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.
This office action is a response to applicant’s response to election submitted January 12, 2026. The claims filed February 16, 2023 are examined herein. This application was filed February 16, 2023.
Claims 1-23 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 1-6, 11-16, and 21-23.
Claims 7-10 and 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 1-6, 11-16, and 21-23 are encompassed by the elected species and examined herein.
Drawings
The drawings are objected to because the X-axis labels on Figures 1-2 have overlapping texts, rendering X-axis labels illegible.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
Structures in the table on pages 8-9 are blurry, rendering them illegible, specifically GL-Cap-9 (pgs. 8-9).
The circles surrounding base units in structural formulas are unclear if they are meant to be dotted lines or solid lines, could present an issue of clarity, for example:
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(pgs. 3, 6, formula (I), pg. 7, formula (IA), pg. 8, formula (IB),
Appropriate correction is required.
The use of the term CleanCap® (abstract, pg. 2, para. 3 for example) (CLEANCAP, trademark registry, USPTO, 2018, cited on PTO-892), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 1 and 15 are objected to because of the following informalities:
In claim 1 the circles surrounding base units in structural formulas are unclear if they are meant to be dotted lines or solid lines, could present an issue of clarity, for example:
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. (see also withdrawn claims 8 and 11).
In claim 15 the last structure is b blurry, rendering it illegible (pgs. 8-9).
Appropriate correction is required.
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 1-6, 11-16, 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.
Claims 1-6, 11-16, and 21-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: Connectivity between the 5’ Cap analog and mRNA.
Claim 22 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: The claim recites a method of synthesizing the mRNA modified with 5’-cap analog of claim 1 in vitro without reciting any active steps.
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 1-6, 15, and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable 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).
Regarding claims 1-6, 15, and 22-23: Ekambareswara teaches mRNA 5’ cap analogs and methods of making and using them (pg. 1, para. 0006). Ekambareswara also teaches mRNA containing the 5’ cap analogs (pg. 1, para. 0007). Ekambareswara teaches the 5’-cap analogs of the invention can improve transcription, mRNA stability, and mRNA translation efficiency and durability (pg. 1, para. 0007). Ekambareswara teaches the preparation of mRNA cap analog with the following structure:
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which is identical to the elected mRNA cap analog (pgs. 67-68, para. 0343, example 18). Ekambareswara teaches methods of synthesizing an mRNA molecule in vitro with incorporation of the 5’ caps of the invention (pgs. 2-3, para. 0038). Ekambareswara teaches the mRNA capped molecules can be administered in formulations for in vivo evaluation (i.e. a compositions, pgs. 69-70, para. 0355, 0363).
Ekambareswara 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 Ekambareswara 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 to improve transcription, mRNA stability, and mRNA translation efficiency and durability of the IL12 mRNA for immunomodulatory purposes.
Claims 1-6, 11-16, 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 on PTO-892). The English translation of Kim has been provided.
Regarding claims 1-6, 11-16, and 22-23: Kim teaches the 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 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 (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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-6, 11-16, and 22-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18057714 (US 20230250127, cited on IDS filed October 14, 2025) in view of Frederick (WO 2017/201325, cited on PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1-6, 11-16, and 22-23: The copending claims teach the following compound
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and
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(copending claim 15). The copending claims teach an RNA molecule in which the 5’ end comprises a compound, including the compounds above (claim 16). The copending claims teach a method of capping an RNA transcript using a compound (copending claim 21). The copending claims teach a kit comprising the compound, the RNA molecule, and a polymerase (copending claims 18-20). This kit necessarily results in a composition comprising the compound.
The copending claims do 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 the copending claims 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 to improve mRNA stability of the IL12 mRNA for immunomodulatory purposes.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed in this 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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/S.L.G./Examiner, Art Unit 1693
/ANDREA OLSON/Primary Examiner, Art Unit 1693