Prosecution Insights
Last updated: April 19, 2026
Application No. 18/246,263

PIPERAZINE-BASED CATIONIC LIPIDS

Non-Final OA §112§DP
Filed
Mar 22, 2023
Examiner
ANDERSON, REBECCA L
Art Unit
1626
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Translate Bio, Inc.
OA Round
1 (Non-Final)
73%
Grant Probability
Favorable
1-2
OA Rounds
2y 5m
To Grant
97%
With Interview

Examiner Intelligence

Grants 73% — above average
73%
Career Allow Rate
749 granted / 1022 resolved
+13.3% vs TC avg
Strong +24% interview lift
Without
With
+24.0%
Interview Lift
resolved cases with interview
Typical timeline
2y 5m
Avg Prosecution
44 currently pending
Career history
1066
Total Applications
across all art units

Statute-Specific Performance

§101
0.6%
-39.4% vs TC avg
§103
17.0%
-23.0% vs TC avg
§102
25.0%
-15.0% vs TC avg
§112
31.8%
-8.2% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1022 resolved cases

Office Action

§112 §DP
DETAILED ACTION Claims 1, 3-8, 20, 25, 27, 31-35, 39, 40, 47 and 48 are currently pending in the instant application. Claims 1, 3, 5, 20, 25, 27, 31-35, 39, 40, and 47 are rejected. Claims 4, 6-8 and 48 are objected. 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 . Election/Restrictions Applicant’s election without traverse of Group I and the species: PNG media_image1.png 230 562 media_image1.png Greyscale in the reply filed on 8 December 2025 is acknowledged. According to MPEP 803.02, the examiner has determined whether the elected species is allowable. Applicants’ elected species is allowable. Therefore, the search and examination has been extended to the entirety of claims 1, 3-8, 20, 25, 27, 31-35, 39, 40, 47 and 48. Claim Objections Claims 4, 6-8 and 48 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Claim Rejections - 35 USC § 112 The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. Claim 32 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims must, under modern claim practice, stand alone to define an invention, and incorporation into claims by express reference to the specification is not permitted. Ex parte Fressola, 27 USPQ 2d 1608 (1993). Instant claim 32 references the specification Tables A-D which renders claim 32 indefinite as the claim has express reference to the specification. It is suggested that claim 32 be amended to list the species of Tables A-D in the claim. Claims 33-35, 39 and 40 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, claims 33 and 35 provide the limitation “the cationic lipid” in reference to claim 1. There is insufficient antecedent basis for this limitation in the claim as claim 1 is “A compound” claim and is not a “cationic lipid”. It is therefore unclear what cationic lipid is present in claim 33-35, 39 and 40 as there is no “cationic lipid” in claim 1 as claim 1 is a “compound”. It is suggested that “the cationic lipid” of claims 33 and 35 should be amended to “the compound”. 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. Claims 1, 3, 5, 20, 25, 27, 31, 32, and 47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 9, 10, 15, 23, 24, 31, 49-52 and 54 of copending Application No. 17/923,839 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims are drawn to methods of delivery of a dynein axonemal intermediate chain (DNAI1) protein comprising administering an MRNA encoding the DNAI protein (conflicting claim 1), wherein the mRNA is encapsulated in a liposome (conflicting claim 3) which comprises one or more cationic lipids, non-cationic lipids, and one or more PEG-modified lipids (conflicting claim 4) wherein the cationic lipids can be HEP-E4-E10 or HEP-E3-E10 (conflicting claim 5) and wherein the cationic lipid is 30-60% of the liposome by molar ratio (conflicting claims 9 and 10). Conflicting claims 52 and 54 provide compositions comprising the mRNA encapsulated in a liposome. HEP-E4-E10 is: PNG media_image2.png 178 634 media_image2.png Greyscale Page 83 of the conflicting specification. HEP-E3-E10 is PNG media_image3.png 276 590 media_image3.png Greyscale . HEP-E4-E10 and HEP-E3-E10 corresponds to the instant claims, for example; in formula PNG media_image4.png 192 570 media_image4.png Greyscale each R is (ii) PNG media_image5.png 108 126 media_image5.png Greyscale ; R2 is alkyl, specifically, PNG media_image6.png 36 116 media_image6.png Greyscale ; a is 3 for compound HEP-E3-E10 and a is 4 for compound HEP-E4-E10; A1 is PNG media_image7.png 84 106 media_image7.png Greyscale ; and Z1 is PNG media_image8.png 98 118 media_image8.png Greyscale . HEP-E3-E10 corresponds to compound A9 in Table A (instant claim 32): PNG media_image9.png 264 622 media_image9.png Greyscale and corresponds to the first compound in claim 47. HEP-E4-E10 corresponds to compound A17 in Table A (instant claim 32): PNG media_image10.png 172 620 media_image10.png Greyscale and corresponds to the first compound on page 10 of claim 47. Methods of use conflicting claims anticipate the products utilized, which in this case is HEP-E4-D10 and HEP-E3-E10 and the compositions comprising HEP-E4-D10 and HEP-E3-E10. In regards to instant claims 20 and 25, R1 which is further defined, is not required to be present on the formula (I’), therefore, claims 20 and 25 are included in the provisional rejection as R can be (ii). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Claims 1, 3, 5, 20, 25, 27, 31-34, 40, and 47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 8-24 of copending Application No. 17/522,754 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims are claiming a composition comprising an nRNA encapsulated in a lipid nanoparticle wherein the lipid nanoparticle comprises HEP-E3-E10 or HEP-E4-E10 (conflicting claims 1-2) wherein the lipid nanoparticle further comprises a non-cationic lipid and a PEG-modified lipid (conflicting claim 3) and a cholesterol-based lipid (conflicting claim 4). Conflicting claims 20, and 21 are methods utilizing the composition of conflicting claim 1. In regards to instant claims 20 and 25, R1 which is further defined, is not required to be present on the formula (I’), therefore, claims 20 and 25 are included in the provisional rejection as R can be (ii). Please see the above provisional nonstatutory double patenting rejection as being unpatentable over copending Application No. 17/923,839 for the discussion relevant to HEP-E3-E10 and HEP-E4-E10. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Claims 1, 3, 5, 20, 25, 27, 31-34, 40, and 47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 54, 56, 77, 84, 85, 124, and 135 of copending Application No. 18/552,165 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because conflicting claim 54 claims a lipid nanoparticle comprising a cationic lipid, a non-cationic lipid, a PEG-modified lipid and a cholesterol-based lipid wherein the cationic lipid is HEP-E3-E10 or HEP-E4-E10 (conflicting claim 56). The additional conflicting claims claim compositions and formulations of the lipid nanoparticle, kits comprising the lipid nanoparticle, and methods of utilizing the lipid nanoparticle. Methods of use conflicting claims anticipate the products utilized, which in this case is HEP-E4-D10 and HEP-E3-E10 and the compositions comprising HEP-E4-D10 and HEP-E3-E10. In regards to instant claims 20 and 25, R1 which is further defined, is not required to be present on the formula (I’), therefore, claims 20 and 25 are included in the provisional rejection as R can be (ii). Please see the above provisional nonstatutory double patenting rejection as being unpatentable over copending Application No. 17/923,839 for the discussion relevant to HEP-E3-E10 and HEP-E4-E10. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Claim 1, 3, 5, 20, 25, 27, 31-34, 40, and 47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-7, 9-12, 17-18, 20-24, 26—27, 29, 34-38, 47, 58-61, 67-70, and 72-75 of copending Application No. 18/575,019 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims are drawn to compositions comprising a lipid nanoparticle (conflicting claim 1) wherein the lipid nanoparticle comprises one or more cationic lipids, one or more non-cationic lipids, and one or more PEG-modified lipids (conflicting claim 34) wherein the cationic lipid can be HEP-E3-E10 or HEP-E4-E10 (conflicting claim 35) wherein the lipid nanoparticle further comprises one or more cholesterol-based lipids (conflicting claim 38). Conflicting claims 58-61, 67-71 and 72-75 are methods which utilize the lipid nanoparticle. Methods of use conflicting claims anticipate the products utilized, which in this case is HEP-E4-D10 and HEP-E3-E10 and the compositions comprising HEP-E4-D10 and HEP-E3-E10. In regards to instant claims 20 and 25, R1 which is further defined, is not required to be present on the formula (I’), therefore, claims 20 and 25 are included in the provisional rejection as R can be (ii). Please see the above provisional nonstatutory double patenting rejection as being unpatentable over copending Application No. 17/923,839 for the discussion relevant to HEP-E3-E10 and HEP-E4-E10. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Claims 1, 3, 5, 20, 25, 27, 31, 32, and 47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 9-10, 13-14, 18, 20, 22, 38-39, 46, 49-51 and 64 of copending Application No. 18/661,393 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims are drawn to methods of treating primary ciliary dyskinesia (PCD) by administering an mRNA wherein the mRNA is encapsulated in a liposome (conflicting claim 20) which comprises one or more cationic lipids, one or more non-cationic lipids, and one or more PEG-modified lipids (conflicting claim 20), wherein the cationic lipid can be HEP-E4-E10 or HEP-E3-E10 (conflicting claim 22). Methods of use conflicting claims anticipate the products utilized, which in this case is HEP-E4-D10 and HEP-E3-E10 and the compositions comprising HEP-E4-D10 and HEP-E3-E10. In regards to instant claims 20 and 25, R1 which is further defined, is not required to be present on the formula (I’), therefore, claims 20 and 25 are included in the provisional rejection as R can be (ii). Please see the above provisional nonstatutory double patenting rejection as being unpatentable over copending Application No. 17/923,839 for the discussion relevant to HEP-E3-E10 and HEP-E4-E10. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Claims 1, 3, 20, 25, 27, and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, 6, and 9 of copending Application No. 18/847,135(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims are drawn to compounds of the formula (I’z): PNG media_image11.png 196 606 media_image11.png Greyscale wherein A1 and Z1 are different (conflicting claim 1), compounds of the formula (III’z) PNG media_image12.png 222 604 media_image12.png Greyscale wherein RA, RB, RC, and RD are not all identical (conflicting claim 3), compounds of the formula (Iaz) PNG media_image13.png 294 574 media_image13.png Greyscale wherein A1 and Z1 are different, compounds of the formula (IIIaz): PNG media_image14.png 304 614 media_image14.png Greyscale wherein RA, RB, RC and RD are not all identical, with specific compounds found in claims 9 and 20 such as: PNG media_image15.png 240 650 media_image15.png Greyscale , A3-A6, and A8 which correspond to the instant formula PNG media_image16.png 188 566 media_image16.png Greyscale wherein A1 is PNG media_image17.png 76 106 media_image17.png Greyscale , Z1 is -S-S-; a is 3 or 4; and each R is (ii) PNG media_image18.png 94 122 media_image18.png Greyscale wherein R2 is optionally substituted alkyl or optionally substituted alkenyl. In regards to instant claims 20 and 25, R1 which is further defined, is not required to be present on the formula (I’), therefore, claims 20 and 25 are included in the provisional rejection as R can be (ii). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA L ANDERSON whose telephone number is (571)272-0696. The examiner can normally be reached Monday-Friday from 6am-2pm. 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, Andrew Kosar can be reached at 571-272-0913. 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. /REBECCA L ANDERSON/Primary Examiner, Art Unit 1626 ____________________ 28 January 2026 Rebecca Anderson Primary Examiner Art Unit 1626, Group 1620 Technology Center 1600
Read full office action

Prosecution Timeline

Mar 22, 2023
Application Filed
Jan 28, 2026
Non-Final Rejection — §112, §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

1-2
Expected OA Rounds
73%
Grant Probability
97%
With Interview (+24.0%)
2y 5m
Median Time to Grant
Low
PTA Risk
Based on 1022 resolved cases by this examiner. Grant probability derived from career allow rate.

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