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
The amendment to the claims filed after non-final office action on January 20, 2026 is acknowledged. Claims 1, 4-5, 7-11 were amended, claims 2-3, 6 and 12-33 were canceled and claims 1, 4-5, 7-11 are pending in the instant application. The restriction was deemed proper and made final previous office action.
The restriction is deemed proper and is made FINAL in this office action.
Claims 1, 4-5, 7-11 are examined on the merits of this office action.
Withdrawn Rejections/Objections
The rejection of claims 1-11 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of amendment of the claims filed January 20, 2026 to include requirement of a polynucleotide encoding human Dok-7 as the NMJ targeting agent.
The rejection of claims 1-11 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, scope of enablement, is withdrawn in view of amendment of the claims filed January 20, 2026 to include polynucleotide encoding human Dok-7 as the NMJ targeting agent and narrowing the patient population to treating motor impairment in patients that are 60 years or older and excluding specific patient populations.
The rejection of claims 8 and 10 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of amendment of the claims filed January 20, 2026.
The rejection of claim(s)1, 4, 6-10 under 35 U.S.C. 102(a)(1) as being anticipated by Miyoshi (EMBO Mol Med, 2017 May 10;9(7):880–889) is withdrawn in view of amendment of the claims filed January 20, 2026.
The rejection of claim(s)1-5, 7-11 under 35 U.S.C. 102(a)(1) as being anticipated by Haramizu (WO2013058229, English translation attached) is withdrawn in view of amendment of the claims filed January 20, 2026.
The objection to the specification is withdrawn in view of removal of all references to specific sequences and SEQ ID Nos. The examiner agrees that a sequence listing is not required and Applicants have support for the human Dok-7 sequence in the specification.
*Applicant’s arguments are moot in light of amendment of the claims, withdrawal of the previous rejections and the new rejection under 35 U.S.C. 103 presented below.
New Objection
Claim 1 is objected to for the following informality: the limitation of “..targeting agent, which is a polynucleotide that encodes human DoK-7” should be replaced with -.targeting agent, wherein the NMJ targeting agent comprises
New Rejections
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 4-5, 7-11 are rejected under 35 U.S.C. 103 as being unpatentable over Haramizu (WO2013058229, English translation attached, cited previously) in view of Miyoshi (EMBO Mol Med, 2017 May 10;9(7):880–889, cited previously).
Haramizu teaches a method for treating an age related dysfunction in a subject by administering a therapeutically effective amount of an NMJ targeting agent (see claims 1-9, 15-18). Specifically, Haramizu teaches that aging leads to skeletal muscle atrophy, weakness and decline in NMJ integrity and the administration of milk fat globule membrane component increases skeletal muscle mass, suppresses muscle atrophy and promotes NJM formation (see Examples 1-3, figures 1-5, Example 3 is specifically treating aged mice with fat globule membrane component and also claims 15-18). Haramizu specifically teaches “when the fat globule membrane component was administered to aging-promoted mice, gene expression or protein decrease of molecules (Dok-7) involved in the formation of the neuromuscular junction was suppressed”(see page 3 of translation, bottom of paragraph 0003).
Haramizu teaches administration of the MGFM composition to elderly subjects such as aged individuals with muscle weakness or reduced strength due to normal aging (see claims 18-19, “suppresses muscle atrophy associated with aging”, “NMJ dysgenesis associated with aging” (claim 19), “age related muscle weakness (sarcopenia)” (see page 3, paragraph 005)). The disclosure encompasses treatment of normal, age related NMJ function via treating age related weakness such as sarcopenia.
Haramizu is silent to using a polynucleotide encoding Dok-7 as the NMJ targeting agent or NMJ formation promoter.
However, Miyoshi teaches administration of AAV vector encoding DOK7 and that treatment restored NMJ integrity, suppressed atrophy and improved motor function (see page 881, Abstract and intro; Figure 1 (E-G)(NMJ restoration); Figure 2 (A-E)(myofiber CSA increase); figure 3 (F-G)(motor activity). Miyoshi explicitly teaches an AAV vector encoding human Dok-7 (see methods section, page 886, left column, “in vivo AAV injection”). Miyoshi demonstrates enhanced motor activity (figure 3 (F-G)). Miyoshi teaches AAV-DOK7 suppressed NMJ denervation and maintained nerve terminal contacts (see Figure 1E-G, text page 887, “the paper explained, results”). Miyoshi teaches that NMJ morphology and muscle strength are restored to levels greater than those of healthy controls (Figures 1E-G). Taken together, Miyoshi demonstrates that increasing Dok-7 expression restores NMJ structure and improves motor function.
It would have been obvious before the effective filing date of the claimed invention to one of ordinary skill in the art to administer a polynucleotide encoding human DOK-7, as taught by Miyoshi, to subjects experiencing age related motor impairment (including muscle atrophy and sarcopenia) as taught by Haramizu. One of ordinary skill in the art would have been motivated to do so because Haramizu teaches that aging is associated with skeletal muscle atrophy, weakness, and decline in NMJ integrity/function, and further teaches that reduced expression or activity of molecules involved in NMJ formation, including DOK-7, contributes to age related NMJ dysfunction. Miyoshi teaches that increasing Dok-7 expression via administration of an AAV vector encoding human DOK7 restores NMJ integrity, suppresses NMJ denervation, reduces muscle atrophy and improves motor function in vivo.
Accordingly, because Haramizu identifies Dok-7 signaling as a contributing factor in age related motor impairment, and Miyoshi demonstrates that restoring Dok-7 expression improves NMJ structure and motor performance, one of ordinary skill in the art would have had a reasonable expectation that increasing Dok-7 expression in aged subjects would restore NMJ integrity and improves muscle strength.
Regarding claim 1, Haramizu in view of Miyoshi teaches treatment of age related muscle atrophy and sarcopenia with MFGM administration (see page 4, paragraphs 1-2, “age related muscle weakness (sarcopenia)”) thus meeting the limitations without MG, ALS etc.. as claimed in instant claim 1. Regarding treatment of human subjects who are 60 years or older, Haramizu does not expressly recite treatment limited to humans that are 60 years or older. However, Haramizu does teach that “Our skeletal muscles decrease at a rate of about 5% every 10 years after the age of 30, and the rate of reduction further accelerates after the age of 60” (see paragraph 3). Haramizu further teaches that “decrease in skeletal muscle mass and muscle function associated with aging causes injury due to falls, resulting in a decrease in physical activity, and accordingly increases the risk of metabolic disorders such as osteoporosis, obesity and insulin resistance” (see paragraph 0003). Thus, Haramizu recognizes that age 60 and older as a clinically significant stage of age related skeletal muscle decline and associated motor impairment. Accordingly, one of ordinary skill in the art would have understood that treatment of age related motor impairment as taught by Haramizu would reasonably encompass subjects 60 years or older, as this age group is specifically identified as experiencing accelerated skeletal muscle degeneration. Selecting subjects 60 years or older for treatment of age related motor impairment would have been obvious because Haramizu identifies 60 as stage of accelerated skeletal muscle decline.
Regarding claims 1, 4, Haramizu teaches treatment of age related motor impairment and weakness (see page 4, paragraphs 1-2, “age related muscle weakness (sarcopenia)”).
Regarding claim 5, Haramizu teaches treatment of age related muscle atrophy and sarcopenia (see page 4, paragraphs 1-2, “age related muscle weakness (sarcopenia)”) and Haramizu in view of Miyoshi render obvious treating sarcopenia with Dok-7.
Regarding claim 7, the limitation of “treatment is effective to improve motor function or muscle strength” is a result oriented effect of the method. Haramizu in view of Miyoshi render obvious the same method, same agent and same patient population and thus, this result would necessarily be achieved.
Regarding claim 8, the limitation of “wherein the subjects motor function or muscle strength is significantly improved in comparison with a younger subject who is without CMS, MG, MD….” is a result oriented effect of the method. Haramizu in view of Miyoshi render obvious the same method, same agent and same patient population and thus, this result would necessarily be achieved.
Although Haramizu in view of Miyoshi does not expressly perform this comparison (with a “younger subject…”), such improvement naturally results of the disclosed method. This comparative relationship therefore exists inherently, and no active measurement is required to practice the claim.
Regarding claim 9, the limitation of “wherein said treatment is effective to reduce age related NMJ denervation ….” is a result oriented effect of the method. Haramizu in view of Miyoshi render obvious the same method, same agent and same patient population and thus, this result would necessarily be achieved.
Regarding claim 10, the limitation of “said NMJ denervation is significantly reduced in comparison with a younger ….” is a result oriented effect of the method. Haramizu in view of Miyoshi render obvious the same method, same agent and same patient population and thus, this result would necessarily be achieved.
Although Haramizu in view of Miyoshi does not expressly perform this comparison (with a “younger subject…”), such improvement naturally results of the disclosed method. This comparative relationship therefore exists inherently, and no active measurement is required to practice the claim.
Regarding claim 11, Haramizu in view of Miyoshi render obvious the same method, same agent and same patient population (administering Dok-7 to elderly subjects) and thus, this result would necessarily be achieved. This is further evidenced by the fact that AAV-D7 treatment increased proportion of myofibers with larger diameter in Miyoshi (Figure 2). Nevertheless, it would have been obvious to further induce muscle hypertrophy when treating age related sarcopenia, as increasing muscle mass is a conventional therapeutic objective in age related muscle weakness and one of ordinary skill in the art would have been motivated to do so.
Conclusion
No claims are allowed.
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 ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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, Lianko Garyu can be reached at 571-270-7367. 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.
/ERINNE R DABKOWSKI/Examiner, Art Unit 1654