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 .
Applicant’s response filed 08/05/2026 has been received and considered entered. This is a response to amendments and arguments filed 08/05/2026.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1, 2, 17, 23, 25, 28, 33, 34, 43, 51, 57, 60, 62, 65) in the reply filed on 03/23/2026 was acknowledged in the Office action mailed 05/06/2026.
Claims 70-71, 137, 140-141 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/23/2026.
Applicant’s election without traverse of a polypeptide of SEQ ID NO:691 was acknowledged. The species election requirement for a zinc finger protein sequence (e.g., SEQ ID NO:691) stands maintained.
Claims Status
Claims 3-16, 18-22, 24, 26-27, 29-32, 35-42, 44-50, 52-56, 58-59, 61, 63-64, 66-69, 72-136, 138-139, 142-145 is/are cancelled and claim 146 is newly added. Claims 1-2, 17, 23, 25, 28, 33-34, 43, 51, 57, 60, 62, 65, 70-71, 137, 140-141, 146 is/are currently pending with claims 70-71, 137, 140-141 withdrawn. Claims 1-2, 17, 23, 25, 28, 33-34, 43, 51, 57, 60, 62, 65, 146 is/are under examination.
Claim Interpretation
Claim 1 recites “a DNA region having the nucleic acid sequence” SEQ ID NOs:121, 123, or 125 (lines 3-6). A “DNA region” is not defined in the specification such as to limit the size of said region, and the claim does not require that the DNA region be limited to the length and sequence of SEQ ID NOs:121, 123, or 125. The specification also does not exclude the verb “to have” from encompassing “to comprise”. The MPEP states that the term “having” may be interpreted as open terminology in light of the specification, see MPEP § 2111.03(IV). As such, the DNA region of claim 1 encompasses the entirety of the FOXP3 expression control region, which comprises SEQ ID NOs:121, 123, and 125, and claim 1 encompasses any FOXP3 disrupting agent which targets any sequence within the FOXP3 expression control region, wherein the FOXP3 expression control region comprises SEQ ID NOs:121, 123, or 125.
The claims contain limitations preceded by the term “optional”. All claim limitations recited as “optional” are interpreted as not required. As such, prior art can be applied to teach these limitations, but does not need to be applied.
Claim Objections
Claim 2 is objected to because of the following informalities: “a a polyamide or a polynucleotide” should read “a polyamide or a polynucleotide” (lines 2-3). Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2, 25, 28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (a product of nature) without significantly more. This rejection is maintained. The claim(s) recite(s) a site-specific FOXP3 disrupting agent targeting a FOXP3 expression control region encompassing the entire FOXP3 expression control region (see Claim Interpretation above), which disrupting agent encompasses naturally-occurring transcriptional repressors of FOXP3 gene. This judicial exception is not integrated into a practical application because the claims do not recite additional elements which amount to more than the judicial exception. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no such additional elements are recited, nor does it meet any other considerations under MPEP 2106.05(a-h). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The only required elements recited in claims 1-2, 25, and 28 are that the FOXP3 disrupting agent targets a FOXP3 expression control region “having” (encompassing “comprising”, see Claim Interpretation) SEQ ID NOs:121, 123, or 125 (claim 1), comprises a FOXP3 targeting moiety (claim 1), comprises a polypeptide or a modification (claim 2), is comprised in a cell (claim 25), and is comprised in a composition (claim 28), all of which requirements encompass naturally-occurring FOXP3 transcriptional repressors expressed by cells.
Claims 1-2, 25, 28 recite a site-specific FOXP3 disrupting agent, which constitutes a composition—one of the statutory categories of invention.
Claims 1-2, 25, and 28 recite products which encompass products of nature as described in MPEP § 2106.04(b)(II). These recited compositions encompass naturally-occurring proteins which specifically bind to sequences within the expression control region of the FOXP3 gene (Haiqi, 2011; proteins such as NFAT, AP1, STAT5, RUNX, Smad3, and CREB were known to bind to the expression control region of the FOXP3 gene and disrupt expression of FOXP3). The specification teaches that a “site-specific FOXP3 disrupting agent” “refers to any agent that specifically binds to a target FOXP3 expression control region and, e.g., modulates expression of a FOXP3 gene” (page 15 lines 19-21).
According to Step 2A, Prong Two, set forth in MPEP § 2106.04(II)(A)(2), the claims are next evaluated with respect to whether the judicial exception is integrated into a practical application. These considerations are set forth in MPEP § 2106.05(a)-(h). This analysis turns to the additional steps or elements recited within the claims. Claims 1-2, 25, and 28 do not recite any additional steps or elements beyond what has been determined to be a judicial exception.
There are no additional elements that reflect an implementation with a particular additional element nor is it transformed or reduced to a different state, nor which meets any other considerations under MPEP § 2106.05(a)-(h), such that the claimed product amounts to significantly more than the judicial exceptions.
For all these reasons, claims 1-2, 25, and 28 are directed to judicial exceptions without significantly more and are rejected.
Response to Arguments
Applicant's arguments filed 08/05/2026 have been fully considered but they are not persuasive. Applicant argues on pages 15-16 that the amendment to claim 1 renders the rejection of claims under 35 USC 101 moot. However, as described under Claim Interpretation and in the rejection of claims above, the amendment of claim 1 does not require that the targeting moiety bind to SEQ ID NOs:121, 123, or 125, but that the targeting moiety binds to a FOXP3 expression control DNA region which comprises SEQ ID NOs:121, 123, or 125, which encompasses the entirety of the FOXP3 expression control region. Rephrasing “wherein the site-specific FOXP3 targeting moiety binds to a DNA region having the nucleic acid sequence” to “wherein the site-specific FOXP3 targeting moiety binds to the nucleic acid sequence of” in claim 1 would be remedial and would limit the targeting moiety of claim 1 to a targeting moiety which binds SEQ ID NOs:121, 123, or 125.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-2, 23, 25, 28, 33-34, 43, 51, 57, 60, 62, 65, 146 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gersbach (WO2018031762A1). This rejection is amended to address the claim amendments and is maintained.
Regarding claim 1, Gersbach teaches a site-specific FOXP3 disrupting agent, comprising a site-specific FOXP3 targeting moiety which targets a FOXP3 control region (the FOXP3 promoter) (claims 1-4, 7, 9). Gersbach teaches that the site-specific FOXP3 targeting moiety comprises a polypeptide (a fusion protein) and a polynucleotide (a guide RNA) (claim 1). Gersbach teaches that the guide RNA may comprise the sequence of SEQ ID NO:13 (SEQ ID NO:13 is 23 nucleotides long, including the PAM sequence, and comprises a 20-nucleotide sequence 100% complementary to instant SEQ ID NO:121 and 100% identical to instant SEQ ID NO:120, see alignments below) (claim 36).
SEQ ID NO:121:
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SEQ ID NO:120:
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Regarding claim 2, Gersbach teaches that the site-specific FOXP3 targeting moiety comprises a polypeptide (a fusion protein) and a polynucleotide (a guide RNA) (claim 1). Gersbach teaches that the target sequence is upstream of the FOXP3 transcription start site (claims 4-9). Gersbach teaches that the disrupting agent comprises a modification (claim 16, the fusion protein is modified to be nuclease-dead). Gersbach teaches that the guide RNA may comprise the sequence of SEQ ID NO:13 (SEQ ID NO:13 is 23 nucleotides long, including the PAM sequence, and comprises a 20-nucleotide sequence 100% complementary to instant SEQ ID NO:121 and 100% identical to instant SEQ ID NO:120, see alignments below) (claim 36).
SEQ ID NO:121:
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SEQ ID NO:120:
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Regarding claim 23, Gersbach teaches a vector encoding the FOXP3 disrupting agent (paragraph [0081]).
Regarding claim 25, Gersbach teaches an isolated cell comprising the FOXP3 disrupting agent (claim 28; paragraph [00143]).
Regarding claim 28, Gersbach teaches that the FOXP3 disrupting agent may be present in a pharmaceutical composition (paragraphs [00133]-[00134]).
Regarding claims 33-34, 43, 51, and 57, Gersbach teaches that the site-specific FOXP3 disrupting agent comprises a dCas9-p300 fusion protein and one or more guide RNAs targeting different sequences in the FOXP3 expression control region, and wherein the dCas9-p300 fusion protein comprises SEQ ID NO:26 (SEQ ID NO:26 is 97.6% identical to instant SEQ ID NO:10 and comprises a p300 sequence 100% identical to instant SEQ ID NO:65, see alignments below) (claims 1-13, 15, 19, 27).
SEQ ID NO:26 vs instant SEQ ID NO:10:
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SEQ ID NO:26 vs instant SEQ ID NO:65:
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Gersbach teaches that the guide RNA may comprise the sequence of SEQ ID NO:13 (SEQ ID NO:13 is 23 nucleotides long, including the PAM sequence, and comprises a 20-nucleotide sequence 100% complementary to instant SEQ ID NO:121 and 100% identical to instant SEQ ID NO:120, see alignments below) (claim 36).
SEQ ID NO:121:
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SEQ ID NO:120:
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Regarding claim 60, Gersbach teaches a vector encoding the FOXP3 disrupting agent (paragraph [0081]).
Regarding claim 62, Gersbach teaches a cell comprising the FOXP3 disrupting agent (claim 28).
Regarding claim 65, Gersbach teaches that the FOXP3 disrupting agent may be present in a pharmaceutical composition (paragraphs [00133]-[00134]).
Regarding claim 146, Gersbach teaches that a vector comprising the FOXP3 disrupting agent may be a DNA or RNA vector encoding the FOXP3 disrupting agent (paragraph [0081]).
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) 1-2, 17, 23, 25, 28, 33-34, 43, 51, 57, 60, 62, 65, 146 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gersbach (WO2018031762A1), in view of Joung (US20160024524A1). This rejection is amended to address the claim amendments and is maintained.
Regarding claim 1, Gersbach teaches a site-specific FOXP3 disrupting agent, comprising a site-specific FOXP3 targeting moiety which targets a FOXP3 control region (the FOXP3 promoter) (claims 1-4, 7, 9). Gersbach teaches that the site-specific FOXP3 targeting moiety comprises a polypeptide (a fusion protein) and a polynucleotide (a guide RNA) (claim 1). Gersbach teaches that the guide RNA may comprise the sequence of SEQ ID NO:13 (SEQ ID NO:13 is 23 nucleotides long, including the PAM sequence, and comprises a 20-nucleotide sequence 100% complementary to instant SEQ ID NO:121 and 100% identical to instant SEQ ID NO:120, see alignments below) (claim 36).
SEQ ID NO:121:
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SEQ ID NO:120:
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Regarding claim 2, Gersbach teaches that the site-specific FOXP3 targeting moiety comprises a polypeptide (a fusion protein) and a polynucleotide (a guide RNA) (claim 1). Gersbach teaches that the target sequence is upstream of the FOXP3 transcription start site (claims 4-9). Gersbach teaches that the disrupting agent comprises a modification (claim 16, the fusion protein is modified to be nuclease-dead). Gersbach teaches that the guide RNA may comprise the sequence of SEQ ID NO:13 (SEQ ID NO:13 is 23 nucleotides long, including the PAM sequence, and comprises a 20-nucleotide sequence 100% complementary to instant SEQ ID NO:121 and 100% identical to instant SEQ ID NO:120, see alignments below) (claim 36).
SEQ ID NO:121:
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SEQ ID NO:120:
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Regarding claim 17, Gersbach teaches that the FOXP3 targeting moiety comprises a guide RNA sequence of SEQ ID NO:14 (SEQ ID NO:14 is 100% identical to the first 20 nucleotides of instant SEQ ID NO:109, of Table 2, which first 20 nucleotides are indicated in Table 2 as complementary to the target sequence, see alignment below) (claim 11). Gersbach also teaches that the complementary region of the gRNA is 12-22 nucleotides long, obviating truncations of SEQ ID NO:14 resulting in a 20-nucleotide-long sequence in place of the 23-nucleotide-long sequence of SEQ ID NO:14 (claim 10).
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Regarding claim 23, Gersbach teaches a vector encoding the FOXP3 disrupting agent (paragraph [0081]).
Regarding claim 25, Gersbach teaches a cell comprising the FOXP3 disrupting agent (claim 28).
Regarding claim 28, Gersbach teaches that the FOXP3 disrupting agent may be present in a pharmaceutical composition (paragraphs [00133]-[00134]).
Regarding claims 33-34, 43, 51, and 57, Gersbach teaches that the site-specific FOXP3 disrupting agent comprises a dCas9-p300 fusion protein and one or more guide RNAs targeting different sequences in the FOXP3 expression control region, and wherein the dCas9-p300 fusion protein comprises SEQ ID NO:26 (SEQ ID NO:26 is 97.6% identical to instant SEQ ID NO:10 and comprises a p300 sequence 100% identical to instant SEQ ID NO:65, see alignments below) (claims 1-13, 15, 19, 27).
SEQ ID NO:26 vs instant SEQ ID NO:10:
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SEQ ID NO:26 vs instant SEQ ID NO:65:
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Gersbach teaches that the guide RNA may comprise the sequence of SEQ ID NO:13 (SEQ ID NO:13 is 23 nucleotides long, including the PAM sequence, and comprises a 20-nucleotide sequence 100% complementary to instant SEQ ID NO:121 and 100% identical to instant SEQ ID NO:120, see alignments below) (claim 36).
SEQ ID NO:121:
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SEQ ID NO:120:
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Regarding claim 60, Gersbach teaches a vector encoding the FOXP3 disrupting agent (paragraph [0081]).
Regarding claim 62, Gersbach teaches a cell comprising the FOXP3 disrupting agent (claim 28).
Regarding claim 65, Gersbach teaches that the FOXP3 disrupting agent may be present in a pharmaceutical composition (paragraphs [00133]-[00134]).
Regarding claim 146, Gersbach teaches that a vector comprising the FOXP3 disrupting agent may be a DNA or RNA vector encoding the FOXP3 disrupting agent (paragraph [0081]).
However, Gersbach does not teach the tracrRNA sequence of the guide RNA required for the guide RNA to bind to the Cas9 nuclease (required by claim 17; the guide RNA sequences of Table 2 each comprise a crRNA and a tracrRNA).
Joung teaches single guide RNA (sgRNA) comprising a crRNA sequence complementary to a target sequence and 20 nucleotides long, and a tracrRNA sequence.
Regarding claim 17, Joung teaches that an sgRNA for use with S. pyogenes Cas9 (paragraphs [0094], [0132]) comprises a 17-20 nucleotide-long crRNA sequence (sequence complementary to a target sequence) linked at its 3’ terminus to a tracrRNA of SEQ ID NO:15 (Fig. 1; paragraphs [0071]-[0072]; claims 3, 11, 14, 29).
Gersbach does not teach any particular tracrRNA sequence (either separate or in the same sgRNA as the described crRNA sequences). However, Gersbach does teach that Type II effector systems such as Cas9 systems require a tracrRNA and a crRNA, either as separate molecules or joined in an sgRNA (paragraphs [0085]-[0087]). An artisan would look to the prior art regarding S. pyogenes Cas9 systems to determine an appropriate tracrRNA sequence for the sgRNAs described by Gersbach. Joung teaches multiple tracrRNA sequences usable with an S. pyogenes Cas9 system, and an artisan would find it obvious to use such tracrRNA sequences with the S. pyogenes Cas9 system of Gersbach. As Cas9 requires a tracrRNA sequence in order to bind to a guide RNA, it would have been obvious to an artisan that the addition of the tracrRNA sequence of Joung to the gRNA of Gersbach would enable the gRNA of Gersbach to bind to the Cas9 of Gersbach and direct editing of the FOXP3 expression control region.
Response to Arguments
Applicant's arguments filed 08/05/2026 have been fully considered but they are not persuasive. Applicant argued that Gersbach does not anticipate or render obvious, and that the combination of Gersbach and Joung do not render obvious, FOXP3 disrupting agents which target SEQ ID NOs:121, 123, or 125. However, as described in the rejections under 35 USC 102 and 103 above, Gersbach does teach gRNA targeting instant SEQ ID NO:121. As such, the rejections under 35 USC 102 and 103 are amended to address the amendments to the claims and are maintained.
Conclusion
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.
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/KIMBERLY CHONG/ Primary Examiner, Art Unit 1636
