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 .
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.
Response to Amendment
The amendment filed June 8, 2026 has been entered. Claims 15-23 have been amended, claims 1-14 have been cancelled. Claims 17-20 are withdrawn due to a non-elected invention. Applicant’s amendments to the claims have overcome the objections to the specification, drawings and claims, the 112(b) rejections previously set forth in the Non-Final Office Action mailed February 6, 2025. Applicants claim of ownership over Ekambareswara (US 2023/0250127, IDS filed October 14, 2025, effectively filed November 24, 2021) overcomes the 103 rejections over Ekambareswara (US 2023/0250127, IDS filed October 14, 2025, effectively filed November 24, 2021) in view of Frederick (WO 2017/201325, cited on PTO-892) previously set forth. The terminal disclaimer over copending application 18057714 is approved, which overcomes the double patenting rejections previously set forth. Applicants cancellation of claims 1-14 have rendered the corresponding rejections/objections moot. As such, these rejections and objections are hereby withdrawn.
Applicant’s arguments filed June 8, 2026 were fully considered but they were not persuasive. Maintained and new rejections necessitated by Applicant’s amendment are addressed below.
Claims 15-23 are pending in this application.
Election
Applicant’s election of
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and SEQ ID 8 in the reply filed January 12, 2026 is acknowledged.
Claim 21 was found free of the prior art with respect to the specific mRNA SEQ ID 8 as recited, thus the election was expanded to SEQ ID 1, which is also free of prior art. The election was expanded to mRNA comprising from 5' to 3', an interleukin 12 subunit ß (IL12B) polypeptide coding sequence and an interleukin 12 subunit α (IL12A) polypeptide coding sequence as recited by instant claim 1.
Upon discovery of additional species during search, the election was expanded to include the following species:
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which are encompassed by claims 15-16, and 21-23.
Claims17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Because applicant did not distinctly and specifically point out the supposed errors in the election requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 15-16, and 21-23 are encompassed by the elected species and examined herein.
New Claim Rejections - 35 USC § 112 (b)
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.
Claims 15-16, and 21-23 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.
Claim 15 recites the following compounds:
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. The first compound possesses a
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group which is undefined. The second compound does not possess this group. This leads to a lack of clarity because it is unclear whether the second compound has the same or different attachment point. The lack of clarity renders the claim and dependent claims 16, and 21-23 indefinite. The Examiner suggests amending for consistency, and defining the point of attachment if the
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is used.
Maintained Claim Rejections - 35 USC § 103
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.
Claims 15-16 and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (WO 2022/086140 IDS filed October 14, 2025,) in view of Frederick (WO 2017/201325, cited in previous action). The English translation of Kim has been provided in a previous action.
Regarding claims 15-16 and 22-23: Kim teaches a novel oligonucleotide primer used for the synthesis of 5’-capped RNA (English translation, abstract). Kim teaches the primer of formula 1 can be utilized in the fields of nucleic acid therapeutic agents or vaccines (English translation, abstract). Kim teaches a compound of formula 1 includes the following species
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(Original document pg. 6, compound 5, English translation, pg. 14, last sentence, English translation, pg. 17, last structure 5). Kim teaches pharmaceutical formulations for RNA therapeutics or vaccines may be formulated for administration (i.e. a composition, English translation, pg. 25, paras. 5-7). Kim teaches the incorporation of the primer for RNA capping can be performed in vitro (English translation, pg. 24, paras. 2, 9). Kim teaches the in vitro transcription occurs in the presence of ATP, UTP, CTP, GTP, a polynucleotide template and RNA polymerase (English translation, pg. 30, experimental example 2). Kim teaches the novel oligonucleotide of the present invention is utilized for the synthesis of 5’-capped RNA to improve the RNA production process and efficacy of a nucleic acid therapeutic of vaccine (eg, RNA stability and/or protein expression efficiency) and improvement and side effects reduction (eg, immunogenicity reduction) effect (English translation, pg. 25, para. 9).
Kim does not teach wherein the mRNA comprises from 5' to 3', an interleukin 12 subunit ß (IL12B) polypeptide coding sequence and an interleukin 12 subunit α (IL12A) polypeptide coding sequence from either mice or human.
However, Frederick teaches methods for the preparation of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide (abstract). Frederick also teaches the polynucleotide can encode an IL-12 polypeptide which comprises IL12B and IL12A subunits (pgs. 81-82, para. 320). The IL-12 polypeptide comprises human or murine IL-12 polypeptide (pg. 82, para. 321). Frederick teaches the mRNA encoding an IL-12 polypeptide can further include a 5’ terminal cap (pg. 83, para. 0324). Frederick teaches 5’ caps are useful to increase mRNA stability (pg. 239, para. 714). Frederick teaches acceptable caps include synthetic 5’ cap analogs (pg. 239, para. 716). Frederick teaches exemplary cap structures which are comparable to the 5’ cap structures claimed (pgs. 240-241, para. 723, i.e. canonical 5'-5'-triphosphate linkage between the 5'-terminal nucleotide of a polynucleotide and a guanine cap nucleotide).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to apply the incorporate the cap analog of Kim to the preparation of immunomodulatory mRNA comprising IL12B and IL12A from murine or human as taught by Frederick. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as incorporation of cap analogs into this type of mRNA is known in the art in order RNA to improve the RNA production process and efficacy of the IL12 mRNA for immunomodulatory purposes.
Response to Arguments
Applicant’s arguments filed June 8, 2026 with respect to the claims have been fully considered but they are not persuasive.
On page 13 of Applicant’s response, Applicant argues Kim does not disclose the mRNA comprises an IL12B polypeptide and Il12A polypeptide coding sequence and demonstrates that some examples showed better protein expression rates compared to ARCA (last para.). Applicant argues that while some Cap compounds showed better expression rates, these results do not directly establish improvements in mRNA stability, immunogenic properties, or therapeutic outcomes (last para.). Applicant points to the priority application of Kim which discloses compound 1 showed worse protein expression rates compared to Cleancap (last para.). On page 14 of Applicant’s response, Fredrick does not teach using the claimed caps to modify IL-12 polypeptides (para. 1). On page 14 of Applicant’s response, Applicant argues Kim and Frederick do not teach the claimed caps to modify IL-12 polypeptides and a person of ordinary skill in the art would not reasonably expect that modifying IL-12 polypeptides with GL-Cap 5 or GL-Cap 9 would improve the stability, immunogenicity, and antitumor efficacy of mRNA with a reasonable expectation of success (para. 2).
However, compound 1 of Kim is not the elected compound. Additionally, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. As discussed above, Kim teaches compound 5
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(Original document pg. 6, compound 5). Kim teaches the invention is utilized for the synthesis of 5’-capped RNA to improve the RNA production process and efficacy of a nucleic acid therapeutic of vaccine (eg, RNA stability and/or protein expression efficiency) and improvement and side effects reduction (eg, immunogenicity reduction) effect (English translation, pg. 25, para. 9). A person of ordinary skill would recognize the cap structure of Kim being applicable to the IL12 polypeptide coding sequences of Frederick, and it would be expected to see improved RNA stability and/or protein expression efficiency and improvement and side effects reduction (eg, immunogenicity reduction) as that is the purpose of the caps as taught by Kim.
On page 14 of Applicant’s response, Applicant argues the instant application demonstrates unexpected results of the claims IL-12 mRNA exhibited unexpected results of improved anti-tumor efficacy and improved higher expression when compared to CleanCap® (para. 1).
However, this result is not found to be persuasive when Kim teaches the claimed Cap and suggests it improves protein expression rates in cancer cell lines (English translation, pg. 31, para. experimental example 3). Kim teaches the invention is utilized for the synthesis of 5’-capped RNA to improve the RNA production process and efficacy of a nucleic acid therapeutic of vaccine (eg, RNA stability and/or protein expression efficiency) and improvement and side effects reduction (eg, immunogenicity reduction) effect (English translation, pg. 25, para. 9). Thus it cannot be considered unexpected that incorporation of the cap of Kim results in the claimed properties.
Applicant’s reply is considered to be a bona fide attempt at a response and is being accepted as a complete response. The 35 USC § 112(b) and 103 rejections are maintained for reason of record and foregoing discussion.
Conclusion
No claims are allowed in this action.
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 SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Y Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/S.L.G./Examiner, Art Unit 1693
/ANDREA OLSON/Primary Examiner, Art Unit 1693
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