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 .
DETAILED ACTION
The examiner for this case has changed.
Status of Application/Amendment/Claims
This office action is in response to the communication filed 09/10/2025.
No amendments have been made in the communication filed 09/10/2025.
Claims 1, 4, 8-13, 15, and 17-20 remain pending and are under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/29/2026 was filed after the mailing date of the non-final Office action on 04/10/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Withdrawn Rejections and/or Objections
Any rejection and/or objection not repeated herein is hereby withdrawn.
Maintained Rejections and/or Objections
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.
Claim(s) 1, 4, 8, 12, 13, 15, 17, 18, and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Maier et al., (US 20170275626, filed 8/14/2015), Freier et al., (US 20070066549), Bramsen et al., (Front. Genet. (2012) 3:154), Angart et al., (Pharmaceuticals (2013) 6: 440-468).
Maier taught double stranded RNA agents capable of inhibiting expression of a target gene by RNA interference (abstract and [0002]). The agents have a sense (passenger) strand and an antisense (guide) strand, each of 14 to 40 nucleotides ([0011]). Each strand may comprise chemical modifications. In particular embodiments the sense and antisense strands comprise or consist of 2’-F and 2’-O-methyl nucleotides.
In one particular embodiment (paragraphs [0154]-[0163]), the dsRNA agent comprises:
(a) a sense strand having: (i) a length of 21 nucleotides; (ii) three GalNAc derivatives attached through a trivalent branched linker to the 3’-end; (iii) 2′-OMe modifications at positions 1 to 6, 8, 10, and 12 to 21, 2′-F modifications at positions 7, and 9, and a deoxy-nucleotide (e.g. dT) at position 11 (counting from the 5′ end); and (iv) phosphorothioate internucleotide linkages between nucleotide positions 1 and 2, and between nucleotide positions 2 and 3 (counting from the 5′ end); and
(b) an antisense strand having: (i) a length of 23 nucleotides; (ii) 2′-OMe modifications at positions 1, 3, 7, 9, 11, 13, 15, 17, and 19 to 23, and 2′-F modifications at positions 2, 4 to 6, 8, 10, 12, 14, 16, and 18 (counting from the 5′ end); and (iii) phosphorothioate internucleotide linkages between nucleotide positions 1 and 2, between nucleotide positions 2 and 3, between nucleotide positions 21 and 22, and between nucleotide positions 22 and 23 (counting from the 5′ end).
In another particular embodiment (paragraphs [0164]-[0173]), the dsRNA agents of the present invention comprise: (a) a sense strand having: (i) a length of 21 nucleotides; (ii) three GalNAc derivatives attached through a trivalent branched linker to the 3’-end; (iii) 2′-OMe modifications at positions 1 to 6, 8, 10, 12, 14, and 16 to 21, and 2′-F modifications at positions 7, 9, 11, 13, and 15; and (iv) phosphorothioate internucleotide linkages between nucleotide positions 1 and 2, and between nucleotide positions 2 and 3 (counting from the 5′ end); and (b) an antisense strand having: [0171] (i) a length of 23 nucleotides; (ii) 2′-OMe modifications at positions 1, 5, 7, 9, 11, 13, 15, 17, 19, and 21 to 23, and 2′-F modifications at positions 2 to 4, 6, 8, 10, 12, 14, 16, 18, and 20 (counting from the 5′ end); and (iii) phosphorothioate internucleotide linkages between nucleotide positions 1 and 2, between nucleotide positions 2 and 3, between nucleotide positions 21 and 22, and between nucleotide positions 22 and 23 (counting from the 5′ end).
Maier did not teach a guide strand comprising a 23-nucleotide sequence in which positions 2, 12, 14, and 16 were 2’-F nucleotides and the other 19 nucleotides were 2’-O-methyl nucleotides.
Freier taught double stranded compounds for inhibiting gene expression via RNA interference (abstract and paragraphs [0025] and [0034]. The compounds may be of 19-24 nucleobases in length [0034] and comprise an antisense (guide) strand complementary to a target mRNA and a sense (passenger strand) complementary to the antisense strand [0202].
Freier taught that “the relative duplex stability [in an RNA-RNA duplex] can be enhanced by replacement of 2'-OH groups with 2'-F groups” [0118], and that the same can be expected of 2’-alkoxy substitutions [0119]-[0120]. Freier compared constructs consisting of a combination of 2’-F and 2’-O-methyl nucleotides corresponding unmodified constructs (see Examples 29-31). For several of the constructs, an alternating 2'-O-methyl/2'-fluoro (2'-OMe/2’-F) modification pattern was shown to be comparable to or better than the parent (unmodified RNA) construct in efficacy of target mRNA reduction. Furthermore, the stability of an alternating 2'-OMe/2’-F modified construct was more than 8-fold that of the unmodified compound (see [0314] and [0316] and example 32. Freier also exemplified a construct comprising a guide strand consisting of blocks of 2’F and blocks of 2’-O-methyl nucleotides (see paragraphs Tables 12 and 13 pages 52-54).
Bramsen taught that modification of the ribose2’-OH is the most popular approach in siRNA design, and that the most widely used modifications were small electronegative substitutions such as 2’-F, DNA, and 2’-OMe. 2’-F is among the best tolerated modification types and therefore allows the creation of highly modified, active siRNAs: both strands tolerate 2′-F modification at most positions and substitution of all siRNA pyrimidines was reported to greatly enhance serum stability and to support effective silencing in vitro and in vivo (see last full paragraph of left column on page 6). Bramsem states “[t]he 2’-OMe modification has been extensively used to increase siRNA nuclease resistance and proven particular successful in combination with other 2′-modifications, e.g., 2′-F, to generate fully substituted, nuclease resistant, yet functional siRNAs” (see sentence bridging columns on page 6). However, Bramsen taught that the effects of 2’-OMe modifications on siRNA activity may be too sequence specific for general siRNA design (page 8, penultimate sentence of left column), implying that the effects of this type of modification on siRNA activity may vary with the nucleobase sequence of the siRNA. See last full sentence of right column on page 6.
Angart taught that the most common siRNA modifications include altering 2’-OH to 2’-F or 2’-OMe to prevent recognition of the RNA by nucleases and TLR7 and TLR8, but that “no rules exist defining which chemical modifications are most useful and how they are best applied.”
In view of the teachings of Maier and Freier, it was routine in the art to make siRNAs with guide and passenger strands consisting of 2’-O-methyl and 2’-F nucleotides, and to vary the number and position of these nucleotides in the process of developing inhibitory agents. Moreover, the fact that there were no established per se rules limiting the distribution these modifications, and the fact that the effectiveness of such modifications may be influenced by the nucleobase sequence of the siRNA, would motivate one of skill to engage in optimization in order to determine the most effective pattern. Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to have arrived at the patterns of 2’-F and 2’-O-methyl nucleotides in instant claims 1, 4-6, 13, 16, 18, and 20 absent secondary considerations such as unexpected results commensurate in scope with the claims. With regard to claims 8, 12, 15, and 17, Maier also taught sense strands having phosphorothioate (PS) linkages between the first and second nucleotides and the second and third nucleotides, as well as antisense strands having phosphorothioate linkages between nucleotides 1-2, 2-3, 21-22, and 22-23. Thus, the invention as a whole was prima facie obvious.
Claims 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Maier et al., (US 20170275626, filed 8/14/2015), Freier et al., (US 20070066549), Bramsen et al., (Front. Genet. (2012) 3:154), Angart et al., (Pharmaceuticals (2013) 6: 440-468) as applied to claims 1, 4, 8, 12, 13, 15, 17, 18, and 20 above, and further in view of Butler et al., (US 20150211006).
The Maier and Freier references rendered obvious polynucleotide molecules for inhibiting gene expression comprising passenger and guide strands wherein the guide strand comprises a 23-nucleotide sequence of 5'-nNfnnnnnnnnnNfnNfnNfnnnnnnn-3 ' wherein Nf is a 2’F nucleotide and n is a 2’-O-methyl nucleotide, and wherein the guide strand comprises two phosphorothioate linkages at each end (between nucleotides 1-2, 2-3, 21-22, and 22-23).
These references did not teach stereochemically enriched phosphorothioate linkages.
It was apparent from the teachings of Butler that the inclusion of stereospecific phosphorothioate linkages at the termini of siRNA antisense strand could influence potency of the siRNA.; Specifically, an siRNA comprising Rp stereochemistry at the 5' end (between nucleotides n1 and n2) combined with a Sp stereochemistry at the 3' end (between nucleotides n20 and n21) of the antisense strand showed a significant target mRNA knockdown improvement over stereo-random control siRNA. See [2045].
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to have modified the guide (antisense) strand resulting from the combination oof Maier and Freier by modifying one of the phosphorothioate linkages at the 5’ end to be a stereo-enriched an Rp linkage, and by modifying one of the phosphorothioate linkages at the 3’ end to be a stereo-enriched Sp linkage. One would have been motivated to do so because Butler taught that such a modification increased the effectiveness of an siRNA.
Thus, the invention as a whole was prima facie obvious.
Applicant’s Arguments Regarding Claim Rejections Under 35 USC § 103
Applicant's arguments filed 09/10/2025 have been fully considered but they are not persuasive.
Applicant argues that the specification demonstrates that different patterns of 2-Omethyl and 2’-fluoro modifications can result in different levels of gene silencing activity and therefore that the claimed modification pattern was not obvious to optimize. Applicant further relies on comparisons between compounds Z89 and Z90, and between Z24 and Z90 and Z162 and Z222, including the data presented in Tables 4 and 14, and Figure 15, as evidence of unexpected results.
The arguments are not persuasive for the following reasons:
First, the pending claims are directed to a modified polynucleotide molecule, not to methods of treatment or methods requiring any particular biological performance. Although the preamble recites “a polynucleotide molecule for inhibiting a target gene expression,” the body of the claim does not require any particular degree of inhibition, duration of inhibition, dose potency, or in vivo efficacy. Thus, evidence directed to improved inhibition at a particular dose (e.g., 0.25 mg/kg), at selected time points, or for a particular duration is not commensurate with the scope of the claimed polynucleotide molecule.
Second, Applicant’s evidence is likewise not commensurate in scope with the claims because the relied-upon data were generated using a small number of AT3-targeting RNAi molecules. The pending claims, however, are not limited to any particular sequence or target gene. As previously noted, Bramsen teaches that the effects of 2”-O-methyl modifications on siRNA activity are sequence dependent. Consequently, any advantage observed for one particular sequence cannot reasonably be extrapolated across the full scope of the presently claimed genus.
Third, Applicant has not compared the claimed modified polynucleotide molecule to the closest prior art. Evidence of unexpected results is most probative when the claimed invention is compared with the closest prior art. Here, Applicant compares the claimed modification pattern to Applicant’s own internally developed modified molecules (e.g., Z24, Z90, Z162, and Z222) rather than to the modification patterns disclosed by Maier and the other applied references. Accordingly, the submitted comparisons do not persuasively demonstrate that the claimed modified polynucleotide molecule possesses unexpected properties over the closest prior art.
Fourth, the Examiner does not agree that the submitted data establish a surprising or unexpected improvement in performance. Applicant characterizes Figure 15 as demonstrating that Z90 outperforms Z24 across all tested time points at 0.25 mg/kg. However, the data do not demonstrate a consistent or pronounced superiority throughout the study, as evidenced by time points at 10 days and 30-60 days. Moreover, Table 14 and its corresponding Figure 17 does not report statistical analyses sufficient to establish that the observed differences are statistically significant. That is, Table 14 does not report variance and the variance reported as error bars in Figure 17 among molecules at each timepoint is indistinguishable, making it impossible to determine whether the observed numerical differences reflect meaningful biological differences other than ordinary experimental variability.
Furthermore, the differences reported between the compared molecules are relatively modest and are consistent with the degree of variability expected in the RNA interference art when different modification patterns are evaluated. The applied references themselves recognize that different arrangements of 2’-O-methyl and 2’-fluoro modifications may produce varying levels of activity while nevertheless remaining functional siRNA molecules. Thus, the variability relied upon by Applicant is consistent with the expectations of one of ordinary skill in the art and does not rise to the level of an unexpected result sufficient to overcome a prima facie case of obviousness.
Applicant additionally argues that the specification demonstrates that certain modification patterns can substantially reduce activity or even render molecules inactive. The Examiner agrees that different modification patterns may produce different levels of activity; however, such variability does not undermine the rationale for optimization relied upon in the rejection. The applied references collectively teach that 2’-O-methyl and 2’-fluoro modification were routinely varied in both number and position to optimize siRNA properties and further teach that no universal positional rules existed. Routine optimization of known variables where prior art provides a reasonable expectation that functional molecules will results remains obvious even though different modification patterns may exhibit differing degrees of activity. Indeed, Maier demonstrates that different patterns of 2’-O-methyl and 2’-fluoro modifications result in varying degrees of knockdown activity. Accordingly, the level of variation relied upon by Applicant is consistent with the variability already observed in the prior art rather than evidence of an unexpected result.
Accordingly, Applicant’s evidence is insufficient to establish unexpected results sufficient to outweigh prima facie case of obviousness established by the applied prior art. Therefore, the rejection under 35 USC § 103 is maintained.
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, 4, 13, 18 and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 53-69 of copending Application No. 18/614396 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The ‘396 patent claimed a nucleic acid molecule comprising an antisense strand of SEQ ID NO: 14 and a sense strand of SEQ ID NO: 13. SEQ ID NO: 14 is a 23mer with 2’F modifications at positions 2, 12, 14, and 16, and the remaining nucleotides are 2’-O-methyl nucleotides. SEQ ID NO: 13 is a 21mer wherein positions 7, 9, and 11 are 2’F nucleotides and the remaining nucleotides are 2’-O-methyl nucleotides. See e.g. claims 59 and 60. Thus ‘396 accounts for all of the limitations of instant claims 1, 4-6, 13, and 16.
The ‘396 application also claimed such nucleic acid molecules wherein an asialoglycoprotein receptor targeting moiety such as GalNAc, was conjugated to the 3’ end of the sense strand via a linker. See claims 61-67. Thus the ‘396 claims accounted for the limitations of instant claims 18 and 20.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 8-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 53-69 of copending Application No. 18/614396 as applied to claims 1, 4, 13, 18 and 20 above and further in view of Butler et al., (US 20150211006).
The ‘396 patent claimed a nucleic acid molecule comprising an antisense strand of SEQ ID NO: 14 and a sense strand of SEQ ID NO: 13. SEQ ID NO: 14 is a 23mer with 2’F modifications at positions 2, 12, 14, and 16, and the remaining nucleotides are 2’-O-methyl nucleotides. SEQ ID NO: 13 is a 21mer wherein positions 7, 9, and 11 are 2’F nucleotides and the remaining nucleotides are 2’-O-methyl nucleotides. See e.g. claims 59 and 60. Thus ‘396 accounts for all of the limitations of instant claims 1, 4-6, 13, and 16.
The ‘396 application did not claim molecules with phosphorothioate linkages.
It was apparent from the teachings of Butler that the inclusion of stereospecific phosphorothioate linkages at the termini of siRNA antisense strand could influence potency of the siRNA.; Specifically, an siRNA comprising Rp stereochemistry at the 5' end (between nucleotides n1 and n2) combined with a Sp stereochemistry at the 3' end (between nucleotides n20 and n21) of the antisense strand showed a significant target mRNA knockdown improvement over stereo-random control siRNA. See [2045].
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to have modified the guide (antisense) strand of the ‘396 claims by modifying one of the phosphorothioate linkages at the 5’ end to be a stereo-enriched an Rp linkage, and by modifying one of the phosphorothioate linkages at the 3’ end to be a stereo-enriched Sp linkage. One would have been motivated to do so because Butler taught that such a modification increased the effectiveness of an siRNA.
Thus, the invention as a whole was prima facie obvious.
Claims 8, 12, 15, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 53-69 of copending Application No. 18/614396 as applied to claims 1, 4, 13, 18 and 20 above and further in view of Maier et al., (US 20170275626).
The ‘396 patent claimed a nucleic acid molecule comprising an antisense strand of SEQ ID NO: 14 and a sense strand of SEQ ID NO: 13. SEQ ID NO: 14 is a 23mer with 2’F modifications at positions 2, 12, 14, and 16, and the remaining nucleotides are 2’-O-methyl nucleotides. SEQ ID NO: 13 is a 21mer wherein positions 7, 9, and 11 are 2’F nucleotides and the remaining nucleotides are 2’-O-methyl nucleotides. See e.g. claims 59 and 60. Thus ‘396 accounts for all of the limitations of instant claims 1, 4-6, 13, and 16.
The ‘396 application did not claim molecules with phosphorothioate linkages.
Maier taught that various combinations of 2'-F, 2'-OMe and phosphorothioate modifications can stabilize siRNA in serum (0008] and phosphorothioates are desirable for nuclease protection ([0680]). IN certain embodiments, Maier disclosed siRNAs in which the passenger strand was modified with phosphorothioate linkages between nucleotide positions 1 and 2, between nucleotide positions 2 and 3, and the guide strand was modified with phosphorothioate linkages between nucleotide positions 1 and 2, between nucleotide positions 2 and 3, between nucleotide positions 21 and 22, and between nucleotide positions 22 and 23 (counting from the 5′ end). See e.g. paragraphs [0154-[0173]) especially at [0154], [0158], [0163], and [0167].
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to have used the phosphorothioate modification pattern of Maier in the molecules of the ‘396 claims. One would have been motivated to do so because Maier taught that such linkages protected oligomers from nuclease. One of ordinary skill appreciates that modification of oligonucleotide termini, as exemplified by Maier provides protection against exonucleases. In so doing one would have arrived at the PS modification patterns of instant claims 8, 12, 15, and 17 Thus the invention as a whole was prima facie obvious.
Applicant’s Arguments Regarding Double Patenting
Applicant’s arguments, see pages 7-8, U.S. Patent No. 11,981,703 as a referenced patent, filed 09/10/2025, with respect to claims 1, 4, 8, 12, 13, 15, and 17-20 have been fully considered and are persuasive. The rejection of claims 1, 4, 8, 12, 13, 15, and 17-20 has been withdrawn.
Applicant's arguments filed 09/10/2025 have been fully considered but they are not persuasive regarding the provisional nonstatutory double patenting rejection as there is still a 103-rejection remaining.
New Ground of Rejection(s)
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 19 is rejected under 35 U.S.C. 103 as being unpatentable over Maier et al., (US 20170275626, filed 8/14/2015), Freier et al., (US 20070066549), Bramsen et al., (Front. Genet. (2012) 3:154), and Angart et al., (Pharmaceuticals (2013) 6: 440-468) as applied to claims 1, 4, 8, 12, 13, 15, 17, 18, and 20 above, and further in view of Ouahabi AA., et al., (J Am Chem Soc. 2015 Apr 29;137(16):5629-35).
The teachings of Maier, Freier, Bramsen, and Angart are incorporated herein by reference to the maintained 103 rejection above.
Neiher Maier, Freier, Bramsen, nor Angart teach the linker X2 as recited in instant claim 19.
Ouahabi teaches the linker X2 as recited in instant claim 19, see abstract and rest of article. Ouahabi further teaches that such a Phosphoramidite chemistry was found to be a rapid and convenient method for the synthesis of non-natural sequence-encoded polyphosphates, and that long sequence-defined polymers can be synthesized using phosphoramidite chemistry, see conclusion.
It would have been obvious to a person having ordinary skill in the art (PHOSITA) to employ the linker X2 as recited in instant claim 19 at the 3’ terminus to conjugate a ligand to the modified polynucleotide molecule. A PHOSITA would have been motivated to do because Quahabi teaches that X2 is a known linker suitable for phosphoroamidate-based oligonucleotide synthesis and conjugation, and substituting one known linker for another known linker used for the same purpose represents a predictable use of prior art elements according to their established functions. A PHOSITA would have had a reasonable expectation of success because Ouahabi explicitly teaches its applicability to oligonucleotide constructs using established phosphoroamidate chemistry.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to COREY LANE BRETZ whose telephone number is (571)272-7299. The examiner can normally be reached M-F 7:30am - 6:30pm.
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/COREY LANE BRETZ/Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
Prosecution Insights