DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8-5-2026 has been entered.
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 .
Claims 15, 18-20 and 22-26 are pending and under examination.
The text of Title 35 of the U.S. Code not reiterated herein can be found in the previous office action.
Rejections Maintained
Claims 15, 18-20 and 22-26 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement for reasons set forth for claims 15-26 in the Office actions mailed 1-12-2026, 5-5-2026, 7-9-2026 and herein.
Applicants’ arguments have been considered but are not persuasive. Applicant has presented a claim that indicates administering to a subject having differentiated thyroid cancer an immune cell comprising a chimeric antigen receptor (CAR) and that the claim does not state therapeutic effect and teaches how to make and administer the agent by various means is enabled. Applicants review the pages of the specification which provide specific guidance on how the agent is administered. The purpose of administration, whether explicitly called out in the claims is described in the specification for “various methods, such as treatment methods, or compositions” (page 1, lines 26-30). The specification is replete with statements that the administration is for treatment of cancer, the effective means is targeted killing of thyroid cancers expressing thyroid specific hormone receptor (THSR) (see page 3, lines 14-25). Applicant argues that the specification states that the in vitro data of killing THSR expressing cancer cells, provides evidence of correlation with in vivo efficacy for treatment or killing of THSR expressing cancer cells and that the Office has not provide any evidence that contradicts the expectation or the correlation. This is not persuasive as the Office has provided evidence to the reason to doubt the assertion of the “expected” outcome stated in the specification. This is because the cell culture environment does not reflect the in vivo environment for differentiated thyroid cancer. Tumor cell lines in vitro are easily accessible by CAR-Tcells, whereas differentiated thyroid cancer is well established in the art to be a solid tumor(s) and not easily accessible by cells. Thus, the barriers to treatment of solid tumors by CAR-Tcells presented in peer reviewed publications are directly relevant to the claimed invention. Applicant’s statements of in vitro to in vivo correlation for solid tumors using CAR-Tcells or for any other immune cell expressing the recited CAR antigen had not been realized at the time of the effective filing date of this application (4/29/2016) for differentiated thyroid cancer. The Office has appropriately cited evidence which is reason to doubt the objective truth of these statements contained in Applicant’s specification. (In re Marzocchi and Horton, 169 USPQ 367 (CCPA 1971)). Applicant argues that clinical efficacy is not required for enablement. Applicant’s specification provides that administration provides for “treatment” and/or cell killing. No in vivo cell killing has been demonstrated. The Office is not required to provide a reference to specifically state that the claimed invention will not work in order to establish that the skilled artisan would have reason to doubt the claims of the specification. The art establishes the barriers and the reasons to doubt that the CAR T cells would be effective in killing TSHR expressing differentiated thyroid cancer cells in vivo given that they are a solid tumor type. While FDA efficacy results are not required, there must be a reasonable correlation between in vitro and in vivo results, and the art establishes the difficulties in accessing and providing a functional CAR-T cell in a tumor environment. Unlike hematological malignancies, where CAR-T have found great success, the same is not true for solid tumors. The solid tumor cells are not accessible like hematological malignancies. Killing cells in vitro where they are clearly accessible to the CAR-Tcells does not represent the tumor environment. As such, Example 1 of the specification does not provide for the ability of the CAR-Tcells to kill tumor cells in vivo where they are found in a solid tumor and not freely accessible as in the cell culture environment.
For all the reasons of record, the claims are not enabled for administration of a TSHR CAR immune cell to a subject having differentiated thyroid cancer for either disclosed purpose in the specification (cell killing or therapy).
Status of Claims
All claims stand rejected.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Patricia Duffy whose telephone number is (571)272-0855. The examiner can normally be reached 8:00 am - 4 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Patricia Duffy/Primary Examiner, Art Unit 1645
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