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 14, 2026.
Currently, claims 3-12, 16, and 18-24 are pending in the instant application. Claims 5-6, 16, 19, and 21-22 are withdrawn from further consideration as being drawn to nonelected inventions, there being no allowable generic or linking claim. Accordingly, claims 3-4, 7-12, 18, 20, and 23-24 are 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Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.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 3-4, 7-12, 18, and 20 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 14, 2026 and for the reasons stated below.
Applicant's arguments filed on August 14, 2026 have been fully considered but they are not persuasive. Applicant argues that the claims as currently amended are adequately described by the instant specification by pointing out Examples 2 and 6-7 and Figures 10 and 13. Applicant further argues that one of ordinary skill in the art would have had “a reasonable expectation” that fragments comprising SEQ ID NO:3 would provide “a similar enhancing effect” provided by “CARD-CRE12”, which allegedly showed “a modest enhancement”. Contrary to applicant’s argument, the passages and Figures pointed out by applicant do not whatsoever adequately describe a representative number of species within the claimed genus of regulatory element sequences that are required to be “functional” fragments of SEQ ID NO:3.
The objective fact is that a “functional” fragment of SEQ ID NO:3 is not identified in the instant specification, wherein the functional fragment is required to have the “regulatory” function when operably linked to a heart/muscle promoter and a transgene, wherein the “regulatory” function includes enhancing “heart- and/or muscle-specific gene expression” as evidenced by claim 24 that is newly added. Now, it is noted that SEQ ID NO:3 is named as “CARD-CRE11” and SEQ ID NO:4 (a 495-mer sequence at positions 14-508 of SEQ ID NO:3) is named as “CARD-CRE12” in the instant application, wherein the AAV vector comprising “CARD-CRE11” provided “the highest level” of transgene expression, while that comprising “CARD-CRE12” provided “a relatively modest” level of transgene expression (see page 57), wherein the description pertaining to the results in the “CARD-CRE12” injected mouse is factually incorrect. Note that the specification, see page 57, explicitly discloses that the vector comprising “CARD-CRE3 failed to increase luciferase activity” when in fact, the mice injected with the vector comprising “CARD-CRE3” are shown to have stronger luciferase expression intensity than the mouse injected with the vector comprising “CARD-CRE12”. In fact, the mouse treated with “CARD-CRE12” showed even lower luciferase expression compared to the control mice “AAV-Luc (No CRE control)”, wherein the CARD-CRE12-injected mouse showed little or no (almost undetectable) transgene (luciferase) expression in the muscle/heart compared to the clearly detectable transgene expression in mice injected with the vector comprising “CARD CRE11” in the heart and muscle tissues (see Figures 5A-5C). That is, the actual objective data in Figure 3 of the instant specification explicitly show the vector comprising SEQ ID NO:4 failed to provide transgene expression compared to the negative control or the “CARD-CRE3”-containing vector, which is disclosed as having “failed to increase luciferase activity” in the instant specification. When the objective, factual data are considered, SEQ ID NO:4, which is a 495-mer fragment of SEQ ID NO:3, is clearly and unequivocally a non-functional fragment of SEQ ID NO:3, contrary to the description disclosed at page 57 of the specification. The very fact that a 495-mer fragment of SEQ ID NO:3 is experimentally demonstrated to be non-functional supports the examiner’s position that the instant specification fails to disclose a representative number of species within the claimed genus of the functional variants of SEQ ID NO:3 and also the fact that the claimed subject matter confers a high level of unpredictability as evidenced by the factual data disclosed in the instant application, wherein one of ordinary skill in the art would not be able to extrapolate a functional fragment of SEQ ID NO:3 based on the negative data pertaining to SEQ ID NO:4, regardless of applicant’s opinion that there is only “a limited variation” of SEQ ID NO:3. Taken together, the examiner does not find applicant’s assertions and arguments persuasive at all as they are not supported by factual evidence disclosed in the instant application such as Figure 3.
In view of the foregoing, this rejection is maintained.
New Rejections Necessitated by Amendment
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 8-9 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 8 recites that the expression cassette comprises an intron that “is operably linked to the promoter and the transgene.” The claim fails to particularly point out and distinctly claim the position of the “intron” relative to the promoter and the transgene. That is, it is unclear whether the “intron” is placed in between the promoter and the transgene, or following the transgene, or upstream of the promoter. As such, the metes and bounds of the structure of the nucleic acid expression cassette of claim 8 cannot be clearly ascertained.
Claim 9 recites that the expression cassette comprises a polyadenylation signal that “is operably linked to the promoter and the transgene.” The claim fails to particularly point out and distinctly claim the position of the “polyadenylation signal” relative to the promoter and the transgene. That is, it is unclear whether the “polyadenylation signal” is placed in between the promoter and the transgene, or following the transgene, or upstream of the promoter. As such, the metes and bounds of the structure of the nucleic acid expression cassette of claim 9 cannot be clearly ascertained.
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 23-24 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 23-24 directly depend from claim 3, which is found insufficient to comply with the written description requirement as explained hereinabove, which is fully incorporated by reference herein thus will not be repeated.
Regarding claim 23 reciting the “maximum length of 2000 nucleotides” for the regulatory element comprising a 495-mer SEQ ID NO:4, the instant specification fails to describe a representative number of species within the claimed genus of 2,000-mer comprising SEQ ID NO:4 is “functional”, because SEQ ID NO:4 per se is shown to be non-functional in providing transgene expression in mice, let alone the specified muscle/heart tissues. Further, even for a 2,000-mer comprising the 1,640-mer sequence of SEQ ID NO:3, which is shown to be functional, the specification does not describe which nucleotide sequence should constitute the additional 360-mer sequence so as to retain the “functional” feature of SEQ ID NO:3.
Regarding claim 24 reciting the functional feature of the nucleic acid regulatory element, which “enhances heart- and/or muscle-specific gene expression”, it is noted that SEQ ID NO:3 is one and only nucleotide sequence that is adequately described to enhance transgene expression in the heart and muscle of a subject, wherein the single species cannot whatsoever constitute a representative number of species within the claimed genus encompassing substantial structural variations, especially in view of the negative data pertaining to SEQ ID NO:4, which is a 495-mer fragment of SEQ ID NO:3.
Accordingly, the instant specification fails to adequately describe the instantly claimed genus in such a manner to reasonably convey that the instant co-inventors had possession of the entire genus as of the filing date sought in the instant case.
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
