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 .
Election/Restrictions
Applicant’s election without traverse of Group I, species E6-1 in the reply filed on 26 June 2026 is acknowledged.
Claims 12-14 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. Election was made without traverse in the reply filed on 26 June 2026.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 2, 4, and 11, to the extent readable on the elected cationic lipid species E6-1 of Example 6.1, is/are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Ansell et al., U.S. Patent Publication No. 2017/0119904 (“Ansell”).
Ansell was published May 4, 2017, before the effective filing date of October 15, 2021, and therefore qualifies as prior art under 35 U.S.C. § 102(a)(1). Ansell is directed to novel lipids and lipid nanoparticle formulations for delivery of nucleic acids. Ansell, title and publication information, lines 0–5 and 30–41.
With respect to claim 1, Ansell discloses ionizable/cationic lipid compounds of structure (I). Ansell teaches that L1 and L2 may be ester linkers, including —O(C═O)— and —(C═O)O—; G1 and G2 may be C1–C12 alkylene; G3 may be C1–C24 alkylene; R1 and R2 may be C6–C24 alkyl or alkenyl groups; and R3 may be OH. Ansell, lines 890–905, 921–944. These teachings correspond to the Formula (1) cationic lipid genus recited in claim 1, which requires a nitrogen center, ester/linker groups, alkylene spacing groups, hydrophobic aliphatic substituents, and a terminal hydroxyl-containing substituent.
Ansell further discloses specific compound 17. In Example 22, Ansell prepares compound 17 by reacting 2-hexyldecyl 6-bromohexanoate with 4-amino-1-butanol in the presence of potassium carbonate, cesium carbonate, and sodium iodide, followed by purification to give compound 17 as a colorless oil. Ansell, Example 22, lines 1184–1187. The disclosed synthesis necessarily provides a tertiary amino lipid having a nitrogen bearing a hydroxybutyl substituent and two hexylene-linked ester hydrophobic chains.
The elected species E6-1 of Example 6.1 in the present application corresponds to Formula (1), wherein B1 and B2 are both hexylene groups, L1 and L2 are both ester groups —C(═O)O—, X is N, L3 is a butylene group, R3 is a hydroxyl group, and the total molecular weight is approximately 767 Da. The present application further reports E6-1 as obtained in 1.25 g and having MALDI-TOF molecular weight 766.87 Da. Instant specification, Example 6.1, lines 1351–1359.
Ansell’s compound 17 and the elected E6-1 species have the same material structural features: a tertiary nitrogen center; a hydroxybutyl substituent on the nitrogen; two hexylene spacer groups; two ester linkages; and two branched C16 hydrophobic groups. Thus, Ansell discloses the elected E6-1 species, and a prior-art species anticipates a generic claim that reads on that species.
Claim 1 is anticipated because Ansell’s compound 17 is a cationic lipid falling within Formula (1). Claim 2 is anticipated because Ansell’s compound 17 includes branched aliphatic hydrophobic groups corresponding to the claimed C1–30 aliphatic hydrocarbon group alternatives. Claim 4 is anticipated because Ansell’s compound 17 includes hexylene groups, and hexylene is one of the recited C1–20 alkylene groups. Claim 11 is anticipated to the extent the claim recites or reads on the elected E6-1 structure, because Ansell discloses the same elected species.
Accordingly, Ansell discloses each and every limitation of the claims under examination as arranged in the elected E6-1 species. Claims 1, 2, 4, and 11 are therefore anticipated by Ansell.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
In the alternative, and to the extent Ansell is not considered to identically disclose the elected E6-1 species, claims 1, 2, 4, and 11, to the extent readable on the elected cationic lipid species E6-1 of Example 6.1, is/are rejected under 35 U.S.C. § 103 as being unpatentable over Ansell in view of Peer et al., WO 2018/087753 (“Peer”), and further in view of Baumhof et al., U.S. Patent Publication No. 2020/0163878 (“Baumhof”).
Ansell teaches the closest lipid scaffold. Ansell discloses compounds of structure (I) in which L1 and L2 may be ester linkers, including —O(C═O)— and —(C═O)O—; G1 and G2 may be C1–C12 alkylene; G3 may be C1–C24 alkylene; R1 and R2 may be C6–C24 alkyl or alkenyl groups; and R3 may be OH. Ansell, lines 890–905, 921–944. Ansell also expressly discloses representative compounds including compound 17 in Table 1 and provides a working synthesis of compound 17 using 2-hexyldecyl 6-bromohexanoate and 4-amino-1-butanol. Ansell, lines 946–966 and 1184–1187.
Peer teaches that cationic lipids for nucleic-acid delivery may include two fatty acid residues linked to a functional nitrogen-containing group and that the fatty-chain portions may include C10–C22 alkyl, alkenyl, or alkynyl groups, including groups containing ester linkages Z selected from —O—C(═O)—, —C(═O)—O—, or —O—. Peer, lines 834–890. Peer further discloses Lipid 24, made from 6,6′-(1-(2-(dimethylamino)ethyl)hydrazine-1,2-diyl)bis(hexan-1-ol) and 2-hexyldecanoic acid, thereby teaching cationic lipids having nitrogen-containing head groups, hexylene spacers, ester linkages, and branched 2-hexyldecanoate hydrophobic residues. Peer, lines 1881–1907.
Baumhof teaches lipid nanoparticle mRNA vaccines using cationic lipids of Formula III and confirms that this ionizable lipid design space was known for mRNA/LNP delivery before the effective filing date. Baumhof teaches Formula III cationic lipids in which L1 and L2 may be —O(C═O)— or —(C═O)O—, R3 may be OH, G3 may be C1–C24 alkylene or alkenylene, and representative Formula III compounds are used in LNP-III-3 mRNA formulations. Baumhof, lines 3577–3617 and 4952–4966.
It would have been obvious to one of ordinary skill in the art before October 15, 2021 to use Ansell’s compound 17, or to select a structurally corresponding tertiary amino lipid species having two hexylene ester-linked branched hydrophobic chains and a hydroxybutyl nitrogen substituent, because Ansell expressly teaches those structural features in the same ionizable/cationic lipid delivery context. Peer provides additional motivation to use nitrogen-containing cationic lipids with ester-linked branched fatty residues for nucleic-acid delivery, and Baumhof confirms the use of closely related ester-linked, hydroxy-substituted ionizable lipids in mRNA lipid nanoparticle systems.
A person of ordinary skill would have had a reasonable expectation of success because Ansell, Peer, and Baumhof each teach cationic or ionizable lipids having hydrophobic chains, nitrogen-containing head groups, ester linkages, and alkylene spacer groups for nucleic-acid or mRNA lipid nanoparticle delivery. The selection of hexylene spacers, ester linkages, branched C16 hydrophobic groups, and a hydroxybutyl tertiary amine head group would have been a predictable selection from known, finite, structurally related lipid components taught for the same delivery purpose.
Claim 1 is obvious because Ansell, alone or in view of Peer and Baumhof, teaches the Formula (1) lipid scaffold and the elected E6-1-type species. Claim 2 is obvious because the references teach branched hydrophobic alkyl chains suitable for cationic/ionizable lipid delivery. Claim 4 is obvious because Ansell and Peer disclose hexylene spacer groups and Baumhof teaches C1–C24 alkylene spacer options. Claim 11 is obvious to the extent it recites or reads on the elected E6-1 structure because the elected species is either expressly disclosed by Ansell or, at minimum, would have been an obvious structural selection from the closely related ionizable lipid teachings of Ansell, Peer, and Baumhof.
Accordingly, even if the elected E6-1 species is not treated as identically disclosed by Ansell for purposes of anticipation, the subject matter of claims 1, 2, 4, and 11 would have been obvious over Ansell in view of Peer and Baumhof.
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.
Claims 1, 2, 4, and 11–24 is/are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Regarding claim 1, the claim recites a cationic lipid represented by Formula (1), including the variables R1, R2, L1, L2, B1, B2, X, L3, and R3. However, the claim does not clearly and distinctly define the full scope of the variables in Formula (1). In particular, the claim recites that X is N and then recites linker, alkylene, aliphatic hydrocarbon, and terminal-group alternatives, but the amended language does not clearly establish which alternatives define R1, which alternatives define R2, which alternatives define R3, and which alternatives define the L1, L2, and L3 linking groups. Thus, the metes and bounds of the claimed cationic lipid genus cannot be determined with reasonable certainty.
Claim 1 is further indefinite because it recites that the alkylene group and aliphatic hydrocarbon group are each independently “substituted or unsubstituted,” but the claim does not define the permissible substituents, number of substituents, substitution positions, or whether the substituents may alter the cationic lipid functionality. As a result, one of ordinary skill in the art cannot determine the full scope of the substituted alternatives encompassed by the claim.
Claim 2 is rejected under 35 U.S.C. § 112(b) as being indefinite. Claim 2 recites that the C1–30 aliphatic hydrocarbon group is a linear alkyl group, branched alkyl group, linear alkenyl group, branched alkenyl group, linear alkynyl group, or branched alkynyl group. Claim 2 then recites a structural formula for branched alternatives and further states that the C1–30 aliphatic hydrocarbon group is “specifically selected from the following structures.” It is unclear whether the specifically recited structures are required closed-list alternatives, optional examples, species within the preceding branched formula, or additional alternatives separate from the preceding formula.
Claims 4 and 11 are rejected under 35 U.S.C. § 112(b) at least because they depend from claim 1 and therefore incorporate the indefinite limitations of claim 1. Claim 4 depends from claim 1 and further limits B1 and B2 to selected alkylene groups. Claim 11 depends from claim 1 and recites specific cationic lipid structures. Because the base cationic lipid genus of claim 1 is indefinite, the scope of claims 4 and 11 is likewise indefinite.
/DEBORAH D CARR/Primary Examiner, Art Unit 1691
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