DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Objections
Claim 5 objected to because of the following informalities: claim 5 does not end in a period. Appropriate correction is required.
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.
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, the alternating fields having a frequency and field strength (abstract; an electric field necessarily has a field strength), 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
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bhisma Mehta can be reached at 571-272-3383. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
LAURA A. BOUCHELLE
Primary Examiner
Art Unit 3783
/LAURA A BOUCHELLE/Primary Examiner, Art Unit 3783