DETAILED ACTION
Receipt of Arguments/Remarks filed on February 3 2026 is acknowledged. Claims 5 and16-25 were/stand cancelled. Claims 1 and 26 were amended. Claims 1-4, 6-15 and 26 are pending. Claims 6-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 August 28 2026. Claim 1-4 and 26 are directed to the elected invention.
Support for the amendments to claim 26 can be found in paragraph 0046 of the PGPUB. Examples of such single-stranded oligonucleotides can be found in WO 2012/074038 wherein USPGPUB No. 20130253038 is the English language equivalent.
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 .
Withdrawn Objections/Rejections
The amendments to the drawings are sufficient to overcome the objection of the drawings. The drawings now recite FIG.
The amendments to the specification and sequence listing are sufficient to overcome the objection of the sequence disclosures.
The amendments filed February 3 2026 are sufficient to overcome the rejection of claims 1-4 and 26 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 claims limit the target gene to be in the hepatic parenchymal cells.
The amendments filed February 3 2026 are sufficient to overcome the rejection of claims 1-4 and 26 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. Claim 1 as amended does not recite an active method step.
The certified translation of the Foreign priority documents filed February 3 2025 is sufficient to disqualify Koizumi et al. WO2019172286 as prior art under 35 USC 102(a)(1). The effective filing date of the instant application, in light of the certified translation, is September 10 2019 which is before the publication date of September 12 2019 of WO2019172286. Therefore, the rejection of the claims under 35 USC 102(a)(1) over Koizumi et al. is withdrawn.
The statement filed February 3 2026, specifically page 2 of the remarks, is sufficient to invoke the 35 USC 102(b)(2)(C) exception based on a joint research agreement. The statement in combination with the amendment to the specification to name the parties to the JRA. Therefore, the rejection under 35 USC 102 (a)(2) over Koizumi et al. is withdrawn.
In light of the disqualification of Koizumi et al. as prior art, the rejection of claims 1-4 and 25 under 35 USC 103 over Hansen et al. in view of Koizumi et al. is withdrawn.
Modified Rejections Necessitated by the Amendments filed February 3 2026
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 1-4 and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11958878 as evidenced by Mikuriya et al. (World J Heptol, 2012). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims a conjugate of an oligonucleotide having a pharmacological effect in hepatic parenchymal cells with a biantennary GalNAc of formula 1 wherein the oligonucleotide is an RNA interfering oligonucleotide and/or a gene expression inhibitor oligonucleotide with activity on a target gene in the hepatic parenchymal cells.
Patent ‘878 claims a conjugate of an oligonucleotide and a GalNAc unit. Specific conjugates claimed are SEQ ID NO 40 and X18 and SEQ ID NO: 174 and X20. X18 and X20 are exactly the same as instantly claimed X18 and X20. As shown below SEQ ID No: 40 is the same as instantly taught SEQ ID NO: 40 and SEQ ID NO: 174 is the same as instantly taught SEQ ID NO: 95.
SEQ ID NO: 40 (Qy) and SEQ ID NO: 40 (Db)
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SEQ ID NO: 95 (Qy) and SEQ ID NO: 174 (Db)
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As claimed the conjugates are used for treating glycogen storage disease type Ia.
As evidenced by Mikuriya et al. glycogen storage disease type I is an autosomal recessive disorder caused by glucose-6-phosphate deficiency in the liver, kidneys and intestinal mucosa. The disease is characterized by the impaired conversion of glucose form glucose-6-phosphate in the liver (page 194, discussion). Hepatic parenchyma cells are specifically taught (abstract; page 192 right paragraph; page 193-194, bridging paragraph).
Therefore, the scopes of the patent claims and the instant application overlap and thus they are obvious variants of one another as both claim oligonucleotides with the same GalNAc conjugate. Regarding the claimed delivery specifically to hepatic parenchymal cells, Patent ‘878 claims the same conjugates. Note MPEP 2112.01: "Products of identical chemical composition cannot have mutually exclusive properties." A chemical composition and its properties are inseparable. Therefore, if the prior artteaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705,709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Furthermore, Patent ‘878 claim the conjugates treat glycogen storage disease type I which as evidenced by Mikuriya et al. is caused by glucose-6-phosphate deficiency in the liver. Suggesting the oligonucleotides are for delivery to hepatic (aka liver) parenchymal cells and to target genes in the hepatic parenchymal cells.
Claims 1-4 and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 109-111 of copending Application No. 17769483 (US PGPUB NO. 20230348522) as evidenced by Mikuriya et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Copending ‘483 claims a method for producing an oligonucleotide. The oligonucleotide consists of a sequence represented by formula GSD AO01 to GSD AO16. This oligonucleotide includes either X18 or X20 which is the same instantly claimed. One compound claimed is SEQ ID NO: 29 with X20. As shown below SEQ ID NO: 29 is the same as instantly taught SEQ ID No: 95.
SEQ ID NO: 95 (Qy) and SEQ ID NO: 29 (Db)
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Copending ‘483 teaches the compounds are for the treatment of glycogen storage disease (GSD) type 1a (page 186).
As evidenced by Mikuriya et al. glycogen storage disease type I is an autosomal recessive disorder caused by glucose-6-phosphate deficiency in the liver, kidneys and intestinal mucosa. The disease is characterized by the impaired conversion of glucose form glucose-6-phosphate in the liver (page 194, discussion). Hepatic parenchyma cells are specifically taught (abstract; page 192 right paragraph; page 193-194, bridging paragraph).
Therefore, the scopes of the copending claims and the instant application overlap and thus they are obvious variants of one another as both claim oligonucleotides with the same GalNAc conjugate. Regarding the claimed delivery specifically to hepatic parenchymal cells, Copending ‘483 claims the same conjugates. Note MPEP 2112.01: "Products of identical chemical composition cannot have mutually exclusive properties." A chemical composition and its properties are inseparable. Therefore, if the prior artteaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705,709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Furthermore, copending ‘483 teaches the conjugates are GSD which is taught as glycogen storage disease type I which as evidenced by Mikuriya et al. is caused by glucose-6-phosphate deficiency in the liver. Suggesting the oligonucleotides are for delivery to hepatic (aka liver) parenchymal cells and to target genes in the hepatic parenchymal cells.
Response to Arguments
Applicants’ arguments filed February 3 2026 have been fully considered but they are not persuasive.
Applicants’ argue that (1) all of the conjugates of the ‘878 patent are oligonucleotides that comprise a sequence that is complementary to a region comprising any site between the 82nd and the 92nd nucleotide form the 5’ end of exon 5 of the G6PC gene with a c.648c>T mutation and that the claimed oligonucleotide repairs the mutation. None of the claimed conjugates are disclosed or suggest to have RNA interference and/or gene expression inhibitor activity on a target gene in a liver cell.
Regarding Applicants’ first argument, firstly, as set forth above since the oligonucleotides are for treating glycogen storage disease which is a disease of the liver, the conjugates of patent ‘878 have activity on a target gene in hepatic parenchymal cells. As set forth above patent ‘878 claims sequences which are exactly the same as instantly claimed SEQ ID No: 40 and 95. The instant specification (see paragraph 0463 of the specification as filed) teaches that SEQ ID NO: 1-48 and 93-96 are antisense oligonucleotides (reading on inhibitory oligonucleotides) Applicants had elected SEQ ID NO: 96 originally (though the species election was expanded to all species within the scope). Both SEQ ID NO: 40 and 95 are taught as antisense oligonucleotides which is the same as SEQ ID NO: 96. Therefore, the claims do not distinguish the oligonucleotide sequence claimed from those claimed in the patent. The examiner notes that SEQ ID No: 1-48 and 93-96 are the only specifically taught sequences in the instant specification. The claims do not clearly exclude any of these sequences.
Applicants argue that (2) the ‘483 application does not describe a function for the oligonucleotide conjugate. However, there is a reference to WO2019/172286 as providing additional information. The corresponding English equivalent is US Patent NO. 11958878. The oligonucleotides of the ‘483 have the same deficiencies as the ‘878 patent identified above.
Regarding Applicants second argument, firstly, as set forth above since the oligonucleotides are for treating glycogen storage disease which is a disease of the liver, the conjugates of copending ‘483 have activity on a target gene in hepatic parenchymal cells. As set forth above copending ‘483 claims sequences which are the same as instantly taught. The instant specification (see paragraph 0463 of the specification as filed) teaches that these sequences are antisense oligonucleotides (reading on inhibitory oligonucleotides) specifically SEQ ID NO: 1-48 and 93-96. Applicants had elected SEQ ID NO: 96 originally (though the species election was expanded to all species within the scope) this sequence as indicated in the response to the election filed August 28 2025 expressly states it is an RNA interfering oligonucleotide and/or gene inhibitor oligonucleotide. SEQ ID NO: 95 is taught as antisense oligonucleotides which is the same as SEQ ID NO: 96. Therefore, the claims do not distinguish the oligonucleotide sequence claimed from those claimed in the patent.
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). 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 ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
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/ABIGAIL VANHORN/ Primary Examiner, Art Unit 1636
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