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 November 5, 2025 are acknowledged. Claims 9, 12, 32, 33, 36, 47, 49, and 50 have been canceled. Claims 30, 31, 41, and 46 were amended. Claims 1-8, 10, 11, 13-31, 34, 35, 37-46, and 48 are pending.
Election/Restrictions
Applicant’s election without traverse of Group II (claims 30-48) in the reply filed on July 14, 2025 is acknowledged.
Claims 1-8, 10, 11, and 13-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 July 14, 2025.
Claims 30, 31, 34, 35, 37-46, and 48 are examined on the merits herein.
Priority
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Withdrawn Objections
In view of Applicant’s amendments and response, the objection to the specification is withdrawn.
Withdrawn Rejections
In view of Applicant’s amendments and response, the 35 U.S.C 112(b) and 35 U.S.C 112(d) rejections are withdrawn.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the abstract is less than 50 words in length. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 31 is objected to because of the following informality:
Claim 31 recites “2’-methoxyethylribonucleotides” and should recite “2-O- methoxyethylribonucleotides”.
Appropriate correction is required.
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.
Claims 30, 31, 34, 35, 37-46, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (European Journal of Human Genetics 2004), as evidenced by Marquez et al. (Genome Research 2015), in view of Metelev et al. (WO 94/02498).
Regarding claims 30, 31, 34, 35, 37-46, and 48, Kim et al. teaches phosphorothioated antisense oligodeoxynucleotides corresponding to nucleotides 1-20 of the translation initiation site of the PKD1 mRNA [page 434, left column, third full paragraph]. Kim et al. also teaches that certain regions of a target mRNA are chosen to be annealing sites for antisense oligodeoxynucleotides and the resulting formation of an RNA-DNA duplex abolishes protein synthesis either by directly blocking translation or by mediating the degradation of target mRNA through RNase H activity [page 434, left column, first paragraph]. Further, Kim et al. teaches that the presence of PKD1 antisense oligodeoxynucleotide substantially reduced the expression of polycystin-1 in transfected 293 cells and MDCK cells as expected [page 436, right column, first paragraph]. Kim et al. also teaches a composition comprising the antisense oligonucleotide and Lipofectamine [page 434, Antisense ODNs] which is suitable for delivery to living cells [page 436, PKD1 antisense ODN causes cell proliferation; Fig. 3].
Marquez et al. is cited only to show that PKD1 pre-mRNA contains a retained intron [Supplemental Table]. Marquez et al. teaches that exitrons (exonic introns) are alternatively spliced internal regions of protein-coding exons wherein the protein-coding sequences are directly flanked by protein-coding exonic sequences [page 996, left column, first paragraph]. Thus, the antisense oligonucleotide taught by Kim et al. would be complementary to a pre-mRNA of PKD1 containing a retained intron. In addition, the antisense oligonucleotide of Kim et al. would be complementary to a pre-mRNA that contains an exon that flanks the 5’ splice site of the retained intron and an exon that flanks the 3’ splice site of the retained intron.
However, Kim et al. does not teach an antisense oligonucleotide comprising a region of 2 to 4 consecutive deoxyribonucleotides at the 5’ end or 3’ end of the antisense oligonucleotide or that the antisense oligonucleotide is single stranded. Kim et al. also does not teach that the remaining nucleotides of the antisense oligonucleotide are 2’-substituted, non-ionic or constrained sugar nucleotides, or combinations thereof. Kim et al. also does not teach that at least half or all of the internucleotide linkages are phosphorothioate.
Metelev et al. teaches that the activity of an antisense oligonucleotide depends on the binding of the oligonucleotide to the target nucleic acid, thus disrupting the function of the target, either by hybridization arrest or by destruction of target RNA by RNase H. RNase H activation (the ability to activate RNase H when hybridized with target RNA) is implicated when the target nucleic acid is RNA, since such activation can lead to the effective destruction of the target RNA molecule [page 7, second paragraph]. Metelev et al. teaches oligonucleotides ranging from about 6 to about 50 nucleotides in length [page 10, first full paragraph]. Preferably, oligonucleotides of the invention contain four or more deoxyribonucleotides in a contiguous block to provide an activating segment for RNase H wherein the segment may be present at any location within the oligonucleotide [page 10, last paragraph] and can range from 1-49 deoxyribonucleosides [page 11, first paragraph]. Further, the oligonucleotides of the invention contain ribonucleosides, 2’-substituted ribonucleosides or combinations thereof, preferably 6 or more ribonucleosides and/or 2’-substituted ribonucleosides to enhance duplex stability and can be present singly, in pairs, or in larger contiguous segments at any position within the oligonucleotide [page 11, second paragraph]. Metelev et al. illustrates in Figure 2 (reproduced below) an antisense oligonucleotide that is single stranded and is 100% complementary over its entire length to a portion of the target RNA.
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Metelev et al. teaches Oligo E in Table II (reproduced below) which comprises 8 contiguous 2’-OMe modified ribonucleosides in the 5’ end. Metelev et al. also teaches that all internucleotide linkages are phosphorothioate linkages as shown in Table II [page 20].
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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 antisense oligonucleotide of Kim et al. with the modifications taught by Metelev et al. to decrease the expression of PKD1 by degrading the transcript because Metelev et al. taught that hybrid oligonucleotide E demonstrated site specific cleavage of RNA by RNase H [page 24, first paragraph]. Further, Metelev et al. taught that varying the numbers and positions of phosphorothioate internucleotide linkages, deoxyribonucleosides, and ribonucleosides or 2’-substituted ribonucleosides allows investigators to evaluate the effect of RNase H activation [page 12, first full paragraph].
Response to Arguments
Applicant's arguments filed November 5, 2025 have been fully considered but they are not persuasive.
Applicant asserts the following:
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Applicant further asserts that the claimed product does not permit RNase H cleavage of the target pre-mRNA and instead is specifically designed to act in a different way than the antisense oligonucleotides in the prior art.
These arguments are not found persuasive. The specification filed on March 17, 2022 discloses that the term “antisense oligonucleotide” is defined as a single-stranded oligonucleotide having a nucleobase sequence that permits hybridization to a corresponding region or segment of a target nucleic acid [page 5, lines 26-28]. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., instantly claimed oligonucleotides are directed to modulating RNA splicing) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant asserts that the teachings of Metelev et al. relied upon by the Examiner teaches away from the instantly claimed invention because the instantly claimed oligonucleotides do not activate RNase H. Further, Applicant fails to see the relevance of Metelev et al. Oligo E which comprises 8 contiguous 2’-OMe modified ribonucleosides in the 5’ end.
These arguments are not found persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., instantly claimed oligonucleotides are directed to modulating RNA splicing) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In addition, claim 30 recites in part “wherein the antisense oligonucleotide comprises 1 region comprising from 2 to 4 consecutive deoxyribonucleotides”. The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). Therefore, Metelev et al. Oligo E which comprises 8 contiguous 2’-OMe modified ribonucleosides in the 5’ end meets the limitation of claim 30 as currently written.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 at (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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