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 . 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.
Claim Objections
Claims 23-24 are objected to because of the following informalities: Claims 23-24, line 1 of each claim, should recite the word “in”, immediately after the word “use”. Appropriate correction is required.
Claim Rejections - 35 USC § 112 –
Indefiniteness and Broad Limitation followed by Narrow Limitation
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 1-5 and 7-9 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claims 1-2 and 7 recite the broad recitations “RNA containing lipid nanoparticles” and “empty lipid nanoparticles”, and the claims also recite “(RNA-LNPs)” and “(empty LNPs)” which are the narrower statements of the range/limitation.
In the present instance, claims 3 and 9 recite the broad recitations “self-amplifying mRNA” and “SAM-containing lipid nanoparticles”, and the claim also recites “(SAM)” and “(SAM-LNPs)” which are the narrower statements of the range/limitation.
In the present instance, claim 8 recites the broad recitation “mRNA-containing lipid nanoparticles”, and the claim also recites “(mRNA-LNPs)” which is the narrower statements of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The Applicant is encouraged to remove the parentheses from the claims, at each instance of occurrence.
Claim Rejections - 35 USC § 103 - Obviousness
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.
Claim(s) 1-2, 6-8, 10, 13-14, 15-19 and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Karve et al (US 2021/0275689 A1), in view of Sagi et al (US 2022/0047519 A1).
Karve taught mRNA-loaded lipid nanoparticles, mixed with empty lipid nanoparticles, to yield a mixture of mRNA-loaded and empty lipid nanoparticles [0081]. The lipid nanoparticles were formed in aqueous solution [0024, 0081, 0151, 0230-0231]. In some embodiments, the mRNA molecules encoded for an antigen (e.g., reads on wherein said RNA encodes at least one immunogen) [0309]. Low dose levels of mRNA were taught [0126, 0272, 0278, 0342].
Karve differs from the instant invention in that Karve was silent lyophilizing, as recited in claim 1.
Sagi taught that lyophilized products, that can be subsequently reconstituted prior to administration, improves the storage capabilities of lipid nanoparticle formulations. Lyophilized lipid nanoparticle compositions can be stored at more practical temperatures, allowing more convenient modes of distribution and administration [0006]. Sagi provided high quality lyophilized lipid nanoparticle compositions that showed a maintained integrity and efficacy upon reconstitution [0007-0008].
Since Karve taught lipid nanoparticle compositions, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Karve, lyophilization, as taught by Sagi. The ordinarily skilled artisan would have been so motivated, because lyophilization improves the storage capabilities of lipid nanoparticle formulations. The ordinarily skilled artisan would have been motivated to provide high quality lyophilized lipid nanoparticle compositions that showed a maintained integrity and efficacy upon reconstitution, and that could be stored at practical temperatures, thereby allowing convenient modes of distribution and administration, as taught by Sagi [0006-0008].
Karve, in view of Sagi, reads on claims 1-2 and 7-8.
Claim 6, 10, 15-19, 22 and 23-24 are rendered prima facie obvious because Karve taught vaccines [0285, 0309-0310] for injection [0052, 0152, 0283-0284, 0287]. Administration to a subject was taught [0278, 0280].
Claims 13-14 are rendered prima facie obvious because Karve taught buffers, including aqueous buffers, and sodium chloride [0073, 0081, 0153-0154, 0156, 0230-0231, 0271]. Water for injection was taught [0052, 0152].
The instant claim 14 recites “a dry buffer component, such that when the lyophilized vaccine composition is mixed with sterile water for injection, an injectable aqueous pharmaceutically acceptable aqueous composition is formed”. The limitation of mixing, with sterile water for injection, such than an injectable aqueous composition is formed, is a product-by-process limitation. Product by process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.
Even though the product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, then the claim is unpatentable even though the prior product was made by a different process. In the instant case, Karve’s pharmaceutical lipid nanoparticle vaccine reads on the claimed vaccine. As such, the patentability of the instant composition does not depend on its method of production, and the Applicant’s limitation regarding the process of mixing the vaccine with sterile water for injection, such that an injectable aqueous composition is formed, is not patentable, in view of Karve et al. MPEP 2113.
Claim(s) 3-5 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Karve et al (US 2021/0275689 A1), in view of Sagi et al (US 2022/0047519 A1) and further in view of Zhu et al (US 2023/0312659 A1).
The 35 U.S.C. 103 rejection over Karve and Sagi was previously discussed.
Additionally, Karve generally taught nucleic acids [0112]. At ¶ [0033], Karve taught a first set of mRNA-encapsulating LNPs and a second set of empty LNPs, with a ratio of, or greater, than 1:20.
Sagi taught lyophilization, as previously discussed.
Although Karve generally taught mRNA and nucleic acids in general, Karve was not specific self-amplifying mRNA, as recited in claims 3 and 9.
Zhu taught mRNA compositions [abstract] (e.g., lipid nanoparticles, taught at ¶s 0060, 0074, 0079]), wherein the mRNA were, preferably, self-amplifying mRNA [claim 35; ¶s 0032, 0034]. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. In the instant case, it is prima facie obvious to select a self-amplifying mRNA for incorporation into a mRNA composition, based on its recognized suitability for its intended use as a mRNA, as taught by Zhu [abstract, claim 35, ¶s 0032, 0034].
The instant claim 5 recites empty LNPs present in an amount up to 25 % dry weight.
Karve taught a first set of mRNA-encapsulating LNPs and a second set of empty LNPs, with a ratio of or greater than 1:20. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
Claim(s) 11, 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Karve et al (US 2021/0275689 A1), in view of Sagi et al (US 2022/0047519 A1), further in view of Zhu et al (US 2023/0312659 A1) and further in view of Smith et al (US 2023/0285297 A1).
The 35 U.S.C. 103 rejection over Karve, Sagi and Zhu was previously discussed.
As discussed Karve taught vaccines. Additionally, Karve taught single doses [0076-0080, 0082, 0288, see also the Examples throughout].
The combined teachings of Karve, Sagi and Zhu were not specific an amount of nucleic acid of less than 60 µg, as recited in claim 11; kits comprising needles and containers, as recited in claims 20-21.
Smith taught a composition for, or method of, vaccinating a subject, comprising administering to the subject, a nucleic acid vaccine comprising one or more RNA, at a dosage of 1-400 µg/dose [0877; see also ¶s 0384 and 0386 for teachings of a single unit dose]. Lipid (loaded) nanoparticles and empty lipid nanoparticles were taught [0896]. Multiple doses were taught, as desired (e.g., a first and a second, or booster dose) [0882-0883, 0966].
In some aspects, Smith provided pharmaceutical kits comprising containers [0078-0083, 1528-1554]. Needles were taught as suitable devices for administration [0924]. The formulations were provided for ease of use and administration, for bedside and/or point-of-care formulations [0110, 0318, 0964].
Since Karve taught vaccines comprising RNA, it would have been prima facie obvious to one of ordinary skill in the art to include, within the combined teachings of Karve, Sagi and Zhu, a RNA dosage of 1-400 µg/dose, as taught by Smith. The ordinarily skilled artisan would have been motivated to provide an effective dosage.
It would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Karve, kits comprising containers and needles. The ordinarily skilled artisan would have been motivated to provide formulations for ease of use and administration, or for bedside and/or point-of-care formulations, as taught by Smith [0078-0083, 0110, 0318, 0924, 0964, 1528-1554]. Furthermore, the ordinarily skilled artisan would have been motivated to include multiple administrations, or dosages, as desired, as taught by Smith [0882-0883, 0966].
The instant claim 11 recites a RNA dosage of less than 60 µg.
Smith taught RNA, at a dosage of 1-400 µg. A prima facie case of obviousness exists because of overlap, as discussed above.
Claim(s) 12 is rejected under 35 U.S.C. 103 as being unpatentable over Karve et al (US 2021/0275689 A1), in view of Sagi et al (US 2022/0047519 A1) and further in view of Smith et al (US 2023/0285297 A1).
The 35 U.S.C. 103 rejection over Karve, Sagi and Zhu was previously discussed.
As discussed, Karve taught vaccines. Additionally, Karve taught single doses [0076-0080, 0082, 0288, see also the Examples throughout].
The combined teachings of Karve, Sagi and Zhu were not specific an amount of nucleic acid of 1-6 µg, as recited in claim 12.
Smith taught a composition for or method of vaccinating a subject comprising administering to the subject a nucleic acid vaccine comprising one or more RNA, at a dosage of 1-400 µg/dose [0877; see also ¶s 0384 and 0386 for teachings of a single unit dose]. Lipid (loaded) nanoparticles and empty lipid nanoparticles were taught [0896].
Since Karve taught vaccines comprising RNA, it would have been prima facie obvious to one of ordinary skill in the art to include, within the combined teachings of Karve, Sagi and Zhu, a RNA dosage of 1-400 µg/dose, as taught by Smith. The ordinarily skilled artisan would have been motivated to provide an effective dosage.
The instant claim 12 recites a RNA dosage of 1-6 µg.
Smith taught RNA, at a dosage of 1-400 µg. A prima facie case of obviousness exists because of overlap, as discussed above.
Conclusion
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/CELESTE A RONEY/Primary Examiner, Art Unit 1612