Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Acknowledgment is made of applicants' claim for foreign priority to European applications 20216198.0 filed on 12/21/2020. Certified copies of the foreign priority document(s) are present in the application file.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/20/2023 and 07/30/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Interpretation
Preferable embodiments in claims are not given patentable weight as they are not required by the claim.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 15 is rejected under 35 U.S.C. 101 because the claim is directed to a non-statutory subject matter.
The claim does not fall within at least one of the four categories of patent eligible subject matter because it is directed to a use of a modified Parapoxvirus or Parapoxvirus vector. The claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e. results in a claim which is not a proper process under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ678 (Bd.App.1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp.131, 149 USPQ 475 (D.D.C.1966).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 15 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth the subject matter which the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the applicant regards as the invention.
Claim 15 provides for the use of a modified Parapoxvirus or Parapoxvirus vector, but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Diel et al (J Virol. 2011 Mar; hereinafter "Diel;" See PTO-892).
Regarding claims 1-2: Diel was directed to modulation of host cell responses regulated by the nuclear factor-κB (NF-κB) signaling pathway using orf virus ORFV121, encoding a gene unique to parapoxviruses, a novel viral NF-κB inhibitor that binds to and inhibits the phosphorylation and nuclear translocation of NF-κB-p65. Diel taught that “infection of cells with an ORFV121 deletion mutant virus (OV-IA82Δ121) resulted in increased NF-κB-mediated gene transcription, and the expression of ORFV121 in cell cultures significantly suppressed NF-κB-regulated reporter gene expression.” (See Diel Abstract). Diel disclosed that expression of ORFV121 decreases NF-κB-mediated transcription induced by LPS and TNF-α suggesting reduced immunogenicity. (p. 2041, col. 1, 2nd para). Diel also disclosed that “OV-IA82Δ121 infection results in increased expression of NF-κB-regulated genes in primary OFTu cells.” (i.e., increased immunogenicity) (See Figure 3, p. 2040, col. 2, 2nd para), as required by claims 1 and 2.
Claims 1, 3-4, 7-8, 10, 12-13 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Martins et al (Virology. 2017 Nov; hereinafter "Martins;" See IDS of 06/20/2023).
Regarding claims 1, 3-4, 7-8, 12 and 15: Martins was directed to the construction and characterization of two recombinant ORFV vectors expressing the rabies virus (RABV) glycoprotein (G). (See Martins Abstract). Martins disclosed that “ORFV recombinant virus expressing the PEDV S protein and lacking the NF-κB inhibitor ORFV121 induces neutralizing antibody responses that led to protection from clinical disease and reduced virus shedding after challenge in pigs” (See Martins p. 231, col. 2, para 4). Martins disclosed “an ORFV recombinant virus expressing the PEDV S protein and lacking the NF-κB inhibitor ORFV121 induces neutralizing antibody responses that led to protection from clinical disease and reduced virus shedding after challenge in pigs.” (Martins p. 231, col. 2, para 4). Martins disclosed generation of “ORFV vectors expressing the RABV glycoprotein (ORFVΔ024RABV-G and ORFVΔ121 RABV-G). The RABV-G was inserted either into the ORFV024 or ORFV121 gene loci and the immunogenicity of the resultant recombinant viruses (ORFVΔ024RABV-G or ORFVΔ121RABV-G, respectively) was evaluated in pigs and cattle (As required by claim 8). Immunization of the target species with ORFVΔ024RABV-G and ORFVΔ121RABV-G elicited robust neutralizing responses against RABV. Notably, neutralizing antibody titers detected in ORFVΔ121RABV-G-immunized animals (pigs and cattle) were significantly higher than those detected in ORFVΔ024RABV-G-immunized animals, indicating a higher immunogenicity of ORFVΔ121-based vector on these species.” As such Martins taught mutating the NF-κB locus and generating a vector for delivery of rabies antigen (as required by claim 12), anticipating the subject claims.
Regarding claim 10: Martins used an early/late promoter, VV7.5, to drive expression of the RABG antigen.
Regarding claim 13: Martins used “OFTu cells cultured in 6-well plates [were] inoculated with ORFVΔ024RABV-G or ORFVΔ121RABV-G recombinant virus (MOI = 10) and harvested at 2, 4, 6, 8, 12 and 24 h pi to assess the expression kinetics of RABV-G.” As such Martins disclosed a OFTu cell comprising ORF vector as required by the claim.
Claims 1, 3, and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nagendraprabhu et al (PLoS Pathog. 2017 Dec 15; hereinafter "Nagendraprabhu;" See IDS of 06/20/2023).
Regarding claim 1, 3 and 6: Nagendraprabhu disclosed that ORFV119, inhibits NF-κB signaling very early in infection (≤ 30 min post infection). Nagendraprabhu also demonstrated “increased transcription of multiple NF-κB regulated genes in cells infected with OV-IA82-Δ119 compared to cells infected with OV-IA82 virus, suggesting that ORFV119 inhibits NF-κB signaling.” (See Nagendraprabhu p. 14, para 2). Further Fig. 4A of Nagendraprabhu showed increased TNF-alpha and other pro-immunogenic genes in response to deletion of ORF119. As such, Nagendraprabhu disclosed a parapoxvirus vector comprising a mutation in an ORF 119 NFKB inhibitor, wherein the virus comprises increased immunogenicity compared to the same vector without the mutation, thus anticipating claim 6.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Martins et al (Virology. 2017 Nov; hereinafter "Martins;" See IDS of 06/20/2023), in view of Rhiza et al (Viruses. 2019 Jan 30; hereinafter "Rhiza;" See IDS of 6/20/2023).
Regarding claims 5: The teachings of Martins are set forth above. In brief, Martins taught increased inmmunogenicity of ORFVΔ121-based vector in vaccines, compared to mutation in other regions. Martins did not teach a D1701 strain of parapoxvirus. It is however noted that Martins disclosed that cell culture adapted and highly attenuated ORFV strain D1701 have demonstrated the efficiency of ORFV as a vaccine delivery platform in non-permissive species, including mice, cats, dogs, rabbits and swine (See Martins p. 233, col. 2, para 2). Rzhia taught a D1701 strain of parapoxvirus with “an attenuated phenotype and excellent immunogenic capacity is successfully used for the generation of recombinant vaccines against different viral infections.” (See Rzhia Abstract). Rzhia taught that D1701-V, “in comparison to the predecessor strain D1701-B revealed the loss of 7 open reading frames (ORF008, ORF101, ORF102, ORF114, ORF115, ORF116, ORF117)” (Rzhia Abstract).
It would have been obvious for a person of ordinary skill in the art to combine the teachings of Martins, in view of Rzhia, to arrive at a parapoxvirus vector comprising mutation in the NF-kappa inhibitor region, for generation of vaccines in order to produce greater immunogenicity. Martins explicitly stated that “[g]iven the immunogenicity of ORFVΔ121-vector in both swine and cattle, this vector represents an excellent candidate for novel vaccine designs for use in these animal species.” (See Martins p. 236, last para, col. 2). As such there is clear suggestion, teaching and motivation to delete or mutate NF-κB in an alternative strain such as D1701.
Claims 9, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Martins et al (Virology. 2017 Nov; hereinafter "Martins;" See IDS of 06/20/2023).
Regarding claim 9: The teachings of Martins are set forth above. In brief, Martins taught increased immunogenicity of ORFVΔ121-based vector in vaccines, compared to mutation in other regions. Martins did not teach a parapoxvirus vector comprising more than 1 antigen in the NF-κB inhibitor encoding region. However, as indicated above, Martins taught insertion of one antigen (Rabies glycoprotein) in the NF-κB inhibitor encoding region. It would have been obvious to a person of ordinary skill in the art to insert more than one antigen in the ORF and expect increased immunogenicity, as taught by Martins, to broaden immune protection or to generate a multivalent vaccine. As such Martins demonstrated that the NF-κB inhibitor encoding region can carry foreign genes leading a person of ordinary skill in the art to have a reasonable expectation of success to insert many antigens. Such duplication or tandem arrangement of antigens represents routine optimization and predictable use of the system demonstrated by Martins.
Regarding claim 14: Teachings of Martins are set forth above. It is specifically noted that Martins taught the potential of the ORFVΔ121RABV-G recombinant virus as a vaccine candidate for use in cattle. A person of ordinary skill in the art would have been motivated to formulate the recombinant parapoxvirus vector as a pharmaceutical composition (e.g., suspended in a pharmaceutically acceptable carrier or buffer) for use as a vaccine in cattle or other animals. It is submitted that preparation of such a composition involves routine formulation steps well known in the art by combining a live recombinant viral vector with a physiologically acceptable diluent, stabilizer, or adjuvant for subcutaneous or intradermal administration and would have been carried out with a reasonable expectation of success given Martins’ experimental results and explicit statement of vaccine potential.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Martins et al (Virology. 2017 Nov; hereinafter "Martins;" See IDS of 06/20/2023) in view of WO2017013023A1 (Published Jan 26, 2017; See PTO-892).
Regarding claim 11: The teachings of Martins are set forth above. Martins taught use of a VV7.5 promoter to express a foreign antigen gene. Martins did not teach a promoter comprising any one of SEQ ID NOs: 1-5 as required, However, WO2017013023A1 disclosed SEQ ID NOs: 1-5 which are 100% identical to instant SEQ ID NOs: 1-5 as promoters for driving expression of exogenous genes. (see alignment below). A person of ordinary skill in the art, motivated by Martins’ teaching to insert antigen cassettes at ORFV121 and by WO2017013023’s disclosure of functional parapoxvirus promoters, would have found it obvious to employ the promoter sequences of WO2017013023 to drive expression of a heterologous antigen placed in the ORFV121 locus. The combination requires only routine cloning and homologous recombination techniques that Martins describes; there is a reasonable expectation of success and no teaching in the prior art of any unexpected incompatibility. Accordingly, the claimed subject matter would have been obvious.
Query 1 AAAAATTGAAAAATTA 16
||||||||||||||||
Sbjct 1 AAAAATTGAAAAATTA 16
Alignment of SEQ ID NO: 1 of instant application to SEQ ID NO: 1 of WO2017013023A1
Query 1 AAAAATTGAAATTCTA 16
||||||||||||||||
Sbjct 1 AAAAATTGAAATTCTA 16
Alignment of SEQ ID NO: 2 of instant application to SEQ ID NO: 2 of WO2017013023A1
Query 1 AAAAATTGAAAAAYTA 16
||||||||||||||||
Sbjct 1 AAAAATTGAAAAAYTA 16
Alignment of SEQ ID NO: 3 of instant application to SEQ ID NO: 3 of WO2017013023A1
Query 1 AAAAGTAGAAAATTA 15
|||||||||||||||
Sbjct 1 AAAAGTAGAAAATTA 15
Alignment of SEQ ID NO: 4 of instant application to SEQ ID NO: 4 of WO2017013023A1
Query 1 CAAAATGTAAATTATA 16
||||||||||||||||
Sbjct 1 CAAAATGTAAATTATA 16
Alignment of SEQ ID NO: 5 of instant application to SEQ ID NO: 5 of WO2017013023A1
Conclusion
No claim is free of art.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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, Christopher M. Babic can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JAGAMYA NMN VIJAYARAGHAVAN/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633