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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/16/26 has been entered.
Applicant’s amendments to the claims dated 1/16/26 are acknowledged. Claims 1-4, 11-14, 16-18, 21 and 24 are pending and subject to prosecution. Claims 1, 11, 17, and 21 are amended. Claims 9-10 and 15 were cancelled with the amendment of 1/16/26.
WITHDRAWN REJECTIONS/RESPONSE TO ARGUMENTS
RE: The 103 rejection of claims 1-18, 21 and 24 over Johnson, in view of Corredor, 2008, as evidenced by Genbank AC_00014 and Genbank AC_00013, Baker, Francois, and Corredor, 2010
The rejection of claims 5-10 and 15 is WITHDRAWN in light of the cancellation of these claims.
The rejection over claims 1-4, 11-14, 16-18, 21 and 24 is WITHDRAWN in light of Applicant’s amendments to the claims. Applicant argues that none of the cited art teaches or suggests the amendment to claim 1, wherein the fowl adenovirus 9 viral vector is a dual vector encoding two exogenous nucleotide sequences encoding for two polypeptides, wherein each exogenous nucleotide sequence is operably linked to a different promoter (pages 6-7 of the Reply dated 1/16/26). The Examiner agrees, and the rejection is WITHDRAWN.
The new limitations are derived in part from cancelled claim 10, which required the vector was a dual vector encoding two nucleotides of interest coding two peptides of interest. The requirement wherein the two nucleotides of interest are operably linked to separate promoters is a new concept under prosecution.
PRIORITY
The instant application, filed 4/29/21, is a CONTINUATION of US 15/743,459 (abandoned), filed 01/23/2018, which is a 371 of PCT/CA2016/050811, filed 07/11/2016, which claims priority to US Provisional Application No. 62/190,913, filed 07/10/2015. Thus, the earliest possible priority for the instant application is 07/10/2015.
CLAIMS
Independent claim 1 is directed to
A fowl adenovirus 9 (FAdV-9) recombinant viral vector comprising at least one deletion of a non-essential region selected from ORF19 and ORF17, wherein the vector comprises at least one of the following:
(a) the nucleotide sequence as shown in SEQ ID NO: 1, wherein nucleotides 575 to 2753 and 38,807 to 42,398 have been deleted;
(b) the nucleotide sequence as shown in SEQ ID NO: 1, wherein nucleotides 847 to 2753 and 38,807 to 42,398 have been deleted;
(c) the nucleotide sequence as shown in SEQ ID NO: 1, wherein nucleotides 847 to 2753 and 34,220 to 36,443 have been deleted; and
(d) the nucleotide sequence as shown in SEQ ID NO: 1, wherein
nucleotides 847 to 2753, 34,220 to 36,443 and 38,807 to 40,561 have been deleted or
nucleotides 847 to 2753, 34,220 to 36,443 and 41,461 to 42,398 have been deleted,
and wherein the vector is a dual vector comprising two exogenous nucleotide sequences coding for two polypeptides of interest, each of said exogenous nucleotide sequences being operably linked to a different promoter sequence.
CLAIM INTERPRETATION
Claim 1, drawn to a fowl adenovirus vector limited to full-length SEQ ID NO:1, upon which the claimed deletions are numbered. All vector genomes comprise an N-terminal (left-end) deletion (ORF0 through ORF2, or ORF1 through ORF2) AND at least one C-terminal (right-end) deletion (ORF19 or ORF17), relative to SEQ ID NO:1.
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SEQ ID NO: 1 is 100% identical to nucleotides 1 to 45063 of Genbank Accession No: AC_00013, of record, cited on Applicant’s IDS dated 12/20/21. Genbank Accession No: AC_00013 discloses the claimed deletions encompass specific identified regions of the Fowl Ad9 genome (not to scale):
Nucleotides 575-2753 comprises deletion of ORF0 through ORF2;
Nucleotides 847-2753 comprises deletion of ORF1 through ORF2;
Nucleotides 38,807 to 42,398 comprises deletion of Repeat Region (RR) through ORF11;
Nucleotides 34,220 to 36,443 comprises deletion of ORF19;
Nucleotides 38,807 to 40,561 comprises deletion of RR; and
Nucleotides 41,461 to 42,398 comprises deletion of RR through ORF11.
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Claim 1(a) genomes would have ORF0 through ORF2 and RR through ORF11 deleted:
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Claim 1(b) genomes would have ORF1 through ORF2 and RR through ORF11 deleted:
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Claim 1(c) genomes would have ORF1 through ORF2 and ORF19 deleted:
Claim 1(d) genomes would have
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(1) ORF1 through ORF2, ORF19 and RR deleted:
Or
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(2) ORF1 to ORF2 deleted, ORF19, and ORF11 deleted:
As noted above, claim 1 comprises the new claim limitation, “wherein the vector is a dual vector comprising two exogenous nucleotide sequences coding for two polypeptides of interest, each of said exogenous nucleotide sequences being operably linked to a different promoter sequence.” The claim does not require the inserted one or more exogenous nucleotide sequences are inserted into the one or more deleted sequences of the adenoviral genome, the size of the inserted sequence or its expressed polypeptide size. The claim does not require where within the genome the two different promoters are located.
In addition, the specification does not define the upper or lower number of nucleotide sequences that are inserted, or the minimum or maximum size of the corresponding encoded polypeptide of interest (paragraphs [0024], [0077]). The specification does not define or limit a polypeptide of interest (paragraph [0081], [0085]). The specification does not define or limit where within the vector genome the foreign exogenous nucleotide sequences encoding for a polypeptide are inserted. The specification discloses the inserted exogenous nucleotide sequences can be inserted into, and operably linked to endogenous (“native”) promoters or exogenous promoters (paragraphs [0083], [0084], Example 2). The specification discloses an exogenous nucleotide sequence is operably linked to a promoter if the promoter controls the transcription of the sequences, and sequences which are operably linked may, or may not be, contiguous (paragraph [0084]), and contemplates the use of IRES sites to link nucleic acid sequences (example 4), would allow a nucleotide sequence 3’ of the IRES site to be driven by a promoter it was not directly adjacent to.
As such, the broadest reasonable interpretation of the new limitations of the claim, consistent with the specification, reasonably encompasses, at least,
an exogenous nucleotide sequence coding for a polypeptide comprises a minimum of 6 nucleotides that encodes at least 2 contiguous amino acids, thus reading on a “polypeptide;”
exogenous nucleotide sequences can be inserted anywhere within the viral genome; and
exogenous nucleotide sequences operably linked to an endogenous promoter are expressed by the endogenous promoter, but need not be directly adjacent to the endogenous promoter.
.
NEW REJECTIONS OF RECORD
Claim Rejections - 35 USC § 103
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 1-4, 11-14, 16-18, 21 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over
US Patent No. 6,296,852 to Johnson, of record; further in view of
Corredor et al. Sequence Comparison of the Right End of Fowl Adenovirus Genomes. Virus
Genes, 2008. 36:331-344, of record, (Corredor 2008), as evidenced by Genbank Accession No.
AC_00014, of record, and as evidenced by Genbank Accession No. AC_00013, of record;
US Patent No. 6,335,016 to Baker, of record,
Francois et al. Construction of Avian Adenovirus CELO Recombinants in Cosmids. Journal of
Virology, 2001. 75: 5288-5301, of record,
Corredor et al. A Region at the Left End of Fowl Adenovirus 9 Genome That is Non-Essential In
Vitro has Consequences In Vivo. Journal of General Virology, 2010. 91: 51-58, Corredor 2010, of
record, further in view of
Logunov et al. Identification of HI-Like Loop In CELO Adenovirus Fiber for Incorporation of
Receptor Binding Motifs. Journal of Virology, 2007. 81(18):9641-9652.
With regard to claim 1, Johnson discloses fowl adenovirus recombinant viral vectors that comprise heterologous nucleotide sequences that encode heterologous peptides (Abstract; Column 2, lines 15-26; Column 5, lines 11-35). Johnson discloses the fowl adenovirus viral vector can be from serotype 9 –CFA19 therein-- (FadV-9), and is preferable over serotype-1 (CELO) viruses (Column 5, lines 5-20; Column 8, lines 34-36). Johnson discloses the heterologous nucleotide sequences that encode heterologous peptides are inserted into the FAdV genome by insertion or deletion into/of one or more “nonessential regions” within the FAdV genome, which include the left-end and right-end regions of the viral genome (Column 6, lines 31-38). Johnson discloses by generating deletions of the genome, the recipient genome is capable of carrying larger insertions that are beyond the normal packaging constraints of the virus (Column 8, lines 14-24). Johnson discloses generating right-end deletions of non-essential regions from map units 70 to 100, or 60 to 100 (Column 6, lines 31-38).
Johnson discloses the FAdV-9 genome restriction map in FIG 2 has 100 map units, and every 1 map unit = 4500 bases (Column 10, lines 1-8). Thus, Johnson discloses the full-length FAdV-9 genome is approximately 45,000 bases.
Johnson discloses generating right-end deletions of non-essential regions from map units 70 to 100, or 60 to 100 (column 6, lines 31-38). Rough estimations of right-end deletions taught by Johnson
Range from base 27,000 (4500 x 60) to base 45,000 (4500 x 100) or
from base 31,500 (4500 x 70) to base 45,000 (4500 x 100).
Figure 6 of Johnson is an alignment of the right-end regions for 4 FAdV homologues: FAdV -1 (CELO), FAdV-10, FAdV-9 and FAdV-8, which shows ORF19 and ORF17 (20.9) within the 4 genomes, which are located within map units 60 to 100 of the full-length genomes. Johnson discloses the development of new FAdV recombinant virus serotypes, such as FAdV-10, FAdV-9 and FAdV-8, is based off of work in FAdV-1 (CELO) because fowl adenovirus genomic structure is too structurally and functionally distant from mammalian adenoviruses, and because CELO was the only FAdV homologue with any significant molecular use or functional studies at the time (Column 3, line 1 – Column 5, line 23).
Johnson discloses the vectors comprise one or more heterologous nucleotide sequences encoding proteins of interest (Column 5, line 59 – Column 6, line 17; Column 6, lines 27-30; Column 6, line 67 – Column 7, line 4). At Column 6, lines 27-35, Johnson states,
“The DNA of interest which may comprise heterologous genes coding for antigenic determinants or immunopotentiator molecules may be located in at least one nonessential region of the viral genome.
Nonessential regions of the viral genome which may be suitable for the purposes of replacement with or insertion of heterologous nucleotide sequences may be non-coding regions at the right terminal end of the viral genome and/or the left terminal end of the viral genome.”
Johnson discloses the nucleotide sequence encoding a protein of interest is operably linked to promoter, including a FadV-9 promoter, such as the MLP promoter (Column 6, lines 39-53), or operably linked to a heterologous promoter, such as a CMV promoter (Column 6, lines 56-59).
Taken together, Johnson renders obvious recombinant FadV-9 viral vector genomes comprising deletions of both left-end and right-end non-essential sequences, wherein ORF9 and ORF17 are located within right-end non-essential regions suitable for deletion:
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wherein the viral vector comprises a dual vector encoding 2 separate heterologous nucleotide sequences encoding two polypeptides of interest, wherein the heterologous nucleotide sequences are inserted into one or more of the left-end and right-end nonessential regions of the FadV-9 genome, and wherein the heterologous nucleotide sequences are operably linked to an adenoviral promoter or a heterologous promoter.
However, Johnson does not disclose wherein the full-length FAdV9 genome is identified by a specific nucleotide sequence therein, or wherein the FAdV9 comprises deletions of ORF0 through ORF2 or ORF1 through ORF2 and deletions of ORF19, or Repeat Region (RR) through ORF11, or ORF19 and RR, or ORF19 and ORF11, or that the two separate nucleotide sequences encoding two polypeptides are operably linked to separate promoters, as required by instant claim 1.
Corredor 2008 discloses the arrangement, orientation and nucleic acid positions of ORFs within the right-hand end of fowl adenovirus serotype-1 (CELO) and serotype-9. Corredor 2008 discloses the right-hand end of fowl adenovirus serotype-1 (CELO) and serotype-9 are conserved, and comprise a “core” of ORFs which include ORF 19 and ORF17, and which are arranged in the same orientation and order with in the genomes (Abstract; page 334-336; FIG2; Table 4 page 340). Corredor 2008 also discloses ORF11 as an additional “core” ORF, with homologues in CELO, serotype 9, serotype 2, and serotype 8 (page 336, last paragraph, page 337, Table 3). Corredor 2008 further discloses tandem repeat region (TR-2) of FAdV-9 has already been shown to be dispensable for viral replication, and can be replaced with a heterologous nucleotide sequence (page 332, first column).
Corredor 2008 discloses the sequences for CELO are from Genbank Accession No. AC_00014 and FAdV-9 are from AC_000013 (page 333). Genbank Accession No. AC_00014 and Genbank Accession No. AC_00013 are cited as evidence to show an inherent property of the vectors of Corredor.
Genbank Accession No. AC_00014 encoding CELO discloses ORF 19 spans from nucleotides 34,238 to 36,144, ORF 17 spans from 38,717 to 39,256, ORF 11 from 41958 to 42973.
Genbank Accession No. AC_00013 encoding FAdV-9 discloses ORF19 spans from nucleotides 34220 to 36443, TR-2 spans from 38,807 to 38,942, ORF17 spans from 40,596 to 41,066, and ORF11 spans from 41,461 to 42398.
Thus, taken together, Corredor discloses the arrangement, orientation and nucleic acid positions of ORF 19, ORF 17, and ORF11 for both FAvD-1 (CELO) and FAdV-9 at FIG:2, and dispensable TR-2 region in FAdV-9 (as modified below):
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Baker discloses recombinant fowl adenovirus vectors based on serotype-1 (FaDV-1, CELO) that comprises modifications comprising one or more insertions and/or deletions and/or mutations in the genome, wherein the CELO vectors are useful for gene therapy or vaccines (Abstract; Column 5, lines 43-54). Baker discloses the insertions and/or deletions and/or mutations of the CELO genome suitable for modification are identified as Sections A-C: “A” which includes nucleotides from about 201 to about 5000, and includes the left- end; Section “B” which includes nucleotides from about 31,800 to about 43,734, and which includes the right-end, and Section “C” which includes nucleotides from about 28,111 to about 30,495 and encodes for the fiber 1 gene (Column 5, lines 43-54).
Baker discloses that sections A-C exclude the ITR and packaging sequences, suggesting that modifications outside of the ITR and packaging sequences “ensures that the genes affected by the modification are non-functional or are deleted” (Column 5, lines 34-42). In light of the disclosure of Corredor and Genbank Accession No. AC_00014, Section B of CELO disclosed in Baker necessarily comprises ORF 19 and ORF 17:
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Baker discloses deletions within the adenoviral genome increases the packaging capacity of the viruses, wherein nonessential regions can be deleted outright or the deleted portions are provided in trans in a complementing cell line (Column 7, line 59 – Column 8, line 18, Column 9, lines 62-64). Baker discloses the heterologous nucleotide sequences are inserted into, or replace, one or more sequences from sections A-C (Column 5, line 59- Column 6, line 2). Baker discloses the heterologous nucleotide sequences encode peptides, or fragments thereof, of therapeutic peptides, antigenic peptides, and/or peptides which alter the virus’s tropism by modification of the fiber gene (Column 6, lines 8-67, Column 7, lines 25-38, Column 8, lines 39-46; column 11, lines 52-54) and are operably linked to endogenous or exogenous promoters (Column 7, lines 44-48). Further, Baker discloses the one or more heterologous nucleotide sequences are inserted in tandem or spaced apart in different sections of the genome (Column 7, lines 40-43; Claims 4 and 13).
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At Example 5, Baker generates a FAdV-1 recombinant vector wherein nucleotides 34426-36648 are deleted and replaced with a heterologous gene (pCELOΔ 34426-36648Luc). This FAdV-1 vector necessarily comprises a deletion of ORF19:
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Francois discloses generating recombinant fowl adenovirus vectors based on serotype-1 (FaDV-1, CELO) that introduce a stop codon into the right-end ORFs of the genome (Abstract; page 5289; 5294, FIG 3, Table 1). The ORFs included are ORFs 11 and ORF 17 (Table 1), these viruses are deficient for ORF 10 and ORF17. Francois discloses the ORF11 and ORF17 mutated viruses were capable of replication and infection (Table 2). Francois further discloses deleting the entirety of ORF9 and ORF10, ORF10 and ORF11, and ORF9, ORF10 and ORF11 from CELO, and shows these viruses are also capable of replication (page 5295, Table 3). In addition, Francois inserts a single constructs of heterologous nucleotide sequences encoding multiple peptides. Francois inserts a complete IBDV A segment, which encodes IBDV structural proteins VP2, VP3, VP4 and VP5 (rCELO-IBDA), a partial IBDV A segment, encoding the capsid proteins VP2 and VP3 (rCELO-IBDAΔ), and a recombinant fusion protein comprising a IBDV VP2 and VP3 fused to GFP (rCELO IBDAΔ-GFP) into the deleted ORF9 – ORF11 region (page 5296, Table 4, FIG 10). All three FaDV-1 viruses successfully expressed the VP2, VP3 and/or VP3-GFP fusion proteins (FIG 10, Table 4). Thus, Francois establishes a FaDV vector is capable of encoding, packaging and expressing a transgene encoding at least two heterologous proteins.
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Corredor 2010 generates FAdV-9 viral vectors comprising left-end deletions, also based on Genbank Accession No. AC_000013. As noted above, SEQ ID NO: 1 is 100% identical to nucleotides 1-45,063 of AC_000013. Corredor 2010 generates left-end deletion vectors FAdV-9dΔ4, comprising deletion of nucleotides 854-2782, which comprises a deletion of ORF1 through ORF2, and FAdV-9dΔ7, comprising deletion of nucleotides 400-2782, which comprises a deletion of ORF0 through ORF2 (FIG 1). Corredor 2010 shows FAdV-9dΔ4 is capable of viral replication both in vitro and in vivo (pages 52-54, FIG2, FIG3).
Logunov discloses recombinant FadV-1 CELO viruses wherein heterologous nucleotide sequences encoding an RGD binding motif peptide are inserted into the HI-like loop of the CELO fiber 1 gene, and wherein nucleotide sequences encoding a reporter peptide are inserted into a deleted portion of the genome from nucleotides 41731 to 43685 (Abstract, page 9642, FIG2). The deletion from nucleotides 41731 to 43685 necessarily deleted ORF11, as evidenced by Corredor 2008 above. Logunov discloses the nucleotide sequences, encoding the RGD binding motif, are 27 nucleotides in length, and encode a polypeptide of 9 amino acids, are inserted into the endogenous fiber 1 gene via PCR mutagenesis (page 9642, page 9643-9645, FIG 2). Because the Logunov the nucleotide sequences encoding the RGD binding motif, are inserted into the endogenous gene, they are operably linked to an endogenous promoter. Logunov discloses the nucleotide sequences encoding the reporter peptide are operably linked to a CMV promoter (page 9642). Logunov discloses viruses encoding the nucleotide sequences encoding an RGD binding motif peptide and the reporter peptide are capable of forming infectious particles (page 9642, 9646, FIG. 3).
Thus, Logunov exemplifies wherein a recombinant fowl adenoviral vector is a dual vector comprising two exogenous nucleotide sequences coding for two polypeptides of interest, wherein each of said exogenous nucleotide sequences being operably linked to a different promoter.
It would have been obvious to combine the disclosure of Johnson on fowl adenovirus serotype-9 recombinant viral vectors comprising deletions in one or more nonessential regions of the genome, wherein the vector further comprises two different heterologous nucleotide sequences that encode two different heterologous peptides, further with the disclosures of Corredor 2008, as evidenced by Genbank Accession No. AC_00014 and as evidenced by Genbank Accession No. AC_00013, Baker, Francois, Corredor 2010 and Logunov.
With regard to the claimed requirements wherein the FAdV-9 genome comprises deletions in non-essential regions in both the right-end and left-end of the genome: A skilled artisan would have been motivated to generate deletions in the right-hand and left-hand region of FAdV-9 because deletions of non-essential regions from FAdV genomes increases the packaging capacity of the virus, as taught by Johnson and Baker. A skilled artisan would be motivated to generate right-end deletions comprising ORF19, ORF17, ORF11, TR-2, and left-end deletions comprising ORF0-ORF2 in the genome of serotype-9 because Baker, Corredor 2008, Francois, Corredor 2010 and Logunov disclose these regions are nonessential and/or capable of deletion for FAdV-1 viruses or FAdV-9 viruses through reduction to practice, and Johnson discloses FAdV-9 is preferable over FAdV-1. Francois and Logunov further establish generating deletions of an individual ORF was known. Combining known deletions from one serotype into another FAdV serotype would have been obvious in order to replicate the deletions already known as nonessential in order to increase the normal packaging capacity of the virus (Combining prior art elements according to known methods to yield predictable results supports a conclusion of Obviousness, MPEP 2143I(A)).
With regard to the claimed requirements wherein the FAdV-9 genome comprises SEQ ID NO: 1, and wherein the deletions are identified by nucleotide sequence: It would have been obvious to use a FAdV-9 genome comprising SEQ ID NO: 1 because Corredor 2010 generates FAdV-9 viruses with deletions non-essential ORF0 through ORF2 in a genome comprising SEQ ID NO:1.
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Corredor 2008, as evidenced by Genbank Accession No. AC_00014 and Genbank Accession No. AC_00013 establishes the arrangement, orientation and sequences for ORF19, TR-2, ORF 17 and ORF11 were known and readily available:
Thus, deletions of the specific nucleotide sequences of the left-end and right-end deletions of non-essential regions within the FAdV-9 genome recited in claim 1 wherein
nucleotides 575 to 2753 and 38,807 to 42,398 have been deleted;
nucleotides 847 to 2753 and 38,807 to 42,398 have been deleted;
nucleotides 847 to 2753 and 34,220 to 36,443 have been deleted; and
nucleotides 847 to 2753, 34,220 to 36,443 and 38,807 to 40,561 have been deleted or
nucleotides 847 to 2753, 34,220 to 36,443 and 41,461 to 42,398 have been deleted were identifiable and obvious from the prior art.
A skilled artisan would have had a reasonable expectation of success in generating the left-end and right-end deletions of non-essential regions of a FAdV-9 genome because the deletions of either the left-end or right-end had been reduced to practice in either a FAdV-9 genome or the conserved FAdV-1 (CELO) genome, and Baker discloses wherein any genes that are deleted may be provided in trans if necessary.
With regard to the claimed requirements wherein the FAdV-9 genome is a dual vector comprising two different heterologous nucleotide sequences operably linked to two different promoters: A skilled artisan would have been motivated to modify a FAdV-9 viral vector comprising two different heterologous nucleotide sequences to be operably linked to two different promoters because Johnson and Baker disclose the heterologous nucleotide sequences are operably linked to an adenoviral promoter or a heterologous promoter, Baker discloses the one or more heterologous nucleotide sequences are inserted in tandem or spaced apart in left-end, center (including the fiber 1 gene) or right-end sections of the genome, wherein the sequences encode therapeutic polypeptides or modify the fiber 1 gene, and Logunov exemplifies FAdV-1 (CELO) dual vector comprising a first heterologous nucleotide sequence coding for an RGD peptide inserted into the fiber 1 gene, and a second heterologous nucleotide sequence coding for a reporter protein, wherein each heterologous nucleotide sequence is operably linked to a different promoter. A skilled artisan would have had a reasonable expectation of success in practicing the claimed invention because a recombinant FAdV-1 (CELO) virus expressing two separate heterologous nucleotide sequences has been exemplified, and Francois exemplifies a FAdV-9 virus encoding a single heterologous sequence encoding two different proteins operably linked to a heterologous promoter, thus showing a recombinant FAdV-9 is capable of packaging the total length of such heterologous sequences.
With regard to claims 2-3, wherein the recombinant FAdV-9 vector comprises a deletion of ORF17 or ORF19, these claims are obvious for the reasons stated above for claim 1.
With regard to claim 4, wherein the vector further comprises a deletion of one or more of the following non-essential regions: ORF0, ORF1, ORF2, TR2 and ORF11, Johnson does not disclose the vector further comprise a deletion to one or more of these regions. However, Francois discloses generating CELO (FAdV-1) mutants with deletions of ORF1, ORF2 and ORF11 (page 5289, second column; page 5295- page 5297; FIG 5; Table 3). Francois discloses the CELO (FAdV-1) mutants were capable of producing infectious particles (FIG 5; Table 3). Corredor 2010 also generates FAdV-9 viral vectors also based on Genbank Accession No. AC_000013. As noted above, SEQ ID NO: 1 is 100% identical to nucleotides 1-45,063 of AC_000013. Corredor 2010 generates left-end deletion vectors FAdV-9dΔ4, comprising deletion of nucleotides 854-2782, which comprises a deletion of ORF1 through ORF2, and FAdV-9dΔ7, comprising deletion of nucleotides 400-2782, which comprises a deletion of ORF0 through ORF2 (FIG 1).
Combining known deletions from one serotype into another FAdV serotype would have been obvious in order to replicate the deletions already known as nonessential in order to increase the normal packaging capacity of the virus (Combining prior art elements according to known methods to yield predictable results supports a conclusion of Obviousness, MPEP 2143I(A)). A skilled artisan would have had a reasonable expectation of success in practicing the claimed invention as generating recombinant FAdV-9 vectors, and generating recombinant FAdV with deletions in nonessential ORF was known in the art at the time of the invention.
With regard to claims 11-13, Johnson discloses the heterologous nucleotide sequences encode antigens, including those directed to Avian influenza, infectious bronchitis, inclusion body hepatitis, infectious laryngotracheitis, New Castle Disease, etc. (column 5, line 59 – column 6, line 13; column 6, lines 27-30; Column 6, line 67 – column 7, line 4). Johnson exemplifies encoding an antigenic peptide VP2 from infectious bursal disease virus (IBDV) (column 13, lines 12-24, Column 18, lines 9-54).
Johnson states, “The DNA of interest which may comprise heterologous genes coding for antigenic determinants or immunopotentiator molecules may be located in at least one nonessential region of the viral genome.” At column 6, lines 27-30, emphasis added. Claim 25 of Johnson is directed to a method of protecting birds against a disease, comprising administering a recombinant virus encoding “at least one heterologous nucleotide sequence encoding an antigenic determinant” of said disease.” Johnson also discloses methods of the simultaneous delivery of two viruses, each encoding different foreign genes (column 8, lines 30-33).
Francois discloses FAdV-1 viruses encoding the A segment of the IBDV genome, encoding putative antigenic capsid peptides VP2 and VP3 (CELO-IBDV A segment and CELO-IBDVAΔ.
With regard to claim 14, which recites wherein the vector encodes a “sequence corresponding to” at least one sequence selected from SEQ ID NOs:10-21 “or a homolog thereof” it is noted that the claim does not require the vector encode SEQ ID NOs:10-21, but rather sequences “corresponding to” or “a homolog thereof.” SEQ ID NOs 10-21 encode Influenza A virus hemagglutinin, Laryngotracheitis virus (ILT) glycoprotein B, Laryngotracheitis virus (ILT) glycoprotein D, New Castle Disease Virus HN gene, New Castle Disease Virus Hemagglutinin neuramidase gene, VP1 gene of Chicken anemia virus, VP2 gene of Chicken anemia virus, Fowl Adenovirus short fiber gene, Infectious bronchitis virus D spike glycoprotein, and Gene F of Avian metapneumovirus. Johnson discloses the vectors “hemaglutininin-neuraminidase (HN) from Newcastle Disease Virus (column 12, lines 64-65), glycoprotein B from Marek’s disease virus (column 12, lines 65-66), VP2 of infectious Bursal Disease Virus (column 12, lines 66-67), which are homologues of the claimed sequences. Thus, Johnson renders obvious claim 14.
With regard to claims 16 and 17, directed to a host cell comprising the viral vector, and methods of making the viral vector, Johnson discloses the viruses are produced into cell lines following transfection of heterologous nucleic acids encoding the peptides and an empty FAV vector to generate infection clones (Examples). However, Johnson only exemplifies amplification and insertion of one heterologous nucleotide sequence operably linked to either an adenoviral promoter or a exogenous promoter. The insertion of a first heterologous nucleotide sequence operably linked to one promoter, and a second heterologous nucleotide sequence operably linked to a second different promoter, is obvious Johnson in view of Baker and Logunov. Thus, Johnson in view of Baker and Logunov render obvious host cells comprising the vector, and methods of making the viral vector as claimed.
With regard to claim 18, Johnson discloses the vectors comprise one or more heterologous nucleotide sequences encoding antigens, including those directed to Avian influenza, infectious bronchitis, inclusion body hepatitis, infectious laryngotracheitis, New Castle Disease, etc. (column 5, line 59 – column 6, line 13; column 6, lines 27-30; Column 6, line 67 – column 7, line 4).
With regard to claim 21, Johnson discloses the viral vectors are immunogenic and further comprise a pharmaceutically acceptable carrier or adjuvants (column 6, line 63 – column 7, line 4; column 7, lines 18-42; claims 27-28).
With regard to claim 24, Johnson discloses administering the vector to generate an immune response in a subject (column 7, lines 45 – 52; Column 8, lines 25 - 67).
No claims are allowed.
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/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633