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 .
Election/Restrictions
Applicant’s election without traverse of claims 9-16 (Group II) in the reply filed on 02/10/2026 is acknowledged. Acknowledgment is further made of Applicant’s election of SEQ ID NO: 5. In view of the results from searching the prior art, the species election requirement is hereby withdrawn.
Claims 1-8 and 17-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 02/10/2026.
Accordingly, claims 9-16 are pending and under consideration.
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. The earliest effective filing date to which the instant application is entitled is 11/23/2020.
Information Disclosure Statement
The information disclosure statement filed 05/23/2023 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
Receipt of an additional information disclosure statement on 07/06/2023 is acknowledged. The signed and initialed PTO-1449 has been mailed with this action.
Drawings
The drawings are objected to for the following reasons:
37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."”. In the current case, the view numbers for Figures 1-8 are preceded by the word "Figure" instead of the abbreviation "FIG.". It would be remedial to label each of the drawings “FIG.” instead of “Figure.”.
Figure 4a is of insufficient quality to be clearly interpretable. It would be remedial to provide an image of higher quality that is more clearly interpretable.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112(a)
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 9-16 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.
Claims 9-16 are drawn to a set of pharmaceutical compositions comprising at least one pharmaceutically acceptable excipient and an oligonucleotide that specifically hybridizes to a Let-7c microRNA binding sequence in a utrophin mRNA 3’-untranslated region (UTR). The rejected claims thus encompass a set of pharmaceutical compositions that comprise up to an unlimited number of pharmaceutically acceptable excipients.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification describes solubilization of therapeutic oligonucleotides in saline prior to injection of the said therapeutic oligonucleotides (Paragraph [0107]). Saline is a single pharmaceutically acceptable excipient. No description is provided of pharmaceutical compositions comprising up to an unlimited number of pharmaceutically acceptable excipients, as is encompassed by the instant claim language.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of a pharmaceutical composition comprising a single pharmaceutically acceptable excipient rather than of a pharmaceutical composition comprising up to an unlimited number of pharmaceutically acceptable excipients, as is encompassed by the instant claim language. The disclosed results are thus not necessarily predictive of a set of pharmaceutical compositions that comprise up to an unlimited number of pharmaceutically acceptable excipients, as is encompassed by the instant claim language. Therefore, it is impossible for one to extrapolate from the examples described herein those pharmaceutical compositions comprising up to an unlimited number of pharmaceutically acceptable excipients that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of pharmaceutical compositions that comprise up to an unlimited number of pharmaceutically acceptable excipients.
Therefore, the skilled artisan would have reasonably concluded that Applicants were not in possession of the claimed invention for claims 9-16. Claims 10-16 depend directly from independent claim 9 and do not resolve the basis of the written description rejection set forth above. Therefore, they are included in the rejection of independent claim 9.
Further, with specific regard to claim 16: claim 16 is drawn to a set of compositions comprising at least one additional oligonucleotide that specifically hybridizes to at least one additional microRNA binding sequence in the utrophin mRNA 3’-UTR. The rejected claims thus encompass a set of compositions that comprise up to an unlimited number of oligonucleotides that specifically hybridize to up to an unlimited number of additional microRNA binding sequences in the utrophin mRNA 3’-UTR.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. While the instant specification contemplates targeting of additional microRNAs (either alone or in combination) (Paragraph [0102]), no description is provided of administration of a composition comprising up to an unlimited number of oligonucleotides that specifically hybridize to up to an unlimited number of additional microRNA binding sequences in the utrophin mRNA 3’-UTR, as is encompassed by the instant claim language. Therefore, it is impossible for one to extrapolate from the examples described herein those compositions comprising up to an unlimited number of oligonucleotides that specifically hybridize to up to an unlimited number of additional microRNA binding sequences in the utrophin mRNA 3’-UTR that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a composition comprising up to an unlimited number of oligonucleotides that specifically hybridize to up to an unlimited number of additional microRNA binding sequences in the utrophin mRNA 3’-UTR.
Therefore, the skilled artisan would have reasonably concluded that Applicants were not in possession of the claimed invention for claim 16.
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 9 and 16 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.
Claim 9 recites the limitation "Let-7 microRNA" in line 5, while “Let-7c microRNA” is recited in lines 2-3. It is thus unclear whether Applicant is claiming targeting of Let-7c microRNA binding sites to prevent Let-7c microRNA binding, targeting of Let-7c microRNA binding sites to prevent Let-7 microRNA binding, or even targeting of Let-7 microRNA binding sites to prevent Let-7 microRNA binding. These are all reasonable interpretations of the instant claim language, as it is currently written. Given that the Let-7 family of microRNAs includes numerous isoforms (reviewed in Roush and Slack, 2008: see especially Figure 2), clarity as to what microRNA binding sites are being targeted for purposes of blocking binding of which microRNA is crucial. For purposes of examination and in the interest of compact prosecution, the Examiner has interpreted the recited limitation of “Let-7 microRNA” as reciting “Let-7c microRNA” (bolded and underlined emphasis added). It would be remedial to amend the instant claim language to clearly define the scope of protection sought regarding the species of the targeted microRNA binding sites (and the microRNAs associated with the same).
Claim 16 recites the limitation "the additional microRNA" (bolded emphasis added) in lines 3 and 6. There is insufficient antecedent basis for this limitation in the claim. It would be remedial to amend the instant claim set such that there is sufficient antecedent basis for every claim term, for example by reciting “the at least one additional microRNA,” which would more clearly read on the previously recited “at least one additional microRNA.”
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 9 and 12-16 is/are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by US 2019/0300879 A1 (hereinafter Khurana; of record; as cited in the IDS filed 05/23/2023).
With regard to claim 9, which recites “a pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and an oligonucleotide that specifically hybridizes to a Let-7c microRNA binding sequence in a utrophin mRNA 3’-untranslated region (UTR), wherein the oligonucleotide is present in an amount effective in a human subject to inhibit binding of Let-7 microRNA to its utrophin mRNA 3’-UTR,” Khurana discloses methods for enhancing utrophin protein production in a cell by inhibiting a utrophin microRNA molecule, said methods comprising administrating pharmaceutical compositions that include an antisense oligonucleotide that specifically hybridizes to a microRNA binding sequence in a utrophin mRNA 3’ UTR, thereby inhibiting the binding of the microRNA to the 3’-UTR utrophin mRNA (abstract; paragraph [0011]). Such inhibited microRNAs include Let-7c, as instantly claimed (paragraphs [0011] and [0013]). The pharmaceutical compositions disclosed in Khurana further comprise at least one pharmaceutically acceptable excipient, and the antisense oligonucleotide targeting the Let-7c microRNA binding sequence is provided in an amount effective in a human subject to inhibit the binding of Let-7 microRNA with its utrophin mRNA 3’-UTR binding sequence (paragraph [0013]), as instantly claimed. Thus, Khurana discloses each and every limitation of instant claim 9.
With regard to claim 12, which recites “the oligonucleotide [of the composition of claim 9] is a morpholino or phosphorodiamidite morpholino (PMO) oligonucleotide,” Khurana further discloses that the antisense oligonucleotides taught therein may be morpholino or phosphorodiamidite morpholino oligonucleotides (paragraph [0117]), as instantly claimed. Thus, Khurana discloses each and every limitation of instant claim 12.
With regard to claim 13, which recites “the oligonucleotide [of the composition of claim 9] is between 24 and 29 nucleotides long,” Khurana further discloses that the antisense oligonucleotides taught therein have a length of about 26 nucleotides (claim 17), which is within the instantly claimed range of 24 to 29 nucleotides. Thus, Khurana discloses each and every limitation of instant claim 13.
With regard to claim 14, which recites “the composition [of claim 9] is formulated for systemic administration to a subject,” Khurana further discloses that the pharmaceutical composition comprising antisense oligonucleotides targeting the Let-7c microRNA binding sequence taught therein (set forth above) may be formulated for systemic administration (paragraphs [0011], [0013], and [0135]; claim 20). Thus, Khurana discloses each and every limitation of instant claim 14.
With regard to claim 15, which recites “the composition [of claim 9] is formulated for intramuscular administration to a subject,” Khurana further discloses that the pharmaceutical composition comprising antisense oligonucleotides targeting the Let-7c microRNA binding sequence taught therein (set forth above) may also be formulated for intramuscular administration (paragraphs [0011], [0013], and [0135]; claim 21). Thus, Khurana discloses each and every limitation of instant claim 15.
With regard to claim 16, which recites “the composition of claim 9, further comprising at least one additional oligonucleotide that specifically hybridizes to at least one additional microRNA binding sequence in the utrophin mRNA 3’-UTR, wherein the additional microRNA is selected from the group consisting of miR-133b, miR-150, miR-196b, miR-206, and miR-296-5p, and wherein the additional oligonucleotide is present in an amount effective in a human subject to inhibit binding of the additional microRNA to its corresponding utrophin mRNA 3’-UTR binding sequence,” Khurana further discloses that the pharmaceutical composition comprising antisense oligonucleotides targeting the Let-7c microRNA binding sequence taught therein (set forth above) may also further comprise at least one additional antisense oligonucleotide (claim 22). The at least one additional antisense oligonucleotide of Khurana is disclosed to specifically hybridize to at least one additional microRNA binding sequence in the utrophin mRNA 3’-UTR and to inhibit the binding of the associated at least one additional microRNA to the utrophin mRNA 3’-UTR, wherein the additional microRNA is selected from the group consisting of miR-133b, miR-150, miR-196b, miR-206, and miR-296-5p (claim 22). Furthermore, the at least one additional antisense oligonucleotide of Khurana is recited to be present in amount effective in a human subject to inhibit binding with the associated utrophin mRNA 3’-UTR binding sequence (claim 22), as instantly claimed. Thus, Khurana discloses each and every limitation of instant claim 16.
Claim Rejections - 35 USC § 103
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0300879 A1 (hereinafter Khurana; of record; as cited in the IDS filed 05/23/2023) as applied to claim 9 above, and further in view of Askari and McDonnell, 1996 (hereinafter Askari).
The disclosure of Khurana is described above and applied as before. However, this disclosure does not teach the specific nucleic acid sequences of instant claim 10.
With regard to claim 10, which recites “the oligonucleotide [of the composition of claim 9] comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-5,” as set forth above, Khurana discloses the pharmaceutical composition of claim 9. However, while Khurana discloses antisense oligonucleotides comprising sequences such as SEQ ID NO: 24 (paragraph [0013]), which comprises 100% identity to instant SEQ ID NO: 1, as shown in the alignment below.
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However, the antisense oligonucleotides of Khurana are RNA oligonucleotides, while the more generically claimed oligonucleotides of instant claim 10 are DNA oligonucleotides, as reflected in the sequence listing. Thus, while the SEQ ID NO: 24 disclosed in Khurana is identical to instant SEQ ID NO: 1, they are different species of nucleic acids. However, antisense DNA oligonucleotides are well-known in the art and function in the same manner as antisense RNA oligonucleotides, as reviewed in Askari (see in particular page 316, column 2, paragraph 2).
Given that Khurana discloses pharmaceutical compositions comprising antisense oligonucleotides that specifically hybridizes to a microRNA binding sequence (such as Let-7c) in a utrophin mRNA 3’ UTR, thereby inhibiting the binding of the microRNA to the 3’-UTR utrophin mRNA, said oligonucleotides including the RNA antisense molecule of SEQ ID NO: 24 (which comprises 100% identity to instant SEQ ID NO: 1), and that Askari discloses that both DNA and RNA oligonucleotides are effective antisense oligonucleotides, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to substitute the DNA oligonucleotides taught in Askari for the RNA oligonucleotides disclosed in Khurana to predictably hybridize to a Let-7c microRNA binding site in a utrophin mRNA 3’-UTR, thereby inhibiting the binding of the microRNA to the 3’-UTR utrophin mRNA, as instantly claimed. One would have been motivated to make such a modification in order to receive the expected benefit of inhibiting the binding of the Let-7c microRNA to the 3’-UTR utrophin mRNA.
Claims 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0300879 A1 (hereinafter Khurana; of record; as cited in the IDS filed 05/23/2023) as applied to claim 9 above, and further in view of US 2023/0272433 A1 (hereinafter Amendola; effectively filed 09/29/2020), Stenvang and Kauppinen, 2008 (hereinafter Stenvang), Chan et al., 2006 (hereinafter Chan), and Askari and McDonnell, 1996 (hereinafter Askari), as evidenced by Liu et al., 2021 (hereinafter Liu).
The disclosure of Khurana is described above and applied as before. However, this disclosure does not teach the specific nucleic acid sequences of instant claim 10.
With regard to claims 10 and 11, which respectively recite “the oligonucleotide [of the composition of claim 9] comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-5” (bolded emphasis added), and that “the oligonucleotide [of the composition of claim 9] comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO: 5” (bolded emphasis added), as set forth above, Khurana discloses the pharmaceutical composition of claim 9. While Khurana discloses antisense oligonucleotides comprising sequences such as SEQ ID NO: 24 (paragraph [0013]), which is 100% identical to instant SEQ ID NO: 1, as set forth above and shown in the alignment above, Khurana is silent as to an oligonucleotide comprising instant SEQ ID NO: 5, as recited at instant claims 10 and 11. However, this deficiency is cured by Amendola, which discloses a target sequence comprising instant SEQ ID NO: 5, as instantly claimed.
Amendola discloses methods of enhancing utrophin expression in a cell by inducing mutations within a target sequence comprising a utrophin regulatory element (such as a Let7c binding site, as instantly claimed) using a gene editing enzyme (paragraphs [0001], [0006], and [0033]). The target sequences comprising utrophin repressor binding sites disclosed therein include SEQ ID NO: 18 (Table 1; paragraph [0046]). As shown in the alignment below, the entirety of SEQ ID NO: 5 is capable of binding to the disclosed Let7c target site of Amendola
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(SEQ ID NO: 18).
As is known to those of ordinary skill in the art, the approach of regulating activity by blocking miRNA binding sites is well-known as miRNA-masking, wherein antisense oligonucleotides mask the binding site of the target miRNA (reviewed in Stenvang: see page 69, column 2, paragraph 1), such as the Let7c target site disclosed in Amendola, which comprises instant SEQ ID NO: 5, as instantly claimed and set forth above.
Therefore, while the methods of Amendola and Khurana differ from each other, the end result of both methods is the same: blocking binding to a utrophin regulatory element (such as the repressive microRNA Let7c) to increase utrophin expression (Amendola: paragraphs [0001], [0006], and [0033]; Khurana: paragraphs [0011] and [0013]). Amendola discloses that SEQ ID NO: 18 taught therein is a suitable target sequence for blocking of binding, as set forth above. Given that Khurana discloses that antisense oligonucleotides accomplish the same blocking of binding (as set forth above), it would have been obvious to someone of ordinary skill in the art prior to the effective filing date of the claimed invention to block binding to utrophin regulatory elements with antisense oligonucleotides targeting utrophin regulatory element sequences known in the field, for example SEQ ID NO: 18 of Amendola (as reviewed in Stenvang). Design of such antisense oligonucleotides is routine and well-understood in the art. As disclosed in Chan, design of antisense oligonucleotides considers at least four parameters, including prediction of the secondary structure of the RNA, identification of preferable RNA secondary local structures, motifs searching and GC content calculation, and binding energy prediction (see section ANTISENSE OLIGONUCLEOTIDE DESIGN). Therefore, given that the target sequence comprising instant SEQ ID NO: 5 was disclosed in Amendola, design of suitable antisense oligonucleotides per the methods of Chan would predictably generate a limited number of antisense oligonucleotides targeting said sequence, including instant SEQ ID NO: 5. As set forth above, antisense DNA oligonucleotides such as instant SEQ ID NO: 5 are well-known in the art and function in the same manner as antisense RNA oligonucleotides, as reviewed in Askari (see in particular page 316, column 2, paragraph 2).
As reviewed in Chan, antisense oligonucleotide drugs have been approved for in vivo therapeutic use, and other antisense oligonucleotide drugs are in clinical trials (see section ANTISENSE OLIGONUCLEOTIDE DRUGS IN CLINICAL TRIALS). The same is not true of CRISPR-based gene editing tools, such as those disclosed in Amendola (paragraph [0052]). While Liu has a post-filing publication date, it is applied as an evidentiary reference that is representative of the state of the art at the time of filing. At the time of filing, applying CRISPR editing to patients in vivo was an underdeveloped and unpredictable topic in the art. As reviewed in Liu, there are a number of hurdles to overcome before in vivo CRISPR therapy is commonplace, including editing efficiency, effective delivery of the editing machinery, off target effects, and immunogenicity (see sections “Editing efficiency,” “Delivering methods,” “Off-target effects,” and “Immunogenicity”). Therefore, in the interest of therapeutically targeting utrophin regulatory element sequences known in the field (for example SEQ ID NO: 18 of Amendola) in patients in need thereof, it would have been obvious to someone of ordinary skill in the art prior to the effective filing date of the instant invention to design antisense oligonucleotides (such as DNA antisense oligonucleotides, as reviewed in Askari) per the methods of Chan, as motivated by Khurana, to predictably arrive at a limited number of antisense oligonucleotide sequences targeting the Let7c binding sequence disclosed in Amendola, said limited number including instant SEQ ID NO: 5. Antisense oligonucleotides produced via these methods would predictably block Let-7c binding and increase utrophin expression, as disclosed in Khurana and supported by Amendola. One would have been motivated to practice these methods in order to produce therapeutic antisense oligonucleotides for in vivo use in patients in need thereof, as the CRISPR editing disclosed in Amendola was an underdeveloped and unpredictable topic in the art at the time of filing, with no CRISPR drugs approved for in vivo use in patients.
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 9 and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13, 14, and 19 of U.S. Patent No. 9,458,459 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 13 of patent ‘459 is drawn to a pharmaceutical composition, recited to “compris[e] an antisense oligonucleotide that specifically hybridizes to a micro-RNA binding sequence in a 3’ UTR of a utrophin mRNA and inhibits the binding of the microRNA molecule to the 3’ UTR utrophin mRNA, wherein said microRNA is selected from the group consisting of Let-7c…and at least one pharmaceutically acceptable excipient.” Claim 14 of patent ‘459 explicitly limits the microRNA targeted for disruption of binding to Let-7c, as in the instant claim set. Furthermore, claim 19 of patent ‘459 recites that the antisense oligonucleotide of the pharmaceutical composition claimed therein “is about 24 nucleotides long.”
In comparison, instant claim 9 recites “a pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and an oligonucleotide that specifically hybridizes to a Let-7c microRNA binding sequence in a utrophin mRNA 3’-untranslated region (UTR), wherein the oligonucleotide is present in an amount effective in a human subject to inhibit binding of Let-7 microRNA to its utrophin mRNA 3’-UTR.” Thus, claims 13 and 14 of patent ‘459 read on each and every limitation of instant claim 9.
Furthermore, instant claim 13 recites “the oligonucleotide is between 24 and 29 nucleotides long,” meaning claim 19 of patent ‘459 also reads on each and every limitation of instant claim 13.
Thus, instant claims 9 and 13 are not patentably distinct from claims 13, 14, and 19 of patent ‘459.
Claims 9, 15, and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 5 of U.S. Patent No. 11,028,389 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of patent ‘389 is drawn to a pharmaceutical composition, recited to “compris[e] an antisense oligonucleotide that specifically hybridizes to a Let-7c microRNA binding sequence in a 3’-UTR of a utrophin mRNA 3’ untranslated region (UTR) and inhibits the binding of the Let-7c microRNA to the utrophin mRNA 3’-UTR and at least one pharmaceutically acceptable excipient, wherein the antisense oligonucleotide is present in an amount effective in a human subject to inhibit the binding of Let-7 microRNA with its utrophin mRNA 3’-UTR binding sequence…”.
In comparison, instant claim 9 recites “a pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and an oligonucleotide that specifically hybridizes to a Let-7c microRNA binding sequence in a utrophin mRNA 3’-untranslated region (UTR), wherein the oligonucleotide is present in an amount effective in a human subject to inhibit binding of Let-7 microRNA to its utrophin mRNA 3’-UTR.” Thus, claim 1 of patent ‘389 reads on each and every limitation of instant claim 9.
Claim 4 of patent ‘389 recites “the composition of claim 1…is formulated for intramuscular administration to the subject.”
In comparison, instant claim 15 recites “the composition of claim 9…is formulated for intramuscular administration to the subject. Thus, claim 4 of patent ‘389 reads on each and every limitation of instant claim 15.
Claim 5 of patent ‘389 recites “the composition of claim 1, further compris[es]at least one additional antisense oligonucleotide that specifically hybridizes to at least one additional microRNA binding sequence in the utrophin mRNA e’-UTR and inhibits the binding of the at least one additional micro RNA to the utrophin mRNA 3’-UTR, wherein the additional micro RNA is selected from the group consisting of miR-133b, miR-150, miR-196b, miR-206, and miR-296-5p, and wherein the additional antisense oligonucleotide is present in an amount effective in a human subject to inhibit its binding with its corresponding utrophin mRNA 3’-UR binding sequence.”
In comparison, instant claim 16 recites “the composition of claim 9, further comprising at least one additional oligonucleotide that specifically hybridizes to at least one additional microRNA binding sequence in the utrophin mRNA 3’-UTR, wherein the additional microRNA is selected from the group consisting of miR-133b, miR-150, miR-196b, miR-206, and miR-296-5p, and wherein the additional oligonucleotide is present in an amount effective in a human subject to inhibit binding of the additional microRNA to its corresponding utrophin mRNA 3’-UTR binding sequence.” Thus, claim 5 of patent ‘389 reads on each and every limitation of instant claim 16.
Thus, instant claims 9, 15, and 16 are not patentably distinct from claims 1, 4, and 5 of patent ‘389.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 of U.S. Patent No. 12,104,152 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of patent ‘152 recites “an oligonucleotide comprising one or more arabinonucleotides, wherein the oligonucleotide specifically hybridizes to a Let-7c microRNA binding sequence in a utrophin mRNA 3’ untranslated region (UTR) and inhibits the binding of the Let-7c microRNA to the utrophin mRNA 3’-UTR,” while claim 6 of patent ‘152 recites “a pharmaceutical composition comprising the oligonucleotide of claim 1 and at least one pharmaceutically acceptable excipient.”
In comparison, instant claim 9 recites “a pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and an oligonucleotide that specifically hybridizes to a Let-7c microRNA binding sequence in a utrophin mRNA 3’-untranslated region (UTR), wherein the oligonucleotide is present in an amount effective in a human subject to inhibit binding of Let-7 microRNA to its utrophin mRNA 3’-UTR.” Thus, claims 1 and 6 of patent ‘152 read on each and every limitation of instant claim 9.
Thus, instant claim 9 is not patentably distinct from claims 1 and 6 of patent ‘152.
Claims 9, 10, 13, and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8 and 13-15 of U.S. Patent No. 12,104,152 B2in view of Askari and McDonnell, 1996 (hereinafter Askari).
Claim 8 of patent ‘152 recites “a method of treating Duchenne Muscular Dystrophy (DMD) in a human subject, the method comprising: administering to the subject an effective amount of an oligonucleotide according to claim 1 [set forth above].” Therefore, the method of patent ‘152 requires the oligonucleotide of claim 1 recited therein, which is not patentably distinct from instant claim 9, as set forth above.
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The oligonucleotide of the method of patent ‘152 is further recited to “ha[ve] a nucleic acid sequence set forth in SEQ ID NOs: 26-55 and 64-75” at claim 13. As shown in the alignment below, instant SEQ ID NO: 1 comprises 100% identity to SEQ ID NO: 26 of patent ‘152.
However, the antisense oligonucleotides of patent ‘152 are RNA oligonucleotides, while the oligonucleotides of instant claim 10 are DNA oligonucleotides, as reflected in the sequence listing. Thus, while the SEQ ID NO: 26 of patent ‘152 comprises 100% identity to instant SEQ ID NO: 1, they are different species of nucleic acids. However, antisense DNA oligonucleotides are well-known in the art and function in the same manner as antisense RNA oligonucleotides, as reviewed in Askari (see in particular page 316, column 2, paragraph 2). Thus, instant claims 9 and 10 are not patentably distinct from claims 8 and 13 of patent ‘152.
Given that patent ‘152 recites a method of administering an effective amount of oligonucleotides that specifically hybridize to a microRNA binding sequence (such as Let-7c) in a utrophin mRNA 3’ UTR, thereby inhibiting the binding of the microRNA to the 3’-UTR utrophin mRNA, said oligonucleotides including the RNA molecule of SEQ ID NO: 26 (which comprises 100% identity to instant SEQ ID NO: 1), and that Askari discloses that both DNA and RNA oligonucleotides are effective antisense oligonucleotides, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to substitute the DNA oligonucleotides taught in Askari for the RNA oligonucleotides recited in patent ‘152 to predictably hybridize to a Let-7c microRNA binding site in a utrophin mRNA 3’-UTR, thereby inhibiting the binding of the microRNA to the 3’-UTR utrophin mRNA, as instantly claimed. One would have been motivated to make such a modification in order to receive the expected benefit of inhibiting the binding of the Let-7c microRNA to the 3’-UTR utrophin mRNA.
Claim 14 of patent ‘152 further recites that “the oligonucleotide [of the method claimed therein] is between 20 and 32 nucleotides long.”
In comparison, instant claim 13 recites “the oligonucleotide [of the composition of claim 9] is between 24 and 29 nucleotides long,” the range of which is completely encompassed by the recited range of claim 14 of patent ‘152. Thus, instant claim 13 is not patentably distinct from claim 14 of patent ‘152.
Claim 15 of patent ‘152 further recites that “the oligonucleotide [of the method claimed therein] is administered systemically.”
In comparison, instant claim 14 recites “the composition [of claim 9] is formulated for systemic administration to a subject.” As set forth above, the administration of an oligonucleotide necessarily anticipates said oligonucleotide. Similarly, systemic administration of an oligonucleotide necessarily anticipates formulation of said oligonucleotide for systemic administration. Thus, instant claim 14 is not patentably distinct from claim 15 of patent ‘152.
Conclusion
No claims are allowed.
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/SARAH E ALLEN/Examiner, Art Unit 1637
/J. E. ANGELL/Primary Examiner, Art Unit 1637