DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 June 11, 2026, has been entered.
Claims 3, 4, 6, 7, 9, 10, 12, 13, 16, 18, 19, 21, 23, 24, 27, 28, 30, 32-35, 38, 39, and 42-44 are canceled.
Claims 1, 2, 5, 8, 11, 14, 15, 17, 20, 22, 25, 26, 29, 31, 36, 37, 40, and 41 are pending.
Claims 29, 31, 36, 37, 40, and 41 are withdrawn.
Claims 1, 2, 5, 8, 11, 14, 15, 17, 20, 22, 25, and 26 are examined on the merits.
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 2, 15, 17, 20, 22, and 25 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 2 is indefinite because it is unclear how step (iii) is extracting the at least one cellular-component into at least one of the at least one electroporation-electrode, since parent claim 1 recites that this extraction is “via an extraction element configured for molecular collection.” It is unclear whether claim 2 is requiring that (a) the “extraction element configured for molecular collection” is “at least one of said at least one electroporation-electrode,” or (b) extracting the at least one cellular-component into both the “extraction element configured for molecular collection” and the “at least one of said at least one electroporation-electrode.”
Claim 15 is indefinite because it is unclear how the extraction in step (iii) is by suction via at least one hollow electroporation-electrode, since parent claim 1 recites that this extraction is “via an extraction element configured for molecular collection.” It is unclear whether claim 15 is requiring that (a) the “extraction element configured for molecular collection” is at least one hollow electroporation-electrode, or (b) extracting the at least one cellular-component via both the “extraction element configured for molecular collection” and the at least one hollow electroporation-electrode. Since claim 15 is indefinite, then its dependent claim, claim 17, is rendered indefinite. Therefore, claims 15 and 17 are rejected under 35 U.S.C. 112(b).
Claim 20 is indefinite because it is unclear how the extraction in step (iii) is by suction via the cannula of the at least one electroporation-electrode, since parent claim 1 recites that this extraction is “via an extraction element configured for molecular collection.” It is unclear whether claim 20 is requiring that (a) the “extraction element configured for molecular collection” is the retentive cannula of the at least one electroporation-electrode, or (b) extracting the at least one cellular-component via both the “extraction element configured for molecular collection” and the cannula of the at least one hollow electroporation-electrode. Since claim 20 is indefinite, then its dependent claim, claim 22, is rendered indefinite. Therefore, claims 20 and 22 are rejected under 35 U.S.C. 112(b).
Claim 25 is rendered indefinite by the recitation “the at least one cellular-component released to the extracellular matrix is analyzed or identified in step (iv) outside the body of the subject after releasing said at least one cellular-component therefrom” in the last three lines of the claim. Because of order of the word “therefrom” in relation to “the body of the subject” in the recitation, the recitation in the last line of the claim sets forth releasing at least one cellular-component from the body of the subject. However, this lacks antecedent basis since parent claim 1 recites releasing at least one cellular-component from the solid tissue or SOL (see step (ii)), as opposed to releasing at least one cellular-component from the body of the subject. It is noted that claim 25 does not require that the at least one cellular-component is reversibly adsorbed, associated with, and/or linked to the adhesive material of the solid rod of the at least one electroporation-electrode – the recited capability of the adhesive material does not signify that the reversible association/linking is performed.
Notice Re: Prior Art Available Under Both Pre-AIA and AIA
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.
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.
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, 5, 8, 11, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Onik (US 2016/0367310. Previously cited) in view of Franzen (Molecular Oncology. 2018. 12: 1415-1428. Available online August 9, 2018. Previously cited).
Onik discloses a method of non-thermally ablating undesirable soft tissue in the body of a subject, such as cancerous tumors and non-cancerous tissue, using pulsed electrical fields (abstract; paragraph [0059]; claim 1 of Onik). The undesirable soft tissue may or may not be malignant (paragraph [0048]). Thus, the undesirable soft tissue targeted by Onik can be a solid tissue of a subject comprising a tumor that is benign (i.e. not malignant) or malignant, meeting limitations of the claimed invention.
In the invention, electrical pulses are delivered to generate an appropriate electric field, and the electrical field is generated by therapeutic probes placed in proximity to the soft tissue or cancerous cells within the body of the subject (paragraph [0016]). Claim 1 of Onik refers to the probes as at least one electrode, and Onik discloses that typically from 1 to 6 needle type probe electrodes are used (paragraph [0048]). The probes, i.e. electrodes, of Onik are directed to ‘at least one electroporation-electrode’ as claimed since any electrode is suitable for electroporation. Additionally, Onik discloses that the electrodes are introduced into position in and around the treatment site (paragraphs [0018] and [0048]). With reference to Figure 9, Onik teaches that the therapeutic probes 20 (electrodes) are inserted directly into, or placed around the target tissue 11 (paragraph [0039]). Therefore, Onik discloses step (i) of instant claim 1 since Onik teaches placing at least one electroporation-electrode within a solid tissue (comprising a tumor which may or may not be malignant) or in proximity thereto, wherein said solid tissue or SOL is within a body of the subject.
The method of Onik uses electrical pulses that cause immediate cellular membrane breakdown non-thermally so that sensitive tissue structures are spared and the intra-cellular and membrane proteins are spilled into the extracellular space without denaturing (paragraph [0013]). See also claim 1 of Onik, disclosing an electric field (generated by the at least one electrode) sufficient to cause electrical membrane breakdown of a plurality of cells of the soft tissue, causing immediate and simultaneous spillage of all intracellular components into an extracellular space. Since the membrane of the cells are broken down, then the cells are permeabilized. Also, the extracellular space inherently comprises the extracellular matrix. Therefore, the spillage of the intracellular components into the extracellular space is directed to the release of the intracellular components (directed to ‘at least one cellular-component’) to an extracellular matrix between and surrounding the ablated cells. As such, Onik discloses step (ii) of instant claim 1 since Onik teaches applying pulsed electric field (PEF) via the at least one electroporation-electrode to thereby induce permeabilization of cells of the solid tissue, and consequently release at least one cellular-component therefrom to an extracellular matrix between and surrounding said cells.
Onik differs from the claimed invention in that Onik does not discloses a method for determining if a solid tissue of a subject comprises a benign or malignant tumor, or if a space occupying lesion (SOL) within said solid tissue is malignant or benign, nor does Onik disclose step (iii) of extracting the at least one cellular-component from the extracellular matrix via an extraction element configured for molecular collection, and step (iv) of identifying or analyzing the at least one cellular-component extracted so as to identify or determine the presence and type of the tumor within the solid tissue or determine if the SOL is malignant or benign.
However, Onik discloses that their method may include the biopsy of a portion of the treated target tissue to verify treatment efficacy immediately after completion of the treatment while the patient is still in position for additional treatment (paragraph [0053]). Alternatively, because the intracellular environment comprises a unique chemical composition, spillage of the cell contents can be detected by methods such as placing one or more needle probes into critical locations of the treatment area to measure chemical levels using chemical reagents, electrical impedance or resistance measurements, pH measurements, spectroscopy, or the like (paragraph [0054]). Needle probes that are outfitted with one or more sensors have the added benefit of allowing the treatment provider to observe and quantify the level of target cell destruction (paragraph [0055]). Measurement techniques for cellular contents are not limited to those described in Onik, but may be carried out by any means known in the art of measuring chemical compositions of a targeted treatment area in vivo and/or in real time (paragraph [0056]).
Franzen discusses fine-needle aspiration (FNA) biopsy for providing ready access to relevant tissues (abstract). FNA sampling is a well-established cancer diagnostic procedure, wherein tissue fragments and/or fluid may be recovered from tumor tissue via puncture using a thin-gauge needle (page 1416, left column, second paragraph). The minimally traumatic FNA is often used for diagnosis of small nonpalpable, deeply located, or otherwise hard-to-reach lesion, both for primary tumors and for metastases (page 1416, left column, second paragraph). Also, FNA samples have proven useful for mRNA profiling via RT-PCR to strengthen the diagnosis (page 1416, left column, third paragraph).
Franzen discloses a study which explored molecular profiling of FNA samples, primarily at the protein level but also via RNA (page 1416, left column, second-to-last paragraph). Two different technology platforms were selected for analysis of FNA cell lysates from leftover FNA-needle material: protein profiling using proximity extension assays (PEA), mRNA expression profiling by NanoString (page 1416, left column, second-to-last paragraph through right column, second paragraph). FNA samples were taken from patients with mammography-detectable lesions (paragraph bridging pages 1416 and 1417), cells were collected (page 1417, left column, second paragraph), and cells were lysed (page 1417, left column, third paragraph). Protein profiling and mRNA profiling were performed on the samples (page 1417, right column, second paragraph through page 1418, left column, first paragraph). The study included protein-based modeling of cancer versus benign lesions (page 1423). The study summarized differences between cancer and benign lesions as protein signatures through multiple regression modeling (page 1423, left column). The algorithm identified an 11-protein signature that appears to completely discriminate benign samples from malignant lesions (page 1423, right column). Franzen concluded that their results show that PEA-based protein profiles in FNA samples may allow reliable distinction of cancer and benign lesions and thus provide support for a conclusive diagnosis, which would be very important for early diagnosis of breast cancer (BC) (page 1426, left column, second paragraph).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to obtain a biopsy of the spilled intracellular components in the extracellular space (directed to the claimed ‘extracting said at least one cellular-component from said extracellular matrix’ of step (iii)), and then perform protein profiling and/or mRNA profiling to detect cancer from the spilled intracellular components, including determining whether the tumor is benign or malignant in the case when the tumor is a mammography-detectable lesion suspected of being breast cancer, when performing the method of Onik. One of ordinary skill in the art would have been motivated to do this because the diagnosis of cancer is desirable in patients and because Onik teaches applying their invention to treating cancerous tumors and ablating many types of cancerous as well as non-cancerous tissue (paragraph [0059]). The determination of a tumor being benign or malignant would have been desirable after the treatment of Onik in order to determine whether the tumor that is treated is indeed cancerous, as well as to determine the efficacy of the treatment. There would have been a reasonable expectation of obtaining a biopsy of the spilled intracellular components because Onik discloses obtaining a biopsy of the treated target tissue and because biopsies such as fine-needle aspiration (FNA) biopsies are well-established cancer diagnostic procedures, as indicated in Franzen. Also, there would have been a reasonable expectation of diagnosing cancer from the intracellular components because proteins and mRNA obtained from tumor lysates had been successfully used for diagnosing cancer, including determining whether a mammography-detectable lesion is malignant or benign, as indicated in Franzen; the intracellular components of Onik inherently include proteins and RNA. In the invention rendered obvious by Onik in view of Franzen, protein profiling and/or mRNA profiling of the intracellular components is directed to ‘identifying/analyzing the at least one cellular-component extracted’ of step (iv) of instant claim 1, and the cancer diagnosis and tumor determination (as benign or malignant) is directed to the claimed ‘identify/determine the presence and type of the tumor within said solid tissue’ of step (iv) of instant claim 1, wherein type of tumor is malignant or benign.
Furthermore, before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to use a tool such as a fine-needle (as in fine-needle aspiration biopsies taught in Franzen) in order to obtain the biopsy of the spilled intracellular components in the extracellular space since such a biopsy cannot be performed by hand and tools such as a fine-needle are recognized for biopsies. A tool such as fine-needle is directed to an ‘extraction element configured for molecular collection’ of step (ii) of instant claim 1 because the biopsy sample of the spilled intracellular components comprises molecules.
Thus, Onik in view of Franzen renders obvious instant claim 1.
Regarding instant claim 5, the electric field of Onik inherently is characterized by pulse number, pulse duration, electric field strength, and pulse frequency. Moreover, Onik discloses that important characteristics of the applied electric field include the field strength, frequency, duration, and number (paragraph [0017]). Thus, the invention rendered obvious by Onik in view of Franzen meets the claimed limitation of ‘wherein said PEF is characterized by pulse number, pulse duration, electric field strength, and pulse frequency.’ Instant claim 5 also recites alternative embodiments (i)-(iv) (“or” is recited before the last embodiment “(iv)” in the last line). Onik discloses that it is preferred that a series of not less than 100 electric pulses in a pulse train is applied (paragraph [0017]). See also claim 8 of Onik. This range of pulse number overlaps the claimed range of ‘from 1 to about 10,000’ of (i) of instant claim 5, thereby rendering it obvious. Also, Onik discloses that the pulse duration is preferably from 100 to 1,000 µs (paragraph [0017]). 100 µs converts to 100,000 ns, and 1,000 µs converts to 0.001 second. Thus, the preferred pulse duration of Onik overlaps the claimed range of ‘from about 50 ns to about 1 s’ of (ii) of instant claim 5, thereby rendering it obvious. Additionally, Onik discloses that the electric field strength is preferably in the range of 1,500 V/cm to 10,000 V/cm (paragraph [0017]), i.e., 1.5 to 10 kV/cm. This range overlaps the claimed range of ‘from about 0.1 to about 100 kV/cm’ of (iii) of instant claim 5, thereby rendering it obvious. Since Onik in view of Franzen renders obvious embodiments (i)-(iii) of instant claim 5, then instant claim 5 is rendered obvious.
Regarding instant claim 8, the references do not expressly disclose repeating steps (ii) and (iii), and optionally step (iv), several times, each time at a different location within the solid tissue, without removing the electrode(s) (directed to the claimed ‘at least one electroporation-electrode’) therefrom, and wherein the intracellular components (directed to the claimed ‘at least one cellular-component’) that is released into the extracellular matrix at each location, is kept apart for separate analysis in step (iv). However, Onik discloses verifying treatment efficacy by biopsy of a portion of the treated target tissue, and additional treatment may be immediately administered based on the biopsy result and visual determination of treatment efficacy (paragraph [0053]). Based on this, it would have been obvious that the ablation of Onik may not include all portions of the entire tissue, including portions that are undesirable (e.g. malignant tumor). As such, it would have been prima facie obvious to the person of ordinary skill in the art to repeat steps (ii)-(iv) rendered obvious by Onik in view of Franzen to ensure that ablation of additional portions of the treated tissue, including the undesirable portions where ablation is desired, and also to ensure cancer diagnosis is made for all ablated portions of the treated tissue. Therefore, instant claim 8 is rendered obvious.
Regarding instant claim 11, as discussed above, Onik discloses that typically from 1 to 6 needle type probe electrodes are used (paragraph [0048]). Also, as shown in Figure 9 of Onik, one or more therapeutic probes 20 (electrodes) are inserted directly into, or placed around the target tissue 11 (paragraph [0039]). Thus, Onik in view of Franzen renders obvious using two electrodes (directed to two electroporation-electrodes) to generate the pulsed electric field between them. Since the electrodes are inserted directly into, or placed around the target tissue, then it would have been obvious to insert the electrodes (including the embodiment of two electrodes) in any of these locations. An electrode placed around the target tissue meets the claimed limitation of placement in proximity to the solid tissue. Also, since the electrodes are inserted directly into the target tissue (paragraph [0039] of Onik), then the references also meet the claimed limitation of positioning the other electrode in the body of the subject. Thus, the references render obvious (1) both electroporation-electrodes placed within said solid tissue, or in proximity thereto; and (2) one electroporation-electrode is placed within said solid electrode, or in proximity thereto, and the other electroporation-electrode is positioned in the body of said subject. As such, instant claim 11 is rendered obvious.
Regarding instant claim 26, the mRNA profiling disclosed in Franzen is via RT-PCR (page 1416, left column, third paragraph). Also, the protein profiling disclosed in Franzen uses a proximity extension assay (PEA) which is an immunoassay in which microfluidic qPCR is used to measure the amount of a target protein (page 1416, paragraph bridging left and right columns). Therefore, performing the protein profiling and/or mRNA profiling of the invention rendered obvious by Onik in view of Franzen is directed to analyzing or identifying the intracellular components (directed to the claimed ‘at least one cellular-component’) by PCR, and wherein the cancer diagnosis (directed to identifying or determining the presence and type of tumor) is according to at least one of the identified or analyzed intracellular components. Thus, instant claim 26 is rendered obvious.
Claim 14, 15, 17, 20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Onik and Franzen as applied to claims 1, 5, 8, 11, and 26 above, and further in view of Lax (US 5,486,161. Previously cited).
As discussed above, Onik in view of Franzen renders obvious claims 1, 5, 8, 11, and 26. Regarding claim 14, since the electrodes (directed to the claimed ‘at least one electroporation-electrode’) are inserted into the target tissue or in proximity to it (paragraphs [0018], [0039], and [0048] of Onik), then the electrodes penetrate into the target tissue, or in proximity thereto. Therefore, Onik in view of Franzen meets the limitation ‘wherein said at least one electroporation-electrode each independently is designed to enable penetration into said solid tissue…or in proximity thereto’ of claim 14. The references differ from claim 14 in that they do not expressly disclose that each electrode (directed to claimed ‘electroporation-electrode’) is: (i) a hollow tube; (ii) a solid rod engulfed in a retentive cannula; or (iii) a solid rod at least partially coated with an adhesive material capable of reversibly adsorbing, associating with, and/or linking at least one of the at least one cellular-component.
The references further differ from claim 15 in that they do not expressly disclose that the electrode(s) (the claimed ‘at least one electroporation-electrode’) is a hollow tube, and the intracellular components (directed to the claimed ‘at least one cellular-component’) released to the extracellular matrix are extracted in step (iii) by suction via the hollow electrode(s), and wherein said method further comprises a step of inserting at least one liquid into the soft tissue (directed to the claimed ‘solid tissue’), or into a SOL or in proximity thereto, via the hollow electrode(s), and the intracellular components released to the extracellular matrix are extracted in step (iii) by suction together with said at least one liquid via said at least one hollow electroporation-electrode. The references further differ from claim 17 in that they do not expressly disclose that the at least one liquid is: (i) an aqueous solution, wherein the intracellular components (directed to the claimed ‘at least one cellular-component’) released to the extracellular matrix are diluted therein for extraction; (ii) an oil, wherein the intracellular components (claimed ‘at least one cellular-component’) released to the extracellular matrix are encapsulated by said oil to form a micelle that is then extracted by suction; or (iii) an aqueous solution and an oil inserted sequentially in that order, wherein the intracellular components (claimed ‘at least one cellular-component’) released to the extracellular matrix are first diluted in the aqueous solution, and then encapsulated by said oil to form a micelle that is extracted by suction.
The references further differ from claim 20 in that they do not expressly disclose that the electrode(s) (directed to the claimed ‘at least one electroporation-electrode’) is a solid rod engulfed in a retentive cannula, and the intracellular components (directed to the claimed ‘at least one cellular-component’) released to the extracellular matrix are extracted in step (iii) by suction via said cannula after extraction of the solid rod therefrom, and wherein said method further comprises a step of inserting at least one liquid into the soft tissue (directed to the claimed ‘solid tissue’), or into a SOL or in proximity thereto, via said cannula, and the intracellular components (the claimed ‘at least one cellular-component’) released to the extracellular matrix are extracted in step (iii) by suction together with said at least one liquid (interpreted as ‘said at least one liquid’) via said cannula. The references further differ from claim 22 in that they do not expressly disclose the at least one liquid is: (i) an aqueous solution, wherein the intracellular components (directed to the claimed ‘at least one cellular-component’) released to the extracellular matrix are diluted therein for extraction; (ii) an oil, wherein the intracellular components (claimed ‘at least one cellular-component’) released to the extracellular matrix are encapsulated by said oil to form a micelle that is then extracted by suction; or (iii) aqueous solution and an oil inserted sequentially in that order, wherein the intracellular components (claimed ‘at least one cellular-component’) released to the extracellular matrix are first diluted in the aqueous solution and then encapsulated by said oil to form a micelle that is extracted by suction.
Lax discloses a device and method for penetrating body tissues for medical purposes such as reducing tissue mass and fluid substance delivery, for example (column 1, lines 21-24). The device penetrates tissue to the precise target selected in order to deliver energy to the tissue and/or deliver substances (column 1, lines 24-26). The device is suitable for reducing the mass of tissues of any type, such as cancer and noncancerous tumors (column 1, lines 33-35). The medical ablation device of Lax comprises a flexible RF electrode wire or tube, terminal portion thereof extending through an insulating sleeve axially moveable thereon (column 2, lines 43-46). The electrode and surrounding sleeve extend through a portion of a rigid tube having a distal end adapted to be inserted into the body of a patient (column 2, lines 46-48). An electrode wire is directed to a ‘solid rod,’ so an electrode wire in a surrounding sleeve and rigid tube is directed to a solid rob engulfed in a retentive cannula (the surrounding sleeve and tube are each directed to a cannula), meeting (ii) of instant claim 14. Additionally, Lax teaches that the electrode can also be a hollow tube (column 2, line 59). This meets (i) of instant claim 14.
For an electrode that is a hollow tube, the proximal end thereof is adapted to be connected to a suction source for aspiration of tissue adjacent its distal end (column 2, lines 61-63). Also, when the electrode is a hollow tube, it can be a conduit for aspiration during treatment (column 5, lines 6-7). Lax also discloses the device comprising a hollow Rf electrode having an electrode lumen serving as a fluid conduit for delivering fluid through the open, distal end of the electrode, wherein fluid is delivered through the electrode lumen to irrigate the tissue ablation site (claim 1 of Lax).
Before the effective filing date of the claimed invention, it would have been obvious to substitute the electrode(s) of the method rendered obvious by Onik in view of Franzen with a device comprising an electrode wire or an electrode that is a hollow tube, wherein the electrode is extended through an insulating sleeve, and wherein the electrode and the surrounding sleeve extend through a portion of a rigid tube having a distal end adapted to be inserted into the body of a patient, as in the invention of Lax. It would have been a matter of simple substitution of electrodes for insertion into a subject’s body for delivering energy to a tissue for other such electrodes. Also, a person of ordinary skill in the art would have been motivated to make the substitution because it would have permitted delivering the electric field to difficult to access tissues, based on Lax’s teaching regarding the object of their invention (column 2, lines 35-37). There would have been a reasonable expectation of using said device for applying electrical pulses to cause cellular membrane breakdown such that intracellular contents spill into the extracellular space as required by Onik (e.g., paragraph [0013]) because an electrode in general would have been suitable for delivering the electric field taught by Onik. Therefore, Onik in view of Franzen and further in view of Lax renders obvious instant claim 14 (either of embodiments (i) and (ii)).
Regarding instant claims 15 and 17, when the electrode is a hollow tube for performing the method rendered obvious by Onik, Franzen, and Lax, it would have been obvious to also connect the electrode to a suction source and deliver a fluid through the electrode’s lumen in order to irrigate the ablated tissue, according to Lax. One of ordinary skill in the art would have been motivated to do this because it would have permitted aspiration of the treated area, thereby permitting the biopsy of the method rendered obvious by Onik in view of Franzen discussed above (biopsy by aspiration was taught Franzen) and foregoing the need for a separate device (e.g. a fine-needle as taught in Franzen) for performing aspiration for a biopsy. In making this modification, then instant claim 15 is rendered obvious. Moreover, it would have been obvious to use an aqueous solution as the fluid delivered through the electrode’s lumen when performing the method rendered obvious by Onik, Franzen, and Lax because any fluid, including an aqueous solution, would have been suitable for irrigation and aspiration of ablated tissue (in particular, its intracellular contents in the extracellular space). Thus, instant claim 17 (embodiment (i)) is rendered obvious.
Regarding instant claims 20 and 22, when the electrode is an electrode wire (directed to the claimed ‘solid rod’) which is engulfed in a retentive cannula (the surrounding sleeve and rigid tube) for performing the method rendered obvious by Onik, Franzen, and Lax, it also would have been obvious to connect the surrounding sleeve and rigid tube to a suction source and deliver a fluid through the sleeve/tube in order to irrigate the ablated tissue. One of ordinary skill in the art would have been motivated to do this because it would have permitted aspiration of the treated area, thereby permitting the biopsy of the method rendered obvious by Onik in view of Franzen discussed above (biopsy by aspiration was taught Franzen) and foregoing the need for a separate device (e.g. a fine-needle as taught in Franzen) for performing aspiration to perform a biopsy. In making this modification, then instant claim 20 is rendered obvious. Moreover, it would have been obvious to use an aqueous solution as the fluid delivered through the sleeve/tube when performing the method rendered obvious by Onik, Franzen, and Lax because any fluid, including an aqueous solution, would have been suitable for irrigation and aspiration of ablated tissue (in particular, its intracellular contents in the extracellular space). Thus, instant claim 22 (embodiment (i)) is rendered obvious.
Response to Arguments
Applicant’s arguments, filed June 11, 2026, with respect to the rejection under 35 U.S.C. 112(b) of claims 1, 2, 5, 8, 11, 14, 15, 17, 20, 22, 25, and 26, and the rejection under 35 U.S.C. 112(a) of claims 1, 2, 5, 8, 11, 14, 15, 17, 20, 22, 25, and 26, have been fully considered and are persuasive. The rejection under 35 U.S.C. 112(b) on page 2, last paragraph through page 3, first paragraph, of the last Office Action has been overcome by the amendment to claim 1. The rejection under 35 U.S.C. 112(a) has been overcome by the amendment to claim 1. Therefore, these rejections have been withdrawn.
However, Applicant’s arguments are unpersuasive with respect to the rejections under 35 U.S.C. 112(b) of claims 2, 15, 17, 20, 22, and 25, the rejection under 35 U.S.C. 103 of claims 1, 5, 8, 11, and 26 as being unpatentable over Onik in view of Franzen, and the rejection under 35 U.S.C. 103 of claims 14, 15, 17, 20, and 22 over Onik and Franzen in further view of Lax.
Regarding the rejection under 35 U.S.C. 112(b) of claim 2, Applicant argues that the claim’s language “into at least one of said at least one electroporation-electrode” plainly specifies that the extraction element is the electrode itself, which is interpretation (a) identified by the Examiner. The Examiner disagrees, and suggests that claim 2 be amended to recite that the extraction element is at least one of said at least one electroporation-electrode. Regarding the rejection under 35 U.S.C. 112(b) of claims 15 and 17, Applicant asserts that claim 15 clearly identifies the hollow electroporation-electrode as the extraction element. The Examiner disagrees, and suggests that claim 15 be amended to recite that the at least one hollow electroporation-electrode is the extraction element. Regarding the rejection under 35 U.S.C. 112(b) of claims 20 and 22, Applicant asserts that claim 20 clearly identifies the retentive cannula as the extraction element. The Examiner disagrees, and suggests that claim 20 be amended to recite that the retentive cannula is the extraction element. Regarding the rejection under 35 U.S.C. 112(b) of claim 25, Applicant asserts that the phrase “releasing said at least one cellular-component therefrom” refers to releasing the cellular-component from the adhesive material coating on the solid rod electrode, not from the body of the subject. However, the last two lines recite “outside the body of the subject after releasing said at least one cellular-component therefrom.” The recitation of “outside the body of the subject” in relation to “releasing said at least one cellular-component therefrom” creates confusion. The Examiner suggests that claim 25 be amended to recite “releasing said at least one cellular-component from the adhesive material” in the last two lines for clarity.
With respect to the rejection under 35 U.S.C. 103 over Onik in view of Franzen, Applicant argues that while the claimed invention seeks to preserve and collect molecular information from tissue, Onik seeks to destroy tissue and trigger an immune response. However, the claims do not foreclose the destruction of tissue, so the destruction of tissue of Onik and the triggered immune response (due to the spilled cellular contents) is not contradictory to the claims. Moreover, Onik recites that their method may include the biopsy of a portion of the treated target tissue (paragraph [0053]) and the detection of the spillage of the cell contents (paragraph [0054]) which permits for diagnostics including testing of released cellular components. Though Onik does not expressly disclose the extraction of the released cellular components (their spillage of cell contents) and identifying or analyzing the released cellular components to identify or determine the presence and type of the tumor within solid tissue or determine if a SOL is malignant or benign (steps (iii) and (iv) of instant claim 1), these limitations are obvious for reasons set forth in the rejection under 35 U.S.C. 103. It is noted that the rejection under 35 U.S.C. 103 has been modified to make it clear that one of ordinary skill in the art would have been motivated to obtain a biopsy of the spilled intracellular components in the extracellular space and perform profiling to diagnose cancer (including determining whether the tumor is benign or malignant) because the diagnosis of cancer is desirable in patients and because Onik teaches applying their invention to treating cancerous tumors and ablating many types of cancerous as well as non-cancerous tissue (paragraph [0059]). As further stated in the modified rejection, the determination of a tumor being benign or malignant would have been desirable after the treatment of Onik in order to determine whether the tumor that is treated is indeed cancerous, as well as to determine the efficacy of the treatment.
Applicant emphasizes that in Onik, the intracellular components and internal constituents are left in the extracellular space of the subject, wherein an immunologic process of the subject is activated to remove. Applicant asserts that the claimed invention takes the diametrically approach in which the cellular component(s) is extracted from the extracellular matrix. Applicant likewise emphasizes that leaving the spilled contents in the body is the operative mechanism of Onik’s method. However, taking a sample of the released intracellular components would not be considered contrary to the Onik invention since it permits the determination of the efficacy of the treatment disclosed by Onik, and since Onik recognizes taking a biopsy of the treated target tissue, which necessarily would at least include the released intracellular components depending on the precision of the biopsy.
Applicant also points to the Electrical Membrane Breakdown (EMB) disclosed in Onik, asserting that it applied higher energy levels than prior art methods to rupture the cell membrane than to electroporate. It is argued that the claimed invention is in contrast to Onik by applying a pulsed electric field via an electroporation electrode(s) to induce permeabilization of cells of the solid tissue or SOL, not destroying the cells entirely. However, “permeabilization” as recited in the claims encompasses cell rupture as disclosed in Onik since the claims do not recite the extent of permeabilization (e.g., irreversible or reversible). Moreover, the claims do not have limitation requiring that the cells are not destroyed.
Regarding Applicant’s argument that the biopsy of Onik, Applicant points out that it is a post-treatment efficacy check, not a diagnostic step for determining tumor type. However, this is addressed with the modified rejection. Determining treatment efficacy indeed include determining tumor type since it would ensure whether the treatment is effective such that the tumor is not malignant.
Applicant also argues against Franzen by highlighting that it collects intact cells before any permeabilization. However, Franzen also recognizes recovering tissue fragments (page 1416, left column, second paragraph).
Conclusion
No claims are allowed.
Claims 2 and 25 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
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Sef
/SUSAN E. FERNANDEZ/Examiner, Art Unit 1651
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