DETAILED ACTION
Applicant’s amendment and Arguments/Remarks received on 09 September 2025 have been entered. Claims 1-20 were previously pending in the application. Claims 2 and 19 have been cancelled. Claims 1, 3-18, and 20 are currently pending in the application. Claims 1, 16, 17, and 18 are independent claims. The following election of species remains in effect in the instant application:
4)c. costimulatory factor: OX40.
Claims 4-7 and 11-12 remain withdrawn from consideration as being directed to a nonelected species. Claims 1, 3, 8-10, 13-18, and 20 are currently pending and under examination in the instant application. An action on the merits follows.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US20/24674, filed 25 March 2020, which claims priority to U.S. provisional Application No. 62/823,215, filed 25 March 2019.
Thus, the earliest possible priority for the instant application is 25 March 2019.
Information Disclosure Statement
The information disclosure statement filed 30 May 2025 has been considered by the Examiner. Examiner notes the filing of IDS Size Fee assertions for the IDS filed 30 May 2025, as required under 37 CFR 1.98, indicating that no fee is required under 37 CFR 1.17(v) at this time.
Specification
The objection to the specification of the disclosure for use of the terms “Megalign” and “DNASTAR” on page 10 line 24, is withdrawn in view of the amendment to the specification adding the proper symbol indicating use in commerce.
Claim Objections
The objection to amended independent claim 18 for reciting the abbreviation “UTR” in line 3 without first writing out the term for which “UTR” is an abbreviation is withdrawn in view of the amendment to claim 18 writing out “3’ untranslated region (3’ UTR)”.
Claim Rejections - 35 USC § 112(b)
The rejection of cancelled and amended claims 2, 10, and 19 under 35 U.S.C. 112(b) as failing to particularly point out and distinctly claim the subject matter which the inventor(s) regards as the invention for reciting a sequence which is “selected from the group comprising …. or …”, such that the group is comprising recited sequences which are listed in the alternative is withdrawn in view of Applicant’s amendments to the claims such that claims 2 and 19 have been cancelled and claim 19 now recites, “selected from the group consisting of … and …”.
The rejection of amended independent claim 18 under 35 U.S.C. 112(b) as failing to particularly point out and distinctly claim the subject matter which the inventor(s) regards as the invention for reciting “a method of increasing protein expression”, which comprises introducing an engineered mRNA into a cell, wherein the mRNA comprises an RPS27A 5’UTR, a heterologous nucleic acid, and an RPS27A 3’ UTR, is withdrawn in view of Applicant’s amendments to the claims such that amended independent claim 18 no longer recites “of increasing protein expression”.
**The following new rejection is necessitated by amendments to the claims.**
Amended, previously presented, and original claims 1, 3, 8-10, 13-18, and 20 are 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. Claims 3, 8-10, 13-17, and 20 are included in this rejection due to their dependence on or encompassing of claim 1 or 18.
Amended independent claims 1 and 18 each now recite, “wherein the engineered RPS27A 5’UTR sequence comprises SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84” in lines 6-7 and 8-9, respectively, which has multiple issues of indefiniteness.
Firstly, there is insufficient antecedent basis for “the engineered RPS27A 5’UTR sequence” in the claim. Neither claim 1 nor claim 18 have any prior recitation of an engineered RPS27A 5’ UTR sequence.
Secondly, “comprises SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84” is indefinite because mRNAs can comprise mRNA sequences, but not sequence identifiers themselves. Additionally, to the extent that “comprises SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84” is meant to encompass comprising sequences according to SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84, it is further unclear whether the engineered RPS27A 5’UTR sequence is meant to comprise the full length sequence of SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84 or whether the engineered RPS27A 5’UTR sequence is meant to comprise a sequence according to SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84 such that the engineered RPS27A 5’UTR sequence may comprise any fragments of SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84.
As such, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 112(a)
The rejection of amended, cancelled, and previously presented claims 18-20 under 35 U.S.C. 112(a) for being enabling for
a method of increasing protein expression of a target protein encoded by a heterologous nucleic acid sequence comprised within an engineered mRNA, wherein the mRNA comprises a first nucleic acid sequence comprising an RPS27A 5’ UTR sequence or an engineered 5’ UTR sequence, a second nucleic acid sequence comprising a heterologous nucleic acid sequence encoding a target protein, and a third nucleic acid sequence comprising an RPS27A 3’ UTR sequence,
does not reasonably provide enablement for
a method of increasing protein expression comprising the steps of introducing into a cell an engineered mRNA, wherein the mRNA comprises a first nucleic acid sequence comprising an RPS27A 5’ UTR sequence or an engineered 5’ UTR sequence, a second nucleic acid sequence comprising any heterologous nucleic acid sequence, and a third nucleic acid sequence comprising an RPS27A 3’ UTR sequence,
is withdrawn in view of Applicant’s amendments to the claims such that claim 18 no longer recites “of increasing protein expression” in line 1.
Claim Rejections - 35 USC § 103
The rejection of amended, previously presented, original, and cancelled claims 1-3, 8-10, 13-20 under 35 U.S.C. 103 as being unpatentable over Enenkel et al. (US20080131969A1, published 05 June 2008); in view of Stewart et al. (US10953033B2, published 23 March 2021 with priority to U.S. provisional Application Nos. 62/676,688 filed 25 May 2018 and 62/599,547 filed 15 December 2017); Kunert (2018, Adoptive T cell Therapy Against Solid Tumors: Success Requires Safe TCRs and Countering Immune Evasion. [Doctoral Thesis, Erasmus University Rotterdam]. Erasmus Universiteit Rotterdam (EUR), published 04 April 2018); and Thess (US20170029847A1, published 2 February 2017), is withdrawn over cancelled claims 2 and 19 and maintained over amended, previously presented, and original claims 1, 3, 8-10, 13-18, and 20. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant amended independent claims 1 and 18 to recite, “wherein the engineered RPS27A 5’UTR sequence comprises SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84” in lines 6-7 and 8-9, respectively. However, neither claim 1 nor claim 18 have any prior recitation of an engineered RPS27A 5’UTR sequence. To the extent that the engineered RPS27A 5’UTR sequence is meant to refer to either the RPS27A 5’UTR sequence or the engineered 5’ UTR sequence, the other option is still not limited by the SEQ ID NOs recited. As such, the recited sequences according to SEQ ID NOs: 82-84 are options of the claims, but are not required by the claims as written.
Enenkel was cited in the prior action for teaching an engineered mRNA comprising an RPS27A 5’ UTR, a heterologous coding sequence encoding a heterologous gene of interest/ target protein such as a fluorescent protein, and an RSP27A 3’ UTR [0022, 0048, 0053, 0067, 0096, Figure 1].
Claim 10 was amended to recite, “wherein the RPS27A 3’UTR sequence is selected from the group consisting of SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 87, SEQ ID NO: 89, and SEQ ID NO: 91. Thess was cited in the prior action for teaching 3’ UTR sequences for human RPS27A which are, or comprise, a sequence which is a 100% full-length identity match to SEQ ID NOs: 25 and 26 of the instant application (e.g., SEQ ID NO: 74), and for mouse RPS27A which is a 100% full-length identity match to SEQ ID NO: 24 of the instant application (e.g., SEQ ID NO: 176).
Therefore, the amendment to claims 1, 10, and 18 do not alter the scope of the claim sufficiently to overcome the rejection of record under 35 USC 103.
Applicant argues that none of the references cited by the Office disclose or otherwise suggest an engineered mRNA sequence including an engineered RPS27A 5’UTR sequence, wherein the engineered RPS27A 5’UTR sequence comprises SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84, and as such claims 1 and 18, and claims dependent thereon, are patentable over the cited references.
This is not agreed.
It is agreed that none of the references cited by the Office disclose or otherwise suggest an engineered mRNA sequence including an engineered RPS27A 5’UTR sequence, wherein the engineered RPS27A 5’UTR sequence comprises SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84. However, as written, amended independent claims 1 and 18 do not require an engineered RPS27A 5’UTR sequence comprising SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84. As discussed above, neither claim 1 nor claim 18 have any prior recitation of an engineered RPS27A 5’UTR sequence. To the extent that the engineered RPS27A 5’UTR sequence is meant to refer to either the RPS27A 5’UTR sequence or the engineered 5’ UTR sequence, the other option is still not limited by the SEQ ID NOs recited. As such, the recited sequences according to SEQ ID NOs: 82-84 are limiting options of the claims, but are not required by the claims as written in that the other option is not limited by the SEQ ID NOs recited.
Therefore, Applicant’s arguments do not overcome a finding of obviousness under 35 USC 103, and the rejection is maintained.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
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DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634
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