DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 December 10, 2025 has been entered.
Status of Claims/Rejections
Claims 2, 5-6, and 9-14 are currently pending in the instant application. Claim 10 is withdrawn from further consideration as being drawn to a nonelected invention. Accordingly, claims 2, 5-6, 9, and 11-14 are under examination on the merits in the instant application.
Any rejections not repeated in this Office action are withdrawn, and the following rejections are the only rejections applied in this application.
Response to Arguments
Applicant’s arguments with respect to previous grounds rejection filed on December 10, 2025 have been considered but are moot because they do not pertain to the new rejections set forth hereinbelow necessitated by claim amendments.
Claim Rejections - 35 USC § 112
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.
Claims 5-6 and 12-13 are 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.
Claims 5 and 12 each recite that the “modification comprises a modified backbone.”
It is noted that claim 2 and claim 11 each recite “a phosphorodiamidate morpholino oligomer (PMO) modification.” As such, the oligonucleotide of claim 2 and claim 11 already comprises a specific type of modified backbone. Hence, the generic recitation of “a modified backbone” broadens the subject matter of claim 2 and claim 11, thereby failing to further limit the subject matter of claim 2 and claim 11.
Claims 6 and 13 each recite that the modified backbone of the oligonucleotide of claims 2 and 11 is “a morpholino backbone.” It is noted that claim 2 and claim 11 each recite “a phosphorodiamidate morpholino oligomer (PMO) modification.” As such, the oligonucleotide of claims 2 and 11 already comprises a morpholino backbone thus claims 6 and 13 fail to further limit the subject matter of claims 2 and 11.
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.
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 2, 5-6, 9, and 11-14 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. This includes a new matter rejection.
The instant claims are now strictly directed to a 25-mer PMO comprising SEQ ID NO:37 (a 19-mer sequence) or SEQ ID NO:38 (a 23-mer sequence that comprises SEQ ID NO:37) and a pharmaceutical composition thereof.
The instant specification does not disclose the instantly claimed 25-mer PMOs that induce skipping of human dystrophin mRNA and have a pharmaceutical function.
The instant specification identifies the 19-mer oligonucleotide of SEQ ID NO:37 as “PS 187” and the 23-mer oligonucleotide of SEQ ID NO:38 as “PS 194”, wherein the two oligonucleotides are fully modified with 2’-O-methyl RNA and phosphorothioate backbones and show DMD exon 44 skipping in patient cells in vitro. See Table 1A; Figures 1A-1B; paragraph 0112. Hence, not only is the claimed 25-mer comprising SEQ ID NO:37 or SEQ ID NO:38 undisclosed in the instant specification, but the specifically claimed PMO-modified 25-mer is not disclosed in the instant specification.
The instant specification generically discloses length ranges encompassing 25 and enumerates “25” in paragraph 0048. The specification also generically discloses “Phosphorodiamidate morpholino oligomers” (PMO) and “Morpholino oligonucleotides”. See paragraphs 0059-0060 and 0063. However, such generically disclosed embodiments and the paragraphs pointed out by applicant in the remarks filed on December 10, 2025 for providing support for the claim amendments are far from adequately describing the specifically claimed 25-mer PMO comprising a non-25-mer sequence (SEQ ID NO:37 and SEQ ID NO:38) in such a manner to reasonably convey that the instant co-inventors had possession of the claimed PMO as exactly claimed as of the filing date sought in the instant application. In fact, a 25-mer PMO comprising an 18-mer of SEQ ID NO:37 or SEQ ID NO:38 (nucleotide positions 2-19) was not deemed effective in inducing exon 44 skipping by relevant artisans shortly after the earliest filing date sought in the instant application. See Sazani et al. (US 2010/0130591 A1, applicant’s citation) who report that the 25-mer PMO of SEQ ID NO:7 (5’-CCATTTCTCAACAGATCTGTCAAAT) that differs from SEQ ID NO:37 by only one nucleotide was not selected as an effective exon-skipping PMO for further evaluation. See paragraph 0294 that discloses “a series of PPMOs, each 25 bases in length, were made (SEQ ID NOS:1-20) as shown in FIG. 5A. The PPMOs were evaluated for exon skipping efficacy by treating RD cells at various concentrations as described above in the Materials and Methods. Five PPMOs (SEQ ID NOS:4, 8, 11, 12 and 13) were identified as effective in inducing exon-skipping and selected for additional evaluation.” As such, it is clear that a 19-mer or 23-mer oligonucleotides fully modified with 2’-O-methyl with phosphorothioate backbone cannot represent a PMO composition that is 25 nucleotides in length having the intended exon skipping activity, which is necessary for the claimed pharmaceutical composition. Therefore, the instant specification fails to adequately describe the required structure-function correlation for the undisclosed 25-mer PMO and its recited function in the rejected claims.
Since the 25-mer PMO comprising nucleotides 2-19 of SEQ ID NO:37 was deemed ineffective in inducing dystrophin exon 44 skipping in a post-filing reference, and since the instant specification is completely silent regarding an actual exon skipping 25-mer PMO comprising the 19-mer SEQ ID NO:37 or the 23-mer SEQ ID NO:28, a person of ordinary skill in the art would reasonably conclude that the instantly claimed 25-mer PMO compositions are not adequately described by the instant specification in a way to reasonably convey to the person of ordinary skill in the art that the instant co-inventors had possession of the instantly claimed 25-mer PMO compositions as of the filing date sought in the instant application.
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 2, 5-6, 9, and 11-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 13-14 of copending Application No. 18/179,064 in view of Gebski et al. (Human Molecular Genetics, 2003, 12:1801-1811)
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed by and/or rendered obvious by the ‘064 claims drawn to and require an antisense oligonucleotide comprising one of SEQ ID NOs:20-25, 254-259, and 2070-2080, which comprise SEQ ID NO:37 claimed in the instant case, or one of SEQ ID NOs:2055-2069, which comprise SEQ ID NO:38 claimed in the instant case. It would have been obvious to replace the BNA modification in the ‘064 claims with a 25-mer PMO claimed in the instant case because a 25-mer PMO was known to induce successful dystrophin exon skipping as taught by Gebski thus one of ordinary skill in the art would have tried making a 25-mer PMO comprising one of the aforementioned SEQ ID NOs claimed in the ‘064 claims, thereby arriving at the instant claims.
Conclusion
No claim is allowed.
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/DANA H SHIN/Primary Examiner, Art Unit 1635