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 .
DETAILED ACTION
Claim status
Claims 1-20 are pending
Claims 1-20 are under examination
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 4/19/2023 and 6/01/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 20 is rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by O’Shea (WO2016/049201, filed 9/23/2015, published 3/31/2016, see IDS filed 4/19/2023).
The applied reference has a common inventor with the instant application. Based upon the earlier publication date/effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(1)/(a)(2).
Applicant may rely on the exception under 35 U.S.C. 102(b)(1)(A) to overcome this rejection under 35 U.S.C. 102(a)(1) by a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application, and is therefore not prior art under 35 U.S.C. 102(a)(1). Alternatively, applicant may rely on the exception under 35 U.S.C. 102(b)(1)(B) by providing evidence of a prior public disclosure via an affidavit or declaration under 37 CFR 1.130(b).
This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
O’Shea (WO2016) teaches the synthetic adenovirus AdSyn-CO174 vector of SEQ ID NO:71 (p. 66, Table 3, see also Fig. 23D), which is 36,949 nucleotides in length and 100% identical to instant SEQ ID NO:2 (Search 11/20/2025, rng.file, result #1), which comprises an Ad5 backbone, DE1-EF1a-luc-GFP-miR122 construct, a chimeric Ad5/Ad11 fiber knob, and hexon with a E451Q substitution.
Accordingly, O’Shea anticipates instant claim.
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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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 3-4, 6, 8-10, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Betz et al., (US 2005/0136042, filed 8/11/2004, see IDS filed 4/19/2023), in view of Lieber et al., (US 7,094,398, filed 6/01/2000, see IDS filed 4/19/2023)
In regard to claims 1 and 6, Betz teaches methods and compositions for expressing a transgene in a subject and for promoting bone repair comprising a synthetic adenovirus comprising a transgene (Abstract, Summary [0008, 0011-0012, 0115-117, 0146-0156]).
In regard to claim 3, Betz teaches the transgene can comprises an enzymatic reporter such as LacZ (Example 1, [0222]).
In regard to claims 4, 8-10, Betz teaches the transgene comprises a factor that promotes bone repair or regeneration, such as BMP-2 ([0041, 0080, 0091, 0222]). Furthermore, in regard to claim 10, Betz teaches that more than one transgene can be used [0091, 0102, 0194-0195, 0198].
However, although Betz teaches the Ad5 serotype adenovirus is used [0156], which comprises an Ad5 shaft and Ad5 knob, they are silent with respect to modifying the synthetic Ad5 adenovirus to comprise an Ad5 shaft and Ad11 knob chimeric fiber protein.
Lieber et al., teaches methods and compositions for expressing a transgene in a subject comprising a synthetic adenovirus comprising a chimeric fiber protein (Abstract, Summary of the Invention). In regard to claims 1, 6, and 14, Lieber teaches a chimeric Ad5/Ad11 chimeric fiber protein (col 16, last para.). Specifically, in regard to claim 14, although Lieber explicitly teaches an Ad5 capsid comprising a fiber tail domain of Ad5 fused to the fiber shaft and knob domains of Ad11, Lieber teaches the minimum necessary component for retargeting Ad5 is the knob domain of Ad11, and discloses other Ad5 chimeras wherein the Ad5 fiber tail and shaft are fused to a different knob domain, as well as the understanding that the chimeric Ad5 viruses were typically generated by substituting only the Ad5 knob, thereby maintaining the long Ad5 fiber shaft and not disturbing their spatial arrangement by short-shafted heterologous fibers (e.g., Ad11 shaft is 1/3 the size of the Ad5 shaft) (col 2, last para., col 16, second to last para., col 56, 3rd para.).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice a method of expressing a transgene by an adenoviral vector in bone tissue for bone repair or regeneration in a subject as taught by Betz and substitute and Ad5/Ad11 chimeric fiber protein as taught by Lieber with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Lieber because the Ad11 knob domain of the fiber protein can retarget the Ad5 vector to human bone marrow (col 16, 4th para.).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 2 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Betz et al., (US 2005/0136042, filed 8/11/2004, see IDS filed 4/19/2023), in view of Lieber et al., (US 7,094,398, filed 6/01/2000, see IDS filed 4/19/2023), as applied to claims 1 and 6, in further view of Baltzer et al., (US 7,105,494, filed 4/28/2000, see IDS filed 4/19/2023)
As stated supra, Betz and Lieber suggest methods and compositions for expressing one or more transgenes in bone marrow cells that promote bone repair or regeneration in a subject comprising a synthetic adenovirus comprising an Ad5/Ad11 chimeric fiber protein that targets bone marrow cells of bone tissue.
In regard to claims 2 and 7, although Betz teaches the femur is a bone to target, they do not reduce to practice a method comprising administering an adenoviral vector wherein transgene expression is in bone marrow cells of the femur.
Nevertheless, co-inventors of Betz et al. (2005) were also co-inventors of Baltzer et al. (2006).
Baltzer et al. reduces to practice a method for expressing a transgene (i.e., luciferase) in the femur comprising administering an adenoviral vector that transduces bone marrow cells (col 4, 5th para., col 14, 4th para. col 17, 1st para. see Figs. 4, 7 & 8).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice a method of expressing a transgene by an adenoviral vector in bone marrow cells for bone repair or regeneration in a subject comprising the femur bone suggested by Betz with a reasonable expectation of success as demonstrated by Baltzer. The ordinary skilled artisan would have been motivated to choose the femur as taught by Betz because it is the bone used in established animal models for bone repair ([0224, 0230] of Betz, but see also Example 3 of Baltzer). Thus, when the artisan conduced the taught method in the femur, it would have been comparable to other experiments performed in this animal model. In regard to the reasonable expectation of success of promoting bone repair in the femur, Baltzer teaches that BMP-2 was well known to contribute to bone formation after adenoviral infection of bone marrow cells (col 2, 5th para.).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Betz et al., (US 2005/0136042, filed 8/11/2004, see IDS filed 4/19/2023), in view of Lieber et al., (US 7,094,398, filed 6/01/2000, see IDS filed 4/19/2023), as applied to claim 1, in further view of O’Shea et al. (US2013/0231267, filed 2/15/2013, published 9/05/2013, see IDS filed 6/1/2023), and NCBI Blast alignment, (1/15/2022, p.1-17, see IDS filed 4/19/2023), Uetsuki et al. (GenBank J04617, 11/07/1994, p. 1-3, see IDS filed 4/19/2023), and Wu et al., (US 2009/0176260, filed 12/04/2008, see IDS filed 4/19/2023), and Davison et al. (GenBank BK001453, 10/24/2003, p. 1-11, see IDS filed 4/19/2023)
As stated supra, Betz and Lieber suggest methods and compositions for expressing one or more transgenes that promote bone repair or regeneration in a subject comprising a synthetic adenovirus comprising an Ad5/Ad11 chimeric fiber protein.
In regard to claim 5, although Betz teaches an E1/E3 modified synthetic Ad5 vector comprising a reporter gene (Example 1), Betz and Lieber do not provide the nucleic acid sequence of the vector and are silent to the synthetic adenovirus being at least 95% identical to SEQ ID NO:2, which is 36,949 nucleotides in length.
O’Shea (2013) teaches methods and compositions for expressing a transgene in a subject comprising a synthetic adenovirus comprising a chimeric fiber protein (Abstract, [0002-0009]). In regard to claim 5, O’Shea (2013) teaches the nucleic acid sequences for an E1/E3 modified synthetic Ad5 vector comprising a GFP-luciferase reporter gene, SV40 polyA containing two copies of a miR-122 binding site, a hexon with a E451Q substitution, and an Ad5/11 chimeric fiber protein comprising the fiber stem of Ad5 and the knob domain of Ad11 (see map from Fig. 43 below, as well as Fig. 44 “Ad5/11 EF1a-GFP”, and “E3-031” from Table 3, p. 25).
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In regard to the nucleic acid sequences of the synthetic adenovirus vector of O’Shea, she teaches the backbone is the wild-type Ad5 vector, which is 35,938 nucleotides in length and corresponds to SEQ ID NO:137 of O’Shea ([0054], see Fig. 43).
By comparison to SEQ ID NO:2, nucleotides 1-447 of SEQ ID NO:2 are 100% identical to nucleotides 1-447 of SEQ ID NO: 137 (447 total coverage), which is followed by about 4 kb deletion in the E1 region of SEQ ID NO: 2 where the GFP-Luc reporter gene is inserted. Subsequently, by comparison nucleotides 4,419-33,203 of SEQ ID NO:2 comprising the E2 and L3 regions that are 99% identical to nucleotides 3,514-32,249 of SEQ ID NO: 137 (28,784 total coverage), which is followed by about a 500 bp deletion in the E3 region of SEQ ID NO:2 where the chimeric fiber protein is inserted. Subsequently, by comparison the terminal nucleotides 33,773-36,949 of the E4 region of SEQ ID NO:2 are 99% identical to the terminal nucleotide 32,783-35,938 of SEQ ID NO: 137 (3,177 total coverage).
Thus, 32,408 nucleotides of SEQ ID NO:2 are over 99% identical to wildtype Ad5 of SEQ ID NO: 137 of O’Shea (see attached BLAST alignment of 1/15/2022).
As far as the first 4kb deletion in the E1 region of SEQ ID NO:2, similar to Betz, O’Shea teaches the insertion of a reporter gene operably linked to human promoter. Specifically, after nucleotides 1-447 of Ad5, O’Shea teaches the modified Ad genome should have the E1 region replaced with transgene comprising a sequence comprising an EF1alpha promoter operably linked to a luciferase-GFP fusion protein ([0054], p. 23-24, Table 2, see also Fig. 43).
As far as the EF1alpha promoter, Uetsuki et al. (1994) disclose the human EF1 alpha promoter and deposit it as GenBank J04617. By comparison nucleotides 483-1666 of SEQ ID NO:2 are over 99% identical to nucleotide 373-1,560 of SEQ ID J04617 (1,184 total coverage) (see highlighted region of J04617).
As far as the luciferase-GFP fusion reporter, the prior art of Wu et al (2009) teach such a fusion protein and provides SEQ ID NO:10. By comparison nucleotides 1734-4114 of SEQ ID NO:2 are 99% identical to nucleotide 1,237-3,626 of SEQ ID NO: 10 (2,380 total coverage) (see SCORE search 1/11/2022, rng.file, result #25).
As far as the second 500 bp gap in the E3 region of SEQ ID NO:2 comprising the Ad5/Ad11 chimeric fiber protein, similar to Betz and Lieber, O’Shea teaches the modified Ad genome should have the E3 region replaced with a retargeting sequence comprising an Ad5/Ad11 fiber chimera comprising the Ad11 fiber knob corresponding to nucleotides 31,213-31,785 of GenBank sequence BK001453 (Fig. 43). By comparison nucleotides 33,195-33,772 of SEQ ID NO:2 are 100% identical to the cited Ad5 knob region (577 total coverage) (see highlighted region of BK001453).
Thus, 32,408 nucleotides of SEQ ID NO:2 are over 99% identical to wildtype Ad5 of SEQ ID NO: 137, while there are also 3,564 nucleotides over 99% identical to the EF1a-Luc-GFP fusion of SEQ ID NO:2 and 557 nucleotides over 99% identical to the Ad5/Ad11 chimeric fiber of SEQ ID NO:2, for a total of 36,529 out of 36,949 nucleotides of SEQ ID NO:2 that were known in the prior art (nearly 99% coverage).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice a method of expressing a transgene reporter by an Ad5/Ad11 chimeric adenoviral vector in bone marrow cells for bone repair or regeneration in a subject as suggested by Betz et al and choose the and synthetic adenovirus comprising the Ad5/Ad11 chimeric fiber protein comprising at least 95% sequence identity to SEQ ID NO: 2 as taught by O’Shea et al. with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by O’Shea for several reasons. First, O’Shea provides an enabling disclosure for constructing the synthetic Ad5/Ad11 chimeric vector suggested by Betz and Lieber, and provides the protein domains and nucleotide sequences to be used. Note that the successful cloning and sequencing of the cDNA encoding a known protein is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009). Furthermore, in regard to claim 3 and substituting the LacZ reporter gene of Betz with the Luc-GFP reporter gene of Shea, Wu makes obvious to one of ordinary skill that the dual emission reporter comprises distinct advantages as far as being able to visualize expression in both single cells by GFP fluorescence, and in groups of cells in vivo by Luc luminescence [0183, 0189, 0225-0226, 0371]. Finally, Applicant’s disclosure provides no evidence that sequences that range from 95% to 99% are critical to the function of the synthetic Ad5/Ad11 vector that it taught by the prior art, and in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art a prima facie case of obviousness exists.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Betz et al., (US 2005/0136042, filed 8/11/2004, see IDS filed 4/19/2023), in view of Lieber et al., (US 7,094,398, filed 6/01/2000, see IDS filed 4/19/2023), as applied to claims 6 and 10, in further view of Clancy et al. (US 2003/0170208, filed 5/31/2002, see IDS filed 4/19/2023) and Yu et al., (J Bone Min Res, 2012, 27:2001-2014, see IDS filed 4/19/2023)
As stated supra, Betz and Lieber suggest methods and compositions for expressing one or more transgenes that promote bone repair in a subject comprising a synthetic adenovirus comprising an Ad5/Ad11 chimeric fiber protein.
In regard to claim 11, although Betz teaches the transgene include a BMP, Wnt, and IGF-I [0090-0091, 0093, 0102], they are silent to a combination of BMP, Wnt, IGF-I and PTH.
Clancy et al., teaches methods and compositions for expressing a transgene such as BMP in an adenoviral vector in order to promote bone repair or regeneration (Abstract, Summary of the Invention). In regard to claim 11, Clancy teaches other transgenes including a combination of BMP, in addition to Wnt, IGF and PTH [0015, 0033].
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice a method of expressing a transgene by an adenoviral vector in bone tissue for bone repair or regeneration in a subject comprising administering multiple transgenes including BMP, Wnt, and IGF-I as taught by Betz and substitute a combination of BMP, Wnt, IGF and PTH as suggested by Clancy with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Clancy because these osteogenic transgenes act in concert and sometimes synergistically with BMP [0043]. For example, Yu et al. (2012) demonstrates that PTH enhancing the bone forming abilities of BMP and Wnt in bone marrow (Introduction, p. 2). Furthermore, it would have been prima facie obvious to combine these factors each of which is taught by the prior art to be useful for the same purpose, in order to form a vector composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Betz et al., (US 2005/0136042, filed 8/11/2004, see IDS filed 4/19/2023), in view of Lieber et al., (US 7,094,398, filed 6/01/2000, see IDS filed 4/19/2023), as applied to claim 6, in further view of O’Shea et al. (US 2013/0231267, filed 2/15/2013, published 9/05/2013, see IDS filed 6/1/2023)
As stated supra, Betz and Lieber suggest methods and compositions for expressing one or more transgenes that promote bone repair or regeneration in a subject comprising a synthetic adenovirus comprising an Ad5/Ad11 chimeric fiber protein.
In regard to claims 12 and 13, although Lieber teaches the adenovirus comprises modified hexon protein (col 2, 3rd para.), they are silent to modified hexon protein that detargets the adenovirus from the liver.
O’Shea et al., teaches methods and compositions for expressing a transgene in a subject comprising a synthetic adenovirus comprising a chimeric fiber protein (Abstract, [0002-0009]). In regard to claims 12 and 13, O’Shea teaches the adenovirus comprises a modified hexon with an E451Q mutation ([0054], see Fig. 43).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice a method of expressing a transgene by an adenoviral vector in bone tissue for bone repair or regeneration in a subject as taught by Betz et al., and substitute the modified hexon as taught by O’Shea with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by O’Shea because the modified hexon reduces liver uptake and therefore reduces liver inflammation and toxicity ([0003, 0004], see Fig. 1, line 8, Fig. 29 A).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Betz et al., (US 2005/0136042, filed 8/11/2004, see IDS filed 4/19/2023), in view of Lieber et al., (US 7,094,398, filed 6/01/2000, see IDS filed 4/19/2023), as applied to claim 6, in further view of Moutsatsos et al., (US 2011/0111505, filed 1/19/2011, see IDS filed 4/19/2023) and Hou et al. (PNAS, 1999, 96:7294-7299, see IDS filed 4/19/2023).
As stated supra, Betz and Lieber suggest methods and compositions for expressing one or more transgenes that promote bone repair or regeneration in a subject comprising a synthetic adenovirus comprising an Ad5/Ad11 chimeric fiber protein.
In regard to claims 15 and 16, Betz et al. are silent to a tissue specific promoter active in bone.
Moutsatsos et al., teaches methods and compositions for expressing a transgene such as BMP in a host cell such as a bone marrow cell in a subject in order to promote bone repair or regeneration (Abstract, Summary of the Invention). In regard to claims 15 and 16, Moutsatsos teaches the transgenes are operably linked to a tissue specific promoter that is active in bone such as the osteocalin promoter [0016].
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice a method of expressing a transgene by an adenoviral vector in bone tissue for bone repair or regeneration in a subject as taught by Betz and combine the tissue specific osteocalcin promoter as suggested by Moutsatsos with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Hou et al. (1999) who expresses a transgene reporter operably linked to the osteocalcin promoter in bone marrow cells and teaches that the gene therapy approaches using genetically modified bone marrow cells should take advantage of the osteocalcin promoter to confine expression of genes to bone (Abstract, Discussion, p. 7299).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Betz et al., (US 2005/0136042, filed 8/11/2004, see IDS filed 4/19/2023), in view of Lieber et al., (US 7,094,398, filed 6/01/2000, see IDS filed 4/19/2023), as applied to claim 6, in further view of O’Shea et al. (US2013/0231267, filed 2/15/2013, published 9/05/2013, see IDS filed 6/1/2023) and Qiao et al. (Gene Ther, 2011, 18:403-410, see IDS filed 4/19/2023)
As stated supra, Betz and Lieber suggest methods and compositions for expressing one or more transgenes that promote bone repair or regeneration in a subject comprising a synthetic adenovirus comprising an Ad5/Ad11 chimeric fiber protein.
In regard to claims 17-19, although Betz teaches the adenoviral vector comprises regulatory sequences [0107], they are silent to a liver specific microRNA binding site.
O’Shea et al., teaches methods and compositions for expressing a transgene in a subject comprising a synthetic adenovirus comprising a chimeric fiber protein (Abstract, [0002-0009]). In regard to claims 17-19, O’Shea teaches the adenovirus comprises a miR-122 binding site in the 3’UTR of the transgene (p. 23, Table 2, last lines, see Fig. 43).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice a method of expressing a transgene by an adenoviral vector in bone tissue for bone repair or regeneration in a subject as taught by Betz et al., and combine a miR-122 binding site in the 3’UTR of the transgene as taught by O’Shea with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Qiao et al., (2011), who teaches that incorporation of the liver-specific miR122 into viral vectors efficient inhibits transgene expression in the liver (Abstract, Figs. 1& 2), which O’Shea teaches reduces liver inflammation and toxicity ([0003, 0004]).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Allowable subject matter
SEQ ID NO:6 is free of the prior art.
Specifically, SEQ ID NO:6 is 40,150 nucleotides in length encoding the adenovirus AdSyn-CO277 vector, which comprises an Ad5 backbone, a DE1-EF1a-Cre-miR122 construct, a chimeric Ad5/Ad11 fiber knob, and hexon with a E451Q substitution.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631