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 .
Response to Arguments
Applicant's arguments filed 5/21/2026 have been fully considered.
Regarding the objection of claim 5, the amendment to the claim overcomes the objection and the objection is therefore withdrawn.
Regarding the 103 rejection, Applicant’s argument have been considered and are not convincing. Applicant argues that Griffin is a simple review article that discusses the role that ion channels hold in gliomagenesis and fails to teach or suggest using chloride ion channel inhibitor with an alternating electric field. This argument is not convincing. First, the use of TTF is taught by Tran, and therefore Griffin is not relied upon to teach the step of applying TTF. Second, the examiner does not agree that Griffin does not teach or suggest using chloride ion channel inhibitors with an alternating electric field. Griffin discloses that studies show evidence that ion channel inhibitors may be efficacious in a combinatorial approach with mainstay cancer therapies, and then further describes such mainstay therapies as including TTF, and further that TTF is not as effective when used as a monotherapy (pages 13-14).
Applicant notes that Griffin acknowledges that TTF has an effect onion channels and describes treatment with ion channel inhibitors, but concludes that this does not provide motivation to combine these treatments. The examiner does not agree. Griffin teaches that both ion channel inhibitors and TTF have shown efficacy as combinatorial treatments, and therefore a person of ordinary skill in the art would find motivation to combine these treatments, particularly in combination with the teachings of Tran.
Applicant further argues that the instant application shows superior and surprising results in experiments using TTFs in combination with a chloride ion channel inhibitor compared to either therapy alone. The examiner argues that this is not a surprising result as Griffin states that studies have shown that both drugs that target ion channels and TTFs are suggested for use in combinational treatment approaches as either has limited efficacy alone and therefore it is not unexpected that the combination therapy is more effective.
Regarding the rejection over Tran, Griffin, and Gritti or Angelini, Applicant argues that the rejection is insufficient for the same reasons as those described above, and therefore the arguments are not convincing for the same reasons.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-3, 9-12, 14-16, 24, 47-50 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tran et al (TW I815047 B) in view of Griffin et al (Ion Channels as Therapeutic Targets in High Grade Gliomas, Cancers 2020, 12, 3068). For ease of discussion, all citations for Tran refer to machine translation provided herewith.
Regarding claim 1, Tran discloses a method of treating a subject having cancer (abstract) comprising, applying alternating electric fields to a target site of the subject for a period of time (abstract), wherein the target site comprises one or more cancer cells (abstract), and administering an adjunct therapy (abstract).
Claim 1 differs from Tran in calling for the step of administering a chloride ion channel inhibitor to the subject. Tran discloses administering a second therapy in addition to the alternative electric field, but fails to disclose specifically administering a chloride ion channel inhibitor. Griffin teaches that chloride ion channel inhibitors have shown effectiveness in slowing cancel cell progression and invasion (page 13, first paragraph), and such drugs may be efficacious in combination with mainstay cancer therapies (page 13, last paragraph), such as alternating electric fields (TTF) where there are clear indications for TTF as a combination therapy with mainstay and novel therapeutics (page 14). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Tran to include delivery of a chloride ion channel inhibitor because Griffin teaches that chloride ion channel inhibitors provide a positive effect on cancer cell proliferation, and studies show that both chloride ion channel inhibitors and TTF benefit from combination therapy.
Regarding claim 2, Griffin further teaches that the chloride ion channel inhibitor is a chloride intracellular channel (CLIC) inhibitor (page 10, table 2). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method described above with regard to claim 1 to include the chloride ion channel inhibitor being a CLIC as taught by Griffin because this is the particular drug that has been found to be useful in reducing cancer cell proliferation.
Regarding claim 3, Griffin teaches that the CLIC as discussed above with regard to claim 2, and further that the CLIC is specifically CLIC1 (page 10, table 2).
Regarding claim 9, the alternating electric fields and the chloride ion channel inhibitor reduce proliferation of the cancer cells (Griffin: page 8, paragraph 4; page 14, last paragraph).
Regarding claim 10, Tran discloses that the cancer is glioblastoma (abstract).
Regarding claim 11, Tran discloses that the therapy is delivered in cycles (page 5, 3rd paragraph) and therefore in the combination of Tran in view of Griffin described above, the chloride ion channel inhibitor is administered prior to applying the alternating electric fields.
Regarding claim 12, Tran discloses that the adjunct drug is delivered after the alternative fields (page 9, 3rd paragraph).
Regarding claim 14, Tran discloses a method of reducing cancer cell proliferation (page 2, 3rd paragraph: mitotic arrest or delay means reduced cell proliferation) comprising, exposing the cancer cell to alternating electric fields for a period of time, the alternating fields having a frequency and field strength (abstract; an electric field necessarily has a field strength), and administering an adjunct therapy (abstract).
Claim 14 differs from Tran in calling for the step of administering a chloride ion channel inhibitor to the subject. Tran discloses administering a second therapy in addition to the alternative electric field, but fails to disclose specifically contacting the cancer cells with a chloride ion channel inhibitor. Griffin teaches that chloride ion channel inhibitors have shown effectiveness in slowing cancel cell progression and invasion (page 13, first paragraph), and such drugs may be efficacious in combination with mainstay cancer therapies (page 13, last paragraph), such as alternating electric fields (TTF) where there are clear indications for TTF as a combination therapy with mainstay and novel therapeutics (page 14). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Tran to include delivery of a chloride ion channel inhibitor because Griffin teaches that chloride ion channel inhibitors provide a positive effect on cancer cell proliferation, and studies show that both chloride ion channel inhibitors and TTF benefit from combination therapy.
Regarding claim 15, Griffin further teaches that the chloride ion channel inhibitor is a chloride intracellular channel (CLIC) inhibitor (page 10, table 2). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method described above with regard to claim 1 to include the chloride ion channel inhibitor being a CLIC as taught by Griffin because this is the particular drug that has been found to be useful in reducing cancer cell proliferation.
Regarding claim 16, Griffin teaches that the CLIC as discussed above with regard to claim 2, and further that the CLIC is specifically CLIC1 (page 10, table 2).
Regarding claim 24, Tran discloses that the cancel cell is in a subject (page 3, 3rd paragraph).
Regarding claim 47, Tran discloses that the alternating electric field frequency is between 100 and 500kHz (abstract). This range substantially overlaps with the claimed range of 50kHz and 1MHz and is sufficiently specific to anticipate the claimed range.
Regarding claim 48, Tran discloses that the alternating electric field frequency is between 100 and 500kHz (abstract). This anticipates the claimed 200kHz frequency.
Regarding claim 49, Griffin teaches that alternating electric field therapy includes a field strength of 1.0 V/cm (page 14, 2nd paragraph). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide a field strength as taught by Griffin as this is the field strength that provides a therapeutic effect.
Regarding claim 50, Griffin teaches that alternating electric field therapy includes a field strength of 1.0 V/cm (page 14, 2nd paragraph). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide a field strength as taught by Griffin as this is the field strength that provides a therapeutic effect.
Claim(s) 5, 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tran in view of Griffin as applied to claim 3 above, and further in view of Gritti et al (Metformin repositioning as antitumoral agent: selective antiproliferative effects in human glioblastoma stem cells, vie inhibition of CLIC1-mediated ion current. Oncotarget, 2014 Oct 21; 5(22): 11252-11268).
Regarding claim 5, Griffin teaches the CLIC inhibitor as discussed above, but fails to specifically disclose that the inhibitor is IAA94. Gritti teaches that IAA94, a CLIC1 inhibitor, is a suitable alternative to metformin (the CLIC1 inhibitor taught by Griffin) for decreasing tumor cell proliferation (page 4, page 8). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Tran in view of Griffin as discussed above with regard to claim 3 to include the CLIC1 inhibitor in the form of IAA94 because Gritti teaches that IAA94 targets tumor cells to reduce proliferation and can be used in place of metformin.
Regarding claim 18, Griffin teaches the CLIC inhibitor as discussed above, but fails to specifically disclose that the inhibitor is IAA94. Gritti teaches that IAA94, a CLIC1 inhibitor, is a suitable alternative to metformin (the CLIC1 inhibitor taught by Griffin) for decreasing tumor cell proliferation (page 4, page 8). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Tran in view of Griffin as discussed above with regard to claim 3 to include the CLIC1 inhibitor in the form of IAA94 because Gritti teaches that IAA94 targets tumor cells to reduce proliferation and can be used in place of metformin.
Claim(s) 6, 7, 18, 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tran in view of Griffin as applied to claim 2 above, and further in view of Angelini (Role of CLIC1 and L-Type calcium channels in the pathophysiology of glioblastoma and ventricular arrhythmias, IRIS Institutional Research Information System – AIR Archivio Instituzionale della Ricerca, 2015).
Claim 6 differs from the teachings above in calling for the CLIC inhibitor to be a siRNA. Angelini teaches that siRNA therapy inhibits the CLIC1 protein and thereby causes the cells to proliferate less efficiently (page 2). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the CLIC inhibitor taught by Griffin as discussed with regard to claim 2 above to be siRNA as taught by Angelini because siRNA knocks down the CLIC1 protein thereby reducing cell proliferation.
Regarding claim 7, Angelini teaches that the siRNA inhibits the expression of the CLIC1 protein as discussed above with regard to claim 6.
Claim 18 differs from the teachings above in calling for the CLIC inhibitor to be a siRNA. Angelini teaches that siRNA therapy inhibits the CLIC1 protein and thereby causes the cells to proliferate less efficiently (page 2). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the CLIC inhibitor taught by Griffin as discussed with regard to claim 2 above to be siRNA as taught by Angelini because siRNA knocks down the CLIC1 protein thereby reducing cell proliferation.
Regarding claim 20, Angelini teaches that the siRNA inhibits the expression of the CLIC1 protein as discussed above with regard to 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA A BOUCHELLE whose telephone number is (571)272-2125. The examiner can normally be reached Mon-Fri 8:00-5:00 CST.
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LAURA A. BOUCHELLE
Primary Examiner
Art Unit 3783
/LAURA A BOUCHELLE/Primary Examiner, Art Unit 3783
Prosecution Insights