable over Routamaa in view of Morris, Chung, and Palmer, as applied to claim 27 above, and further in view of Fauver.
Regarding claim 47, Routamaa, as modified by Morris, Chung, and Palmer hereinabove, discloses the system of claim 27. Routamaa, as modified by Morris, Chung, and Palmer hereinabove, does not disclose wherein the at least one image is processed using a computer vision algorithm.
However, Fauver discloses wherein the at least one image is processed using a computer vision algorithm (col. 11 lines 49-56, “computer vision algorithm”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Morris, Chung, and Palmer hereinabove, such that the at least one image is processed using a computer vision algorithm, in view of the teachings of Fauver, as this would aid in detecting and describing local features in images and detecting the presence of the biological specimen (Fauver, col. 11 lines 49-56).
Claim 51 is rejected under 35 U.S.C. 103 as being unpatentable over Routamaa in view of Morris, Chung and Palmer, as applied to claim 27 above, and further in view of Kelso.
Regarding claim 51, Routamaa, as modified by Morris, Chung, and Palmer hereinabove, discloses the system of claim 27. Routamaa, as modified by Morris, Chung, and Palmer hereinabove, does not disclose wherein the system has a throughput of at least 16, at least 32, or at least 48 sample collectors per minute.
However, Kelso discloses wherein the system has a throughput of at least 16, at least 32, or at least 48 sample collectors per minute (0058, 0095], methods for then efficiently removing the unwanted cells can provide for a much higher throughput and less costly clone production process; culture plate wells may be processed at a rate of at least 16, … or at least 20 wells per minute; larger numbers of discrete regions or wells on a substrate may be advantageous in terms of increasing the processing throughput of the disclosed methods)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Routamaa, as modified by Morris, Chung, and Palmer hereinabove, such that the system has a throughput of at least 16, at least 32, or at least 48 sample collectors per minute, in view of the teachings of Kelso, as this would aid in increasing the processing throughput by incorporating the substrate having a larger number of discrete regions such that the methods for efficiently removing the unwanted cells can provide for a much higher throughput.
Conclusion
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/A.E.H./Examiner, Art Unit 3791
/AURELIE H TU/Primary Examiner, Art Unit 3791