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 .
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1, 8-13, and 16-17; drawn to a method facilitating neointima formation over an endovascular device) in the reply filed on May 7, 2024, is acknowledged.
Claims 18 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (Groups II and III), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 7, 2024.
Applicant further elected the following species:
a. eGFP as the exogenous gene and the reporter protein
b. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) as the baculovirus
c. Aedes pseudoscutellaris as the mosquito cell
In light of the Applicant’s elected species, claim 11 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
DETAILED ACTION
The amended claims filed on March 13, 2026, have been acknowledged. Claims 2-7, 14-15, and 19 were cancelled. Claim 1 was amended. In light of the Applicant’s elected invention and species, claims 11, 18, and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1, 8-10, 12-13, and 16-17 are pending and examined on the merits.
Applicant’s response filed March 13, 2026, has been considered. Rejections and/or objections not reiterated from the previous office action mailed January 9, 2026, are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Declaration under 37 CFR 1.132
The declaration under 37 CFR 1.132 filed by Dr. Hui-Chung Lin on March 13, 2026, has been considered but is insufficient to overcome the rejections of instant claims based upon 35 U.S.C 103 as set forth in the current Office action for the following reasons:
The declaration argues that Colunga-Saucedo does not teach or suggest using a baculovirus expression system to express CHIKV genes. Therefore, it is unclear how a person having ordinary skill in the art would have generated a recombinant baculovirus expressing CHIKV genes based on the plasmid designs disclosed in Colunga-Saucedo (page 2, paragraph 2).
Further Applicant argues that Varrikodan teaches two distinct baculovirus expression systems that are intended for expression in insect cells or mammalian cells. These are distinct expression platform that utilize different promoters and host cells. Thus, Varrikodan provides no teaching or suggestion to integrate two separate constructs into a single baculovirus vector, let alone a baculovirus vector that contains a CMV promoter or is specifically designed for VRP production (page 2, paragraph 3-page 3, paragraph 1).
Applicant argues that Naik merely teaches that AcMNPV is a commonly used baculovirus for foreign gene expression and can transduce Aedes pseudoscutellaris cells, but Naik provides NO disclosure directed to any construct encoding CHIKV proteins (page 3, paragraph 2).
Lin teaches a recombinant baculovirus using the hr1pag1 promoter to express Zika virus-like particles in mosquito cells such and does NOT extend to constructs for CHIKV proteins (page 3, paragraph 3).
Applicant's arguments have been fully considered but they are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
As stated in the rejection below, Colunga-Saucedo identifies that their plasmids encoding the full length genome are useful in examining virology of the Chikungunya virus, as well as for developing antivirals while Naik specifically identifies that their baculovirus transfer system is useful for studying mosquito-borne viruses, such as Chikungunya, and mosquito-pathogen interactions (abstract). Furthermore, Naik reduces to practice that viral genes can be expressed in their baculoviral transfer system (influenza virus neuroaminidase) and Varikkodan successfully reduces to practice that recombinant baculoviruses can express the Chikungunya structural proteins (Capsid and E3-E2-6K-E1), the Chikungunya nonstructural proteins 1-4 and a reporter gene (EGFP under the control of a subgenomic promoter). Additionally, Naik teaches that flow cytometry revealed that plasmid transfection efficiencies in mosquito cells were around 15–20%, while baculovirus transduction efficiencies were around 60% and relative transgene expression levels were significantly higher by baculovirus transduction than plasmid DNA transfection. Furthermore, Naik identifies that AcMNPV has a capacity of ~100 kbp which would allow fit all of the genes of the CHIKV plasmids and is currently the most commonly used baculovirus for foreign gene expression. Therefore, it would have been obvious to place the Chikungunya (a mosquito-borne virus) and a reporter gene encoded by the plasmid of Colunga-Saucedo within a AcMNPV baculovirus transfer vector to examine mosquito-pathogen interactions in a mosquito cell as AcMNPV baculovirus transduction efficiencies were around 3-4x better than when using a plasmid and showed higher transgene expression.
Regarding the hr1pag1 promoter, Lin identifies it as a known promoter for driving expression of genes in mosquito cells and successfully reduces to practice that it can be used to drive expression of a viral protein encoded in a baculovirus (Figures 1-2). Therefore, it would have been obvious to one of ordinary skill that they could use the hr1pag1 promoter to drive expression of the Chikungunya structural proteins in a mosquito cell.
The Lin Declaration further argues vector design varies across different expression systems and is not a matter of routine substitution. Each element in a vector, such as promoter and reporter protein selection and position thereof must be tailored to the host system, accordingly; success in one expression system does not render adaptation to another system predictable or obvious to a person having ordinary skill in the art. The present invention employs a delicate genetic engineering strategy to introduce an additional promoter with defined strength and positioning, thereby achieving controlled expression balance for VRP production (page 3, paragraph 5-page 4, paragraph 1).
Applicant's arguments have been fully considered but they are not persuasive.
MPEP 2145(I) states that an argument by the applicant is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art. Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness."). See MPEP § 716.01(c) for examples of applicant statements which are not evidence and which must be supported by an appropriate affidavit or declaration. As such, although Applicant claims it would have not been obvious to make the modifications identified in the 103 rejection, the Lin Declaration only provides assertions that it wouldn’t work, but does not provide any evidence. The Lin Declaration does not point out any technical reasoning as to why the modifications cannot be performed. Therefore, these assertions are considered an opinion with no clear set of evidence that the modifications recited in the 103 rejection wouldn’t work.
The existing method for producing the safe surrogate is not a facile method for producing the alphavirus VRP. In addition, uncontrolled expression of alphavirus non-structural protein 2 (nsP2) or capsid protein may render cytopathic effects (CPE) in mammalian cells, in turn limiting the production of the alphavirus VRP. While Colunga-Saucedo describes the CPE observed during CHIKV infection and the CPE is not identified as a technical problem to be addressed, nor is any solution proposed to mitigate the effect. The present invention aims to reduce CPE in mosquito cells more effectively than alternative methods do in mammalian cells (page 4, paragraph 2-page 5, paragraph 1).
Applicant's arguments have been fully considered but they are not persuasive.
As an initial matter, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., reducing CPE in mosquito cells) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In response to applicant's argument that the combined teachings of Colunga-Saucedo, Varrikodan, Naik, and Lin do not identify a reduction of CPE in mosquito cells as a technical problem to be solved, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
As stated in the rejection below, Colunga-Saucedo identifies that their plasmids encoding the full length genome are useful in examining virology of the Chikungunya virus, as well as for developing antivirals while Naik specifically identifies that their baculovirus transfer system is useful for studying mosquito-borne viruses, such as Chikungunya, and mosquito-pathogen interactions (abstract). Furthermore, Naik reduces to practice that viral genes can be expressed in their baculoviral transfer system (influenza virus neuroaminidase) and Varikkodan successfully reduces to practice that recombinant baculoviruses can express the Chikungunya structural proteins (Capsid and E3-E2-6K-E1), the Chikungunya nonstructural proteins 1-4 and a reporter gene (EGFP under the control of a subgenomic promoter). Additionally, Naik teaches that flow cytometry revealed that plasmid transfection efficiencies in mosquito cells were around 15–20%, while baculovirus transduction efficiencies were around 60% and relative transgene expression levels were significantly higher by baculovirus transduction than plasmid DNA transfection. Furthermore, Naik identifies that AcMNPV has a capacity of ~100 kbp which would allow fit all of the genes of the CHIKV plasmids and is currently the most commonly used baculovirus for foreign gene expression. Therefore, it would have been obvious to place the Chikungunya (a mosquito-borne virus) and a reporter gene encoded by the plasmid of Colunga-Saucedo within a AcMNPV baculovirus transfer vector to examine mosquito-pathogen interactions in a mosquito cell as AcMNPV baculovirus transduction efficiencies were around 3-4x better than when using a plasmid and showed higher transgene expression.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Claim Rejections - 35 USC § 103
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 8-10, 12-13, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Colunga-Saucedo et al. (Viruses 15: 1-15. 2023. Published December 2022), and further in view of Varikkodan et al. (Int. J. Mol. Sci. 22: 1-18. 2021), Naik et al. (Scientific Reports 8: 1-14. 2018), and Lin et al. (J Med Sci 41:134‑139. 2021).
Regarding claim 1, Colunga-Saucedo teaches a plasmid encoding the Chikungunya full-length genome comprising a replicon comprising:
A CMV promoter operably linked to a first polynucleotide encoding non-structural proteins 1-4 of Chikungunya;
A helper comprising a subgenomic promoter (SGP) driving expression of capsid and E3-E2-6K-E1 structural proteins of Chikungunya;
Wherein the helper is downstream of the replicon (Figure 1 (pVax-CHIKV and pACNR-CHIKV), page 2, paragraph 3-page 3, paragraph 2, and page 5, paragraph 5-page7, paragraph 2).
Colunga-Saucedo teaches that the pACNR-CHIKV plasmids can be used to produce infectious particles to study the virology of Alphaviruses, to determine the neutralizing of vaccine candidates, or to find antivirals that inhibit the CHIKV infectious cycle (page 11, paragraphs 3-4).
Colunga-Saucedo does not teach wherein the Chikungunya genes are placed within a recombinant baculovirus.
However, Varikkodan teaches that they generated recombinant baculoviruses that express the Chikungunya structural proteins (Capsid and E3-E2-6K-E1) and an EGFP or the Chikungunya nonstructural proteins 1-4 and an EGFP under the control of a subgenomic promoter (Figure 1 and page 3, paragraphs 2-3).
Naik teaches that Mosquitoes are ubiquitous insects, responsible for transmitting many deadly arboviruses causing millions of human deaths every year. The lack of efficient and flexible gene delivery strategies in mosquitoes are among the major hurdles for the study of mosquito biology and mosquito-pathogen interactions. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) can efficiently transduce mosquito cells without viral propagation, allowing high level gene expression upon inducement by suitable promoters without obvious negative effects on cell propagation and viability. Moreover, AcMNPV can transduce both larvae and adults of essentially all blood-sucking mosquito genera. Naik teaches that the transgene capacity of AcMNPV is very large, probably extending beyond 100 kbp and that AcMNPV is currently the most commonly used baculovirus for foreign gene expression.
Naik teaches that the most commonly used method to express foreign genes in mosquito hosts is the classical plasmid transfection approach. They compared transgene expression levels by AcMNPV baculovirus transduction versus plasmid DNA transfections. Flow cytometry revealed that plasmid transfection efficiencies were around 15–20%, i.e., much lower than the baculovirus transduction efficiencies of around 60% at MOI = 1. Furthermore, relative transgene expression levels were significantly higher by baculovirus transduction than plasmid DNA transfection (abstract, page 2, paragraphs 1-3, and page 4, paragraph 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used a AcMNPV baculovirus transfer vector instead of a plasmid transfer vector for expressing the full-length Chikungunya genome as designed in the pVax-CHIKV or pACNR-CHIKV in Colunga-Saucedo to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to use a baculovirus transfer vector instead of a plasmid with a reasonable expectation of success because Colunga-Saucedo identifies that their plasmids encoding the full length genome are useful in examining virology of the Chikungunya virus, as well as for developing antivirals while Naik specifically identifies that their baculovirus transfer system is useful for studying mosquito-borne viruses, such as Chikungunya, and mosquito-pathogen interactions (abstract). Furthermore, Naik reduces to practice that viral genes can be expressed in their baculoviral transfer system (influenza virus neuroaminidase) and Varikkodan successfully reduces to practice that recombinant baculoviruses can express the Chikungunya structural proteins (Capsid and E3-E2-6K-E1), the Chikungunya nonstructural proteins 1-4 and a reporter gene (EGFP under the control of a subgenomic promoter). Additionally, Naik teaches that flow cytometry revealed that plasmid transfection efficiencies in mosquito cells were around 15–20%, while baculovirus transduction efficiencies were around 60% and relative transgene expression levels were significantly higher by baculovirus transduction than plasmid DNA transfection. Furthermore, Naik identifies that AcMNPV has a capacity of ~100 kbp which would allow fit all of the genes of the CHIKV plasmids and is currently the most commonly used baculovirus for foreign gene expression. Therefore, it would have been obvious to place the Chikungunya (a mosquito-borne virus) and a reporter gene encoded by the plasmid of Colunga-Saucedo within a AcMNPV baculovirus transfer vector to examine mosquito-pathogen interactions in a mosquito cell as AcMNPV baculovirus transduction efficiencies were around 3-4x better than when using a plasmid and showed higher transgene expression. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
The combined teachings of Colunga-Saucedo, Varikkodan, and Naik do not teach wherein the second promoter is an hr1pag1 promoter.
However, Lin teaches that they used hr1pag1 to express a Zika virus viral protein and identifies the hr1pag1 promoter as being a mosquito promoter (Figure 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used a hr1pag1 promoter for driving expression of the structural proteins Capsid and E3-E2-6K-E1 in the baculovirus of the combined teachings of Colunga-Saucedo, Varikkodan, and Naik to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to use the hr1pag1 promoter for driving expression of the structural proteins Capsid and E3-E2-6K-E1 with a reasonable expectation of success because Lin identifies it as a known promoter for driving expression of genes in mosquito cells and successfully reduces to practice that it can be used to drive expression of a viral protein encoded in a baculovirus (Figures 1-2). Therefore, it would have been obvious to one of ordinary skill that they could use the hr1pag1 promoter to drive expression of the Chikungunya structural proteins in a mosquito cell. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding whether the baculovirus of the combined teachings of Colunga-Saucedo, Varikkodan, Naik, and Lin is capable of producing a Chikungunya virus-like replicon particle in a mosquito cell, Naik, as stated supra, teaches that AcMNPV baculoviruses can efficiently transduce mosquito cells without viral propagation (abstract). Furthermore, Colunga-Saucedo (abstract and page 6, paragraph 2-page 7, paragraph 2) and Lin (abstract) identify that their expression systems generate virus-like particles. Thus, expression of the baculovirus genes of the combined teachings of Colunga-Saucedo, Varikkodan, Naik, and Lin within a mosquito cell would generate a virus-like particle.
Regarding claims 8-10, Colunga-Saucedo (Figure 1) and Varikkodan (Figure 1) teach that the non-structural proteins contain a subgenomic promoter that can drive expression of an exogenous gene, mKate2 and EGFP, respectively.
Therefore, it would have been obvious to use the subgenomic promoter within the non-structural proteins to drive expression of a reporter gene, as done by Colunga-Saucedo and Varikkodan, as this allows for one to visualize which cells have been infected by the baculovirus. Furthermore, it would have been obvious to use EGFP as the reporter gene as Varikkodan has successfully reduced to practice that the EGFP reporter can be expressed using a subgenomic promoter in the non-structural proteins.
Regarding claims 12-13, as stated supra, Naik teaches that the baculovirus species is AcMNPV (abstract).
Regarding claims 16-17, Naik teaches that AcMNPV baculoviruses were able to transduce Aedes pseudoscutellaris cells (page 5, paragraph 3). Therefore, the baculovirus of the combined teachings of Colunga-Saucedo, Varikkodan, Naik, and Lin would also be capable of transducing a Aedes pseudoscutellaris cell to produce the virus-like replicon particle.
Response to Arguments
Applicant's arguments filed March 13, 2026, are acknowledged.
Applicant argues Colunga-Saucedo neither teaches nor suggests placing the CHIKV full-length genes within a recombinant baculovirus, nor does Varikkodan teach or suggest introducing both CHIKV replicon vector encoding a reporter protein and other promoter-driven structural proteins into a single baculovirus, a person having ordinary skill in the art would not have arrived at the presently claimed recombinant baculovirus, much less been motivated to further modify the system based on Naik and Lin. Furthermore, Applicant argues there would be no expectation of success for similar reasons (page 7, paragraph 2 and page 10, paragraph 1).
Applicant's arguments have been fully considered but they are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
As stated in the rejection above, Colunga-Saucedo identifies that their plasmids encoding the full length genome are useful in examining virology of the Chikungunya virus, as well as for developing antivirals while Naik specifically identifies that their baculovirus transfer system is useful for studying mosquito-borne viruses, such as Chikungunya, and mosquito-pathogen interactions (abstract). Furthermore, Naik reduces to practice that viral genes can be expressed in their baculoviral transfer system (influenza virus neuroaminidase) and Varikkodan successfully reduces to practice that recombinant baculoviruses can express the Chikungunya structural proteins (Capsid and E3-E2-6K-E1), the Chikungunya nonstructural proteins 1-4 and a reporter gene (EGFP under the control of a subgenomic promoter). Additionally, Naik teaches that flow cytometry revealed that plasmid transfection efficiencies in mosquito cells were around 15–20%, while baculovirus transduction efficiencies were around 60% and relative transgene expression levels were significantly higher by baculovirus transduction than plasmid DNA transfection. Furthermore, Naik identifies that AcMNPV has a capacity of ~100 kbp which would allow fit all of the genes of the CHIKV plasmids and is currently the most commonly used baculovirus for foreign gene expression. Therefore, it would have been obvious to place the Chikungunya (a mosquito-borne virus) and a reporter gene encoded by the plasmid of Colunga-Saucedo within a AcMNPV baculovirus transfer vector to examine mosquito-pathogen interactions in a mosquito cell as AcMNPV baculovirus transduction efficiencies were around 3-4x better than when using a plasmid and showed higher transgene expression. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding the hr1pag1 promoter, Lin identifies it as a known promoter for driving expression of genes in mosquito cells and successfully reduces to practice that it can be used to drive expression of a viral protein encoded in a baculovirus (Figures 1-2). Therefore, it would have been obvious to one of ordinary skill that they could use the hr1pag1 promoter to drive expression of the Chikungunya structural proteins in a mosquito cell. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Applicant further argues that the determination of obviousness is based on hindsight analysis. The Examiner is reminded that conclusory assertions must be supported by articulated reasoning providing a rationale for combining the elements and accounting for the claimed relationships among the elements. The cited references provide no motivation to combine or modify their teachings, nor has the Examiner articulated any reasoning explaining how or why such a combination would prompt the presently claimed invention. The assertion that "because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success" relies on impermissible hindsight. Since the teaching of the recombinant baculovirus as claimed is present in the Applicant's own disclosure, it logically flows that the Examiner has improperly relied on elements gleaned solely from Applicant's own disclosure, instead of the facts from the prior art, which is nothing but hindsight bias (page 7, paragraph 3-page 8, paragraph 4).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
As stated in the rejection above, Colunga-Saucedo identifies that their plasmids encoding the full length genome are useful in examining virology of the Chikungunya virus, as well as for developing antivirals while Naik specifically identifies that their baculovirus transfer system is useful for studying mosquito-borne viruses, such as Chikungunya, and mosquito-pathogen interactions (abstract). Furthermore, Naik reduces to practice that viral genes can be expressed in their baculoviral transfer system (influenza virus neuroaminidase) and Varikkodan successfully reduces to practice that recombinant baculoviruses can express the Chikungunya structural proteins (Capsid and E3-E2-6K-E1), the Chikungunya nonstructural proteins 1-4 and a reporter gene (EGFP under the control of a subgenomic promoter). Additionally, Naik teaches that flow cytometry revealed that plasmid transfection efficiencies in mosquito cells were around 15–20%, while baculovirus transduction efficiencies were around 60% and relative transgene expression levels were significantly higher by baculovirus transduction than plasmid DNA transfection. Furthermore, Naik identifies that AcMNPV has a capacity of ~100 kbp which would allow fit all of the genes of the CHIKV plasmids and is currently the most commonly used baculovirus for foreign gene expression. Therefore, it would have been obvious to place the Chikungunya (a mosquito-borne virus) and a reporter gene encoded by the plasmid of Colunga-Saucedo within a AcMNPV baculovirus transfer vector to examine mosquito-pathogen interactions in a mosquito cell as AcMNPV baculovirus transduction efficiencies were around 3-4x better than when using a plasmid and showed higher transgene expression.
Regarding the hr1pag1 promoter, Lin identifies it as a known promoter for driving expression of genes in mosquito cells and successfully reduces to practice that it can be used to drive expression of a viral protein encoded in a baculovirus (Figures 1-2). Therefore, it would have been obvious to one of ordinary skill that they could use the hr1pag1 promoter to drive expression of the Chikungunya structural proteins in a mosquito cell.
Therefore, there is a clear scientific rationale for modifying the plasmid of Colunga-Saucedo based on the teachings of Varrikodan, Naik, and Lin to generate a baculovirus encoding the Chikungunya genes and a reporter gene as identified by the Colunga-Saucedo as AcMNPV baculovirus transduction efficiencies were around 3-4x better than when using a plasmid and showed higher transgene expression and to use the hr1pag1 promoter.
Furthermore, Applicant argues that a determination of obviousness must consider not only the subject matter literally recited in the claims, but also the inherent properties of the claimed invention. Accordingly, the Examiner is reminded that it is impermissible to pick and choose from any one reference only so much of it as will support a given position. Thus, the Examiner's assertion that it would have been obvious to replace the plasmid transfer vectors disclosed in Colunga-Saucedo with an AcMNPV baculovirus transfer vector, and that the combined teachings of Colunga-Saucedo, Varikkodan, Naik, and Lin are capable of producing a Chikungunya virus-like replicon particle in a mosquito cell, is based on an improper selective extraction of isolated elements from the cited references and a failure to consider the claimed invention as a whole, and therefore constitutes impermissible hindsight based on Applicant's disclosure. Applicant cites to the declaration in which Dr. Lin explained that the present invention employs a deliberate genetic engineering strategy involving selected promoters with defined strength and positioning in a recombinant baculovirus. This configuration in the recombinant baculovirus achieves controlled expression balance for efficient VRP production, minimizes CPE in mosquito cells, and provides a technical advantage not taught or suggested by the cited references. These interrelated features are integral to the claimed invention as a whole, yet were not evaluated in the Examiner's analysis (page 9, paragraphs 1-3).
Applicant's arguments have been fully considered but they are not persuasive.
As an initial matter, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a balance of efficient VRP production and reducing CPE in mosquito cells) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In response to applicant's argument that the combined teachings of Colunga-Saucedo, Varrikodan, Naik, and Lin do not identify a reduction of CPE in mosquito cells as a technical advantage, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
As stated in the rejection above, Colunga-Saucedo identifies that their plasmids encoding the full length genome are useful in examining virology of the Chikungunya virus, as well as for developing antivirals while Naik specifically identifies that their baculovirus transfer system is useful for studying mosquito-borne viruses, such as Chikungunya, and mosquito-pathogen interactions (abstract). Furthermore, Naik reduces to practice that viral genes can be expressed in their baculoviral transfer system (influenza virus neuroaminidase) and Varikkodan successfully reduces to practice that recombinant baculoviruses can express the Chikungunya structural proteins (Capsid and E3-E2-6K-E1), the Chikungunya nonstructural proteins 1-4 and a reporter gene (EGFP under the control of a subgenomic promoter). Additionally, Naik teaches that flow cytometry revealed that plasmid transfection efficiencies in mosquito cells were around 15–20%, while baculovirus transduction efficiencies were around 60% and relative transgene expression levels were significantly higher by baculovirus transduction than plasmid DNA transfection. Furthermore, Naik identifies that AcMNPV has a capacity of ~100 kbp which would allow fit all of the genes of the CHIKV plasmids and is currently the most commonly used baculovirus for foreign gene expression. Therefore, it would have been obvious to place the Chikungunya (a mosquito-borne virus) and a reporter gene encoded by the plasmid of Colunga-Saucedo within a AcMNPV baculovirus transfer vector to examine mosquito-pathogen interactions in a mosquito cell as AcMNPV baculovirus transduction efficiencies were around 3-4x better than when using a plasmid and showed higher transgene expression.
Furthermore, regarding the Applicant’s argument that the rejection is based on an improper selective extraction of isolated elements from the cited references and a failure to consider the claimed invention as a whole, Applicant has not identified any aspect of the cited prior art that was selectively extracted. Therefore, it is not clear what Applicant considers to be the selectively extracted information that would be at issue.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEENAN A BATES whose telephone number is (571)270-0727. The examiner can normally be reached M-F 7:30-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Doug Schultz can be reached at (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KEENAN A BATES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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