Prosecution Insights
Last updated: April 19, 2026
Application No. 17/760,908

NUCLEIC ACID COMPLEX

Final Rejection §102§DP
Filed
Mar 16, 2022
Examiner
SHIN, DANA H
Art Unit
1635
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Takeda Pharmaceutical Company Limited
OA Round
2 (Final)
27%
Grant Probability
At Risk
3-4
OA Rounds
3y 6m
To Grant
55%
With Interview

Examiner Intelligence

Grants only 27% of cases
27%
Career Allow Rate
311 granted / 1149 resolved
-32.9% vs TC avg
Strong +28% interview lift
Without
With
+27.5%
Interview Lift
resolved cases with interview
Typical timeline
3y 6m
Avg Prosecution
86 currently pending
Career history
1235
Total Applications
across all art units

Statute-Specific Performance

§101
3.8%
-36.2% vs TC avg
§103
29.3%
-10.7% vs TC avg
§102
15.2%
-24.8% vs TC avg
§112
31.4%
-8.6% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1149 resolved cases

Office Action

§102 §DP
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 October 14, 2025. Currently, claims 1-12 and 14-18 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 Response to Arguments and Amendments Withdrawn Rejections Any rejections/objections not repeated in this Office action are hereby withdrawn.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 § 102 Claims 1-6, 8-12, 14-16, and 18 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Seth et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims removing the limitation “analog thereof” is sufficient to overcome the rejection because Seth does not teach the second nucleic acid bound to “a C22-35 alkyl group optionally substituted with a hydroxy group”. In response, it is noted the term “analog” is defined as “a compound having a similar structure and property, having the same or a similar basic backbone.” See paragraph 0078. In the instant case, Seth’s second oligonucleotide is conjugated to a C26 or C30 lipid group, not a compound “having a similar structure”. Further, applicant’s attention is directed to the fact that the term “optionally” is a mere option, which is thus not required. As such, the claimed second nucleic acid that is bound any of an alkyl group of C22-C35 satisfies the claimed limitations, which do not require a hydroxy group-substituted C22-35 alkyl group. Accordingly, this rejection is maintained. Claims 1-2, 4-6, 8-12, and 14-18 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yano et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims removing the limitation “analog thereof” is sufficient to overcome the rejection because Yano does not teach the second nucleic acid bound to “a C22-35 alkyl group optionally substituted with a hydroxy group”. In response, it is noted the term “analog” is defined as “a compound having a similar structure and property, having the same or a similar basic backbone.” See paragraph 0078. In the instant case, Yano’s second oligonucleotide is conjugated to docosanoic acid (C22H44O2) thus having a C22 alkyl group, not a compound “having a similar structure” to the C22 alkyl group. Further, applicant’s attention is directed to the fact that the term “optionally” is a mere option, which is thus not required. In fact, Yano’s docosanoic acid is identical in structure as “IY1” disclosed in Table 2 of this application, which is disclosed as being “compounds” within the claimed alkyl group. As such, the claimed structural limitations are fully satisfied by Yano’s composition. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims removing the limitation “analog thereof” is sufficient to overcome the rejection because Yokota does not teach the second nucleic acid bound to “a C22-35 alkyl group optionally substituted with a hydroxy group”. In response, it is noted the term “analog” is defined as “a compound having a similar structure and property, having the same or a similar basic backbone.” See paragraph 0078. In the instant case, Yokota’s second oligonucleotide is conjugated to “a docosahexaenoic acid (DHA)” having the formula of C22H32O2 thus comprising a C22 alkyl group, not a compound “having a similar structure” to the C22 alkyl group. As such, the claimed structural limitations are fully satisfied by Yokota’s composition. Accordingly, this rejection is maintained. Claims 1-2, 7-12, and 18 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Biscans et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims removing the limitation “analog thereof” is sufficient to overcome the rejection because Biscans does not teach the second nucleic acid bound to “a C22-35 alkyl group optionally substituted with a hydroxy group”. In response, it is noted the term “analog” is defined as “a compound having a similar structure and property, having the same or a similar basic backbone.” See paragraph 0078. In the instant case, Biscans’s second oligonucleotide is conjugated to docosanoic acid or docosahexaenoic acid thus having a C22 alkyl group, not a compound “having a similar structure” to the C22 alkyl group. Further, applicant’s attention is directed to the fact that the term “optionally” is a mere option, which is thus not required. As such, the claimed structural limitations are fully satisfied by Biscans’s composition. Accordingly, this rejection is maintained. Double Patenting Claims 1-12 and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,816,089 B2 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d reproduced below. PNG media_image1.png 340 420 media_image1.png Greyscale PNG media_image2.png 352 820 media_image2.png Greyscale Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,190,117 B2 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,329,567 B2 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,337,006 B2 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,028,387 B2 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 7-14 of U.S. Patent No. 11,034,955 B2 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,260,134 B2 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,433,089 B2 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,674,141 B2 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,851,654 B2 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 12,305,169 B2 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 8-37 of U.S. Patent No. 12,344,841 B2 (issued in Application No. 17/332,249) in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 and 42 of copending Application No. 17/442,663 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9-30, 32-40 of copending Application No. 17/602,035 for the reasons as set forth in the Office action mailed on May 16, 2025 because applicant did not provide any substantial rebuttal arguments addressing the supposed errors of this rejection. Claims 1-12 and 14-18 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-20 of copending Application No. 17/767,663 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 17/815,473 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of copending Application No. 18/392,869 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12, 14-17, 19, 21-22 of copending Application No. 18/563,128 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 63-99 of copending Application No. 18/690,457 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 9-13, 17-19, 22, 33, 42-43, 49-51 of copending Application No. 18/706,530 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 and 34-38 of copending Application No. 19/115,981 in view of Yokota et al. for the reasons as set forth in the Office action mailed on May 16, 2025 and for the reasons set forth below. Applicant's arguments filed on October 14, 2025 have been fully considered but they are not persuasive. Applicant argues that the instant claims as currently amended are not taught by Yokota and that Yokota’s Example 19 teaches away from the instantly claimed subject matter because “DHA-HDO” did not suppress the target RNA in the brain. In response, the instant claims as amended recite that the second nucleic acid strand “is bound to a C22-35 alkyl group optionally substituted with a hydroxy group”. Yokota’s second nucleic acid strand is conjugated to a docosahexaenoic acid (DHA), which has a C22 alkyl group. Regarding Yokota’s Example 19, which allegedly teaches away from the instantly claimed subject matter, it is noted that Figure 37a-d referenced in Example 19 do expressly demonstrate that the DHA-conjugated nucleic acid molecule provides brain region-specific delivery such that the DHA conjugation preferentially delivers the nucleic acid to the cerebellum and striatum while not being delivered to the hippocampus. See Figures 37b-d. Hence, one of ordinary skill in the art desiring to deliver a nucleic acid molecule to the cerebellum or the striatum but not to the hippocampus would have been sufficiently motivated to utilize the art-recognized DHA conjugation taught by Yokota. Accordingly, this rejection is maintained. Claims 1-12 and 14-18 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/179,469 for the reasons as set forth in the Office action mailed on May 16, 2025 because applicant did not provide any substantial rebuttal arguments addressing the supposed errors of 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. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. 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. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /DANA H SHIN/Primary Examiner, Art Unit 1635
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Prosecution Timeline

Mar 16, 2022
Application Filed
May 13, 2025
Non-Final Rejection — §102, §DP
Oct 14, 2025
Response Filed
Jan 13, 2026
Final Rejection — §102, §DP (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

3-4
Expected OA Rounds
27%
Grant Probability
55%
With Interview (+27.5%)
3y 6m
Median Time to Grant
Moderate
PTA Risk
Based on 1149 resolved cases by this examiner. Grant probability derived from career allow rate.

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