DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Applicant's submission filed on 11 June and 6 July 2026 have been entered and the arguments presented therein 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Claim Interpretation
The examiner has provided the following annotated structure of claim 1, with annotation by the examiner.
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The above-indicated nitrogen atoms are amine nitrogen atoms, and not amide, carbamate, or urethane nitrogen atoms. This is because the subscripts “a” and “b” must be at least 1. In view of this, the above-indicated nitrogen atoms are not next to a carbonyl carbon and are not amide, carbamate, or urethane nitrogen atoms.
The examiner notes that amines are significantly different from amides, carbamate, or urethanes because amines can be protonated at physiological pH or pH values slightly below physiological pH. In contrast, amides, carbamates, or urethanes generally cannot be protonated in aqueous solution. This is because the carbonyl bond withdraws electrons from the electron lone pair on the nitrogen atom by resonance from the amide/carbamate/urethane nitrogen atom. This prevents said nitrogen atom in an amide/carbamate/urethane from engaging in a covalent bond with a hydrogen ion using the lone electron pair on the nitrogen atom. In contrast, in an amine, there is no functional group withdrawing the electron lone pair by resonance; this frees the electron lone pair to engage in covalent bonding with a hydrogen ion and form a protonated amine (i.e. substituted ammonium ion).
This distinction is relevant because ionizable cationic lipids are useful for forming lipid nanoparticles to deliver nucleic acids. Were all of the above-indicated nitrogen atoms to be amides/carbamates/urethanes and therefore incapable of protonation, the resultant lipid would not have been an ionizable cationic lipid and would not have been expected to have formed a lipid nanoparticle capable of delivering a nucleic acid.
Regarding claim 1, the claim has been amended, as per the claim set on 8 June 2026, to recite the following limitation.
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The examiner understands this newly added limitation to further limit the following limitation, as of earlier in claim 1.
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As such, the newly added limitation is understood to further limit the alkyl, alkenyl, alkynyl or acyl groups that are part of R1A and R1B and/or the alkyl or alkenyl groups that are part of W1 and/or X1.
Claim 38 recites the phrase “encapsulation percentage.” This phrase is disclosed in the specification, e.g. as of page 51, paragraph 0154. However, this phrase does not appear to define the term “encapsulation percentage.” For the purposes of examination under prior art, the examiner takes the position that an encapsulation percentage of at least 70% means that at least 70% of the total weight of the lipid nanoparticle is mRNA.
The examiner further notes here that the presence of multiple numerical ranges in the alternative does not appear to be a cause for indefiniteness. The mere fact that a compound (or in this case composition) may be embraced by more than one member of a Markush group recited in the claim does not necessarily render the scope of the claim unclear. For example, the Markush group, "selected from the group consisting of amino, halogen, nitro, chloro and alkyl" should be acceptable even though "halogen" is generic to "chloro." See MPEP 2173.05(h)(I), last paragraph in section. Similarly, a claim reciting the broad range “at least 70%” and the narrower range “at least 95%” appears to be acceptable even though “at least 70%” is generic to “at least 95%.” The examiner also notes that the subject matter descried in MPEP 2173.05(c) does not appear to be applicable here because claim 38 recites ranges that are clearly presented in the alternative, and does not recite preferences or examples.
Regarding claims 50-51, which were newly added during the course of examination, the examiner notes that the instant application as filed does not disclose the term “immunogen” but does disclose the term “antigen” as of at least page 3, paragraph [013] of the instant specification. For the purposes of examination under prior art, the examiner understands the terms “immunogen” and “antigen” to have the same meaning. Additionally, although the specification does not clearly disclose that the antigen is a protein, the skilled artisan would have understood the disclosed antigen to have been a protein because mRNA encodes proteins.
Claim Rejections - 35 USC § 112(b) – Indefiniteness
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.
Claims 1-2, 15-26, 30-32, 36, 38, 42, and 44-55 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.
Claim 1 recites the following, wherein relevant text from the claim has been reproduced below with annotation by the examiner.
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The variable R’ does not appear to have been defined by the claim, thereby resulting in a prima facie case of indefiniteness.
For the purposes of examination under prior art, the examiner will proceed with the understanding that R’ is a typographical error, and that R’’ should have been recited instead of R’. As such, the examiner will proceed with the understanding that R’ is limited in the same manner as R’’.
Substantial Duplicate Claims – Warning
Applicant is advised that should claim 26 be found allowable, claim 44 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 26 and claim 44 appear to be substantial duplicates because both claims are drawn to the case wherein R1A and R1B in claim 1 are unsubstituted.
Claim Rejections - 35 USC § 112(d) – Failure to Limit Parent Claim
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 45 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 45 further limits R1A and R1B. However, these variables appear to have been limited in the same manner by claim 1. As such, claim 45 does not appear to further limit claim 1, thereby resulting in an issue under 35 U.S.C. 112(d).
Note Regarding GL-HEPES-E3-E12-DS-4-E10
The examiner notes that the term “GL-HEPES-E3-E12-DS-4-E10” is understood to refer to a lipid with the following structure, as of the instant specification on page 136, paragraph 0297, reproduced below.
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This is relevant in the rejections set forth below on the grounds of non-statutory double patenting in which the term “GL-HEPES-E3-E12-DS-4-E10” is recited in various conflicting and copending claims.
Withdrawn Obviousness Rejection Due to AIA Exception 35 U.S.C. 102(b)(2)(C)
The instant claims were previously rejected as obvious over Karmakar et al. (WO 2022/066916 A1). In response, applicant has presented the following response, as of page 70 of applicant’s response on 6 February 2026, reproduced below.
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The above-reproduced text is understood to be sufficient to invoke an exception under AIA 35 U.S.C. 102(b)(2)(C) regarding the above-applied prior art. See MPEP 2154.02(c). As such, the previously applied prior art rejection has been withdrawn by the examiner.
Claim Rejections - 35 USC § 102(a)(1) – Anticipation
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.
Claim(s) 32 and 48 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Benenato et al. (US 2019/0167811 A1).
Benenato et al. (hereafter referred to as Benenato) is drawn to lipid compositions for polynucleotide delivery, as of Benenato, title and abstract. Benenato teaches the following formulations, as of page 112, Example 3, table reproduced in part below.
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The above-reproduced formulations comprise 10% phospholipid (i.e. the non-cationic lipid), 1.5% PEG-lipid, and between about 18.5-48.5% sterol, all of which are in the claimed range.
The examiner notes that the above-reproduced formulations from Benenato do not teach the compound of claim 1. However, the compound of claim 1 is an optional element of claims 32 and 48; see the following text reproduced from claim 32 for an explanation of this.
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As such, the teachings of Benenato need not include the compound of claim 1 to meet the instantly claimed requirements.
In order to overcome this rejection, applicant should amend claims 32 and 48 such that the lipid of claim 1 is a required element rather than an optional element.
Relevant Art – No Rejection
Kim Reference: As relevant prior art, the examiner cites Kim et al. (Sciences Advances, Vol. 7, 2021, pages 1-12 and 11 supplemental pages). Kim et al. (hereafter referred to as Kim) teaches ionizable lipids for targeting different cell types in the liver, as of Kim, page 1, title and abstract. One lipid taught by Kim has the following structure, as of Kim, second supplemental page, figure S1, reproduced below.
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The above-reproduced chemical structure differs from the claimed chemical structure because it fails to teach the required functional groups A1 and Z1. There would have been no motivation for the skilled artisan to have modified the above chemical structure to have included these functional groups.
Karve ‘427 and ‘611 References: The examiner notes Karve et al. (WO 2020/219427 A1) and Karve et al. (WO 2020/257611 A1). Karve ‘427 teaches a chemical structure on page 46, paragraph 0181, that appears to have essentially the same deficiency as the structure of Kim. Karve ‘611 teaches a chemical structure as of page 45, paragraph 0190, that has essentially the same deficiency as that of Kim.
Heartlein Reference: Also as relevant prior art, the examiner cites Heartlein (WO 2022/006527 A1), which was effectively filed earlier than the effective filing date of the instant application. Heartlein is drawn to compositions for administration of mRNA, as of Heartlein, title and abstract. The compositions administered by Heartlein may include one of various ionizable cationic lipids. One ionizable cationic lipid taught by Heartlein is the following, as of Heartlein, page 49, structure reproduced below with annotation by the examiner.
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As such, the structure of Heartlein includes a carbonyl group not present in the instantly claimed chemical structure. This renders the compound of Heartlein to be an amide where the claims require an amine at the indicated location. There would have been no motivation for the skilled artisan to have modified Heartlein to have achieved the claimed chemical structure.
Heartlein also teaches the following chemical structure, as of page 42, paragraph 0174, reproduced below.
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This structure differs from the claimed subject matter because it lacks the required functional groups A1 and Z1. This is the same reason that Kim differs from the claimed invention.
Zhang References: The examiner further notes Zhang et al. (WO 2019/226925 A1) and Zhang et al. (WO 2020/097384 A1) – these references appear to be deficient for essentially the same reason that Heartlein is deficient.
Chivukula Reference: The examiner further notes Chivukula et al. (WO 2022/264109 A1). Chivukula et al. (hereafter referred to as Chivukula) is drawn to mRNA influenza vaccines comprising lipid nanoparticles, as of Chivukula, title and abstract. The lipids taught by Chivukula, page 15, formula 3 would appear to comprise all of the claimed requirements. Nevertheless, Chivukula was published in 2022, and appears to have been effectively filed as of 18 June 2021. This is not as early as the earliest effective filing date of the instant application, which is 15 April 2021. As such, Chivukula is not prior art under AIA 35 U.S.C. 102(a)(1) and is not prior art under 35 U.S.C. 102(a)(2).
Casimiro References: As relevant art, the examiner cites Casimiro et al. (WO 2022/099003 A1). Casimiro et al. (hereafter referred to as Casimiro) teaches lipids that appear to have the same structure as the claimed lipid on page 17.
Casimiro was published in 2022, which is after the effective filing date of the instant application. As such, Casimiro is not prior art under AIA 35 U.S.C. 102(a)(1).
Regarding the effective filing date of Casimiro and issues relating to 35 U.S.C. 102(a)(2), the examiner notes the following, wherein the front page of the Casimiro reference is reproduced below with annotation by the examiner.
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Casimiro claims priority to provisional application 63/110,965, filed on 6 November 2020. Nevertheless, this provisional application fails to support the subject matter in Casimiro that has the same chemical structure as what is required by the instant claims. As such, no rejection over Casimiro is written because the subject matter in Casimiro that is within the claim scope was not effectively filed prior to the effective filing date of the instant application. As such, Casimiro is not prior art under AIA 35 U.S.C. 102(a)(2).
This rationale also applies to Casimiro et al. (US 2022/0142923 A1).
Karve ‘085 Reference: As relevant prior art, the examiner cites Karve et al. (WO 2020/227085 A1). Karve ‘085 is drawn to a dithioester cationic lipid for delivery of mRNA, as of Karve ‘085, title and abstract. Karve ‘085 teaches the following chemical structure, as of page 2, paragraph 007, which is reproduced below with annotation by the examiner regarding the differences between the structure of Karve ‘085 and the claimed invention.
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The examiner notes that in Karve ‘085, the thioester groups are oriented such that the carbonyl carbon faces the interior ring, and the sulfur atom faces the exterior amine and long carbon chains. This contrasts with the claimed invention, where the sulfur atom faces the interior ring and the carbonyl carbon faces the exterior amines and long carbon chains.
Hope Reference: As relevant prior art, the examiner cites Hope et al. (WO 2011/075656 A1), which was cited on the information disclosure statement (IDS) submitted on 6 February 2026. Hope et al. (hereafter referred to as Hope) teaches various cationic lipids for delivery of nucleic acids, as of Hope, title and abstract. Hope teaches the following lipid in one embodiment, as of Hope, page 30, relevant chemical structure reproduced below.
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The above-reproduced lipid differs from the claimed compound at least because (a) the above-reproduced lipid has five nitrogen atoms, whereas the claimed lipid has four nitrogen atoms. Also (b) the above-reproduced lipid has quaternary ammonium groups, whereas the claimed lipid has tertiary amines.
Non-Statutory 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 1-2, 15-32, 36, 38, 42, and 44-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-53 of U.S. Patent No. 11,771,653.
Claims 1-2, 15-32, 36, 38, 42, and 44-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-45 of U.S. Patent No. 12,239,735.
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
The instant claims are drawn to a compound with a particular chemical structure. This lipid can be used to form a lipid nanoparticle comprising mRNA, as well as treating or preventing a disease using the delivered mRNA, as of claim 42.
The conflicting claims of both patents are drawn to a lipid nanoparticle comprising the cationic lipid GL-HEPES-E3-E12-DS-4-E10. The examiner understands GL-HEPES-E3-E12-DS-4-E10 to have the following chemical structure.
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See the section above entitled “Note Regarding GL-HEPES-E3-E12-DS-4-E10.”
The conflicting claims differ from the instant claims because the conflicting claims recite specific percentages of PEG lipid, cholesterol and helper lipid, as of conflicting claim 1. This is not required by instant claim 1, and instant claim 32 recites additional lipids, albeit at broader ranges. Nevertheless, the subject matter of the conflicting claims is within the scope of the instant claims, thereby effectively anticipating the subject matter of the instant claims. This results in a prima facie case of anticipatory-type non-statutory double patenting.
Claims 1-2, 15-25, 28, 36, 38, 42, and 44-58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 18/856,198 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
The instant claims are drawn to a compound with a particular chemical structure. This lipid can be used to form a lipid nanoparticle comprising mRNA, as well as treating or preventing a disease using the delivered mRNA, as of claim 42.
Copending claim 1 recites a compound with the following structure, which is reproduced below with annotation by the examiner.
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The structure of the compound of the copending claim appears to be essentially the same as that required by the instant claims with the exception of the portions pointed out in boxes drawn by the examiner.
Nevertheless, the examiner notes that the concept of including the indicated ester appears to have been recited by the portion of instant claim 1 reciting and defining R1A and R1B as -W1-X1-Y1.
This rejection does not apply to instant claims 26-27, 29, 44, and 56-58 because the compound recited by these claims does not include the ester functional groups indicated above in boxes.
Claims 1-2, 15-32, 36, 38, 42, and 44-58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 17-22 of copending Application No. 19/414,473 (reference application).
Claims 1-2, 15-32, 36, 38, 42, and 44-58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7, 12, 16, 18-19, 21-22, 28, 31, 42, 45, 48-49, and 55-56 of copending Application No. 19/330,237 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
The instant claims are drawn to a compound with a particular chemical structure. This lipid can be used to form a lipid nanoparticle comprising mRNA, as well as treating or preventing a disease using the delivered mRNA, as of claim 42.
The copending claims of the ‘473 application are drawn to a composition comprising the following ionizable cationic lipids, as of copending claim 8, relevant chemical structures reproduced below.
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These lipids appear to be within the claim scope.
Copending claim 3 of the ‘237 application recites GL-HEPES-E3-E10-DS-4-E10, which is the same lipid as recited above. The claims of the ‘237 application also recites other lipids.
The subject matter of copending claim 8 of the ‘473 application and copending claim 3 of the ‘237 application differs from that of instant claim 1 because the copending claims require a nanoparticle and additional ingredients such as a structural lipid, a helper lipid, or a stealth lipid, which are not required by instant claim 1. Nevertheless, the subject matter of the copending claims appears to be within the scope of that recited by the instant claims. As such, the subject matter of the copending claims effectively anticipates that of the instant claims, thereby resulting in a prima facie case of anticipatory-type non-statutory double patenting.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 15-32, 36, 38, 42, and 44-58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/553,069 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
The instant claims are drawn to a compound with a particular chemical structure. This lipid can be used to form a lipid nanoparticle comprising mRNA, as well as treating or preventing a disease using the delivered mRNA, as of claim 42.
Copending claim 1 is drawn to a compound with the following structure.
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Compounds recited by the copending claims include but are not limited to the following.
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The instant and copending claims differ because the instant claims require hydroxyl groups on the carbon atoms that are two carbons away from the non-piperazine ring nitrogen atoms. In contrast, these hydroxyl groups appear to be optional in the subject matter recited by the copending claims. Additionally, the copending claims recite an ester group in the A1 position and a disulfide group in the Z1 position, whereas the instantly claimed structure may include other functional groups at these positions. Nevertheless, the copending claims recite compounds in which there are two hydroxyl groups at the required positions, which are thereby within the scope of the instant claims. As such, the subject matter of the copending claims appears to effectively anticipate that of the instant claims, resulting in a prima facie case of anticipatory-type non-statutory double patenting.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Withdrawn Double Patenting Rejection – Application 18/246,263
Previously in the prosecution history, the examiner rejected the instant claims on the grounds of provisional non-statutory double patenting over the claims of copending application 18/246,263. The examiner has decided to withdraw this rejection. The examiner presents the following rationale for withdrawing this double patenting rejection.
The copending claims are drawn to a compound with the following chemical structure, as of copending claim 1, reproduced below with annotations by the examiner.
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The examiner notes that at the above-indicated positions in the copending claims, there are methyl groups. In contrast, at the above-indicated position in the instantly claimed chemical structure, there are only hydrogen atoms. Upon further review and in contrast to positions previously taken by the examiner during the course of prosecution, the examiner currently takes the position that it would not have been prima facie obvious for one of ordinary skill in the art to have modified the chemical structure of the copending claims to have achieved the chemical structure of the instant claims. The examiner presents the following rationale in support of this position:
Lack of Reasonable Expectation of Success: The modification of the chemical structure of the copending claims to achieve that of the instant claims (or vice versa) would appear to be an example of alkane de-functionalization (or functionalization). Although the entirety of the structure of the copending and instant claims includes multiple functional groups, the relevant portion of the molecule where the structure of the copending claims differs from that of the instant claims appears to include solely carbon-carbon and carbon-hydrogen bonds, and does not include a double bond, a heteroatom, and is not adjacent to a carbonyl group. As such, this portion of the molecule would appear to lack a reaction functional group and effectively be an alkane; as such, prior art related to alkane functionalization would appear to be relevant regarding the achievement of such a chemical modification.
Alkane functionalization is difficult because alkanes have the least reactivity of organic molecules; see e.g. Tang et al. (Chemical Science, Vol. 9, 2018, pages 288-299), page 288, left column. Various alkane functionalization methods are known, e.g. as taught by Tang; however, some involve high temperatures (e.g. of 400-600°C, as of Tang, page 288, left column), which would have risked destroying the remainder of the molecule. Other problems with alkane functionalization entails lack of regioselectivity, as of Tang, page 288, left column, bottom paragraph. This is relevant because any attempt to functionalize or defunctionalize the compound of the copending claims would likely have resulted in substantial amounts of products wherein the undesired site was functionalized. While Tang teaches the use of metals and metal containing ion complexes for achievement of alkane functionalization, these complexes may not have been operable due to potential coordination between the metal in the complex and the amine groups of the composition of the copending or instant claims. This is evident because Tang teaches metals or other non-metallic electropositive elements (e.g. boron) coordinated to amines in some of the catalysts, as of Tang, page 290, right column, bottom figure and page 291, right column.
As such, in view of the difficulties with alkane functionalization, there would have been no reasonable expectation that the compound of the copending claims could have been successfully interconverted to have formed the compound of the instant claims.
Different Uses of Piperazine and Dimethylpiperazine: The core of the structure of the instantly claimed compound is piperazine. In contrast, the core of the structure of the compound of the copending claims is a dimethylpiperazine. The examiner conducted a search which found that piperazine is an anthelmintic (i.e. a compound to treat a certain type of worm infection). See Mayo Clinic (https://www.mayoclinic.org/drugs-supplements/piperazine-oral-route/description/drg-20065522 accessed 30 September 2026). In contrast, there does not appear to be evidence that dimethylpiperazine was available on the market for treating worm infections prior to the effective filing date of the instant application. In view of this, the examiner takes the position that the differences in chemical structure between the structure of the copending claims and that of the instant claims may reflect a difference in properties, especially with regard to anti-parasitic effects.
As such, in view of these issues, the examiner currently takes the position that the previously applied provisional non-statutory double patenting rejection over copending application 18/246,263 was made improperly, and this rejection has now been withdrawn.
Withdrawn Double Patenting Rejections – Patent 12,502,424 and Application 18/052,600
The examiner previously rejected the instant claims on the grounds of non-statutory double patenting over the claims of US Patent 12,502,424 and US application serial number 18/052,600. Upon further review, the examiner has withdrawn these rejections. This is because
There do not appear to be common inventors between the ‘424 Patent and the instant application. There also do not appear to be common inventors between the ‘600 application and the instant application.
The ‘424 patent and ‘600 application are assigned to Sanofi, whereas the instant application is assigned to Translate Bio. As such, there does not appear to be a common assignee between the ‘424 patent and ‘600 application and the instant application.
As such, the examiner concludes that the previously applied double patenting rejections over US Patent 12,502,424 and Application 18/052,600 were made in error and have been withdrawn by the examiner.
Response to Arguments Regarding Double Patenting Rejections
Applicant has presented arguments regarding the previously applied double patenting rejections, as of applicant’s response on 8 June 2026 (hereafter referred to as applicant’s response). These arguments have been addressed below.
Patents 11,771,653 and 12,239,735: Applicant addressed these patents on page 65 of applicant’s response but did not present arguments regarding these rejections. As such, the double patenting rejections over these patents has been maintained.
Applicant 18/856,198: Applicant presents the following arguments on page 67, relevant text reproduced below.
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This is not persuasive because the provisional non-statutory double patenting rejection over US application 18/856,298 is not the only remaining rejection. As such, this rejection has been maintained.
Other arguments related to other double patenting rejections have not been addressed substantively by the examiner as they appear to relate to double patenting rejections that have been withdrawn. As such, these arguments are moot and have not been addressed substantively by the examiner.
Relevant Patent – No Double Patenting
As a relevant patent, the examiner cites US Patent 12,263,213.
As an initial matter, the ‘213 patent was published and effectively filed later than the effective filing date of the instant application. As such, this reference is not prior art.
The claims of this patent recite the lipid GL-HEPES-E3-E12-DS-4-E10, which is understood to be within the scope of claim 1.
Nevertheless, no double patenting rejection over the ‘213 patent has been written because:
There appears to be no common inventors between the ‘213 patent and the instant application; and
The ‘213 patent does not appear to be commonly assigned with the instant application because the ‘213 patent is assigned to Sanofi whereas the instant application is assigned to Translate Bio.
The examiner takes the position that this rationale also applies to copending applications reciting a lipid appearing to be within the scope of what is recited by claim 1 but which have no common inventors with the instant application and are assigned to Sanofi rather than Translate Bio. For this reason, no provisional non-statutory double patenting rejection has been written over application 17/843,445.
Conclusion
No claim is allowed.
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
