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 .
Status of Application/Amendment/Claims
This Office action is in response to the communications filed on August 5, 2026.
Currently, claims 38, 40, 44, and 47-56 are pending and under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
Maintained Rejections
Claim Rejections - 35 USC § 112
Claims 38, 40, 44, and 47-56 remain rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement for the reasons as set forth in the Office action mailed on May 13, 2026 and for the reasons stated below.
Applicant's arguments filed on August 5, 2026 have been fully considered but they are not persuasive. Applicant argues that the claims as currently amended comply with the written description requirement because the activity of SEQ ID NO:82 in significantly increasing SHANK3, whereas “the saRNA of SEQ ID NO: 7 did not produce a noticeable increase” in patient-derived model by pointing out the §1.132 declaration filed on August 5, 2026. The declaration under 37 CFR 1.132 filed on August 5, 2026 is insufficient to overcome the rejection because of the following reasons:
The declarant states that SEQ ID NO:82 resulted in a significant increase in SHANK3 expression when assessed by qRT-PCR, “while SEQ ID NO: 7 did not cause a noticeable increase” in patient-derived brain organoids by pointing out Figure 1 provided at page 3 of the declaration, thereby “supporting its potential therapeutic effect in a brain model system”. See paragraphs 8-9. As an initial matter, the examiner wishes to make it clearly on the record that the experimental results provided in the instant application as originally filed are not consistent with the post-filing data provided in the §1.132 declaration. That is, the examiner is bewildered by the conflicting results in Figure 1B of the instant application versus Figure 1 of the declaration when the only difference is the cell type.
See Figure 1B showing qRT-PCR results in KG-1 cells (human acute myelogenous leukemia cells) showing the highest level of SHANK3 mRNA upregulation by SEQ ID NO:7.
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For discussion purpose, Figure 1 included in the §1.132 declaration is copied below.
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Now, applicant’s attention is directed to the fact that the written description inquiry occurs as of the filing date sought in the instant application, not years (about 6 years) after the filing date sought in the instant case. Note that use of “Shank3 Organoids” is not even contemplated or disclosed in the instant specification. Regarding the disclosure of the instant specification, which is the foundation of the written description inquiry, the mere increase in SHANK3 mRNA expression in KG-1 cells in vitro when transfected with the double-stranded RNA comprising SEQ ID NO:82 with dTdT and its complementary sequence with dTdT (SEQ ID NO:87) is not whatsoever representative or indicative of the required function of “treating/ameliorating/preventing an intellectual disability” in a subject. Further, even if Figure 1 of the §1.132 declaration were to be disclosed in the earliest priority document and/or in the instant application, the mere increase in SHANK3 mRNA expression level in four 3D spheres formed by pluripotent stem cells obtained from one patient having autism spectrum disorder (ASD) is not descriptive of the instantly claimed method of “treating/ameliorating/preventing an intellectual disability” in a subject. Note that the SHANK3 3D spheres did not show any statistically significant reduction in network size post-stimulation. Note that page 9 of the Perets reference pointed out by the declarant discloses factually incorrect information: “Figure 4J” does not pertain to “SHANK3 organoids”. It is Figure 4I showing statistically non-significant (“ns”) difference in the average network size. See also Figure 4K, which clearly shows “ns” for all time points. In fact, SHANK3 organoids (Figure 4I) showed the least difference in network size among those tested in the post-filing reference, which thus fails to adequately support the treatment or prevention effect of increasing SHANK3 in a subject having or prone to have intellectual disability.
Now, turning to the “double stranded saRNA molecule” as currently claimed in the instant case, it is noted that the instant specification at best adequately describes a double-stranded RNA comprising SEQ ID NO:82 with dTdT and its complementary sequence with dTdT (SEQ ID NO:87), wherein the RNA upregulates SHANK3 mRNA in KG-1 cells. That is, only a 21-bp duplex formed by SEQ ID NO:82 and SEQ ID NO:87 with dTdT 3’ overhang in both strands without a hairpin loop is described to upregulate SHANK3 mRNA. The “double stranded” structure as generically claimed is defined to read on a duplex containing “one or more mismatches and/or one or more bulges” and a duplex that is linked by a “hairpin structure” or “a loop”. See page 11 of the specification. As broadly written without the sense strand sequence and the “95%” sequence homology to SEQ ID NO:82, the instantly claimed saRNA molecule reads on multiple structural variants, which are not represented by the single disclosed species consisting of SEQ ID NO:82 and SEQ ID NO:87 with 3’-dTdT in both strands. Furthermore, it is noted that applicant completely dismissed and failed to address the issues pertaining to the non-disclosure pertaining to the required “SHANK3 protein” expression upregulation in the instant application. As noted in the last Office action and reiterated above, the instant specification at best describes an increased expression level in SHANK3 mRNA, not protein.
In view of the foregoing, this rejection is maintained.
Claims 54-56 remain rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement for the reasons as set forth in the Office action mailed on May 13, 2026 and for the reasons stated below.
Applicant's arguments filed on August 5, 2026 have been fully considered but they are not persuasive. Applicant argues that the instant rejection should be withdrawn because there is no need for “extensive screening” for identifying a working asRNA molecule as currently amended. Applicant further points out the §1.132 declaration and argues that the claimed asRNA molecule increase SHANK3 expression in a proper model, which is “directly relevant to the claimed neurological disorders.” Applicant then concludes that there is no need for undue experimentation to make and use the claimed saRNA. Contrary to applicant’s arguments, the claims as amended are not sufficient to enable the method of “treating/ameliorating/preventing an intellectual disability”. As an initial matter, the saRNA of claim 38 as currently amended is not directed to the actual saRNA structure that provided SHANK3 mRNA upregulation in KG-1 cells or in 3D spheres formed by iPSCs obtained from a patient having SHANK3 haploinsufficiency, wherein the 3D spheres that showed increased SHANK3 mRNA expression when transfected with the asRNA consisting of SEQ ID NOs:82 and 87 with 3’ dTdT are not whatsoever indicative of the required, claimed effects of “treating/ameliorating/preventing an intellectual disability” in a subject, especially when the 3D spheres formed by iPSCs obtained from a patient having SHANK3 haploinsufficiency showed no statistically significant difference in network reduction as evidenced by the actual Figures, not the incorrection description, in the post-filing reference mentioned in the §1.132 declaration as explained in detail in the written description rejection above. Applicant did not adequately and satisfactorily elaborate on how the results in the §1.132 declaration fully enable the instantly claimed intellectual disability treatment/prevention method when the saRNA tested by the applicant and the declarant is not even shown to increase SHANK3 “protein” as required by the claims and when the 3D spheres is not an art-recognized in vivo model for investigating intellectual disability treatment/prevention effects, wherein the intellectual disability reads on but is not limited to PMS, ASD, and schizophrenia.
In view of the foregoing, this rejection is maintained.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 53 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 53 requires that the composition of claim 49, which depends from claim 38, comprises “at least two different saRNA molecules.” It is noted that claim 38 as currently amended is directed to an saRNA comprising SEQ ID NO:82. That is, claim 38 is not drawn to two or more (“at least two”) “differment” saRNA molecules. Hence, claim 53 requiring multiple “different” saRNA molecules fails to further limit the subject matter of claim 49 or claim 38.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 38, 49, and 53 are 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 53 requires “at least two different saRNA molecules.” It is unclear whether the saRNA molecule of claim 38, which is also claimed in claim 49, is intended to read on structurally “different” saRNA molecules such that the saRNA molecules of claim 38 reads on a structure whose sense strand sequence that is complementary to SEQ ID NO:82 encompasses multiple different sequences. Similarly, it is unclear whether the “different” saRNA molecules read on different nucleotide sequence variants of SEQ ID NO:82 depending on the sequence homology levels (e.g., “95%”, 100%). As such, the structural metes and bounds of claimed saRNA encompassing “at least two different saRNA molecules” cannot be clearly ascertained.
Conclusion
No claim is 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 DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, RAM SHUKLA can be reached at 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
