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 .
The rejection under section 112(a) is withdrawn in view of Applicant’s amendments.
The ejection under section 103 is withdrawn since the claims have been amended to require a "PMO molecule consist[ing] of the nucleic acid sequence of any one of SEQ ID NOs: 100-169”. The following is a new ground of rejection necessitated by this amendment, namely, adding WO2025072246 for the proposition that a PMO molecule consisting of the nucleic acid sequence of any one of SEQ ID NOs: 100-169 was known at the time of the invention:
Claim Rejections - 35 USC § 103
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.
Claims 1 and 3-12 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication No. 20200325237 based on an application by Darimont et al. (Darimont); or Hammond et al., JCI Insight. 2022 Dec 22;7(24) (Hammond);
both in view of: WO 2025072246 (WO 246), as evidenced by GenCore version 6.5.2, Copyright (c) 1993 – 2025, Biocceleration Ltd., ID BRB86178, WO 2025072246-A1, Human DMD gene exon 50 targeted antisense oligo (24mer-17), SEQ 611.
The primary references teach anti-transferrin antibody oligonucleotide conjugates for exon skipping in human DMD pre-RNA:
Claims 1, 11, 12: Hammond demonstrate that anti-transferrin phosphorodiamidate morpholino antibody conjugates were known in the art. For example, Darimont teaches anti-transferrin phosphorodiamidate morpholino antibody conjugate which is a therapeutic molecule where an antibody specifically designed to target the transferrin receptor is chemically linked to a phosphorodiamidate morpholino oligonucleotide (PMO):
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Conjugates targeting dystrophy are also taught.
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Claim 6-9: The disclosed linkers are taught, see paragraphs 0309+.
Claims 5 and 6: Different antibodies and fragments are taught, see description bridging pages 1 and 2.
Claims 1, 5-12: Primary reference Hammond also teaches anti-transferrin-PMO conjugates delivering antisense oligonucleotides in mouse models of the neurodegenerative disease spinal muscular atrophy:
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In particular, Hammond teaches the benefits of anti-transferrin PMO conjugates (“conjugation to the anti-TfR antibody may facilitate improved cellular uptake of the PMO via TfR on the target cells compared with the control antibody. . . [t]he BBB and BSCB represent significant barriers to the delivery of biologic drugs, both protein and nucleic acid based. Improving CNS exposure using anti-TfR antibodies, which allow transcytosis across the BBB, can be exploited for the delivery of drugs to the brain. We have found that systemic dosing of an anti-TfR antibody–PMO conjugate can access the central compartment”) see page 13.
The primary references may not explicitly teach PMO conjugates with the recited polynucleotides (see specific nucleotide sequences in specifically in claims 1-4). However, it is for that proposition that the examiner joins WO 246 which teaches oligonucleotide that binds to exon 50 in a pre-mRNA transcript of human dystrophin gene (DMD) to cause exon skipping. In a preferred embodiment, the oligonucleotide that binds to exon 50 in a pre-mRNA transcript of human dystrophin gene (DMD) is SEQ ID NO. 611, which corresponds to the instant PMO molecule consisting of SEQ ID NO: 152:
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See GenCore version 6.5.2, Copyright (c) 1993 – 2025, Biocceleration Ltd., ID BRB86178, WO 2025072246-A1, Human DMD gene exon 50 targeted antisense oligo (24mer-17), SEQ 611.
In this way, those of ordinary skill could have applied the recited polynucleotides to the conjugates in the manner required in a predictable fashion for the purposes of providing anti-transferrin antibody oligonucleotide conjugates for exon skipping in human DMD pre-RNA. As outlined above, the primary references teach anti-transferrin PMO antibody oligonucleotide conjugates for treating dystrophy. WO 246 is added for the proposition that the recited polynucleotides are applicable to these conjugates. Specifically, WO 246 teaches that the particular known technique of using the recited polynucleotides binds to exon 50 in a pre-mRNA transcript of human dystrophin gene (DMD) to cause exon skipping was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known technique in those therapies that bind to exon 50 in a pre-mRNA transcript DMD, such as the antisense therapy taught by the primary references, would have yielded predictable results. Accordingly, using the recited polynucleotides in anti-transferrin PMO conjugates for the purposes of providing anti-transferrin antibody oligonucleotide conjugates for exon skipping in human DMD pre-RNA would have been prima facie obvious.
The double patenting rejections are withdrawn in favor of the following new grounds of rejection, necessitated by Applicant’s amendments:
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 and 3-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-10 of copending Application No. 18/903,935 in view of WO 246.
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims cover the following embodiments, corresponding to those covered in the rejected claims:
A phosphorodiamidate morpholino oligonucleotide (PMO) conjugate comprising an anti-transferrin receptor antibody or antigen binding fragment thereof conjugated to a PMO molecule, wherein the PMO molecule consists of SEQ ID NO: 118, claims 1, 3 and 4.
wherein the anti-transferrin receptor antibody or antigen binding fragment thereof comprises a humanized antibody or antigen binding fragment thereof, chimeric antibody or antigen binding fragment thereof, monoclonal antibody or antigen binding fragment thereof, monovalent Fab', divalent Fab2, single chain variable fragment (scFv), diabody, minibody, nanobody, single domain antibody (sdAb), or camelid antibody or antigen binding fragment thereof, claim 5.
wherein the PMO molecule is conjugated to the anti-transferrin receptor antibody or antigen binding fragment thereof via a linker, wherein the linker is a cleavable linker, a non-cleavable linker, or is selected from the group consisting of a heterobifunctional linker, a homobifunctional linker, a maleimide group, a dipeptide moiety, a benzoic acid group or derivatives thereof, a C1-C5 alkyl group, and a combination thereof, claims 6-9.
wherein the PMO conjugate has an average drug-antibody ratio (DAR) of about 1:1, 2:1, 3:1, 4:1 5:1, 6:1, 7:1, 8:1 or higher, claims 10-12.
WO 246 is added for the proposition that the recited polynucleotides are applicable to these conjugates, as outlined above. Accordingly, using the recited polynucleotides in anti-transferrin PMO conjugates for the purposes of providing anti-transferrin antibody oligonucleotide conjugates for exon skipping in human DMD pre-RNA would have been prima facie obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 3-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12071621 in view of WO 246. Although the claims at issue are not identical, they are not patentably distinct from each other.
The conflicting claims recite conjugates that anticipate those covered by the rejected claims. The embodiments are substantially the same as those covered in the rejection above:
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Alternatively, the difference between the conjugates covered by the rejected claims and those covered by the conflicting claims is that the conflicting claims do not cover the instant conjugates with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQe2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the instant conjugates with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
WO 246 is added for the proposition that the recited polynucleotides are applicable to these conjugates, as outlined above. Accordingly, using the recited polynucleotides in anti-transferrin PMO conjugates for the purposes of providing anti-transferrin antibody oligonucleotide conjugates for exon skipping in human DMD pre-RNA would have been prima facie obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's acting supervisor, Gregory Emch, can be reached at telephone number 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646