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 .
Claim Status
Claims 1-30 are pending.
Claims 14-30 are withdrawn from examination as being part of non-elected inventions.
Claims 1-13 are being examined.
All previous objections and rejections not set forth below have been withdrawn in view of applicant’s amendments to the claims.
The claim amendments by the Applicant by adding new issues, which was not present in any of the claims before, allowed the Examiner to use new prior art reference(s). However, the Examiner modified the previous Office action dated 8/29/2025, and without adding any new prior art, to address the new issues, as discussed below.
Claim Rejections - 35 USC § 112(b)
Response to Applicants’ arguments: Amendments made to the claims and the arguments filed in Applicant’s response submitted on 12/01/2025 overcame the rejections of record.
Claim Rejections - 35 USC § 102
Claims 1-2, 4-8, 10 and 12-13 remain rejected under 35 U.S.C. 102(a)(1)) as anticipated by Rybicki et al. (GB2574609A).
Claim 1 are drawn to a virus-like particle (VLP) comprising an icosahedral mammalian virus capsid protein and containing a replicon comprising a mammalian promoter operably linked to a heterologous polynucleotide, wherein the 5' and 3' ends of the replicon consist of a geminiviral long intergenic region (LIR) sequence, and wherein the replicon does not comprise a polynucleotide encoding Rep or RepA.
Rybicki et al. describes a mammalian porcine circovirus (PCV) pseudovirion comprising a PCV capsid protein encoded by a replicating geminiviral (BeYDV) vector (abstract) and produced in a plant cell (page 2. Para 2, line 2-3), as recited in claim 2. It is known in the art that all circovirus capsid is icosahedral1. The replicating vector comprises a mammalian promoter operably linked to the heterologous capsid polypeptide (Abstract). Rybicki et al. teaches that pseudovirions (PsVs) are produced in animals while the same or similar substances produced in plants are termed as “virus like particles” (VLPs) (page 1, last para; page 2, first para). Rybicki et al. describes 5' and 3' ends of the amplicon (also known as replicon) consisting of a geminiviral long intergenic region (LIR) sequence of geminivirus BeYDV (Fig. 2; page 5, para 2; page 11 last line and page 12 first 2 lines).
It is known in the art that plant produced Virus-Like Particles (VLPs) do not need Rep/RepA, which are needed for replication of specific sequence(s) recognized by the proteins, because VLPs are non-infectious, lacking the viral genome and replication machinery, serving purely for delivery or vaccine purposes (as in this invention), not self-propagation that needs replication of the polynucleotide in the VLP2. Rybicki et al. describes VLPs that do not contain the Rep/RepA gene in its pseudogenome (page 9, para 3, line 5-6), which is a polynucleotide encoding specific proteins and packaged in a VLP.
Regarding claim 4, Rybicki et al. describes a cytomegalovirus expression cassette (page 18, para 3, line 14-16). It is acknowledged in the art that a cytomegalovirus expression cassette includes a cytomegalovirus promoter3.
Regarding claim 5, Rybicki et al. teaches a heterologous polynucleotide encoding the capsid protein (abstract; page 2, para 2, line 8-9).
Regarding claim 6, Rybicki et al. teaches an antigenic polypeptide, a hormone, an antibody, or an enzyme (page 3, pare 2, line 1-4).
Regarding claim 7, Rybicki et al. describes expressing PCV capsid protein in the VLP, as discussed above. VLPs minimally require a viral capsid protein for spontaneous formation of a VLP structure (spec, page 3, last 2 lines). The structure of VLPs mimics the native virus from which the capsid proteins are derived, and the capsid proteins are exposed on the surface of a virus. Naturally, the VLP, as described by Rybicki et al., presents the capsid protein encoded by the heterologous polynucleotide on its surface.
Regarding claim 8, the heterologous polynucleotide encoding the capsid protein, also encodes an RNA (mRNA) which is needed to make the protein.
Regarding claim 10, Rybicki et al. describes a replicon (an amplicon produced by the amplification/replication of the PCV genome in the host cell) comprising a geminiviral short intergenic region (SIR) sequence (page 5, para 2, line 6; Fig. 2; page 6, para 3, line 1; Fig. 7; page 12, para 1, line 1-2 and 5) that flanks the heterologous polynucleotide on its 3'end (Fig. 2A).
Regarding claim 11, Rybicki et al. teaches that the gene encoding the Rep/RepA protein can be present on another vector (and not in the replicating vector) (page 10, para 1, line 1-2). It also teaches Rep and/or RepA being expressed under the control of the CaMV 35S promoter in an expression cassette (page 12, para 1, like 2-3). CaMV35 promoter does qualify as a “mammalian promoter” as it is functional in mammalian cells4 and reads on to the definition of "mammalian promoter" as described by the Applicant (Spec, page 6, line 1-2).
If it is determined that 35S is not a mammalian promoter, then it would have been obvious to use (other) mammalian promoters, as described later.
Regarding claim 13, Rybicki et al. teaches a pharmaceutical composition comprising the VLP of claim 1 and a pharmaceutically acceptable carrier (Abstract and claim 14).
Response to Applicants’ arguments: The Applicant argues, “Rybicki does not disclose all of the limitations of claim 1, as amended, Applicant submits that claims 1-2, 4-8, 10, and 12-13 are not anticipated by Rybicki” (response, page 6, para 3, line 8-9).
The Examiner disagrees because, as discussed above, Rybicki et al. also teach VLPs that do not contain the Rep/RepA gene in its pseudogenome (page 9, para 3, line 5-6).
Claims 3 is rejected under 35 U.S.C. 103 as being unpatentable over Rybicki et al., as applied to claims 1-2, 4-8, 10, 12-13 above, and further in view of Lai et al.
Claim 3 depends from claim 1 and is drawn to a icosahedral mammalian virus capsid protein is a Norwalk virus capsid protein (NVCP).
Rybicki et al. describes a plant-expressed virus-like particles (VLPs) comprising an icosahedral mammalian virus capsid protein and containing a replicon comprising a mammalian promoter operably linked to a heterologous polynucleotide, wherein the 5' and 3' ends of the replicon consist of a geminiviral long intergenic region (LIR) sequence, as discussed above. Rybicki et al. also describes VLPs that do not contain the Rep/RepA gene in its pseudogenome (page 9, para 3, line 5-6).
However, Rybicki et al., does not describe any Norwalk virus capsid protein (NVCP).
Lai et al. describes obtaining a high-level expression of virus-like particles (VLP) derived from the Norwalk virus capsid protein (NVCP) in a plant using the same geminiviral (bean yellow dwarf virus, BYDV) based replicon system (abstract). The NVCP based VLPs are used as a therapeutic agent against Ebola and West Nile viruses (abstract).
Before the effective filing date of the invention, it would have been obvious to an ordinarily skilled artisan to modify the method described by Rybicki et al. to use the Norwalk virus capsid protein (NVCP) for high level expression, as described by Lai et al., and consequently more efficient production of the NVCP based VLP to be used as a therapeutic agent.
Before the effective filing date, one ordinarily skilled artisan would have been motivated to use the Norwalk virus capsid protein (NVCP) for high level expression, and consequently more efficient production, of the NVCP based VLP to be used as a therapeutic agent.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Rybicki et al. as applied to claims 1-2, 4-8, 10, 12-13 above, and further in view of Arhancet et al.
Claim 9 recites, “wherein the RNA is a small interfering RNA (siRNA), short hairpin RNA (shRNA), anti-sense RNA, microRNA (miRNA), or guide RNA (gRNA)”
Rybicki et al. describes a plant-expressed virus-like particles (VLPs) comprising an icosahedral mammalian virus capsid protein and containing a replicon comprising a mammalian promoter operably linked to a heterologous polynucleotide, wherein the 5' and 3' ends of the replicon consist of a geminiviral long intergenic region (LIR) sequence, as discussed above. Rybicki et al. also describes VLPs that do not contain the Rep/RepA gene in its pseudogenome (page 9, para 3, line 5-6).
However, Rybicki et al. does not describe any heterologous polynucleotide encoding an RNA.
Arhancet et al. describes producing VLPs expressing nucleic acid constructs comprising short RNAs selected from siRNA, shRNA, sshRNA, lshRNA and miRNA (page 1, para 0010; claims 5-6). Such VLPs are used to produce double stranded RNA molecules (claim 5) in the target host cells for various purposes including- silencing one or more endogenous gene(s) using RNA interference (RNAi) (page 8, para 0068); introducing short RNA sequences aimed at inducing RNAi in specific target cells (page 9, para 0071); targeting endogenous RNA strands essential for the survival of the host taking up such RNAs within VLPs (page 23, para 0202).
Before the effective filing date of the invention, it would have been obvious to an ordinarily skilled artisan to modify the method described by Rybicki et al. to express an RNA molecule encoded by the heterologous polynucleotide and encapsulated in the VLP with the realistic objective to silencing one or more endogenous gene(s) in the target host cells using RNA interference (RNAi), as described by Arhancet et al.
Before the effective filing date, one ordinarily skilled artisan would have been motivated to express an RNA molecule encoded by the heterologous polynucleotide and being encapsulated in the VLP with the realistic objective to silencing one or more endogenous gene(s) in the target host cells using RNA interference (RNAi).
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Rybicki et al. as applied to claims 1-2, 4-8, 10, 12-13 above, and further in view of Kennedy, P. (HPV Pseudovirion Production in Plants, 2013, Thesis presented for the degree of Master of Science in the department of Molecular Biology, University of Cape Town, South Africa).
Claim 11 depends from claim 1 and is drawn to a construct comprising a mammalian promoter operably linked to a polynucleotide encoding Rep and/or RepA. If it is determined that 35S is not a mammalian promoter, as described by Rybicki et al. (as discussed above), then it would have been obvious to an ordinarily skilled artisan to use (other) mammalian promoters.
Rybicki et al. describes a virus-like particle (VLP) comprising an icosahedral mammalian virus capsid protein and containing a replicon comprising a mammalian promoter operably linked to a heterologous polynucleotide, wherein the 5' and 3' ends of the replicon consist of a geminiviral long intergenic region (LIR) sequence, as discussed above.
However, Rybicki et al. does not explicitly describe a construct comprising a mammalian promoter (other than CaMV35S) operably linked to a polynucleotide encoding Rep and/or RepA.
Rybicki et al. uses a replicating vectors derived from the geminivirus BeYDV (abstract, line 2-3). Kennedy, P. describes that the Rep and RepA are the only (Gemini)viral components required for replication (page 26, last para, line 6) and can initiate replication in the host cell (page 31, para 1, line 4-5). Kennedy, P. also describes that insertion of a mammalian promoter into the vector resulting in high copy number of the replicon leading to increased expression of the gene (including the gene encoding Rep/RepA) under the control of the mammalian promoter (page 33, para 2, line 3-7).
Before the effective filing date of the invention, it would have been obvious to an ordinarily skilled artisan to modify the method described by Rybicki et al. to make a vector construct comprising a mammalian promoter operably linked to a polynucleotide encoding Rep and/or RepA to achieve higher expression of the heterologous polynucleotide in the mammalian host cells, as described by Kennedy, P.
Before the effective filing date, one ordinarily skilled artisan would have been motivated to make a vector construct comprising a mammalian promoter operably linked to a polynucleotide encoding Rep and/or RepA operably linked to mammalian promoter to achieve higher expression of the heterologous polynucleotide in the mammalian host cells.
Regarding claim 12, Rybicki et al. describes a replicon which is capable of replicating in mammalian cells (page 9, para 3, line 1-3).
Response to Applicants’ arguments: The Applicant argues that, “Rybicki does not disclose a VLP having the structure (i.e., “wherein the replicon does not comprise a polynucleotide encoding Rep or RepA”) required in amended claim 1, from which claims 3, 9 and11 depends” (response, page 7, para 1; page 7, para 3; and page 7, para 4).
The Examiner disagree because, as discussed above, Rybicki et al. also teach VLPs that do not contain the Rep/RepA gene in its pseudogenome (page 9, para 3, line 5-6). Moreover, presence of a polynucleotide encoding Rep/RepA protein in the VLP is irrelevant in the context of the invention, as described above.
Conclusion
No claim is allowed.
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.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAY CHATTERJEE whose telephone number is (703)756-1329. The examiner can normally be reached (Mon - Fri) 8.30 am to 5.30 pm..
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Jay Chatterjee
Patent Examiner
Art Unit 1662
/Jay Chatterjee/Examiner, Art Unit 1662
/Amjad Abraham/SPE, Art Unit 1663
1 Nath et al. (Structural Perspectives of Beak and Feather Disease Virus and Porcine Circovirus Proteins, 2021, Viral Immunology, 34:49-59) provides the evidence that circovirus capsid is icosahedral (page 50, left column, 1st para).
2 Virology Research Services (The viral system of the month: Virus-like Particles, published in 2019) provides the evidence that VLPs lack the viral genetic material needed to replicate (para 1, line 3).
3 Durocher et al. (High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cells, 2002, Nucleic acids research, 30:e9) provides the evidence cytomegalovirus expression cassette includes a cytomegalovirus promoter which is highly active in human cell lines (abstract; page 1, right column, para 2, line 16-25).
4 Tepfer et al. (Transient expression in mammalian cells of transgenes transcribed from the Cauliflower mosaic virus 35S promoter, Environ. Biosafety Res. 3:91–97) provides the evidence that CaMV35S is functional in mammalian cells (title and abstract).