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
Applicant’s amendments and remarks filed on May 27, 2026 are acknowledged. Claims 2-7 and 13-38 have been canceled. Claims 1, 44, and 46 were amended. Claims 1, 8-12, and 39-49 are pending and are examined on the merits herein.
Withdrawn Objections
In view of Applicant’s amendments and response, the nucleotide sequence disclosure deficiency is withdrawn.
In view of Applicant’s amendments and response, the objections to the specification and claims 44 and 46 are withdrawn.
Withdrawn Rejections
In view of Applicant’s amendments and response, the 35 U.S.C. 112(b), 35 U.S.C. 112(a) enablement, and 35 U.S.C. 112(d) rejections are withdrawn.
Specification
The disclosure is objected to because of the following informality:
Paragraph [0049] reads in part “rabbis” and should read “rabbits”.
Appropriate correction is required.
New Grounds of Rejections Necessitated by Amendment
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.
The following is a new rejection, necessitated by the amendment to the claims in the reply filed May 27, 2026.
Claims 1, 8-12, 39, and 47-49 are rejected under 35 U.S.C. 103 as being unpatentable over Swayze (WO 2008/049085; reference previously cited by the Examiner) in view of Bennett et al. (US 2006/0003953).
Regarding claims 1 and 8, Swayze teaches gapmer oligomeric
compounds for reduction of target RNA in vivo comprising different nucleotide modifications within one or both wing regions [abstract]. Swayze teaches compositions containing two or more antisense compounds targeted to different regions of the same nucleic acid target [page 38, lines 5-6]. Swayze also teaches gap-widened antisense oligonucleotides that are 18 to 24 nucleotides in length with various wing-gap-wing motifs such as 5-13-5 [page 11, fourth paragraph bridging to page 12]. Further, in certain embodiments, the nucleotides in the gap are unmodified and the nucleotides in the wings are modified. In addition, in certain embodiments, the modification(s) within each wing are the same [page 11, second paragraph]. Swayze also teaches that each internucleoside linkage of a gapmer antisense oligonucleotide is a phosphorothioate modified internucleoside linkage [page 3, line 36]. Further, in certain embodiments, oligomeric compounds comprise one or more nucleosides having a modified sugar moiety (e.g., 2’-OCH3) to increase the affinity of the antisense compound for its target and/or increase nuclease resistance [page 19, last paragraph bridging to page 20]. Although Swayze does not explicitly teach the claimed modification pattern of the oligonucleotide as recited in claim 1, it would have been obvious to try because Swayze taught gap-widened antisense oligonucleotides with a 5-13-5 wing-gap-wing motif wherein the nucleotides in the wings comprise the same modification. One of ordinary skill in the art would have had a reasonable expectation of success because Swayze taught that oligomeric compounds comprising one or more nucleosides having a modified sugar moiety such as 2’-OCH3 increases the affinity of the antisense compound for its target and/or increases nuclease resistance.
Regarding claim 9, Swayze teaches that the antisense compounds
can be utilized in pharmaceutical compositions by adding an effective amount of a compound to a suitable pharmaceutically acceptable diluent or carrier [page 39, lines 7-8].
Regarding claims 10 and 11, Swayze teaches that 50 nM to 300 nM of
antisense oligonucleotide is used when the antisense oligonucleotide is transfected using a liposome reagent [page 41, second full paragraph].
Regarding claim 12, Swayze teaches that the concentration of oligonucleotide used varies from cell line to cell line. To determine the optimal oligonucleotide concentration for a particular cell line, the cells are treated with a positive control oligonucleotide at a range of concentrations. Although Swayze teaches that 50 nM to 300 nM of antisense oligonucleotide is used when the antisense oligonucleotide is transfected using a liposome reagent [page 41, second full paragraph], Swayze does not explicitly teach that the oligonucleotide concentration is at least 300 nM. However, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the claimed concentration in the process of optimizing the antisense oligonucleotide concentration.
Regarding claim 39, Swayze teaches that the compositions can also be
combined with other non-antisense compound therapeutic agents [page 38, line 7].
Regarding claim 47, Swayze teaches that the pharmaceutical
compositions may be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated. In a preferred embodiment, administration is topical to the surface of the respiratory tract (e.g., by inhalation) [page 37, third full paragraph].
Regarding claims 48 and 49, with regard to the functional language recited
in the claims, the structure in the prior art is indistinguishable from the structure that is claimed, and absent evidence to the contrary the recited function is inherent in the structure. See MPEP 2112.
However, Swayze does not teach that the plurality of oligonucleotide molecules comprise a non-targeting nucleotide base sequence.
Bennett et al. teaches compounds and compositions capable of modulating the expression of a bone growth modulator in a cell, tissue or animal [abstract]. Bennett et al. teaches that control oligonucleotides are used to determine the optimal oligomeric compound concentration for a particular cell line. Furthermore, when oligomeric compounds are tested in oligomeric compound screening experiments or phenotypic assays, control oligonucleotides are tested in parallel with the compounds. In some embodiments, the control oligonucleotides are used as negative control oligonucleotides, i.e., as a means for measuring the absence of an effect on gene expression or phenotype. Bennett et al. also teaches that control oligonucleotides are shown in Table 2 wherein certain compounds are chimeric oligonucleotides composed of a central "gap" region consisting of 2'-deoxynucleotides, which is flanked on both sides (5' and 3') by "wings" [0271]. Specifically, Table 2 discloses ISIS 29848 (SEQ ID NO: 41) which has the following sequence (5’ to 3’):
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and a 5-10-5 motif. Further, paragraph [0297] discloses that ISIS 29848 is a 20-nucleotide oligomeric compound with a randomized sequence that was used as a negative control.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Swayze wherein a plurality of oligonucleotide molecules comprise a non-targeting nucleotide base sequence because Swayze taught compositions containing two or more antisense compounds targeted to different regions of the same nucleic acid target, Swayze taught gapmer oligomeric compounds for reduction of target RNA in vivo that are 18 to 24 nucleotides in length with various wing-gap-wing motifs such as 5-13-5, Bennett et al. taught that control oligonucleotides (chimeric oligonucleotides composed of a central "gap" region consisting of 2'-deoxynucleotides, which is flanked on both sides (5' and 3') by "wings") are used to determine the optimal oligomeric compound concentration for a particular cell line or used as a negative control oligonucleotide as a means for measuring the absence of an effect on gene expression or phenotype, and Bennett et al. taught that control oligonucleotides are tested in parallel with oligomeric compounds in screening experiments or phenotypic assays. One of ordinary skill in the art would have made such a modification because it would have amounted to a simple substitution of one known element for another to obtain predictable results.
Claims 40-42 are rejected under 35 U.S.C. 103 as being unpatentable over Swayze (WO 2008/049085; reference previously cited by the Examiner) in view of Bennett et al. (US 2006/0003953) as applied to claims 1, 8-12, 39, and 47-49 above, and further in view of Zhang et al. (US 2021/0228615; reference previously cited by the Examiner).
Regarding claims 40-42, the teachings of Swayze and Bennett et al. are discussed above.
However, Swayze and Bennett et al. do not teach that the additional therapeutic agent comprises at least one chemotherapeutic drug such as a HDAC inhibitor.
Zhang et al. teaches SMN2 oligonucleotides and compositions capable of treating SMN2-related conditions, disorders, and diseases such as SMA (spinal muscular atrophy) and ALS (amyotrophic lateral sclerosis) [abstract]. Zhang et al. also teaches that a provided chirally controlled oligonucleotide composition is a gapmer [0765]. Further, one or more additional therapeutic agents may be administered together with provided oligonucleotides wherein the additional therapeutic agent is a histone deacetylase (HDAC) inhibitor [1226].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Swayze and Bennett et al. wherein the additional therapeutic agent comprises at least one chemotherapeutic drug such as a HDAC inhibitor because Swayze and Bennett et al. taught a composition comprising oligonucleotide molecules wherein a plurality of the oligonucleotide molecules are single-stranded DNA molecules and comprise a non-targeting nucleotide base sequence and Zhang et al. taught that compositions comprising oligonucleotides and a histone deacetylase (HDAC) inhibitor are capable of treating spinal muscular atrophy and amyotrophic lateral sclerosis. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements to yield predictable results.
Claims 43 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Swayze (WO 2008/049085; reference previously cited by the Examiner) in view of Bennett et al. (US 2006/0003953) as applied to claims 1, 8-12, 39, and 47-49 above, and further in view of Iversen (US 2011/0118334; reference previously cited by the Examiner) and Shaw et al. (US 2013/0090367; reference previously cited by the Examiner).
Regarding claims 43 and 44, the teachings of Swayze and Bennett et al. are discussed above.
However, Swayze and Bennett et al. do not teach that the additional therapeutic agent comprises at least one immunomodulatory agent such as an interferon.
Iversen teaches antisense oligonucleotides for use in treating an influenza virus infection and antiviral treatment methods employing the oligonucleotides [0003]. Iversen also teaches that modulating agents utilized according to the methods may comprise RNAi oligonucleotides such as chimeric oligonucleotides, or "chimeras," which contain two or more chemically distinct regions, each made up of at least one monomer unit, i.e., a nucleotide in the case of an oligonucleotide compound [0217].
Shaw et al. teaches that therapeutic or prophylactic agents can be used in combination with the compounds described for the prevention, treatment and/or management of influenza virus infection wherein the agents include immunomodulatory agents such as interferon [0358].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Swayze and Bennett et al. wherein the additional therapeutic agent comprises at least one immunomodulatory agent such as an interferon because Swayze and Bennett et al. taught a composition comprising oligonucleotide molecules wherein a plurality of the oligonucleotide molecules are single-stranded DNA molecules and comprise a non-targeting nucleotide base sequence, Iversen taught antisense oligonucleotides for use in treating an influenza virus infection, and Shaw et al. taught that compositions comprising an immunomodulatory agent such as interferon are capable of treating an influenza virus infection. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements to yield predictable results.
Claims 45 and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Swayze (WO 2008/049085; reference previously cited by the Examiner) in view of Bennett et al. (US 2006/0003953) as applied to claims 1, 8-12, 39, and 47-49 above, and further in view of Swayze et al. (WO 2012/145697; reference previously cited by the Examiner) and Bhat et al. (US 2008/0261904; reference previously cited by the Examiner).
Regarding claims 45 and 46, the teachings of Swayze and Bennett et al. are discussed above.
However, Swayze and Bennett et al. do not teach that the additional therapeutic agent comprises at least one anti-viral drug such as acyclovir.
Swayze et al. teaches antisense compounds and methods for decreasing HBV mRNA, DNA and protein expression to treat, prevent, or ameliorate HBV-related diseases, disorders or conditions [abstract]. In certain embodiments, compounds useful for modulating expression of HBV mRNA and protein are antisense oligonucleotides [page 2, fourth full paragraph]. Swayze et al. also teaches that antisense compounds having a gapmer motif are considered chimeric antisense compounds [page 89, last paragraph].
Bhat et al. teaches modified oligomeric compounds and compositions of oligomeric compounds capable of modulating gene expression [abstract]. Bhat et al. teaches that antiviral drugs such as acyclovir may be combined in the pharmaceutical composition [0278].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Swayze and Bennett et al. wherein the additional therapeutic agent comprises at least one anti-viral drug such as acyclovir because Swayze and Bennett et al. taught a composition comprising oligonucleotide molecules wherein a plurality of the oligonucleotide molecules are single-stranded DNA molecules and comprise a non-targeting nucleotide base sequence, Swayze et al. taught antisense compounds capable of treating HBV-related diseases, disorders, or conditions, and Bhat et al. taught that compositions comprising oligonucleotides and an antiviral drug such as acyclovir are capable of modulating gene expression. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements to yield predictable results.
Response to Arguments
Applicant's arguments filed May 27, 2026 have been fully considered but they are not persuasive.
Applicant asserts the following:
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With respect to Applicant’s arguments, the Examiner agrees that Swayze does not teach that the plurality of oligonucleotide molecules comprise a non-targeting nucleotide base sequence. However, Bennett et al. teaches compounds and compositions capable of modulating the expression of a bone growth modulator in a cell, tissue or animal [abstract]. Bennett et al. teaches that control oligonucleotides are used to determine the optimal oligomeric compound concentration for a particular cell line. Furthermore, when oligomeric compounds are tested in oligomeric compound screening experiments or phenotypic assays, control oligonucleotides are tested in parallel with the compounds. In some embodiments, the control oligonucleotides are used as negative control oligonucleotides, i.e., as a means for measuring the absence of an effect on gene expression or phenotype. Bennett et al. also teaches that control oligonucleotides are chimeric oligonucleotides composed of a central "gap" region consisting of 2'-deoxynucleotides, which is flanked on both sides (5' and 3') by "wings". Therefore, based on the teachings of Bennett et al., one of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to modify the composition of Swayze wherein a plurality of oligonucleotide molecules comprise a non-targeting nucleotide base sequence because it would have amounted to a simple substitution of one known element for another to obtain predictable results.
Conclusion
No claims are 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 CHRISTINA TRAN whose telephone number is (571)270-0550. The examiner can normally be reached M-F 7:30 - 5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached on (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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