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 .
Status of claims
Claims 1, 4-15 are pending an under exam. Claims 2-3 are cancelled.
WITHDRAWN REJECTIONS
Claim Rejections - 35 USC § 102
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).
The rejection is withdrawn following claim amendments.
Claim Rejections - 35 USC § 112
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.
The claim amendments reciting a step of administering overcomes this rejection. As such the rejection is withdrawn.
MAINTAINED REJECTIONS
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).
Response to Arguments: Applicants alleged that they amended the claims to recite an active step. It is reiterated that use-type claims are ineligible subject matter under the U.S. Patent practice. As such this rejection is maintained.
NEW REJECTIONS NECESSITATED AND ADAPTED DUE TO CLAIM AMENDMENTS
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, 4, 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, 4 and 6: Nagendraprabhu disclosed “a recombinant virus containing an ORFV119 mutation which abrogates its interaction with pRb together with experiments performed in cells lacking or with reduced pRb levels indicate that ORFV119 mediated inhibition of NF-κB signaling is largely pRb dependent.” (Nagendraprabhu Abstract). The reference taught a recombinant ORFV comprising an ORFV119-mutation. The reference further taught that ORFV119 is an inhibitor of NF-κB signaling and that ORFV119-mediated inhibition of NF-κB signaling is largely pRB dependent. Accordingly, the disclosed mutation in ORFV119 reduces the NF-κB inhibitory activity of ORFV119 relative to the wild-type protein.
Claims 1, 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, 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.
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
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Sbjct 1 AAAAATTGAAAAATTA 16
Alignment of SEQ ID NO: 1 of instant application to SEQ ID NO: 1 of WO2017013023A1
Query 1 AAAAATTGAAATTCTA 16
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Sbjct 1 AAAAATTGAAATTCTA 16
Alignment of SEQ ID NO: 2 of instant application to SEQ ID NO: 2 of WO2017013023A1
Query 1 AAAAATTGAAAAAYTA 16
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Sbjct 1 AAAAATTGAAAAAYTA 16
Alignment of SEQ ID NO: 3 of instant application to SEQ ID NO: 3 of WO2017013023A1
Query 1 AAAAGTAGAAAATTA 15
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Sbjct 1 AAAAGTAGAAAATTA 15
Alignment of SEQ ID NO: 4 of instant application to SEQ ID NO: 4 of WO2017013023A1
Query 1 CAAAATGTAAATTATA 16
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Sbjct 1 CAAAATGTAAATTATA 16
Alignment of SEQ ID NO: 5 of instant application to SEQ ID NO: 5 of WO2017013023A1
Response to Arguments: Applicants argued that “claim 1 incorporates the features and limitations of previous claim 3, which the Office acknowledged to be novel over Diel.” Further Applicants argued that “present claim 1 incorporates the features and limitations of previous claim 2, which the Office acknowledged to be novel over Martins.” Applicant’s arguments have been fully considered but are not persuasive.
It is pointed out that absence of rejection over Diel, Martins and/or Nagendraprabhu for claims 2 and/or 3 do not constitute an affirmative finding that the claims are patentable/novel over the cited references. The Office did not make any express determination that the indicated claims are novel over the cited art in general. Rather, the prior rejection reflected the grounds applied at that stage of examination. Upon further examination of the amended claims and prior art of record, the indicated references are properly applicable to the subject matter of presently amended claims. Accordingly, Applicant’s assertion that the Office previously acknowledged novelty over any of the cited references is not supported by the record.
Conclusion
No claim is free of art. No claim is allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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.
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/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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