DETAILED ACTION
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 the Claims
Claims 26-27 and 30-31 have been withdraw as being directed to a non-elected invention. Claim 11 has been withdrawn as being directed to a non-elected species. Claims 1-3, 6-9,12-13,16-18 and 34 are under examination at this time.
Withdrawn Rejections
The rejection of claim 5 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, has been withdrawn in view of the cancelation of claim 5.
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.
Claims 1-3, 12-13, 16-18 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Mu et al. (CA3114658; effectively filed September 27, 2018) and further in view of Antrobus et al. (www.moleculartherapy.org, 2014, 22(3): 668–674; cited by applicant).
The instant claims are directed to a composition comprising a viral vector comprising nucleic acid having a polynucleotide sequence encoding at least one epitope of the varicella-zoster virus (VZV) Gly E antigen, wherein the viral vector is ChAdOx1, and wherein the composition is adjuvant-free.
Mu et al. discloses an adenoviral vector encoding and expressing only gE from VZV or expressing various gE-flagellin fusion proteins (see the abstract; paragraph bridging pages 4-5; and Figure 3). Mu et al. also teaches that the adenoviral vector used to express VZV gE can be a chimpanzee adenoviral vector, such as ChAd68. Specifically, Mu et al. teaches “the adenovirus vector is a human adenovirus vector ( e.g., adenovirus type-5 vector (Ad5)), a chimpanzee adenovirus vector (e.g., ChAd68), a gorilla adenovirus vector, or other human-suitable adenovirus vectors (see page 10, last paragraph).
While Mu et al. teaches that a chimpanzee adenovirus can be used, Mu et al. does not specifically teach using chimpanzee adenovirus ChAdOx1. Antrobus et al. teaches the use of chimpanzee adenoviral vector ChAdOx1 to deliver viral antigens. Antrobus et al. states that simian adenoviruses like ChAdOx1 do not suffer from the problems of human adenoviruses (e.g., AdHu5) such as widespread seroprevalence of antibodies which limits the utility of human Ad5 viruses as vaccine vectors in humans (see the Introduction). Antrobus et al. constructed a replication-deficient chimpanzee adenovirus-vectored vaccine expressing the conserved influenza antigens, nucleoprotein (NP), and matrix protein 1 (M1). Antrobus et al. found that the ChAdOx1 constructs were safe and immunogenic and that ChAdOx1 is a promising vaccine vector that could be used to deliver vaccine antigens where strong cellular immune responses are required for protection (see, for example, the abstract).
Based on the teachings of Mu et al. and Antrobus et al., it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use chimpanzee adenovirus vectors known in the art, including ChAdOx1, as the chimpanzee adenoviral vector in the constructs of Mu et al. for expressing the gE protein. One would have been motivated to do so given and there would have been a reasonable expectation of success given the teachings of Mu et al. [chimpanzee adenovirus vectors can be used generally] and given the teachings of Antrobus et al. [ChAdOx1 is a promising vaccine vector that could be used to deliver vaccine antigens where strong cellular immune responses are required for protection; ChAdOx1 does not suffer from widespread seroprevalence of antibodies].
Regarding the limitation “adjuvant-free”, Mu et al. teaches that the adjuvant may have side effects (see page 3 and page 48, top). Mu et al. further teaches that immune adjuvants have different enhancing properties and may cause various adverse side effects (see page 4). Mu et al. states:
In order to overcome the above-mentioned drawbacks of the marketed vaccines and reduce the adverse reactions, the present invention develops a novel immune composition by two different methods. One method is to produce a recombinant gE protein or gE-based fusion immunogen which is capable of inducing strong neutralizing antibodies and CD4+ T cell responses and has reduced side effects; the other method is to construct a safer replication-defective adenovirus vector to express the gE gene or gE-:flagellin fusion protein gene so as to elicit neutralizing antibody responses and broader CD4+ T cell and CD8+ T cell immunity . . . .
(see paragraph bridging pages 4-5).
Mu et al. found that the recombinant adenovirus vector expressing the gE protein induced high neutralizing antibodies (see Figure 11, page 44 and Table 5). Mu et al. also found that “all immune components have high immunogenicity and can induce strong gE-specific antibodies and in vitro functional neutralizing antibodies related to the protection; meanwhile, the immune components can induce CD4+ Th1 and Th2 T cell immunity, which plays an important role in the prevention and recovery of shingles” and that “non-replicating adenovirus vector expressing gE or gE-:flagellin fusion protein can not only induce good gE-specific antibodies, VZV neutralization responses and CD4+ T cell responses, but also induce the body to generate CD8+ T cell immunity, thereby further destroying cells infected by VZV” (see page 48).
Accordingly, the construct of Mu et al. does not comprise an adjuvant. Further, Mu et al. teaches compositions comprising an adenoviral vector encoding only VZV gE (see page 15 and the claims). Further, one of ordinary skill in the art desiring to reduce or eliminate the potential side/adverse effects of adjuvants would be motivated to use the adenovirus vector (e.g., ChAdOx1) expressing gE alone (as exemplified in Figure 3 of Mu et al.). One would have been motivated to do so and there would have been a reasonable expectation of success given the teachings of Mu et al. outlined above.
Regarding claim 2, Mu et al. uses the entire gE gene. Thus, there are CD4 and CD8 T-cell epitopes present.
Regarding claim 3, Mu et al. teaches that the adenovirus vector is human, chimpanzee, or other human-suitable adenovirus vector (see page 10, last paragraph).
Claims 12, 13, 16-18 and 34 are directed to the composition of claim 1 configured in various ways, however, no additional structure or description is provided for each claim. Accordingly, claims 12, 13, 16-18 and 34 are interpreted as being directed to the composition of claim 1.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 6 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Mu et al. (CA3114658; effectively filed September 27, 2018) and Antrobus et al. (www.moleculartherapy.org, 2014, 22(3): 668–674; cited by applicant) as applied to claims 1-3, 12-13, 16-18 and 34 above, and further in view of Cho et al. (WO2016064063; published April 28, 2016) and Kew et al. (WO2006042156; published April 20, 2006).
The instant claims are directed to the composition of claim 1 where the gE has the amino acid sequence of instant of SEQ ID NO: 1 or 2 (claim 6) or the gE has the polynucleotide sequence of SEQ ID NO: 3 or 4 (claim 7).
The teachings of Mu et al. and Antrobus et al. are outline above and incorporated herein. Mu et al. and Antrobus et al. do not teach instant SEQ ID NOs: 1 or 2 or instant SEQ ID NOs: 3 or 4. However, Cho et al. discloses a sequence that is 100% identical to instant SEQ ID NO: 1 (see the alignment below).
Query Match 100.0%; Score 3380; Length 641;
Best Local Similarity 100.0%;
Matches 623; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MGTVNKPVVGVLMGFGIITGTLRITNPVRASVLRYDDFHIDEDKLDTNSVYEPYYHSDHA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 19 MGTVNKPVVGVLMGFGIITGTLRITNPVRASVLRYDDFHIDEDKLDTNSVYEPYYHSDHA 78
Qy 61 ESSWVNRGESSRKAYDHNSPYIWPRNDYDGFLENAHEHHGVYNQGRGIDSGERLMQPTQM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 79 ESSWVNRGESSRKAYDHNSPYIWPRNDYDGFLENAHEHHGVYNQGRGIDSGERLMQPTQM 138
Qy 121 SAQEDLGDDTGIHVIPTLNGDDRHKIVNVDQRQYGDVFKGDLNPKPQGQRLIEVSVEENH 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 139 SAQEDLGDDTGIHVIPTLNGDDRHKIVNVDQRQYGDVFKGDLNPKPQGQRLIEVSVEENH 198
Qy 181 PFTLRAPIQRIYGVRYTETWSFLPSLTCTGDAAPAIQHICLKHTTCFQDVVVDVDCAENT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 199 PFTLRAPIQRIYGVRYTETWSFLPSLTCTGDAAPAIQHICLKHTTCFQDVVVDVDCAENT 258
Qy 241 KEDQLAEISYRFQGKKEADQPWIVVNTSTLFDELELDPPEIEPGVLKVLRTEKQYLGVYI 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 259 KEDQLAEISYRFQGKKEADQPWIVVNTSTLFDELELDPPEIEPGVLKVLRTEKQYLGVYI 318
Qy 301 WNMRGSDGTSTYATFLVTWKGDEKTRNPTPAVTPQPRGAEFHMWNYHSHVFSVGDTFSLA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 319 WNMRGSDGTSTYATFLVTWKGDEKTRNPTPAVTPQPRGAEFHMWNYHSHVFSVGDTFSLA 378
Qy 361 MHLQYKIHEAPFDLLLEWLYVPIDPTCQPMRLYSTCLYHPNAPQCLSHMNSGCTFTSPHL 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 379 MHLQYKIHEAPFDLLLEWLYVPIDPTCQPMRLYSTCLYHPNAPQCLSHMNSGCTFTSPHL 438
Qy 421 AQRVASTVYQNCEHADNYTAYCLGISHMEPSFGLILHDGGTTLKFVDTPESLSGLYVFVV 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 439 AQRVASTVYQNCEHADNYTAYCLGISHMEPSFGLILHDGGTTLKFVDTPESLSGLYVFVV 498
Qy 481 YFNGHVEAVAYTVVSTVDHFVNAIEERGFPPTAGQPPATTKPKEITPVNPGTSPLLRYAA 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 499 YFNGHVEAVAYTVVSTVDHFVNAIEERGFPPTAGQPPATTKPKEITPVNPGTSPLLRYAA 558
Qy 541 WTGGLAAVVLLCLVIFLICTAKRMRVKAYRVDKSPYNQSMYYAGLPVDDFEDSESTDTEE 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 559 WTGGLAAVVLLCLVIFLICTAKRMRVKAYRVDKSPYNQSMYYAGLPVDDFEDSESTDTEE 618
Qy 601 EFGNAIGGSHGGSSYTVYIDKTR 623
|||||||||||||||||||||||
Db 619 EFGNAIGGSHGGSSYTVYIDKTR 641
In addition, Kew et al. discloses a sequence that is 100% identical to instant SEQ ID NO: 3 (see the alignment below)
Query Match 100.0%; Score 1872; Length 1872;
Best Local Similarity 100.0%;
Matches 1872; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGGGGACAGTTAATAAACCTGTGGTGGGGGTATTGATGGGGTTCGGAATTATCACGGGA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGGGGACAGTTAATAAACCTGTGGTGGGGGTATTGATGGGGTTCGGAATTATCACGGGA 60
Qy 61 ACGTTGCGTATAACGAATCCGGTCAGAGCATCCGTCTTGCGATACGATGATTTTCACATC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ACGTTGCGTATAACGAATCCGGTCAGAGCATCCGTCTTGCGATACGATGATTTTCACATC 120
Qy 121 GATGAAGACAAACTGGATACAAACTCCGTATATGAGCCTTACTACCATTCAGATCATGCG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GATGAAGACAAACTGGATACAAACTCCGTATATGAGCCTTACTACCATTCAGATCATGCG 180
Qy 181 GAGTCTTCATGGGTAAATCGGGGAGAGTCTTCGCGAAAAGCGTACGATCATAACTCACCT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GAGTCTTCATGGGTAAATCGGGGAGAGTCTTCGCGAAAAGCGTACGATCATAACTCACCT 240
Qy 241 TATATATGGCCACGTAATGATTATGATGGATTTTTAGAGAACGCACACGAACACCATGGG 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TATATATGGCCACGTAATGATTATGATGGATTTTTAGAGAACGCACACGAACACCATGGG 300
Qy 301 GTGTATAATCAGGGCCGTGGTATCGATAGCGGGGAACGGTTAATGCAACCCACACAAATG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GTGTATAATCAGGGCCGTGGTATCGATAGCGGGGAACGGTTAATGCAACCCACACAAATG 360
Qy 361 TCTGCACAGGAGGATCTTGGGGACGATACGGGCATCCACGTTATCCCTACGTTAAACGGC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 TCTGCACAGGAGGATCTTGGGGACGATACGGGCATCCACGTTATCCCTACGTTAAACGGC 420
Qy 421 GATGACAGACATAAAATTGTAAATGTGGACCAACGTCAATACGGTGACGTGTTTAAAGGA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GATGACAGACATAAAATTGTAAATGTGGACCAACGTCAATACGGTGACGTGTTTAAAGGA 480
Qy 481 GATCTTAATCCAAAACCCCAAGGCCAAAGACTCATTGAGGTGTCAGTGGAAGAAAATCAC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GATCTTAATCCAAAACCCCAAGGCCAAAGACTCATTGAGGTGTCAGTGGAAGAAAATCAC 540
Qy 541 CCGTTTACTTTACGCGCACCGATTCAGCGGATTTATGGAGTCCGGTACACCGAGACTTGG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 CCGTTTACTTTACGCGCACCGATTCAGCGGATTTATGGAGTCCGGTACACCGAGACTTGG 600
Qy 601 AGCTTTTTGCCGTCATTAACCTGTACGGGAGACGCAGCGCCCGCCATCCAGCATATATGT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 AGCTTTTTGCCGTCATTAACCTGTACGGGAGACGCAGCGCCCGCCATCCAGCATATATGT 660
Qy 661 TTAAAACATACAACATGCTTTCAAGACGTGGTGGTGGATGTGGATTGCGCGGAAAATACT 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 TTAAAACATACAACATGCTTTCAAGACGTGGTGGTGGATGTGGATTGCGCGGAAAATACT 720
Qy 721 AAAGAGGATCAGTTGGCCGAAATCAGTTACCGTTTTCAAGGTAAGAAGGAAGCGGACCAA 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 AAAGAGGATCAGTTGGCCGAAATCAGTTACCGTTTTCAAGGTAAGAAGGAAGCGGACCAA 780
Qy 781 CCGTGGATTGTTGTAAACACGAGCACACTGTTTGATGAACTCGAATTAGACCCCCCCGAG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 CCGTGGATTGTTGTAAACACGAGCACACTGTTTGATGAACTCGAATTAGACCCCCCCGAG 840
Qy 841 ATTGAACCGGGTGTCTTGAAAGTACTTCGGACAGAAAAACAATACTTGGGTGTGTACATT 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 ATTGAACCGGGTGTCTTGAAAGTACTTCGGACAGAAAAACAATACTTGGGTGTGTACATT 900
Qy 901 TGGAACATGCGCGGCTCCGATGGTACGTCTACCTACGCCACGTTTTTGGTCACCTGGAAA 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 TGGAACATGCGCGGCTCCGATGGTACGTCTACCTACGCCACGTTTTTGGTCACCTGGAAA 960
Qy 961 GGGGATGAAAAAACAAGAAACCCTACGCCCGCAGTAACTCCTCAACCAAGAGGGGCTGAG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 GGGGATGAAAAAACAAGAAACCCTACGCCCGCAGTAACTCCTCAACCAAGAGGGGCTGAG 1020
Qy 1021 TTTCATATGTGGAATTACCACTCGCATGTATTTTCAGTTGGTGATACGTTTAGCTTGGCA 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 TTTCATATGTGGAATTACCACTCGCATGTATTTTCAGTTGGTGATACGTTTAGCTTGGCA 1080
Qy 1081 ATGCATCTTCAGTATAAGATACATGAAGCGCCATTTGATTTGCTGTTAGAGTGGTTGTAT 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 ATGCATCTTCAGTATAAGATACATGAAGCGCCATTTGATTTGCTGTTAGAGTGGTTGTAT 1140
Qy 1141 GTCCCCATCGATCCTACATGTCAACCAATGCGGTTATATTCTACGTGTTTGTATCATCCC 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 GTCCCCATCGATCCTACATGTCAACCAATGCGGTTATATTCTACGTGTTTGTATCATCCC 1200
Qy 1201 AACGCACCCCAATGCCTCTCTCATATGAATTCCGGTTGTACATTTACCTCGCCACATTTA 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 AACGCACCCCAATGCCTCTCTCATATGAATTCCGGTTGTACATTTACCTCGCCACATTTA 1260
Qy 1261 GCCCAGCGTGTTGCAAGCACAGTGTATCAAAATTGTGAACATGCAGATAACTACACCGCA 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 GCCCAGCGTGTTGCAAGCACAGTGTATCAAAATTGTGAACATGCAGATAACTACACCGCA 1320
Qy 1321 TATTGTCTGGGAATATCTCATATGGAGCCTAGCTTTGGTCTAATCTTACACGACGGGGGC 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 TATTGTCTGGGAATATCTCATATGGAGCCTAGCTTTGGTCTAATCTTACACGACGGGGGC 1380
Qy 1381 ACCACGTTAAAGTTTGTAGATACACCCGAGAGTTTGTCGGGATTATACGTTTTTGTGGTG 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 ACCACGTTAAAGTTTGTAGATACACCCGAGAGTTTGTCGGGATTATACGTTTTTGTGGTG 1440
Qy 1441 TATTTTAACGGGCATGTTGAAGCCGTAGCATACACTGTTGTATCCACAGTAGATCATTTT 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 TATTTTAACGGGCATGTTGAAGCCGTAGCATACACTGTTGTATCCACAGTAGATCATTTT 1500
Qy 1501 GTAAACGCAATTGAAGAGCGTGGATTTCCGCCAACGGCCGGTCAGCCACCGGCGACTACT 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 GTAAACGCAATTGAAGAGCGTGGATTTCCGCCAACGGCCGGTCAGCCACCGGCGACTACT 1560
Qy 1561 AAACCCAAGGAAATTACCCCCGTAAACCCCGGAACGTCACCACTTCTACGATATGCCGCA 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 AAACCCAAGGAAATTACCCCCGTAAACCCCGGAACGTCACCACTTCTACGATATGCCGCA 1620
Qy 1621 TGGACCGGAGGGCTTGCAGCAGTAGTACTTTTATGTCTCGTAATATTTTTAATCTGTACG 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 TGGACCGGAGGGCTTGCAGCAGTAGTACTTTTATGTCTCGTAATATTTTTAATCTGTACG 1680
Qy 1681 GCTAAACGAATGAGGGTTAAAGCCTATAGGGTAGACAAGTCCCCGTATAACCAAAGCATG 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 GCTAAACGAATGAGGGTTAAAGCCTATAGGGTAGACAAGTCCCCGTATAACCAAAGCATG 1740
Qy 1741 TATTACGCTGGCCTTCCAGTGGACGATTTCGAGGACTCGGAATCTACGGATACGGAAGAA 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 TATTACGCTGGCCTTCCAGTGGACGATTTCGAGGACTCGGAATCTACGGATACGGAAGAA 1800
Qy 1801 GAGTTTGGTAACGCGATTGGAGGGAGTCACGGGGGTTCGAGTTACACGGTGTATATAGAT 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1801 GAGTTTGGTAACGCGATTGGAGGGAGTCACGGGGGTTCGAGTTACACGGTGTATATAGAT 1860
Qy 1861 AAGACCCGGTGA 1872
||||||||||||
Db 1861 AAGACCCGGTGA 1872
It would be obvious and routine for one of ordinary skill in the art to select gE amino acid sequences or gE polynucleotide sequences known in the art for use in the construct of Mu et al. and the result would be predictable (expression of VZV gE from the ChAdOx1 vector).
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Mu et al. (CA3114658; effectively filed September 27, 2018) and Antrobus et al. (www.moleculartherapy.org, 2014, 22(3): 668–674; cited by applicant) as applied to claims 1-3, 12-13, 16-18 and 34 above, and further in view of GenBank Accession number AH009106.2 (Feb 1, 2000) and GenBank Accession number KY978851 (May 9, 2017).
The instant claims are directed to the composition of claim 1 where the construct comprises the bgh polyadenylation signal of instant SEQ ID NO: 6 (claim 8) or the CMV promoter of instant SEQ ID NO: 7 (claim 9).
The teachings of Mu et al. and Antrobus et al. are outline above and incorporated herein. Mu et al. and Antrobus et al. further teach a pAd5-CMV plasmid with the CMV promoter and the gE gene with or without SV40 polyA (referred to as pAd5-CMV (VZV)) (see page 34, section 1.2.2). Mu et al. and Antrobus et al. do not teach instant SEQ ID NOs: 6 or 7. However, GenBank Accession number AH009106.2 discloses the bgh poly(A) signal that is 100% identical to instant SEQ ID NO: 6 (see the alignment below).
LOCUS AH009106 2204 bp DNA linear MAM 10-JUN-2016
DEFINITION Bos taurus growth hormone (bGH) gene, partial cds.
ACCESSION AH009106 AF117346 AF117347 AF117348 AF117349 AF117350
VERSION AH009106.2
SEQ6 1 CTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1771 CTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCC 1830
SEQ6 61 TGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1831 TGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTC 1890
SEQ6 121 TGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1891 TGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATT 1950
SEQ6 181 GGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGG 225
|||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1951 GGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGG 1995
In addition, GenBank Accession number KY978851 discloses a CMV promoter sequence that is 100% identical to instant SEQ ID NO: 7 (see the alignment below)
LOCUS KY978851 3415 bp DNA linear SYN 09-MAY-2017
DEFINITION Synthetic construct Pfs28-SnoopTag gene, complete cds.
ACCESSION KY978851
VERSION KY978851.1
SEQ7 1 ATCGCCATTTTTCCAAAAGTGATTTTTGGGCATACGCGATATCTGGCGATAGCGCTTATA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 262 ATCGCCATTTTTCCAAAAGTGATTTTTGGGCATACGCGATATCTGGCGATAGCGCTTATA 321
SEQ7 61 TCGTTTACGGGGGATGGCGATAGACGACTTTGGTGACTTGGGCGATTCTGTGTGTCGCAA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 322 TCGTTTACGGGGGATGGCGATAGACGACTTTGGTGACTTGGGCGATTCTGTGTGTCGCAA 381
SEQ7 121 ATATCGCAGTTTCGATATAGGTGACAGACGATATGAGGCTATATCGCCGATAGAGGCGAC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 382 ATATCGCAGTTTCGATATAGGTGACAGACGATATGAGGCTATATCGCCGATAGAGGCGAC 441
SEQ7 181 ATCAAGCTGGCACATGGCCAATGCATATCGATCTATACATTGAATCAATATTGGCCATTA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 442 ATCAAGCTGGCACATGGCCAATGCATATCGATCTATACATTGAATCAATATTGGCCATTA 501
SEQ7 241 GCCATATTATTCATTGGTTATATAGCATAAATCAATATTGGCTATTGGCCATTGCATACG 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 502 GCCATATTATTCATTGGTTATATAGCATAAATCAATATTGGCTATTGGCCATTGCATACG 561
SEQ7 301 TTGTATCCATATCATAATATGTACATTTATATTGGCTCATGTCCAACATTACCGCCATGT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 562 TTGTATCCATATCATAATATGTACATTTATATTGGCTCATGTCCAACATTACCGCCATGT 621
SEQ7 361 TGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 622 TGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGC 681
SEQ7 421 CCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 682 CCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCC 741
SEQ7 481 AACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 742 AACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGG 801
SEQ7 541 ACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACAT 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 802 ACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACAT 861
SEQ7 601 CAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCC 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 862 CAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCC 921
SEQ7 661 TGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTA 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 922 TGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTA 981
SEQ7 721 TTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAG 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 982 TTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAG 1041
SEQ7 781 CGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTT 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1042 CGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTT 1101
SEQ7 841 TGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAA 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1102 TGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAA 1161
SEQ7 901 ATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCCCTATCAGTGAT 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1162 ATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCCCTATCAGTGAT 1221
SEQ7 961 AGAGATCTCCCTATCAGTGATAGAGATCGTCGACGAGCTCGTTTAGTGAACCGTCAGATC 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1222 AGAGATCTCCCTATCAGTGATAGAGATCGTCGACGAGCTCGTTTAGTGAACCGTCAGATC 1281
SEQ7 1021 GCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGC 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1282 GCCTGGAGACGCCATCCACGCTGTTTTGACCTCCATAGAAGACACCGGGACCGATCCAGC 1341
SEQ7 1081 CTCCGCGGCCGGGAACGGTGCATTGGAACGCGGATTCCCCGTGCCAAGAGTGACGTAAGT 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1342 CTCCGCGGCCGGGAACGGTGCATTGGAACGCGGATTCCCCGTGCCAAGAGTGACGTAAGT 1401
SEQ7 1141 ACCGCCTATAGAGTCTATAGGCCCACCCCCTTGGCTTCTTATGCATGCTATACTGTTTTT 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1402 ACCGCCTATAGAGTCTATAGGCCCACCCCCTTGGCTTCTTATGCATGCTATACTGTTTTT 1461
SEQ7 1201 GGCTTGGGGTCTATACACCCCCGCTTCCTCATGTTATAGGTGATGGTATAGCTTAGCCTA 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1462 GGCTTGGGGTCTATACACCCCCGCTTCCTCATGTTATAGGTGATGGTATAGCTTAGCCTA 1521
SEQ7 1261 TAGGTGTGGGTTATTGACCATTATTGACCACTCCCCTATTGGTGACGATACTTTCCATTA 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1522 TAGGTGTGGGTTATTGACCATTATTGACCACTCCCCTATTGGTGACGATACTTTCCATTA 1581
SEQ7 1321 CTAATCCATAACATGGCTCTTTGCCACAACTCTCTTTATTGGCTATATGCCAATACACTG 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1582 CTAATCCATAACATGGCTCTTTGCCACAACTCTCTTTATTGGCTATATGCCAATACACTG 1641
SEQ7 1381 TCCTTCAGAGACTGACACGGACTCTGTATTTTTACAGGATGGGGTCTCATTTATTATTTA 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1642 TCCTTCAGAGACTGACACGGACTCTGTATTTTTACAGGATGGGGTCTCATTTATTATTTA 1701
SEQ7 1441 CAAATTCACATATACAACACCACCGTCCCCAGTGCCCGCAGTTTTTATTAAACATAACGT 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1702 CAAATTCACATATACAACACCACCGTCCCCAGTGCCCGCAGTTTTTATTAAACATAACGT 1761
SEQ7 1501 GGGATCTCCACGCGAATCTCGGGTACGTGTTCCGGACATGGGCTCTTCTCCGGTAGCGGC 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1762 GGGATCTCCACGCGAATCTCGGGTACGTGTTCCGGACATGGGCTCTTCTCCGGTAGCGGC 1821
SEQ7 1561 GGAGCTTCTACATCCGAGCCCTGCTCCCATGCCTCCAGCGACTCATGGTCGCTCGGCAGC 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1822 GGAGCTTCTACATCCGAGCCCTGCTCCCATGCCTCCAGCGACTCATGGTCGCTCGGCAGC 1881
SEQ7 1621 TCCTTGCTCCTAACAGTGGAGGCCAGACTTAGGCACAGCACGATGCCCACCACCACCAGT 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1882 TCCTTGCTCCTAACAGTGGAGGCCAGACTTAGGCACAGCACGATGCCCACCACCACCAGT 1941
SEQ7 1681 GTGCCGCACAAGGCCGTGGCGGTAGGGTATGTGTCTGAAAATGAGCTCGGGGAGCGGGCT 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1942 GTGCCGCACAAGGCCGTGGCGGTAGGGTATGTGTCTGAAAATGAGCTCGGGGAGCGGGCT 2001
SEQ7 1741 TGCACCGCTGACGCATTTGGAAGACTTAAGGCAGCGGCAGAAGAAGATGCAGGCAGCTGA 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2002 TGCACCGCTGACGCATTTGGAAGACTTAAGGCAGCGGCAGAAGAAGATGCAGGCAGCTGA 2061
SEQ7 1801 GTTGTTGTGTTCTGATAAGAGTCAGAGGTAACTCCCGTTGCGGTGCTGTTAACGGTGGAG 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2062 GTTGTTGTGTTCTGATAAGAGTCAGAGGTAACTCCCGTTGCGGTGCTGTTAACGGTGGAG 2121
SEQ7 1861 GGCAGTGTAGTCTGAGCAGTACTCGTTGCTGCCGCGCGCGCCACCAGACATAATAGCTGA 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2122 GGCAGTGTAGTCTGAGCAGTACTCGTTGCTGCCGCGCGCGCCACCAGACATAATAGCTGA 2181
SEQ7 1921 CAGACTAACAGACTGTTCCTTTCCATGGGTCTTTTCTGCA 1960
||||||||||||||||||||||||||||||||||||||||
Sbjct 2182 CAGACTAACAGACTGTTCCTTTCCATGGGTCTTTTCTGCA 2221
It would be obvious and routine for one of ordinary skill in the art to select CMV promoter and polyadenylation signals known in the art and the result would be predictable (transcription of VZV gE from the CMV promoter and nuclear export and stability of the mature transcripts due to the poly(A) signal).
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Arguments
In the reply dated 10/72025, applicant argues that Mu et al. teaches using a recombinant adenovirus vector that expresses VZV gE glycoprotein and the flagellin fusion protein and uses said vector to raise antibody and humoral immune responses. Applicant’s arguments have been considered and not found persuasive.
Mu et al. discloses an adenoviral vector encoding and expressing only gE from VZV or expressing various gE-flagellin fusion proteins (see the abstract; paragraph bridging pages 4-5; and Figure 3). Mu et al. found that the recombinant adenovirus vector expressing the gE protein induced high neutralizing antibodies (see Figure 11, page 44 and Table 5).
Applicant next argues that one of ordinary skill in the art would have no reason (motivation) to make the “very specific selection” of ChAdOx1 as the chimpanzee adenoviral vector in the construct of Mu et al. “since the skilled artisan would have had no way to predict the surprising advantageous effect that a large cell-mediated immune response results when using ChAdOx1”. Applicant’s arguments have been considered and not found persuasive.
As outlined above, Mu et al. teaches that any chimpanzee vector can be used. Mu et al. exemplified ChAd68. However, the prior art establishes that ChAdOx1 is a very suitable vector. In this regard, Antrobus et al. teaches that ChAdOx1 is a safe, immunogenic, and promising vaccine vector that could be used to deliver vaccine antigens where strong cellular immune responses are required for protection. Further, ChAdOx1 does not suffer from widespread seroprevalence of antibodies. Antrobus et al. concludes by stating “Replication-deficient simian adenovirus vectors are ideal for infectious disease vaccines where cellular immunity is required as they induce broad, potent, and well-maintained immune responses after a single vaccination, so it could be used to confer broad immunity rapidly”. These findings and teachings provide motivation for one of ordinary skill in the art to select ChAdOx1 as the chimpanzee vector that can induce strong cellular immune responses. Accordingly, contrary to applicant’s assertion, one of ordinary skill in the art would expect “a large cell-mediated immune response” when using ChAdOx1.
Applicant next argues that claim 1 lacks an adjuvant and that an adjuvant-free vaccine is not envisaged by the prior art. Applicant’s arguments have been considered and not found persuasive.
While Mu et al. teaches the use of a “self-adjuvanted bacterial flagellin protein”, Mu et al. also teaches the use of an adenoviral vector expressing the VZV gE protein alone. In this regard, Mu et al. found that the recombinant adenovirus vector expressing the gE protein alone induced high neutralizing antibodies (see Figure 11, page 44 and Table 5). Mu et al. further states that an adenovirus vector expressing gE or gE-flagellin fusion protein can not only induce good gE-specific antibodies, VZV neutralization responses and CD4+ T cell responses, but also induce the body to generate CD8+ T cell immunity, thereby further destroying cells infected by VZV. Thus, Mu et al. teaches a composition that is adjuvant free.
Applicant next argues that the chimpanzee vector ChAdOx1 produces unexpected results. Applicant’s arguments have been fully considered and not found persuasive.
Applicant’s alleged unexpected results are for cell-mediated immune responses and not for humoral immune responses. Further, applicant’s alleged unexpected results are limited to a comparison with Shingrix and comparing ChAdOx1 and ChAdOx2 (no other chimpanzee adenoviral vectors were tested). Lastly, it is not clear if the alleged unexpected results are from i) using an adjuvant-free composition, ii) using ChAdOx1, or using i) and ii). Additionally, applicant’s alleged unexpected results are for limitations that are not in the claims [humoral immunity vs cellular immunity].
It is noted that the claims are directed to a composition and not a method of immunizing. As outlined above, the combined teachings of Mu et al. [any chimpanzee adenovirus vectors can be used as well as no adjuvant] and Antrobus et al. [ChAdOx1 is a promising vaccine vector that could be used to deliver vaccine antigens where strong cellular immune responses are required for protection; ChAdOx1 does not suffer from widespread seroprevalence of antibodies] render the claimed viral vector and composition obvious.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nicole Kinsey White whose telephone number is (571)272-9943. The examiner can normally be reached M to Th 6:30 am to 6:00 pm.
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/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672