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 .
Applicant’s arguments have been considered but are moot in view of the new grounds of rejection necessitated by the claim amendments.
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 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.
Claims 1, 6-10, 15, 22-23, 26, 33-34 and 36-41 are rejected under 35 U.S.C. 103 as being unpatentable over D11 and further in view of D2.2
With regard to claim 1, D1 teach method of imaging a cytologic sample (see ¶ 45), the method comprising:(a) dispersing a cytologic sample in a preparation solution to prepare a sample solution, wherein the cytologic sample comprises diagnostic analytes and non- diagnostic analytes, wherein the preparation solution comprises an agent configured to preserve the diagnostic analytes (see ¶¶ 39-40: reagent for fixing cells; see ¶ 34: diagnostic and non-diagnostic analytes such as such as epithelial cells, while allowing the fluid and other debris (e.g., protein aggregates, urinary casts, or ruptured cells) or blood elements (e.g., red blood cells)); (b) filtering the sample solution by directing the sample solution through a flow channel intersected by a filter, thereby removing at least a portion of non- diagnostic analytes and generating a concentrated layer of diagnostic analytes adhered to the filter (see ¶¶ 16, 34: polycarbonate filter to isolate cancer cells); (c) mounting the concentrated layer of diagnostic analytes adhered to the filter using a carrier (see ¶¶ 80, 89, 91, 105: mounting with ProLong mounting medium and covered with coverslip or carrier); and (d) generating a digital microscopic image of the layer of diagnostic analytes adhered to the filter, thereby imaging the cytologic sample (see ¶¶ 45, 80: imaging using electron microscope).
D1 fails to explicitly teach an agent configured to lyse the non-diagnostic analytes, however D2 teach the missing features (see abstract, p. 126 ¶ 3: lysing reagent).
One skilled in the art before the effective filing date would have found it obvious to combine the teachings to arrive at the claimed invention. D2 teaches using a lysing reagent to selectively destroy or lyse red blood cells or other debris. One skilled in the art would have found it obvious to incorporate known teachings of D2 into the configuration of D1 by using a lysing reagent to destroy or lyse non-diagnostic analytes such as debris or red blood cells that are not of interest in the analysis yielding predictable results.
With regard to claim 6, D1 teach wherein generating the digital microscopic image is accomplished by at least one of: stimulated Raman scattering (SRS) microscopy, coherent anti-Stokes Raman scattering (CARS) microscopy, fluorescent microscopy (FM), deconvolution microscopy (DM), confocal fluorescence (CF) microscopy, confocal reflection (CR) microscopy, multiphoton fluorescence microscopy (MPM), light-sheet microscopy (LSM), microscopy with ultraviolet surface excitation (MUSE), or structured light illumination microscopy (SLIM) (see ¶ 80: Leica DMIRE2 inverted microscope uses fluorescence imaging).
With regard to claim 7, D1 teach wherein the layer of analytes comprises a layer of cells (see abstract, ¶ 16: cells).
With regard to claim 8, D1 teach wherein the filter and the carrier are adjacent after said mounting (see ¶¶ 80, 89, 91, 105: filter covered with coverslip or carrier, inherently adjacent).
With regard to claim 9, D1 teach wherein the layer of analytes and the carrier are adjacent after said mounting (see ¶¶ 80, 89, 91, 105: filter with layer of analytes covered with coverslip or carrier, inherently adjacent).
With regard to claim 10, D1 teach wherein the preparation solution comprises water, saline, a phosphate buffer, an agent for lysing cells, an agent for preventing clotting of cells and extracellular contents, an agent for fixing the cells, a fluorescent contrast agent, or a combination thereof (see ¶¶ 39-40: reagent for fixing cells).
With regard to claim 15, D1 teach the agent for lysing cells comprises ammonium chloride, acetic acid, glacial acetic acid, potassium carbonate, CytoLyt solution, CytoRich solution, or any combination thereof; (ii) the agent for preventing clotting of cells and extracellular contents comprises heparin, ammonium oxalate, potassium Ethylenediaminetetraacetic acid (EDTA), Citrate, or potassium oxalate, or any combination thereof; (iii) the agent for fixing the cells further comprises methanol, ethanol, formaldehyde, formalin, acetone, Glutaraldehyde, Osmium tetroxide, Potassium Dichromate, Mercuric Chloride, Zenker's fixative, Helly's fixative, Bouin's Fixative, Carnoy's fixative, or Saccomanno Fluid, or any combination thereof; and (iv) the fluorescent contrast agent further comprises at least one of: 4' ,6-diamidino-2-phenylindole, DAPI, acridine orange, DRAQ5, eosin Y, fluorescein, Thiazine dye, methylene blue, azure A, Hoechst 33342, rhodamine, CellLight nucleus-cfp, NucBlue, CellLight Histone 2B-GFP, CellLight Nucelue-GIP, Syto 9 Green, CellLight Histon 2B-RFP, CellLight Nucelus-RFP, Propidium Iodide, Syto 82 Orange, SytoX Orange, NucReld Live 647, Syto 59 Red, or oil red, or any combination thereof (see ¶¶ 39-40: formaldehyde).
With regard to claim 22, D1 teach comprising diluting the sample solution prior to filtration (see ¶¶ 80, 97: dilution).
With regard to claim 23, D1 teach wherein the filtering the dispersed sample comprising applying a pressure or gravity, wherein the pressure comprises a positive pressure or a negative pressure (see ¶¶ 12, 16: passing through filter, polycarbonate filter are pressure driven or vacuum driven).
With regard to claim 26, D1 teach method of claim 22 wherein the filtering the dispersed sample comprises using a syringe, using a pump, or using centrifugation (see ¶¶ 5-6, 13: centrifugation).
With regard to claim 33, D1 teach wherein the filter comprises a cellulose acetate filter, a mixed cellulose esters (MCE) filter, a polycarbonate filter, a PVP-free polycarbonate filter, a MilliPore filter, or a NuclePore filter (see ¶¶ 16, 23: polycarbonate filter).
With regard to claim 34, D1 teach wherein the method further comprises analyzing the microscopic image to determine at least one of: adequacy of the sample, presence of tumor in the sample, or diagnosis, or any combination thereof (see abstract: diagnosis)
With regard to claim 36, D1 the method of claim 34, wherein the analyzing the microscopic image is by a human reader or by means of a computer-assisted image interpretation, wherein the computer-assisted image interpretation is based on a convolutional neuronal network (see ¶ 80: cells counted by visual inspection).
With regard to claim 37, D1 teach method of claim 36, wherein the analyzing comprises determining: adequacy of the sample, presence of tumor in the sample, a diagnosis, or a combination thereof (see abstract: diagnosis).
With regard to claim 38, D1 teach method of claim 36, but fails to explicitly teach wherein the computer-assisted image interpretation comprises creating image patches of individual cells or clusters of cells for further analysis. However, Examiner takes Official Notice to the fact that computer assisted image interpretation is extremely well known in the art before the effective filing date and that one skilled in the art would have been motivated to incorporate computer vision into D1 to process, analyze or classify images of cells yielding predictable and enhanced results.
With regard to claim 39, D1 fails to explicitly teach wherein the method further comprises re-processing the sample for immunochemistry or molecular or cytogenic techniques. However, Examiner takes Official Notice to the fact that re-processing of sample is extremely well known in the art before the effective filing date and that one skilled in the art would have been motivated to use known teachings of re-processing the sample to further analyze the cells.
With regard to claim 41, D1 teach method of claim 40, but fails to explicitly teach wherein the re-processing comprises re- suspending the filter with the sample in a re-processing solution, wherein the re-processing further comprises applying mechanical agitation. However, Examiner takes Official Notice to the fact that re-processing of sample is extremely well known in the art before the effective filing date and that one skilled in the art would have been motivated to use known teachings of re-processing the sample to further analyze the cells.
With regard to claim 40, D1 teach method of claim 39, wherein the immunochemistry or molecular or cytogenic techniques comprise DNA sequencing, RNA sequencing, PCR assay, or any combination thereof (see ¶¶ 68-69: hybridization between target and probe, DNA sequencing).
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over D1 and D2 and further in view of D3.3
With regard to claim 2, D1 teach method of claim 1, but fails to explicitly teach wherein dispersing the cytologic sample comprises applying mechanical agitation, wherein the mechanical agitation comprises vortexing, ultrasonic actuation, aspiration, or any combination thereof, however D3 teach the missing feature (see D3 ¶ 212: mechanical agitation; see ¶¶ 204, 206: vortex mixer). One skilled in the art before the effective filing date would have found it obvious to combine the teachings to arrive at the claimed invention. In particular, it would have been obvious to incorporate known teachings of mechanical agitation of a sample as taught by D3 into the configuration of D1 yielding predictable and enhanced results of disaggregation of cells by mechanical agitation.
With regard to claim 3, D1 teach wherein the cytological sample comprises blood (see ¶ 34).
Conclusion
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 AVINASH YENTRAPATI whose telephone number is (571)270-7982. The examiner can normally be reached on 8AM-5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sumati Lefkowitz can be reached on (571) 272-3638. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AVINASH YENTRAPATI/Primary Examiner, Art Unit 2672
1 US Publication No. 2014/0193833
2 Bossuyt, Xavier, Gerald E. Marti, and Thomas A. Fleisher. "Comparative analysis of whole blood lysis methods for flow cytometry." Cytometry: The Journal of the International Society for Analytical Cytology 30.3 (1997): 124-133.
3 US Publication No. 2008/0262384.
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