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
Status of Application/Amendment/Claims
Applicant's response filed 01/22/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 10/22/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 01/22/2026, claims 1, 8, 21-23, 25, 48 and 89-96 are pending and are currently under examination.
The rejection of claims 1, 8, 21-23, 25, 48 and 87-95 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in response to claim amendments.
The 102 and 103 rejections are withdrawn in view of claim amendments and in view of the new rejections herein.
The Double Patenting rejection is withdrawn as the conflicting claims in the co-pending application 17,781,569 have been canceled.
Claim Rejections - 35 USC § 102 – necessitated by claim amendments
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 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.
Claim(s) 1, 8, 25, 91, 92, 94 and 96 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schlingensiepen et al. (US 20050130927).
Claim interpretation
The specification defines an antisense oligonucleotide as any nucleic acid having sufficient complementarity to a target RNA (page 11) and teach antisense sequences having SEQ ID Nos. 110-127 that target cryptic splice sites within intron 1 of SCL6A1 (Table 4).
This is interpreted to mean any prior art teaching a nucleic acid sequence with the same structure as the claimed antisense would meet the limitations of an antisense oligonucleotide that binds to a target region of an SLC6A1 RNA. Sufficient complementarity is interpreted to mean the sequence does not have to be 100% complementary to the target region.
Regarding claims 1, 8, 91, 92, 94 and 96, Schlingensiepen et al. teach an antisense oligonucleotide having SEQ ID No. 1747 that comprises 13 nucleotides of SEQ ID No. 112. Schlingensiepen et al. teach the antisense can have modifications such as 2’-MOE and phosphorothioate (0025, 0041).
Regarding claim 25, the instantly claimed SEQ ID No. 112 is described as binding to regions 11006348-11006371 of a cryptic splice sites within intron 1 of SCL6A1 (Table 4). Table 2 describes target region having SEQ ID No. 68 as within this region and thus the antisense sequence of Schlingensiepen et al. meet the limitations of this claim.
Because Schlingensiepen et al. teach an antisense oligonucleotide having one or more modifications and targets a cryptic splice site, the function of increasing the expression of GAT-1 is an inherent property.
Thus Schlingensiepen et al. anticipates the instant claims.
Claim Rejections - 35 USC § 103– necessitated by claim amendments
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 21, 93 and 95 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schlingensiepen et al. (US 20050130927) and Watt (6,492,170).
Schlingensiepen et al. is relied upon as above but does not teach the antisense comprises a LNA or a 5-methylcytosine.
Regarding claims 93 and 95, Watt teach modifications of antisense compounds which are known to increase stability and teach modifications include LNA and 5-methylcytosine (col. 7-8).
Regarding claim 21, Watt et al. teach the oligonucleotide can include attached functional groups which meets the limitations of a ligand in claim 21 (col. 10). It would have been obvious to include these known modifications into the antisense oligonucleotide taught by Schlingensiepen et al. to increase stability.
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Claim 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schlingensiepen et al. (US 20050130927) and Geary et al. ("Pharmacokinetic/pharmacodynamic properties of phosphorothioate 2ʹ-O-(2-methoxyethyl)-modified antisense oligonucleotides in animals and man." Antisense Drug Technology. CRC Press, 2007).
Schlingensiepen et al. is relied upon as above but does not teach the antisense comprises the modification pattern of claim 22 wherein the antisense is fully modified with 2ʹ-O-(2-methoxyethyl) modifications and phosphorothioate internucleoside linkages.
Geary et al. teach the advantages of modifying an antisense with all 2ʹ-O-(2-methoxyethyl) and phosphorothioate modifications such as increased stability and affinity to the target as well as improved stability for oligodeoxynucleotides compared with phosphodiester (DNA) but also much improved distribution and pharmacokinetics (see page 894 Discussion). It would have been obvious to one of ordinary skill in the art to modify the antisense oligonucleotide for these reasons.
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Claim 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schlingensiepen et al. (US 20050130927) and Subramanian, Romesh R., et al. "Enhancing antisense efficacy with multimers and multi-targeting oligonucleotides (MTOs) using cleavable linkers." Nucleic Acids Research 43.19 (2015): 9123-9132 of record cited on 892 mailed 10/22/2025)
Schlingensiepen et al. is relied upon as above but does not teach the antisense is a multimeric antisense oligonucleotide.
Subramanian et al. teach the use of multimer antisense oligonucleotides linked together provide increase binding, distribution and increased in vivo efficacy (see abstract and discussion page 9129-91630), making it obvious to one of ordinary skill in the art to make a multimeric antisense oligonucleotide using the antisense taught by Schlingensiepen et al.
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Allowable Subject Matter
Claim Objections
Claim 23 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Sequences consisting of SEQ ID Nos. 110-127 of claim 23 are free of the prior art searched. Schlingensiepen et al. (cited above) teach an antisense having 13 nucleotides of SEQ ID No. 112 but does not teach the full length of 20 nucleotides and does not provide motivation to increase the length from 13 to consist of 20 nucleotides of the claimed sequence.
The prior art of Philippi et al. (US Application 20080213765 cited on 892 mailed 10/22/2025) teach antisense oligonucleotides that binds to a target region in a SLC6A1 RNA transcript (para [0025]) wherein the target region comprises a splice modulatory element (para [0061]) wherein the splice modulatory element comprises one or more of a non-productive splice site, an exonic splicing enhancer, an exonic splicing silencer, an intronic splicing enhancer, or an intronic splicing silencer (para [0061]). Phillipe et al. do not teach or make obvious reasons to specifically target a 3’ or 5’ cryptic splice site of a SLC6A1 RNA transcript.
Mattison et al. (SLC6A1 variants identified in epilepsy patients reduce y- aminobutyric acid transport, Epilepsia, Sep. 2018, 59(9): e135-e141. Epub Aug. 21, 2018 cited on IDS filed 08/06/2025) teach SLC6A1 encodes the electrogenic sodium and chloride-coupled y-aminobutyric acid (GABA) transporter, GAT-1, which is responsible for the reuptake of the inhibitory neurotransmitter GABA from the synapse (introduction page e135). Mattison et al. discloses target regions in an SLC6A1 RNA transcript that comprise a splice modulatory element (Abstract and Figure 1) and these target regions were found to reduce GAT-1 protein function (Abstract and Discussion pages e139-140). Mattison et al. do not teach specifically targeting a 3’ or 5’ cryptic splice site and do not make it obvious to try targeting these regions.
SLC6A1 is identified as GenBank NM_003042 and programs such as Blast and Powerblast are known (Zhang et al., PowerBLAST: A New Network BLAST Application for Interactive or Automated Sequence Analysis and Annotation, Genome Research, June 1, 1997, Volume 7, Number 6, pp. 649-656 cited on IDS filed 08/06/2025) to map out the specific sequence of the splice modulatory elements however neither these programs or the prior art identify targeting 3’ or 5’ cryptic splice site and do not make it obvious to try targeting these regions using an antisense oligonucleotide consisting of SEQ ID Nos. 110-127.
Conclusion
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).
706.07(a) Final Rejection, When Proper on Second Action [R-07.2015]
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Second or any subsequent actions on the merits shall be final, except where the examiner introduces a new ground of rejection that is neither necessitated by applicant’s amendment of the claims, nor based on information submitted in an information disclosure statement filed during the period set forth in 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p). Where information is submitted in an information disclosure statement during the period set forth in 37 CFR 1.97(c) with a fee, the examiner may use the information submitted, e.g., a printed publication or evidence of public use, and make the next Office action final whether or not the claims have been amended, provided that no other new ground of rejection which was not necessitated by amendment to the claims is introduced by the examiner. See MPEP § 609.04(b).
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY CHONG at 571-272-3111. The examiner can normally be reached Monday thru Friday 9-5 pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/Primary Examiner, Art Unit 1636