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 .
Claims Status
Claims 1, 4, and 10 are amended. Claims 2 and 7-8 are cancelled. Claims 1, 3-6, 9-12 are pending and are examined on the merits.
Objections Withdrawn
All objections to the claims with regard to drawings and specification are withdrawn in view of Applicant’s amendments.
Rejections Withdrawn
Claims 2 and 7-8 are cancelled, rendering all previous rejections moot.
Rejection of Claim 4 under 35 U.S.C. 112(b) is withdrawn with applicant amendment of the claim.
Rejection of claim 10 under 35 U.S.C. 112(a) is withdrawn with applicant amendment of the claim.
Rejection of claims 1-5 and 7-10 under 35 U.S.C. 102(a)(1) are withdrawn.
Rejection of claims 1-10 under 35 U.S.C. 103 are withdrawn with applicant amendment of claims necessitating new rejections.
Rejections Maintained/New Rejections Necessitated by Claim Amendments
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.
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, 3, 4, and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Sahin et al (WO2013/143555, IDS entered on 5/2/22; hereinafter Sahin ‘555) and further in view of Wen et al (Nanomedicine (Lond.), 2019, 14(5):627-648; hereinafter Wen).
Sahin ‘555 discloses lipid nanoparticles comprising (1) tumor antigens (including negatively charged RNAs (reads on anion drug), (2) cationic lipids, such as DOTMA, DDAB, DOTAP, DOSPA and DODPA, which is applicant’s DODMA, and cholesterol analogs and derivatives thereof, (3) phospholipids comprising phospholipids having 14-22 aliphatic carbons and (4) adjuvant (summary, pages 15-18, 33-38, page 38, first full paragraph and entire reference). The lipid nanoparticles are used in pharmaceutical compositions for the treatment and prevention of cancer (Page 10, second paragraph and page 11, second paragraph). The adjuvants include CpG oligonucleotides (page 53-54).
However, Sahin ‘555 does not teach a lipid nanoparticle wherein the tumor-associated antigen conjugated to the DSPE-PEG derivative is oriented on the surface of the lipid nanoparticle and wherein the CpG oligonucleotide is bound by electrostatic interaction to the cationic lipid.
The deficiency is resolved by Wen et al.
Wen describes using DSPE-PEG derivatives in vaccine nanoparticles, such as the melanoma vaccine described in Table 2. Wen also teaches the lymphatic-targeted mannosylated DOTAP liposomes (LP-Man) that were constructed by incorporating mannosylate DSPE-PEG into DOTAP were used to achieve targeting behavior via the mannose receptor on APCs, and demonstrated significantly higher cellular uptake of Ovalbumin (OVA) compared with nontargeted LP-OVA in mouse bone marrow derived cells (BMDCs) in vitro and in vivo in spleen and DLNs (Table 2, page 633, paragraph 3). Wen further teaches LCP vaccine nanoparticles wherein the vaccine nanoparticle could codeliver both tumor antigen Trp2 peptide and adjuvant CpG oligonucleotides at +25mV zeta potential (Table 2, “LCP”). Finally, Wen teaches a study performed by Moon and colleagues wherein they compared the antigen cross-presentation behavior of cationic liposomes composed of 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) with tertiary amine groups to negatively charged liposomes composed of EPC/Chol/DSPE-mPEG. Wen discloses that this study demonstrated that the cationic liposomes (CLs) including DOTAP-CLs and DC-Chol-CLs showed antigen cross-presentation/priming of CD8+ T cells in bone marrow-derived DCs by acidic interactions with lysosomes given that amine-functionalization provided buffering capacities and enhanced protection of loaded antigens before reaching targets of interest (page 631, last paragraph – page 632, first paragraph).
Regarding instant claims 1, 3, and 4, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the lipid nanoparticle comprising a tumor-associated antigen, a phospholipid comprising 14 to 22 aliphatic carbon atoms, a cationic lipid e.g. DDAB, and CpG oligonucleotides of Sahin ‘555 and modify it wherein (i) the phospholipid is DSPE-PEG; (ii) the tumor-associated antigen conjugated to DSPE-PEG is oriented on the surface of the lipid nanoparticle; and (iii) the CpG oligonucleotide is bound by electrostatic interaction to the cationic lipid as taught by Wen. This is obvious because, Sahin ‘555 discloses lipid nanoparticles comprising tumor antigens, cationic lipids, phospholipids comprising 14-22 aliphatic carbons, and an adjuvant wherein the adjuvants include CpG oligonucleotides, and Wen teaches LCP vaccine nanoparticles comprising tumor antigen Trp2 peptide and adjuvant CpG nucleotides at +25mV zeta potential, and cationic liposomes showing antigen cross-presentation/priming of CD8+ T cells in bone marrow-derived DCs. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to take the lipid nanoparticle comprising a tumor-associated antigen, a phospholipid comprising 14 to 22 aliphatic carbon atoms, a cationic lipid e.g. DDAB, and CpG oligonucleotides of Sahin ‘555 and modify it wherein (i) the phospholipid is DSPE-PEG; (ii) the tumor-associated antigen conjugated to DSPE-PEG is oriented on the surface of the lipid nanoparticle; and (iii) the CpG oligonucleotide is bound by electrostatic interaction to the cationic lipid as taught by Wen to form the instant lipid nanoparticle comprising a (i) tumor-associated antigen wherein the tumor-associated antigen is conjugated to a DSPE-PEG derivative and oriented on the surface of the instant lipid nanoparticle; (ii) a phospholipid comprising a DSPE-PEG derivative wherein the phospholipid is a phospholipid comprising 14-22 aliphatic carbon atoms; (iii) a cationic lipid, e.g. DDAB; and (iv) CpG oligonucleotides, wherein the CpG oligonucleotide is bound by electrostatic interaction to the cationic lipid.
Regarding instant claims 9 and 10, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the lipid nanoparticle comprising a (i) tumor-associated antigen wherein the tumor-associated antigen is conjugated to a DSPE-PEG derivative and oriented on the surface of the lipid nanoparticle; (ii) a phospholipid comprising a DSPE-PEG derivative; (iii) a cationic lipid,; and (iv) CpG oligonucleotides, wherein the CpG oligonucleotide is bound by electrostatic interaction to the cationic lipid as taught by the combined teachings of Sahin ‘555 and Wen, and form a vaccine composition comprising the lipid nanoparticle as the active ingredients, wherein the vaccine composition is for treating cancer as taught by Sahin ‘555. This is obvious because, the combined teachings of Sahin ‘555 and Wen teach a lipid nanoparticle comprising a tumor-associated antigen, a phospholipid, a cationic lipid, and CpG oligonucleotides, wherein (i) the phospholipid is a DSPE-PEG derivative; (ii) the tumor-associated antigen conjugated to the DSPE-PEG derivative is oriented on the surface of the lipid nanoparticle; and (iii) the CpG oligonucleotide is bound by electrostatic interaction to the cationic lipid, and Sahin ‘555 teaches Sahin ‘555 discloses a method of treating cancer comprised of administering pharmaceutical composition comprising the lipid nanoparticles comprising a tumor antigen. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to take the lipid nanoparticle comprising a (i) tumor-associated antigen wherein the tumor-associated antigen is conjugated to a DSPE-PEG derivative and oriented on the surface of the lipid nanoparticle; (ii) a phospholipid comprising a DSPE-PEG derivative; (iii) a cationic lipid,; and (iv) CpG oligonucleotides, wherein the CpG oligonucleotide is bound by electrostatic interaction to the cationic lipid as taught by the combined teachings of Sahin ‘555 and Wen, and form a vaccine composition comprising the lipid nanoparticle as the active ingredients, wherein the vaccine composition is for treating cancer as taught by Sahin ‘555 to form the instant vaccine composition comprising a lipid nanoparticles as an ingredient for treating cancer, wherein the instant lipid nanoparticle comprises a (i) tumor-associated antigen wherein the tumor-associated antigen is conjugated to a DSPE-PEG derivative and oriented on the surface of the instant lipid nanoparticle; (ii) a phospholipid comprising a DSPE-PEG derivative; (iii) a cationic lipid; and (iv) CpG oligonucleotides, wherein the CpG oligonucleotide is bound by electrostatic interaction to the cationic lipid.
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Sahin et al (WO2013/143555, IDS entered on 5/2/22; hereinafter Sahin ‘555) and Wen et al (Nanomedicine (Lond.), 2019, 14(5):627-648; hereinafter Wen), as applied to claim 1 above, and further in view of Lee et al (Theranostics, 2016, vol. 6, p. 192-203, IDS entered on 5/2/22; hereinafter Lee).
The combined teachings of Sahin ‘555 and Wen are discussed above.
However, the combined teachings of Sahin ‘555 and Wen do not teach a lipid nanoparticle wherein the cationic lipid is a cationic cholesterol derivative, wherein the cationic cholesterol is mono arginine-cholesterol (MA-Chol).
The deficiency is resolved by Lee.
Lee discloses a cationic cholesterol derivative, mono arginine-cholesterol (MA-Chol), and its use in lipid nanoparticles in combination with helper lipids and siRNA (page 192, Abstract). Lee also teaches that MA-Chol has several favorable attributes as a complexing agent, such as exhibiting much lower cytotoxicity than other cationic lipids, such as DC-Chol, because other cationic lipids, e.g. DC-Chol, have a non-cleavable cationic head group linked to cholesterol whereas MA-Chol is comprised of the arginine linked to cholesterol via a cleavable ester bond, yielding two nontoxic endogenous compounds upon hydrolysis—arginine and cholesterol (page 196, “Design and Synthesis of a new cationic cholesterol derivative” section).
Regarding instant claims 5 and 6, it would have been obvious for a person having ordinary skill in the art at the time of filing to substitute the cationic lipid of the lipid nanoparticle comprising a (i) tumor-associated antigen wherein the tumor-associated antigen is conjugated to a DSPE-PEG derivative and oriented on the surface of the instant lipid nanoparticle; (ii) a phospholipid comprising a DSPE-PEG derivative; (iii) a cationic lipid, e.g. DDAB; and (iv) CpG oligonucleotides of Sahin and Wen, with the cationic cholesterol derivative MA-Chol of Lee. This is obvious because, the combined teachings of Sahin ‘555 and Wen teach a lipid nanoparticle comprising a tumor-associated antigen, a phospholipid, a cationic lipid, and CpG oligonucleotides, wherein (i) the phospholipid is a DSPE-PEG derivative; (ii) the tumor-associated antigen conjugated to the DSPE-PEG derivative is oriented on the surface of the lipid nanoparticle; and (iii) the CpG oligonucleotide is bound by electrostatic interaction to the cationic lipid, and Lee discloses the cationic cholesterol derivative, MA-Chol, and its use in lipid nanoparticles in combination with helper lipids and siRNA, wherein MA-Chol was used as a complexing agent since it exhibits much lower cytotoxicity than other cationic lipids, such as DC-Chol. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to substitute the cationic lipid of the lipid nanoparticle comprising a (i) tumor-associated antigen wherein the tumor-associated antigen is conjugated to a DSPE-PEG derivative and oriented on the surface of the instant lipid nanoparticle; (ii) a phospholipid comprising a DSPE-PEG derivative; (iii) a cationic lipid, e.g. DDAB; and (iv) CpG oligonucleotides of Sahin and Wen, with the cationic cholesterol derivative MA-Chol of Lee to form the instant lipid nanoparticle comprising a (i) tumor-associated antigen wherein the tumor-associated antigen is conjugated to a DSPE-PEG derivative and oriented on the surface of the instant lipid nanoparticle; (ii) a phospholipid comprising a DSPE-PEG derivative; (iii) a cationic lipid wherein the cationic lipid is a cationic cholesterol derivative wherein the cationic cholesterol derivative is MA-Chol; and (iv) CpG oligonucleotides, wherein the CpG oligonucleotide is bound by electrostatic interaction to the cationic lipid.
Claim(s) 11-12 remained rejected under 35 U.S.C. 103 as being unpatentable over Sahin et al WO 2013/143555 (IDS of 5/2/22) in view of Zhao et al J. Immunol. Res. Article ID 3673295 (9/20418) (IDS of 5/2/22) and Pravda US 7312243(PTO-892).
Sahin et al ‘555 has been discussed above.
The only difference between the reference and the claimed invention is the formation of a kit and the combination of the nanoparticles with anti-PD-L1 and anti-PD-1 antibodies.
Zhao et al disclose the combination therapy of nanoparticles and checkpoint blockade antibodies, such as anti-PD-1 and anti-PD-L1 antibodies (page 2-9).
Pravda et al discloses the formation of kits for the ease of administration to a person (col. 7, lines 10-15 and col. 12, line 65-col. 13, line 25.
Since Zhao et al disclose the combination therapy of nanoparticles and checkpoint blockade antibodies, such as anti-PD-1 and anti-PD-L1 antibodies, and since Sahin et al discloses lipid nanoparticles for treatment of cancers, it would have been obvious to use the nanoparticles of Sahin et al in combination with anti-PD-1 and anti-PD-L1 antibodies with the expected benefit of treating cancer. As disclosed by Pravda et al formation of kits for the ease of administration to a person it known in the art. Thus, it would have also been obvious to form a kit using the nanoparticle and the anti-PD-1 and anti-PD-L1 antibodies. With respect to the kit comprising a first and second vaccine composition, this is within the purview of one skilled in the art.
Response to Arguments
Applicant's arguments filed 9/22/2025 have been fully considered but they are not persuasive.
Applicant discloses that claims 11-12 are patentable, because claims 11-12 depend upon the amended claim 1. In response, claims 11-12 filed on 9/22/2025 are not dependent on the amended claim 1. In claim 11, the claim recites a “lipid nanoparticle including a tumor-associated antigen, a phospholipid, a cationic lipid, and an anionic drug as a first vaccine”, which does not depend on claim 1. Claim 12 depends on claim 11. Therefore, claims 11 and 12 remain obvious over the prior art of record.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jieun Ham whose telephone number is (571)272-7779. The examiner can normally be reached Monday - Friday 7-2.
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/J.H./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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