DETAILED ACTION
Applicant’s response filed June 12, 2026 has been received and entered into the application file. All arguments have been fully considered. Claims 1, 4-9, 19-20, 22, 39-40, 42-43, 46, 48 and 54-55 are currently pending.
Claims 2-3, 10-18, 21, 23-38, 41, 44-45, 47 and 49-53 are cancelled.
Claims 5, 7-8, 39-40, 42-43, 46 and 48 are withdrawn.
Claims 1, 4, and 9 are currently amended.
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 .
Nucleotide and/or Amino Acid Sequence Disclosures
Applicant’s amendment submitted 6/12/2026 has amended the specification at paragraphs [0166], [0177], [0276] and [0327] by providing the appropriate sequence identifiers in accordance with 37 CFR 1.821(d). The amendment has been entered.
REJECTION(S) WITHDRAWN
Claim Rejections - 35 USC § 112
RE: Rejection of Claim 10 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite:
Applicant’s amendment of 6/12/2026 has cancelled claim 10, thus obviating the previous rejection of record.
Claim Rejections - 35 USC § 103
RE: Rejection of Claim(s) 1-3, 6-10, 12, 19-20 and 22 under 35 U.S.C. 103 as being unpatentable over WO 2019/118919 (“WO ‘919”, IDS 5/22/2023), as evidenced by Cowling et al., (Biochem J. (2010) 425, 295-302) (“Cowling”); and
Rejection of Claim 4 under 35 U.S.C. 103 as being unpatentable over WO ‘919, as evidenced by Cowling, and further in view of Tusup et al., (EPH-International Journal of Medical and Health Science, Volume-3, Issue-3, Sep, 2017, pages 20-24) (“Tusup”):
Applicant’s arguments, in view of claim amendments submitted 6/12/2026, have been fully considered and are persuasive. Therefore, the previous rejections of record have been withdrawn.
However, Applicant’s amendment has necessitated new grounds of rejection as set forth below.
REJECTION MAINTAINED/UPDATED
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 4, 6, 9, 19, 20 and 22, and new claims 54-55, are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more.
The rejection has been updated in view of Applicant’s amendment.
The rationale set forth below conforms to current Office practice for examination of claims under § 101.
These claims are analyzed for eligibility in accordance with their broadest reasonable interpretation. All of the claims are directed to a statutory category, e.g., a composition (Step 1: YES).
The next part of the analysis involves whether the claimed invention recites or is directed to one or more judicial exceptions (Step 2A, prong one).
Claim 1: Claim 1 is directed to a pharmaceutical composition comprising:
(a) a polyribonucleotide comprising a 5' modified guanosine cap and a first binding region;
(b) a circular polyribonucleotide; and
(c) a pharmaceutically acceptable excipient, wherein the circular polyribonucleotide comprises a second binding region and the first binding region specifically binds to the second binding region.
As is recognized by the instant specification, the excipient encompasses non-carrier aqueous solvents such as phosphate buffered saline (paragraphs [0360]) or solvents including water, or isotonic agents such as sucrose or trehalose ([0426]).
Further regarding a circular polyribonucleotide, it is noted that Legnini et al (see IDS 5/22/2023) notes that studies show that circular RNA (circular polyribonucleotides) are commonly produced by thousands of genes (INTRODUCTION, left col, page 22), and circular RNA (circRNA) is highly conserved across species and particularly abundant in mammalian neuronal tissues. Legnini et al specifically identifies circRNAs that are regulated during murine and human muscle differentiation, and whose expression is altered in Duchenne muscular dystrophy (DMD) myoblasts (INTRODUCTION, right col, page 22).
As to the recited polyribonucleotide comprising a 5' modified guanosine cap and a first binding region, it is noted that Filipowicz et al., (previously cited) evidences that native messenger RNA (from Artemia salina embryos) comprises a 5’ modified guanosine cap and a cap binding region (first binding region), wherein the cap binding protein(s) may influence the initiation of protein synthesis by promoting ribosomal binding of cap-containing messengers through recognition of the modified guanosine cap, m7GpppN (ABSTRACT). Filipowicz further notes that many viral and eukaryotic mRNAs have a m7G(5’)pppN cap at the 5’ end, and this cap is important for translation, as well as being required for binding the messenger to 40S or 80S ribosomes (first paragraph, left col, page 1559).
Xie further teaches native microRNAs (miRNAs, polyribonucleotides) that are gene regulators and produced from primary transcripts, wherein the pre-miRNAs have 5’ modified guanosine cap, i.e., 7-methylguanosine-capped, and binding region for exporting via the PHAX-exportin 1 pathway (Summary, page 1568; Introduction, page 1568-1569).
Panda et al., (see PTO-892) further sets forth that binding interactions occur between circular RNA and mRNA via first and second binding regions (Figure 2).
Thus, the claim recites a combination of natural products.
The claim as a whole, considering all claim elements both individually and in combination, does not amount to significantly more. There is no indication in the specification that in combining an excipient comprising water or sucrose with either the polyribonucleotide comprising a 5' modified guanosine cap and a first binding region or circular RNA, that any characteristics (structural, functional, or otherwise) are developed by either the polyribonucleotide comprising a 5' modified guanosine cap and a first binding region, or circular RNA, that are not present in the individual parts. The combination does not improve or change in any way each components natural functioning. Thus, the claim as a whole, considering all claim elements both individually and in combination, does not amount to significantly more.
There is no indication in the specification that the limitations recited in dependent claims 4, 6, 9, 19-20, 22 and 54-55 limit the claimed composition in such a way that is markedly different in structure, or biological and/or pharmacological function from their natural counterparts.
Accordingly, the claims are directed to an exception (Step 2A, prong one: YES). Thus, the claims do not qualify as eligible subject matter, and are rejected under 35 U.S.C. 101.
The next part of the analysis involves whether the claimed invention recites additional elements that integrate the judicial exception into a practical application (Step 2A, prong two).
Given the claims are directed to a composition, the claims do not recite additional steps that integrate the judicial exception into a practical application (Step 2A, prong two: No).
The final part of the analysis involves whether the claimed invention, as a whole, recite something “significantly more” than the judicial exceptions (Step 2B).
In view of the above and considered as a whole, the claimed composition does not have markedly different characteristics from what occurs in nature and such elements discussed above are not significantly more than the indicated judicial exceptions. Thus, the claims do not qualify as eligible subject matter, and are rejected under 35 U.S.C. 101 (Step 2B: NO).
Response to Remarks:
Applicant asserts that the claimed composition is not merely isolated from nature but has been structurally altered through human intervention, as discussed at Applicant’s remarks (page 7).
Applicant’s remarks have been carefully considered, but are not found persuasive since the claims do not recite any specificity as to limitations that are not found in nature, and as set forth above at the updated rejection under 35 USC 101, Panda et al further sets forth binding interactions between circular RNA and mRNA via first and second binding regions (Figure 2).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 6, 9, 20 and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Panda et al., (WIREs RNA 2016. doi: 10.1002/wrna.1386, 9 pages; see PTO-892) (“Panda”), as evidenced by Cowling (previously cited).
Panda discusses the emerging roles and context of circular RNAs (circRNAs), noting that circRNAs are a large class of noncoding RNAs, and have been shown to effect increases in translation and stability of microRNA targets due to circRNA’s ability to suppress microRNAs (Abstract).
Regarding claims 1, 6, 9, 20 and 22, Panda teaches that circRNAs form RNA-RNA complexes with long noncoding RNAs (lncRNAs) and mRNAs, wherein the circRNA-mRNA complexes may alter mRNA stability or translation (page 2, first paragraph).
Figure 2 of Panda illustrates CircRNA-mRNA interaction via first and second complementary binding regions, CircRNA-lncRNA interaction via first and second binding regions, and binding of miRNAs.
It is further noted that Cowling evidences that eukaryotic mRNA is modified by the addition of the 7-methylguanosine ‘cap’ to the first transcribed nucleotide (Abstract and Introduction).
Thus, the mRNA disclosed in Panda is considered to comprise a 5’-modified guanosine cap, specifically comprising 7-methyl-guanosine, thus the teaching of Panda anticipates claims 1, 6, 9, 20 and 22.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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) 19 and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Panda et al., (WIREs RNA 2016. doi: 10.1002/wrna.1386, 9 pages; see PTO-892) (“Panda”), as evidenced by Cowling.
The teaching of Panda, as evidenced by Cowling is set forth above.
Regarding claim 19 and the limitation the first binding region comprises 5 to 100 nucleotides in length, it is noted that Figure 2 of Panda does not comment on how may nucleotides are represented by the illustrated binding regions, which appear to include complementarity between at least 3 pair of nucleotides for each binding region.
Although Panda does not specifically illustrate 5 to 100 nucleotides in length, a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05).
One of ordinary skill would recognize that the length of the binding region complementary nucleotides can be optimized as a matter of routine experimentation. Absent any teaching of criticality by the Applicant concerning the nucleotide length, it would be obvious that one of ordinary skill in the art would recognize the length of complementary nucleotides is a result effective variable that achieves stronger complementation between the two molecules. “[W[here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. “ In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05).
Regarding claim 54, although Figure 2 of Panda does not further comment on the exact length of the mRNA (polyribonucleotide), however, absent evidence to the contrary, it is reasonable to consider, based on the illustration, the polynucleotide comprises a nucleotide length that lies within, or overlapping, of the claimed range. “[W[here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. “ In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05).
Claim(s) 55 is rejected under 35 U.S.C. 103 as being unpatentable over Panda et al., (WIREs RNA 2016. doi: 10.1002/wrna.1386, 9 pages; see PTO-892) (“Panda”), as evidenced by Cowling, and further in view of Salzman et al., (PLOS Genetics 9(9): e1003777; see PTO-892) (“Salzman”).
The teaching of Panda, as evidenced by Cowling, is set forth above.
Regarding claim 55, Figure 2 of Panda does not further comment on the exact length of the circular RNA. However, Figure 1 of Panda illustrates the splicing events that occur to produce various sizes of circular RNA and Salzman further teaches of various circular RNA isoforms (Figure 1) having a variety of sizes ranging from 130 nt (ABTB1) to 3283 nt (FAT1). Thus, absent evidence to the contrary, it is reasonable to consider, based on Figure 2 of Panda and the teaching of Salzman, the prior art circular RNA comprises a nucleotide length that lies within, or overlapping, of the claimed range. “[W[here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. “ In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05).
Response to Remarks:
As set forth above, Applicant’s arguments, in view of claim amendments submitted 6/12/2026, have been fully considered and are persuasive in overcoming the previous rejections of record. However, new grounds of rejection are set forth above, specifically addressing the newly amended limitations.
Allowable Subject Matter
Claim 4 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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 E. YVONNE PYLA whose telephone number is (571)270-7366. The examiner can normally be reached M-F 9am - 6pm.
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E. YVONNE PYLA
Primary Examiner
Art Unit 1633
/EVELYN Y PYLA/ Primary Examiner, Art Unit 1633
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