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 Status
Claim listing filed on March 27, 2026 is pending. Claims 2-4 and 6 are canceled. Claims 13 and 17 are amended. Claims 14 and 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species. Claims 1, 5, 7-13, 15-18, and 21-24 are examined upon their merits.
Withdrawn Claim Rejections
The rejection of Claims 13 and 17 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of Applicant’s amendments. The claims no longer recite the phrase "e.g." or trademarks.
Claim Rejections - 35 USC § 112 (Maintained)
The rejection of Claims 1, 5, 7-13, 15-18, and 21-23 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 is maintained.
Applicant's arguments filed March 27, 2026 have been fully considered but they are not persuasive. Applicant argues that suitable reference levels can be determined using methods known in the art such as standard clinical trial methodology and cites Exhibit A to demonstrate said clinical trial methodology. The protocols of Exhibit A further support that biomarker levels of patients expected to respond to therapy are expected to vary from patient to patient (hence the need for statistical prediction algorithms). MPEP § 2173.05(b).II teaches that in Ex parte Brummer, 12 USPQ2d 1653 (Bd. Pat. App. & Inter. 1989), the Board held that a limitation in a claim to a bicycle that recited "said front and rear wheels so spaced as to give a wheelbase that is between 58 percent and 75 percent of the height of the rider that the bicycle was designed for" was indefinite because the relationship of parts was not based on any known standard for sizing a bicycle to a rider, but on a rider of unspecified build. The metes and bounds of the claim were unclear because they were based on a variable entity (the height of a bicyclist). Similarly, the instant claims are based on a variable entity (the level of biomarker in a subject expected to respond to checkpoint inhibitors without additional intervention). The variability in PD-L1 in subjects expected to respond to checkpoint inhibitors is discussed in detail in the non-final office action filed 11/28/2025 (Shukuya et al. J Thorac Oncol. 2016 and Patel et al. J Immunother Cancer 2019; of record). Even less is understood in the art about levels of IRF2 in a subject expected to respond to checkpoint inhibitors. The argument that the reference levels could be measured by means known in the art is not persuasive in view of the case law. Methods of measuring the height of a bicyclist were clearly understood, but that did not overcome the problem that the claims were directed to a variable entity lacking objective boundaries. The same is true for the instant claims. It is critical to the claimed method to understand the metes and bounds of the reference levels because the reference levels directly dictate what therapies are administered to the subject.
Applicant cites Exxon Research & Eng’g Co. v. United States to argue that “the fact that some experimentation may be necessary to determine the scope of the claims does not render the claims indefinite.” This statement is context-specific. For example, MPEP § 2173.05(b).II teaches that a claim limitation specifying that a certain part of a pediatric wheelchair be "so dimensioned as to be insertable through the space between the doorframe of an automobile and one of the seats" was held to be definite. Orthokinetics, Inc. v. Safety Travel Chairs, Inc., 806 F.2d 1565, 1 USPQ2d 1081 (Fed. Cir. 1986). The court stated that the phrase "so dimensioned" is as accurate as the subject matter permits despite minor experimentation necessary to determine claim scope (i.e. testing the wheelchair by inserting it between the doorframe of an automobile and one of the seats). This is an example where minor experimentation was necessary to determine claim scope, and the claims were rendered definite. Examiner maintains that the instant claims align with the example outlined in the paragraph above (the variable height of a bicyclist in Ex parte Brummer) wherein the claims are indefinite because there is substantial variability in the “reference levels” even if they are determined experimentally. The claims lack objective boundaries and potential infringement could not be enforced.
Claim Rejections - 35 USC § 103 (Maintained)
The rejection of Claims 1, 5, 7-13, and 21-24 under 35 U.S.C. 103 as being unpatentable over Higgs J Clin Oncol 34, 2016 (of record), Wu et al. EMBO J. 2018 (of record), and Liao et al. Cancer Cell March 2019 (of record), in view of Mimura et al. Cancer Sci. 2017 (of record) is maintained.
Applicant argues that Higgs is silent regarding IRF2, and the Office relies on Wu to overcome this deficiency. Applicant argues that Wu fails to credit IRF2 as a factor in controlling PD-L1 expression and specifically cites instant specification page 12 that recites “the role of IRF2 on PD-L1 expression had not been directly examined” in Wu. Examiner maintains that Wu directly measures the relationship between IRF2 and PD-L1 expression in Fig. 5B (of record and as shown below). The Fig. 5B caption recites “knockdown IRF2 restores PD-L1 expression.” This experimental data supports the teachings of Wu that IRF2 is a transcriptional repressor of PD-L1 (abstract and Fig. 7E; of record). Note, the experiment of Wu Fig. 5B is very similar to instant specification Example 3 that teaches IRF2-KO cells expressing higher levels of PD-L1 mRNA as compared to wild-type controls. Therefore, Wu does effectively establish that IRF2 represses PD-L1 expression.
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Applicant argues that Liao does not teach that IRF2 expression is positively correlated with IFNγ expression and cites Liao page 563 that “points to other mechanisms.” Examiner asserts that this quotation of Liao has been taken out of context. This section of Liao (titled “KRAS* Suppresses Interferon Responses in CRC”) teaches that KRAS* tumors showed downregulation of IFNγ and that IRF2 deletion is mutually exclusive with KRAS mutation. This teaching shows a correlation where IFNγ is downregulated when IRF2 is deleted. Liao goes on to demonstrate that “IPA analysis revealed that IFN-a/γ signatures were upregulated in IRF2-overexpressed iKAP cells compared with iKAP cells (Figure 3C)” (of record). Based on these teachings of Liao (and those of record) and without evidence to the contrary, Examiner maintains that one of ordinary skill would understand that IRF2 and IFNγ are positively correlated because overexpression of IRF2 upregulated IFNγ signatures. One of ordinary skill would mechanistically understand the reverse to be true as well (i.e. if overexpression of IRF2 causes IFNγ signature upregulation, then under expression of IRF2 would cause IFNγ signature downregulation).
Applicant argues that a POSA would not have had a reasonable expectation of success at arriving at the claimed invention and cites specification page 38 that “IRF2 is constitutively expressed and minimally affected by interferon induction.” Examiner believes this quotation is taken out of context. The cited paragraph (bottom of page 38) states that whereas IRF2 is constitutively expressed and minimally affected by interferon induction, IRF1 is significantly upregulated in response to interferon, and such upregulation of IRF1 causes IRF1 to compete with IRF2 for binding to the TAP2, ERAP1, and PD-L1 promoters. This section of the specification is comparing the balance of IRF1 and IRF2 which is not applicable to the argument of a POSA having a reasonable expectation of success at arriving at the claimed invention from the cited references. Note, MPEP § 2144.IV teaches that Examiner can rely on a different rational/motivation to establish a prima facie case of obviousness than is used by the Applicant. Applicant’s arguments are not persuasive, and the rejection is maintained.
The rejection of Claims 15-18 under 35 U.S.C. 103 as being unpatentable over Higgs J Clin Oncol 34, 2016 (of record), Wu et al. EMBO J. 2018 (of record), Liao et al. Cancer Cell March 2019 (of record), and Mimura et al. Cancer Sci. 2017 (of record) as applied to Claims 1, 5, 7-13, and 21-24 above, and further in view of Lai et al, Oncogene. 2018 (of record) and Hicks et al, Oncoimmunology. 2018 (of record) is maintained.
Applicant's arguments filed March 27, 2026 have been fully considered but they are not persuasive. Applicant argues that Lai and Hicks do not remedy the deficiencies of Higgs, Wu, Liao, and Mimura. The supposed deficiencies of Higgs, Wu, Liao, and Mimura are addressed above, and the rejection is maintained.
Conclusion
No claim is allowed.
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 SARAH COOPER PATTERSON whose telephone number is (703)756-1991. The examiner can normally be reached Monday - Friday 8:00am - 5:00pm EST.
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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