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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4/27/2026 has been entered.
Claims 18 and 21 are pending. Claims 1-17 and 19-20have been cancelled.
Based upon he elected species of TNFRSF18 made in the reply filed 6/02/2025, Claim 21 is withdrawn as drawn to a nonelected species.
The following rejections are newly applied.
This action is NONFINAL.
Withdrawn Rejections
The 35 USC 112b made in the previous office action is withdrawn based upon the cancellation of the claims.
The 35 USC 102 rejection made in the previous office action is withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 18 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claim is drawn to collecting any biologic sample comprising mRNA from a patient having a brain tumor, measuring an expression level of a TNFRSF18 mRNA is increased and administering an immune cell therapy to the patient determined to have a high responsiveness.
The instant specification does not provide guidance as to the critical structures needed to determine which of these species would functionally provide responsiveness of any immune cell therapy.
The specification states using an immune checkpoint inhibitor which induces activation of T cells by suppressing binding of PD-L1 (p. 1). The specification does not limit immune cell therapy to this but rather states that immune cell therapy may be induces activation of T cells by suppressing binding of PD-L1, NK cell therapy, T cell therapy, CAR-immune, DC vaccine, CTL therapy, anti-PD-L1, anti-PD1 (p. 4). The specification appears to provide measurements with NK cell immunotherapy (p. 26). However, the specification does not describe administering any immune cell therapy in patients with increased TNFRSF18 expression. In particular it is not clear if there is an association between this increased expression and any of the encompassed therapies.
Accordingly, the specification has not provided the critical elements needed in the structure to predictive functionally. Therefore the specification lacks written description of any subject representative of the broadly claimed genus.
In analysis of the claims for compliance with the written description requirement of 35 U.S.C. 112, first paragraph, the written description guidelines note regarding genus/species situations that “Satisfactory disclosure of a ``representative number'' depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed.” (See: 'Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.)
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.
Claim 18 is 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 18 is indefinite over the phrase “the patient determined to have a high responsiveness thereto”. It is not clear which patients are determined to have a high responsiveness, It is not clear if the claim is intended to referee to the patients that have increased expression or some other determination. Further, the term “high responsiveness” in claim 18 is a relative term which renders the claim indefinite. The term “high responsiveness” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In particular it is not clear which patients would be considered responsive as there is no comparison.
Claim Rejections - 35 USC § 103
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.
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.
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.
Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sade-Feldman et al. (WO2018/209324 November 15, 2018 previously cited) in view of Hamilton et al. (Cancer Vol 119 August 2013 pgs 2737-2746)..
With regard to claim 18, Sade-Feldman et al. teaches a method of mRNA expression of TNFRSF18 (para 11-12 and 108). As such Sade-Feldman et al. teaches collecting a sample and measuring mRNA expression of TNFRSF18. Sade-Feldman et al. teaches providing conventional therapy (para 28)
Sade-Feldman et al. teaches that a patient has a higher response to immune therapy with expression of mRNA as compared to a control (para 9-11, 14, 28-29).
Although Sade-Feldman et al. does not specifically teach brain tumor examples, Sade-Feldman et al. teaches that the sample can be brain tumors (para 166 and 242).
With regard to claim 18, Hamilton teaches that mRNA from melanoma patients can be detected in brain tumors (p. 2740-2742).
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Sade-Feldman et al. to detect expression levels of brain tumor samples as is suggested by Sade Feldman et al. The ordinary artisan would be motivated as Hamilton teaches mRNA from metastatic melanoma patients is detectable in brain tumors. As such it would be obvious to one of ordinary skill in the art to modify the method of Sade-Feldman et al to further screen mRNA levels in patients having a brain tumor.
Response to arguments
The reply traverses the rejection. A summary of the arguetmsn is provided below with response to arguments following.
The reply asserts that Sade-Feldman et al. is directed to melanoma cancer samples which is distinct from brain cancer, even if Sade-Feldman suggests brain cancer (p. 5). The reply asserts that TNFRSF18 is considered a non-responder marker in melanoma (p. 5-6).
These arguetmsn have been reviewed but have not been found persuasive.
Although Sade-Feldman et al. does not specifically teach brain tumor examples, Sade-Feldman et al. teaches that the sample can be brain tumors (para 166 and 242). Hamilton teaches that mRNA from melanoma patients can be detected in brain tumors (p. 2740-2742). Furthermore the claims do not require that the therapy is administered to a patient with an increased expression level, rather the claims are drawn to “administering an immune cell therapy to the determined to have high responsiveness”. As there is no correlation to expression and no clear indication of “high responsiveness” the claims are drawn to treating any patient that is within the population of treating.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Cheng (Winston) Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682
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