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 .
Election/Restrictions
Applicant's election with traverse of species E18 (SEQ ID NO:19) in the reply filed on 12/16/2026 is acknowledged. The traversal is on the ground(s) that Hoernes et al. does not disclose an mRNA in which, in at least two codons within the coding region, the first nucleotide is a sugar modified nucleotide. Therefore, polynucleotides defined by claim 1 should now be considered to share the same or corresponding special technical feature. Thus, the above feature is the special technical feature. The Examiner contends that Hoernes et al. indicates that "incorporation of several modified nucleotides within one codon or several codons results in an additional effect". However, Hoernes et al. is silent about the above-noted specific structural feature recited in claim 1. This is not found persuasive because Hoernes et al. indicates that although single site modification is focused in this experiment, incorporation of several modified nucleotides within one codon or several codons results in an additional effect (page 861, left column, first paragraph).
The requirement is still deemed proper and is therefore made FINAL.
No prior art was found for the specific species E18. The examination has been extended to all the claims 1-25.
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 1-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 18/575,623(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim a polynucleotide comprising a translated region from a start codon to a stop codon wherein the translated region contains at least two codons in which a first nucleotide is a sugar modified nucleotide; they both claim sugar portion of identical formula; they both claim that the polynucleotide can contain a base modified nucleotide of identical formula, a poly A chain, and a phosphorothioate structure. They both claim a pharmaceutical comprising said polynucleotide.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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.
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) 1-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hoernes, Thomas Philipp et al., Nucleic Acids Research, 2016, vol. 44, no. 2, pp. 852-862 (Hoernes 1) in view of Hoernes, Thomas Philipp et al., Genes, 25 January 2019, vol. 10, no. 84, pp. 1-12 (Hoernes 2) further in view of Monia et al., The Journal of Biological Chemistry, 1993, 268(19), pp 14514-14522, Kore et al. Bioorganic & Medicinal Chemistry 18, (2010) 8061-8065, Chakraborty US20160022840, and WATTS, Jonathan K. et al., Drug Discovery Today, 2008, Vol. 13, No. 19/20, pages 842-855.
Hoernes 1 indicates that nucleotide modification such as 2'-O-methylation is introduced at three positions within a codon of a bacterial EfmCL mRNA, and the effect thereof on transcription thereof was confirmed (abstract); and reduction of transcription activity in mRNAs into which a 2'-O-methyl group is introduced at first, second, and third positions, respectively, were 10-15%, 90%, and 50%, respectively (page 858, left column, second paragraph). Hoernes 1 also indicates that although single site modification is focused in this experiment, incorporation of several modified nucleotides within one codon or several codons results in an additional effect (page 861, left column, first paragraph).
Hoernes 2 indicates that among mRNAs into which a 2'-O-methylated nucleotide (Nm) is introduced at the first, second, and third positions, respectively, the mRNA into which a 2'-O-methyl group is introduced at the second position showed the strongest reduction in protein yield (page 6, first paragraph, and figure 3); and recently, it has been revealed that a large number of Nms are present in coding sequences (CDSs) in yeasts and HeLa cells (page 8, second paragraph).
Although mRNAs specifically disclosed in Hoernes 1 and Hoernes 2 have a sugar modification on the first nucleotide in one codon, the invention of the present application differs therefrom in that the first nucleotide in at least two codons is a sugar modified nucleotide. However, Hoernes 1 suggests the introduction of multiple modified nucleotides in multiple codons, and Hoernes 2 indicates that a large number of Nms are present in CDSs in multiple cell types. A person skilled in the art could easily have conceived of introducing a sugar modification into a nucleotide at the first position, which is an especially advantageous position, in a plurality of codons within a CDS of an mRNA. Further, base modifications (such as 5-methylation of pyridine) is common in conjunction with sugar modifications (see Watts et al. page 846).
With regards to claims 15-19, where the polynucleotide comprises a 5’ cap, and Poly A chain, are well known in the art. Traditionally, the basic components of an mRNA molecule include at least a coding region, a 5′UTR, a 3′UTR, a 5′ cap and a poly-A tail, and optimization of modified mRNA molecules via optimization of their terminal architecture is well known. For example 5’cap modification shields the mRNA’s 5’end from enzymes (exonucleases) protecting mRNA from degradation, enhance stability, and promotes efficient translation in gene therapy (see Kore et al. Abstract, Introduction and conclusion; see also Chakraborty US20160022840) .
With regards to claims 21-25, where the polynucleotide comprises nucleotides linked to each other via phosphonothioate are well known in the art. Monia et al. discloses a polynucleotide that contains multiple codons, wherein the first nucleotides in at least two codons are sugar modified nucleotides (2'-O-methyl modifications are shown inboxes) and phosphorothioate (see abstract, Fig. 1, 7, 8 and 9). Monia et al. discloses chemical modifications placed in the backbone, sugar, or base of a nucleotide offer many potential advantages for oligonucleotide pharmacology, increased potency conferred by high affinity 2' sugar modifications, …. Increased cell penetration by oligonucleotides containing lipophilic 2' sugar modifications (page 14522).
Therefore, one of ordinary skill in the art seeking to solve the stated problem, according to the circumstances, would have been motivated to modify the primary references in the manner of the claims, without exercising inventive skill, to achieve the expected benefits, optimizations and/or expanded applications as this is well known practice in the art.
MPEP states wherein the “[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 Alter, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Routine optimization is not considered inventive and no evidence has been presented that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEZIA RILEY whose telephone number is (571)272-0786. The examiner can normally be reached 7:30-6:00pm.
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/JEZIA RILEY/ Primary Examiner, Art Unit 1681 10 January 2026