DETAILED ACTION
Election/Restrictions
Applicant’s election of Group I, species SEQ ID NO: 5, 157, 281, 284 and 287, in the reply filed on 11/26/2025 is acknowledged. Because Applicant did not distinctly and specifically point out any supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Specification
The disclosure is objected to because of the following informalities:
The use of the terms LUMINEX®, VARIVAX®, BD GOLGISTOP™, BD GOLGIPLUG™, BD CYTOFIX/CYTOPERM™, LSRFORTESSA™, among others, which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required.
Claims Summary
Claim 1 is directed to an RNA molecule comprising at least one ORF encoding a VZV glycoprotein E (gE) polypeptide, wherein the polypeptide is full-length, truncated, fragment or a variant thereof (claim 2). According to the specification, referencing the published application US20230233671, a “fragment” is a part of an amino acid sequence, and encompasses a percentage of the amino acid sequence, as well as sequence identity with the amino acid sequence (see paragraph [0099]). A “variant” refers to a protein or polypeptide whose amino acid sequence is altered (see paragraphs [0098] and [0105]). The polypeptide comprises at least one mutation (claim 3). The polypeptide has at least 90% identity, for example, to SEQ ID NO: 5 (elected species). According to Table 4 of the specification, SEQ ID NO: 5 is 538 aa, and represents gE having a deletion TM and a deletion of CT (aa 539-623 deleted), termed ms6. The ORF is transcribed from a nucleic acid sequence having at least 90% identity to SEQ ID NO: 157 (elected species) (claims 6 and 7). SEQ ID NO: 157 represents ms6 CO2 (Codon Optimized with about 66% G/C content (see paragraph [0042] and [0044]). The ORF comprises a G/C content of at least 55% (claim 14).
The RNA molecule further comprises a 5’ UTR (claim 8), comprising SEQ ID NO: 281 (elected species) (claim 9). The RNA molecule further comprises a 3’ UTR (claim 10), comprising SEQ ID NO: 284 (elected species) (claim 11). The RNA molecule further comprises a 5’ cap moiety and/or a poly-A tail (claim 12), the poly-A tail comprising SEQ ID NO: 287 (elected species) (claim 13).
The encoded VZV polypeptide localizes in the cellular membrane, in the Golgi, and/or is secreted (claim 15). The RNA molecule comprises at least one modified nucleotide (claim 16). Each uridine in the RNA molecule is replaced by N1-methylpseudouridine (ψ) (claim 17). The RNA is mRNA (claim 18).
Also claimed is a composition comprising the RNA molecule formulated in a LNP (claim 19), wherein the LNP comprises at least one of a cationic lipid, a PEGylated lipid, a neutral lipid, and a steroid or steroid analog (claim 20). The cationic lipid is ALC-0315 (claim 21). The PEGylated lipid is PEG-modified phosphatidylethanolamine, for example (claim 22). The neutral lipid is, for example, DSPC (claim 23). The steroid or steroid analog is cholesterol (claim 24).
Claim Objections
Claims 4 and 6 are objected to because of the following informalities:
Claims 4 and 6 recite “90%, 95, 96%” etc. There should be a percent sign after “95”, consistent with the other numbers. 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.
Claim 22 is 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.
The phrases “e.g.” and "such as" render the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 2, 4, 8, 10, 12, 15 and 18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more. The claims are directed to an RNA molecule comprising at least one ORF encoding a VZV gE polypeptide. This reads on an mRNA molecule comprising at least one ORF encoding a VZV gE polypeptide, as in claim 18. Such an mRNA molecule is not markedly different from the naturally occurring mRNA produced during translation of VZV gE DNA to mRNA because it conveys the same genetic information. Truncated molecules, fragments (portions of the molecule), and variants (to the extent that they encompass portions of the molecule) are not markedly different from their naturally occurring mRNA portions produced during translation of VZV gE DNA to mRNA because they convey the same genetic information. Molecules of mRNA that include a 5’ UTR, a 3’ UTR, a 5’ cap and a poly-A tail are not markedly different from the naturally occurring mRNA produced during translation of VZV gE DNA to mRNA because they also have a 5’ UTR, a 3’ UTR, a 5’ cap and a poly-A tail. See the abstract of Lai et al. (J. Mol. Biology, 2022, 434:167877, 16 pages) which notes the presence of these elements in mRNA molecules. With regard to claim 15, wherein the encoded VZV polypeptide localized in the cellular membrane, the presence of the polypeptide in the cellular membrane is an expected outcome of being expressed since it is an envelope protein on the surface of VZV.
This judicial exception is not integrated into a practical application because the claims are limited to the molecules.
The claims do not recite any additional elements, thus the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Therefore, the claims are directed to a judicial exception and are not patent eligible.
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 1-4, 8, 10, 12, 15-20 and 22-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ciaramella (WO 2017/070601 A1, cited in the IDS filed 6/2/2023). The claims are summarized above and correlated with the teachings of the prior art in bold font below.
Ciaramella discloses mRNA molecules encoding a VZV gE open reading frame (see abstract and page 3, lines 25-35, and page 4, lines 6-18) (claims 1, 2 and 18). Ciaramella’s SEQ ID NO: 18 is 99.9% identical to Applicant’s SEQ ID NO: 5 (see alignment below) (claim 4). The gE polypeptide is truncated or comprises at least one mutation (see pages 4-5, bridging paragraph, and page 5, first full paragraph) (claims 2 and 3). The mRNA comprises a 5’ UTR, a 3’ UTR, and a polyA tail (see page 32, lines 5-6, and page 61, lines 29-30) (claims 8, 10 and 12). The RNA comprises N1-methylpseudouridine in place of uridine (see Ciaramella, claim 54) (claims 16 and 17). Also disclosed is a vaccine comprising mRNA formulated with a lipid nanoparticle comprising a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic, neutral lipid (see Ciaramella, claims 53 and 54) (claims 19 and 20). The PEG-modified lipid is, for example, PEG-cDMA (see page 77, lines 28-30) and the sterol is cholesterol (see Ciaramella, claim 54) (claims 22 and 24). The neutral lipid is, for example, DSPC (see page 77, line 8) (claim 23). The encoded polypeptide is secreted (see page 125, lines 21-24) (claim 15). Therefore, the claimed embodiments are anticipated by the prior art.
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.
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.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Ciaramella (WO 2017/070601 A1, cited in the IDS filed 6/2/2023) as applied to claim 1 above, and further in view of Hanon et al. (US Patent 7,939,084, cited in the IDS filed 11/26/2025, “Hanon”).
Claim 4 is directed to an embodiment wherein the VZV polypeptide has at least 90% identity to SEQ ID NO: 5 (elected species). As outlined above, Ciaramella discloses a gE sequence that is 99% identical to SEQ ID NO: 5. It would have been obvious to have used any other known sequence of VZV gE in Ciaramella’s RNA construct with a reasonable expectation of success, since Ciaramella does not limit gE to any particular sequence, but rather discloses gE generically (see page 4, third full paragraph). Hanon’s SEQ ID NO: 1 is 100% identical to Applicant’s SEQ ID NO: 5. Therefore, the claimed embodiment would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 9, 11 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Ciaramella (WO 2017/070601 A1, cited in the IDS filed 6/2/2023) as applied to claim 1 above, and further in view of Rauch et al. (WO 2021/156267 A1, “Rauch”).
Claim 9 is directed to an embodiment wherein the 5’ UTR comprises SEQ ID NO: 281 (elected species). As outlined above, Ciaramella discloses mRNA molecules comprising a 5’ UTR, a 3’ UTR, and a polyA tail (see page 32, lines 5-6, and page 61, lines 29-30). It would have been obvious to have used any known 5’ UTR sequence in Ciaramella’s RNA construct with a reasonable expectation of success, since Ciaramella does not limit the 5’ UTR to any particular sequence, but rather discloses the 5’ UTR generically. Rauch discloses mRNA sequences comprising any of a number of 5’ UTR, including SEQ ID NO: 22,856 is 100% identical to Applicant’s SEQ ID NO: 5 (see Rauch, page 52, lines 25-32, page 53, lines 26-28 and page 60, lines 13-14).
Claim 11 is directed to an embodiment wherein the 3’ UTR comprises SEQ ID NO: 284 (elected species). As outlined above, Ciaramella discloses mRNA molecules comprising a 5’ UTR, a 3’ UTR, and a polyA tail (see page 32, lines 5-6, and page 61, lines 29-30). It would have been obvious to have used any known 3’ UTR sequence in Ciaramella’s RNA construct with a reasonable expectation of success, since Ciaramella does not limit the 3’ UTR to any particular sequence, but rather discloses the 5’ UTR generically. Rauch discloses RNA sequences comprising any of a number of 3’ UTR, including SEQ ID NO: 22,887 is 100% identical to Applicant’s SEQ ID NO: 5 (see Rauch, page 50, line 36, and page 52, lines 9-11).
Claim 21 is directed to an embodiment wherein the cationic lipid is ALC-0315. Ciaramella discloses the use of any known cationic lipid, but does not name ALC-0315 (see pages 75-76, bridging paragraph). It would have been obvious to have used Rauch’s ALC-0315 cationic lipid in Ciaramella’s LNP formulation, with a reasonable expectation of success, given that Rauch is also directed to mRNA in LNPs having similar formulations of cationic lipid, neutral lipid, steroid and PEGylated lipid (see Rauch, page 100, lines 31-34). Therefore, the claimed embodiments would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Ciaramella (WO 2017/070601 A1, cited in the IDS filed 6/2/2023) as applied to claim 1 above, and further in view of Sahin et al. (US Patent 10,301,368, “Sahin”).
Claim 13 is directed to an embodiment wherein the poly-A tail comprises SEQ ID NO: 287 (elected species). As outlined above, Ciaramella discloses mRNA molecules comprising a 5’ UTR, a 3’ UTR, and a polyA tail (see page 32, lines 5-6, and page 61, lines 29-30). It would have been obvious to have used any known polyA sequence in Ciaramella’s RNA construct with a reasonable expectation of success, since Ciaramella does not limit the polyA to any particular sequence, but rather discloses the polyA generically. Sahin discloses RNA molecules comprising a polyA tail, including A120, SEQ ID NO: 17, nucleotides 25-134, which are identical to Applicant’s SEQ ID NO: 287 (see col. 22, lines 52-57, col. 23, lines 34-37, and Table 4). Therefore, the claimed embodiment would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Ciaramella (WO 2017/070601 A1, cited in the IDS filed 6/2/2023) as applied to claim 1 above, and further in view of Kudla et al. (PLoS Biology, June 2006, 4(6):e180, pages 0933-0942, “Kudla”).
Claim 14 is directed to an embodiment wherein the ORF comprises a G/C content of at least 55%. Ciaramella’s teachings are outlined above. Ciaramella discloses that optimized RNA may have an increased amount of G/C content to improve stability, but does not disclose any particular amount of G/C content (see page 34, lines 17-25). However, it would have been obvious to have increased the G/C content to levels above 90%, with a reasonable expectation of success, as is demonstrated by Kudla. Kudla discloses high (above 90%) G/C content increases levels of mRNA in mammalian cells (see abstract, page 0934, right column, top paragraph, and Figure 2C). Therefore, the claimed embodiment would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Alignment of Applicant’s SEQ ID NO: 5 (“Qy”) with Ciaramella’s SEQ ID NO: 18 (“Db”).
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Conclusion
No claim is allowed.
Claim 7, with regard to the elected species, SEQ ID NO: 157, is objected to for being dependent on a rejected claim. SEQ ID NO: 157 is free of the prior art of record.
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/STACY B CHEN/Primary Examiner, Art Unit 1672