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 .
Summary
Claims 1-20 are pending in this office action. All pending claims are under examination in this application.
Priority
The current application was filed on June 12, 2023. The current application claims foreign priority to CN2023105920502, CN2022109949172, CN2022108970458, and CN2022106617762 filed on May 24, 2023, August 18, 2022, July 28, 2022, and June 13, 2022, respectively.
Information Disclosure Statement
Receipt of the Information Disclosure Statements on June 12, 2023 and January 2, 2024 are acknowledged. A signed copy of the two documents are attached to this office action.
Claim Objections
Claims 4-5, 7-9, and 18-19 are objected to because of the following informalities: Claims 4-5, 7-9, and 18-19 have acronyms within the text of the claim. Please define the acronyms. Thereafter, the acronym can be used within the claims. Appropriate correction is required.
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 1-4, 6-9, 13, 15-18, and 20 are rejected under 35 U.S.C. 102(a)/1 as being anticipated by Karve et al. (WO2020/232276A1).
Karve et al. teach an improved process of preparing mRNA-loaded lipid nanoparticles (see title). Furthermore, Karve et al. disclose that the present invention provides an improved process for lipid nanoparticle formulation and mRNA encapsulation. In some embodiments, the present invention provides a process for enhanced encapsulation of messenger RNA (mRNA) in lipid nanoparticles comprising a step of heating the mRNA-encapsulated lipid nanoparticles in a drug product formulation solution (see abstract).
Regarding instant claim 1, Karve et al. teach a composition comprising lipid nanoparticles. The necessary citations of Karve et al. that pertain to instant claim 1 are presented in Table I.
Table I
Instant Claim 1
Karve et al. Citations
A composition comprising lipid nanoparticles encapsulating an aqueous solution therein or comprising an aqueous solution therein,
Karve et al. disclose (see whole document; paragraph [0004-0034]; Examples; and claims) processes for improving m RNA-loaded lipid nanoparticles. The process involves encapsulating messenger RNA (mRNA) in lipid nanoparticles (LNPs) comprising the steps of:
(a) mixing one or more lipids in a lipid solution with one or more mRNAs in an mRNA solution to form mRNA encapsulated within the LNPs (mRNA-LNPs) in a lipid
nanoparticle (LNP) formation solution;
(b) exchanging the LNP formation solution for a drug product formulation solution to provide mRNA-LNP in a drug product formulation solution; and
(c) heating the mRNA-LNP in the drug product formulation solution;
(see claim 1).
Furthermore, Karve et al. disclose the use of an aqueous mRNA solution (see paragraph [0025]).
wherein the aqueous solution comprises a mRNA for encoding a substance for treating or preventing a disease and the aqueous solution has a pH of 4.5-6.8.
Karve et al. disclose that the present invention may be used to formulate and encapsulate mRNAs encoding a variety of proteins (see paragraph [0086]). Non-limiting examples of mRNAs suitable for the present invention include mRNAs encoding spinal motor neuron 1 (SN1N), alpha-galactosidase (GLA),
argininosuccinate synthetase (ASS 1), omithine transcarbamylase (OTC), Factor IX (FIX),
pheny lalanine hydroxylase (PAH), erythropoietin (EPO), cystic fibrosis transmembrane conductance receptor (CFTR) and firefly luciferase (FFL) (see paragraph [0088]). Karve et al. further defines the term "treat," "treatment," or "treating" refers to any
method used to partially or completely alleviate, ameliorate, relieve, inhibit, prevent, delay onset
of, reduce severity of and/or reduce incidence of one or more symptoms or features of a
particular disease, disorder, and/or condition (see paragraph [0069]). Moreover, Karve et al. disclose the pH of the drug formulation solution is between 5.0 and 7.0 (see claim 27).
Regarding instant claims 2-4 and 15-18, Karve et al. teach wherein the aqueous solution comprises a buffer with a pH of 4.5-6.0. Karve et al. disclose the pH of the drug formulation solution is between 5.0 and 7.0 (see claim 27) using a citrate buffer (see paragraph [0128] and claim 18).
Regarding instant claims 6 and 20, Karve et al. teach wherein the lipids comprise ionizable lipids, cholesterol, phospholipids, or PEGylated lipids. Karve et al. disclose the use of ionizable lipids, cholesterol, phospholipids, and PEGylated lipids (see paragraph [0011-0015]).
Regarding instant claim 7, Karve et al. teach wherein the ionizable lipids comprise one or more of the following: C12-200, MC3, DLinDMA, DLin-MC3- DMA, DLinkC2DMA, cKK-E12, ICE, HGT5000, HGT5001, OF-02, DODAC, DDABDMRIE, DOSPA, DOGS, DODAP, DODMA, DMDMA, DODAC, DLenDMA, DMRIE, CLinDMA, CpLinDMA, DMOBA, DOcarbDAP, DLinDAP, DLincarbDAP, DLinCDAP, KLin-K-DMA, DLin-K-XTC2-DMA, SM-102, ALC-0315, HGT4003, or JK-102-CA. Karve et al. disclose that in some embodiments, the one or more cationic lipids are selected from the group consisting of cKK-E12, OF-02, C12-200, MC3, DLinDMA, DLinkC2DMA, ICE (Imidazol-based), HGT5000, HGT5001, HGT4003, DODAC, DDAB, DMRIE, DOSPA, DOGS, DODAP, DODMA and DMDMA, DODAC, DLenDMA, DMRIE, CLinDMA, CpLinDMA, DMOBA, DOcarbDAP, DLinDAP, DLincarbDAP, DLinCDAP, KLin-K-DMA, DLin-K-XTC2-DMA, 3-(4-(bis(2-hydrnxydodecyl)amino)butyl)-6-(4-((2-hydroxydodecyl)(2-
hydroxyundecyl)amino)buty 1)-1,4-dioxane-2,5-dione (Target 23), 3-(5-(bis(2-
hydroxydodecyl)amino)pentan-2-yl)-6-(5-((2-hydroxydodecyl)(2- hydroxyundecyl)amino)pentan-2-yl)-1,4-dioxane-2,5~dione (Target 24), NIGL, N2GL, VlGL and combinations thereof (see paragraph [0012]).
Regarding instant claim 8, Karve et al. teach wherein the phospholipids comprise one or more of the following: ceramide, cephalin, cerebroside, diacylglycerol, DPPG, DSPE, DSPC, DPPC, DOPE, DOPC, DPPE, DMPE, DOPG, POPE, POPC, SOPE, orsphingomyelin. Karve et al. disclose use of helper lipids are selected from distearoylphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidy lglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), dioleoylphosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoyl-phosphatidylethanolamine (POPE), dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), dipalmitoyl phosphatidylethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), distearoyl-phosphatidylethanolamine (DSPE), 1,2-dierucoyl-sn-glycero-3-phosphoethanolamine (DEPE), 16-0-monomethyl PE, 16-0-dimethyl PE, 18-1-trans PE, 1-stearoyl-2-oleoyl-phosphatidyethanolamine (SOPE), and combinations thereof (see claim 5).
Regarding instant claim 9, Karve et al. teach wherein the PEGylated lipids comprise one or more of the following: DMG-PEG1000, DMG-PEG1300, DMG-PEG1500, DMG-PEG1800, DMG-PEG2000, DMG-PEG2200, DMG-PEG2500, DMG- PEG2700, DMG-PEG3000, DMG-PEG3200, DMG-PEG3500, DMG-PEG3700, DMG-PEG4000, DMG-PEG4200, DMG-PEG4500, DMG-PEG4700, DMG-PEG5000, ALC-0159, M-DTDAM-2000, C8-PEG, DOGPEG, ceramide-PEG, or DSPE-PEG. Karve et al. disclose that in some embodiments, a suitable lipid solution includes one or more PEGylated lipids. For example, the use of polyethylene glycol (PEG)-modified phospholipids and derivatized lipids such as derivatized ceramides (PEG-CER), including N-Octanoyl-Sphingosine-1-[Succinyl(Methoxy Polyethylene Glycol)-2000] (C8 PEG-2000 ceramide) is also contemplated by the present invention (see paragraph [0124]; DMG-PEG2K see paragraph [0126]).
Regarding instant claim 13, Karve et al. teach a method for delivering a composition comprising: using a microneedle to deliver the composition comprising lipid nanoparticles, wherein said lipid nanoparticles comprise an aqueous solution therein, and said aqueous solution comprises a mRNA for encoding a substance for treating or preventing a disease. Please see the discussion and citations within instant claim 1. The compositions appear suitable for administration via a microneedle (see paragraph [0005]).
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 non-obviousness.
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, 4-6, 10-14, and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Karve et al. in view of Casimiro et al. (WO2022/099003A1) and Beckwith et al. (WO2016/037053A1).
[The Examiner is going to introduce each new reference and then combine them where appropriate to reject the instant claims.]
1. Casimiro et al.
Casimiro et al. teaches lipid nanoparticles for delivering mRNA vaccines (see title). In addition, Casimiro et al. disclose that provided are novel lipid nanoparticles for delivering nucleic acids such as mRNA. Also provided are methods of making
and using lipid nanoparticles for delivering nucleic acids such as mRNA (see abstract).
2. Beckwith et al.
Beckwith et al. teach lipid and lipid compositions for the delivery of active agents (see title). Additionally, Beckwith et al. disclose that this invention provides for a
compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RA, RB, R2 and R4 are defined herein. The compounds of formula (I) and pharmaceutically acceptable salts thereof are cationic lipids useful in the delivery of biologically active agents to cells and tissues (see abstract).
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The teachings of Karve et al. are outlined above for instant claims 1-4, 6-9, 13, 15-18, and 20 within the 35 U.S.C. §102 Section.
The remaining claim limitations (instant claims 5, 10-12, 14, and 19) are taught by the combination of Karve et al. and Casimiro et al. or the combination of Karve et al., Casimiro et al., and Beckwith et al.
Combination of Karve et al. and Casimiro et al.
Motivation to combine: This analogous art would allow the primary reference of Karve et al. to expand their mRNA lipid nanoparticle into the vaccine therapeutic area.
Regarding instant claims 5 and 19, Karve et al. and Casimiro et al. teach wherein the Tris buffer comprises Tromethamine, Tris hydrochloride (Tris HCL), glacial acetic acid, sodium acetate trihydrate; the acetate buffer comprises sodium acetate buffer, or thesodium acetate buffer comprises sodium acetate, glacial acetic acid. Buffering agents are common within synthetic organic chemistry labs. For example, the acetate buffer consisting of the sodium acetate and glacial acetic acid is known and often used to adjust the pH. Both the Karve et al. reference (see paragraph [0025] within Karve et al.) and the Casimiro et al. reference (see paragraphs [00131-00133] within Casimiro et al.) use buffered solutions.
Regarding instant claim 10, Karve et al. and Casimiro et al. teach wherein the mass ratio of said ionizable lipids: cholesterol: phospholipids: PEGylated lipids is (9-10): (3-4): (2-3): 1. Both Karve et al. and Casimiro et al. report the use of molar ratios (see claim 8 within Karve et al.; and see paragraphs [00030] and [00092] within Casimiro et al.). Since the molecular weight of the different lipids varies based on structure, the Examiner believes that the molar ranges supported in the above references support the rejection. If the Applicant believes otherwise, they are invited to submit representative examples for the Examiner to then accurately convert to molar amounts.
Regarding instant claim 12, Karve et al. and Casimiro et al. teach wherein the substance is an mRNA vaccine or a bispecific antibody. Casimiro et al. disclose the use of mRNA vaccines (see title and paragraph [0095] within Casimiro et al.).
Regarding instant claim 14, Karve et al. and Casimiro et al. teach wherein said administration is an intradermal administration or a subcutaneous administration. Casimiro et al. disclose that The mRNA-LNP vaccines can be packaged for parenteral (e. g., intramuscular, intradermal or subcutaneous) administration or nasopharyngeal (e. g., intranasal) administration (see paragraph [00188] within Casimiro et al.).
Combination of Karve et al., Casimiro et al., and Beckwith et al.
Motivation to combine: This analogous art would allow the primary reference of Karve et al. and secondary reference of Casimiro et al. to expand their mRNA lipid nanoparticle into other therapeutic areas by adding additional active agents.
Regarding instant claim 11, Karve et al., Casimiro et al., and Beckwith et al. teach wherein the substance comprises a protein, a peptide, an antibody or an antibody fragment, an antigen or an antigen fragment. Beckwith et al. disclose the use of the following therapeutic agents…antibodies, peptides, and proteins (see page 33, lines 24-32, within Beckwith et al.).
Analogous Art
The Karve et al., Casimiro et al., and Beckwith et al. references are directed to the same field of endeavor as the instant claims, that is, a composition comprising lipid nanoparticles encapsulating an aqueous solution therein or comprising an aqueous solution therein, wherein the aqueous solution comprises a mRNA for encoding a substance for treating or preventing a disease and the aqueous solution has a pH of 4.5-6.8.
Obviousness
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the mRNA lipid nanoparticle disclosed by Karve et al., using the teachings of Casimiro et al. and Beckwith et al. to incorporate the necessary claim limitations. Starting with Karve et al., the skilled person only had to try the necessary claim limitations disclosed by Casimiro et al. and Beckwith et al. The combination of Karve et al., Casimiro et al., and Beckwith et al. would allow one to arrive at the present application without employing inventive skill. This combination of the mRNA lipid nanoparticle taught by Karve et al. along with the use of the necessary claim limitations taught by Casimiro et al. and Beckwith et al. would allow a research and development scientist (POSITA; person of ordinary skill in the art) to develop the invention taught in the instant application. It would have only required routine experimentation to modify the mRNA lipid nanoparticle disclosed by Karve et al. with the use of the necessary claim limitations taught by Casimiro et al. and Beckwith et al. This combined modification would have led to an enhanced composition comprising lipid nanoparticles that would be beneficial for patients.
Conclusion
No claims are allowed.
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/JOHN W LIPPERT III/Examiner, Art Unit 1615 /DANAH AL-AWADI/ Primary Examiner, Art Unit 1615