DETAILED ACTION
The present application is a domestic application filed 21 November 2022, which claims priority to US Provisional Application No. 63/283,046, filed 24 November 2021.
Claims 1-22 are pending in the current application. Claims 21 and 22 are withdrawn as being drawn to a non-elected invention, see below. Claims 8-10 are withdrawn as being drawn to a non-elected species. Claims 1-7 and 11-20 are examined on the merits herein.
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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-20 in the reply filed on 21 November 2022 is acknowledged.
Claims 21 and 22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 21 November 2022.
Applicant’s election without traverse of the 7th compound of claim 15:
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in the reply filed on 26 March 2026 is acknowledged.
Although the elected species is rejected under 35 U.S.C. §103(a) obviousness, to advance prosecution of this application, the Examiner has included a search of the 5th compound of claim 15:
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The examiner has also included a search of the following compound:
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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 1-14 and 16-20 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.
Regarding claims 17 and 20, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The recitation “LNA” in claim 1, renders the claim and dependent claims 2-14 and 16-20 herein indefinite. The definition of R3 and R4 includes “LNA”. According to the Specification, “LNA” is known as “locked nucleic acid”, and it refers to a methylene bridge between the 2’O and 4’C of the nucleotide (see para [0248] of the published application). The Specification illustrates the following structures, which look identical:
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. The Specification discloses LNA includes “those described in WO 99/14226”. The abstract of WO99/14226 (cited in PTO-892) shows four different structures, including some which contain an ethylene bridge (not methylene). And some of these structures have the bridge between the 2’O and 3’O positions:
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Thus, it is not clear which structures may be encompassed or excluded by the present claims.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-7, 11-16, 18 and 19 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kim et al. (US Patent Application Publication No. 2023/0382943, cited in PTO-892).
Kim et al. is concerned with preparing novel oligonucleotide primers for synthesizing 5’-capped RNA (abstract). Kim et al. teach RNA cap analogs maintains mRNA stability in vivo, improves translation efficiency, and/or reduces side effects such as immunogenicity when they are applied as vaccines (para [0005]). Kim et al. teach the compound of formula (5):
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(claim 10), as an exemplary compound of formula 1:
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. Kim et al. teach Z1 and Z2 are each independently -OH, -O(C1-4 alkyl), -O(C1-4alkyl)O(C1-4alkyl), -CH2O(C1-4alkyl), or -halo (claim 1). Kim et al. teach an RNA molecule comprising the oligonucleotide primer for RNA capping according to claim 1 (claim 12). The oligonucleotide primer is attached to the 5’-end of the RNA molecule (claim 13). Kim et al. teach a mixture of the RNA and an RNA polymerase. The RNA molecule is an mRNA comprising at least one coding sequence (claim 14).
The compound of formula (5) anticipates present claim 1, when n is 0, B1 is a modified nucleobase, B2 is a nucleobase, R is H, R1 and R2 are OR5 and R5 is H, and R3 is LNA.
The compound of formula (5) anticipates claim 2, because ring B1 is a modified guanine, B4 is guanine, and B2 is adenine.
When n is 0, the definitions for R4 and ring B3 are not further limiting.
Thus, the disclosure of Kim et al. anticipates claims 1-7, 11-16, 18 and 19 of the present application.
Claim(s) 1, 3-7, 16, 18 and 19 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Jooss et al. (WO2021/216776, cited in PTO-892).
Jooss et al. is concerned with preparing novel oligonucleotide primers for synthesizing 5’-capped RNA (abstract). Jooss et al. teach RNA cap analogs maintains mRNA stability, allows for large scale synthesis of mRNAs, eliminates/reduces bi-directional initiation during transcription, results in higher yields of mRNA, and costs less to produce mRNA (para [0004]). Jooss et al. disclose compound 2:
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(claims 5 and 38). Jooss et al. disclose an RNA oligonucleotide comprising any one of the compound of claims 1-5 (claim 6). The compounds above are at the 5’end of the RNA molecule (claim 132). Jooss et al. teach providing the m7G-ppp-N1’-N2’ in combination with an RNA polymerase (claim 132). Jooss et al. teach mRNA comprising the 5’-capped oligonucleotide described above (para [00128]).
Compound 2 of Jooss et al. anticipates the present compound of formula (II), where B1 is a modified nucleobase (modified guanine), B2 is adenine and B4 is uracil; R is H, R1 and R2 are both OR5 and R5 is hydrogen, R3 is halogen, n is 0.
Thus, the disclosure of Jooss et al. anticipates claims 1-7, 11-16, 18 and 19 of the present application.
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) 1-7, 11-16, 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (cited above) in view of Kore et al. (Bioorganic & Medicinal Chemistry Letters, 2007, vol. 17, pp. 5295-5299, cited in PTO-892).
Kim et al. teach as discussed above.
Kim et al. do not expressly disclose
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, i.e. the difference between the compound disclosed by Kim et al. and the elected species is a 2’-fluoro substitution (elected species, 7th compound of present claim 15).
Kore et al. teach preparing 2’-fluoro-substituted cap analogs, i.e. m7, 2’FGpppG (title and abstract). Kore et al. found mRNA poly(A) capped with 2’-fluoro-substituted cap analogs were translated ~2.4-fold more efficiently than mRNA capped with conventional m7GpppG.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify
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of Kim et al., to include a 2’-fluoro substitution to give a m7,2’FG trinucleotide derivative.
Kim et al. and Kore et al. are concerned with preparing 5’-cap oligonucleotide derivatives to improve the translation efficiency of mRNA. Kim et al. expressly teach a genus encompassing a compound of formula 1, where Z1 and Z2 are independently -OH, -Oalkyl, -Oalkoxy-O-alkyl, -CH2Oalkyl, or halo.
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. Furthermore, Kim et al. exemplify compound (1), which contains a fluoro-derivative. And Kore et al. teach 2’-fluoro substitution to give a m7,2’FG dinucleotide cap, wherein mRNA poly(A) capped with 2’-fluoro-substituted cap analogs were translated ~2.4-fold more efficiently than mRNA capped with conventional m7GpppG.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 1-7 and 11-20 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (cited above) in view of Rumfield et al. (ImmunoTargets and Therapy, 2020, vol. 9, pp. 167-200, cited in PTO-892).
Kim et al. teach as discussed above. Kim et al. teach the use of the oligonucleotide primer for RNA capping, which can be used in the fields of nucleic acid therapeutic agents or vaccines (abstract; claims 20-24). For example, the vaccine may be used as an RNA vaccine (para [0071]). The RNA vaccine may be administered to a subject and translated in vivo to produce the desired peptide (see also claims 17, 19).
Kim et al. do not expressly disclose the mRNA molecule contains polynucleotide sequences encoding HPV E6-E7 antigen polypeptides (present claims 17 and 20).
Rumfield et al. teach human papillomavirus (HPV) is a small dsDNA virus, some of which confer a low risk of cancer development, high risk of cancer development, or genital warts (p.167, second para). All types of HPV encode “early proteins”, including E6 and E7 (p.167, third para). The E6 and E7 proteins drive cell proliferation. RNA vaccines can be prepared from mRNA, and are advantageous in that encoded antigens are delivered in a non-HLA-restricted manner, synthetic mRNA is inexpensive and easily produced, it is rapidly degraded and cleared. Rumfield et al. teach an E7-trimix RNA vaccine, which consists of an mRNA-based vaccine encoding for CD40L, constitutively active TLR4, and CD70, which was administered together with mRNA encoding HPV16 E7 (p.190, third para). Rumfield et al. teach therapeutic vaccines against HPV-associated malignancies commonly target the E6 and E7 oncoproteins to elicit a T-cell response against these proteins (p.190, last para).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide an RNA molecule, which is mRNA, and the mRNA encodes for HPV E6-E7 antigen proteins and having the 5’-cap from Kim et al.
Starting from Kim et al., the ordinary artisan would have looked to the teaching of Rumfield et al., because they are both concerned with the development of mRNA vaccine technology. The ordinary artisan would have been motivated to use the 5’-cap oligonucleotide as part of an mRNA that encodes HPV E6-E7 antigen proteins, because the 5’-cap oligonucleotide maintains mRNA stability in vivo, improves translation efficiency, and/or reduces side effects such as immunogenicity when they are applied as vaccines.
The ordinary artisan would have had a reasonable expectation of success, because the use of 5’-cap oligonucleotides is a known solution for improving the stability and translation efficiency of RNA molecules.
With respect to claim 19, the ordinary artisan would have been motivated to combine the 5’-cap oligonucleotide with RNA polymerase and an RNA molecule to synthesize an mRNA sequence having the 5’-cap oligonucleotide at the 5’-terminus.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art .
Claim(s) 1-7 and 11-20 are rejected under 35 U.S.C. 103 as being unpatentable over Jooss et al. (cited above) in view of Rumfield et al. (ImmunoTargets and Therapy, 2020, vol. 9, pp. 167-200, cited in PTO-892).
Jooss et al. teach as discussed above.
Jooss et al. do not expressly disclose the mRNA molecule contains polynucleotide sequences encoding HPV E6-E7 antigen polypeptides (present claims 17 and 20).
Rumfield et al. teach as discussed above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide an RNA molecule, which is mRNA, and the mRNA encodes for HPV E6-E7 antigen proteins, and having the 5’-cap of Jooss et a.
Starting from Jooss et al., the ordinary artisan would have looked to the teaching of Rumfield et al., because they are both concerned with the development of mRNA vaccine technology. The ordinary artisan would have been motivated to use the 5’-cap oligonucleotide as part of an mRNA that encodes HPV E6-E7 antigen proteins, because the 5’-cap oligonucleotide maintains mRNA stability in vivo, improves translation efficiency, and/or reduces side effects such as immunogenicity when they are applied as vaccines.
The ordinary artisan would have had a reasonable expectation of success, because the use of 5’-cap oligonucleotides is a known solution for improving the stability and translation efficiency of RNA molecules.
With respect to claim 19, the ordinary artisan would have been motivated to combine the 5’-cap oligonucleotide with RNA polymerase and an RNA molecule to synthesize an mRNA sequence having the 5’-cap oligonucleotide at the 5’-terminus.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art .
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 1-7 and 11-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 18/170,512 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘512 application encompass tri- to tetranucleotide sequences having the same compound of formula (I). The claims of the ‘512 application anticipate present claims 1-7 and 11-16 of the present application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAHAR A CRAIGO whose telephone number is (571)270-1326. The examiner can normally be reached M-F: Noon-8pm ET.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
Prosecution Insights