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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
This application is a 371 of PCT/EP2022/080590 filed 11/02/2022.
This application also claims foreign benefit of EPO EP21205909.1 filed 11/02/2021.
Accordingly, claims 1-19 of this application are afforded the effective filing date of 11/02/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/26/2024 has been considered by the examiner and initialed copies of the IDS are included with the mailing of this office action.
Election/Restrictions
Applicant's election with traverse of compound 10-21 (disclosed on page 20 of the specification) as the species of compound of Formula I in the reply filed on 03/23/2026 is acknowledged.
However, upon further consideration, the Examiner hereby withdraws the election of species requirement and extend the search to all species of compound of Formula I.
Status of the Claims
Claims 1-19 are pending in this instant application, and examined herein on the merits for patentability.
Claim Objections
Claim 2 is objected to because of the following informalities: the recitation of “selected from butylene, pentylene and hexylene” is an improper Markush language. When materials recited in a claim are so related as to constitute a proper Markush groups, they may be recited in the conventional manner, or alternatively. For example, if “wherein R is a material selected from the group consisting of A, B, C and D” is a proper limitation, then “wherein R is A, B, C or D” shall also be considered proper. Appropriate correction is required.
Claim 3 is objected to because of the following informalities: recitation of “each RA, RB, and RC is selected from … and C20 branched alkyl” is an improper Markush language. Please see above for proper Markush language. Appropriate correction is required.
Claim 14 is objected to because of the following informalities: for claim language clarity, please amend the acronym “DOPE” to their full chemical name (e.g., 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)). Appropriate correction is required.
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 8, 12-15, and 17 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.
Regarding claims 8 and 14, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance:
claim 8 recites the broad recitation “F1, F2 and F3 are esters,” and the claim also recites “in particular wherein F1RA, F2RA and F3RC are according to formula -O-C(=O)-R wherein R denotes RA, RB and RC, respectively,” which is the narrower statement of the limitation.
claim 14 recites the broad recitation “a phospholipid,” and the claim also recites “said phospholipid is preferably DOPE,” which is the narrower statement of the limitation.
The claim(s) 8 and 14 are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claims 12 and 14, the recitations of “said LNP” renders said claims 12 and 14 indefinite because said claims 12 and 14 are dependent from claim 9, yet claim 9 does not recite or contain “LNP.” Thus, there is lack of antecedent basis for “said LNP” in claim 9 and thereby, unclear what “said LNP” is claims 12 and 14 referencing to, as the lipid nanoparticle of claim 9 does not contain “LNP.” If “LNP” is intended to be the acronym of “lipid nanoparticle,” it is suggested that Applicant amend claims 12 and 14 to change “LNP” to “lipid nanoparticle.” Clarification by amendment in claims 12 and 14 are required.
Regarding claim 13, the recitations of “said lipid nanoparticle comprises at least one second ionizable liquid” and “said ionizable lipids” render claim 13 indefinite because claim 13 is dependent from claim 9, yet claim 9 does not recite that the lipid nanoparticle contain ionizable lipids. Thus, it is unclear what “said ionizable lipids” is claim 13 referencing to and how the lipid nanoparticle of claim 13 can contain “at least one second ionizable lipid” when the lipid nanoparticle of claim 9 does not contain a first ionizable lipid. Clarification by amendment in claim 9 or 13 is required.
Regarding claim 13, the recitation of “lipid-like compounds” renders claim 13 indefinite because “lipid-like” is an indefinite terminology, as “lipid-like” include elements not actually disclosed (those encompassed by “like”), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d). It unclear what how like or dislike, or similar or dissimilar does the compounds has to be, so as to be considered a “lipid-like”. Clarification by amendment in claim 13 is required.
Regarding claim 15, the recitation of “said sterol” renders claim 15 indefinite because claim 15 is dependent from claim 9, yet the lipid nanoparticle of claim 9 does not contain a sterol. Thus, there is lack of antecedent basis for “said sterol” in claim 9 and thereby, unclear what “said sterol” is claim 13 referencing to, as claim 9 does not contain a sterol.
Claim 17 is indefinite in the recitation “one or more lipid nanoparticles as defined in claim 9”. The phrase is indefinite because the exact meaning of the phrase is unclear and the term “defined” according to the Merriam-Webster online dictionary (www.m-w.com/dictionary.htm) means to determine or identify the essential qualities or meaning of, or to fix or mark the limits of. Thus, it is unclear if the aforementioned recitation is a requirement or merely a definition of the instant claims. Accordingly, the phrase “one or more lipid nanoparticles as defined in claim 9” of claim 17 renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). To obviate this rejection, it is suggested that “as defined” is removed from said claim 17 and amend claim 17 such that there is proper antecedent basis to the lipid nanoparticle of claim 9.
As a result, claims 8, 12-15, and 17 do not clearly set for the metes and bounds of patent protection desired.
Claim Rejections - 35 USC § 102
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) 1-6, 8-13, 15, and 17-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Anderson et al (US 2016/0114042 A1).
Regarding claims 1-6 and 8, Anderson teaches amine-containing lipidoid having the following formula:
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(Abstract; [0005]-[0006], [0008], [0047]-[0049], [0110], [0117], [0163]-[0164], [0175], [0182], [0194]-[0195], [0197]-[0210]).
Regarding claims 9 and 10, Anderson teaches a lipid nanoparticle containing the amine-containing lipidoid and a polynucleotide or oligonucleotide such as DNA or RNA ([0197]-[0243] and [0255]).
Regarding claim 11, Anderson teaches the lipid nanoparticle contains PEG or DMG-PEG, cholesterol, and a phospholipid such as DSPC, DOPC, or DOPE ([0207]-[0210] and [0255]).
Regarding claim 12, Anderson teaches the lipid nanoparticle contains 38.5 mol% of the amine-containing lipidoid ([0255]).
Regarding claim 13, Anderson teaches the lipid nanoparticle contains a plurality of amine-containing lipidoids, wherein the lipidoids are present in the lipid nanoparticle at total concentration of 38.5% ([0255]).
Regarding claim 15, Anderson teaches the lipid nanoparticle contains 50 mol% of cholesterol ([0255]).
Regarding claim 17, Anderson teaches a pharmaceutical composition comprising the amine-containing lipidoid, and a pharmaceutical acceptable carrier ([0221]-[0255]).
Regarding claim 18, as discussed above, Anderson teaches a pharmaceutical composition comprising the amine-containing lipidoid and thus, the recitation of “for use in the treatment and/or prophylaxis of a disease” as recited in claim 18 is a recitation of intended use. It is noted that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Regarding claim 19, as discussed above, Anderson teaches the compound of claim 1 and thus, the recitation of “for use in the preparation of a pharmaceutical composition for therapeutic use comprising an RNA encoding a gene of interest” as recited in claim 19 is a recitation of intended use. It is noted that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
As a result, the aforementioned teachings from Anderson are anticipatory to claims 1-6, 8-13, 15, and 17-19 of the instant invention.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-13, 15, and 17-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Anderson et al (US 2016/0114042 A1), and further in view of Adami et al (US 2017/0020819 A1).
The compound and lipid nanoparticle of claims 1-6, 8-13, 15, and 17-19, respectively, are discussed above, said discussion being incorporated herein in its entirety.
Regarding claim 7, while the compound of Anderson contains an primary amine instead of an hydroxyl as recited for Z1 position in the compound of claim 1, it would have been obvious to one of ordinary skill in the art to modify the compound of Anderson such that the primary amine is an hydroxyl group in view of the guidance from Adami.
Adami teaches lipid nanoparticle containing an amine-containing ionizable lipid of the following compound:
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(Abstract; [0008]-[0014], [0028], [0107]-[0119], [0202]-[0213], [0216]-[0217], [0222]-[0299]). Adami teaches hydroxyalkyl group on the compound can be modified with an aminoalkyl ([0204]-[0208], [0216]-[0217]).
It would have been obvious to one of ordinary skill in the art to modify the amine containing lipidoid of Anderson such that the aminoalkyl that is attached to the piperazine ring (
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) is an hydroxyalkyl (
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), and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Anderson and Adami are commonly drawn to lipid nanoparticles comprising amine containing lipidoids, and Adami provided the guidance for modifying the lipidoid of Anderson such that the aminoalkyl is substituted with an hydroxyalkyl, as both aminoalkyl and hydroxyalkyl are suitable for attachment to the piperazine ring so as to produce an ionizable lipid (Adami: [0204]-[0208], [0216]-[0217]). Thus, it would have been merely simple substitution of an aminoalkyl for an hydroxyalkyl per guidance from Adami, and achieve Applicant’s claimed compound with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 1-6 and 8-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Anderson et al (US 2016/0114042 A1), and further in view of Parmar et al (WO 2020/072605 A1).
The compound and lipid nanoparticle of claims 1-6, 8-13, 15, and 17-19, respectively, are discussed above, said discussion being incorporated herein in its entirety.
Regarding claims 14 and 16, Parmar teaches a lipid nanoparticle comprising an ionizable amine lipid, PEG or DMG-PEG, cholesterol, and a phospholipid, wherein the lipid nanoparticles contains from about 30 mol-% to about 70 mol- % of the ionizable amine lipid, from about 30 mol-% to about 50 mol-% of the cholesterol (helper lipid), from about 0 mol-% to about 20 mol-% of the phospholipid (neutral lipid), and from about 1 mol- % to about 10 mol-% of the PEG or DMG-PEG (Abstract; pages 1-5, 13-15, 17-20, 30-35, 37-42, 103-107 and 117-124). Parmar teaches the lipid nanoparticle contains 50 mol% of the ionizable amine lipid, 10 mol% of phospholipid, 38.5 mol% of cholesterol, and 1.5 mol% of DMG-PEG (pages 107 and 117-124).
It would have been obvious one of ordinary skill in the art to optimize the mol% of phospholipid to a concentration of 0.5-35 mol% and the mol% of PEG conjugate (DMG-PEG) to a concentration of 0.5-5 mol% in the lipid nanoparticle of Anderson, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because both Anderson and Parmar are commonly drawn to lipid nanoparticles comprising an ionizable amine lipid, PEG or DMG-PEG, cholesterol, and a phospholipid, and Parmar provided the guidance for optimizing the mol% concentrations of phospholipid and PEG conjugate in the lipid nanoparticle of Anderson from about 0 mol-% to about 20 mol-% of the phospholipid, particularly 10 mol% and from about 1 mol- % to about 10 mol-% of DMG-PEG, particularly 1.5 mol%, which are mol% concentrations that meets the claimed ranges of 0.5-35 mol% for phospholipid and 0.5-5 mol% for DMG-PEG. Thus, it is feasible for an ordinary artisan to optimize the mol% concentrations of phospholipid and PEG conjugate in the lipid nanoparticle of Anderson to 10 mol% for the phospholipid and 1.5 mol% for the DMG-PEG per guidance from Parmar, and achieve Applicant’s claimed lipid nanoparticle with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
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/DOAN T PHAN/ Primary Examiner, Art Unit 1613
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