DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of Group I in the reply filed on 11/26/2025 is acknowledged. For the species election, applicant has elected, without traverse, the species as recited in claim 3.
3. Claims 1-5, 7-15, 17-18, 25-26, 29, 31-33, 51, 53 and 60 are pending in the application. Claims 2, 4, 17, 32-33, 51, 53 and 60 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1, 3, 5, 7-15, 18, 25-26, 29 and 31 are currently under examination.
Claim Rejections - 35 USC § 112
4. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. Claims 1, 3, 5, 7-15, 18, 25-26, 29 and 31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation “the one or more cap genes” in line 9. There is insufficient antecedent basis for this limitation in the claim.
Claims 3, 5, 7-15, 18, 25-26, 29 and 31, each of which depends from claim 1, are also rejected for the same reason.
Claim Rejections - 35 USC § 103
6. 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.
7. 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.
8. 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.
9. Claims 1, 3, 5, 7-11, 15, 18, 25-26, 29 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Zolotukhin et al. (WO 2018/156654 A1, cited in the Office action dated 8/28/2025) in view of Chavez et al. (US 2017/0183647 A1).
Regarding claim 1
Zolotukhin et al. teach, throughout the whole document, a method for identifying an AAV cap gene suitable for vectorization, comprising: transducing host cells with a library of replication-incompetent AAV, wherein the replication-incompetent AAV comprise a genome comprising two AAV ITRs flanking a reporter gene (e.g., gene encoding mCherry) and a cap gene (e.g., gene encoding AAV capsid protein variant) (see Examples 2 and 10; Figures 2 and 20); detecting reporter gene, and selecting one or more host cells in which expression of the reporter gene is detected (see Examples 2 and 10; Figures 2 and 20; Table 3); isolating DNA from the selected one or more host cells (see Examples 2 and 10; Figure 2); and recovering the one or more cap genes from the DNA, thereby identifying one or more AAV cap genes suitable for vectorization (see Examples 2 and 10; Figure 2; Table 3). The method of Zolotukhin et al. involves DNA-based analysis rather than RNA-based analysis as used in the instantly claimed method.
However, Chavez et al. teach that RNA-based analysis can be used for such method of identifying desirable AAV cap gene(s) (see the whole document, particularly paragraphs [0057]-[0058] and Figure 1B). Chavez et al. further teach that the RNA-based analysis approach can provide advantages relative to DNA-based analysis, because “the latter can sometimes contain, for example, non-expressed or inactive capsid sequences that differ from the active capsid sequence of interest, and which can confound efforts to identify and confirm the sequence of the mutant capsid of interest” (see paragraph [0180]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute DNA-based analysis in the method of Zolotukhin et al. with RNA-based analysis as taught by Chavez et al. thus arriving at the instantly claimed invention, because: 1) substituting equivalents known for the same purpose is prima facie obvious (see MPEP 2144.06.II); 2) RNA-based analysis approach would provide advantages relative to DNA-based analysis, because “the latter can sometimes contain, for example, non-expressed or inactive capsid sequences that differ from the active capsid sequence of interest, and which can confound efforts to identify and confirm the sequence of the mutant capsid of interest” (see Chavez et al., paragraph [0180]). Given the teachings of the prior art and the level of the ordinary skilled artisan at the effective filing date of the claimed invention, it must be considered, absent evidence to the contrary, that said skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Regarding claims 3, 5 and 7
According to Zolotukhin et al., the reporter gene is operably linked to a first promoter (e.g., CBA promoter) and the cap gene is operably linked to a second promoter (e.g., SV40 or p40 promoter), wherein the first promoter is a ubiquitous and/or constitutive promoter, wherein the second promoter is an AAV promoter (see Examples 2 and 10; paragraph bridging pages 12-13; Figure 20).
Regarding claim 8
The method according to Zolotukhin et al. in view of Chavez et al., wherein the cap gene comprises a 3’ UTR and/or a 5’ UTR (see Chavez et al., paragraphs [0071] and [0083]).
Regarding claims 9-10
The method according to Zolotukhin et al. in view of Chavez et al., wherein the reporter gene comprises a barcode, wherein the barcode is at the 3’ end of the reporter gene (see Zolotukhin et al., Example 10 and Figure 20).
Regarding claim 11
The method according to Zolotukhin et al. in view of Chavez et al., wherein the detecting step further comprises converting the RNA to cDNA; amplifying and sequencing the barcode in the cDNA to identify one or more enriched barcodes; and identifying DNA that contains one of the enriched barcodes; and e) comprises recovering the one or more cap genes from the DNA identified as containing one of enriched barcodes (see Zolotukhin et al., Example 10; Chavez et al., paragraphs [0057]-[0058] and Figure 1B).
Regarding claim 15
The method according to Zolotukhin et al. in view of Chavez et al., wherein the genome comprises an intron between the first promoter and the reporter gene (see Zolotukhin et al., Figure 20).
Regarding claim 18
The method according to Zolotukhin et al. in view of Chavez et al., wherein: the genome comprises a poly adenylation sequence (Zolotukhin et al., Figure 20); and/or recovering the one or more cap genes comprises amplification of the one or more cap genes (see Zolotukhin et al., Example 2; Chavez et al., paragraph [0204] and Figure 1B).
Regarding claim 25
The method according to Zolotukhin et al. in view of Chavez et al., wherein when a plurality of cap genes are recovered, further comprising producing a plurality of replication-incompetent AAV with the plurality of cap genes (see Zolotukhin et al., Example 10 and Figure 2).
Regarding claim 26
The method according to Zolotukhin et al. in view of Chavez et al., further comprising repeating the steps one or more times (see Zolotukhin et al., Example 10 and Figure 2; Chavez et al., Figure 1B).
Regarding claim 29
The method according to Zolotukhin et al. in view of Chavez et al., wherein the selecting step comprises selecting a subpopulation of host cells in which expression of a detectable marker is detected, such that the one or more host cells selected are a subpopulation of the host cells (see Zolotukhin et al., Example 10 and Figure 2).
Regarding claim 31
The method according to Zolotukhin et al. in view of Chavez et al., further comprising producing one or more AAV vectors using the one or more cap genes identified for vectorization (see Zolotukhin et al., Example 10).
Conclusion
10. No claim is currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAIJIANG ZHANG whose telephone number is (571)272-5207. The examiner can normally be reached Monday - Friday, 8:30 am - 5 pm.
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/KAIJIANG ZHANG/Primary Examiner, Art Unit 1684