DETAILED ACTION
Final Rejection
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election of Group I (claims 1-11) in the reply filed on 04/19/2024 is acknowledged.
Species election:
For the first election regarding claim 1 drawn to an immunogenic composition comprising a chimeric gene comprising at least one nucleic acid sequence encoding for a sequence having at least 80% sequence homology with any one or more of SEQ ID NOS. 1-101, and any combination thereof, applicant elects SEQ TD NO: 5.
For the second election regarding the immunogenic compositions of claim 2, applicant elects a combination of SEQ TD NOS. 5, 37, 62, and 100.
For the third election regarding claims 6-7 drawn to immunogenic composition as related to use of a vector, applicant elects the bovine parainfluenza virus type 3 genotype c (BPIV3c) vector.
For the fourth election regarding claim 8 drawn to immunogenic composition, applicant elects SEQ ID NO: 103.
For the fifth election regarding claim 10 drawn to immunogenic composition comprising an antigen from another disease-causing organism, applicant elects Japanese Encephalitis Virus.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Status of Claims
3. Claims 1, 3-4 and 8-11 are pending as per claim listing filed dated 01/02/2026.
4. Claims 2, 5-7 and 12-15 are cancelled by the applicant.
5. Claims 1, 3-4 and 8-11 are under examination in this office action.
Information Disclosure Statement
6. The information disclosure statement (IDS) submitted on 09/22/2022 and 05/23/2025 is in compliance with the provisions of 37 CFR 1.97 and is being considered by the examiner.
Claim Rejections - 35 USC § 112, First Paragraph
7. 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.
8. Claims 1, 3-4 and 8-11 are 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 and additionally constitutes new matter. 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. This is a written description rejection.
The Instant claim 1 and dependent claims 3-4 and 8-11 requires an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3Vc) vector to comprise or clone or introduce chimeric genes comprising at least two nucleic acid sequences with each encoding for a sequence having at least 80% sequence homology with any one or more of SEQ ID NOS: 1-101, and any combination thereof.
The specification para [0015], [0023], [0031], [0056], [0107] recites, the vector is an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c). Para [0031] recites in still other forms, the multicistronic cassette utilizes an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) as the vector. Para [0056] recites preferred vectors for the expression of polypeptides of the disclosure include an attenuated bovine parainfluenza virus type 3genotype 3C (BPIV3C). Para [0107] the term "transfected into a viral vector" means and is used as a synonym for "introducing" or "cloning" a heterologous DNA sequence encoding a desired antigen into a viral vector, such as for example into an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c).
When a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed. However, the presence of multiple species within a claimed genus does not necessarily demonstrate possession of the genus. See, In re Smyth, 178 U.S.P.Q. 279 at 284-85 (CCPA 1973) (stating “where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus or combination claimed at a later date in the prosecution of a patent application.”); and University of California v. Eli Lilly and Co., 43 USPQ2d 1398, at 1405 (Fed Cir 1997)(citing Smyth for support).
The applicable standard for the written description requirement can be found in MPEP§ 2163; University of California v. Eli Lilly, 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. v. Gen-Probe Inc., 63 USPQ2d 1609; Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111; and University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 (CAFC 2004). To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. In the instant case, there are no structural features recited or provided in the specification except that “the vector is an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c)”. There is no disclosure of structure, sequence (nucleotide and or amino acid), or physical properties of the starting material (parent virus sequence) or the finished material the attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c). Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus. The instant claims encompass an infinite genus of BPI3Vc viruses or attenuated BPI3Vc viruses that could be identical to any unidentified BPI3Vc viruses parental sequence starting material and sequence variants.
Amgen Inc. vs Sanofi (2017-1480, Fed Cir, 2017) states that "an adequate written description must contain enough information about the actual makeup of the claim products - a precise definition such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other material," which may be present in "function "terminology "when the art has established a correlation between structure and function" (page 17,1st paragraph).
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description” Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, Fri. January 5, 2001, see especially page 1106 column 3). In the instant case, the specification does not provide adequate written description of an or the attenuated BPI3Vc virus. The legal standard for sufficiency of a patent's (or a specification’s) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the claimed subject matter", Vas-Cath, Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the applicant had possession at the time of invention of the claimed invention. The full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
9. Claims 1, 3-4 and 8-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a genus an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector, does not reasonably provide enablement for a species or strain of an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including the nature of the invention, the state of the prior art, the breadth of the claims, the amount of guidance in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, and the quantity of experimentation necessary. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention: The claims are drawn to an immunogenic composition, inter alia, comprising a chimeric gene inserted into an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector.
State of the prior art: At the time the invention was made, it was known that a vaccine based on a host range-attenuated bovine parainfluenza virus type 3 (BPIV3) vector backbone, for mucosal immunization in rhesus monkeys, expressing G and F major protective antigens of RSV placed under the control of human PIV3 transcription signals and inserted individually or in homologous pairs as supernumerary genes in the promoter proximal position of rBPIV3/HPIV3. The level of replication of rBPIV3/HPIV3-RSV chimeric viruses in the respiratory tract of rhesus monkeys was similar to that of their parent virus rBPIV3/HPIV3, and each of the chimeras induced a robust immune response to both RSV and HPIV3 (Schmidt et al 2002, J Virol. 2002 Feb;76(3):1089-99). It was also know that Bovine Parainfluenza Virus Type 3 (BPIV3) Fusion and Hemagglutinin-Neuraminidase Glycoproteins make an important contribution to the restricted replication of BPIV3 in primates (Schmidt et al 2000, J Virol. 2000 Oct;74(19):8922-9). It was also known that Haller et al 2003 has developed a Bovine parainfluenza virus type 3 (bPIV3) expressing the RSV attachment and fusion proteins that protects hamsters from challenge with human PIV3 and RSV (Journal of Virology, Volume 84, Issue 8).
The instant application is directed to immunogenic composition for African Swine Fever virus wherein an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector comprise and is expected to express the immunogenic antigen(s) of African Swine Fever virus with an intended species for immunization as a porcine species or Swine. The prior art does not provide viral genetic markers for attenuation of BPIV3c genotype vector for a porcine species or swine.
Breadth of the claims: The claims are very broad, encompassing a genus of an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector.
Working examples: No working example is disclosed in the specification showing an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector comprising a chimeric gene(s) encoding sequences for immunogenic antigens.
Guidance in the specification: The specification provides little guidance regarding making of the claimed method. The specification recites in para [0015], [0023], [0031], [0056], [0107] recites, the vector is an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c). Para [0031] recites in still other forms, the multicistronic cassette utilizes an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) as the vector. Para [0056] recites preferred vectors for the expression of polypeptides of the disclosure include an attenuated bovine parainfluenza virus type 3genotype 3C (BPIV3C). Para [0107] the term "transfected into a viral vector" means and is used as a synonym for "introducing" or "cloning" a heterologous DNA sequence encoding a desired antigen into a viral vector, such as for example into an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c).
Predictability of the art: Based on the specification provided in the application and available prior art an unpredictable amount of research and efforts are required to arrive at the claimed inventions.
Amount of experimentation: In absence of recitation of viral genetic markers, amino acid mutations in gene or mutations in viral genetic regulatory element of bovine parainfluenza virus type 3 genotype c (BPIV3c) to show attenuated phenotype in a porcine species or swine an undue amount of experimentation would be required to make an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector for its use in swine as a viral vector for expression of chimeric gene encoding ASFV immunogenic antigens or sequences.
Given the breadth of the claims, the lack of guidance in the specification, and the lack of predictability of the art, it would require an undue amount of experimentation for one skilled in the art to make the claimed composition to arrive at the instant claims 1, 3-4 and 8-11.
Response to Arguments 35 U.S.C. 112(a) Rejections
Applicant's arguments regarding rejections under 35 U.S.C. 112(a) filed on 01/02/2026 have been fully considered but they are not persuasive for the following reasons:
Applicant’s argument 1: Claims 1, 3-4 and 8-11 were rejected under 35 USC 112(a) or 35 USC 112 (pre-AIA ), first paragraph, as allegedly failing to comply with the written description requirement and additionally constituting new matter. Specifically, it was alleged that the specification failed provide sufficient written description for an attenuated BPIV3c vector including a lack of identifying characteristics for the same.
Applicants respectfully traverse this rejection and provide the following support for this position. First, the application expressly identifies an attenuated BPIV3c vector (see, Specification as filed, paragraphs [0015], [0023], [0031], [0056], and [0107]). At the time of filing, complete, annotated genome sequences of multiple BPIV3 genotype C isolates were publicly available, providing concrete structural identification of the genus. For example, Neill JD, Ridpath JF, Valayudhan BT., "Identification and genome characterization of genotype B and genotype C bovine parainfluenza type 3 viruses isolated in the United States," BMC Veterinary Research (2015) identified the genotypes in the Abstract. Further, Table 2 ("Viruses used in this study") lists genotype C isolates TVMDL16 (GenBank KJ647285) and TVMDL20 (GenBank KJ647287) with complete genome lengths. Figure 1 (phylogenetic tree) showed genotype C clustering and Table 4 (neutralization) evidenced antigenic differences across genotypes (e.g., titer against SF-4 vs. genotype C). The accompanying GenBank records (of record) for TVMDL16 (KJ647285.1) and TVMDL20 (KJ647287.1) include complete annotations for N, P/C/V, M, F, HN, and L genes and coding sequences, thereby providing the "actual makeup" of genotype C backbones needed for vector construction. Accordingly, those of skill in the art were well aware of the BPIV3c genome and the details of the genome were publicly available.
Established reverse genetics enabled construction and rescue of recombinant BPIV3 vectors from cDNA prior to filing (Haller 2000; Haller 2003; Liang 2014). These known methods, coupled with public BPIV3c genome sequences, constitute "relevant identifying characteristics" (MPEP § 2163) sufficient to convey possession of a BPIV3c vector genus as claimed. The claimed chimeric ASFV gene is supported by the provided SEQ ID NOS and identity thresholds; representative ASFV sequences aligning to elected species are documented in the Office Action (see alignments to Mwangi/Borca). Collectively, the specification, in view of the state of the art at filing, reasonably conveys possession of the claimed subject matter.
For all of the foregoing reasons, Applicants assert that this rejection should be withdrawn.
In Response 1: The claim instant claim 1 and dependent claims are directed to an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector comprising the chimeric genes encoding ASFC antigens. The instant specification recites prior arts on BPIV3 or wild type BPIV3c nucleic acid sequences and complete annotation of genes and coding sequences the backbone needed to develop vector construction. However, the specification does not provide a written description for reduction to practice of an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c). The attenuation of a virus (e.g. BPIV3c) depends on require achieving a balance in (i) reduced infectivity and pathogenicity to the target host (e.g pigs), and (ii) efficient replication ability in the target host (e.g. pig) to induce an efficient immune response against the chimeric ASFV antigens encoded by the attenuated BPIV3c to confer the protection. Attenuation can be determined by modifications in coding genes and non-coding regulator sequences (regulation of replication and gene transcription/expression of the BPIV3c backbone). The BPIV3c genome sequences on record that are recited in the specification are not reduced to the product or composition for practice by producing attenuated BPIV3c vector for the target animal species and different age group of the species (e.g. pigs). Based on the specification by reciting the prior arts on record the applicant provides a written description for a genus BPIV3c but fails to provide a written description for a species of attenuated BPIV3c vector. The BPIV3c genome sequences vary among strains and therefore reduction to the practice using a particular BPIV3c as a vector would show possession of the invention at the species level. Applicant does not provide an attenuated BPIV3c vector construct a sequence in the specification. In addition, the annotation and in silico design of a BPIV3c vector construct is not necessarily meet the requirement of an intended attenuated BPIV3c vector backbone unless it is reduced to practice demonstrating as actually attenuated in a species of anima (e.g. pig) for use as a vaccine vector. As recited supra in the office action, Wang et al 2015 evaluated safety of inoculation of bovine parainfluenza virus 3 as potential vaccine vector in pigs and found that virus-inoculated pigs displayed few observable clinical signs related to respiratory diseases (See, above and refer Want et al 2015, Virusdisease, 2015 Jun;26(1-2):89-91).
Amgen Inc. vs Sanofi (2017-1480, Fed Cir, 2017) states that "an adequate written description must contain enough information about the actual makeup of the claim products - a precise definition such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other material," which may be present in "function "terminology "when the art has established a correlation between structure and function"
Therefore, the claim 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, at the time the application was filed, had possession of the claimed invention.
Therefore, the rejection of claims 1, 3-4 and 8-11 under 35 USC 112(a) for written description requirement as recited supra is maintained.
Applicant’s argument 2: Claims 1, 3-4, and 8-11 were rejected under 35 U.S.C. 112(a) for lacking enablement for a species or strain of an attenuated BPIV3c vector commensurate in scope with the claims.
Applicants respectfully disagree and traverse this rejection. In support of Applicant's position, Applicants note that the nature of the invention is a recombinant PIV3 vector platform expressing ASFV antigens. The state of the art provides infectious cDNA clones and rescue of BPIV3 vectors (Haller 2000); attenuation via L substitutions and polygenic determinants (Haller 2001; Skiadopoulos 2003); and insert-position impact on expression/attenuation (Liang 2014); porcine permissivity (Wang 2015). As noted above, BPIV3c genomes were already known (TVMDL16 and TVMDL20 (Neill 2015; Table 2; GenBank KJ647285.1 and KJ647287.1)). Applicants assert that a person of skill in the art would use the publicly known BPIV3c sequences to build an antigenomic cDNA, select an insert position guided by PIV3 literature (e.g., pre-N vs. N-P), engineer standard 2A linkers between ASFV sequences as described in the specification as filed, and implement known attenuation strategies, followed by routine testing. Such vector engineering, and well within the ordinary skill in the art and is thus not undue experimentation. With specific reference to the enablement of a "species or strain of attenuated BPIV3c", Applicants assert this issue is addressed by (i) the public availability of specific BPIV3c genomes (species/strain-level sequences) and (ii) known approaches to impart attenuation (e.g., L gene ts substitutions) using reverse genetics (Haller 2001; Haller 2000).
For all of the foregoing reasons, Applicants assert that this rejection should be withdrawn.
In Response 2: “Undue” experimentation burden: Making of an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector species puts an undue burden of experimentation on one of the ordinary skills in the art and the burden is achieving a right balance in attenuation and replication of the intended attenuated BPIV3c vector species that would require genome manipulation in laboratory and testing in animal species of different ages (e.g., adult pigs, baby pig). The reason is that the instant specification recites prior arts on BPIV3 or wild type BPIV3c nucleic acid sequences and complete annotation of genes and coding sequences the backbone needed to develop vector construction. However, the specification does not provide a written description for reduction to practice of an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector. The attenuation of a virus (e.g. BPIV3c) depends on and require achieving a balance in (i) reduced infectivity and pathogenicity to the target host for different age groups (e.g., adult pigs, baby pig), and (ii) a reasonable or efficient replication ability in the target host (e.g. pig) to induce an effective and efficient immune response against the chimeric ASFV antigens encoded by the attenuated BPIV3c to confer the protection. Attenuation can be achieved by modifications in coding genes (amino acid mutations/substitution) and nucleotide sequences in non-coding regulatory sequences (regulation of replication and gene transcription/expression of the BPIV3c backbone). The BPIV3c genome sequences on record that are recited in the specification are not reduced to the product or composition for practice at a species level by producing attenuated BPIV3c vector for the target animal species and different age group of the species (e.g., adult pigs, baby pig). Based on the specification by reciting the prior arts on record the applicant provides a written description for a genus BPIV3c but fails to provide a written description for a species of attenuated BPIV3c vector that is reduced to the actual practice of the invention, a make and use requirement for enablement. The BPIV3c genome sequences vary among strains and therefore reduction to the practice of a particular BPIV3c virus as an attenuated BPIV3c vector would show possession of the invention at the species level. Applicant does not provide an attenuated BPIV3c vector construct a sequence in the specification. In addition, the annotation and in silico design of a BPIV3c vector construct is not necessarily meet the requirement of an intended attenuated BPIV3c vector backbone unless it is reduced to practice demonstrating as actually attenuated in a species of anima (e.g. adult pig, baby pig) for use as a vaccine vector. As recited supra in the office action, Wang et al 2015 evaluated safety of inoculation of bovine parainfluenza virus 3 (the wild type virus) as potential vaccine vector in pigs and found that virus-inoculated pigs displayed few observable clinical signs related to respiratory diseases (See, above and refer Want et al 2015, Virusdisease, 2015 Jun;26(1-2):89-91). Therefore, the claim and specification contain subject matter which was not enabled for a species or strain of an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector at the time the application was filed.
In Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Supreme Court, held that claims drawn to a genus of monoclonal antibodies, which were functionally claimed by their ability to bind to a specific protein, PCSK9, were invalid due to lack of enablement. The claims at issue were functional, in that they defined the genus by its function (the ability to bind to specific residues of PCSK9) as opposed to reciting a specific structure (the amino acid sequence of the antibodies in the genus). The Supreme Court concluded that the patents at issue failed to adequately enable the full scope of the genus of antibodies that performed the function of binding to specific amino acid residues on PCSK9 and blocking the binding of PCSK9 to a particular cholesterol receptor, LDLR. See, MPEP 2164.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.” Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). See, See, MPEP 2164, 2164.01(a).
Therefore, the rejection of claims 1, 3-4 and 8-11 under 35 USC 112(a) for lack of enablement as recited supra.
Claim Rejections - 35 USC § 103
10. 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.
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.
11. Claims 1, 3-4, 8 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Crosby et al 2017 (published in Journal of Virology, volume 91 (2), pages 1-12), and further in view of Mwangi et al (WO2017096341A2, published 08 June 2017, with a priority to application US 62/263,424 filed on 04 December 2015), Borca et al (US9463234B2, published 11 October 2016), Liu et al 2017 (Sci Rep. 2017 May 19;7(1):2193), Liu et al 2016 (Virus Research 222 (2016) 34–40), Lokhandwala et al 2017 (PLoS One. 2017 May 8;12(5):e0177007), and Haller et al 2003 (Journal of Virology, Volume 84, Issue 8), Neill et al 2015 (BMC Veterinary Research (2015) 11:112), Wang et al 2015 (Virus Disease. 2015 Jun;26(1-2):89-91), Haller et al 2000 (Journal of Virology, 2000, Vol. 74, No. 24, p. 11626-11635), Skiadopoulos et al 2003 (Journal of Virology, 2003, Vol. 77, No. 2, p.1141-1148), Bailly et al 2000 (Virus Genes 20:2, 173-182, 2000), Haller et al 2001 (Virology 2001, 288, 342-350) and Liang et al 2014 (Journal of Virology, vol 88 (8), p. 4237–4250).
Claims 1 and 3: An immunogenic composition comprising a chimeric gene inserted into an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector or a single cycle replicon adenovirus, wherein said chimeric gene comprises at least two nucleic acid sequences with each encoding for a sequence having at least 80% sequence homology with any one or more of SEQ ID NOs: 1-101, and any combination thereof (claim 1 limitations); and the added limitation of claim 3, wherein said chimeric gene includes a self-cleaving peptide linker between each of the at least two nucleic acid sequences (Claim 3 limitation).
Prior Arts on Single-cycle Replicon Adenovirus Vector
Crosby et al 2017 is in the art and disclose immunogenic composition comprising a single-cycle replicon adenovirus vector (SC-Ad) expressing influenza A virus HA protein and induce amplified or enhanced immune response against HA protein (See, Crosby et al 2017, abstract, page 4-figure 1).
Crosby et al 2017 do not teach instant claim 1 limitation wherein said chimeric gene comprises at least two nucleic acid sequences with each encoding for a sequence having at least 80% sequence homology with any one or more of SEQ ID NOS: 1-101, and any combination thereof.
Mwangi et al 2017 is in the adenovirus-vectored multivalent vaccine art and disclose an immunogenic composition (a vaccine) comprising an ASFV chimeric gene as a multivalent vaccine expressed by an adenovirus-vector (See, page 9, lines 15-21; page 6, Brief description of sequences, lines 31-33 and page 7, lines 4-5), wherein antigenic proteins or fragments of ASFV chimeric gene are fused in-frame to generate chimeric proteins. Given is an example of a nucleic acid sequence of p32 of ASFV fused to ASFV p17 and p12 to generate an antigenic chimera in context to the SEQ ID Nos: 1-2 or 9-12 of Mwangi et al (WO2017096341A2). Mwangi et al teaches the instant claim 1 elected species SEQ ID NO: 5 by disclosing a nucleotide sequence that has 99.8% identity/similarity with sequence encoded in instant claim 1 SEQ ID NO:5. The alignment of the sequences is shown below as, Instant SEQ ID NO:5 is shown as Qy that matches at 99.7% with Mwangi et al WO2017096341A2, SEQ ID NO:5 available in the database sequence.
PCT-US16-64880-5
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
Sequence 5, PC/TUS1664880
GENERAL INFORMATION
APPLICANT: THE TEXAS A&M UNIVERSITY SYSTEM
TITLE OF INVENTION: ADENOVIRUS-VECTORED MULTIVALENT VACCINE
FILE REFERENCE: TAM.135XPCT
CURRENT APPLICATION NUMBER: PCT/US16,64880
CURRENT FILING DATE: 2016-12-05
NUMBER OF SEQ ID NOS: 22
SEQ ID NO 5
LENGTH: 1668
TYPE: DNA
ORGANISM: African swine fever virus
FEATURE:
NAME/KEY: CDS
LOCATION: (1)..(1665)
Alignment Scores:
Length: 1668
Score: 2802.00 Matches: 528
Percent Similarity: 99.8% Conservative: 0
Best Local Similarity: 99.8% Mismatches: 1
Query Match: 99.7% Indels: 0
Gaps: 0
US-17-309-272-5 (1-530) x PCT-US16-64880-5 (1-1668)
Qy 2 ProSerAsnMetLysGlnPheCysLysIleSerValTrpLeuGlnGlnHisAspProAsp 21
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 52 CCCTCCAACATGAAGCAGTTCTGTAAAATCTCTGTCTGGCTCCAGCAGCACGACCCCGAC 111
Qy 22 LeuLeuGluIleIleAsnAsnLeuCysMetLeuGlyAsnLeuSerAlaAlaLysTyrLys 41
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 112 CTCCTCGAAATTATCAACAATCTCTGCATGCTCGGAAATCTGAGCGCCGCTAAGTACAAA 171
Qy 42 HisGlyValThrPheIleTyrProLysGlnAlaLysIleArgAspGluIleLysLysHis 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 172 CACGGCGTGACCTTCATCTATCCCAAGCAGGCCAAAATCCGGGACGAGATTAAGAAACAT 231
Qy 62 AlaTyrSerAsnAspProSerGlnAlaIleLysThrLeuGluSerLeuIleLeuProPhe 81
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 232 GCCTACTCTAACGATCCCAGCCAGGCTATCAAGACCCTGGAGTCCCTCATCCTGCCTTTT 291
Qy 82 TyrIleProThrProAlaGluPheThrGlyGluIleGlySerTyrThrGlyValLysLeu 101
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 292 TACATTCCTACACCAGCTGAGTTCACCGGAGAGATTGGCTCTTATACCGGGGTGAAACTG 351
Qy 102 GluValGluLysThrGluAlaAsnLysValIleLeuLysAsnGlyGluAlaValLeuVal 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 352 GAGGTCGAAAAGACAGAAGCCAACAAAGTGATCCTGAAGAACGGAGAGGCTGTGCTCGTC 411
Qy 122 ProAlaAlaAspPheLysProPheProAspArgArgLeuAlaValTrpIleMetGluSer 141
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 412 CCTGCCGCTGACTTCAAGCCCTTTCCTGATCGCCGGCTGGCCGTGTGGATCATGGAATCT 471
Qy 142 GlySerMetProLeuGluGlyProProTyrLysArgLysLysGluGlyGlyGlyAsnAsp 161
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 472 GGGAGCATGCCACTGGAGGGACCCCCTTACAAAAGAAAGAAAGAGGGAGGAGGAAACGAC 531
Qy 162 ProProValProLysHisIleSerProTyrThrProArgThrArgIleAlaIleGluVal 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 532 CCACCCGTGCCCAAGCACATCTCTCCATATACCCCCAGGACAAGAATCGCCATTGAGGTG 591
Qy 182 GluLysAlaPheAspAspCysMetArgGlnAsnTrpCysSerValAsnAsnProTyrLeu 201
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 592 GAAAAGGCTTTCGACGATTGCATGCGCCAGAATTGGTGTTCCGTGAACAATCCTTACCTG 651
Qy 202 AlaLysSerValSerLeuLeuSerPheLeuSerLeuAsnHisProThrGluPheIleLys 221
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 652 GCCAAATCCGTCTCTCTGCTCAGCTTTCTCTCCCTGAACCACCCAACCGAGTTCATCAAG 711
Qy 222 ValLeuProLeuIleAspPheAspProLeuValThrPheTyrLeuLeuLeuGluProTyr 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 712 GTGCTCCCCCTGATTGACTTCGATCCTCTGGTCACCTTTTACCTGCTCCTGGAACCCTAT 771
Qy 242 LysThrHisGlyAspAspPheLeuIleProGluThrIleLeuPheGlyProThrGlyTrp 261
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 772 AAGACACACGGCGACGATTTTCTGATCCCTGAGACCATTCTCTTCGGGCCAACAGGATGG 831
Qy 262 AsnGlyThrAspLeuTyrGlnSerAlaMetLeuGluPheLysLysPhePheThrGlnIle 281
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 832 AACGGCACCGACCTGTACCAGAGCGCCATGCTGGAGTTCAAGAAATTCTTTACCCAGATT 891
Qy 282 ThrArgGlnThrPheMetAspIleAlaAspSerAlaThrLysGluValAspValProIle 301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 892 ACACGGCAGACCTTCATGGACATCGCCGATTCCGCTACCAAAGAAGTGGACGTGCCAATT 951
Qy 302 CysTyrSerAspProGluThrValHisSerTyrAlaAsnHisValArgThrGluIleLeu 321
||||||||||||||||||||||||||||||||| ||||||||||||||||||||||||
Db 952 TGCTACTCCGATCCCGAGACAGTGCACTCTTATACCAATCATGTCAGGACAGAGATCCTG 1011
Qy 322 HisHisAsnAlaValAsnLysValThrThrProAsnLeuValValGlnAlaTyrAsnGlu 341
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1012 CACCATAACGCCGTGAATAAGGTCACCACACCCAACCTGGTGGTCCAGGCTTACAATGAG 1071
Qy 342 LeuGluGlnThrAsnThrIleArgHisTyrGlyProIlePheProGluSerThrIleAsn 361
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1072 CTGGAACAGACCAACACAATCAGACACTATGGCCCTATTTTTCCAGAAAGCACCATCAAC 1131
Qy 362 AlaLeuArgPheTrpLysLysLeuTrpGlnAspGluGlnArgPheValIleHisGlyLeu 381
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1132 GCCCTGCGCTTCTGGAAGAAACTCTGGCAGGACGAGCAGCGGTTCGTGATCCACGGGCTG 1191
Qy 382 HisArgThrLeuMetAspGlnProThrTyrGluThrSerGluPheAlaGluIleValArg 401
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1192 CATAGGACCCTCATGGATCAGCCTACATACGAGACCTCTGAATTTGCCGAGATCGTGCGC 1251
Qy 402 AsnLeuArgPheSerArgProGlyAsnAsnTyrIleAsnGluLeuAsnIleThrSerPro 421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1252 AACCTGCGGTTCAGCAGGCCAGGAAACAATTACATCAACGAGCTGAATATTACCAGCCCC 1311
Qy 422 AlaMetTyrGlyAspLysHisThrThrGlyAspIleAlaProAsnAspArgPheAlaMet 441
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1312 GCCATGTATGGCGACAAGCACACCACAGGGGACATCGCTCCAAATGATCGGTTCGCCATG 1371
Qy 442 LeuValAlaPheIleAsnSerThrAspPheLeuTyrThrAlaIleProGluGluLysVal 461
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1372 CTGGTGGCTTTTATTAACTCCACCGACTTCCTGTATACAGCCATCCCCGAGGAAAAAGTG 1431
Qy 462 GlyGlyAsnGluThrGlnThrSerSerLeuThrAspLeuValProThrArgLeuHisSer 481
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1432 GGCGGGAACGAGACCCAGACAAGCTCCCTCACCGATCTGGTCCCTACAAGGCTGCACAGC 1491
Qy 482 PheLeuAsnHisAsnLeuSerLysLeuLysIleLeuAsnArgAlaGlnGlnThrValArg 501
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1492 TTCCTCAACCATAATCTCTCCAAGCTGAAAATTCTCAATAGAGCCCAGCAGACCGTGCGC 1551
Qy 502 AsnIleLeuSerAsnAspCysLeuAsnGlnLeuLysHisTyrValLysHisThrGlyLys 521
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1552 AACATCCTGTCCAATGACTGTCTGAACCAGCTCAAGCACTACGTCAAACATACCGGGAAG 1611
Qy 522 AsnGluIleLeuLysLeuLeuGlnGlu 530
|||||||||||||||||||||||||||
Db 1612 AACGAAATCCTGAAACTCCTGCAGGAG 1638
Borca et al 2016 (US9463234B2) is in a vaccine art and teaches instant claim 1, SEQ ID NO: 37 (Qy) by disclosing 100% identity with SEQ ID NO 3 (Database) as disclosed by Borca et al (US9463234B2).
RESULT 8
US-14-495-540A-3/c
Sequence 3, US/14495540A
Patent No. 9463234
GENERAL INFORMATION
APPLICANT: Borca, Manuel V.
APPLICANT: Holinka-Patterson, Lauren G.
APPLICANT: Gladue, Douglas
APPLICANT: Risatti, Guillermo R.
APPLICANT: O'Donnell, Vivian K.
TITLE OF INVENTION: Attenuated African Swine Fever Virus Strain Induces Protection Against Challenge With Homologous Virulent Parental Virus Georgia
TITLE OF INVENTION: 2007 Isolate
FILE REFERENCE: DN 122.14
CURRENT APPLICATION NUMBER: US/14/495,540A
CURRENT FILING DATE: 2014-09-24
NUMBER OF SEQ ID NOS: 24
SEQ ID NO 3
LENGTH: 191496
TYPE: DNA
ORGANISM: African swine fever virus
Alignment Scores:
Length: 191496
Score: 1866.00 Matches: 354
Percent Similarity: 100.0% Conservative: 0
Best Local Similarity: 100.0% Mismatches: 0
Query Match: 100.0% Indels: 0
Gaps: 0
US-17-309-272-37 (1-354) x US-14-495-540A-3 (1-191496)
Qy 1 MetAlaLeuThrThrHisSerGlyLysLeuIleProGluLeuGlnPheLysAlaHisHis 20
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102829 ATGGCCCTAACGACCCATTCAGGGAAGCTAATTCCTGAACTACAGTTCAAAGCACATCAT 102770
Qy 21 PheIleAspLysThrThrValLeuTyrGlyProSerLysThrGlyLysThrValTyrVal 40
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102769 TTTATAGATAAAACAACTGTGCTATATGGCCCCTCAAAAACAGGCAAAACCGTGTACGTT 102710
Qy 41 LysHisIleMetLysIleLeuGlnProHisIleGluGlnIleLeuValValAlaProSer 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102709 AAACATATTATGAAAATCCTGCAACCCCATATTGAACAAATTTTAGTGGTTGCCCCCTCG 102650
Qy 61 GluProSerAsnArgSerTyrGluGlyPheValHisProThrLeuIleHisTyrArgLeu 80
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102649 GAACCCTCAAATCGTTCATATGAGGGTTTTGTACATCCAACTCTAATACACTACCGCTTG 102590
Qy 81 TrpLeuAlaAspLysGlnLysLysAsnAspAsnLysGlyAlaGluArgPheLeuGluAla 100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102589 TGGCTCGCCGATAAGCAAAAAAAAAATGACAACAAGGGCGCTGAACGCTTTTTGGAGGCC 102530
Qy 101 IleTrpGlnArgGlnThrMetMetSerSerIleTyrSerArgValAsnAsnIleAspMet 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102529 ATCTGGCAGCGGCAAACTATGATGTCCTCCATCTACAGTCGAGTAAACAACATCGATATG 102470
Qy 121 LeuLysThrLeuTyrHisLysLeuProIleAspIleGlnGlnLysGluAsnLysAsnIle 140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102469 CTAAAAACATTGTATCATAAACTTCCGATCGATATACAGCAAAAGGAAAACAAAAATATT 102410
Qy 141 AlaLysValGluCysLeuLysAlaGluGlnThrAspGlnLysLysGluGluLysIleThr 160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102409 GCAAAAGTGGAGTGCTTAAAGGCTGAACAAACGGACCAAAAAAAAGAAGAAAAGATTACA 102350
Qy 161 SerLeuTyrGlnGlnLeuLeuLysLysIleIleIleGlnAsnIleHisMetTyrLysAsn 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102349 TCGCTTTATCAGCAACTTTTAAAAAAAATTATTATACAGAACATTCATATGTATAAAAAC 102290
Qy 181 LeuCysLeuThrGluAspGluLysPheThrLeuAsnTyrIleAsnLeuAsnProArgLeu 200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102289 TTATGCCTTACAGAGGATGAAAAGTTTACGTTAAACTATATCAATCTTAATCCTCGTTTA 102230
Qy 201 LeuLeuIleLeuAspAspCysAlaAlaGluLeuHisProLeuPheThrLysGluIlePhe 220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102229 CTTTTAATATTAGACGACTGCGCGGCCGAACTGCACCCATTATTTACAAAAGAAATTTTT 102170
Qy 221 LysLysPhePheTyrGlnAsnArgHisCysPheIleSerMetIleIleCysCysGlnAsp 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102169 AAAAAGTTTTTTTACCAAAATCGTCACTGTTTTATTTCGATGATTATTTGCTGCCAAGAT 102110
Qy 241 AspThrAspLeuProAlaAsnLeuArgLysAsnAlaPheValSerIlePheThrAsnAla 260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102109 GATACCGATTTACCCGCCAATCTTCGTAAAAACGCATTTGTTTCCATTTTTACAAATGCC 102050
Qy 261 SerIleCysMetSerAsnPheSerArgGlnSerAsnArgTyrSerLysGlnAspLysGlu 280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 102049 TCTATTTGTATGTCGAATTTTTCCCGTCAAAGCAACCGCTATTCCAAACAGGATAAGGAG 101990
Qy 281 TyrValGluGluIleSerHisIleValPheLysGlyTyrArgLysLeuValTyrIleArg 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 101989 TATGTGGAAGAAATTAGCCATATTGTGTTTAAAGGATATAGGAAACTTGTGTACATCCGC 101930
Qy 301 GluAspGluHisArgGlnHisPheTyrHisSerThrValProLeuProThrAlaPheSer 320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 101929 GAGGATGAACATCGGCAACATTTTTACCATAGTACAGTGCCGCTTCCCACTGCCTTCAGC 101870
Qy 321 PheGlySerLysAlaLeuLeuLysLeuCysLysAlaValTyrSerLysGluValValIle 340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 101869 TTTGGCTCTAAAGCATTATTAAAATTATGTAAAGCCGTTTATAGTAAAGAGGTGGTCATT 101810
Qy 341 AspLysSerAsnProTyrTrpSerLysPheArgLeuAsnPhe 354
||||||||||||||||||||||||||||||||||||||||||
Db 101809 GATAAAAGTAATCCTTATTGGAGCAAATTTCGGCTTAATTTT 101768
Liu et al 2017 teaches cloning and expression of multiple (two, three or four genes) genes in a single vector by incorporating 2A "self-cleaving" peptides encoding nucleotides sequences between different genes for cleavage of expressed proteins (See, Figs 1-4, abstract and entire article).
Mwangi et al (WO2017096341A2) teaches added limitation of instant claim 11 (dependent on claim 1), further comprising at least one pharmaceutical-acceptable carrier by disclosing pharmaceutical-acceptable carrier, solvents, dispersion media, antibacterial, phosphate buffered saline isotonic solution, for the immunogenic composition that includes (See, page 15, lines 1-33). Comprising pharmaceutical carrier in the vaccine composition for stability and application of the product for vaccination or immunization is a well-known and routine in the vaccine art.
Prior Arts on BPIV3 or BPIV3 genotype c
Haller et al 2003 teaches Bovine parainfluenza virus type 3 (bPIV3) expressing the RSV attachment and fusion proteins protects hamsters from challenge with human PIV3 and RSV (See, abstract).
However, Haller et al 2003 do not teach Bovine parainfluenza virus type 3 genotype c (bPIV3c) and said chimeric gene comprises at least two nucleic acid sequences with each encoding for a sequence having at least 80% sequence homology with any one or more of SEQ ID NOs: 1-101, and any combination thereof.
Neill et al 2017 teaches identification and genome characterization of genotype C bovine parainfluenza type 3 viruses isolated in the United States and comparison of genetic identity with genotype C and B viruses isolated from different countries (See, abstract, p. 3 table 2 Genotype C, GenBank accession numbers for sequences, Figs 1-4, See, PDF printouts of Bovine parainfluenza virus 3 isolate TVMDL16 (GenBank acc no. KJ647285) and isolate TVMDL20 ( KJ647287) , complete genome and amino acid sequences encoded by genes).
Wang et al 2015 teaches safety of inoculation of bovine parainfluenza virus 3 as potential vaccine vector in pigs. To investigate whether NM09 can infect pigs and determine BPIV3 defense in these animals, BPIV3 antibody-free pigs were inoculated intramuscularly with the BPIV3 NM09 strain in a continuous passage. Clinical signs were observed each day after inoculation. Viral nucleic acid was detected in nasal and anal secretions. Results showed that virus-inoculated pigs displayed few observable clinical signs related to respiratory diseases. The antibody was identified, but the virus could not be detected in the second continuous passage in pigs. Thus, BPIV3 is a potential vaccine vector for genetic engineering (See, abstract, entire article).
Prior Arts on Chimeric Gene SEQ ID NOs
Mwangi et al 2017 as recited supra teaches the instant claim 1 elected species SEQ ID NO: 5 by disclosing a nucleotide sequence that has 99.8% identity/similarity with sequence encoded in instant claim 1 SEQ ID NO:5.
Borca et al 2016 (US9463234B2) as recited supra is in a vaccine art and teaches instant claim 1, SEQ ID NO: 37 (Qy) by disclosing 100% identity with SEQ ID NO 3 (Database) as disclosed by Borca et al (US9463234B2).
Additional prior arts teaching an approach for attenuation of BPIV3.
Haller et al 2000 teaches expression of the surface glycoproteins of human parainfluenza virus type 3 by bovine parainfluenza virus type 3, a novel attenuated virus vaccine vector. To test the potential of the bPIV3 vaccine strain as a vector, an infectious DNA clone of bPIV3 was assembled and recombinant bPIV3 (r-bPIV3) was rescued. r-bPIV3 displayed a temperature-sensitive phenotype for growth in tissue culture at 39 degrees C and was attenuated in the lungs of Syrian golden hamsters. Despite the attenuation phenotypes observed for r-bPIV3 and bovine/human PIV3, both of these viruses protected hamsters completely upon challenge with hPIV3. In summary, bPIV3 was shown to function as a virus vector that may be especially suitable for vaccination of infants and children against PIV3 and other viruses (See, abstract, entire article).
Skiadopoulos et al 2003 teaches determinants of the host range restriction of replication of bovine parainfluenza virus type 3 in rhesus monkeys are polygenic (See, abstract, entire article).
Bailly et al 2000 teaches sequence determination and molecular analysis of two strains of bovine parainfluenza virus type 3 that are attenuated for primates (See, abstract, entire article).
Haller et al 2001 teaches a single amino acid substitution in the viral polymerase creates a temperature-sensitive and attenuated recombinant bovine parainfluenza virus type 3 (See, abstract and entire article).
Liang et al 2014 teaches chimeric bovine/human parainfluenza virus type 3 expressing respiratory syncytial virus (RSV) F glycoprotein: effect of insert position on expression, replication, immunogenicity, stability, and protection against RSV infection. Chimeric bovine/human parainfluenza virus type 3 characterized were rB/HPIV3 viruses expressing RSV F from the first (pre-N), second (N-P), third (P-M), and sixth (HN-L) genome positions. The inserts in the second, third, and sixth positions conferred increased temperature sensitivity: this was greatest for the third position and was the most attenuating in vivo. Each rB/HPIV3 vector induced a high titer of neutralizing antibodies in hamsters against RSV and HPIV3. Protection against RSV challenge was greater for position 2 than for position 6 (See, abstract and entire article).
Schmidt et al (2002). Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA-derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone. J Virol. 2002 Feb;76(3):1089-99, pages 1089-1099.2002. PMID: 11773385.
Obviousness analysis for a single-cycle replicon adenovirus vector comprising chimeric ASFV gene sequences: It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the disclosure of Crosby et al on a single-cycle replicon adenovirus vector expressing influenza virus HA gene by replacing the influenza A virus HA gene with the SEQ ID NO: 5 of Mwangi et al and SEQ ID NO: 3 Borca et al, as recited supra and 2A self-cleaving peptide of Liu et al to arrive at the invention of instant claim 1 to develop a single-cycle replicon adenovirus vector based vaccine comprising said chimeric gene comprises at least two nucleic acid sequences with each encoding for a sequence having at least 80% sequence homology with any one or more of SEQ ID NOS: 1-101 that would be multivalent and induce broad immune response. One of the ordinary skills would have been motivated to use a single-cycle replicon adenovirus of Crossby et al teaches that single-cycle replicon adenovirus (SC-Ad) vectored influenza vaccine generates amplified vaccine response as compared to replication-defective adenovirus vectored influenza vaccine (See, abstract). Crosby et al teaches SC-Ad amplify transgene expression 100-fold and produce markedly stronger and persistent immune responses than RD-Ad vectors in Syrian hamsters and rhesus macaques. To express equal amounts of influenza virus HA in vivo approximately 33 times less SC-Ad was required than RD-Ad. SC-Ad influenza HA vaccine induced markedly higher HA binding and hemagglutination inhibition (HAI) titers than RD-Ad in Syrian hamsters. SC-Ad-vaccinated cotton rats had markedly lower influenza titers than RD-Ad-vaccinated animals after challenge with influenza A/PR/8/34 virus. Thus single-cycle adenovirus offers more potent vaccine platform for amplified immune response and higher immunogen expression (See, page 1, abstract, page 4 figure 2, page 5 figure 3, page 6 figure 4, page 7-8 figure 5-6). Sc-Ad vector replicate its DNA genome 3300-fold in human cells (See, page 9, paragraph 5, These data in two animal models ……). Another advantage or motivation to use single-cycle replicon adenovirus (SC-Ad) vector would be the vector expresses transgene encoded antigens at high level and cover a greater number of animals or people with less amount of immunogen to help achieve a superior performance and broader coverage with a cost-effective vaccine in a low resource setting and commercial success.
Obviousness analysis for attenuated BPIV3c genotype vector comprising chimeric ASFV gene(s) sequences: It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the disclosure of Haller et al 2003 on bPIV3 to incorporate the teachings of Neill et al 2017 on bPIV3 genotype c, additional prior arts teachings on bPIV3 and bPIV3 genotype c (as recited supra) on attenuated bPIV3 virus vector and incorporate the teachings on ASFV antigen encoding sequences of Mwangi et al 2017 (SEQ ID NO:5) and Borca et al 2016 (SEQ ID NO:3) and Liu et al 2017 on incorporating 2A "self-cleaving" peptides in between the two genes to arrive at the alternate invention of claim 1 comprising attenuated bPIV3c encoding chimeric ASFV SEQ ID NO: 5 and SEQ ID NO: 37. The motivation would be to develop an attenuated bPIV3 genotype c as a vector for expression of chimeric ASFV immunogenic antigens for protection against ASFV in porcine species or swine and for commercial success. One of ordinary skill in the art would have a reasonable expectation of success given the recited prior art teachings, as recited supra, to arrive at the invention of claims 1 and 3 based on the single-cycle adenovirus virus vector or attenuated bPIV3 genotype c vector. See, KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), examples of rationales, A-B and E-G.
Claim 4: The immunogenic composition of claim 1, wherein said immunogenic composition is in the form of a multicistronic cassette.
The immunogenic composition of claim 1 is taught by the combined prior art teachings as recited supra.
Liu et al 2016 further teaches polycistronic cassette, IRES, comprised in recombinant adenoviruses coexpressing Japanese encephalitis virus envelope and porcine interleukin-6 proteins that induces enhanced immune responses against Japanese encephalitis virus in mice (See, Liu et al 2016, abstract and figure 1 for adenovirus vector construct and legends and for immune response fig 2-6 and legend). Liu et al 2017 teaches cloning of multiple transgene and expression wherein nucleic acid sequence encoding different proteins are linked by a self-cleaving peptide sequence in a polycistronic vector or multicistronic cassette format demonstrating successful expression of different genes at high or similar levels (See, abstract on page 1; page 2 for figure 1, page 5-6 for figure 3 and 4 showing multicistronic expression of different proteins).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior art teachings applied to the instant claim 1 invention on single-cycle replicon adenovirus vector or attenuated bBIV3 genotype c with the teachings of Liu et al 2016 and Liu et al 2017 to comprise the adenovirus vector with multicistronic cassette to express the SEQ ID NO:5 and SEQ ID NO: 37 as recited in claim 1 to arrive at the invention of instant claim 4. The motivation would be Liu et al 2016 and Liu et al 2017 teaches that transgene expression in multicistronic cassette leads to relatively high-level downstream protein expression compared to other strategies of multi-gene co-expression such as fusion approach because self-cleaving peptides are smaller in size 18-22 amino acids and lower a risk of interfering with function of co-expressed genes (See, page 1, abstract lines 1-7 and lines 19-22). Based on the teachings of Liu et al 2016 and Liu et al 2017, one of ordinary skill in the art would have been motivated to obtain high level expression of the multiple antigenic proteins of ASFV SEQ ID NO:5 and SEQ ID NO: 37 by expression through multcistronic cassette format comprising single-cycle replicon adenovirus vector (SC Ad) to obtain a multivalent ASFV vaccine with enhanced and broad immune response for superior protection or attenuated bPIV3 genotype c vector to express a multivalent ASFV vaccine with enhanced and broad immune response for superior protection. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention of instant claim 4. See, KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), examples of rationales, G.
Claim 8: The immunogenic composition of claim 1, wherein said chimeric gene is selected from the group consisting of SEQ ID NOS. 102 - 131. (Elected species SEQ ID NO. 103).
The combined teaching of prior arts as recited supra teaches instant claim 1.
Borca et al (US9463234B2) further teaches, SEQ ID NO: 103 of instant claim 4 (See Qy= Query) by disclosing SEQ ID NO 3 that has 100% nucleotide sequence identity with SEQ ID NO 103 of claim 4.
RESULT 9
US-14-495-540A-3/c
Sequence 3, US/14495540A
Patent No. 9463234
GENERAL INFORMATION
APPLICANT: Borca, Manuel V.
APPLICANT: Holinka-Patterson, Lauren G.
APPLICANT: Gladue, Douglas
APPLICANT: Risatti, Guillermo R.
APPLICANT: O'Donnell, Vivian K.
TITLE OF INVENTION: Attenuated African Swine Fever Virus Strain Induces Protection Against Challenge With Homologous Virulent Parental Virus Georgia
TITLE OF INVENTION: 2007 Isolate
FILE REFERENCE: DN 122.14
CURRENT APPLICATION NUMBER: US/14/495,540A
CURRENT FILING DATE: 2014-09-24
NUMBER OF SEQ ID NOS: 24
SEQ ID NO 3
LENGTH: 191496
TYPE: DNA
ORGANISM: African swine fever virus
Alignment Scores:
Length: 191496
Score: 6635.00 Matches: 1286
Percent Similarity: 100.0% Conservative: 0
Best Local Similarity: 100.0% Mismatches: 0
Query Match: 100.0% Indels: 0
Gaps: 0
US-17-309-272-103 (1-1286) x US-14-495-540A-3 (1-191496)
Qy 1 GlyLeuAspLeuAspThrIleGlnLysSerIleIleGluTrpLeuArgGluThrGlnAla 20
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 123271 GGTTTAGACCTAGATACGATTCAAAAAAGCATTATCGAATGGTTACGAGAGACACAAGCT 123212
Qy 21 AlaAsnValAsnArgAlaAsnLeuIleAspTrpLeuGlyArgLysHisGlyAlaIleSer 40
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 123211 GCCAACGTGAACCGCGCCAATCTTATTGACTGGCTCGGAAGAAAACACGGGGCCATCTCT 123152
Qy 41 GluIleArgAsnProGlyLeuValIleLysGluIleAsnMetArgLeuSerMetValTyr 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 123151 GAGATTAGAAATCCAGGATTAGTCATTAAAGAAATCAATATGCGGCTTTCTATGGTGTAC 123092
Qy 61 ProAspProThrThrGluAlaAlaAlaAlaAlaGlnAspArgAsnLeuThrThrGluThr 80
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 123091 CCTGATCCCACTACCGAAGCGGCTGCAGCAGCCCAAGACCGAAATTTAACCACAGAAACT 123032
Qy 81 LeuPheAlaTrpIleValProTyrValGlyIleProAlaGlyGlyGlyValArgProGlu 100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 123031 CTTTTTGCTTGGATTGTACCATATGTGGGTATTCCTGCTGGTGGAGGAGTTCGTCCGGAG 122972
Qy 101 GlnGluLeuAlaAlaArgTyrLeuValAspAsnGlnArgIleMetGlnLeuLeuLeuThr 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122971 CAAGAGTTGGCCGCAAGGTATTTAGTAGATAATCAGCGAATCATGCAGCTCCTGTTGACC 122912
Qy 121 AsnIlePheGluMetThrSerSerPheAsnLysMetValGlnValArgPheProGluThr 140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122911 AATATCTTCGAAATGACCTCCAGTTTTAACAAAATGGTTCAAGTTCGCTTCCCTGAAACC 122852
Qy 141 SerThrAlaGlnValHisLeuAspPheThrGlyLeuIleSerLeuIleAspSerLeuMet 160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122851 AGCACCGCTCAAGTGCATTTAGATTTTACAGGTCTTATTTCCTTAATTGATTCTTTGATG 122792
Qy 161 AlaAspThrLysTyrPheLeuAspLeuLeuArgProHisIleAspLysAsnIleIleGln 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122791 GCCGACACGAAGTATTTTCTTGATCTTCTACGCCCGCATATTGATAAAAACATTATTCAA 122732
Qy 181 TyrTyrGluAsnArgSerAsnProGlySerPheTyrTrpLeuGluGluHisLeuIleAsp 200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122731 TACTATGAAAATAGATCTAATCCTGGCTCATTTTACTGGTTGGAAGAACATTTAATTGAC 122672
Qy 201 LysLeuIleLysProProThrAspAlaGlyGlyArgProLeuProGlyGlyGluLeuGly 220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122671 AAACTTATTAAACCACCTACCGATGCCGGAGGAAGGCCGCTTCCTGGCGGTGAATTGGGC 122612
Qy 221 LeuGluGlyValAsnGlnIleIleAsnLysThrTyrThrLeuLeuThrLysProTyrAsn 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122611 CTGGAGGGGGTTAACCAAATCATTAATAAAACCTACACCTTGCTTACAAAGCCTTATAAT 122552
Qy 241 ValLeuGlnLeuArgGlyGlyAlaGlnArgArgAspAlaAlaAsnIleGlnIleAsnAsn 260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122551 GTACTGCAACTTCGAGGTGGGGCGCAAAGAAGGGACGCGGCTAATATTCAAATAAATAAC 122492
Qy 261 AsnProGlnSerSerGluArgPheGluGlnTyrGlyArgValPheSerArgLeuValPhe 280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122491 AATCCCCAATCCTCTGAACGCTTTGAACAATACGGAAGAGTATTCAGTAGACTCGTATTT 122432
Qy 281 TyrAspAlaLeuGluAsnAsnSerGlyLeuArgValGluGlnValAlaLeuGlyAspPhe 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122431 TACGATGCTTTGGAGAATAACTCTGGACTTCGTGTAGAGCAGGTGGCACTAGGAGACTTT 122372
Qy 301 ArgLeuSerAsnLeuIleArgThrAsnAsnAlaGlnGluGluAsnThrLeuSerTyrTrp 320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122371 AGACTCTCCAATCTTATTCGTACCAACAACGCCCAGGAGGAAAATACTCTTAGCTACTGG 122312
Qy 321 AspAsnIleAlaLeuArgThrTyrAlaAsnValAsnAspAlaAlaAsnAsnLeuArgArg 340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122311 GACAACATAGCGCTCAGAACCTATGCCAATGTCAATGATGCCGCAAACAACCTTCGACGT 122252
Qy 341 TyrArgLeuTyrGlySerAspTyrGlyIleGlnAsnAsnArgSerMetMetMetValPhe 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122251 TATCGCCTATACGGATCAGACTATGGTATTCAAAATAATCGTAGTATGATGATGGTGTTT 122192
Qy 361 AsnGlnLeuIleAlaSerTyrIleThrArgPheTyrAspAlaProSerGlyLysIleTyr 380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122191 AACCAGCTCATAGCTTCATATATTACCCGATTTTATGATGCTCCCAGCGGAAAAATATAT 122132
Qy 381 LeuAsnLeuIleAsnAlaPheAlaAsnGlyAsnPheSerGlnAlaValMetGluMetGly 400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122131 CTAAATCTTATTAATGCATTCGCTAATGGGAACTTTAGCCAAGCAGTGATGGAGATGGGA 122072
Qy 401 TyrAlaHisProAspLeuAlaArgAsnAsnAsnValPheGlyHisArgGlyAspProThr 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122071 TATGCTCACCCTGACTTAGCACGCAATAACAACGTCTTTGGTCATAGAGGCGACCCCACA 122012
Qy 421 GluGlnSerValLeuLeuLeuSerLeuGlyLeuIleLeuGlnArgLeuIleLysAspThr 440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122011 GAGCAGTCGGTGCTTCTTCTGTCTTTGGGACTTATACTTCAGCGGCTTATTAAGGATACC 121952
Qy 441 AsnArgGlnGlyLeuSerGlnHisLeuIleSerThrLeuThrGluIleProIleTyrLeu 460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121951 AATCGCCAGGGCCTGAGTCAGCATCTTATTTCTACTTTAACAGAAATTCCCATTTACCTT 121892
Qy 461 LysGluAsnTyrArgAlaAsnLeuProLeuPheAsnLysMetPheAsnIleLeuIleSer 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121891 AAAGAAAATTATAGAGCCAATCTTCCACTATTTAACAAAATGTTTAATATTCTTATTAGC 121832
Qy 481 GlnGlyGluLeuLeuLysGlnPheIleGlnTyrThrAsnValGlnLeuAlaArgProAsn 500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121831 CAGGGAGAGCTTCTAAAACAATTTATACAATACACAAATGTCCAACTAGCTCGCCCTAAT 121772
Qy 501 LeuThrAlaLeuLeuGlyAlaAsnAsnAspSerValIleTyrTyrAsnAsnAsnAsnVal 520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121771 CTGACGGCACTCTTGGGAGCCAATAATGATTCCGTTATTTATTATAATAATAACAATGTT 121712
Qy 521 ProAlaThrGlyLeuSerValGlyGlnAlaAlaLeuArgGlyIleGlyGlyValPheArg 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121711 CCTGCGACAGGACTATCCGTCGGTCAGGCGGCCCTGCGGGGAATTGGCGGCGTATTTCGT 121652
Qy 541 ProAsnValThrLeuMetProLeuGlyAspAlaGlnAsnAsnThrSerAspValValArg 560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121651 CCCAATGTTACGCTTATGCCCCTAGGAGACGCACAAAATAATACGAGCGATGTTGTGCGA 121592
Qy 561 LysArgLeuValAlaValIleAspGlyIleIleArgGlySerHisThrLeuAlaAspSer 580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121591 AAGCGACTGGTCGCAGTGATCGACGGGATCATTAGAGGCTCTCACACTCTGGCAGATTCT 121532
Qy 581 AlaMetGluValLeuHisGluLeuThrAspHisProIleTyrLeuGluThrGluGluHis 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121531 GCCATGGAGGTCCTGCACGAGCTTACCGATCATCCCATCTATCTTGAAACAGAAGAACAC 121472
Qy 601 PheIleGlnAsnTyrMetSerArgTyrAsnLysGluProLeuMetProPheSerLeuSer 620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121471 TTCATTCAAAACTATATGTCCCGGTACAATAAGGAGCCTCTTATGCCATTTTCACTTTCG 121412
Qy 621 LeuTyrTyrLeuHisAspLeuArgIleGluAsnAsnGluValTyrAspProLeuLeuTyr 640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121411 CTCTATTATTTACATGACCTAAGAATAGAAAATAATGAGGTATATGATCCTCTTCTTTAC 121352
Qy 641 ProAsnLeuGluSerGlySerProGluPheLysLeuLeuTyrGlyThrArgLysLeuLeu 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121351 CCGAACCTTGAAAGCGGCTCCCCCGAGTTTAAACTACTATACGGCACAAGAAAATTACTG 121292
Qy 661 GlyAsnAspProValGlnLeuSerAspMetProGlyValGlnLeuIleMetLysAsnTyr 680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121291 GGAAATGATCCGGTACAGCTCTCAGATATGCCCGGAGTACAGCTTATCATGAAAAACTAT 121232
Qy 681 AsnGluThrValValAlaArgGluGlnIleThrProThrArgPheGluHisPheTyrThr 700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121231 AATGAAACGGTAGTTGCTCGCGAACAAATTACTCCCACGCGATTTGAACACTTTTATACC 121172
Qy 701 HisAlaIleGlnAlaLeuArgPheIleIleAsnIleArgSerPheLysThrValMetMet 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121171 CACGCCATTCAGGCTCTCCGATTTATCATAAATATCCGTAGTTTTAAAACAGTGATGATG 121112
Qy 721 TyrAsnGluAsnThrPheGlyGlyValAsnLeuIleSerGluAsnArgAspAspLysPro 740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121111 TACAATGAAAATACTTTTGGTGGAGTTAATCTTATTAGCGAGAACAGAGACGATAAACCC 121052
Qy 741 IleIleThrAlaGlyIleGlyMetAsnAlaValTyrSerLeuArgLysThrLeuGlnAsp 760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121051 ATTATAACAGCGGGAATAGGGATGAATGCAGTGTATTCGCTTCGTAAAACATTGCAAGAC 120992
Qy 761 ValIleSerPheValGluSerSerTyrGlnGluGluGlnIleAsnHisIleHisLysIle 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120991 GTAATTTCCTTCGTGGAAAGCTCTTACCAAGAGGAGCAAATCAATCATATTCACAAAATA 120932
Qy 781 ValSerProLysGlyGlnThrArgThrLeuGlySerAsnArgGluArgGluArgIlePhe 800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120931 GTGTCGCCGAAAGGTCAAACACGCACTCTTGGCTCTAATAGAGAGCGCGAGCGCATATTT 120872
Qy 801 AsnLeuPheAspMetAsnIleIleProIleAsnValAsnAlaLeuMetArgSerIlePro 820
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120871 AACTTGTTTGATATGAATATTATACCTATCAATGTAAATGCGCTGATGCGATCTATACCA 120812
Qy 821 LeuAlaAsnIleTyrAsnTyrAspTyrSerPheGluGluIleAlaCysLeuMetTyrGly 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120811 CTTGCCAATATTTACAACTATGACTATAGTTTTGAAGAAATTGCTTGTCTTATGTACGGC 120752
Qy 841 IleSerAlaGluLysValArgSerLeuAspThrThrAlaProGlnProAspValAlaGlu 860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120751 ATTTCGGCTGAAAAAGTACGATCTCTGGACACCACGGCTCCTCAACCAGATGTTGCAGAG 120692
Qy 861 ValLeuAsnIleProAsnArgProProIleAsnThrArgGluPheMetLeuLysLeuLeu 880
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120691 GTATTAAACATTCCGAATCGTCCCCCCATAAATACTCGAGAATTTATGCTAAAACTTCTT 120632
Qy 881 IleAsnProTyrValSerValSerIleThrGlnTyrGlyAsnGluLeuLeuSerLysGly 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120631 ATAAACCCCTATGTCTCGGTCTCTATTACTCAATATGGGAATGAGTTACTATCCAAAGGC 120572
Qy 901 AsnAlaGlyTyrMetSerArgIlePheArgGlyAspAsnAlaLeuAsnMetGlyArgPro 920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120571 AACGCCGGATACATGTCACGCATCTTTAGAGGGGACAACGCGCTAAATATGGGCCGCCCT 120512
Qy 921 LysPheLeuSerAspGlnIlePheAsnLysValLeuPheGlySerLeuTyrProThrGln 940
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120511 AAATTTCTTTCTGACCAAATTTTCAATAAAGTGCTATTTGGAAGCCTTTATCCTACACAA 120452
Qy 941 PheAspTyrAspGluAlaGlyProSerLeuAlaAlaGlyIleGlnArgGlyArgGluArg 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120451 TTTGATTATGACGAGGCAGGTCCTAGTTTGGCCGCAGGTATTCAACGTGGACGTGAGCGG 120392
Qy 961 TrpGlyHisProMetSerIleTyrIleAsnGlnAlaLeuHisGluIleValArgThrIle 980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120391 TGGGGCCATCCCATGTCAATATACATAAACCAGGCCTTACATGAAATTGTGCGTACTATA 120332
Qy 981 ArgLeuAlaGluThrValArgGlyLeuArgAsnValIleAspArgAsnGlnIleIleGly 1000
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120331 CGATTGGCTGAAACAGTTCGAGGTTTAAGAAATGTTATTGATAGAAACCAAATTATAGGC 120272
Qy 1001 GluLeuAsnAlaPheArgThrGlnLeuGluAspThrArgArgGluValAsnAsnLeuIle 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120271 GAGTTAAATGCATTTAGGACTCAGCTTGAAGATACACGAAGAGAAGTGAATAATCTAATA 120212
Qy 1021 GlnThrProGluIleGlnAsnAsnProThrProGluIleIleAlaAlaIleGlnAsnTrp 1040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120211 CAAACACCTGAAATTCAAAACAATCCAACCCCTGAGATCATCGCTGCCATTCAAAACTGG 120152
Qy 1041 ValGlnGlnTyrArgGlyGlnIleThrAsnLeuIleAspLeuIleGlyAsnAlaGlyGln 1060
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120151 GTACAACAATATCGAGGTCAAATAACCAATTTAATCGATCTTATAGGAAATGCCGGGCAA 120092
Qy 1061 AlaAsnSerMetIleAsnLeuIleGlnAsnIleThrProGlnThrAlaGlyAlaGlnLeu 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120091 GCCAATTCGATGATAAATTTAATACAAAATATTACGCCCCAAACAGCCGGTGCACAATTA 120032
Qy 1081 ThrAlaLeuPheAsnIleArgGlyLeuProAlaProProProArgGlnAlaLeuGlnAsn 1100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 120031 ACCGCTTTATTCAACATACGTGGATTACCTGCCCCGCCTCCCCGTCAAGCATTACAAAAT 119972
Qy 1101 AspIleGluAlaMetGlnTrpPheMetThrMetValIleAsnHisProProValLeuIle 1120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 119971 GATATTGAAGCAATGCAATGGTTTATGACAATGGTTATAAACCATCCACCTGTTTTAATA 119912
Qy 1121 AlaProPheMetLeuLeuValAsnAsnLeuLysGluPheLeuAsnThrLeuGluArgTyr 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 119911 GCACCCTTCATGCTACTCGTAAATAACCTTAAGGAATTTTTAAATACGCTAGAACGATAT 119852
Qy 1141 ValTyrLysThrProArgTrpLeuGlyProGlyThrAlaArgIleAlaGlnProProVal 1160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 119851 GTTTATAAAACTCCACGATGGTTGGGTCCCGGTACAGCCCGAATTGCACAACCGCCAGTT 119792
Qy 1161 GlyMetAlaProGlyIleAsnMetArgHisHisThrSerTyrThrGluAsnSerValLeu 1180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 119791 GGAATGGCACCAGGTATTAATATGCGACATCATACCTCATATACAGAAAATAGTGTGCTG 119732
Qy 1181 ThrTyrIleThrGluGlnAsnArgGluGluGlyProTrpSerIleValLysGlnValGly 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 119731 ACCTATATCACGGAACAAAATCGGGAAGAAGGACCCTGGTCCATCGTTAAACAAGTGGGA 119672
Qy 1201 ValGlyIleGlnLysProThrLeuValGlnIleGlyLysAspArgPheAspThrArgLeu 1220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 119671 GTTGGAATACAAAAGCCCACCTTAGTACAAATTGGAAAGGATCGCTTTGACACTCGCCTC 119612
Qy 1221 IleArgAsnLeuIlePheIleThrAsnIleGlnArgLeuLeuArgLeuArgLeuAsnLeu 1240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 119611 ATACGCAATCTAATATTTATTACAAATATACAGCGACTATTACGACTGCGTCTAAACCTA 119552
Qy 1241 GluLeuSerGlnPheArgAsnValLeuValSerProAspHisIleIleAsnProSerIle 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 119551 GAACTCTCGCAGTTCAGAAATGTGCTTGTCAGTCCTGACCACATTATAAACCCCAGCATT 119492
Qy 1261 ThrGluTyrGlyPheSerIleThrGlyProSerGluThrPheSerAspLysGlnTyrAsp 1280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 119491 ACAGAGTATGGGTTCTCCATCACAGGACCCAGTGAGACCTTCTCAGATAAACAGTATGAT 119432
Qy 1281 SerAspIleArgIleLeu 1286
||||||||||||||||||
Db 119431 AGTGATATTCGGATTTTA 119414
Borca et al (US9463234B2) is analogous to the claimed invention because it is in the same field of ASFV vaccine or immunogenic composition vaccine art. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified instant claim 1 to incorporate the teachings of Borca et al on providing SEQ ID NO: 103 with 100% identity to arrive at the claimed invention based on either single cycle replicon adenovirus vector or attenuated bPIV3 genotype c virus vector. The recited SEQ ID NO:3 of Borca et al shows 100% identity to sequence from an attenuated ASFV vaccine candidate that is derived from homologues highly virulent ASFV Georgia 2007/1 isolate. Epidemiologically, highly virulent ASFV Georgia 2007/1 isolate pose threat for the US agriculture and pig industry. Therefore, by using SEQ ID NO: 3 of Borca et al. or by combining the SEQ ID NO: 3 disclosed by Borca et al with the SEQ ID NO: 5 of Mwangi et al, one of ordinary skill in the art would have a reasonable expectation of success to develop a vaccine that would be effective against highly virulent ASFV from contemporary ASFV disease outbreaks. One of ordinary skill in the art would have a reasonable expectation of success given the prior art teachings applied to the claim 8. See, KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), examples of rationales, A-B, D, F-G.
Claim 11: The immunogenic composition of claim 1 is taught by the combined prior art teachings as recited supra.
Mwangi et al (WO2017096341A2) teaches added limitation of instant claim 11 (dependent on claim 1), further comprising at least one pharmaceutical-acceptable carrier by disclosing pharmaceutical-acceptable carrier, solvents, dispersion media, antibacterial, phosphate buffered saline isotonic solution, for the immunogenic composition that includes pharmaceutical carrier in the vaccine composition for stability and application of the product for vaccination or immunization is a well-known and routine in the vaccine art (See, abstract, claim 2, page 15, lines 1-33). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior art teachings applied to instant claim 1 with additional teachings of Mwangi et al 2017 (WO2017096341A2) to arrive at the invention of claim 11 for the convenience of end users and commercial success. There would have been a reasonable expectation of success because formulating a vaccine composition into administrable pharmaceutical composition comprising a diluent or carrier is routine in the art. See, KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), examples of rationales G.
12. Claims 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Crosby et al 2017 (published in Journal of Virology, volume 91 (2), pages 1-12), Mwangi et al (WO2017096341A2, published 08 June 2017, with a priority to application US 62/263,424 filed on 04 December 2015), Borca et al (US9463234B2, published 11 October 2016), Liu et al 2017 (Sci Rep. 2017 May 19;7(1):2193), Liu et al 2016 (Virus Research 222 (2016) 34–40), Lokhandwala et al 2017 (PLoS One. 2017 May 8;12(5):e0177007), Haller et al 2003 (Journal of Virology, Volume 84, Issue 8), Neill et al 2017 (BMC Veterinary Research (2015) 11:112), Wang et al 2015 (Virus Disease. 2015 Jun;26(1-2):89-91), Haller et al 2000 (Journal of Virology, 2000, Vol. 74, No. 24, p. 11626-11635), Skiadopoulos et al 2003 (Journal of Virology, 2003, Vol. 77, No. 2, p.1141-1148), Bailly et al 2000 (Virus Genes 20:2, 173-182, 2000), Haller et al 2001 (Virology 2001, 288, 342-350) and Liang et al 2014 (Journal of Virology, vol 88 (8), p. 4237–4250) as applied to claim 1 above, and further in view of Peng et al 2008 (published in Vaccine, volume 26, pages 5802-5807), Weaver and Reisen (published 2010, Antiviral Research, 85 pages 328-345, Huang et al (published 2015, Vector Borne Zoonotic Diseases, 15 (11): 709-711 and Park et al 2018 (published in Scientific Reports, 8:7951).
The instant claims 9-10 are directed to the immunogenic composition (dependent on claim 1), inter alia, comprising an antigen from another disease-causing organism (instant claim 9 limitation), wherein said another disease- causing organism is selected from the group, inter alia, consisting of an elected species Japanese Encephalitis Virus (instant claim 10 limitation).
The combined prior art teachings as applied to instant claim 1, as recited supra, teaches immunogenic composition of claim 1, however, do not teach the added limitations of claims 9-10.
Mwangi et al and Borca et al teaches antigens from ASFV as recited in instant claim 1 SEQ ID NO: 5 and SEQ ID NO: 37 as recited supra. However, do not including an antigen from another disease-causing organism or an antigen from Japanese Encephalitis Virus.
Peng et al is in the analogous adenovirus vector vaccine art and disclose an immunogenic composition comprising a recombinant adenovirus expressing Japanese Encephalitis Virus (JEV) E protein based multiple immunodominant B and T cell epitopes designed as chimeric fusion cassette cloned in adenovirus as a vaccine (See, page 5802, abstract, page 5803 Materials and methods, construction of recombinant adenoviruses rAd-TEP, figure 1, page 5804, figures 2-4). E protein of JEV induces neutralizing antibodies and carries critical B cell epitopes for inducing immune response (See, introduction, paragraph 1, lines 8-16). JEV is an arthropod/mosquito borne virus cause and causes still birth in pregnant swine (See, abstract, line 1-2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior art teachings applied to instant claim 1 on single cycle replicon adenovirus vector or attenuated bPIV3 genotype c virus vector to incorporate the teachings of Peng et al on JEV E protein based multiple immunodominant B and T cell epitopes as a chimeric gene cassette to arrive at the invention claimed in instant claims 9-10 to develop a single cycle replicon adenovirus vaccine vector expressing JEV E protein or attenuated bPIV3 genotype c virus vector expressing JEV E protein. The motivation would be to exploit the superior immune response properties of single cycle replicon adenovirus vaccine vector for expressing JEV E protein or attenuated bPIV3 genotype c virus vector expressing JEV E protein to develop an effective immune response inducing vaccine against JEV. One of ordinary skill in the art would have a reasonable expectation of success in replacing ASFV SEQ ID NO:5 and 37 from the single cycle replicon adenovirus vaccine vector or attenuated bPIV3 genotype c virus vector of claim 1 and incorporate JEV E protein sequence of Peng et al and express JEV E protein based multiple immunodominant B and T cell epitope sequences to generate a chimeric sequence to encode or express only JEV E protein or both JEV protein and SEQ ID NO: 5 and 37 as recited supra for arriving at the invention of instant claim 9-10.
Further, the courts have said: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose . . . . [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.) See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). (See MPEP §2144.06(I) – Combining Equivalents Known For The Same Purpose). In this case, applicants are combining antigens from pathogens that are known to cause disease in swine, ASFV SEQ ID NO:5 sequence of Mwangi et al and SEQ ID NO: 37 of Borca et al a sequence encoding antigen from JEV E protein of Peng et al.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made. It is similar to combining prior art elements according to known methods to yield predictable results to arrive at the claimed invention. See, KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), examples of rationales, A.
In addition, Weaver and Reisen teaches global epidemiology of arthopod-borne (Culex mosquito borne) JEV in swine/pigs and risk of introduction of JEV in the United States (See, abstract, lines 1-3, 10-13, 17-18; page 332, column 2, Future trends, lines 1-4, page 333, column 1 lines 1-8, for JEV spread) through air transport of mosquitoes, and susceptibility of avian host. Huang et al teaches susceptibility of a North American Culex quinquefasciatus mosquitoes’ species to Japanese Encephalitis Virus and the involvement of domestic pigs and avian species in endemic transmission and recites a concern of the potential risk of JEV introduction into North America (See, abstract, lines 1-3, lines 6-12). Park et al teaches North American domestic pigs are susceptible to experimental infection with Japanese encephalitis virus (See, page 1-abstract, and page 2-figure 1).
Based on the teachings of Crossby et al, Mwangi et al and Borca et al as applied to claim 1 and further in view of Peng et al, Weaver and Reisen, Huang et al and Park et al, one of ordinary skill in the art would have been motivated to obtain an immunogenic composition comprising chimeric gene cassette that expresses both ASFV and JEV antigens. A single immunogenic composition for induction of protective immune response in pigs against two arthropod borne viruses, ASFV and JEV, would offer logistic, cost and resources saving on vaccination in pig industry and commercial success This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claim 9-10 inventions. See, KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), examples of rationales, G.
Response to Arguments 35 U.S.C. 103 Rejections
Applicant's arguments regarding rejections under 35 U.S.C. 103 filed on 01/02/2026 have been fully considered but they are not persuasive for the following reasons:
Applicant’s argument 3: Claims 1, 3-4 and 8-11 were rejected under 35 USC 103 as allegedly being unpatentable over Crosby et al 2017, and further in view of Mwangi et al, Borca et al, Liu et al 2017, Liu et al 2016, Lokhandwala et al, and Haller et al 2003, Neill et al 2015, Wang et al, Haller et al 2000, Skiadopoulos et al, Bailly et al, Haller et al 2001, and Liang et al.
Applicants respectfully disagree with the rejection and provide the following arguments in support of their position. To begin, Applicants note that the independent claim consists of, at most, just 4 elements: (1) a chimeric gene; (2) inserted into an attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector; (3) wherein said chimeric gene comprises at least two nucleic acid sequences; and (4) with each chimeric gene encoding for a sequence having at least 80% sequence homology with any one or more of SEQ ID NOS: 1-101. In order to obviate the claimed invention, 14 primary references were needed. While Applicants agree that the number of references used to formulate a rejection is not dispositive of non-obviousness, they nevertheless assert that common sense would lead one to believe that a claim with 4 limitations would not require 14 primary references to formulate an obviousness rejection if it was truly "obvious".
In further support of Applicants' position, Applicants note that none of the prior art utilizes ASFV sequences in a BPIV3c vector. Thus, not only is a limitation missing, no motivation for providing the limitation or reasonable expectation of success for such a modification is provided. Crosby 2017 utilizes SC-Ad influenza, Mwangi utilizes adenovirus-vectored ASFV, and Liu's also utilizes adenovirus multicistron constructs. The cited BPIV3 literature (Haller 2000/2001/2003; Skiadopoulos 2003; Bailly 2000; Liang 2014) discusses bovine or bovine/human PIV3 vectors expressing RSV, not ASFV, antigens in hamsters or primates. Additionally, the PIV is not genotype C. Neill 2015 identifies and characterizes genotype C BPI3V isolates and provides full genomes but does not disclose, teach, or suggest utilizing recombinant BPIV3c vectors for ASFV expression in BPIV3 c. Wang 2015 reports porcine inoculation with BPIV3 NMO9 (not genotype C) as a potential vector in pigs, but provides no teachings on BPIV3c, ASFV multivalent expression, self-cleaving linkers in BPIV3c, or swine attenuation. The multicistronic and self- cleaving peptide strategies (Liu 2016/2017) are taught in adenoviral or general expression systems, not in BPIV3c vectors. In short, no reference or combination of references discloses, teaches or suggests a BPIV3c vector engineered to express a multivalent ASFV chimeric gene comprising at least two ASFV sequences with each chimeric gene encoding for a sequence having at least 80% sequence homology with any one or more of SEQ ID NOS: 1-101. The additional limitations provided in the dependent claims provide further differentiation. For example, no art suggests having a BPIV3c vector with ASFV sequences therein, wherein the ASFV sequences are linked by self-cleaving peptides, in a multicistronic cassette. Applicants note that these arguments are predicated on the combination of the references, meaning that collectively (not individually), the references fail to disclose, teach, or suggest the claimed invention.
With respect to the combination of references failing to provide the requisite motivation to combine and modify the references as set forth in the Office Action as well as any reasonable expectation of success. Applicants assert that there is no articulated motivation or reasonable expectation of success to select BPIV3c and port adenoviral designs therein to arrive at the claimed invention. The Office Action alleges it would have been obvious to modify Haller'sBPIV3 vectors with Neill's genotype C disclosures and inserting ASFV sequences from Mwangi and Borca with 2A peptides from Liu to obviate the claims. This rationale clearly applies hindsight. Neill 2015 is surveillance/genomic characterization; it does not identify genotype C as a preferable vector for ASFV expression or provide attenuation markers or insert positions in BPIV3c. The PIV3 vector biology is known to be complex and unpredictable: host-range restriction is polygenic (see, Skiadopoulos 2003) and insert position profoundly affects expression, temperature-sensitivity, and attenuation as evidenced by Liang 2014. Haller 2001 shows attenuation via L substitutions. These teachings underscore that substitution of vector backbones and insertion of foreign antigens is not plug-and-play, and a person of skill in the art would not have had a reasonable expectation of success porting adenoviral multicistronic ASFV constructs into BPIV3c. Wang 2015's general statement that BPIV3 is a "potential vaccine vector" in pigs is insufficient to supply a specific motivation to choose genotype C and to expect success with multivalent ASFV chimeras in BPIV3c under the known constraints. Thus, the references taken together fail to provide the requisite motivation and expectation of success required for an obviousness rejection.
With reference to claim-specific points:
Applicants assert that Claim 1 requires a BPIV3c vector with at least two ASFV sequences having at least 80% identity to SEQ ID NOS: 1-101. The Office Action maps "two sequences" via Mwangi/Borca, but only in adenoviral contexts. As amended, that pathway is inapposite. The BPIV3c path lacks teachings to insert multivalent ASFV chimeras into BPIV3c, to select insert positions, and to attenuate/stabilize the same in swine.
Claim 3 requires self-cleaving peptide linkers between each ASFV sequence in BPIV3c. Liu 2016/2017 does not disclose, teach, or suggest implementing such linkers in BPIV3c, nor does it provide any reasonable expectation of success. Given PIV3 insert-position and attenuation sensitivities that are identified in Liang 2014 and Skiadopoulos 2003, one of skill in the art would not reasonably expect that adenoviral 2A multicistrons would translate into BPIV3c without undue uncertainty.
Claim 4 requires a multicistronic cassette in BPIV3c. Liu 2016/2017 (adenoviral contexts) does not establish motivation or reasonable expectation to implement multicistrons in BPIV3c, particularly in light of PIV3 transcription gradients and attenuation dependencies shown in Liang 2014.
Claim 8 selects chimeric ASFV sequences from SEQ ID NOS: 102-131 (the elected species is SEQ ID NO: 103). Even if Borca discloses an ASFV sequence aligning to SEQ ID NO: 103, Borca is silent on BPIV3c vectorization.
Claim 11 (carrier) is routine only if the base composition is obvious. Because claim 1 is not rendered obvious, claim 11 should be withdrawn from the rejection under § 103.
In conclusion, under Graham and KSR, the scope/content of the prior art does not teach or suggest the claimed BPIV3c multivalent ASFV constructs; the differences are substantive; and given the documented complexities of PIV3 vector design (Liang 2014; Skiadopoulos 2003; Haller 2001), a person of ordinary skill in the art lacked a reasonable expectation of success. Accordingly, Applicants respectfully request withdrawal of the § 103 rejection of claims 1, 3-4, 8, and 11.
Claims 9-10 were rejected under 35 USC 103 as allegedly being unpatentable over Crosby et al 2017, Mwangi et al, and Borca et al, Liu et al 2017, Liu et al 2016, Lokhandwala et al, Haller et al 2003, Neill et al 2017, Wang et al, Haller et al 2000, Skiadopoulus et al, Bailly et al, Haller et al 2001, and Liang et al 2014, as applied to claim 1 above, and further in view of Peng et al 2008, Weaver and Reisen, Huang et al, and Park et al 2018.
Claims 9-10 add a second antigen, with claim 10 providing a list of potential species from which the antigen can be provided (with Japanese Encephalitis Virus (JEV) being the elected species). The Office Action cites Peng 2008 (adenoviral JEV E protein) and epidemiological references (Weaver & Reisen 2010; Huang 2015; Park 2018). Applicants assert that none of those references, alone or in combination with any combination of the other 17 references utilized in the rejection teaches co-expression of ASFV and JEV antigens in a BPIV3c backbone for swine, nor offers BPIV3c-specific guidance on insert positioning, transcription control, attenuation markers, or stability for such a dual-pathogen construct. Given the known PIV3 sensitivities identified in Liang 2014 (insert positions) and Skiadopoulos 2003 (polygenicity), the proposed combination is speculative and lacks the required reasonable expectation of success. Additionally, Applicants assert that general motivations (cost/logistics) cited in the Office Action cannot substitute for the required specific teaching or reasoned rationale to select BPIV3c and implement dual ASFV+JEV expression. Accordingly, Applicants respectfully request withdrawal of the § 103 rejection of claims 9-10.
In Response 3:
In response to applicant's argument that the examiner has combined an excessive number of references, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
Applicant's arguments filed on 01/02/2026 have been fully considered but they are not persuasive. The claims 1, 3-4 and 8-11 as rejected under 35 USC 103 are rendered obvious by the applied combined prior art teachings for the claimed genus and species attenuated bovine parainfluenza virus type 3 genotype c (BPIV3c) vector and recited motivation(s) and reasonable expectation of success and knowledge and skills of the ordinary in the art as recited supra in the office action.
Double Patenting
13. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
14. Claims 1, 3-4, 7-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of copending Application No. 17/755,359 in view of in view of Crosby et al 2017 (published in Journal of Virology, volume 91 (2), pages 1-12), and further in view of Mwangi et al (WO2017096341A2, published 08 June 2017, with a priority to application US 62/263,424 filed on 04 December 2015), Borca et al (US9463234B2, published 11 October 2016), Liu et al 2017 (Sci Rep. 2017 May 19;7(1):2193), Liu et al 2016 (Virus Research 222 (2016) 34–40), Lokhandwala et al 2017 (PLoS One. 2017 May 8;12(5):e0177007), and Haller et al 2003 (Journal of Virology, Volume 84, Issue 8), Neill et al 2017 (BMC Veterinary Research (2015) 11:112), Wang et al 2015 (Virus Disease. 2015 Jun;26(1-2):89-91), Haller et al 2000 (Journal of Virology, 2000, Vol. 74, No. 24, p. 11626-11635), Skiadopoulos et al 2003 (Journal of Virology, 2003, Vol. 77, No. 2, p.1141-1148), Bailly et al 2000 (Virus Genes 20:2, 173-182, 2000), Haller et al 2001 (Virology 2001, 288, 342-350) and Liang et al 2014 (Journal of Virology, vol 88 (8), p. 4237–4250).
The instant claims 1, 3-4, 7-10 and copending claims 1-4 are directed to bovine parainfluenza virus type 3 genotype c (BPTV3 c) and antigenic insert sequence from a pathogen/disease causing organism other than BPIV3.
Instant claim 1, 3-4, 7-10 are obvious over copending claims 1-4.
The instant claims 1, 3-4, 7-11 are obvious over co-pending claims in view of the prior arts applied a provisional nonstatutory double patenting rejection as recited supra. The prior art teachings, motivations and reasonable expectation of success to arrive at the inventions of instant claims 1, 3-4, 7-11 as recited supra are incorporated here in entirety by reference and applied for the provisional nonstatutory double patenting rejection.
This is a provisional nonstatutory double patenting rejection.
15. Claims 1, 3-4, 7-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/149,483 in view of Crosby et al 2017 (published in Journal of Virology, volume 91 (2), pages 1-12), and further in view of Mwangi et al (WO2017096341A2, published 08 June 2017, with a priority to application US 62/263,424 filed on 04 December 2015), Borca et al (US9463234B2, published 11 October 2016), Liu et al 2017 (Sci Rep. 2017 May 19;7(1):2193), Liu et al 2016 (Virus Research 222 (2016) 34–40), Lokhandwala et al 2017 (PLoS One. 2017 May 8;12(5):e0177007), and Haller et al 2003 (Journal of Virology, Volume 84, Issue 8), Neill et al 2017 (BMC Veterinary Research (2015) 11:112), Wang et al 2015 (Virus Disease. 2015 Jun;26(1-2):89-91), Haller et al 2000 (Journal of Virology, 2000, Vol. 74, No. 24, p. 11626-11635), Skiadopoulos et al 2003 (Journal of Virology, 2003, Vol. 77, No. 2, p.1141-1148), Bailly et al 2000 (Virus Genes 20:2, 173-182, 2000), Haller et al 2001 (Virology 2001, 288, 342-350) and Liang et al 2014 (Journal of Virology, vol 88 (8), p. 4237–4250).
The instant claim 1, 3-4, 7-11 and co-pending claims are directed to an immunogenic composition comprising chimeric genes comprising nucleic acid sequence encoding for a sequence having at least 80% sequence homology with any one or more of SEQ ID NOS: 1-101, and any combination thereof or said chimeric gene is selected from the group consisting of SEQ ID NOS. 102 -131. The chimeric gene sequences are inserted into a vector and the vector is an adenovirus or an attenuated bovine parainfluenza virus type 3 genotype c (BPTV3 c).
Instant claim 1 and 7 are obvious over copending claims 1-2, 5-7, 12.
Instant claim 3 is obvious over copending claims 3.
Instant claim 4 is obvious over copending claims 4.
Instant claim 8 is obvious over copending claims 8.
Instant claim 9 is obvious over copending claims 9, 13.
Instant claim 10 (Japanese Encephalitis) is obvious over copending claims 10, 14 (Japanese Encephalitis).
Instant claim 11 is obvious over copending claims 11, 15.
Instant Claim 1: The SEQ ID NO: 5 (Qy) of instant application and SEQ ID NO: 5 (Db) co-pending application No. 19/149,483 shows 100% identity shown recited below:
Query Match 100.0%; Score 2811; DB 1; Length 530;
Best Local Similarity 100.0%;
Matches 530; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MPSNMKQFCKISVWLQQHDPDLLEIINNLCMLGNLSAAKYKHGVTFIYPKQAKIRDEIKK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MPSNMKQFCKISVWLQQHDPDLLEIINNLCMLGNLSAAKYKHGVTFIYPKQAKIRDEIKK 60
Qy 61 HAYSNDPSQAIKTLESLILPFYIPTPAEFTGEIGSYTGVKLEVEKTEANKVILKNGEAVL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 HAYSNDPSQAIKTLESLILPFYIPTPAEFTGEIGSYTGVKLEVEKTEANKVILKNGEAVL 120
Qy 121 VPAADFKPFPDRRLAVWIMESGSMPLEGPPYKRKKEGGGNDPPVPKHISPYTPRTRIAIE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VPAADFKPFPDRRLAVWIMESGSMPLEGPPYKRKKEGGGNDPPVPKHISPYTPRTRIAIE 180
Qy 181 VEKAFDDCMRQNWCSVNNPYLAKSVSLLSFLSLNHPTEFIKVLPLIDFDPLVTFYLLLEP 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VEKAFDDCMRQNWCSVNNPYLAKSVSLLSFLSLNHPTEFIKVLPLIDFDPLVTFYLLLEP 240
Qy 241 YKTHGDDFLIPETILFGPTGWNGTDLYQSAMLEFKKFFTQITRQTFMDIADSATKEVDVP 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 YKTHGDDFLIPETILFGPTGWNGTDLYQSAMLEFKKFFTQITRQTFMDIADSATKEVDVP 300
Qy 301 ICYSDPETVHSYANHVRTEILHHNAVNKVTTPNLVVQAYNELEQTNTIRHYGPIFPESTI 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 ICYSDPETVHSYANHVRTEILHHNAVNKVTTPNLVVQAYNELEQTNTIRHYGPIFPESTI 360
Qy 361 NALRFWKKLWQDEQRFVIHGLHRTLMDQPTYETSEFAEIVRNLRFSRPGNNYINELNITS 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NALRFWKKLWQDEQRFVIHGLHRTLMDQPTYETSEFAEIVRNLRFSRPGNNYINELNITS 420
Qy 421 PAMYGDKHTTGDIAPNDRFAMLVAFINSTDFLYTAIPEEKVGGNETQTSSLTDLVPTRLH 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PAMYGDKHTTGDIAPNDRFAMLVAFINSTDFLYTAIPEEKVGGNETQTSSLTDLVPTRLH 480
Qy 481 SFLNHNLSKLKILNRAQQTVRNILSNDCLNQLKHYVKHTGKNEILKLLQE 530
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 SFLNHNLSKLKILNRAQQTVRNILSNDCLNQLKHYVKHTGKNEILKLLQE 530
Instant Claims 1, 2: SEQ ID 5 and 37
The SEQ ID NO: 37 (Qy) of instant application and SEQ ID NO: 37 (Db) co-pending application No. 19/149,483 shows 100% identity shown recited below:
Query Match 100.0%; Score 1866; DB 1; Length 354;
Best Local Similarity 100.0%;
Matches 354; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MALTTHSGKLIPELQFKAHHFIDKTTVLYGPSKTGKTVYVKHIMKILQPHIEQILVVAPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MALTTHSGKLIPELQFKAHHFIDKTTVLYGPSKTGKTVYVKHIMKILQPHIEQILVVAPS 60
Qy 61 EPSNRSYEGFVHPTLIHYRLWLADKQKKNDNKGAERFLEAIWQRQTMMSSIYSRVNNIDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 EPSNRSYEGFVHPTLIHYRLWLADKQKKNDNKGAERFLEAIWQRQTMMSSIYSRVNNIDM 120
Qy 121 LKTLYHKLPIDIQQKENKNIAKVECLKAEQTDQKKEEKITSLYQQLLKKIIIQNIHMYKN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LKTLYHKLPIDIQQKENKNIAKVECLKAEQTDQKKEEKITSLYQQLLKKIIIQNIHMYKN 180
Qy 181 LCLTEDEKFTLNYINLNPRLLLILDDCAAELHPLFTKEIFKKFFYQNRHCFISMIICCQD 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LCLTEDEKFTLNYINLNPRLLLILDDCAAELHPLFTKEIFKKFFYQNRHCFISMIICCQD 240
Qy 241 DTDLPANLRKNAFVSIFTNASICMSNFSRQSNRYSKQDKEYVEEISHIVFKGYRKLVYIR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 DTDLPANLRKNAFVSIFTNASICMSNFSRQSNRYSKQDKEYVEEISHIVFKGYRKLVYIR 300
Qy 301 EDEHRQHFYHSTVPLPTAFSFGSKALLKLCKAVYSKEVVIDKSNPYWSKFRLNF 354
||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 EDEHRQHFYHSTVPLPTAFSFGSKALLKLCKAVYSKEVVIDKSNPYWSKFRLNF 354
Claim 8: SEQ ID 103
The SEQ ID NO: 103 (Qy) of instant application and SEQ ID NO: 103 (Db) co-pending application No. 19/149,483 shows 100% identity shown recited below:
Query Match 100.0%; Score 6635; DB 1; Length 1286;
Best Local Similarity 100.0%;
Matches 1286; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GLDLDTIQKSIIEWLRETQAANVNRANLIDWLGRKHGAISEIRNPGLVIKEINMRLSMVY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GLDLDTIQKSIIEWLRETQAANVNRANLIDWLGRKHGAISEIRNPGLVIKEINMRLSMVY 60
Qy 61 PDPTTEAAAAAQDRNLTTETLFAWIVPYVGIPAGGGVRPEQELAARYLVDNQRIMQLLLT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PDPTTEAAAAAQDRNLTTETLFAWIVPYVGIPAGGGVRPEQELAARYLVDNQRIMQLLLT 120
Qy 121 NIFEMTSSFNKMVQVRFPETSTAQVHLDFTGLISLIDSLMADTKYFLDLLRPHIDKNIIQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 NIFEMTSSFNKMVQVRFPETSTAQVHLDFTGLISLIDSLMADTKYFLDLLRPHIDKNIIQ 180
Qy 181 YYENRSNPGSFYWLEEHLIDKLIKPPTDAGGRPLPGGELGLEGVNQIINKTYTLLTKPYN 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YYENRSNPGSFYWLEEHLIDKLIKPPTDAGGRPLPGGELGLEGVNQIINKTYTLLTKPYN 240
Qy 241 VLQLRGGAQRRDAANIQINNNPQSSERFEQYGRVFSRLVFYDALENNSGLRVEQVALGDF 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 VLQLRGGAQRRDAANIQINNNPQSSERFEQYGRVFSRLVFYDALENNSGLRVEQVALGDF 300
Qy 301 RLSNLIRTNNAQEENTLSYWDNIALRTYANVNDAANNLRRYRLYGSDYGIQNNRSMMMVF 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 RLSNLIRTNNAQEENTLSYWDNIALRTYANVNDAANNLRRYRLYGSDYGIQNNRSMMMVF 360
Qy 361 NQLIASYITRFYDAPSGKIYLNLINAFANGNFSQAVMEMGYAHPDLARNNNVFGHRGDPT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NQLIASYITRFYDAPSGKIYLNLINAFANGNFSQAVMEMGYAHPDLARNNNVFGHRGDPT 420
Qy 421 EQSVLLLSLGLILQRLIKDTNRQGLSQHLISTLTEIPIYLKENYRANLPLFNKMFNILIS 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 EQSVLLLSLGLILQRLIKDTNRQGLSQHLISTLTEIPIYLKENYRANLPLFNKMFNILIS 480
Qy 481 QGELLKQFIQYTNVQLARPNLTALLGANNDSVIYYNNNNVPATGLSVGQAALRGIGGVFR 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 QGELLKQFIQYTNVQLARPNLTALLGANNDSVIYYNNNNVPATGLSVGQAALRGIGGVFR 540
Qy 541 PNVTLMPLGDAQNNTSDVVRKRLVAVIDGIIRGSHTLADSAMEVLHELTDHPIYLETEEH 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 PNVTLMPLGDAQNNTSDVVRKRLVAVIDGIIRGSHTLADSAMEVLHELTDHPIYLETEEH 600
Qy 601 FIQNYMSRYNKEPLMPFSLSLYYLHDLRIENNEVYDPLLYPNLESGSPEFKLLYGTRKLL 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 FIQNYMSRYNKEPLMPFSLSLYYLHDLRIENNEVYDPLLYPNLESGSPEFKLLYGTRKLL 660
Qy 661 GNDPVQLSDMPGVQLIMKNYNETVVAREQITPTRFEHFYTHAIQALRFIINIRSFKTVMM 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GNDPVQLSDMPGVQLIMKNYNETVVAREQITPTRFEHFYTHAIQALRFIINIRSFKTVMM 720
Qy 721 YNENTFGGVNLISENRDDKPIITAGIGMNAVYSLRKTLQDVISFVESSYQEEQINHIHKI 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 YNENTFGGVNLISENRDDKPIITAGIGMNAVYSLRKTLQDVISFVESSYQEEQINHIHKI 780
Qy 781 VSPKGQTRTLGSNRERERIFNLFDMNIIPINVNALMRSIPLANIYNYDYSFEEIACLMYG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 VSPKGQTRTLGSNRERERIFNLFDMNIIPINVNALMRSIPLANIYNYDYSFEEIACLMYG 840
Qy 841 ISAEKVRSLDTTAPQPDVAEVLNIPNRPPINTREFMLKLLINPYVSVSITQYGNELLSKG 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 ISAEKVRSLDTTAPQPDVAEVLNIPNRPPINTREFMLKLLINPYVSVSITQYGNELLSKG 900
Qy 901 NAGYMSRIFRGDNALNMGRPKFLSDQIFNKVLFGSLYPTQFDYDEAGPSLAAGIQRGRER 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 NAGYMSRIFRGDNALNMGRPKFLSDQIFNKVLFGSLYPTQFDYDEAGPSLAAGIQRGRER 960
Qy 961 WGHPMSIYINQALHEIVRTIRLAETVRGLRNVIDRNQIIGELNAFRTQLEDTRREVNNLI 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 WGHPMSIYINQALHEIVRTIRLAETVRGLRNVIDRNQIIGELNAFRTQLEDTRREVNNLI 1020
Qy 1021 QTPEIQNNPTPEIIAAIQNWVQQYRGQITNLIDLIGNAGQANSMINLIQNITPQTAGAQL 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 QTPEIQNNPTPEIIAAIQNWVQQYRGQITNLIDLIGNAGQANSMINLIQNITPQTAGAQL 1080
Qy 1081 TALFNIRGLPAPPPRQALQNDIEAMQWFMTMVINHPPVLIAPFMLLVNNLKEFLNTLERY 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 TALFNIRGLPAPPPRQALQNDIEAMQWFMTMVINHPPVLIAPFMLLVNNLKEFLNTLERY 1140
Qy 1141 VYKTPRWLGPGTARIAQPPVGMAPGINMRHHTSYTENSVLTYITEQNREEGPWSIVKQVG 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 VYKTPRWLGPGTARIAQPPVGMAPGINMRHHTSYTENSVLTYITEQNREEGPWSIVKQVG 1200
Qy 1201 VGIQKPTLVQIGKDRFDTRLIRNLIFITNIQRLLRLRLNLELSQFRNVLVSPDHIINPSI 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 VGIQKPTLVQIGKDRFDTRLIRNLIFITNIQRLLRLRLNLELSQFRNVLVSPDHIINPSI 1260
Qy 1261 TEYGFSITGPSETFSDKQYDSDIRIL 1286
||||||||||||||||||||||||||
Db 1261 TEYGFSITGPSETFSDKQYDSDIRIL 1286
The instant claims 1, 3-4, 7-11 are obvious over co-pending claims in view of the prior arts applied as recited supra. The prior art teachings, motivations and reasonable expectation of success to arrive at the inventions of instant claims 1, 3-4, 7-11 as recited supra are incorporated here in entirety by reference and applied for the provisional nonstatutory double patenting rejection.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments: Nonstatutory Double Patenting Rejection
Applicant's arguments regarding rejections under 35 U.S.C. 103 filed on 01/02/2026 have been fully considered but they are not persuasive for the following reasons:
Applicant’s arguments: Claims 1, 3-4, and 7-10 were provisionally rejected on the ground of nonstatutory double patenting as allegedly being unpatentable over claims 1-4 of copending Application No. 17/755,359 in view of Crosby et al, and further in view of Mwangi et al, Borca et al, Liu et al 2017, Liu et al 2016, Lokhandwala et al, and Haller et al 2003, Neill et al, Wang et al, Haller et al 2000, and Liang et al.
Additionally, Claims 1, 3-4, and 7-10 were provisionally rejected on the ground of nonstatutory double patenting as allegedly being unpatentable over claims 1-15 of copending Application No. 19/149,483 in view of Crosby et al, and further in view of Mwangi et al, Borca et al, Liu et al 2017, Liu et al 2016, Lokhandwala et al, and Haller et al 2003, Neill et al, Wang et al, Haller et al 2000, Skiadopoulos et al, Bailly et al, Haller et al 2001, and Liang et al. Applicants note that these are the same references and reference combinations addressed above.
Applicants respectfully traverse these nonstatutory double patenting rejections and assert that the present claims are patentably distinct. In support of Applicants' position, Applicants assert that the present claims are limited to an attenuated BPIV3 genotype C vector. To the extent the reference claims are directed to adenoviral platforms or non-genotype-C PIV3 backbones, substituting a genotype C backbone is not a mere obvious variant. As Neill 2015 shows, genotypes A, B, and C form distinct phylogenetic groups with antigenic differences (Figure 1; Table 4), and PIV3 vector behavior depends on backbone genotype, insert position, and polygenic determinants (Liang 2014; Skiadopoulos 2003). This unpredictability rebuts any equivalence-based obviousness.
With specific reference to claim limitations, the present claims require (i) a BPIV3c backbone, (ii) a chimeric ASFV gene comprising at least two sequences linked by self-cleaving peptides (claim 3), (iii) a multicistronic cassette (claim 4), (iv) defined sequence identity ranges to SEQ ID NOS: 1-101/102-131 (claims 1 and 8), and (v) optional second-organism antigens including JEV (claims 9-10). The copending references lack one or more of these limitations including (i) and (ii), which appear in the independent claim of the instant application. Because the present claims and the referenced claims are not directed to the same invention and are not obvious variants for the reasons above, a terminal disclaimer is not warranted. If the Office maintains the rejection, Applicants respectfully request a claim-by-claim mapping identifying the specific limitations in the reference claims and the precise rationale for obviousness-type double patenting in light of the BPIV3c limitations and the unpredictability documented in the PIV3 art.
Conclusion: In view of the foregoing, a Notice of Allowance appears to be in order and is therefore courteously solicited.
In Response:
In response to applicant’s argument filed on 01/02/2026 regarding alleged differences in the instant claims and co-pending claims as recited supra for provisional rejection on the ground of nonstatutory double patenting as being unpatentable have been fully considered but they are not persuasive. The prior art teachings as applied for the provisional rejection are analogous and the rejected instant claims and copending and are similar by the standard of obviousness analysis as recited and applied supra.
In response to applicant's argument that prior arts are nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992).
Applicant’s arguments that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
The provisional rejection of the instant claims (as recited supra) over the co-pending claims as recited supra on the ground of nonstatutory double patenting as being unpatentable is maintained.
16. Relevant Prior Art:
Chen et al (2016). Recombinant Newcastle disease virus expressing African swine fever virus protein 72 is safe and immunogenic in mice. Virol Sin. 2016 Apr;31(2):150-9. The prior art teaches a recombinant NDV that expresses ASFV immunogenic antigen encoding gene p72. Both the NDV and bPIV3 are members of the same family Paramyxoviridae and shares similarities in viral gene organization in the genome, replication strategy and morphological structure.
Le Nouën C, Brock LG, Luongo C, McCarty T, Yang L, Mehedi M, Wimmer E, Mueller S, Collins PL, Buchholz UJ, DiNapoli JM. Attenuation of human respiratory syncytial virus by genome-scale codon-pair deoptimization. Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13169-74.
Sato M, Wright PF. Current status of vaccines for parainfluenza virus infections. Pediatr Infect Dis J. 2008 Oct;27(10 Suppl):S123-5.
Kaplan et al (2018). Vaccination of pigs with a codon-pair bias de-optimized live attenuated influenza vaccine protects from homologous challenge. Vaccine. 2018 Feb 14;36(8):1101-1107.
Velazquez-Salinas et al 2016. Recoding structural glycoprotein E2 in classical swine fever virus (CSFV) produces complete virus attenuation in swine and protects infected animals against disease. Virology. 2016 Jul; 494:178-89.
Cai et al 2020. A Lassa Fever Live-Attenuated Vaccine Based on Codon Deoptimization of the Viral Glycoprotein Gene. mBio. 2020 Feb 25;11(1):e00039-20.
Conclusion
17. No claim is allowed.
18. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
19. 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.
20. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMADHAN J JADHAO whose telephone number is (703)756-1223. The examiner can normally be reached M-F 8:00-5:00.
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, Thomas J Visone can be reached at 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMADHAN JAISING JADHAO/Examiner, Art Unit 1672
/BENNETT M CELSA/Primary Examiner, Art Unit 1600