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 .
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1 is rejected under 35 U.S.C. 103 as being unpatentable over Lo et al (US9994839) in view of Liu et al. (WO2017136430).
Referring to claim 1. Lo et al (herein “Lo”) discloses a “Microfluidic Devices To Extract, Concentrate and Isolate Molecules”. See Figs. 1-7 and respective portions of the specification. Lo further discloses a method for analyzing a biological sample comprising: capturing a plurality of analytes in a biological sample using electrodes to generate an AC dielectrophoretic field (See at least Col. 7 L. 22-45). Lo discloses wherein the device employs dielectrophoretic forces to selectively capture biomolecules based on dielectric properties and that the applied electric field may be an AC field producing dielectrophoretic force for molecular capture (See at least Col. 8 L. 60 – Col. 9 L. 20). Lo further discloses detecting a plurality of analytes. More specifically, Lo discloses that captured molecules may be characterized and quantified in a detection region (See at least Co. 7 L. 50 – Col. 8 l. 5). Lo doesn’t disclose wherein the analytes comprise at least two types of analytes, the at least two types of analytes comprising an exosome-bound protein and a non-exosome bound protein. Liu et al (herein “Liu”) discloses an “Exosome-Total-Isolation-Chip Device For Isolation Of Exosome-Based Biomarkers”. See Figs. 1-16 and respective portions of the specification. Liu further discloses that exosomes are extracellular vesicles released into bodily fluids that carry biological analytes including proteins and nucleic acids and are useful biomarkers (See at least Sects. 0004, 0009, 0020, 0044) and discloses a device including a nanoporous membrane configured to retain exosomes while contaminating small molecules such as proteins pass through (thereby distinguishing vesicles-associated proteins from free proteins in the sample) (See at least Abstract, Sect. 0049, 0054) and further teaches that identifying exosomal biomarkers enables early detection and diagnosis of diseases. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate exosome biomarker analysis as taught by Liu into the dielectrophoretic capture device of Lo in order to improve diagnostic sensitivity and specificity by targeting protein contained within vesicles known to reflect disease.
Claim(s) 2-4, 6, 11-16, 21, 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Lo et al (US9994839) in view of Liu et al. (WO2017136430) in further view of Heller et al (WO2009146143).
Referring to claim 2. Lo in view of Liu disclose the combination as described above in detail. Lo doesn’t explicitly disclose capturing the plurality of analytes in the sample using electrodes configured to generate a dielectrophoretic low field region and a dielectrophoretic high field region. Heller discloses a “Ex-Vivo Multi-Dimensional System For The Separation And Isolation of Cells, Vesicles, Nanoparticles and Biomarkers”. See Figs. 1-34 and respective portions of the specification. Heller further discloses a device (300) employing parallel multiplexed electrode arrays creating defined trapping regions based on dielectric properties. It is broadly construed and generally understood that the regions offer differing electric field strengths (low and high). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Heller and implemented regions of differing field strength to improve separation efficiency.
Referring to claims 3-4. Lo in view of Liu disclose the combination as described above in detail. Lo doesn’t explicitly disclose capturing a plurality of analytes in the biological sample comprises preferentially capturing a first analyte using a first electrode and a second analyte using a second electrode or capturing analytes in the sample on the same electrode. Heller discloses a hierarchy of sorting using subsets of electrodes configured to trap different particles and multiplex separation of biological entities including cells, proteins, and biomarkers within the same dielectrophoretic platform/device (See at least Sect. 0057, 0080). It should be noted that is broadly construed and generally understood that using subsets of electrodes to trap different particles suggest preferential capture of different analytes using different electrodes and that multiplex separation of biological entities within the sample DEP device suggest capturing multiple analytes on the same electrode. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Heller to improve separation efficiency and capture/trapping optimization.
Referring to claim 6. Lo discloses wherein the detection comprises quantifying at least two types of analytes in the plurality of analytes (See at least Col. 7 L. 45 – Col. 8 L. 15).
Referring to claim 11. Lo doesn’t disclose wherein the method performance is characterized by an area under the receiver operating characteristic (ROC) curve (AUC) ranging from 0.60 to 1.00. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to evaluated diagnostic performance metrics such as Roc curves ranging from 0.60 to 1.00 as this constitutes routine statistical validation of biomarker assays and represents no more than conventional data analysis.
Referring to claims 12-13. Lo discloses wherein the biological sample is obtained from a subject and comprises a bodily fluid, blood, serum, plasma, urine, saliva, cells, tissue or combination thereof (See at least Col. 3 L. 30, Col. 60 – Col. 5 l. 15).
Referring to claim 14. Lo doesn’t disclose wherein the biological sample comprises cells and the method further comprises lysing the cells. Heller teaches molecular analysis including DNA/RNA assays following electrokinetic separation (See Sect. 0075-0080). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate lysing cells prior to analysis in order to release biomolecules for detection, as it would improve analyte availability and make it more probable for capturing targeted proteins.
Referring to claims 15-16. Lo in view of Liu disclose the combination as described above in detail. Liu further discloses detecting a disease (cancer) or condition in the subject using the at least two types of analytes detected in the biological sample. Liu discloses detecting diseases such as lung cancer using exosomal biomarkers (See at least Sect. 0006-0007, 0049). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the captured analytes for disease detection as Liu explicitly discloses that exosomal biomarkers correlate with disease states and enable early diagnosis, thus incorporating the teachings of Liu of applying known biomarkers within a DEP system to have improved diagnostic accuracy and allow for earlier detection of diseases.
Referring to claim 21. Lo doesn’t disclose wherein an analyte of the plurality of analytes is selected from the group consisting of PD-L1, CA19.9, CA125, GPC-1, CEA, CA 15.3, Prolactin, Ki-67, estrogen receptor alpha, CD30, CD30L, CD10, Alpha-fetoprotein, survivin, prostate-specific antigen, AZU1, beta-human chorionic gonadotropin, and CYFRA-21. Liu discloses identifying diseases via specific biomarker expression patterns including proteins and nucleic acids (See at least Sect. 0049). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to employ teachings of Liu to target specific biomarkers because particular proteins and nucleic acids were recognized as indicators of disease progression and selecting these known biomarkers enhances diagnostic relevance and decision making.
Referring to claim 28. Lo discloses releasing immobilized molecules by reducing the electric field or adjusting pH to transfer molecules elsewhere (elution step) (See at least Col. 6 L. 1-25).
Referring to claims 29-30. Lo doesn’t disclose wherein the dielectrophoretic low field region or high field region is produced using an alternating current having a voltage of 1 volt to 40 volts peak-peak; and/or a frequency of 5 Hz to 5,000,000 Hz. Heller discloses pulsed alternating current dielectrophoresis using controlled electrode arrays (See at least Abstract, 0090-0092). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Heller and select appropriate AC voltage and frequency parameters because DEP manipulation depends on these variables to control particle movement and capture efficiency, thus optimizing voltage and frequency improves separation performance and capture selectivity.
Claim(s) 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Lo et al (US9994839) in view of Liu et al. (WO2017136430) in view of Heller et al (WO2009146143) and in further view Forster (CA3058081).
Referring to claim 18. Lo in view of Liu disclose the combination as described above in detail. Lo doesn’t disclose wherein detecting comprises contacting an analyte of the plurality of analytes with an antibody that specifically binds to the analyte. Forster discloses a “Microfluidic Device For Detection of Analytes”. See Figs. 1-15 and respective portions of the specification. Forster further discloses chambers functionalized with capture agents including antibodies for binding analytes (See at least Pg. 7 L. 5-20). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the anti-body capture agents as taught by Forster because antibodies provide highly specific binging to target analytes and would help reduce false positive and improve assay reliability.
Referring to claims 19-20. Lo doesn’t disclose wherein an antibody comprises a detectable label. Heller discloses fluorescent-antigen complexes for detection and fluorescent dyes for detecting biomolecules with epifluorescent systems (See at least Sect. 0069) It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to employ detectable labels such as fluorescent markers to facilitate visualization and quantification of captured analytes. Further, it should be noted that labeling is a standard detection strategy in molecular assays.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TERRELL HOWARD MATTHEWS whose telephone number is (571)272-5929. The examiner can normally be reached Monday thru Friday; 8:00 AM - 4:30 PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael McCullough can be reached at (571)272-7805. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TERRELL H MATTHEWS/Primary Examiner, Art Unit 3653