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 .
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.
Current Status of 18/548,678
This Office Action is responsive to the amended claims of 22 April 2026.
Claims 1-3, 7-9, 14-15, 18-19, 21-22, 24-25, 32-35, and 37 are currently pending.
Priority
Applicant’s claim for the benefit of the prior-filed patent applications PCT/US2022/018663 (filed 3 March 2022) and 63/156,179 (filed 3 March 2021) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
Response to Amendments
The objections to the drawings, present in the previous office action, are hereby withdrawn due to the replacement drawing sheets.
The objections to the specification, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.
The objections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.
The 35 U.S.C. 112 rejections to the claims, present in the previous office action, are partially withdrawn herein due to Applicant’s amendments and arguments.
The 35 U.S.C. 103 rejections to the claims, present in the previous office action, are maintained herein, although they have been altered as necessitated by Applicant’s amendments.
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 21-22 and 24-25 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 21 depends upon claim 19 and recites “a low expression level of GPX4”. This renders claim 21 indefinite, because it is not clear whether this refers to the same low expression level of GPX4 described in section (b) of claim 19. Applicant may choose to amend the phrase “a low expression level of GPX4” within claim 21 to “the low expression level of GPX4”.
Claim 22 depends upon claim 19 and recites “a high expression level of GPX4”. This renders claim 22 indefinite, because it is not clear whether this refers to the same high expression level of GPX4 described in section (c) of claim 19. Applicant may choose to amend the phrase “a high expression level of GPX4” within claim 22 to “the high expression level of GPX4”.
Claim 24, sections (a) and (b), each recite “a control sample”; however, “a control sample” has already been established within the first portion of the same claim. This renders claims 24-25 indefinite, because it is not clear if this is the same control sample referred to above or a different control sample. Applicant may choose to amend the phrase “a control sample” within sections (a) and (b) to “the control sample”.
Response to Arguments
Applicant's arguments received 22 April 2026 have been fully considered.
Applicant argues that sections (b) and (c) of claim 19 should be allowed to each contain the phrase “a control sample”, because they are referred to only in the alternative. The Examiner thinks that reasoning is acceptable. Applicant tries to make a similar argument for claim 24, but this is not acceptable, because “a control sample” is established outside of sections (a) and (b). Applicant tries to make a similar argument for claims 21 and 22, but there is only one “low expression level” in the parent claim, and one “high expression level”. The argument related to claim 19 does not work therein.
Applicant argues that KUMAR does not provide any data supporting the use of a DHODH inhibitor for the treatment of renal cell carcinoma. Applicant argues that one of ordinary skill in the art; therefore, would not have had any reasonable expectation of success.
KUMAR directly teaches the administration of brequinar, a DHODH inhibitor (claims 12-13 therein), for the treatment of renal cell carcinoma (claim 15). One of ordinary skill in the art, reading the disclosure of a patent application, would have had a reasonable expectation of success when performing the activities directly taught by that patent application.
Applicant argues that one of ordinary skill in the art would have had no reason to combine KUMAR and YANG, specifically because the references don’t direct the artisan to consider GPX4 expression in the context of treatment with a DHODH inhibitor. Applicant appears to argue that KUMAR and YANG have nothing in common with each other.
It would have been natural for one of ordinary skill in the art to connect KUMAR and YANG, because both references teach the use of small molecule therapeutics to combat a rather specific type of cancer, being renal cell carcinoma. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06.
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.
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.
Claims 1-3, 7-9, 14-15, 18-19, 21-22, 24-25, 32-35, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over:
KUMAR (WO 2020/242773 A1, International Publication Date 3 December 2020)
in view of:
YANG (Cited by Applicant in IDS of 2 April 2024, Yang, W.S.; SriRamaratnam, R.; Welsch, M.E.; et al. “Regulation of Ferroptotic Cancer Cell Death by GPX4” Cell 156, 317–331, January 16, 2014).
Regarding claims 1-3 and 7-9: KUMAR generally teaches the use of a DHODH inhibitor to treat cancer through a process described as causing differentiation of myeloid-derived suppressor cells (abstract). KUMAR specifically teaches a method of treating cancer in a subject through the administration of brequinar, being a DHODH inhibitor (claims 12 and 13). KUMAR teaches that this method can be used for the treatment of renal cell carcinoma (claim 15).
Instant claim 1 contains a limitation that states the method is to be used “wherein the cancer has an altered glutathione peroxidase 4 (GPX4) expression as compared to a control sample”. KUMAR teaches the administration of brequinar, a DHODH inhibitor, for the treatment of renal cell carcinoma, and does not mention GPX4 expression. One of ordinary skill in the art would have read the teachings of KUMAR and would have, without any specific teaching regarding GPX4, thought it obvious to apply the method of KUMAR to renal cell carcinoma with all expression levels of GPX4.
YANG teaches determination of GPX4 expression within renal cell carcinoma cells using western blotting (Pg. 328, Right Col.), so the concept of altered GPX4 expression levels in the cancer type discussed by KUMAR was known in the literature before the publication of KUMAR.
By way of analogy, a physician familiar with treating all headaches with compound A, upon hearing that headaches have now been classified into as A- and B-type headaches, would not suddenly have found it novel to treat A-type headaches with compound A. However, there are arguments against this logic. For example, if Applicant can show that the high and/or low expression levels of GPX4 are not commonly encountered in a claimed cancer type, this could aid the argument for nonobviousness.
Regarding claims 14-15, 21-22, and 33: KUMAR does not teach the coadministration of a DHODH inhibitor and a ferroptosis inducer.
Figure 4 of YANG teaches that knockdown of GPX4 increased the lethality of (1S, 3R)-RSL3 against HT-1080 cells (a fibrosarcoma cell line). Figure 4 of YANG also teaches that overexpression of GPX4 in the same HT-1080 cell line decreased the anti-cancer lethality of (1S, 3R)-RSL3, although the (1S, 3R)-RSL3 compound was still lethal at a 10-fold higher concentration. YANG teaches that erastin was found to be particularly effective against renal cell carcinoma cell lines (Pg. 328 Right Col., Fig. 7F). YANG teaches that renal cell carcinoma cells were separately treated with erastin and the RSL3 compound, and both compounds increased the presence of reactive oxygen species (Fig. 7 caption Pg. 330), indicating RSL3-induced ferroptotic cell death (Pg. 320, 5th paragraph).
Taken together, YANG teaches that (1S, 3R)-RSL3 was an effective anti-cancer compound for treating cells with either low or high expression of GPX4, and (1S, 3R)-RSL3 was effective against fibrosarcoma cells and renal cell carcinoma cells.
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to combine the method of treating renal cell carcinoma in a subject, through administration of the DHODH inhibitor brequinar, (taught by KUMAR) with the anti-renal cell carcinoma compound taught by YANG, being (1S, 3R)-RSL3. The artisan would have expected success in this combination, because both compounds are taught to be effective against the same type of cancer. This is an example of combining equivalent therapeutic agents known to be useful for the same purpose. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06.
Regarding claim 18: KUMAR teaches that the subject of the method therein may be a human (Pg. 10, Ln. 29-31).
Regarding claims 19, 24-25, 32, and 34: YANG teaches determination of the GPX4 expression level, via mRNA and protein concentration, from a sample of cells (Fig. 4A-4B). YANG teaches determination of GPX4 expression within renal cell carcinoma cells using western blotting (Pg. 328, Right Col.). YANG also teaches that overexpression of GPX4 decreases the anti-cancer effect of (1S, 3R)-RSL3 (Fig. 4). It would have been obvious to one of ordinary skill in the art to apply the same type of GPX4 expression determination to an intratumoral renal cell carcinoma sample from a patient to determine the expected efficacy of the (1S, 3R)-RSL3 and brequinar combination therapy being applied.
Regarding claim 35: Claim 16 of KUMAR teaches additionally providing the subject with “an agent that inhibits immunosuppression in the subject”.
Regarding claim 37: It would have been obvious to one of ordinary skill in the art to provide the (1S, 3R)-RSL3 and brequinar combination therapy, rendered obvious by KUMAR and YANG, in the form of a single pharmaceutical composition, for the purpose of increasing patient compliance with a dosing regimen.
Conclusion
No claims are currently allowable.
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 JOHN D MCANANY whose telephone number is (571)270-0850. The examiner can normally be reached 8:30 AM - 5:30 PM.
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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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