--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 December 28, 2025 is acknowledged.
Priority
This application is a 371 of PCT/KR2022/008941 filed on 06/23/2022, and claims foreign priority in Republic of Korea application KR10-2021-0082361 filed on 06/24/2021 and KR10-2022-0076212 filed on 06/22/2022.
Claim Status
Claims 1-36 are pending. Claims 3, 4, 6, 7, 8, 18-36 are withdrawn. Claims 1, 2, 5, and 9-17 are examined.
Election/Restriction
Applicant’s election without traverse of Group I (Claims 1-17), drawn to a nanoparticle in the reply filed on December 28, 2025, is acknowledged.
Applicant’s election without traverse of
PNG
media_image1.png
83
587
media_image1.png
Greyscale
as a single ionizable lipid; and
PNG
media_image2.png
83
625
media_image2.png
Greyscale
as a single lipid conjugate of a PEG moiety conjugated to a lipid via a degradable functional group, is acknowledged.
The applicant stated that claims 1-17 read on the elected species. The examiner disagrees because claims 3, 4, and 6 are drawn to PEG-lipid conjugates that have a targeting group L, which is an embodiment of the compound of Formula I when a is 1. These claims do not read on the elected species of PEG-lipid conjugate because the elected compound does not contain a ligand and the variable a is 0. The applicant had a choice to select a mixture or a single compound of Formula I, and the applicant elected a single compound of Formula I. Therefore, claims 7 and 8 do not read on the elected invention because the claims require a mixture of two compounds of Formula I.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 3, 4, 6, 7, 8, and 18-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being withdrawn to a non-elected invention, and non-elected species of the invention, there being no allowable generic or linking claims. Please note that after a final requirement for restriction, the Applicants, in addition to making any response due on the remainder of the action, may petition the Commissioner to review the requirement. Petition may be deferred until after final action on or allowance of claims to the invention elected, but must be filed not later than appeal. A petition will not be considered if reconsideration of the requirement was not requested. (See § 1.181.).
Response to the restriction requirement of October 28, 2025 was timely filed.
Claims 1, 2, 5, and 9-17 are examined on the merits.
The elected species of PEG-lipid conjugate was searched and no relevant prior art was found.
The examiner has selected the following species of an ionizable lipid and pegylated lipid for search and consideration:
an ionizable lipid of formula
PNG
media_image1.png
83
587
media_image1.png
Greyscale
and
a polyethylene glycol moiety-degradable functional group-lipid conjugate of formula
PNG
media_image3.png
142
775
media_image3.png
Greyscale
, which read on claims 1, 2, and 9-17, and an action on these species follows.
For the purpose of compact prosecution, the search of the species was expanded to
an ionizable lipid of formula
PNG
media_image1.png
83
587
media_image1.png
Greyscale
and
PEGylated dimyristoyl phosphatidyl ethanolamine (DMPE-PEG 2000), which read on claims 1 and 9-15 read on the elected species, and an action on these species follows.
Claim Objections
Claim 1 is objected to because “a lipid formulations” and “the lipid formulations”. The phrases should be amended to singular “formulation”.
Claim 5 is 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. The chemical structure was searched and no relevant prior art was found.
Claim 17 is objected to because it recites RNA, DNA, and PNA without providing the full name at least once. 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 16 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.
Claim 16 recites “protein-nucleic acid structures”. The phrase is indefinite because the specification does not define the phrase nor provide any examples said structures. The phrase was searched, and it appears in patent literature, however none of the recovered references explain its meaning.
Claim 17 depends from claim 16 and further defines the nucleic acid. The claim is indefinite because it does not clarify the meaning of protein-nucleic acid structures. The claim is further indefinite because it is not clear if “the nucleic acid” is only intended to further limit “protein-nucleic acid structures” or other listed drugs. For example, claim 17 recites PNA, which is interpreted to mean “peptide nucleic acid”, which is a synthetic peptide similar to DNA or RNA. Claim 17 recites peptides, protein drugs, and anionic biopolymer-drug conjugates in the list of drugs. It is unclear which drugs are intended to be further defined by “the nucleic acid” in claim 17.
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.
Claims 1 and 9-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Viger-Gravel (The Journal of Physical Chemistry B, 2018, 122, 2073-2081, Supporting Information appended thereto).
The claims encompass a lipid nanoparticle comprising
an ionizable lipid of formula
PNG
media_image1.png
83
587
media_image1.png
Greyscale
and
a polyethylene glycol moiety-degradable functional group-lipid conjugate
PEGylated dimyristoyl phosphatidyl ethanolamine (DMPE-PEG 2000), and
a drug, a nucleic acid, or combination thereof encapsulated in the lipid formulation.
Viger-Gravel teaches lipid nanoparticles containing siRNA or mRNA (Title). The nanoparticles comprise ionizable cationic lipid Dlin-MC3-DMA of formula
PNG
media_image4.png
83
586
media_image4.png
Greyscale
(Figure 1), a phospholipid distearoylphosphatidylcholine, cholesterol, and PEG dimyristoyl phosphatidyl ethanolamine (DMPE-PEG 2000) of formula
PNG
media_image5.png
92
318
media_image5.png
Greyscale
(Abstract and Figure 1).
Supporting Information section 1.3 describes how the nanoparticles were formed, and teaches prior to lipid nanoparticle preparation, the lipids were mixed together at a molar percentage ratio of 50% cationic lipid, 10% DSPC, 37.5% cholesterol 1.5% DMPE-PEG 2k.
Claims 1 and 11 are anticipated because lipid nanoparticles comprise the ionizable lipid DLin-MC3-DMA, and a pegylated lipid conjugate that contains a PEG-moiety bonded to lipid via an amide group, which is a degradable functional group.
Claim 9 is anticipated because the claimed range encompass the prior art value of 1.5 mole %.
Claim 10 is anticipated by Table S1 which discloses number average particle size of LNPs having encapsulated siRNA and mRNA where the sizes include 36 nm, 43 nm, 42 nm, and 53 nm. The claimed particle size range encompasses the prior art values.
Regarding claims 12-15, lipid nanoparticles contain cholesterol and DSPC.
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.
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, 2, 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
PNG
media_image1.png
83
587
media_image1.png
Greyscale
, and
a polyethylene glycol moiety-degradable functional group-lipid conjugate of formula
PNG
media_image3.png
142
775
media_image3.png
Greyscale
; 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). Rajeev teaches a compound of formula (I), where an example of the compound has the formula
PNG
media_image3.png
142
775
media_image3.png
Greyscale
(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
PNG
media_image1.png
83
587
media_image1.png
Greyscale
.
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
PNG
media_image3.png
142
775
media_image3.png
Greyscale
where n is 25-100 because Rajeev teaches said compound as an example of a pegylated lipid.
It would have been obvious to have selected
PNG
media_image1.png
83
587
media_image1.png
Greyscale
as the cationic lipid, with a reasonable expectation of success because Viger-Gravel teaches
PNG
media_image6.png
53
375
media_image6.png
Greyscale
(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
PNG
media_image3.png
142
775
media_image3.png
Greyscale
, 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, 2, and 11, the claimed invention is obvious because Rajeev’s (or alternatively Viger-Gravel’s) modified lipid nanoparticle contains:
PNG
media_image3.png
142
775
media_image3.png
Greyscale
which is relevant to polyethylene glycol moiety-degradable functional group-lipid conjugate when
a is 0,
M is H,
P is -CH2CH2O(CH2CH2O)qCH2-,
q is 25-100,
L6 is -OC(O)-,
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 C17 alkyl, and
R3 is -CH2-Y-R where Y is -OC(O)- and R is a C17 alkyl;
PNG
media_image1.png
83
587
media_image1.png
Greyscale
, 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 0.5% 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.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alma - Pipic whose telephone number is (571)270-7459. The examiner can normally be reached M-F 9:00am-5:00pm.
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, Michael Hartley can be reached on 571-272-0616. 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.
/ALMA PIPIC/Primary Examiner, Art Unit 1617