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
Claim Status
Claims 77-98 are pending. Claims 96-98 have been added. Claims 77-78 have been amended. Claims 77-84 and 87-98 are being examined in this application. In response to the restriction requirement, Applicants elected Group V, SEQ ID NO: 13 (first targeting moiety), wherein the first targeting moiety is disposed N-terminal of the first effector moiety, SEQ ID NO: 19 (DNA methyltransferase), SEQ ID NO: 135 (nuclear localization signal), and SEQ ID NO: 137 (linker). Claims 85-86 are withdrawn as being drawn to a nonelected species.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
This rejection has been modified.
Claims 77-84 and 87-96 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.
The claims are drawn to a method of treating cancer in a subject in need thereof comprising administering to the subject a nucleic acid comprising a nucleic acid sequence encoding an expression repressor comprising: i) a first targeting moiety comprising a zinc finger domain, wherein the zinc finger domain comprises the amino acid sequence encoded by the nucleic acid sequence of SEQ ID NO: 46 or 131, or an amino acid sequence with at least 95% identity thereto, or wherein the zinc finger domain comprises the amino acid sequence of SEQ ID NO: 13, or an amino acid sequence with at least 95% identity thereto, and ii) a first effector moiety comprising a DNA methyltransferase.
When referring to the first targeting moiety comprising a zinc finger domain, the specification does not provide any structural attributes.
Without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“A definition by function alone “does not suffice” to sufficiently describe a coding sequence because it is only an indication of what the gene does, rather than what it is”).”
Here, the specification fails to describe what part of the sequence correlates with the required activity (i.e. to be a targeting moiety; and to treat cancer).
A zinc finger domain is a structural motif that coordinates one or more zinc ions to stabilize its folded shape and bind to DNA, RNA, or other proteins. In the instant case, the specification fails to describe what part of the sequence correlates with the required activity.
The MPEP states that a broad genus can be described by a showing of representative number of examples. The claims in the instant application are broad.
Based on the teachings of the specification, the first targeting moiety comprising a zinc finger domain can be any nucleic acid having at least 95% identity to SEQ ID NO: 46 or 131; or a peptide having at least 95% identity to SEQ ID NO: 13.
It is noted that SEQ ID NOs: 46 and 131 consist of 627 nucleotides, thus one would end up with 1.22x1084 (627x626x625……….x599x598x3) possible nucleic acids having at least 95% identity to SEQ ID NO: 46 or 131.
Similarly, SEQ ID NO: 13 consists of 209 amino acids, thus, even considering only natural amino acids, one would end up with 2.55x1024 (209x208x207x206x205x204x203x202x201x200x20) possible peptides having at least 95% identity to SEQ ID NO: 13, and with 869,440 (209x208x20) possible peptides having at least 99% identity to SEQ ID NO: 13.
With respect to claims 79-81, the claimed DNA methyltransferase MQ1 or functional variant or fragment thereof comprises SEQ ID NO: 19 or an amino acid sequence with at least 95% identity to SEQ ID NO: 19. However, the specification does not provide any structural attributes of said DNA methyltransferase.
It is noted that SEQ ID NO: 19 consists of 385 amino acids, thus, even considering only natural amino acids, one would end up with 1,132,454,400 (385x384x383x20) possible peptides having at least 99% identity to SEQ ID NO: 19.
With respect to claim 88-89, the claimed expression receptor comprises SEQ ID NO: 129 or an amino acid sequence with at least 95% identity to SEQ ID NO: 129. However, the specification does not provide any structural attributes of said DNA methyltransferase.
It is noted that SEQ ID NO: 129 consists of 652 amino acids, thus, even considering only natural amino acids, one would end up with 1.5x1018 (652x651x650x649x648x647x20) possible peptides having at least 99% identity to SEQ ID NO: 129.
However, the specification fails to provide a representative number of examples for the: 1) first targeting moiety; 2) DNA methyltransferase MQ1 or functional variant or fragment thereof; and 3) expression receptor.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does “little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate”).
Therefore, since the specification fails to identify any relevant structural characteristics that can be attributed to the claimed function and activity, the claimed invention lacks written description.
Response to Arguments
Applicant’s arguments filed on 9/3/2026 have been fully considered but they are not persuasive.
Applicant argues that “[t]hat claim 77 did not define the first targeting moiety by a desired result of functional activity, and the Office's characterization is inconsistent with the language of claim 77. Rather, claim 77 recited that the first targeting moiety comprising an amino acid sequence having at least 95% sequence identity to a particular amino acid sequence (i.e., SEQ ID NO: 13), or amino acid sequences encoded by specific nucleic acid sequences (i.e., SEQ ID NOs: 46 or 131). These recitations are explicit structural limitations that provide concrete structural boundaries for the targeting moiety. In particular, the specification defines SEQ ID NOs: 46 and 131 as DNA and RNA sequences, respectively, encoding an exemplary zinc finger domain (ZF9), while SEQ ID NO: 13 provides the amino acid sequence of the ZF9 zinc finger domain. With respect to the Office's comments regarding percent identity language for SEQ ID NOs: 46, 131, and 13, Applicant respectfully submits that written description is not evaluated by calculating all theoretically possible sequences falling within the scope of a percent identity range. Rather, the relevant inquiry is whether the specification reasonably conveys to a person of ordinary skill in the art that Applicant possessed the claimed subject matter as of the filing date. The specification provides the complete sequence of the exemplary zinc finger targeting moiety, its corresponding coding sequences, as well as numerous expression repressor constructs that incorporate said targeting moiety. Moreover, the specification provides working examples demonstrating the use of ZF9 as the targeting moiety for an exemplary expression repressor comprising MQ1 as the effector moiety (see, e.g., Examples 5, 6, 10-20, 27-39, 43, and 47-56 of the specification as filed). A person of ordinary skill in the art would reasonably expect that various sequences maintaining at least 95% sequence identity to the sequence of ZF9 would retain the functional efficacy demonstrated for the ZF9 protein in the working examples. Thus, the first targeting moiety is defined by its molecular structure, and the specification provides extensive description and working examples demonstrating that the recited structure would be expected to be effective at repressing expression of a target gene. As such, contrary to the Office's contention, a person of ordinary skill in the art would have recognized, based on the instant disclosure, the structure-function relationship between the structural features recited in claim 77 and the functional activity described in the specification. Nevertheless, without assenting to the propriety of the rejection, and solely to expedite prosecution, Applicant has amended claim 77 to recite, in pertinent part, that the "first targeting moiety comprises a zinc finger domain". The amendment provides additional clarification regarding the structure of the targeting moiety. The specification as filed expressly describes zinc finger targeting moieties for targeting the MYC locus and provides specific examples of such targeting moieties, including the amino acid sequences for ZF9 recited in claim 77”.
Applicant also argues that “[T]he specification provides extensive description of DNA methyltransferases and uses of same as effector moieties. For example, page 109, line 9, through page 110, line 29, of the specification as filed describes a large number of DNA methyltransferases, including MQ1 (as recited in claim 79; see, e.g., page 146, line 4, to page 148, line 32; and page 196, line 1, to page 219, line 25). A person of ordinary skill in the art would be familiar with DNA methyltransferases and would accordingly recognize that DNA methyltransferases can be used effectively as effector moieties in the presently claimed methods. Moreover, the instant specification also provides working examples demonstrating the use of the exemplary DNA methyltransferase MQ1 as the effector moiety for an expression repressor comprising ZF9 as targeting moiety (see, e.g., Examples 5, 6, 10-20, 27-39, 43, and 47-56 of the specification as filed)”.
Applicant’s arguments are not persuasive because claim 77 relates to a method of treating cancer comprising administering an expression receptor comprising a first targeting moiety comprising a zinc finger domain and a first effector moiety comprising a DNA methyltransferase.
Therefore, the claimed first targeting moiety has a required activity (i.e. to be a targeting moiety), and the claimed expression receptor must be capable of treating cancer.
Similarly, the claimed DNA methyltransferase comprising MQ1 has a required activity (i.e. to be a DNA methyltransferase).
The specification provides 16 examples of zinc finger domains (Table 4). However, said examples share common motifs. For instance, they all share the sequences LEPGEKPYKCPECGKSFS, TGKKTS, etc.
On the other hand, the claimed zinc finger domain does not require a specific motif to be present.
Therefore, the specification fails to provide a representative number of examples.
With respect to the claimed MQ1 functional variant or fragment, the specification does not provide any example of said functional variant or fragment. All the Examples discussed by the Applicant relate to MQ1, NOT to variants or fragments.
As discussed in the rejection above, one would end up with:
1) 1.22x1084 possible nucleic acids having at least 95% identity to SEQ ID NO: 46 or 131;
2) 2.55x1024 possible peptides having at least 95% identity to SEQ ID NO: 13;
869,440 possible peptides having at least 99% identity to SEQ ID NO: 13;
3) 1,132,454,400 possible peptides having at least 99% identity to SEQ ID NO: 19;
4) 1.5x1018 possible peptides having at least 99% identity to SEQ ID NO: 129.
However, the specification fails to provide a representative number of examples for the: 1) first targeting moiety; 2) DNA methyltransferase MQ1 or functional variant or fragment thereof; and 3) expression receptor.
Therefore, since the specification fails to identify any relevant structural characteristics that can be attributed to the claimed function and activity, and fails to provide a representative number of examples, the claims are properly rejected under 35 U.S.C. 112(a).
For the reasons stated above the rejection is maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
This rejection has been modified.
Claims 77-84, 87-92 and 96-98 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 11-13, 17, 20-21, 23, 27, 29-32, 34, 39, 47-48 and 50-51 of copending Application No. 18/877408 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they relate to the same method.
With respect to claims 77-79 and 96, ‘408 teaches a method of treating cancer comprising administering a composition comprising a nucleic acid encoding an expression repressor, wherein the expression receptor comprises a targeting moiety and an effector moiety (claims 1 and 48), wherein the first effector moiety comprises MQ1 or a functional variant or fragment thereof (Claim 31), and wherein the first targeting moiety comprises an amino acid sequence according to SEQ ID NO: 13 (claim 32), which corresponds to instant SEQ ID NO: 13.
With respect to claims 80-81 and 97, ‘408 teaches that the first effector moiety comprises SEQ ID NO: 19 (claim 34), which corresponds to instant SEQ ID NO: 19.
With respect to claims 82, 88-89 and 98, ‘408 teaches that the first effector moiety comprises SEQ ID NO: 129 (claim 34), which corresponds to instant SEQ ID NO: 129, wherein the first targeting moiety SEQ ID NO: 13 is disposed N-terminal of the first effector moiety SEQ ID NO: 19.
With respect to claims 83-84, SED ID NO: 129 comprises the NLS SEQ ID NO: 135.
With respect to claim 87, SED ID NO: 129 comprises the linker SEQ ID NO: 137.
With respect to claim 90, ‘408 teaches that the expression receptor decreases expression of MYC (claim 1).
With respect to claim 91, ‘408 teaches that the first targeting moiety binds a target sequence within a genomic locus, wherein the target sequence comprises at least 16 nucleotides of SEQ ID NO: 83 (claim 1).
With respect to claim 92, the expression repressor of ‘408 is the same expression repressor instantly claimed; thus, it would inherently increase methylation at a site within the genomic locus.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s arguments filed on 9/3/2026 have been fully considered but they are not persuasive.
Applicant argues that “[A]ccording to M.P.E.P. 804(I)(B)(l)(b), when "a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent .... " The instant application has an earlier patent term filing date (i.e., December 15, 2021) as compared to the '408 application (i.e., June 22, 2023). Applicant believes that the claims, as amended, are in condition for allowance for at least the reasons provided herein. Therefore, the present provisional double patenting rejection should be withdrawn”
Applicant’s arguments are not persuasive because the provisional nonstatutory double patenting rejection is NOT the only rejection remaining in an application.
For this reason, the rejection is maintained.
Conclusion
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 SERGIO COFFA whose telephone number is (571)270-3022. The examiner can normally be reached M-F: 6AM-4PM.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658
Prosecution Insights