Prosecution Insights
Last updated: April 19, 2026
Application No. 16/948,435

Compositions for Modulating C9ORF72 Expression

Non-Final OA §DP
Filed
Sep 18, 2020
Examiner
ANGELL, JON E
Art Unit
1637
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Ionis Pharmaceuticals Inc.
OA Round
3 (Non-Final)
71%
Grant Probability
Favorable
3-4
OA Rounds
3y 4m
To Grant
92%
With Interview

Examiner Intelligence

Grants 71% — above average
71%
Career Allow Rate
572 granted / 809 resolved
+10.7% vs TC avg
Strong +21% interview lift
Without
With
+21.0%
Interview Lift
resolved cases with interview
Typical timeline
3y 4m
Avg Prosecution
41 currently pending
Career history
850
Total Applications
across all art units

Statute-Specific Performance

§101
5.7%
-34.3% vs TC avg
§103
26.8%
-13.2% vs TC avg
§102
25.0%
-15.0% vs TC avg
§112
25.5%
-14.5% vs TC avg
Black line = Tech Center average estimate • Based on career data from 809 resolved cases

Office Action

§DP
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, 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/17/2025 has been entered. Status of the Claims Claims 88-106 are pending. Claims 94-97, 103-106 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 4/15/2024. Claims 88-93, 98-102 are examined herein. 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 88-93, 98-102 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 9,605,263 (of record, IDS citation) in view of US20120083522 (hereinafter “Monia”). Although the claims at issue are not identical, they are not patentably distinct from each other. The instant claims are drawn to a 5-8-5 gapmer oligonucleotide compound that has the nucleotide sequence of SEQ ID NO: 33 and has phosphodiester or phosphorothioate internucleoside linkages, includes a claim which requires that the oligonucleotide is covalently linked to a conjugate group, and includes claims to pharmaceutical compositions comprising the gapmer oligonucleotide including a pharmaceutically acceptable diluent that is PBS. The ‘263 patent claims a gapmer modified oligonucleotide compound that has the nucleotide sequence of SEQ ID NO: 33 and has phosphodiester or phosphorothioate internucleoside linkages, includes a claim which requires that the oligonucleotide is covalently linked to a conjugate group, and includes claims to pharmaceutical compositions comprising the gapmer oligonucleotide including a pharmaceutically acceptable diluent that is PBS (e.g., see claims 1-20). The only difference between the instantly claimed gapmer oligonucleotide and the gapmer oligonucleotide of the ‘263 patent is that the instant gapmer is a 5-8-5 gapmer while the ‘263 gapmer is a 4-8-6 gapmer. However, 5-8-5 gapmer motif was known in the prior art. For instance, Monia teaches chimeric antisense oligonucleotides designed as 5-10-5 MOE, 5-8-5 and 6-8-6 MOE gapmers and teaches that 5-8-5 gapmers are 18 nucleotides in length, wherein the central gap segment is comprised of eight 2′-deoxynucleotides and is flanked on both sides (in the 5′ and 3′ directions) by wings comprising five nucleotides each, wherein each nucleotide in the 5′ wing segment and each nucleotide in the 3′ wing segment has a 2′-MOE modification and the internucleoside linkages throughout the gapmer are phosphorothioate (P═S) linkages, and wherein all cytidine residues throughout each gapmer are 5-methylcytidines (see [0469]). It is noted that Monia teaches that an unmodified nucleotide is a nucleotide composed of naturally occurring nucleobases, sugar moieties, and internucleoside linkages and can be an unmodified “DNA nucleotide (i.e., β-D-deoxyribonucleotide) (see [0118]). Therefore, it would have been prima facie obvious to modify the 4-8-6 gapmer oligonucleotide having SEQ ID NO: 33 claimed in the ‘263 patent into a 5-8-5 gapmer as taught by Monia, with a reasonable expectation of success. Since Monia teaches the 5-8-5 motif is an effective motif for gapmers, it would have been a matter of simple substitution of one known element (a 5-8-5 motif) for another (4-8-6 motif) to obtain predictable results, and/or use of known technique to improve similar product in the same way, and/or “Obvious to try” – choosing from a finite number of identified, predictable solutions (different known gapmer motifs), with a reasonable expectation of success. The disclosure of Monia indicating that the 5-8-5 motif is an effective gapmer motif provides a reasonable expectation for success. In other words, the gapmer of the ‘263 patent claims having a 5-8-5 motif instead of the claimed 4-8-6 motif, is an obvious variation of the gapmer claimed in the ‘263 patent. It is noted that the Supreme Court indicated in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 USPQ2d 1385 (2007)): “Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.” Response to Arguments Applicant’s arguments filed 10/17/2025 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. It is noted that Applicant’s arguments are directed to the previous double patenting rejection which relied upon the disclosure of the issued patent. Applicant’s arguments are persuasive with respect to rejection’s reliance on the specification of the ‘293 patent. However, upon further consideration, a new ground(s) of rejection is made in view of US20120083522 (Monia), as indicated in the rejection above. That is, the new Double Patenting rejection relies on Monia and not the specification of the ‘293 patent to render the claimed invention an obvious variation of the invention claimed in the ‘293 patent. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to J. E. Angell whose telephone number is (571)272-0756. The examiner can normally be reached Monday-Friday (8:30-5:00). Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. J. E. Angell Primary Examiner Art Unit 1637 /J. E. ANGELL, Ph.D./Primary Examiner, Art Unit 1637
Read full office action

Prosecution Timeline

Sep 18, 2020
Application Filed
Apr 21, 2021
Response after Non-Final Action
Nov 09, 2021
Response after Non-Final Action
Jul 10, 2024
Non-Final Rejection — §DP
Jan 13, 2025
Response Filed
Apr 16, 2025
Final Rejection — §DP
Sep 24, 2025
Examiner Interview Summary
Oct 17, 2025
Request for Continued Examination
Oct 21, 2025
Response after Non-Final Action
Nov 01, 2025
Non-Final Rejection — §DP (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

3-4
Expected OA Rounds
71%
Grant Probability
92%
With Interview (+21.0%)
3y 4m
Median Time to Grant
High
PTA Risk
Based on 809 resolved cases by this examiner. Grant probability derived from career allow rate.

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