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 .
DETAILED ACTION
This Office Action is in response to Applicant’s Arguments and Amendment filed, 05/14/2026, wherein the Amendment amended claims 1 and 3.
Claims 1-10 are pending and examined on the merits herein.
Priority
This application claims the following priority:
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REJECTIONS WITHDRAWN
The status for each rejection and/or objection in the previous Office Action is set out below.
35 U.S.C. § 112(d)
Applicant’s amendment to claim 1, that adds “skin cancer” as a metastatic cancer, is sufficient to overcome this rejection.
35 U.S.C. § 103
Applicant’s amendment to claims 1 and 3, that deletes “liver cancer,” is sufficient to overcome this rejection.
REJECTIONS—NEW
Applicant’s amendment to independent claim 1 that deletes liver cancer as a cancer has resulted in the below new prior art rejections. US PG-PUB 2023/0137849 to Fontenille continues to be relied upon as the primary reference.
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 for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
(New) Claims 1-5 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over US PG-PUB 2023/0137849 to Fontenille (effectively filed on 02/10/20217, PTO-892 of 06/12/2024) in view of Vazquez-Estevez (Sorafenib (SOR) in advanced non-small cell lung cancer (NSCLC): A phase II study of patient progress after several lines of treatment, published 2012, PTO-892).
Fontenille teaches the use of a compound of the diuretics class in admixture with pharmaceutically acceptable excipients, for treating cancer (title, abstract; pg. 20, claim 22; pg. 23, claim 37), wherein:
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(Vd) is a diuretic compound ([0175]; pg. 22, claim 30), and wherein the method is applied to metastasized cancer ([0055], [0192], [0197]; pg. 22, claims 33, 35; pg. 23, claim 36).
Fontenille teaches hydroflumethiazide as an anticancer agent, as a potentiator of an anti-cancer agent, and as an anti-metastatic agent (pg. 22, claim 33).
Fontenille additionally teaches administering hydroflumethiazide with another anti-cancer agent (pg. 22, claim 34).
Fontenille teaches sorafenib as another anti-cancer agent (pg. 23, claim 36, [0226]) and teaches liver cancer as a cancer to be treated (pg. 23, claims 39, 40; [0276]; [0297]).
Fontenille specifically exemplifies administering hydroflumethiazide and the anticancer agent doxorubicin to treat breast cancer ([0412]).
Regarding claim 1, while Fontenille teaches a method of treating metastatic cancer by administering hydroflumethiazide and an anticancer agent, such as sorafenib, it differs from that of the instantly claimed invention in that it does not specifically teach a method of treating metastatic lung cancer by administering sorafenib.
Vazquez teaches sorafenib for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) (abstract).
Vazquez teaches sorafenib as a potent inhibition of c-Raf, b-Raf VEGFR-1/2/3 and PDGFR-beta, wherein in NSCLC, proliferative signaling through the Ras/Raf/MEK/ERK pathway is often activated from K-ras mutations. Sorafenib improves the rate of disease stabilization in patients who had previously been treated with chemotherapy (abstract).
Vazquez teaches the safety profile of this treatment as acceptable, reversible, and manageable without unexpected adverse events (abstract).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select metastatic NSCLC cancer as the cancer and sorafenib as the anticancer agent, in the methods of Fontenille, to arrive at a method of treating metastatic NSCLC cancer by administering a composition comprising sorafenib and hydroflumethiazide. One of ordinary skill in the art would have been motivated to make such selections, with a reasonable expectation of success, because:
-Vazquez teaches sorafenib as inhibiting the Ras/Raf/MEK/ERK pathway and treating metastatic NSCLC,
-Fontenille teaches methods of treating metastatic cancer and teaches hydroflumethiazide as an anti-metastatic agent and/or as a potentiator of an anti-cancer agent, wherein the anti-cancer agent is a chemotherapy agent ([0191]-[0192], [0195], [0197], [0216]), and
-Fontenille teaches liver cancer as a cancer treated by its methods, and teaches sorafenib as an anti-cancer agent in its methods.
As such, an artisan having ordinary skill in the art would have been motivated to make such selections, to predictably arrive at a method of effectively treating metastatic NSCLC by administering hydroflumethiazide and sorafenib, wherein hydroflumethiazide potentiates the effects of sorafenib, and potently treats the metastatic disease to increase overall survival.
Regarding claim 2, the combination of Fontenille and Vazquez teaches sorafenib.
Regarding claim 3, the combination of Fontenille and Vazquez teaches lung cancer.
Regarding claim 4, Fontenille teaches a dosage of 0.1mg/kg to 16mg/kg of the diuretic compounds is taught ([0247]; pg. 23, claim 37), meeting the limitations of this claim.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05.
Regarding claims 5 and 8, Fontenille teaches daily oral administration ([0258]-[0259]; pg. 23, claim 38).
Regarding claim 7, Fontenille teaches tablets, solutions and others as dosage forms ([0260], pg. 23, claim 38).
Claims 1-5 and 7-8 are rendered obvious.
Claims 6 and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over US 2023/0137849 to Fontenille (effectively filed on 02/10/20217, PTO-892 of 06/12/2024) and Vazquez-Estevez (Sorafenib (SOR) in advanced non-small cell lung cancer (NSCLC): A phase II study of patient progress after several lines of treatment, published 2012, PTO-892), as applied to claims 1-5 and 7-8, and further in view of Gurney (BJC, published 2002, PTO-892 of 11/18/2024).
Fontenille and Vazquez are applied to claims 1-5 and 7-8 as discussed in the above rejection and incorporated herein.
While the combination of Fontenille and Vazquez teaches a method of treating metastatic NSCLC cancer by administering hydroflumethiazide and sorafenib, it differs from that of instant claims 6, 9, and 10, in that it does not teach the ratios recited in instant claims 6, 9, and 10.
Fontenille teaches a dosage of 0.1mg/kg to 16mg/kg of the diuretic compounds ([0247]; pg. 23, claim 37).
Vazquez teaches administering 400mg sorafenib, twice a day (abstract).
Gurney teaches how to calculate the dose of chemotherapy. “Body surface area-dosing does not account for the complex processes of cytotoxic drug elimination. This leads to an unpredictable variation in effect. Overdosing is easily recognized but it is possible that unrecognized underdosing is more common and may occur in 30% or more of patients receiving standard regimen. Those patients who are inadvertently underdosed are at risk of significantly reduced anticancer effect. . .The inaccuracy of body surface area-dosing is more than an inconvenience and it is important that methods for more accurate dose calculation are determined, based on the known drug elimination processes for cytotoxic chemotherapy” (abstract). Table 4 details these twelve rules (pg. 1300).
Thus, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to modify the ratio of hydroflumethiazide to sorafenib, in the combined method of Fontenille and Vazquez, to arrive at the instantly claimed ratios. One of ordinary skill in the art would have been motivated to make such modifications, with a reasonable expectation of success, because:
-Fontenille teaches administration of 0.1mg/kg to 16mg/kg hydroflumethiazide and Vazquez teaches administering 400mg sorafenib twice a day,
-Fontenille teaches administration of a 1:1 ratio of diuretic compound to anticancer drug (Figs. 7-8, [0327]-[0328], [0419]-[0420]),
-Gurney teaches that the dose of chemotherapeutic administered is not a set calculation, but is dependent upon different factors, and
-"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP 2144.05(II).
Thus, an ordinary skilled artisan would have been motivated to optimize the amounts and hence the ratio of hydroflumethiazide to sorafenib, to predictably arrive at amounts, and hence a ratio, that optimizes therapeutic efficacy and minimizes side effects, to treat metastatic NSCLC cancer.
Claims 1-10 are rendered obvious.
Response to Arguments
On pg. 5, Remarks, Applicant states that the claims have been amended to delete any reference to liver cancer.
In view of this amendment, the above new prior art rejections are applied to meet the amended claim limitations.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAUREN WELLS/Examiner, Art Unit 1622
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