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 .
DETAILED ACTION
This Office Action is a response to Applicant’s Amendment and Remarks filed May 5, 2026.
Claims 17-20, 22, 23, 25 and 26 have been canceled. New claims 27-29 are acknowledged. Claims 1, 5, 7-9, 11 and 16 have been amended.
Claims 1-5, 7-16 and 27-29 are pending in the present application.
Accordingly, claims 1-5, 7-16 and 27-29 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112
In the previous Office Action mailed February 5, 2026, claims 1-5, 7-16 and 26 were 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 pre-AIA the applicant regards as the invention. This rejection is moot against claim 26 in view of Applicant’s Amendment filed May 5, 2026 to cancel this claim. This rejection is withdrawn against the remaining claims in view of Applicant’s Amendment to the claims filed May 5, 2026.
Claim Rejections - 35 USC § 103
In the previous Office Action mailed February 5, 2026, claims 1-5, 7-9 and 11-16 were rejected under 35 U.S.C. 103 as being unpatentable over WO 2021/226107 A1 (AVIDITY BIOSCIENCES INC.) in view of U.S. Patent Publication 2021/0108201 A1. This rejection is withdrawn in view of Applicant’s Amendment to the claims filed May 5, 2026.
Markush Rejection
In the previous Office Action mailed February 5, 2026, claims 10 and 26 were rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. This rejection is moot against claim 26 in view of Applicant’s Amendment filed May 5, 2026 to cancel this claim. This rejection is withdrawn against claim 10 in view of Applicant’s Arguments filed May 5, 2026 and the P.T.A.B Decisions discussed and referenced in Applicant’s Arguments filed therein.
Double Patenting
In the previous Office Action mailed February 5, 2026, claims 1-5, 7-9 and 11-16 were rejected on the grounds of nonstatutory obviousness-type double patenting as being unpatentable over claims 53 and 57 of U.S. Patent No. 12239710 B2 (hereinafter, “710 Patent”). This rejection is maintained for the reasons of record set forth in the previous Office Action mailed February 5, 2026. NOTE: New claims 27-29 are drawn to subject matter within the scope of the rejected claims and would have been rejected in the prior Office Action. Therefore, the instant rejection applies to new claims 27-29 as well.
Response to Arguments
In response to this rejection, Applicants traverse and argue that the rejection is incomplete since the claims of the '710 patent are directed to an FN3 polypeptide domain linked by a linker to an siRNA molecule comprising sense and antisense strands for use in treating a glycogen storage disease. Applicant submit that none of the claims recites ERT (enzyme replacement therapy) or any co-administration requirement. Applicants argue that ERT appears only in the specification of the '710 patent as an alternative treatment option.
This argument has been fully considered by the Examiner however it is not found persuasive because the '710 patent does not list ERT as an alternative treatment option. Instead, the ‘710 patent is explicit in disclosing:
In some embodiments, the compositions or pharmaceutical compositions provided herein may be administered in combination with GAA enzyme replacement therapy (ERT).
Therefore, it would have been obvious to the skilled artisan to combine the two therapies for beneficial and additive effects of treating a glycogen storage disease.
Applicant also argues that the rejection is insufficient because the present specification demonstrates that the claimed combination produces an unexpected, synergistic therapeutic effect that could not have been anticipated. Applicants point the Examiner to Example 9 of the present Specification.
According to Applicant:
Example 9 of the present specification describes a repeat-dose study to assess pharmacodynamic effect of co-administering a composition comprising an FN3 domain conjugated to a Gys1 targeting siRNA (ABXC-29) with an ERT. This study was conducted in mice lacking glucosidase alpha acid (GAA-/-) and compared: (a) ABXC-29 monotherapy; (b) recombinant human GAA (rhGAA) monotherapy as ERT; and (c) ABXC-29 combined with rhGAA. The ABXC-29 monotherapy (3 mg/kg) reduced muscle glycogen by 23% in the gastrocnemius and 27% in the quadriceps; rhGAA monotherapy reduced muscle glycogen by 33% in the gastrocnemius and 35% in the quadriceps; while the combination of ABXC-29 (3 mg/kg) with rhGAA reduced muscle glycogen by 48% in the gastrocnemius and 42% in the quadriceps, exceeding what either monotherapy achieved alone.
Applicants submit that the specification expressly characterizes these results as demonstrating a synergistic effect, and specifically notes that the combination response achieved at the lower ABXC-29 dose (3 mg/kg) was comparable to ABXC-29 monotherapy at the higher dose (10 mg/kg), which could not have been predicted.
Applicants argue that the presently claimed subject matter has demonstrated a synergistic effect that would not have been reasonably predictable to a person of ordinary skill in the art.
This argument has been fully considered by the Examiner but is not found persuasive. First, Applicants comparing the combination response achieved at the lower ABXC-29 dose (3 mg/kg) to ABXC-29 monotherapy at the higher dose (10 mg/kg) is not persuasive by the Examiner because this is like comparing apples to oranges. Comparison of the ABXC-29 lower dose (even in combination with ERT) with the ABXC-29 higher does is a false equivalence and incommensurable comparison.
Second, the synergistic therapeutic effect Applicants reference in their Specification and arguments is not actually synergy. By definition, “synergistic” is the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone. See National Institutes of Health (NIH) Definition of Synergistic, downloaded from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/synergistic on July 2, 2026.
The results of Example 9 are reported in Table 15 of the present Specification and are show below:
PNG
media_image1.png
190
568
media_image1.png
Greyscale
According to Table 15, a synergistic effect in glycogen levels in muscle cells of the gastrocnemius and quadriceps of the two therapeutics does not exist. That is, the glycogen levels in neither the gastrocnemius nor the quadriceps with the combination of ABXC-29 (3 mg/kg) and rhGAA exceed what either monotherapy achieved alone. As reported in Table 15, the combination of ABXC-29 (3 mg/kg) with rhGAA does not even meet the level of additive effects, much less the standard for synergistic.
Regarding new claims 27-29 which require the siRNA and ERT are administered sequentially or before or after each other, Applicant is reminded that it is held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See In re Aller, 105 USPQ 233. In other words, it is not inventive to discover the optimum or workable ranges by routine experimentation and optimization.
The Examiner maintains that the claims of U.S. Patent No. 12239710 overlaps in scope and fully embraces that which is claimed in the present invention.
A terminal disclaimer disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 12239710 is required, or some other appropriate action.
******
In the previous Office Action mailed February 5, 2026, claims 1-5, 7-9 and 11-16 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, 16, 18, 25 and 29-32 of copending Application No. 18863539 (hereinafter, “539 application”). This rejection is maintained for the reasons of record set forth in the previous Office Action mailed February 5, 2026.
Response to Arguments
In response to this rejection, Applicants traverse and argue that the rejection is incomplete since the claims of the ‘539 application are directed to methods of reducing glycogen levels in a subject comprising administering a composition comprising one or more FN3 domains conjugated to a siRNA molecule targeting GYS1, wherein the FN3 domain binds CD71. Applicant submit that none of the claims recites ERT or any co-administration requirement. Applicants argue that ERT appears only in the specification of the ‘539 application as an alternative treatment option.
This argument has been fully considered by the Examiner however it is not found persuasive because the ‘539 application does not list ERT as an alternative treatment option. Instead, the ‘539 application is explicit in disclosing:
In some embodiments, the compositions or pharmaceutical compositions provided herein may be administered in combination with GAA enzyme replacement therapy (ERT).
Therefore, it would have been obvious to the skilled artisan to combine the two therapies for beneficial and additive effects of treating a glycogen storage disease.
Applicant also argues that the rejection is insufficient because the present specification demonstrates that the claimed combination produces an unexpected, synergistic therapeutic effect that could not have been anticipated. Applicants again point the Examiner to Example 9 of the present Specification
This argument has been fully considered by the Examiner but is not found persuasive because the synergistic therapeutic effect Applicants reference in their Specification and arguments is not actually synergy. See Examiner’s discussion supra. As reported in Table 15, the combination of ABXC-29 (3 mg/kg) with rhGAA does not even meet the level of additive effects, much less the standard for synergistic.
Regarding new claims 27-29 which require the siRNA and ERT are administered sequentially or before or after each other, Applicant is reminded that it is held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See In re Aller, 105 USPQ 233. In other words, it is not inventive to discover the optimum or workable ranges by routine experimentation and optimization.
The Examiner maintains that the claims of the ‘539 application overlap in scope, embrace and encompass that which is claimed in the present invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
******
In the previous Office Action mailed February 5, 2026, claims 1-5, 7-9 and 11-16 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35, 37 and 38 of copending Application No. 18052897 (reference application) in view of U.S. Patent Publication 2021/0108201 A1 (Aro Biotherapeutics Company). This rejection is withdrawn in view of Applicant’s Arguments filed May 5, 2026.
THIS ACTION IS MADE FINAL. 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 Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO's Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO's Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO's PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public.
For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199.
/TERRA C GIBBS/Primary Examiner, Art Unit 1635
Prosecution Insights