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 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. 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examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on February 4, 2026 has been entered.
Status of Claims/Rejections
Claims 1, 8-12, and 19-22 are currently pending and under examination on the merits.
Any rejections not repeated from the rejections affirmed by the PTAB on the decision rendered on December 4, 2025 are hereby withdrawn.
The following rejections are the only rejections applied in this application.
Response to Arguments
Applicant’s arguments filed on February 4, 2026 pertaining to 35 U.S.C. 112(b) and 112(d) rejections of record have been considered but are moot.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 9-12, and 22 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
For this rejection, the “integer between 10 and 18” is interpreted as 11, 12, 13, 14, 15, 16, and 17.
Claims 1 and 9-12 are broadly drawn to a PNA derivative of at least 11 nucleotides in length that is complementary with at least 11 nucleotides of SEQ ID NO:5.
It is noted that the claimed PNA sequence encompasses an 11-mer sequence that is complementary to the first 11-mer of SEQ ID NO:5 (5’-UUGUUUUUGCG), which comprises a 10-mer exon 4 sequence and the single “G” base that is in intron 4 of SCN9A pre-mRNA. There is simply no written description support for such PNA sequence having the inherently required exon skipping function, let alone having the function of treating pain in a subject in need thereof. Note that “Formula I” claimed in the instant case is defined as a compound that “induces alternative splicing of the human SCN9A pre-mRNA, yields SCN9A mRNA splice variant(s) lacking “exon 4”, and is useful to treat pains”. See page 14.
It is noted that the instant specification at best describes SCN9A exon 4 skipping activity by three nucleotide sequence species. That is, the limitation pertaining to “B1, B2,…Bn-1, and Bn” in Formula I is represented by only three different species as following:
1. “ASO 1” and “ASO 4” are each a 14-mer complementary to a 7-mer exon 4 and a 7-mer intron 4 except the mismatches at the two bold bases, wherein the two ASOs differ only at the N-terminus modification (Fmoc vs. Fethoc).
2. “ASO 9” is a 16-mer complementary to a 10-mer exon 4 and a 6-mer intron 4 within SEQ ID NO:5.
3. “ASO 10” is a 17-mer complementary to a 10-mer exon 4 and a 7-mer intron 4 except the mismatches at the two bold bases. All of the above three nucleotide sequence species are designed to be fully complementary to at least 5 bases within intron 4 and fully complementary to 7 or 10 consecutive nucleotides within exon 4. This limited variation of sequence complementarity to SEQ ID NO:5 cannot represent the broad genus of “B1, B2,…Bn-1, and Bn”, wherein “n is an integer between 10 and 18” because the limited variation represented by the above three nucleotide sequences cannot support the SCN9A exon 4 skipping function required by “Formula I” (as evidenced by the definition of “Formula I” at page 14 of the specification) encompassing, for instance, an 11-mer complementary to the first 11-mer of SEQ ID NO:5 (5’-UUGUUUUUGCG), nor can the three nucleotide sequences represent the pain treatment function required by claims 9-12 in view of the art-recognized high level of unpredictability of exon skipping antisense oligonucleotides. For instance, Graham et al. (The Journal of Gene Medicine, 2004, 6:1149-1158) demonstrate target sequence (exon/intron junction)-dependent exon skipping activity by antisense oligonucleotides, which show efficacy when designed to target more of the intron region (see “N”, “O”, and “P”) compared to those targeting more of the exon region. See Figures 2-3. This art-recognized target sequence-dependent exon skipping antisense oligonucleotide activity is also corroborated by Shiraishi et al. (BMC Cancer, 2010, 10:342), who demonstrate “PNA2549 (complementary to 11 bases of exon2 and 4 bases of intron2) showed the highest splicing inhibition among the three nested PNAs”, followed by PNA2545 (complementary to 4 bases of exon 2 and 11 bases of intron 2) and PNA2547 (complementary to 8 bases of exon 2 and 7 bases of intron 2), wherein “PNA2547 did not show any significant splicing inhibition” compared to “no PNA” as shown in Figure 2. See also page 4. Taken together, it was acknowledged in the relevant prior art that exon skipping activity of an exon/intron junction-targeting antisense oligonucleotides including PNA oligonucleotides cannot be reasonably predicted unless actually tested. As such, the exon skipping function inherently required by the genus of “Formula I” and the pain treatment function expressly required by the claimed method reciting the genus of “Formula I” cannot be reasonably extrapolated based on the three nucleotide sequence species disclosed in the instant application. That is, the three nucleotide sequence species is not a representative number of species sufficient to reflect the requisite structure-function correlation for the entire genus encompassing numerous structural variations.
See MPEP §2163 teaching that “when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. …“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)” (emphasis added).
Regarding claims 12 and 22, it is noted that there is no adequate written description support for the instantly claimed dose range of “1 nmole/Kg or less in an aqueous solution” of the PNA of claim 1 or claim 8 administered to a subject for pain treatment. It is noted that the PNA of claim 8 is identified as “ASO9” in the instant specification, which was administered at “100 pmole/Kg” in rats with DPNP. See Examples 18-19. It is noted that “100 pmole/Kg” is equivalent to 0.1 nmole/Kg. Hence, the dose of 1 nmole/Kg that is 10-fold higher than the actually used dose is not supported as being a therapeutically effective amount for treating pain.
It is art-recognized knowledge that a higher dose of exon-skipping oligonucleotides does not translate into a higher in vitro or in vivo efficacy as evidenced by Figure 5 of Graham et al. (The Journal of Gene Medicine, 2004, 6:1149-1158) and FIG. 3 of Khoo et al. (WO 2013/057485 A1), which is reproduced below. Compare 800 nM to 1000 nM in Graham’s Figure 5 and compare 25 mg/kg to 50 mg/kg in Khoo’s FIG. 3.
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In view of the foregoing, it is concluded that the instant specification itself fails to adequately describe the entire genus encompassing substantial variations of “B1, B2,…Bn-1, and Bn”, thereby failing to reasonably convey that the instant co-inventors completed and had possession of the entire genus as of the filing date sought in the instant application.
Response to Arguments
Applicant's arguments filed on February 4, 2026 have been fully considered but they are not persuasive. It is noted that applicant neglected to address how “ASO numbers 1, 4, 9, and 10” representing “three different nucleotide sequences” can possibly represent the entire genus even if the claims were to be construed as incorrectly alleged by applicant in the Appeal Brief of record. See pages 12-13 of Examiner’s Answer mailed on March 5, 2025.
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, 8-12, and 19-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 12,624,068 B2 in view of Thakker et al. (US 8,183,221 B2, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1 and 8 are anticipated by the ‘068 patent claims drawn to a PNA derivative targeting at least a 7-mer intron and a 7-mer exon within a target pre-mRNA. It is noted that the broad scope of the target pre-mRNA is defined to read on SCN9A pre-mRNA including “the junction of exon 4 and intron 4 in the human SCN9A pre-mRNA”, wherein the PNA derivative reads on “Fethoc-AC(102)T-TA(5)-C-G(6)CA-A(5)AA(5)-AC(102)A-A(5)-NH2” identified as “SCN-ASO 7” disclosed in Table 4. See columns 43-46. It is noted that the aforementioned embodiment expressly disclosed as being encompassed by the broad scope of the ‘068 patent claims is 100% identical to the PNA derivative claimed in claim 8 in the instant application.
Note that it is proper to look to the specification of a patent to determine the proper scope of the patent claims.
“To the extent that Pfizer contends that we may not rely on the teachings of the specification or claims in the ′165 patent to reject the claims of the ′068 patent, we disagree. See Geneva, 349 F.3d at 1386. There is nothing that prevents us from looking to the specification to determine the proper scope of the claims.” Pfizer Inc. v. Teva Pharmaceuticals USA Inc., 518 F3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008).
Regarding claims 9-11 and 19-21, it is noted that the method claims are encompassed by and would have been obvious over the method claims of the ‘068 patent claims. It would have been obvious to one of ordinary skill in the art to readily envision that the “disease or condition involving the expression of the target gene”, which is SCN9A, for using the expressly disclosed embodiment of “SCN-ASO-7” is pain including chronic pain and neuropathic pain as evidenced by Thakker’s disclosure that reduction of SNC9A is useful for treating “pain associated with a variety of disorders including, without limitation, PE and PEPD as well as chronic and neuropathic pain.” See column 6.
Response to Arguments
Applicant's arguments filed on February 4, 2026 have been fully considered but they are not persuasive. Applicant argues that this rejection should be withdrawn because the instant rejection is the only outstanding rejection. In response, applicant’s attention is directed to the fact that the instant rejection is not the only rejection in this application. Applicant’s attention is further directed to the fact that this rejection is not a provisional rejection. Hence, applicant’s arguments are found irrelevant and unpersuasive.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, RAM SHUKLA can be reached at 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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