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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/19/2021 and 10/10/2021 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner. See attached copy of PTO-1449.
Response to Restriction
Applicant’s election of Group I (claims 14-19) in the reply filed on 10/10/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
For examining purpose, claims 14-19 of Group I are examined in this office action.
Specification Objections
The disclosure is objected to because of the following informalities: (6Z, 9Z,28Z, 31 Z)-heptatriacont-6, 9,28, 31-tetraene-19-yl 4-( dimethylamino )butanoate (Dlin-MC3-DMA), which should be (6Z, 9Z,28Z, 31 Z)-heptatriaconta-6, 9,28, 31-tetraene-19-yl 4-( dimethylamino)butanoate (Dlin-MC3-DMA). (SPEC pg. 4, lines 2, 26; pg. 24, line 20; pg. 25, line 10; pg. 30, line 34; pg. 31, line 34).
Appropriate corrections are required.
Claim Objections
Claim 16 is objected to because of the following informalities: (6Z, 9Z,28Z, 31 Z)-heptatriacont-6, 9,28, 31-tetraene-19-yl 4-( dimethylamino )butanoate (Dlin-MC3-DMA), which should be (6Z, 9Z,28Z, 31 Z)-heptatriaconta-6, 9,28, 31-tetraene-19-yl 4-( dimethylamino)butanoate (Dlin-MC3-DMA).
Appropriate correction is required.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 14-16 and 19 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jasny et al. (US 20230181713 A1) or Petsch et al. (US 12397048 B2).
Jasny et al. teach
Claim 14 and 19,
Suitable adjuvants may be selected from polycationic compounds for complexation of the inventive mRNA. Associating or complexing the inventive mRNA comprised by the (pharmaceutical) composition or vaccine with polycationic compounds preferably provides adjuvant properties and confers a stabilizing effect to the said mRNA. (0545). The mRNA, (pharmaceutical) composition or vaccine is provided in the form of a lipid-based formulation selected from, but not limited to, liposomes, lipoplexes, nanoliposomes and lipid nanoparticles, (LNPs). (0595). LNPs can include two or more cationic lipids suitable for forming lipid nanoparticles. (0443). In preferred embodiments, the mRNA, (pharmaceutical) composition or vaccine of the invention is provided in lyophilized form. (0594). Lyophilization (freeze-drying) involves drying under a vacuum.
With regard to claim 15,
The inventive mRNA, optionally comprised by the (pharmaceutical) composition or vaccine, is provided in a complexed form, i.e. complexed or associated with one or more (poly-)cationic compounds, preferably with (poly-)cationic polymers, (poly-)cationic peptides or proteins, e.g. protamine, (0435), (Poly-)cationic amino acids (0500), such as poly-L-lysine (PLL), poly-arginine, (0501), cyclodextrin (0506).
With regard to claim 16,
Further preferred (poly-)cationic compounds for complexation or association with the inventive mRNA, optionally comprised by the (pharmaceutical) composition or vaccine as defined herein, include (poly-)cationic lipids, e.g. DOTMA, DC-Chol, DOPC, DOPE, (0506), PEG-lipid, PEG-modified lipid, (0440), DSPC or a mixture thereof (0459).
Petsch et al. teach
Claims 14 and 19
The present invention is to provide an effective vaccine against viruses of the order Bunyavirales. (Col. 4, lines 19-21 & 51) The artificial RNA comprised in the composition may additionally be complexed or at least partially complexed with one or more cationic or polycationic compound, preferably with a cationic or polycationic polymer, cationic or polycationic polysaccharide, cationic or polycationic lipid, cationic or polycationic protein, cationic or polycationic peptide, or any combinations thereof. The artificial RNA comprised in the composition may be at least partially complexed with protamine. (Col. 13, lines 55-66).
In another embodiment, the composition may comprise an RNA complexed with one or more lipids, thereby forming lipid nanoparticles (LNPs). (Col. 14, lines 1-3). The composition, which is preferably a pharmaceutical composition, an immunogenic composition, comprises at least one artificial nucleic acid as described herein, wherein the at least one artificial nucleic acid is complexed or associated with one or more lipids (e.g. cationic lipids and/or neutral lipids), thereby forming liposomes, lipid nanoparticles (LNPs), lipoplexes, and/or nanoliposomes. The term “lipid nanoparticle”, also referred to as “LNP”, is not restricted to any particular morphology, and include any morphology generated when a cationic lipid and optionally one or more further lipids are combined. (Col. 131, lines 40-56). The composition as defined herein for the preparation of a medicament, particularly a vaccine. (Col. 174, lines 1-3). The nucleic acid, particularly the RNA of the composition, pharmaceutical composition, immunogenic composition, vaccine according to the invention is provided in lyophilized form using lyophilization methods, (Col. 171, lines 15-19), which is drying under vacuum.
With regard to claim 15,
The composition, the pharmaceutical composition, the immunogenic composition as defined herein may comprise at least one adjuvant, wherein the at least one adjuvant may be selected from the group consisting of: cationic or polycationic compounds, comprising cationic or polycationic peptides or proteins, including protamine, nucleoline, spermin or spermidine, poly-L-lysine (PLL), poly-arginine. (Col. 166, lines 1-8).
With regard to claim 16,
Such lipids include, but are not limited to, DOTMA, DOTAP, cholesterol, propane. (Col. 132, lines 49-62). ) Additionally, a number of commercial preparations of cationic lipids are available which can be used in the present invention. These include DLin-MC3-DMA, DOPE, DSPC, DOPC. (Col. 133, lines 1-30). In some embodiments, the cholesterol may be PEGylated. (Col. 161, lines 23-65).
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 non-obviousness.
Claim(s) 14 and 17-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jasny et al. (US 20230181713 A1) or Petsch et al. (US 12397048 B2), as described in claim 14 above, in view of and Ketterer et al. (WO 2016/165831 Al).
The teachings of Jasny et al. or Petsch et al. are described in claim 14 above.
Claim 14 and 17,
Jasny et al. teach lyophilized pharmaceutical composition or vaccine, (0594), and dextran (0064), polyethylene glycol, propylene glycol, glycerol (0585), as excipients for (pharmaceutical) compositions or vaccines in liquid form and they are also cryoprotectants as many excipients have dual or multiple effects, but do not explicitly recite they are cryoprotective agents.
Petsch et al. teach the nucleic acid, particularly the RNA of the composition, pharmaceutical composition, immunogenic composition, vaccine according to the invention is provided in lyophilized form (as defined herein using lyophilisation methods as described in WO2016/165831, (Col. 121, lines 24-26), and pharmaceutically acceptable carriers, fillers or constituents thereof are sugars, for example, lactose, glucose, trehalose and sucrose; starches, such as, for example, dextrose; polyols, such as, for example, polypropylene glycol, glycerol, sorbitol, mannitol and polyethylene glycol, (Col 123, lines 14-39), which are also cryoprotective agents. However, Petsch et al. do not explicitly recite they are protective agents.
Ketterer et al. teach lyophilization involves two types of stress, namely freezing and drying. Both types of stress are known to damage nucleic acids, such as non-viral vectors or plasmid DNA. In the literature, a number of cryoprotectants and lyoprotectants are discussed for lyophilization purposes to prevent these damages. (pg. 3, lines 15-18). Glucose (monosaccaride), sucrose and lactose (disaccharides) were used as lyoprotectants. (pg. 5, lines 3-4).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to prepare lipid nanoparticles of nucleic acids/RNA with cationic polymers and lipids to stabilize nucleic acids/RNA and to lyophilize them for long term storage taught by Jasny et al., or Petsch et al., and with cryoprotectant, Glucose, sucrose and lactose taught by Ketterer et al., since they have proven these cryoprotectants increase RNA stability in formulation.
Claim(s) 14 and 18,
Jasny et al. teach prolin-rich peptides, arginine-rich peptides, lysine-rich peptides, MPG-peptide(s), Pep-1, L-oligomers, (0501), in RNA formulation, which play roles in RNA stabilization also, but do not explicitly teach amino acids selected from lysine, arginine, histidine, glutamine, proline, glycine, threonine.
Petsch et al. teach the liquid provided in step a) of the inventive method may additionally contain at least one component selected, e.g., from proteins, amino acids, alcohols, mannitol, polymers or complexing agents, buffers, etc., or a combination thereof.
the composition, the pharmaceutical composition, the immunogenic composition as defined herein may comprise at least one adjuvant, wherein the at least one adjuvant may be selected from the group consisting of: (Col. 166, lines 1-4), polycationic proteins or peptides, selected from the following proteins or peptides having the following total formula: (Arg)l;(Lys)m;(His)n;(Orn)o;(Xaa)x, wherein l+m+n+o+x=8-15, and l, m, n or o independently of each other may be any number selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, provided that the overall content of Arg, Lys, His and Orn represents at least 50% of all amino acids of the oligopeptide; and Xaa may be any amino acid selected from native (naturally occurring) or non-native amino acids except from Arg, Lys, His or Orn; and x may be any number selected from 0, 1, 2, 3 or 4, provided, that the overall content of Xaa does not exceed 50% of all amino acids of the oligopeptide, (Col. 166, lines 54-66). Xaa can be glutamine, proline, glycine or threonine. When l or m or n or x = 8-15 and all others are 0, then they can be oligomers of either Arg, Lys, His, glutamine, proline, glycine or threonine, which play roles in RNA stabilization also, but do not explicitly teach amino acids selected from lysine, arginine, histidine, glutamine, proline, glycine, threonine.
Ketterer et al. teach the liquid provided in step a) of the inventive method may additionally contain at least one component selected, e.g., from proteins, amino acids, polymers or complexing agents, buffers, etc., or a combination thereof. In the context of the present invention, one preferred component may be selected from the group of amino acids. Such group may comprise, without being limited thereto, any naturally occurring amino acid, including glutamic acid, glycine, histidine, lysine, proline, glutamine, arginine, threonine, more preferably glycine, arginine. (pg. 51, lines 24-34)
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to prepare lipid nanoparticles of nucleic acids/RNA with cationic polymers and lipids to stabilize nucleic acids/RNA and to lyophilize them for long term storage taught by Jasny et al., or Petsch et al., and with amino acid, including glutamic acid, glycine, histidine, lysine, proline, glutamine, arginine, threonine taught by Ketterer et al., since they have proven these amino acids increase RNA stability in formulation.
Conclusion
No claim is allowed.
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/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615