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 .
Acknowledgments
In the reply, filed on June 18, 2026, Applicant amended claims 1, 4-7, and 9-19.
In the non-final rejection of December 23, 2025, Examiner noted that the information disclosure statement filed May 14, 2024 (3 pages), fails to comply with 37 CFR 1.98(a)(2). Applicant argued: Applicant submits that neither PCT/IB2023/056285 (WO 2023/042825) nor TW 112122837 were cited on the SB08 and therefore, no copies of these references are necessary. Applicant notes that both of these references are corresponding foreign counterparts to the pending US case and therefore are not considered material to patentability to the current application (Remarks, page 6). Concern is withdrawn.
Examiner objected to the Abstract. Applicant amended the Abstract; however, Applicant did not address all of the objections. Objection is maintained.
Examiner objected to claims 1, 4-7, 10-11, 13-14, and 17. Applicant amended claims 1, 4-7, 10-11, 13-14, and 17. Objection is withdrawn.
Examiner rejected claims 9-19 under 35 U.S.C. 112(b). Applicant amended claims 1 and 9-17. Rejection is withdrawn.
Specification
The abstract of the disclosure is objected to because:
In line 12, “a cell comprising:” should be changed to “a cell, the methods comprising:”
In lines 12-13, “alternating electric fields” should be changed to “the alternating electric fields”
In line 15, “enhancing” should be changed to “the enhancing”
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 14-15 are objected to because of the following informalities:
In regards to claim 14, line 2, “one or more FGF, wherein the FGF is” should be changed to “one or more FGFs, wherein the one or more FGFs are”.
In regards to claim 15, line 2, “one or more FGFR, wherein the FGFR is” should be changed to “one or more FGFRs, wherein the one or more FGFRs are”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-5, 7, 9-16, and 18-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In regards to claim 1, lines 3-5 recite: “applying a single field to a target site of the subject in need thereof, wherein the single field is a single alternating electric field”; however, such is new matter not described in the Specification. Claims 2-5, 9-16, and 18-20 are rejected by virtue of being dependent upon claim 1.
In regards to claim 4, lines 1-3 recite: “wherein the single alternating electric field is applied before, after, or simultaneously with the administering of the one or more FGF inhibitors or FGFR inhibitors”; however, such is new matter not described in the Specification.
In regards to claim 7, lines 3-4 recite: “applying a single field to the cell, wherein the single field is a single alternating electric field”; however, such is new matter not described in the Specification.
In regards to claim 10, lines 1-3 recite: wherein the one or more FGF inhibitors block upregulation of FGF expression “in response to the single alternating electric field”; however, such is new matter not described in the Specification.
In regards to claim 18, lines 1-2 recite: “wherein the single alternating electric field has a frequency between 50 kHz and 1 MHz”; however, such is new matter not described in the Specification.
In regards to claim 19, lines 1-2 recite: “wherein the single alternating electric field has a field strength of between 0.5 and 4 V/cm RMS”; however, such is new matter not described in the Specification.
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.
Claim 16 is 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.
In regards to claim 16, lines 3-5 recite “SSR128129E,… SSR128129E”. It is unclear why the same FGFR inhibitors are listed twice.
In regards to claim 16, line 4 recites “BGJ398,… Infigratinib (BGJ398)”. It is unclear why the same FGFR inhibitors are listed twice.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-5, 7, 9, 11, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ivkov et al (US 2005/0090732).
In regards to claim 1, Ivkov et al teaches a method of treating a subject in need thereof (claim 19: A therapeutic method for treating the body, body part, tissue, cell, or body fluid of a subject), the method comprising:
applying a single field to a target site of the subject in need thereof, wherein the single field is a single alternating electric field (paragraph [0052]: an alternating electric field)
administering one or more fibroblast growth factor (FGF) inhibitors or fibroblast growth factor receptor (FGFR) inhibitors to the subject in need thereof (claim 19: administering at least one other therapy to the target)(claim 40: wherein the at least one other therapy comprises administering… Interferon-α)(Table III: Interferon-α… Inhibits FGF production)
In regards to claim 2, Ivkov et al teaches wherein the subject has mesothelioma, ovarian cancer or lung cancer (Table I: Lung cancer…Mesotheliomas… Ovarian cancer).
In regards to claim 3, Ivkov et al teaches wherein the target site comprises one or more cancer cells (paragraph [0047]: cancer cells).
In regards to claim 4, Ivkov et al teaches wherein the single alternating electric field is applied before, after, or simultaneously with the administering of the one or more FGF inhibitors or FGFR inhibitors (claim 19: administering targeted thermotherapy to a target by supplying a bioprobe to the target and exposing the bioprobe to an alternating magnetic field (AMF), and b. administering at least one other therapy to the target, wherein the at least one other therapy is administered prior to, during, after the targeted thermotherapy administration, or a combination thereof)(paragraph [0052]: an alternating magnetic field is accompanied by an alternating electric field)(claim 40: wherein the at least one other therapy comprises administering… Interferon-α)(Table III: Interferon-α… Inhibits FGF production).
In regards to claim 5, Ivkov et al teaches wherein the one or more FGF inhibitors or FGFR inhibitors are administered intratumorally, intracranially, intraventricularly, intrathecally, epidurally, intradurally, intravascularly, intravenously (targeted or non-targeted), intraarterially, intramuscularly, subcutaneously, intraperitoneally, orally, intranasally, via intratumor injection (e.g. computed tomography-guided, during surgery or biopsy) or via inhalation (paragraph [0160]: Pharmaceuticals involving antiangiogenesis, that are currently under development, are listed in Table III. In one embodiment of the invention, the targeted therapy system is used in combination with at least one of these pharmaceuticals)(Table III: Interferon-α… Inhibits FGF production)(claim 19: administering targeted thermotherapy to a target by supplying a bioprobe to the target)(paragraph [0097]: A method of administering bioprobes 590 to the desired area for treatment and the dosage may depend upon, but is not limited to, the type and location of the diseased material… Other methods of administration include intravascular injection, intravenous injection, intraperitoneal injection, subcutaneous injection, and intramuscular injection. Bioprobes 590 may be formulated in an injectable format (suspension, emulsion) in a medium such as, for example, water, saline, Ringer's solution, dextrose, albumin solution, or oils. Bioprobes 590 may also be administered to the patient through topical application via a salve or lotion, transdermally through a patch, orally ingested as a pill or capsule or suspended in a liquid, or rectally inserted in suppository form. Bioprobes 590 may also be suspended in an aerosol or pre-aerosol formulation suitable for inhalation via the mouth or nose).
In regards to claim 7, Ivkov et al teaches a method (claim 19: A therapeutic method) of increasing cytotoxicity in a cell (paragraph [0008]: Immunotherapeutics fall into at least three classes: (1) deployment of antibodies that, themselves, target growth receptors, disrupt cytokine pathways, or induce complement or antibody-dependent cytotoxicity), the method comprising:
applying a single field to the cell, wherein the single field is a single alternating electric field (paragraph [0052]: an alternating electric field)(paragraph [0047]: cells are exemplary targets)
contacting one or more fibroblast growth factor (FGF) inhibitors or fibroblast growth factor receptor (FGFR) inhibitors to the cell (claim 19: administering at least one other therapy to the target)(claim 40: wherein the at least one other therapy comprises administering… Interferon-α)(Table III: Interferon-α… Inhibits FGF production)(paragraph [0047]: cells are exemplary targets), thereby increasing the cytotoxicity in the cell (paragraph [0008]: Immunotherapeutics fall into at least three classes: (1) deployment of antibodies that, themselves, target growth receptors, disrupt cytokine pathways, or induce complement or antibody-dependent cytotoxicity)
In regards to claim 9, Ivkov et al teaches wherein the one or more FGF inhibitors inhibit or decrease FGF expression (Table III: Inhibits FGF production).
In regards to claim 11, Ivkov et al teaches wherein the one or more FGF inhibitors prevent FGF from interacting or binding to one or more FGF receptors (FGFRs) (Table III states “Inhibits FGF production” from which it is understood that FGF will not be produced and thus will not interact or bind to FGF receptors).
In regards to claim 20, Ivkov et al teaches administering a cancer therapeutic (paragraph [0162]: chemo-… therapy).
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.
Claims 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Ivkov et al, as applied to claim 1 above, and further in view of Ji et al (US 2020/0281907).
In regards to claim 12, Ivkov et al does not teach wherein the one or more FGFR inhibitors prevent FGFR from interacting or binding with one or more FGFs. Ji et al teaches a method of treating a subject in need thereof, wherein the one or more FGFR inhibitors prevent FGFR from interacting or binding with one or more FGFs (paragraph [0006]: Inhibitors of FGFR are currently being developed for the treatment of cancer. For example, pemigatinib)(paragraph [0157]: Pemigatinib can be used in combination with one or more other kinase inhibitors for the treatment of diseases, such as cancer, that are impacted by multiple signaling pathways. For example, a combination can include one or more inhibitors of the following kinases for the treatment of cancer:… FGFR1, FGFR2, FGFR3, FGFR4)(paragraph [0002]: four FGFR proteins (FGFR1-4) that are capable of binding ligands)(paragraph [0003]: FGF ligands). It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the method, of Ivkov et al, with wherein the one or more FGFR inhibitors prevent FGFR from interacting or binding with one or more FGFs, as taught by Ji et al, as such will allow for treating cancer in a patient in need thereof (Abstract) as overexpression of FGF can lead to tumor development, progression, and resistance to conventional cancer therapies (paragraph [0003]).
In regards to claim 13, Ivkov et al does not teach wherein the one or more FGFR inhibitors block one or more FGF receptors (FGFRs). Ji et al teaches a method of treating a subject in need thereof, wherein the one or more FGFR inhibitors block one or more FGF receptors (FGFRs) (paragraph [0006]: Inhibitors of FGFR are currently being developed for the treatment of cancer. For example, pemigatinib)(paragraph [0157]: Pemigatinib can be used in combination with one or more other kinase inhibitors for the treatment of diseases, such as cancer, that are impacted by multiple signaling pathways. For example, a combination can include one or more inhibitors of the following kinases for the treatment of cancer:… FGFR1, FGFR2, FGFR3, FGFR4). It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the method, of Ivkov et al, with wherein the one or more FGFR inhibitors block one or more FGF receptors (FGFRs), as taught by Ji et al, as such will allow for treating cancer in a patient in need thereof (Abstract) as overexpression of FGF can lead to tumor development, progression, and resistance to conventional cancer therapies (paragraph [0003]).
In regards to claim 14, Ivkov et al teaches wherein the one or more FGF inhibitors target one or more FGF (Table III: Interferon-α… Inhibits FGF production); however, Ivkov et al is silent about wherein the FGF is FGF-21, FGF-19, FGF-7, or FGF-basic. Ji et al teaches a method of treating a subject in need thereof, wherein the FGF is FGF-19 (paragraph [0005]: FGF19). It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the method, of Ivkov et al, with wherein the FGF is FGF-19, as taught by Ji et al, as ectopic expression of FGF-19 in transgenic mice was shown to lead to tumor formation in the liver and a neutralizing antibody to FGF-19 was found to inhibit tumor growth in mice (paragraph [0005]).
In regards to claim 15, Ivkov et al is silent about wherein the one or more FGFR inhibitors target one or more FGFR, wherein the FGFR is FGFR1, FGFR2, FGFR3, or FGFR4. Ji et al teaches a method of treating a subject in need thereof, wherein the one or more FGFR inhibitors target one or more FGFR (paragraph [0003]), wherein the FGFR is FGFR1, FGFR2, FGFR3, or FGFR4 (paragraph [0157]: FGFR1, FGFR2, FGFR3, FGFR4). It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the method, of Ivkov et al, with wherein the one or more FGFR inhibitors target one or more FGFR, wherein the FGFR is FGFR1, FGFR2, FGFR3, or FGFR4, as taught by Ji et al, as inhibition of these kinases will allow for the treatment of cancer (paragraph [0157]).
In regards to claim 16, Ivkov et al is silent about wherein the one or more FGFR inhibitors are one or more of BAY 1179470, FPA144, PRO-001, RG7444, SSR128129E, AZD4547, BAY1163877,BGJ398, CH5183284, Erdafitinib, LY2874455, Roblitinib, Infigratinib (BGJ398),SSR128129E, PD-166866, ASP5878, H3B-6527, NSC12, BO-264, Fisogatinib (BLU- 554), FIIN-2, Futibatinib (TAS-120), BLU9931, Pemigatinib (INCB054828),Zoligratinib (Debio-1347). Alofanib (RPT835), PRN1371, Ferulic Acid, or Derazantinib (ARQ-087). Ji et al teaches a method of treating a subject in need thereof, wherein the one or more FGFR inhibitors are Pemigatinib (paragraph [0006]: Inhibitors of FGFR are currently being developed for the treatment of cancer. For example, pemigatinib). It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the method, of Ivkov et al, with wherein the one or more FGFR inhibitors are Pemigatinib, as taught by Ji et al, as such will allow for treating cancer in a patient in need thereof (Abstract) as overexpression of FGF can lead to tumor development, progression, and resistance to conventional cancer therapies (paragraph [0003]).
Claims 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Ivkov et al, as applied to claim 1 above, and further in view of Palti (US 7,565,205).
In regards to claim 18, Ivkov et al is silent about wherein the single alternating electric field has a frequency between 50 kHz and 1 MHz. Palti teaches a method of treating a subject in need thereof, wherein the single alternating electric field has a frequency between 50 kHz and 1 MHz (column 11, lines 40-43: the electric fields that are used are alternating fields having frequencies that are in the range… from about 100 KHz to about 300 KHz). It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the method, of Ivkov et al, with wherein the single alternating electric field has a frequency from about 100 KHz to about 300 KHz, as taught by Palti, which is in the claimed range of between 50 kHz and 1 MHz, as these type of electric fields are also referred to below as "TC fields", which is an abbreviation of "Tumor Curing electric fields", since these electric fields fall into an intermediate category (between high and low frequency ranges) that have bio-effective field properties while having no meaningful stimulatory and thermal effects, and these frequencies are sufficiently low so that the system behavior is determined by the system's Ohmic (conductive) properties but sufficiently high enough not to have any stimulation effect on excitable tissues (column 11, lines 43-52).
In regards to claim 19, Ivkov et al is silent about wherein the single alternating electric field has a field strength of between 0.5 and 4 V/cm RMS. Palti teaches a method of treating a subject in need thereof, wherein the single alternating electric field has a field strength of between 0.5 and 4 V/cm RMS (column 15, lines 51-53: The desired field strength in the tissue being treated is… between about 2 V/cm and 3 V/cm). It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the method, of Ivkov et al, with wherein the single alternating electric field has a field strength of between about 2 V/cm and 3 V/cm, as taught by Palti, which is in the claimed range of between 0.5 and 4 V/cm RMS, as such will cause the electric field to selectively damage cells that are undergoing cell division and leave cells that are not undergoing cell division substantially unharmed (column 32, lines 39-44).
Response to Arguments
Applicant's arguments filed June 18, 2026, have been fully considered but they are not persuasive:
In regards to claims 1 and 7, Applicant argued: Independent claims 1 and 7, and thus all claims that depend therefrom, have been amended to recite, in part, "applying a single field to the cell, wherein the single field is a single alternating electric field." Ivkov fails to teach "applying a single field to the cell, wherein the single field is a single alternating electric field." In fact, Ivkov specifically teaches applying a magnetic field that can be accompanied by an alternating electric field. Thus, at best, when teaching a single field, Ivkov teaches applying a magnetic field which is not an alternating electric field. Furthermore, when Ivkov refers to applying an alternating electric field, it is always in combination with a magnetic field so there is not a single field. Nowhere in Ivkov is there any disclosure or suggestion to use a method without a magnetic field or an alternating electric field without also applying a magnetic field. Regardless of whether Ivkov teaches a combination of an electromagnetic field and a possible FGF inhibitor (e.g., interferon alpha), Ivkov fails to teach applying a single field, wherein the single field is a single alternating electric field (Remarks, page 10). Examiner disagrees. First, Ivkov et al teaches applying a single field to a target site of the subject in need thereof, wherein the single field is a single alternating electric field (paragraph [0052]: an alternating electric field). Second, the preamble of claims 1 and 7 recite: the method “comprising”. The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps (MPEP 211.03). Thus, the additional alternating magnetic field, of Ivkov et al, is not excluded by the claimed method.
Allowable Subject Matter
Claims 6, 8, and 17 are allowed over the prior art of record.
In regards to independent claim 6, the prior art of record does not disclose or render obvious before the effective filing date of the claimed invention the combination of a method of increasing a sensitivity of a cell to an alternating electric field, as claimed, specifically including contacting one or more fibroblast growth factor (FGF) inhibitors or fibroblast growth factor receptor (FGFR) inhibitors to the cell, thereby increasing the sensitivity of the cell to the alternating electric field.
Ivkov et al teaches a method (claim 19: A therapeutic method) comprising:
applying the alternating electric field to the cell (paragraph [0052]: an alternating electric field)(paragraph [0047]: cells are exemplary targets)
contacting one or more fibroblast growth factor (FGF) inhibitors or fibroblast growth factor receptor (FGFR) inhibitors to the cell (claim 19: administering at least one other therapy to the target)(claim 40: wherein the at least one other therapy comprises administering… Interferon-α)(Table III: Interferon-α… Inhibits FGF production)(paragraph [0047]: cells are exemplary targets)
However, Ivkov et al is silent about whether the method is specifically “a method of increasing a sensitivity of a cell to an alternating electric field” and whether contacting one or more fibroblast growth factor (FGF) inhibitors or fibroblast growth factor receptor (FGFR) inhibitors to the cell specifically results in “thereby increasing the sensitivity of the cell to the alternating electric field”.
Thus, independent claim 6 is allowed over the prior art of record. Dependent claims 8 and 17 are allowed over the prior art of record by virtue of being dependent upon independent claim 6.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/SHEFALI D PATEL/Primary Examiner, Art Unit 3783
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