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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on May 22, 2026 and March, 01, 2023. Claims 1, 2, 6, 10-11, 13-14, 18, 40-42, 57, 69, 72, 74, 78, 80 and 91 are pending. Claims 13-14, 18, 40-42, 57, 69, 72, 74, 78, 80 and 91 are withdrawn. Claims 1, 2, 6 and 10-11 are currently examined.
Election/Restrictions
Applicant's election without traverse of Group I (1, 2, 6 and 10-11), in the reply filed on May 22, 2026, is acknowledged.
For species election requirement, applicant elected SEQ ID NO: 1 without traverse.
Accordingly, claims 13-14, 18, 40-42, 57, 69, 72, 74, 78, 80 and 91 are withdrawn as being directed to a non-elected group.
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.
Claims 1, 2, 6 and 10-11 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.
The claims 1, 6 and 10 recite the word “or” between claim 1 (b) (ii) and (iii) (claim 1), among SEQ ID NO: 29, SEQ ID NO:1 and an equivalent, at position “(…nt 226 to nt 465 of SEO ID NO: 2), or an equivalent of each thereof”, at position “… (nt 472 to nt 707 of SEO ID NO: 2), or an equivalent” (claim 6), and at the position “…a complementary sequence of each thereof, or an equivalent” (claim 10), which render the claims indefinite because they contain an improper Markush grouping of alternatives. It is not clear what the encapsidated polynucleotide is among (i) to (iii) in the base claim 1 and what the first polynucleotide, third polynucleotide and fourth polynucleotide are in the claim 6. It is also unclear what the sequence is for the encapsidated polynucleotide as claimed in claim 10. See MPEP 2173.05(h).
. Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claims.
The base claim 1 recites a term “fragment” that renders the claims indefinite. It is unclear what the fragment is and what the relations are with the claimed SARS-CoV-2 N1, SARS-CoV-2 N2 and human RNase P (RP). It is no metes and bounds of the claim.
The claim 2 recites a term “derived” that renders the claim indefinite. It is not clear what the “derive” is represented for. It is not clear how much similarity of structure and function can be derived. One of ordinary skill in the art will not know the metes and bounds of the claim.
The claims 6 and 10 recite a term “an equivalent” that render the claims indefinite. It is unclear what the “an equivalent” means, and how much the similarity of the structure and function can be considered “an equivalent”. One of ordinary skill in the art will not know the metes and bounds of the claim.
For purposes of compact prosecution and applying prior art, the base claim 1 (b) was interpreted herein to encompass any one of “a second polynucleotide encoding a SARS-CoV-2 N1”, “a third polynucleotide encoding a SARS-CoV-2 N2” and “a fourth polynucleotide encoding a human RNase P (RP)”. Claim 6 was interpreted herein to encompass any one of the sequences as claimed. Claim 10 was interpreted herein to encompass SEQ ID NO: 1 as elected.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Claim Rejections - 35 USC § 112 (Written Description)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 6 and 10-11are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings. See MPEP 2163. I.
In Regents of the University of California v. Eli Lilly and Co. 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997), the Court decided that adequate written description of genetic material "requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention." Id. 43 USPQ2d at 1404 (quoting Fiefs, 984 F.2d at 1171, 25 USPQ2d at 1606). In AbbVie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (Court of Appeals, Federal Circuit 2014), the Court ruled that “[W]ith the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus. See Ariad, 598 F.3d at 1353 (The written description requirement guards against claims that “merely recite a description of the problem to be solved while claiming all solutions to it and . . .cover any compound later actually invented and determined to fall within the claim' s functional boundaries.”).”
The base claim 1 is directed to a virus-like particle (VLP) comprising a polynucleotide encapsidated in a coat protein (CP), wherein the encapsidated polynucleotide comprises: (a) an optional first polynucleotide comprising a bacteriophage Qbeta (QB) hairpin loop with affinity for the QB coat protein (CP), or a polynucleotide complementary thereto, and (b) any one or any two or all three of: (i) a second polynucleotide encoding a SARS-CoV-2 N1 or a fragment thereof or a polynucleotide complementary thereto, (ii) a third polynucleotide encoding a SARS-CoV-2 N2 or a fragment thereof or a polynucleotide complementary thereto, or (iii) a fourth polynucleotide encoding a human RNase P (RP) or a fragment thereof or a polynucleotide complementary thereto.
The instant specification discloses that the VLP is consists of 4 segments with the first being a 29-nt Qβ hairpin having high affinity for the Qβ coat proteins and the Qβ hairpin is followed by the 3 target regions: two SARS-CoV-2 N regions (accession NC_045512.2 N1SDM (SARS-CoV-2 Detection Module): gene location: 28271-28443; N2: gene location: 29091-29230) and the human RNase P region (or RP; accession NM_006413: gene location: 1-280). The SDM flanked with a T7 promoter and T7 terminator was cloned into pCDFDuet-Qβ and pET-28a ( +) to generate plasmid Qβ1P-C19 and Qβ 2P-C19, respectively (See [0281]) and in vivo encapsidation of SDM RNAs in QR VLPs was achieved by co-expression of Qβ CPs and SDM RNAs in E. coli using the aforementioned one-plasmid system and two-plasmid system to produce Qβ 1P-C19 VLPs and Q~ 2P-C19 VLPs, respectively (See [0281] to [0282]). The instant specification also discloses that the VLP can be from cowpea chlorotic mottle virus (CCMV) (See [0290]– [0291]). Here the disclosures indicate that VLP is either bacteriophage Qβ-based VLP or the CCMV-based VLP with four specific genes Qβ, N1, N2 and RP. However, the instant claims are directed to a generic VLP with any one of the N1, N2 and RP gene, where the “first polynucleotide comprising a bacteriophage Obeta (QB) hairpin loop with affinity for the QB coat protein (CP), or a polynucleotide Complementary” is optional. Therefore, there is no evidence to support or demonstrate any VLP can be formed with any one of the SARS-CoV-2 N1 or a fragment, SARS-CoV-2 N2 or a fragment, and human RNase P (RP) or a fragment.
Accordingly, the specification does not provide sufficient written description support for the invention as claimed,
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 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Crone et al. (medRxiv preprint doi: https://doi.org/10.1101/2020.05.02.20088344; this version posted May 12, 2020, hereinafter “Crone”).
The base claim 1 is directed to a virus-like particle (VLP) comprising a polynucleotide encapsidated in a coat protein (CP), wherein the encapsidated polynucleotide comprises: (a) an optional first polynucleotide comprising a bacteriophage Qbeta (QB) hairpin loop with affinity for the QB coat protein (CP), or a polynucleotide complementary thereto, and (b) any one or any two or all three of: (i) a second polynucleotide encoding a SARS-CoV-2 N1 or a fragment thereof or a polynucleotide complementary thereto, (ii) a third polynucleotide encoding a SARS-CoV-2 N2 or a fragment thereof or a polynucleotide complementary thereto, or (iii) a fourth polynucleotide encoding a human RNase P (RP) or a fragment thereof or a polynucleotide complementary thereto.
Crone teaches generating a standard for their workflow development, benchmarking, and validation, and engineering non-infectious synthetic virus-like particles (VLP). The ‘Armoured RNA’ is a noninfectious RNA virus surrogate consisting of an MS2 bacteriophage capsid containing an RNA template of choice (See page 4, paragraph 2). Crone discloses that produced and characterized a VLP standard simulating SARS-CoV-2 by containing the genomic RNA segments complementary to the N protein N1, N2, and N3 primer-probe sets specified by the CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic (See page 4, paragraph 3), and the recombinant MS2 bacteriophage VLPs carrying the SARS-CoV-2 N gene were produced in E. coli from an expression plasmid using protocols described previously and modified to transcribe and package the primer-probe target sites for the CoV-2 N protein (See page 6, paragraph 1; Figure 1 a and below). Here the description teaches a VLP comprising a polynucleotide encapsidated in a coat protein (CP) as claimed, where the encapsidated polynucleotide comprises SARS-CoV-2 N1 and N2 as claimed in the base claim 1 (b) (i) and (ii).
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[AltContent: textbox (Figure 1: SARS-CoV-2 VLP production and characterisation. (a) Schematic of the genetic construct of the engineered MS2 SARS-CoV-2-N gene VLP encompassing the MS2 maturation protein (MP) in green and coat proteins (CP) in orange, linked via His-tag (yellow), under transcriptional control of the T7 promoter and T7 terminator sequences. The SARS CoV-2 N protein RNA is packaged using a downstream pac site. (b) The VLP)]
Regarding claim 11, it requires the encapsidated polynucleotide is an RNA polynucleotide. Crone teaches that ‘Armoured RNA’ is a noninfectious
RNA virus surrogate consisting of an MS2 bacteriophage capsid containing an RNA
template of choice, and they produced and characterized a VLP standard simulating SARS-CoV-2 by containing the genomic RNA segments complementary to the N protein N1, N2, and N3 primer-probe sets specified by the CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel (See page 4, paragraphs 4-3). Crone also teaches that they extracted the SARS-Cov-2 N protein RNA encapsulated by the MS2 VLP using heat lysis from the serial dilutions quantified via ddPCR and performed One-Step RT-qPCR using the TaqPath master mix (See page 8, paragraph 1). Here this description teaches the encapsidated polynucleotide is an RNA polynucleotide.
Accordingly, claims 1 and 11 are anticipated by Crone.
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 of this title, 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 2 is rejected under 35 U.S.C. 103 as being unpatentable over Crone et al. (medRxiv preprint doi: https://doi.org/10.1101/2020.05.02.20088344; this version posted May 12, 2020, hereinafter “Crone”) as applied to claims 1 and 11 above in view of Yao et al. (Food Environ Virol. 2019 Dec;11(4):383-392) and Fang et al. (RSC Adv. 2018 Jun 12;8(38):21399-21406).
Claim 2 requires the VLP is derived from a bacteriophage Qβ and the CP comprises a Qβ coat protein.
Relevance of Crone is set forth above, however, it is silent on the bacteriophage Qβ and the CP comprises a Qβ coat protein.
Yao teaches that armored RNA (AR) prepared using the MS2 phage system is a successful positive control for detecting foodborne viruses and is an important quality control process when using real time RT-PCR. In their study, Yao reports a novel technology for preparing AR using bacteriophage Qβ and compare its stability with AR prepared using the MS2 phage system for packaging norovirus detection target RNA. AR could be successfully and efficiently produced using the developed bacteriophage Qβ system. AR prepared using the new bacteriophage Qβ system is more stable than the traditional AR, making the developed strategy a good candidate for AR preparation and quality control (See Abstract). Yao also teaches that unlike MS2, Qβ possesses two cysteine residues per coat protein, and these characteristics of excellent thermal stability would theoretically make Qβ VLP a better strategy than MS2 for AR preparation (See page 390, left column, paragraph 1).
Fang further teaches that packaging of target RNA requires the Qβ hairpin (hp). The Qβ hp is necessary for efficient packaging of essentially any RNA within a Qβ VLP. a-rRNA fused to the Qβ hp (a-rRNA-hp) shows the highest packaging efficiency of any RNA tested here (See page 21403, right column, paragraph 3). Fang teaches a method to generate Qβ VLP using pCDF-CP and pET-RNA plasmids to express Qβ CP (See Fig. 2 and below).
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It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the armored RNA technology using bacteriophage Qβ into Crone’s study to arrive at an invention as claimed. Yao teaches the AR prepared using the developed bacteriophage Qβ packaging system is more stable than that prepared using the conventional MS2 phage, and Fang further teaches the importance of packaging of target RNA requiring the Qβ hairpin and discloses a method for VLP generation, thus, one of skill in the art would have been motivated to use the bacteriophage Qβ-based VLP to develop a more stable VLP, and there would be a reasonable expectation of success to develop such a VLP that is derived from a bacteriophage Qβ and the CP comprises a Qβ coat protein as claimed.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Crone et al. (medRxiv preprint doi: https://doi.org/10.1101/2020.05.02.20088344; this version posted May 12, 2020, hereinafter “Crone”) as applied to claims 1 and 11 above in view of Randazzo et al. (WO 2005/000087 A2, published on Jan. 06, 2005).
Claim 6 requires that the first polynucleotide, the second polynucleotide, the third polynucleotide or the fourth polynucleotide comprises a specific sequence.
Relevance of Crone is set forth above, however, it is silent on a specific sequence for the first polynucleotide, the second polynucleotide, the third polynucleotide or the fourth polynucleotide.
Randazzo teaches an invention provides a method of inhibiting growth of a tumor cell by modulating expression of a gene product, where the gene product is encoded by a gene identified by a sequence selected from the group consisting of: SEQ ID NOS:1-9672 (See page 5, lines 2-3), where the SEQ ID NO: 2747 comprises sequences that is identical to the fourth polynucleotide as claimed in SEQ ID NO: 1 at nt 360 nt to 639 nt (See Table A, highlighted sequences).
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It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the known SEQ ID NOs of Randazzo into Crone’s VLP structure. One of skill in the art would be motivated to substitute one sequence for another (See MPEP 2144.06: Substituting equivalents known for the same purpose). There would be a reasonable expectation of success to develop a VLP as claimed.
Allowable Subject Matter
The nucleic acid sequence SEQ ID Nos: 1, 2 and 29 are free of prior art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am..
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/RUIXUE WANG/ Examiner, Art Unit 1672
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