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 .
Status of Application/Amendment/Claims
This Office action is in response to the communications filed on March 10, 2026.
It is noted that claim numbers “20-24” do not have a claim status. The examiner will consider claims 20-24 as being cancelled.
Currently, claims 1, 3, 11, 13, 17-19, 25, 28, 31, and 37-40 are pending and under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3, 11, 13, 17-19, 25, 28, 31, and 37-40 are rejected under 35 U.S.C. 103 as being unpatentable over Cordoba et al. in view of Peddareddigari et al., June et al., Chen et al., and Kloss et al. (all same references of record) further in view of Ols et al. (WO 2020/123716 A1).
The teachings of each of Cordoba, Peddareddigari, June, Chen, and Kloss are described in the last Office action, which is fully incorporated by reference herein.
The aforementioned references do not teach local expression of IL-12 leads to epitope spreading in the tumor.
Ols teaches, “Local delivery of IL12 to the tumor microenvironment promotes tumor regression in several tumor models.” (emphasis added). See paragraph 0326.
Ols teaches that “local production of Flexi IL12” can be “used to improve the efficacy of the CARS, especially in solid tumor settings, by providing a controlled local signal for tumor microenvironment remodeling and epitope spreading.” (emphasis added). See paragraph 0607.
It would have been obvious to one of ordinary skill in the art before the effective filing date to reasonably expect local delivery of IL-12 to a solid tumor expressing a CAR would promote epitope spreading, thereby improve the efficacy of the CAR and tumor regression in a subject when practicing the method that was rendered prima facie obvious in the last Office action because local delivery of IL-12 to solid tumor microenvironment was not only known to promote tumor regression but also known to promote spreading and tumor microenvironment remodeling in solid tumor expressing the CARS, thereby improving the efficacy of the CARS as taught by Ols. Accordingly, claims 1, 3, 11, 13, 17-19, 25, 28, 31, and 37-40 taken as a whole would have been prima facie obvious before the effective filing date.
Response to Arguments
Applicant's arguments filed on March 10, 2026 have been fully considered but they are not persuasive. Applicant argues that the rejected claims are not obvious because Cordoba does not teach epitope spreading. In response, it is noted that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As clearly set forth in the last Office action, it was art-recognized knowledge that “epitope spreading” is induced as part of “anti-tumor immune response” as taught by June. Furthermore, as currently amended, the newly added limitation requiring the association between local delivery of IL-12 and epitope spreading was already known in the prior art as evidenced by the teachings of Ols as explained in the rejection above.
Applicant argues that Cordoba does not teach using the claimed cells “to treat heterogeneous tumours”. In response, it is noted that none of the rejected claims require treatment of “heterogeneous tumours”. The claims merely recite that “the expression of which target antigen on the solid cancer is heterogenous”, which appears to mean that the target antigen on a solid cancer being treated in the subject has a “heterogeneous” expression. That is, the word “heterogeneous” pertains to the “target antigen” expression in a solid tumor, not “tumours”, wherein heterogeneous target antigen expression in a solid tumor is inherently taught by Cordoba, who discloses using the disclosed CAR-T cell technology for treatment of solid tumours having “varying and very low levels of target antigen”. See page 19. Now, even if the claims were to expressly recite and require treatment of “heterogeneous tumours”, such limitation would have been deemed prima facie obvious because of the art-recognized knowledge that CAR therapy induces “epitope spreading” as part of “anti-tumor immune response” as taught by June in light of the instant specification’s disclosure that “[E]pitope spreading is important for the treatment of a heterogeneous tumour”. See page 67.
Applicant argues that Example 3 of the instant specification provides experimental results pertaining to epitope spreading induced by “ultra-low IL-12 expressing CAR-T cells”. In response, it is noted that “ultra-low” expression of IL-12 in CAR-T cells is not a claimed feature. As such, applicant’s arguments are irrelevant to showing the asserted nonobviousness of the claimed subject matter.
Applicant argues that paragraph 0985 of June suggests that the “mRNA anti-mesothelin CARs” are responsible for epitope spreading. In response, it is noted that the claims as previously presented recited “wherein the cell induces epitope spreading in an anti-tumour immune response”, wherein “the cell” broadly encompassed a cell comprising IL-12 and CAR, wherein “CAR” itself was suggested to show “anti-tumor immune response” that is “consistent with epitope spreading” as disclosed in paragraph 0985 of June. Now, applicant’s attention is directed to the fact that the newly added limitation pertaining to the association between local delivery of IL-12 and epitope spreading is not invented/discovered by the instant co-inventors as expressly evidenced by the teachings of Ols as explained in the rejection above.
In view of the foregoing, applicant’s arguments are not found persuasive.
Double Patenting
The text of the judicially created doctrine not included in this action can be found in a prior Office action.
Claims 31 and 37-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,959,084 B2 in view of Cordoba et al., Chen et al., and Peddareddigari et al. (all same references of record) further in view of Ols et al. (WO 2020/123716 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims overlap in scope with and would have been obvious over the ‘084 patent claims for the reasons stated in the last Office action, further in view of the art-recognized knowledge disclosed by Ols as explained in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 1, 3, 11, 13, 17-19, 25, 28, 31, and 37-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 12,269,860 B2 in view of Cordoba et al., Chen et al., and Peddareddigari et al. (all same references of record) further in view of Ols et al. (WO 2020/123716 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims overlap in scope with and would have been obvious over the ‘860 patent claims for the reasons stated in the last Office action, further in view of the art-recognized knowledge disclosed by Ols as explained in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 31 and 37-40 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 12,304,942 B2 in view of Cordoba et al., Chen et al., and Peddareddigari et al. (all same references of record) further in view of Ols et al. (WO 2020/123716 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘942 patent claims for the reasons stated in the last Office action, further in view of the art-recognized knowledge disclosed by Ols as explained in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 1, 3, 11, 13, 17-19, 25, 28, 31, and 37-40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-33 of copending Application No. 18/590,698 in view of Peddareddigari et al., June et al., Chen et al., and Kloss et al. (all same references of record) further in view of Ols et al. (WO 2020/123716 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims overlap in scope with and would have been obvious over the ‘698 claims for the reasons stated in the last Office action, further in view of the art-recognized knowledge disclosed by Ols as explained in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Response to Arguments
Applicant's arguments filed on March 10, 2026 have been fully considered but they are not persuasive. Applicant argues that the amendments address all double patenting rejections. Applicant’s argument is found moot in view of the teachings of Ols cited in all double patenting rejections.
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 DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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