DETAILED ACTION
It is noted that this application has been transferred to Examiner Joseph G. Dauner of Art Unit 1682. Please direct all future correspondences to Examiner Dauner. Contact information for Examiner Dauner is provided at the end of this Office 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 .
The amended claims dated 6/12/2026 are under consideration.
The amendments and arguments presented in the papers filed 6/12/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 1/12/2026 listed below have been reconsidered as indicated.
a) The rejections of claim(s) 1-5, 7-8, and 20-29 under 35 U.S.C. 103 as being unpatentable over Astier et al. (WO 2019/092269 A1) in view of Maggi et al. (2018) (Maggi et al., Development of a Method to Implement Whole-Genome Bisulfite Sequencing of cfDNA from Cancer Patients and a Mouse Tumor Model, Front Genet., 2018 Jan 23:9:6. doi:10.3389/fgene.2018.00006. eCollection 2018) are withdrawn in view of the amendments to the claims.
b) The rejections of: claim 1 on the ground of nonstatutory double patenting as being unpatentable over claims 12-20 of U.S. Patent No. 11,691,141 in view of Maggi et al. (2018) (Maggi et al. Front Genet., 2018 Jan 23:9:6. doi:10.3389/fgene.2018.00006. eCollection 2018); claim 1 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 8 of U.S. Patent No. 12,311,357 B2 (Astier et al.) in view of Maggi et al. (2018) (Maggi et al. Front Genet., 2018 Jan 23:9:6. doi:10.3389/fgene.2018.00006. eCollection 2018); and claim 1 on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,153,013 in view of Heitzer et al. (2015) (Heitzer et al., Circulating tumor DNA as a liquid biopsy for cancer, Clin Chem., 2015 Jan;61(1):112-23. doi: 10.1373/clinchem. 2014.222679. Epub 2014 Nov 11) and Maggi et al. (2018) (Maggi et al. Front Genet., 2018 Jan 23:9:6. doi:10.3389/fgene.2018.00006. eCollection 2018), are withdrawn in view of the amendments to claim 1.
c) The provisional rejection of claim 1 on the ground of nonstatutory double patenting as being unpatentable over claim 1 and 4 of copending Application No. 17/907,362 (reference application) in view of Heitzer et al. (2015) (Heitzer et al., Circulating tumor DNA as a liquid biopsy for cancer, Clin Chem., 2015 Jan;61(1):112-23. doi: 10.1373/clinchem. 2014.222679. Epub 2014 Nov 11) and Maggi et al. (2018) (Maggi et al. Front Genet., 2018 Jan 23:9:6. doi:10.3389/fgene.2018.00006. eCollection 2018), is withdrawn in view of the amendments to claim 1.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
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) 1-5, 7-8, and 20-29 are rejected under 35 U.S.C. 103 as being unpatentable over Astier (WO 2019/092269 A1, publication date 05/16/2019, PCT/EP20181/081049, filed on 11/13/2018, which claims priority to a US Provisional Patent Application, 62/585,219, filed on 11/13/2017, the effective filing date) in view of Underhill (PLoS Genet. 2016. 12(7):e1006162).
The following are new rejections necessitated by the amendments to the claims.
Regarding claim 1, Astier teaches “devices for effecting epitachophoresis. Epitachophoresis may be used to effect sample analysis, such as by selective separation, detection, extraction, and/or pre-concentration of target analytes such as, for example, DNA, RNA, and/or other biological molecules. Said target analytes may be collected following epitachophoresis and used for desired downstream applications and further analysis.” (See Abstract).
Astier at paragraph [0100] further teaches:
Furthermore, metastatic tumor cells can also be detected at the nucleic acid, such as by using a Next Generation Sequencing panel looking to identify cancer-associated mutations, including mutations present in the primary tumor. As described herein, in exemplary embodiments devices and methods disclosed herein may be used to separate, focus/concentrate, and collect such nucleic acids. Moreover, DNA purified from representative sampling from the primary and lymph nodes, as well as DNA from circulating tumor DNA from any distant metastatic cells could be separated, focused /concentrated, and/or collected in exemplary embodiments
Astier further teaches:
As used herein, the term ‘epitachophoresis’ generally refers to methods of electrophoretic separation that are performed using a circular or spheroid and/or concentric device and/or circular and/or concentric electrode arrangement, such as by use of the circular/concentric and/or polygonal devices as described herein. Due to a circular/concentric or another polygonal arrangement that is used during epitachophoresis; unlike conventional epitachophoresis devices, the cross section area changes during migration of ions and zones, and the velocity of the zone movement is not constant in time due to the changing cross sectional area. Thus, an epitachophoretic arrangement does not strictly follow conventional isotachophoretic principles, wherein the zones migrate with constant velocities. Notwithstanding these significant differences as shown herein epitachophoresis can be used to efficiently separate and focus charged particles by using an electric field to create boundaries or interfaces between materials that may have different electrophoretic mobilities (e.g., between the charged particles and other materials in a solution). LE and TE, as described for use with ITP, can be used for epitachophoresis as well. A description of the movement of the zones under constant current, constant voltage, and constant power for embodiments wherein circular or spheroid device architectures, e.g., devices comprising one or more circular electrodes, may be used, are presented in the Examples section infra. In exemplary embodiments, epitachophoresis may be effected using constant current, constant voltage, and/or constant power. In exemplary embodiments, epitachophoresis may be effected using varying current, varying voltage, and/or varying power. In exemplary embodiments, epitachophoresis may be effected within the context of devices and/or an arrangement of electrodes whose shape may be described in general as circular or spheroid, such that the basic principles of epitachophoresis may be accomplished as described herein. In some embodiments, epitachophoresis may be effected within the context of devices and/or an arrangement of electrodes whose shape may be described in general as polygons, such that the basic principles of epitachophoresis may be accomplished as described herein. In some embodiments, epitachophoresis may be effected by any non-linear, contiguous arrangement of electrodes, such as electrodes arranged in the shape of a circle and/or electrodes arranged in the shape of a polygon.
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See Figs. 1 and 5 reproduced below.
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[0009] FIG. 1 provides a schematic representation of an exemplary device for effecting epitachophoresis.
[0014] FIG. 5 provides a schematic representation of an exemplary device for effecting epitachophoresis wherein the sample is loaded in between loading the leading and terminating electrolytes.
Regarding claim 2, Astier at paragraph [0120], further teaches:
[0120] In some embodiments, the devices and methods described herein may also include the use of at least one detectable label selected from fluorescent molecules or fluorochromes (such as sold by Invitrogen, e.g., see, The Handbook—A Guide to Fluorescent Probes and Labeling Technologies, Invitrogen Detection Technologies, Molecular Probes, Eugene, Oreg., or disclosed in U.S. Pat. No. 5,866,366 to Nazarenko et al.), such as 4-acetamido-4′-isothiocyanatostilbene-2,2′disulfonic acid, acridine and derivatives… (Emphasis added)
Regarding claim 3, Astier at paragraph [0033], further teaches:
An epitachophoretic arrangement does not strictly follow conventional isotachophoretic principles, wherein the zones migrate with constant velocities. Notwithstanding these significant differences as shown herein epitachophoresis can be used to efficiently separate and focus charged particles by using an electric field to create boundaries or interfaces between materials that may have different electrophoretic mobilities ( e.g., between the charged particles and other materials in a solution). LE and TE, as described for use with ITP, can be used for epitachophoresis as well.
As used herein, the terms "in vitro diagnostic application (IVD application)", "in vitro diagnostic method (IVD method)" and the like generally refer to any application and/or method and/or device that may evaluate a sample for a diagnostic and/or monitoring purposes, such as identifying a disease in a human subject, optionally a human subject. In exemplary embodiments, said sample may comprise blood and/or plasma from a subject. In exemplary embodiments, said
sample may comprise nucleic acids and/or target nucleic acids from a subject, optionally further wherein said nucleic acids originated from blood and/or plasma
from a subject.
Regarding claim 4, Astier at paragraph [00275] further teaches:
Recently, methods of diagnosing cancer through the measurement of DNA methylation have been suggested. DNA methylation occurs mainly on the cytosine of CpG islands in the promoter region of a specific gene to interfere with the binding of transcription factors, thus silencing the expression of the gene. Thus, detecting the methylation of CpG islands in the promoter of tumor inhibitory genes greatly assists in cancer research. Recently, an attempt has been actively made to determine promoter methylation, by methods such as methylation-specific PCR (hereinafter referred to as MSP) or automatic DNA sequencing, for the diagnosis and screening of cancer. See WO2009069984A2, which is hereby incorporated by reference in its entirety.
Regarding claim 5, Astier at paragraph [006], further teaches:
In exemplary embodiments, said method may further comprise: a. providing a device for effecting epitachophoresis; b. providing a sample on said device that comprises one or more target analytes; c. providing a leading electrolyte and a trailing electrolyte on said device; d. performing epitachophoresis using said device; and e. collecting said one or more target analytes. In exemplary embodiments, the device may comprise a circular or spheroid or polygonal geometry. In further exemplary embodiments, during said method of sample analysis an epitachophoresis zone of the device may move from the edge of the polygon or circle towards the center of the polygon or circle. Moreover, in exemplary embodiments, said method may use of 1 μl or less, 1 μl or more, 10 μl or more, 100 μl or more, 1 mL or more, 4 mL or more, 5 mL or more, 10 mL or more, or 15 mL or more of sample volume. In exemplary embodiments, said method may comprise extraction, concentration, and/or collection of a target analyte from a sample, e.g., a biological sample. In further exemplary embodiments, said method may comprise extraction of ctDNA from a sample and/or said method may comprise extraction of cfDNA from a sample, e.g., blood or plasma from a pregnant woman. In further exemplary embodiments, said method may comprise extraction, concentration, and/or collection of a target analyte from a sample, e.g., a biological sample, and said target analyte may be used for one or more downstream in vitro diagnostic applications.
Regarding claim 7, Astier at paragraph [00131] and [00135], further teaches:
[00131] Fluids can be applied for pretreatment (e.g., protein-crosslinking, exposing nucleic acids, etc.), denaturation, hybridization, washing (e.g., stringency washing), detection (e.g., linking a visual or marker molecule to a probe), amplifying (e.g., amplifying proteins, genes, etc.), counterstaining, or the like. In various embodiments, the substances include, without limitation, stains (e.g., hematoxylin solutions, eosin solutions, or the like), wetting agents, probes, antibodies (e.g., monoclonal antibodies, polyclonal antibodies, etc.), antigen recovering fluids (e.g., aqueous- or non-aqueous-based antigen retrieval solutions, antigen recovering buffers, etc.), solvents (e.g., alcohol, limonene, or the like), or the like. Stains include, without limitation, dyes, hematoxylin stains, eosin stains, conjugates of antibodies or nucleic acids with detectable labels such as haptens, enzymes or fluorescent moieties, or other types of substances for imparting color and/or for enhancing contrast. See WO2015197742 and WO2015150278, each of which is hereby incorporated by reference in its entirety.
[00135] The visible marker may be a fluorescent dye, colloidal metal, hapten, radioactive marker or an enzyme. Regardless of the method of preparation, maximal signal strength with minimal background or non-specific staining can be desirable to give optimal antigen visualization. See WO2013139555 which is hereby incorporated by reference in its entirety.
Regarding claims 8 and 20-29, Astier in paragraph [0005], further teaches:
Moreover, in exemplary embodiments, said device may comprise dimensions that accommodate 1 μl or less, 1 μl or more, 10 μl or more, 100 μl or more, 1 mL or more, 4 mL or more, 5 mL or more, 10 mL or more, or 15 mL or more of sample volume. (Emphasis added)
Astier does not explicitly teach a clean up step using SPRI-beads as recited in amended claim 1.
However, Underhill teaches a method of “cleaning up” cfDNA nucleic that was extracted from a sample.
Regarding claim 1, Underhill teaches:
All procedures were approved by the University of Utah Internal Review Board prior to study initiation. Blood samples were collected in Streck BCT tubes, stored at 4°C, and processed within 24 hours of collection. Plasma was separated by centrifugation for 10 minutes at 1900g and aspiration to a new tube. Plasma was further centrifuged for 16,000g x 10 minutes to remove any cellular debris, and resulting supernatant was stored at –20°C until cell-free DNA isolation. Custom kits that combined Qiagen lysis and binding buffer with Zymo silica-based columns were assembled to reduce expense during isolation of cell-free DNA. Cell-free DNA was prepared from 8 mL of plasma by adding 800 μL of Proteinase K (20 mg/mL) and 6.4 mL Buffer ACL (Qiagen) followed by incubation at 60°C x 30 minutes. Next, 14.4 mL of buffer ACB (Qiagen) was added to the lysate and incubated on ice for 5 minutes. DNA was isolated from the lysate with Zymo DNA Clean and Concentrator 100 kit according to the manufacturer’s instructions and eluted in 150 μL. A final purification step was performed using two volumes of Ampure XP magnetic beads followed by elution in 25–30 μL 10mM Tris (pH 8.0).
It would have been prima facie obvious to the ordinary artisan to have included a single “SPRI-bead clean up step” with Ampure XP magnetic beads using twice the volume of the cfDNA obtained through the epitachophoresis process of Astier. One would have been motivated to do so as a final purification step, removing any other charged molecules that migrated with and was obtained with the cfDNA after the epitachophoresis process of Astier. The modification has a reasonable expectation of success because Astier describes contacting magnetic particles with the nucleic acids purified through the epitachophoresis process (paragraph [00113]).
Response to the traversal of the 103 rejections
The Remarks address the withdrawn rejection of the claims over Astier and Maggi, focusing on the alleged deficiencies of Maggi (p. 7-8).
The above rejections necessitated by amendments do not rely upon the Maggi references and the arguments are therefore moot.
The Remarks further argue the use of a single SPRI clean up step has an unexpected improvement regarding yield of nucleic acids (p. 8).
The arguments have been fully considered but are not persuasive. In view of the state of the art, one would have reasonably expected higher yield when using fewer SPRI clean up steps. See, Henikoff (WO 2019/060907 A1); Dellaporta (US 2016/0215331); and Aigrain (BMC Genomics. 2016. 17:458).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12-20 of U.S. Patent No. 11,691,141 in view of Underhill (PLoS Genet. 2016. 12(7):e1006162).
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Claims 12-20 of U.S. Patent No. US 11,691,141:
Underhill teaches a method of “cleaning up” cfDNA nucleic that was extracted from a sample.
Underhill teaches:
All procedures were approved by the University of Utah Internal Review Board prior to study initiation. Blood samples were collected in Streck BCT tubes, stored at 4°C, and processed within 24 hours of collection. Plasma was separated by centrifugation for 10 minutes at 1900g and aspiration to a new tube. Plasma was further centrifuged for 16,000g x 10 minutes to remove any cellular debris, and resulting supernatant was stored at –20°C until cell-free DNA isolation. Custom kits that combined Qiagen lysis and binding buffer with Zymo silica-based columns were assembled to reduce expense during isolation of cell-free DNA. Cell-free DNA was prepared from 8 mL of plasma by adding 800 μL of Proteinase K (20 mg/mL) and 6.4 mL Buffer ACL (Qiagen) followed by incubation at 60°C x 30 minutes. Next, 14.4 mL of buffer ACB (Qiagen) was added to the lysate and incubated on ice for 5 minutes. DNA was isolated from the lysate with Zymo DNA Clean and Concentrator 100 kit according to the manufacturer’s instructions and eluted in 150 μL. A final purification step was performed using two volumes of Ampure XP magnetic beads followed by elution in 25–30 μL 10mM Tris (pH 8.0).
It would have been prima facie obvious to the ordinary artisan to have included a single “SPRI-bead clean up step” with Ampure XP magnetic beads using twice the volume of the cfDNA obtained through the epitachophoresis process of the ‘141 claims.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 8 of U.S. Patent No. 12,311,357 B2 (Astier et al.) in view of Underhill (PLoS Genet. 2016. 12(7):e1006162).
Claims 1, 7 and 8 of U.S. Patent No. US 12,311,357:
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As evidenced above, claims 1, 7, and 8 of the ‘357 patent are drawn to a method of analyzing nucleic acids. As evidenced above, the method requires the use of electrophoretic means, and results in “focused zones” of the different nucleic acids present in the sample. As evidenced above, the method also requires the use of first and second electrodes. The teachings of Underhill have been documented above.
It would have been prima facie obvious to the ordinary artisan to have included a single “SPRI-bead clean up step” with Ampure XP magnetic beads using twice the volume of the cfDNA obtained through the epitachophoresis process of the ‘357 claims.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,153,013 in view of Heitzer et al. (2015) (Heitzer et al., Circulating tumor DNA as a liquid biopsy for cancer, Clin Chem., 2015 Jan;61(1):112-23. doi: 10.1373/clinchem. 2014.222679. Epub 2014 Nov 11) and Underhill (PLoS Genet. 2016. 12(7):e1006162).
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Claims 1-11 of U.S. Patent No. US 12,153,013
Heitzer teach that “cfDNA was initially identified by Mandel and Metais in the blood of healthy individuals. However, their pioneering work did not arouse much interest and it took 30 years until Leon et al. reported increased concentrations of cfDNA in the circulation of cancer patients. It took another 10 years until Stroun et al. demonstrated the presence of neoplastic characteristics in the circulation. These findings were then confirmed by several other groups, and in the following years tumor specific aberrations, including mutations in tumor suppressors and oncogenes, microsatellite instability (MSI) (16 ), and DNA methylation (17 ), were identified and
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provided concrete evidence that cfDNA is released into the circulation by tumors (Fig. 3). (See left column, page 114).
Fig. 3. Schematic representation of the liquid biopsy as a tool for cancer monitoring.
Cell-free DNA is released from different tumor locations and healthy/inflamed tissue through multiple mechanisms from cells undergoing apoptosis or necrosis. Tumor-derived DNA (ctDNA) can be extracted from plasma and a variety of tumor-specific genetic changes can be detected. However, the amount of tumor-specific DNA can greatly vary (<1% to >90%) and numerous techniques for the analysis of ctDNA have been proposed. The liquid biopsy may find its clinical application in various clinical settings, including cancer diagnosis, detection of minimal residual disease, prognosis, and therapy monitoring [Taly et al. (65 ), Vogelstein and Kinsler (66 ), Diehl et al. (52 ), Kinde et al. (68 ), Newman et al. (67 ), Forshew et al. (71 ), Chan et al. (11 ), Murtaza et al. (72 ), Heitzer et al. (69 ), Leary et al. (46 ), Chan et al. (10 )]. WGS, whole genome sequencing. (Emphasis added; p. 115)
Heitzer further teaches “A study that analyzed total plasma DNA concentrations and tumor specific KRAS mutations in CRC patients showed that a higher amount of tumor-specific fragments and that a higher number of CTCs were linked to biphasic size distributions of plasma DNA fragments (Fig. 4) (See section “cfDNA AS A DIAGNOSTIC BIOMARKER” on page 117).
Heitzer, at page 116, teaches the use of fluorescent dyes.
The teachings of Underhill have been documented above.
It would have been prima facie obvious to the ordinary artisan to have included a single “SPRI-bead clean up step” with Ampure XP magnetic beads using twice the volume of the cfDNA obtained through the epitachophoresis process of the ‘013 claims.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 and 4 of copending Application No. 17/907,362 (reference application) in view of Heitzer et al. (2015) (Heitzer et al., Circulating tumor DNA as a liquid biopsy for cancer, Clin Chem., 2015 Jan;61(1):112-23. doi: 10.1373/clinchem. 2014.222679. Epub 2014 Nov 11) and Underhill (PLoS Genet. 2016. 12(7):e1006162).
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Claims 1 and 4 of copending Application No. 17/907,362:
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Heitzer teach that “cfDNA was initially identified by Mandel and Metais in the blood of healthy individuals. However, their pioneering work did not arouse much interest and it took 30 years until Leon et al. reported increased concentrations of cfDNA in the circulation of cancer patients. It took another 10 years until Stroun et al. demonstrated the presence of neoplastic characteristics in the circulation. These findings were then confirmed by several other groups, and in the following years tumor specific aberrations, including mutations in tumor suppressors and oncogenes, microsatellite instability (MSI) (16 ), and DNA methylation (17 ), were identified and provided concrete evidence that cfDNA is released into the circulation by tumors (Fig. 3). (See left column, page 114).
Fig. 3. Schematic representation of the liquid biopsy as a tool for cancer monitoring.
Cell-free DNA is released from different tumor locations and healthy/inflamed tissue through multiple mechanisms from cells undergoing apoptosis or necrosis. Tumor-derived DNA (ctDNA) can be extracted from plasma and a variety of tumor-specific genetic changes can be detected. However, the amount of tumor-specific DNA can greatly vary (<1% to >90%) and numerous techniques for the analysis of ctDNA have been proposed. The liquid biopsy may find its clinical application in various clinical settings, including cancer diagnosis, detection of minimal residual disease, prognosis, and therapy monitoring [Taly et al. (65 ), Vogelstein and Kinsler (66 ), Diehl et al. (52 ), Kinde et al. (68 ), Newman et al. (67 ), Forshew et al. (71 ), Chan et al. (11 ), Murtaza et al. (72 ), Heitzer et al. (69 ), Leary et al. (46 ), Chan et al. (10 )]. WGS, whole genome sequencing. (Emphasis added; p. 115)
Heitzer et al. (2015) further teaches “A study that analyzed total plasma DNA concentrations and tumor specific KRAS mutations in CRC patients showed that a higher amount of tumor-specific fragments and that a higher number of CTCs were linked to biphasic size distributions of plasma DNA fragments (Fig. 4) (See section “cfDNA AS A DIAGNOSTIC BIOMARKER” on page 117).
Heitzer et al. (2015), at page 116, teaches the use of fluorescent dyes.
The teachings of Underhill have been documented above.
It would have been prima facie obvious to the ordinary artisan to have included a single “SPRI-bead clean up step” with Ampure XP magnetic beads using twice the volume of the cfDNA obtained through the epitachophoresis process of the ‘357 claims.
Analysis of DNA samples by substitution a Formalin-Fixed Paraffin-Embedded Tissue ("FFPET") sample recited in claim 1 of copending 17/907,362 with Cell-free circulating tumor DNA from a liquid biopsy for cancer detection taught by Heitzer et al. (2015) is prima facie obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
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 JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682
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