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 May 27, 2026.
Currently, claims 199, 258-261, and 263 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Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.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 199, 258-261, and 263 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 January 30, 2026 and for the reasons stated below.
Applicant's arguments filed on May 27, 2026 have been fully considered but they are not persuasive. Applicant argues that the rejection is established based on the fact that SEQ ID NO:400 is listed in Table 16 as one of 452 gRNAs. Contrary to applicant’s argument, the finding that SEQ ID NO:400 is merely listed in Table 16 is only one factor for determining the lack of written description support, which is further corroborated by the unpredictability of the actual gene editing function of SEQ ID NO:400 thus lack of structure-function correlation as extensively explained and elaborated in the last Office action.
Applicant argues that the written description requirement does not require working examples. The examiner does not dispute the fact that an actual reduction to practice is not required to satisfy the written description requirement. Again, applicant’s attention is directed to the fact that the instant rejection is not merely, solely established by the objective fact that SEQ ID NO:400 is listed as one of 452 potential gRNAs in Table 16 without any working examples.
Applicant argues that the explicit listing of the “precise nucleotide sequence” of the instantly claimed SEQ ID NO:400 and SEQ ID NO:25 for providing dual targeting “demonstrates that the inventors possessed these specific molecules as well as the combination”. Contrary to applicant’s argument, the disclosure of the nucleotide sequence of 5’-AGGCACCACTCACCTGTGAT identified as SEQ ID NO:400 is not descriptive of its required function of providing “an insertion, deletion, or mutation” in endogenous human ZC3H12A gene in a human tumor infiltrating lymphocyte for the reasons explained in detail in the last Office action.
“The appearance of
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mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement... If a purported description of an invention does not meet the requirements of the statue, the fact that it appears as an original claim or in the specification does not save it. A claim does not become more descriptive by its repetition, or its longevity.” (emphasis added). Enzo Biochem Inc. v. Gen-Probe Inc. 323 F3d 956, 63 USPQ2d 1609 (Fed. Cir. 2002).
Note that the mere disclosure without satisfying the written description factors generally amounts to a mere wish or future research plan. “A ‘
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mere
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wish or plan’ for obtaining the claimed invention is not adequate written description
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.”” (emphasis added). Centocor Ortho Biotech, Inc. v. Abbott Labs, 636 F.3d 1341, 1348, 97 USPQ2d 1870 (Fed. Cir. 2011).
In view of the foregoing, the mere appearance and the one and only explicit disclosure of SEQ ID NO:400 in Table 16 throughout the entire 179 page-long specification does not meet the written desecration requirement as there is no description of SEQ ID NO:400 providing the function of gene editing in endogenous human ZC3H12A in a human TIL as claimed and required by the claims, wherein the claimed composition imparts a therapeutic function as evidenced by formulating the composition with “a pharmaceutically acceptable carrier.” In addition, there is no adequate written description support that the specific sequence of SEQ ID NO:400 is combined with the specific sequence of SEQ ID NO:25, nor is there any description that reasonably conveys that the instant co-inventors completed and had possession of the specific combination as claimed as of the filing date sought in the instant application. That is, the instant specification is far from adequately describing that the instant co-inventors characterized the claimed function for SEQ ID NO:400 and also for the combination of SEQ ID NOs:400 and 25 in a TILs so as to reasonably convey that the instant co-inventors indeed “possessed these specific molecules as well as the combination” as alleged by applicant.
Applicant argues that the scientific, objective fact that SEQ ID NO:400 is significantly homologous to non-ZC3H12A human sequences is legally irrelevant as the issue of written description has been conflated with enablement/utility issues. In response, applicant’s attention is directed to the fact that it is the instant claims written and presented by applicant that explicitly require that SEQ ID NO:400 should provide “an insertion, deletion, or mutation” in endogenous human ZC3H12A gene in a human tumor infiltrating lymphocyte and be formulated with “a pharmaceutically acceptable carrier”. As such, SEQ ID NO:400 is not a mere nucleotide sequence; it is a functional molecule as required and intended by the rejected claims drafted by applicant. Applicant’s personal opinion that the examiner erred in conflating different rejection with each other thus the examiner applied a legally incorrect standard is far from showing that the instant specification itself describes the instantly claimed subject matter with all claim limitations recited in the rejected claims in such a manner that reasonably conveys that the instant co-inventors had possession of the instantly claimed specific combination composition, wherein SEQ ID NO:400 is required to provide editing of the human ZC3H12A gene in a human TIL.
Applicant argues that SEQ ID NO:400 targets and is complementary to nucleotide positions 5906-5925 of SEQ ID NO:5, which is the genomic DNA sequence, which is targeted by gRNAs thus the examiner erred in using an mRNA sequence for concluding that SEQ ID NO:400 is not adequately supported for its required function. In response, applicant’s attention is directed to the fact that the examiner expressly acknowledged on the record that “the sequence alignment between SEQ ID NO:400 and the disclosed human ZC3H12A sequence of SEQ ID NO:5 reveals that SEQ ID NO:400 is complementary to a 20-mer sequence at positions 5906-5925 of SEQ ID NO:5, wherein the 20-mer sequence appears to be a genomic sequence that is not transcribed as the 20-mer sequence is not found in NM_025079.1.” See pages 5-6 of the last Office action. Hence, contrary to applicant’s allegation, the examiner was fully aware of SEQ ID NO:400 being likely to be complementary to a genomic sequence as the targeted 20-mer sequence is absent in the art-recognized mRNA sequence. Now, the questionable functionality regarding SEQ ID NO:400 targeting nucleotide positions 5906-5925 of SEQ ID NO:5 (note that there is no demonstrated function for SEQ ID NO:400 in the specification) stems from the fact that SEQ ID NO:400 is complementary to a non-transcribed genomic sequence, most likely an intronic sequence, within the human genomic sequence related to ZC3H12A, whereas the demonstrated function of the mouse gRNA sequence of SEQ ID NO:211 is homologous to a murine Zc3h12a sequence, wherein SEQ ID NO:400 shares no sequence homology or similarity with SEQ ID NO:211, thereby extrapolating the function of SEQ ID NO:400 from SEQ ID NO:211 as explained in detail in the last Office action. In fact, it is undisclosed in the instant specification that SEQ ID NO:400 is a structural counterpart of the murine sequence of SEQ ID NO:211 thus there is no adequate written description or guidance that SEQ ID NO:400 would function similarly as SEQ ID NO:211. Again, the instant specification is completely silent as to whether SEQ ID NO:400 is targeted to the same region of the human ZC3H12A genomic sequence that is analogous/homologous to that of the murine Zc3h12a genomic sequence being targeted by SEQ ID NO:211.
The questionable functionality of SEQ ID NO:400 becomes even more apparent in view of the fact that non-ZC3H12A mRNA sequences transcribed from the corresponding human genomic sequences do contain a significant nucleotide sequence identity with SEQ ID NO:400 as explained in the last Office action, wherein such scientific evidence dismissed by applicant as being irrelevant indeed supports the examiner’s position regarding the unpredictable nature of SEQ ID NO:400 as having the required “gRNA” function in human ZC3H12A editing in a TIL. Again, as clearly noted in the last Office action, “SEQ ID NO:400 is not identified by relevant artisans after the filing date as being a candidate gRNA sequence that actually modifies endogenous human ZC3H12A”, wherein the analysis of the specification, the level of predictability, and the level of prior art knowledge all points to “the non-existent level of predictability and knowledge pertaining to SEQ ID NO:400”. See pages 6-7. Note that “for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.” (emphasis added). See MPEP §2163.
Applicant argues that “SEQ ID NO:400 targets a region of the ZC3H12A gene that bridges exon 3 and an intronic sequence.” Contrary to applicant’s argument, SEQ ID NO:400 appears to be complementary to a 20-mer sequence in the exon 2/intron 2 junction of the genomic sequence related to human ZC3H12A. Regardless of whether SEQ ID NO:400 targets the exon 3/intron 3 or exon 2/intron 2 junction, the objective fact remains that there is no adequate written description support in the specification that SEQ ID NO:400 provides “an insertion, deletion, or mutation” in endogenous human ZC3H12A gene in a human tumor infiltrating lymphocyte and further provides a “pharmaceutical” function as intended by the rejected claims.
Applicant argues that the written description requirement has nothing to do with the analysis of potential “off-target activity” thus bears no relevance as to whether “SEQ ID NO:400 is adequately described.” Contrary to applicant’s argument, in view of the complete absence of any description pertaining to SEQ ID NO:400 other than its sequence is listed in Table 16 as one of 452 gRNAs pertaining to human ZC3H12A, the examiner and a relevant artisan of ordinary skill in the art are compelled to determine whether SEQ ID NO:400, which is so insufficiently and inadequately described for the required function recited in the claims, would be reasonably predicted to provide the recited function in a human TIL. The combination of facts found by the examiner – the lack of similarity between SEQ ID NO:400 and SEQ ID NO:211, a significant nucleotide sequence identity to SEQ ID NO:400 in non-ZC3H12A sequences, and a complete lack of relevant prior art knowledge pertaining to SEQ ID NO:400 having the recited function – is thus crucial and should be analyzed in order to determine whether the claimed subject matter as written is indeed adequately described. That is, such time-consuming analysis might not have been necessary if the instant specification itself adequately and clearly described the structure-function correlation required by the claims as written by applicant.
Applicant argues that the partial sequence homology found in non-ZC3H12A sequences is not sufficient evidence that such sequences are cleaved by the Cas9/gRNA-mediated CRISPR mechanism. In response, applicant’s attention is directed to the fact that the examiner did not state that the non-ZC3H12A sequences are or would be cleaved by SEQ ID NO:400. The examiner provided the sequence homology levels between the non-ZC3H12A sequences and SEQ ID NO:400 in order to illustrate that “it is highly questionable as to the actual function/activity of SEQ ID NO:400 in modifying ZC3H12A that is endogenous to a human TIL.” See page 6 of the last Office action. Note that the Office does not have the resources and facilities to test SEQ ID NO:400 for its functionality, which should have been disclosed and adequately described in the instant specification itself in order to fully comply with the written description requirement under 35 U.S.C. 112(a).
Applicant argues that the post-filing reference by Dequeant is not an extensive disclosure of “all functional gRNAs targeting ZC3H12A” and the written description requirement does not require that a post-filing reference should disclose the claimed gRNA sequence. In response, applicant’s attention is directed to the fact that the post-filing reference was cited to support the high level of unpredictability and the complete lack of relevant prior art knowledge pertaining to SEQ ID NO:400 having the required function, which is not adequately described by the instant specification. Note that the examiner did not state that a post-filing reference should disclose the claimed gRNA sequence in order to satisfy the written description requirement.
Applicant argues that the instant co-inventors identified and possessed the precise 20-mer adjacent to the GGG PAM sequence. Again, applicant’s attention is directed to the fact that SEQ ID NO:400 is not claimed to be a mere nucleotide sequence. The rejected claims do require that SEQ ID NO:400 should be a functional molecule that introduces “an insertion, deletion, or mutation” in endogenous human ZC3H12A gene in a human tumor infiltrating lymphocyte. Hence, the mere fact that the instant co-inventors merely utilized the art-recognized methodology of identifying potential gRNA sequences, which involves no inventive effort, is far from adequately describing the instantly claimed composition that explicitly specifies functions associated with SEQ ID NO:400.
In view of the foregoing, this rejection is maintained.
Double Patenting
Claims 199, 258-261, and 263 remain rejected on the ground of nonstatutory double as being unpatentable over claims 1-14 of U.S. Patent No. 11,111,493 B2 in view of Moriarity et al., Hashimoto et al., Herman et al., and NCBI Reference Sequence: NM_025079.1 for the reasons as set forth in the Office action mailed on January 30, 2026 because applicant did not provide any substantial rebuttal arguments addressing this rejection.
Claims 259-261 and 263 remain rejected on the ground of nonstatutory double as being unpatentable over claims 1-16 of U.S. Patent No. 11,421,228 B2 in view of Moriarity et al., Hashimoto et al., Herman et al., and NCBI Reference Sequence: NM_025079.1 for the reasons as set forth in the Office action mailed on January 30, 2026 because applicant did not provide any substantial rebuttal arguments addressing this rejection.
Claims 259-261 and 263 remain rejected on the ground of nonstatutory double as being unpatentable over claims 1-20 of U.S. Patent No. 11,608,500 B2 in view of Moriarity et al., Hashimoto et al., Herman et al., and NCBI Reference Sequence: NM_025079.1 for the reasons as set forth in the Office action mailed on January 30, 2026 because applicant did not provide any substantial rebuttal arguments addressing this rejection.
Claims 199, 258-261, and 263 remain provisionally rejected on the ground of nonstatutory double as being unpatentable over claims 1-2, 4, 8, 10-12, 14-15, 18-20, 26 of Application No. 17/802,080 for the reasons as set forth in the Office action mailed on January 30, 2026 and for the reasons stated below.
Applicant's arguments filed on May 27, 2026 have been fully considered but they are not persuasive. Applicant argues that the rejection should be withdrawn in view of MPEP §804. In response, it is noted that the instant provisional rejection is not the only outstanding rejection in the instant application. Accordingly, this rejection is maintained.
Claims 259-261 and 263 remain provisionally rejected on the ground of nonstatutory double as being unpatentable over claims 289-290 and 292-298 of Application No. 18/065,464 in view of Moriarity et al., Hashimoto et al., Herman et al., and NCBI Reference Sequence: NM_025079.1 for the reasons as set forth in the Office action mailed on January 30, 2026 because applicant did not provide any substantial rebuttal arguments addressing this rejection.
Conclusion
No claim is allowed.
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 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
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