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 Jan. 25, 2024. Claims 2, 5, 8-9, 10, 12, 15-16, 18-23 and 27-30 are pending and are currently examined.
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 2, 8, 10, 12, 15-16, 19-20, 22, 27-30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tseng et al. (Pathogens. 2019 Nov 23;8(4):262).
The base claim 2 is directed to a genetic element comprising: a promoter element; and a nucleic acid sequence encoding an exogenous effector wherein the genetic element is capable of being packaged by a CAV VP1 molecule.
Tseng et al. discloses the preparation of Chicken Anemia Virus (CAV) Virus-Like Particles and Chicken Interleukin-12 for Vaccine Development Using a Baculovirus Expression System, and teaches that they developed a subunit vaccine exploiting the CAV structural proteins, engineered recombinant baculovirus-infected Spodoptera frugiperda (Sf 9) cells that contained both the viral protein 1 (VP1) and VP2 of CAV, and produced single-chain chicken interleukin-12 (chIL-12) in the same system, to serve as an adjuvant. The recombinant VP1 was recognized by chicken anti-CAV polyclonal antibodies in Western blotting and immunofluorescence assays, and the bioactivity of the recombinant chIL-12 was confirmed by stimulating interferon- (IFN-) secretion in chicken splenocytes. Furthermore, the ability of the recombinant VP1 to generate self-assembling virus-like particles (VLPs) is confirmed by transmission electron microscopy. Specific pathogen-free (SPF) chickens inoculated with VLPs and co-administered the recombinant chIL-12 induced high CAV-specific antibodies and cell-mediated immunity. Taken together, the VLPs produced by the baculovirus expression system have the potential to be a safe and effective CIA vaccine. Finally, they demonstrated the utility of recombinant chIL-12 as an adjuvant for poultry vaccine development (See Abstract; Figure 1, page 3 and below), Here the promoter is polyhedron (PH) promoter and the P10, and the foreign gene is EGFP.
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Accordingly, Tseng et al. teaches the base claim 2 for the claimed genetic element, a Baculovirus-based recombinant VP1/VP2 plasmid, comprises a promoter, an exogenous effector/GFP and a CAV VP1, where the Baculovirus-based Chicken Anemia Virus (CAV) Virus-Like Particles is formed/packaged by the recombinant VP1 Protein (See Fig. 4, page 4 and paragraph 1).
Regarding claim 8, Tseng et al. teaches it by stating that the codon-optimized target genes were amplified by PCR using primers with appropriate restriction enzymes (Table 1), and the PCR products were inserted into the pFastBacTM Dual vector (See page 9, paragraph 3 and Table 1 below), which demonstrate that a nucleic acid construct comprising the nucleic acid sequence of the genetic element of claim 2 as claimed.
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Regarding claim 10, Tseng et al. teaches a host cell, Sf9 cell, contains the engineering recombinant baculovirus with CAV structural proteins (See e.g., Abstract).
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Regarding claims 12, 22 and 30, Tseng et al. discloses that this Sf 9-expressed recombinant VP1 formed the self-assembled VLPs, as observed by TEM, necessary to generate neutralizing epitopes (Figure 5). This is the first report to confirm by TEM that the VLPs of CAV can be generated using in vitro protein expression systems (See page 8, and Figure 5, page 5 and below), which teaches that the protein VP1 encapsulates the genetic element (claim 12), where the genetic elements are: promoters (PH and P10), VP2 and GFP. Claim 22 further requires a CAVector and the host cell incubation. Here the VLP of CAV described above meets the genetic element claimed in the claim 22. Furthermore, Tseng et al. teaches the Sf9 is the host cell used for making the VLP based on the recombinant baculoviruses the Bac-to-BacTM Baculovirus Expression System by following the manufacturer’s directions. Sf 9 cells used to generate recombinant baculoviruses and protein production via culture in a Sf-900TM II media at 270C (See page 9, paragraph 3), and also the rVP1 can infect the Sf 9 cell. Here the description also teaches claim 30, where the Sf9 is a host cells comprising the B-VP1-/B-VP2 construct.
Regarding claim 15, Tseng et al. taches that Sf 9 cells were cultured in six-well plates (Nunc, USA) at a density of 1.5 X 10^6/mL, and infected with one of the recombinant baculoviruses, B-VP1/B-VP2 or B-chIL-12, at a multiplicity of infection (MOI) of 1 (See page 10, paragraph 2), where the Sf9 can be a host cell and the constructs comprise the EGFP gene (See Figure 1, above). Also, Tseng et al. teaches that the splenocytes collected from the experimental groups were infected with purified rVP1 (See page 7, paragraph 1), which also teaches that the splenocytes is a target cells.
Regarding claims 16 and 19- 20, Tseng et al. teaches claim 16 by stating that the splenocytes collected from the experimental groups were treated with purified rVP1, and the proliferation response at 28 dpv was quantified. Vaccine-immunized groups showed significantly higher stimulation index (SI) values than the PBS group (p < 0.05; Figure 8a) (See page 7, paragraph 1). The disclosure teaches claim 16(a) by the description that the target cell splenocytes are from a vaccine-immunize subject, whose immune responses, such as producing antibody targeting CAV, is induced by the immunization, and Tseng et al. further teaches CAV antibody titers detected from rVP1-vaccinated chickens using a commercial ELISA kit (See page 6, Figure 7), which means an assessment as claimed. In addition, Tseng et al. teaches claim 16(b) by introducing the rVP1 into the splenocytes cells. Here the anti-CAV antibody can teach the “unwanted immune response to CAV”. Besides the description above, claim 20 also require unwanted immune response to CAV. Tseng et al. teaches using the baculovirus expression system generating CAV VLPs as a vaccine to treat poultry disease caused by chicken anemia virus infection (See Abstract; page 8), which can teach claim 20 as well as claim 19.
Regarding claim 27, Tseng et al. teaches a genetic element, pFB-VP1/VP2 /EGFP construct, where the backbone of the baculovirus is a circular DNA.
Regarding claim 28, Tseng et al. teaches a EGFP gene is inserted into the pFB-VP1/VP2 construct (See Figure 1 above), where the EGFP gene’s primary activity is to produce the Enhanced Green Fluorescent Protein (EGFP) in cells such as human cells to act as a marker or reporter gene. EGFP can be a EGFP to track where that protein goes and what it does.
Regarding claim 29, Tseng’s construct does not comprise the full-length CAV Apoptin gene.
Accordingly, Tseng et al. teaches each and every aspect of claims 2, 8, 10, 12, 15-16, 19-20, 22, 27-30.
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.
Claims 5 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Tseng et al. (Pathogens. 2019 Nov 23;8(4):262) as applied to claims 2, 8, 10, 12, 15-16, 19-20, 22 and 27-30 above and in view of Eltahir et al. (Virol J. 2011 Mar 30;8:145).
These two claims require the genetic element or nucleic acid construct comprise a specific length and percentages of a CAV genome.
Relevance of Tseng et al. is set forth above. However, it is silent on a specific sequence as claimed.
Eltahir et al. describes a molecular epidemiology of chicken anemia virus in commercial farms in China and teaches a total of 25 CAV, approximately full genomes, from different commercial farms were characterized, and all the Chinese CAV genomes characterized in this study had glutamine (Q) at amino acid position 394, which indicated that all are highly pathogenic (See Abstract). Eltahir et al. teaches that their study provides a basis for future epidemiological research on CAV, and would have important consequences for vaccine efficacy and serodiagnosis (See page 1, right column; page 8, left column). They submitted the sequence to GenBank with accession numbers [HQ872023-HQ87204 (See page 3, left column). After analysis, the 1766 bp of HO872023 shows a 96% to a CAV of AF227982 (See the Table A below). This analysis based on the Eltahir teaches claim 5 with 96% to a CAV genome and claim 9 to include all three fragments and no CAV packaging signal.
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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 CAV VP1-3 protein of Eltahir into Zhang’s study and arrive at the invention as claimed. One of skill in the art would have been motivated to do so because Eltahir’s sequences indicated that they are highly pathogenic strain. It is important to introduce the sequences into Tseng’s study for vaccine development. There would be a reasonable expectation of success to develop such a genetic element or nucleic acid construct as claimed.
Claims 18 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Tseng et al. (Pathogens. 2019 Nov 23;8(4):262) as applied to claims 2, 8, 10, 12, 15-16, 19-20, 22 and 27-30 27 and 29-30 above as evidenced by Noteborn et al. (US2006/0073160 A1, published on Apr. 6, 2006).
Regarding claim 18, Tseng et al. teaches that the SPF chickens are immunized with (1) rVP1 only, (2) rVP1 co-administered with 5 ng rchIL-12 [VP1/IL-12(5)], (3) rVP1 co-administered with 10 ng rchIL-12 [VP1/IL-12(10)], (4) a commercial vaccine (positive control), or (5) PBS only (negative control), and the rchIL-12 used here enhanced immune responses in vaccinated chickens and served as a vaccine adjuvant (See page 6, paragraph 1). Although the rchIL-12 in Tseng is administrated as an independent construct for a co-administration, it would have been obvious to one of ordinary skill in the art before the time of the invention to modify the B-VP1/VP2 to provide a genetic element further comprising a nucleic acid sequence encoding the chicken interleukin-12, and the result would be predictable because Tseng already use the cloning technique to insert a GFP gene into the construct. This can also be evidenced by Noteborn’s invention. Noteborn et al. teaches a cloning of CAV virus DNA and discloses the recombinant genetic information according to the invention comprises a CAV-specific nucleotide sequence corresponding with or complementary to a nucleotide sequence having a regulatory function, occurring in a CAV genome, or part thereof. For the “part thereof”, one example is the use of CAV promoter/enhancer elements in combination with sequences coding for a protein other than CAV protein, e.g., to enable expression of such non-CAV proteins in poultry (such as chickens) and other animals in which the regulatory signals of CAV are effective (See [0023]).
Regarding claim 21, Tseng et al. teaches that a EGFP gene is inserted into the genetic element of the pFastBac–VP1–VP2/EGFP plasmid (See Figure 1, page 3 and above). It would be obvious for one of ordinary skill in the art to select an antigen from other pathogen virus and the result would be predictable using the same technique to clone the EGFP gene. This can also be evidenced by Noteborn’s invention. Noteborn et al. teaches that the CAV genome can also itself be made suitable as a living virus vector for the expression of antigens of other viruses. This requires the CAV genome to be changed such that in addition to or instead of CAV proteins “foreign' virus proteins are expressed. CAV vectors therefore can be constructed Such that protection occurs against “foreign” viruses alone or also against CAV, depending on the expression of the viral proteins by the recombinant vector in the vaccinated animal (See [0093]), which also indicates that the nucleotide sequence not derived from a CAV genome, however, may also consist of a nucleotide sequence coding for (part of) a protein other than a CAV protein, e.g., if CAV regulation signals are used to express such a non-CAV protein (or part thereof) in a host accessible to the CAV virus, or if the recombinant DNA is to be used to produce a hybrid or fusion protein in which a CAV protein functions as a carrier for an epitope of a non-CAV protein or, conversely, a non-CAV protein functions as a carrier for an epitope of a CAV protein (See [0025]).
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Tseng et al. (Pathogens. 2019 Nov 23;8(4):262) as applied to claims 2, 8, 10, 12, 15-16, 19-20, 22 and 27-30 above.
Regarding claim 23, Tseng et al. does not explicitly point out their storage time for the pFB-VP1/VP2 plasmid. However, Tseng et al. teaches that the recombinant baculoviruses, B-chIL-12 and B-VP1/-VP2, were generated using the Bac-to-BacTM Baculovirus Expression System following the manufacturer’s directions (See page 9, paragraph 3). The Bac-to-Bac teaches storing virus stock at 4°C, protected from light, and for long-term storage, store an aliquot of the virus stock at −80°C for later reamplification (See page 29) and virus titer can decrease with long-term storage at 4°C or −80°C. Titer baculovirus stock that has been stored for ≥6 months before use in an expression experiment (See page 32).
Although the Tseng et al. does not teach the exact storage time and temperature range as claimed, the viral storage methods vary by time and temperature. According to section 2144.05 of the MPEP, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”). Therefore, one of ordinary skills would be able to test for an optimal temperature and duration for storing the B-VP1-/B-VP2 of Tseng as claimed based on the needs. Thus, the claimed temperature and storage period would have been obvious unless there is evidence showing that they produce unexpected results.
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
/NICOLE KINSEY WHITE/ Primary Examiner, Art Unit 1672