*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 .
Applicants' response dated April 27, 2026 is acknowledged.
Priority
This application is a 3 71 of PCT/KR2022/00894 l filed on 06/23/2022, and claims
foreign priority in Republic of Korea application KR10-2021-0082361 filed on 06/24/2021 and
KRl0-2022-0076212 filed on 06/22/2022.
Claim Status
Claims 1 and 4-36 are pending. Claims 4, 6, 7, 8, and 18-36 remain withdrawn. Claims 2 and 3 were canceled. Claims 1, 16, and 17 were amended. Claims 1, 5, and 9-17 are examined.
Election/Restriction
In response to claim amendments, the examiner has selected the following species of an ionizable lipid and pegylated lipid for search and consideration:
an ionizable lipid of formula
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and
a polyethylene glycol moiety-degradable functional group-lipid conjugate of formula
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in which the first -C(O)O- moiety from the left is replaced with -O-N=C(H)-; and the species read on claims 1 and 9-17, and an action on these species follows.
Withdrawn Claim Objections
Objections to claims 1, 5, and 17 are withdrawn because objections were obviated with claim amendments.
Withdrawn Claim Rejections - 35 USC § 112
Rejections of claims 16 and 17 are withdrawn because rejections were obviated with claim amendments.
Withdrawn Claim Rejections – 35 USC § 102
Rejections of claims 1 and 9-15 as being anticipated by Viger Gravel
(The Journal of Physical Chemistry B, 2018, 122, 2073-2081, Supporting Information
appended thereto) are withdrawn because claim 1 was amended to include limitations of claim 2, which are not anticipated by Viger Gravel.
New Claim Rejections – 35 USC§ 112
Necessitated by Amendment
The following is a quotation of 35 U.S.C. l 12(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, 5, and 9-17 are rejected under 35 U.S.C. l 12(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 limitation “the ionizable liquid” in line 5. There is insufficient antecedent basis for this limitation in the claim. The claim provides support for “the ionizable lipid”,
Claims 5 and 9-17 are indefinite because the claims depend from an indefinite base claim.
Modified Claim Rejections - 35 USC § 103
Necessitated by Amendment
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.
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.
This application currently names joint inventors. In considering patentability of the
claims the examiner presumes that the subject matter of the various claims was commonly
owned as of the effective filing date of the claimed invention(s) absent any evidence to the
contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and
effective filing dates of each claim that was not commonly owned as of the effective filing date
of the later invention in order for the examiner to consider the applicability of 35 U.S.C.
102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 9-17 are rejected under 35 U.S.C. 103 as being unpatentable over Rajeev
(US 9,999,673 B2 Date of Patent June 19, 2018 - of record in IDS dated 12/17/2023) and Viger
Gravel (The Journal of Physical Chemistry B, 2018, 122, 2073-2081, Supporting Information
appended thereto).
The claims encompass a lipid nanoparticle comprising
(a) a lipid formulation containing an ionizable lipid of formula
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a polyethylene glycol moiety-degradable functional group-lipid conjugate of formula
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in which the first -C(O)O- moiety from the left is replaced with -O-N=C(H)-; and
(b) a drug, a nucleic acid, or a combination thereof encapsulated in the lipid formulation.
The teachings of Rajeev are related to pegylated lipids and their use in drug delivery
(Abstract). In one embodiment, the pegylated lipid is an aggregation-reducing lipid of formula (I)
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wherein each of R1 and R2, independently, is a C10 C30 aliphatic group; X is -C(O)O-; Y is -C(O)O-; a is 1; R4 and R4’ are both H; L is -L1-Z1-(L2-Z2)c-L3-; L1 is a bond; Z1 is -C(O)O- or -O-N=C(Ra)-; c is 0; Ra is H; L3 is –(CRaRb)j-; Ra is H; Rb is H; j is 1; A is -L4-; L4 is –(CRaRb)s-O-; Ra is H; Rb is H; s is 2; b is 1-1000; and R3 is -ORc where Rc is alkyl (from column 24 line 26 to column 25 line 67).
Rajeev teaches an example of the compound of formula (I) having the structure
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(last structure on page 7, columns 11 and 12), wherein n is 25-100 (column 21 lines 51-55). The
compound is a pegylated lipid and provides steric stabilization to particles (column 24 lines 15-
25).
One embodiment includes the compound of formula (I), a cationic lipid, a neutral lipid,
and a sterol. The cationic lipid can be present in a molar ratio of about 20% and about 60%; the
neutral lipid can be present in a molar ratio of about 5% to about 25%; the sterol can be present
in a molar ratio of about 25% to about 55%; and the compound of formula (I) can be present in a
molar ratio of about 0.5% to about 15%. The lipid particle can further include an active agent.
The active agent can be a nucleic acid selected from the group consisting of a plasmid, an
immunostimulatory oligonucleotide, an siRNA, an anti sense oligonucleotide, a micro RNA,
an antagomir, an aptamer, and a ribozyme (from column 21 line 60 to column 22 line 50).
Cationic lipids can have certain design features including a head group, one or more
hydrophobic tails, and a linker between the head group and the one or more tails. The head group
can include an amine. Under certain conditions, the amine nitrogen can be a site of positive
charge. For example, when the amine is a primary, secondary, or tertiary amine, the amine will
have a characteristic pKa; in other words, it will undergo reversible protonation in aqueous
media. The extent of positive charge is a function of the pKa and the pH of the aqueous media.
The amine can also be a quaternary amine, in which case it will bear a positive charge regardless
of whether it is in pure form, in aqueous media, or the pH of the aqueous media (column 49 lines
51-64). The particles have a diameter of 30-150 nm and 40-90 nm (column 92 lines 55-65).
Rajeev does not teach
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.
The teachings of Viger-Gravel are related to lipid nanoparticles containing siRNA or
mRNA (Title). The lipid nanoparticles are composed of ionizable cationic lipid Dlin-MC3-
DMA, a phospholipid DSPC, cholesterol, and a pegylated lipid DMPE-PEG 2000, and
encapsulated phosphorothioated siRNA or mRNA (Abstract).
The teachings of Rajeev an Viger-Gravel are related to lipid nanoparticle comprising a
pegylated lipid, a cationic lipid, a neutral lipid, a sterol, and a nucleic acid, and it would have
been obvious to have combined their teachings because they are in the same field of endeavor.
It would have been prima facie obvious to a person of ordinary skill in the art before the
effective filing date of the claimed invention to have formed a lipid nanoparticle comprising
encapsulated nucleic acids, wherein the lipid nanoparticle is formed from a pegylated lipid and a
cationic lipid having a head group comprising an amine, one or more hydrophobic tails, and a
linker between the head group and the one or more tails, with a reasonable expectation of success
because Rajeev teaches a lipid particle having a size in the range of 40-90 nm (a nanoparticle)
wherein the particle comprises a pegylated lipid and a cationic lipid having a head group
comprising an amine, one or more hydrophobic tails, and a linker between the head group and
the one or more tails and an encapsulated nucleic acid.
It would have been obvious to have selected
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where n is 25-100 because Rajeev teaches said compound as an example of a pegylated lipid. It would have been obvious to have modified the compound by replacing the first -C(O)O- moiety from the left with -O-N=C(H)-, with a reasonable expectation of success because Rajeev teaches moieties -C(O)O- and -O-N=C(Ra)- where Ra is H as suitable alternatives for the variable Z1 in the generic chemical compound of formula (I). Replacing one equivalent with another to obtain predictable results supports obviousness.
It would have been obvious to have selected
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as the cationic lipid, with a reasonable expectation of success because Viger-Gravel teaches
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(DLin-MC-DMA, Figure 1) as a cationic lipid suitable for making lipid nanoparticles intended for nucleic acid encapsulation. The selection of a known material based on its suitability for its intended purpose supports
obviousness.
Alternatively, it would have been obvious to have modified Viger-Gravel's nanoparticle
by replacing DMPE-PEG 2000 with
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having the first -C(O)O- moiety from the left replaced with -O-N=C(H)-, with a reasonable
expectation of success because it was known from Rajeev that said pegylated lipid is suitable for
making lipid nanoparticles, and replacing one pegylated lipid with another to obtain predictable
results supports obviousness.
Regarding claims 1 and 11, the claimed invention is obvious because Rajeev's (or
alternatively Viger-Gravel's) modified lipid nanoparticle contains:
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having the first -C(O)O- moiety from the left replaced with -O-N=C(H)-, which is relevant to
polyethylene glycol moiety-degradable functional group-lipid conjugate when
a is 0,
M is H,
P is -CH2CH2O(CH2CH2O)q-CH2-
q is 25-100,
L6 is -O-N=C(H)-,
T is a bond,
R1 is -Y-R where Y is a single bond and R is H,
R2 is -Y-R where Y is -OC(O )- and R is a C 17 alkyl, and
R3 is -CH2-Y-R where Y is -OC(O)- and Risa Cl 7 alkyl;
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, which is an ionizable lipid Dlin-MC3-DMA; and
an encapsulated nucleic acid, which meets the limitation of component (b).
Regarding claim 9, it would have been obvious to have formed the lipid nanoparticle of
Rajeev to contain the pegylated lipid in a molar ratio of about 0.5 to about 15%, with a
reasonable expectation of success because Rajeev teaches that the lipid particle contains the
cationic lipid in a molar ratio of about 20% and about 60%; the neutral lipid in a molar ratio of
about 5% to about 25%; the sterol in a molar ratio of about 25% to about 55%; and the pegylated
lipid in a molar ratio of about O. 5% to about 15%. The claimed range is obvious because it
encompasses the prior art range.
Regrading claim 10, the claimed range is obvious because it encompasses 40-90 nm
range disclosed by Rajeev.
Regarding claims 12-15, it would have been obvious to have formed the lipid
nanoparticles of Rajeev to contain cholesterol and sphingomyelin, with a reasonable expectation
of success because Rajeev teaches that the lipid nanoparticle is formed to comprise a sterol such
as cholesterol (column 55 lines 4-7) and an amphipathic lipid such as sphingomyelin (column 55
lines 8-33).
Claims 16 and 17 are indefinite, however the claims are included in the rejection for the
purpose of compact prosecution. It would have been obvious to have formed the lipid
nanoparticles with an encapsulated active agent wherein the therapeutic agent is a peptide or a
nucleic acid, with a reasonable expectation of success because Rajeev teaches that the lipid
nanoparticle encapsulates an active agent (column 60 lines 41-51), wherein the active agent
comprises a peptide or a nucleic acid (column 61 lines 1-14). It would have been obvious to have
selected peptide nucleic acid as the active agent because Rajeev teaches peptide nucleic acid
(PNA) as a suitable active agent (column 76 lines 45-57). Peptide nucleic acid meets the
limitations of claims 16 and 17.
Response to Arguments
Applicant’s arguments submitted in the remarks dated April 27, 2026 were fully considered but are not sufficient to overcome the rejection over Rajeev because Rajeev teaches pegylated lipids that are encompassed by the instantly claimed genus of pegylated lipids. The examiner has selected another species of the pegylated lipid and the rejection has been modified accordingly to address the claims as amended.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/ALMA PIPIC/Primary Examiner, Art Unit 1617
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