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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on November 26, 2025 has been entered. No claim amendments were submitted with this reply.
Claims 9, 13, 16-18, 20-22, 25-32 and 42-43 are pending in the application and under examination before the Office.
The rejections of record can be found in the previous Office action, dated August 28, 2025.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 26, 2025 was filed after the mailing date of the first Office action on the merits on December 23, 2022. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
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 9, 13, 16-17, 20-22, 29-30, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Clinical Trial NCT03491683 in view of Yan (WO2018064588A2), and Weiner (US20150328298A1).
Clinical trial NCT03491683 teaches a method of treating glioblastoma, comprising administering a combination of three separate DNA plasmids expressing Wilms tumor gene 1 (WT-1) antigen, prostate-specific membrane antigen (PSMA) and human telomerase reverse transcriptase (hTERT) genes, and cemiplimab, an antibody to programmed death-1 (PD-1) protein (pages 5-6). Clinical trial NCT03491683 further teaches that the subject may have a methylated 06-MGMT promoter (pages 5-6).
Clinical trial NCT03491683 further teaches administering a DNA plasmid for expression of human interleukin-12 (IL-12) (pages 5-6).
Clinical trial NCTO3491683 further teaches radiation therapy for three weeks (page 5), which is pertinent to claim 13.
Clinical trial NCT03491683 further teaches that cemiplimab is administered intravenously at a dose of 350 milligrams every three weeks (page 6), which is pertinent to claims 16-17.
Clinical trial NCT03491683 further teaches dosages of 3 milligrams of each of the plasmids comprising WT1, PSMA, and hTERT, and 1 milligram of the plasmid encoding IL-12 (page 5), which is pertinent to claim 20.
Clinical trial NCT03491683 further teaches that the dosages are administered by intramuscular injection followed by electroporation every three weeks for four doses, and then every nine weeks (page 5), which is pertinent to claims 21 and 22.
Clinical trial NCT03491683 further teaches administration of temozolomide daily for 21 days at a dosage of 75 milligrams per square meter (page 5), which is pertinent to claims 29 and 30.
However, Clinical trial NCT03491683 does not teach the claimed DNA sequences.
Yan teaches an immunogenic composition comprising plasmids encoding TERT, WT-1, and PSMA (page 178, lines 23-32). Yan also teaches that the application of this composition reduces tumor volume and increases survival (Figure 28).
Yan further teaches that the above composition is useful in treating glioblastoma (page 57, lines 20-24).
Yan further teaches the hTERT antigen encoded by SEQ ID NO: 19, and the PSMA antigen of SEQ ID NO: 29 as SEQ ID NOs: 45 and 65 of Yan, respectively; furthermore, the plasmids of Yan have the same name as the plasmids of the instant invention (Example 15, pages 206-208). The differences between the claimed sequences and the sequences of Yan are the presence of two stop codons (TGA TAA) added to the 3’ end of the sequences.
Yan also teaches that nucleotide sequences may be operably linked to two stop codons to increase the efficiency of translational termination (page 20, lines 6-25).
Wiener teaches a sequence that encodes WT-1 with SEQ ID NO: 1, which completely encompasses the claimed sequence of SEQ ID NO: 27. Wiener also teaches that WT-1 is implicated in glioblastoma (para. 0005), and that a vaccine of a nucleic acid encoding WT-1 is useful to treat cancer (para. 0013 and 0040).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Clinical trial NCT03491683, Yan, and Weiner to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Clinical trial NCT03491683 and Yan are concerned with combination therapies of hTERT, WT-1, and PSMA for the treatment of glioblastoma. Starting from the treatment and schedule of Clinical trial NCT03491683, a skilled artisan could apply the sequences taught by Yan and Weiner in order to arrive at the claimed invention, with each component performing its known, usual function, and the combination would have yielded nothing more than predictable results.
Applicant argues that the references do not present any evidence of the efficacy of the claimed combination in treating glioblastoma characterized by a methylated 06-methylguanine methyltransferase (MGMT) gene promoter, especially since Yan relies upon trials with a lung cancer line. Applicant asserts that treatment of glioblastoma is highly unpredictable, and in view of the lack of data, one of ordinary skill would not have any reasonable expectation of success.
Applicant's arguments have been considered fully but are not found to be persuasive.
A reasonable expectation of success can be implicitly shown via the prior art teachings or as part of the obviousness analysis. Elekta Ltd. v. ZAP Surgical Sys., Inc., 81 F.4th 1368, 1376-77, 2023 USPQ2d 1100 (Fed. Cir. 2023).
Conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")). MPEP 2143.02(I).
As stated above, Clinical trial NCT03491683 is explicit in a method of treating glioblastoma, comprising administering a combination of three separate DNA plasmids expressing Wilms tumor gene 1 (WT-1) antigen, prostate-specific membrane antigen (PSMA) and human telomerase reverse transcriptase (hTERT) genes, and cemiplimab, an antibody to programmed death-1 (PD-1) protein (pages 5-6). Clinical trial NCT03491683 further teaches that the subject may have a methylated MGMT promoter (pages 5-6).
Additionally, contrary to Applicant's assertion, Yan teaches that a composition comprising plasmids encoding TERT, WT-1, and PSMA is useful in treating glioblastoma (page 57, lines 20-24). Yan also states that the enumerated examples disclosed are illustrative only and not intended to be limiting (page 11, lines 27-28).
The studies by Fekete and Lim, cited by Applicant in their reply, do not rely on the claimed combination of treatments, they instead teach only that radiation therapy with temozolomide (Fekete) and blockade of PD-1 (Lim) were not successful. These teachings cannot extrapolate that all treatments for glioblastoma will be unsuccessful.
The teachings of Clinical trial NCT03491683 clearly show that the authors of this study--who are also Inovio Pharmaceuticals, one of the listed Applicants in this application--had at least some expectation of success in using the claimed combination to treat glioblastoma with a methylated MGMT gene promoter. It is further noted that Inovio Pharmaceuticals is also the assignee of record in Yan, and Yan shares an inventor with the instant application. It is extremely unlikely that Applicant would pursue a clinical trial for a treatment that they believed had no reasonable expectation of success.
Given the explicit teachings of both Clinical trial NCT03491683 and Yan, it is likely that there was at least a reasonable expectation of success in using the claimed combination of treatments to treat glioblastoma.
This rejection is therefore maintained.
Claims 18 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Clinical trial NCT03491683, Yan, and Weiner as applied to claim 12 above, and further in view of Felber (US20090137005A1).
Applicant argues that Felber does not remedy the alleged deficiencies of Clinical trial NCT03491683, Yan, and Weiner. This is not found persuasive, for reasons described supra.
This rejection is therefore maintained.
Claims 25-28, 31, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Clinical trial NCT03491683, Yan and Weiner as applied to claim 13 above, and further in view of Stupp (N Engl J Med. 2005 Mar 10;352(10):987-96, cited in IDS).
Applicant argues that Stupp does not remedy the alleged deficiencies of Clinical trial NCT03491683, Yan, and Weiner. This is not found persuasive, for reasons described supra.
This rejection is therefore maintained.
Conclusion
No claim is allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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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/PETER JOHANSEN/Examiner, Art Unit 1644