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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 27, 2026 has been entered.
Application Status
Applicant’s remarks and amendments to the claims filed July 27, 2026 are acknowledged. Claims 1 and 24 were amended, claims 6, 15, 17, 21, and 23 were cancelled, and claims 27-31 were introduced. Claims 1-2, 4-5, 14, 19, 22, and 24-31 are pending.
Restriction/Election
Claims 25-26 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-2, 4-5, 14, 19, 22, 24, and 27-31 are under examination herein.
Withdrawn Rejections
Applicant’s remarks regarding the unexpectedly advantageous properties are found convincing to overcome the § 103 rejections raised in the prior action over Lenk in view of Monia, GenBank, and Freier, and the aforementioned references in further view of Jafar-Nejad and Peng-Ho. See reasons described in paragraph 13 below. These rejections are withdrawn, accordingly.
Applicant’s remarks and amendments to the claims have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow. Any rejection or objection not reiterated herein has been overcome by amendment.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed provisional application, Application No. 63/186,342, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, Application No. 63/186,342, while disclosing instant SEQ ID NOs: 1-114 and 147-156 (Table 1), does not disclose instant SEQ ID NOs: 115-146. The first disclosure of SEQ ID NOs: 115-146 is in the instant application, filed May 10, 2022. Since all claims under examination encompass SEQ ID NOs: 135 and 144, and these sequences were not disclosed in Application No. 63/186,342, all claims under examination have an effective filing date of May 10, 2022 (i.e., the filing date of the instant application).
Claim Objections
Claim 5 is objected to because of the following informalities:
Claim 5 recites “wherein the composition is provided in a solution or carrier formulated for intrathecal injection.” The claims are directed to a product, and not a method, and therefore, it would be preferable to amend the claim to recite "wherein the composition is formulated
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 4-5, 14, 19, 22, 24, and 27-31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The rejections that follow are new and necessitated by Applicant’s amendments to the claims.
Claim 1 recites “at least one oligonucleotide selected from the group consisting of: SEQ ID NO: 135 in a gapmer… SEQ ID NO: 144 in a gapmer…;,” which would be interpreted as requiring at least one oligonucleotide which is one of the recited SEQ ID NOs in one of the specific modification patterns. However, the claim later recites further modifications of the oligonucleotide: “wherein the oligonucleotide has a length of 20 to 25 bases and, all cytosine bases in the oligonucleotide comprise a 5-methyl modification.” The grouping of oligonucleotides from which the at least one oligonucleotide must be selected would not be interpreted as “open” to additional modifications due to the phrase “selected from the group consisting of,” and therefore, the latter recited limitations which attempt to expand the modification pattern of the selected oligonucleotide are confusing, because it is no longer clear what structure(s) are actually required of the at least one oligonucleotide.
Claims 2, 4-5, 14, 19, 22, 24, and 27-31 are rejected for depending from claim 1 and failing to remedy the indefiniteness. Regarding claims 27, and 30-31, these claims also appear to expand the modification pattern of the selected oligonucleotide (“further comprise at least one hexose ring (HNA),” “further comprise at least one unlinked ribose ring (UNA)”)s, and are confusing for the same reasons described above.
In the interest of compact prosecution, the at least one oligonucleotide is interpreted hereinafter as an oligonucleotide consisting of a nucleotide sequence 20 nucleotides in length (i.e., the length of each of SEQ ID NOs: 135 and 144 from which the claimed oligonucleotide is selected), comprising one or more nucleobase, sugar, and/or backbone modifications, wherein the nucleobase sequence of the oligonucleotide is 100% identical to the sequence set forth in SEQ ID NO: 135 or SEQ ID NO: 144, wherein nucleotides 1-4 and 17-20 of the oligonucleotide each comprise 2’-MOE, wherein nucleotides 5-16 of the oligonucleotide each comprise 2’-H, wherein either the 2nd, 3rd, and 18th linkages, or the 2nd, 3rd, 4th, and 18th linkages of the oligonucleotide are phosphodiester linkages, and all remaining linkages are phosphorothioate linkages, and wherein all cytosine bases in the oligonucleotide comprise 5-methylcytosine.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 28 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The rejection that follows is new and necessitated by Applicant’s amendments to the claims.
Claim 28 recites “The composition of claim 1, wherein the oligonucleotide is lyophilized in a tube.” The term “composition” would be interpreted as a mixture of the at least one oligonucleotide and at least one additional element (e.g., a solution or carrier). Claim 28 is directed to the oligonucleotide lyophilized in a tube, such that the claim no longer appears to include the “composition” of claim 1. Thus, the claim fails to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. It would be remedial to recite, for example, “The composition of claim 1, wherein the oligonucleotide is lyophilizedcomposition is lyophilized
Allowable Subject Matter
Claims 1-2, 4-5, 14, 19, 22, 24, and 27-31 would be allowable if amended to overcome the objection, rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, and rejection(s) under 35 U.S.C. 112(d) or 35 U.S.C. 112 (pre-AIA ), fourth paragraph, set forth in this Office action. See the proposed Examiner’s amendments to the claims attached herein with the Interview Summary, which would be sufficient to place the claims in condition for allowance.
The specification demonstrates that a composition comprising at least one oligonucleotide as interpreted herein exhibits a plateau in SCN8A transcript knockdown (“Fig. 23 shows evidence of a plateau in transcript knockdown in human NGN2 stem cell-derived neurons. It has been observed that Nav1.6 null mice die early… Literature suggests that hypomorphic mice expressing 10% of normal levels of Nav1.6 experience severe dystonia… Evidence suggests that DEE13 mice treated with an ASO that knocks down Scn8a 50% experience decreased seizures and increased lifespan… we hypothesize that the therapeutic window is within the range of 50-90% protein knockdown… these four compositions exhibit a maximal knockdown of about 70-80% for the concentration range tested,” pg. 35-36). Based on the prior art, and as described in Applicant’s remarks, a plateau in transcript knockdown at less than 100% is advantageous for clinical application of the composition comprising the at least one oligonucleotide.
While SCN8A-targeting antisense oligonucleotides, and means to design oligonucleotides comprising various gapmer structures, and combinations of sugar, base, and backbone modifications were known in the art, there is no teaching or suggestion in the prior art that would have allowed the skilled artisan to predict that the oligonucleotide as interpreted herein would have this advantageous effect. In order to arrive at the oligonucleotide as interpreted herein, the skilled artisan would have had to vary essentially every parameter of a known SCN8A-targeting prior art oligonucleotide, e.g., the sequence, gapmer design, and chemical modifications, etc., of the oligonucleotide of Lenk (of record). Given the absence of effective knockdown prediction means in the art, the skilled artisan would have had no direction to arrive at the oligonucleotide out of the many tens of thousands of possible SCN8A-targeting prior art oligonucleotides, and would have had to experimentally validate the knockdown effect of each of the tens of thousands of possible oligonucleotides in vitro and/or in vivo. The instantly claimed compositions comprising the at least one oligonucleotide as interpreted herein are free of the prior art reviewed during examination, accordingly.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNA L PERSONS whose telephone number is (703)756-1334. The examiner can normally be reached M-F: 9-5pm.
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/JENNA L PERSONS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600
