DETAILED ACTION
Applicants’ arguments, filed 15 January 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Interpretation
Claim 180 recites the following, wherein the relevant text is reproduced below with a specific term pointed out by the examiner.
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The transitional phrase "consisting of" excludes any element, step, or ingredient not specified in the claim. See MPEP 2111.03(II).
In this case, the examiner understands the phrase “consists of” to exclude the presence of any lipid that is not explicitly recited by the claim. As such, for the purposes of examination under prior art, the examiner understands that claim 180 excludes the presence of a lipid that is not explicitly recited by the claim. However, claim 180 is not understood to exclude the presence of additional elements that are not lipids.
The examiner notes that PEGylated lipids are frequently included in liposomes and lipid nanoparticles for delivery of nucleic acids. For example, the lipid nanoparticles used to deliver the mRNA COVID-19 vaccines comprise PEGylated lipids. See e.g. Schoenmaker et al. (International Journal of Pharmaceutics 601 (2021) 120586, pages 1-13), page 8, left column and first paragraph of right column, page 4, left column, section 2.2, and page 8, figure 6, reproduced below.
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For the purposes of examination under prior art, instant claim 180 is being interpreted as excluding PEGylated lipids in view of the “consisting of” language presented in the claims.
Claims 182 and 189 and claims dependent thereon are interpreted in a similar manner as these claims have a similar limitation.
Claim Rejections - 35 USC § 112(a) – New Matter
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.
Claims 189-190 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 189-190 recite a Cas protein and guide RNA targeting the huntingtin gene. This appears to be new matter which is not adequately supported by the original application as filed.
The examiner notes that the original application as filed discloses the following, as of pages 13-14, paragraph 0052, relevant text reproduced below.
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The above-reproduced paragraph appears to disclose siRNA targeting huntingtin expression, but is silent as to Cas proteins and guide RNA targeting huntingtin expression.
The instant specification also discloses the following as of page 25, paragraphs 00089-00090, reproduced below.
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Nothing in the above-reproduced text appears to disclose a Cas protein and guide RNA targeting huntingtin expression.
The examiner further notes the instant specification as of page 11, paragraph 00040, which is reproduced below.
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The above-reproduced paragraph appears to disclose a Cas9 targeting human Huntingtin. However, the above-reproduced paragraph does not disclose a guide RNA targeting Human Huntingtin, and does not disclose Cas proteins other than Cas9 targeting Human Huntingtin.
The examiner notes that various arguments presented by applicant in applicant’s response on 15 January 2026 appear to relate to this matter and are addressed below in the section entitled “Response to Arguments and Declaration Under 37 C.F.R. 1.132.”
Relevant Prior Art – No Rejection
As relevant prior art, the examiner cites Zhang et al. (WO 2018/213726 A1), which was previously cited in the file record. Zhang et al. (hereafter referred to as Zhang) is drawn to compositions and methods for nucleic acid editing, as of Zhang, title and abstract. Zhang teaches nucleic acid editing via CRISPR on page 7, top paragraph. Zhang teaches delivery via lipid nanoparticles on pages 10-11, paragraph 0051, which also indicates that particles used for delivering RNA can also be used for CRISPR materials delivery. Zhang provides teachings regarding the makeup of the lipid nanoparticles as of at least page 130, in which Zhang teaches a nanoparticle comprising cationic lipid, DSPC (distearoyl phosphatidylcholine), cholesterol, and a PEGylated lipid; relevant text has been reproduced below.
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The composition of Zhang differs from the composition used in the claimed method for at least the following reasons:
First, the above-indicated example of Zhang includes a PEGylated lipid; namely, PEG-C-DOMG. This renders Zhang different from the claimed invention because the instant claims are understood to exclude a PEGylated lipid. There would have been no motivation for the skilled artisan to have modified Zhang to have removed the indicated PEGylated lipid.
Secondly, the instant claims require that the cationic lipid is DODMA. Zhang does not teach DODMA as the cationic lipid; in contrast, Zhang teaches different cationic lipids.
Third, the instant claims require DOPE. This is not taught by the above example from Zhang (though is taught elsewhere in the broad disclosure of Zhang; namely, as of Zhang, page 137, paragraph 00424).
Fourth, the above-indicated example of Zhang teaches 40 mol% cationic lipid. This exceeds the 20-30 mol% range of cationic lipid DODMA required by the instant claims.
As such, there would have been no motivation for the skilled artisan to have modified the above-indicated example of Zhang (a) to have excluded a PEGylated lipid, (b) to have included both DOPE and DSPC together as helper lipids, let alone in their recited amounts, (c) to have used DODMA instead of the cationic lipids taught by Zhang, and (d) to have reduced the amount of cationic lipid taught by Zhang.
Additionally, the instant application appears to have presented results showing that the use of DODMA results in superior activity of nucleic acid as compared with the different cationic lipid DLinDAP, which was the cationic lipid actually used in the example of Zhang. See the instant specification on page 21, relevant text reproduced below.
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Also see the instant specification on page 22, paragraph 00079, as well as results presented in the declaration added to the file record on 15 January 2026.
As such, for at least these reasons, no rejection has been written over Zhang. The examiner also notes the rationale presented in the notice of allowance mailed on 23 August 2023 in application 17/941,669 (which is a divisional of parent application 17/281,678). The reasons presented there are also relevant in regard to the examiner’s decision not to reject the instant claims over prior art.
Response to Arguments and Declaration Under 37 C.F.R. 1.132
Applicant has presented arguments in applicant’s response on 15 January 2026 (hereafter referred to as applicant’s response). These arguments have been addressed to the extent that they are relevant regarding the currently pending rejections and regarding the currently pending claims.
On page 6 of applicant’s response, applicant addressed the previously applied objections and the previously applied indefiniteness rejections. In response and in view of the claim amendments set forth on 15 January 2026, the previously applied objections and indefiniteness rejections have been withdrawn. As such, applicant’s arguments appear to be moot in view of the withdrawal of the rejections which these arguments address.
Applicant has provided arguments regarding the previously applied rejection for lack of enablement, as of applicant’s response, page 7 and the top two paragraphs of page 8. These arguments are moot in view of the withdrawal of the previously applied rejection for lack of enablement and will not be addressed substantively. The data in the declaration under 37 C.F.R. 1.132 also supports the examiner’s position to withdraw the previously applied rejection for lack of enablement.
In applicant’s arguments as of the last four paragraphs of page 8 as well as the top of page 9, applicant has provided arguments relating to the new claim amendments. These arguments appear to relate to the currently applied new matter rejection and will be addressed substantively.
Applicant makes the following argument on page 8, which is reproduced below.
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Even if, purely en arguendo, all of the facts described in the above-reproduced paragraph are correct, it is not sufficient to overcome the above-applied new matter rejection. The instant specification on pages 13-14, paragraph 00052 discloses siRNA targeting the huntingtin gene, but is silent as to Cas proteins and/or guide RNA targeting the huntingtin gene.
Applicant then makes the following argument on page 8 of applicant’s response.
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This is not persuasive to overcome the above-applied new matter rejection. The instant specification on page 11, paragraph 40 teaches Cas9 targeting the huntingtin gene. This fails to provide support for the full scope of Cas molecules targeting the huntingtin gene. This paragraph also fails to provide support for guide RNA targeting the huntingtin gene.
Regarding the citation of pages 89-90 of the instant specification and the figures cited therein, the examiner notes that while paragraph 90 discloses apparently reduced mRNA levels of huntingtin, nothing in this paragraph discloses that the cause of the reduced mRNA levels is a Cas protein and guide RNA targeting huntingtin.
Applicant then discusses the declaration under 1.132 submitted to the file record with applicant’s response on 15 January 2026. In response, the examiner takes the position that the declaration is sufficient to overcome the previously applied rejection for lack of enablement. However, the declaration is insufficient to overcome the currently applied new matter rejection. This is at least because the experiment described in the declaration, as Exhibit A, was conducted years after the effective filing date of the instant application and does not indicate that the instant application, as of the effective filing date, provides adequate support for a guide RNA targeting huntingtin and for the full scope of Cas proteins targeting Huntingtin.
The examiner further notes here that the disclosure in the instant specification on page 11, paragraph 00040, that a Cas9 protein targets human Huntingtin fails to provide adequate support for the full scope of Cas proteins targeting human Huntingtin. MPEP 2163.05(II), third paragraph, discusses a case in which applicant was not entitled to the benefit of a parent filing date when the claim was directed to a subgenus where the parent application contained a generic disclosure and a specific example that fell within the recited range because the court held that subgenus range was not described in the parent application. See MPEP 2163.05(II) citing In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971). Similarly, in the instant case, the instant specification includes the specific disclosure of a Cas 9 protein targeting huntingtin and a generic disclosure of Cas proteins, but does not disclose that these Cas proteins target huntingtin. As such, a claim limitation drawn to the subgenus of the full scope of Cas proteins targeting huntingtin is not adequately supported by the original application.
As such, nothing in applicant’s arguments is sufficient to show that newly added claims 189-190 have adequate support in the manner required by 35 U.S.C. 112(a).
Applicant then provided arguments regarding the previously applied obviousness rejection, as of pages 9-10 of applicant’s response. These arguments appear to be moot in view of the withdrawal of this rejection, and will not be addressed substantively by the examiner.
Applicant also provided arguments regarding the previously applied double patenting rejections, as of applicant’s response on pages 10-11 of applicant’s response. The double patenting rejections have been withdrawn in view of the submitted terminal disclaimers. As such, applicant’s arguments regarding the previously applied double patenting rejections have not been addressed substantively.
Terminal Disclaimer
The terminal disclaimer filed on 15 January 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent 11,865,190 has been reviewed and is accepted. The terminal disclaimer has been recorded.
The terminal disclaimer filed on 15 January 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US application serial number 18/392,143 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Allowable Subject Matter
Claims 180-183 and 186 are allowed.
Claims 180-183 and 186 are not subject to a prior art rejection. See the section entitled “Relevant Prior Art – No Rejection” which provides an explanation as to why no prior art rejections have been applied to the currently pending claims. Additionally, the above-applied new matter rejection is not applicable to claims 180-183 and 186. This is because claims 180-183 and 186 do not recite a Cas protein and guide RNA targeting the huntingtin gene.
The previously applied rejections on the grounds of lack of enablement and indefiniteness have also been withdrawn in view of applicant’s claim amendments, applicant’s arguments, and the declaration under 37 C.F.R. 1.132 that was provided with applicant’s response. See the above section of the office action entitled “Response to Arguments and Declaration Under 37 C.F.R. 1.132.”
As such, no rejections have been applied to claims 180-183 and 186, and these claims are understood to be in condition for allowance.
Conclusion
Less than all claims are in condition for allowance.
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 ISAAC SHOMER whose telephone number is (571)270-7671. The examiner can normally be reached 7:30 AM to 5:00 PM Monday Through Friday.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612