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 .
Claim Status
The amendment of 03/20/2026 has been entered. Claims 1-3, 5, 7, 11, 13, 16, 18-19, and 21-32 are pending in this US patent application. Claims 16, 18-19, and 21-29 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/17/2025.
Claims 1-3, 5, 7, 11, 13, and 30-32 are currently under examination and were examined on their merits.
Information Disclosure Statement
The information disclosure statement filed in this application on 01/17/2024 has been received and considered.
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 1-3, 5, 7, 11, 13, and 30 remain rejected, and claims 31-32 are newly rejected as necessitated by amendment under 35 U.S.C. 103 as being unpatentable over Meliani et al., Human Gene Therapy Methods 26: 45-53 (2015), in view of Pan et al., Mol. Ther. 25(5S1): 183 (2017; cited on the IDS filed 01/17/2024), and Dane et al., Blood 132(Supplement 1): 2197 (2018).
Meliani teaches a method for the detection of anti-AAV antibodies in a clinical sample (see entire document, including page 46, right column, paragraph 1). The test samples are serially diluted, and controls (no inhibition and no reporter virus) are prepared. The AAV-luciferase vector is added at a defined concentration to each tube containing test samples, controls, and the no inhibition control. The vector/test sample mixtures are then added to cultured cells for a 30-min transduction period. The cells are then lysed, luciferase substrate is added, luciferase activity is detected, and the Nab titer is calculated (page 46, Figure 1; cf. steps (a)-(f) and (i) of claim 1; cf. claims 2, 7, and 30-32; the Examiner notes that Figure 1 states that the transduction step takes place for 30 minutes, which satisfies the limitations of claims 2 and 30-32 and step (c)(i) of claim 1). The cells used in the assay may be HEK 293 cells (page 47, right column, paragraph 3; cf. claim 11), and the AAV serotype may be AAV8 (page 48, left column, paragraph 1).
However, Meliani does not teach the specific luciferase of SEQ ID NO.: 2 or the capsid of SEQ ID NO.: 5 as recited in the instant claims and elected by Applicant.
Pan teaches that in vitro assays for neutralization of AAV in human samples can use a Nanoluciferase reporter gene encoding a high-brightness luciferase variant, allowing for measurement of neutralization in the presence of up to 600-fold lower levels of AAV than other variants of the assay (see entire document, including page 183, right column, paragraph 1; cf. claims 1(ii), 3, and 5; the Examiner notes that instant SEQ ID NO.: 2 as elected by Applicant is Nanoluciferase as used by Pan).
Dane teaches that gene transfer efficiency with AAVS3 is up to 10-fold higher in human cells when compared to AAV8 (see entire document, including page 2, paragraph 2; cf. claim 13; the Examiner notes that instant SEQ ID NO.: 5 is AAVS3 as recited by Dane).
While Meliani does not teach the luciferase of Pan or the AAV serotype of Dane in the method for the detection of anti-AAV antibodies in a clinical sample using luciferase, it would have been obvious to one of ordinary skill in the art to do so because Pan teaches that Nanoluciferase is a high-brightness luciferase variant and results in the ability to measure neutralization in the presence of up to 600-fold lower levels of AAV. In addition, Dane teaches that AAVS3 allows for improved gene transfer efficiency as compared to AAV8 as used by Meliani. One of ordinary skill in the art would have a reasonable expectation that using the luciferase of Pan and the AAV serotype of Dane in the method of Meliani would successfully result in the improved detection of AAV neutralizing antibodies in human clinical samples.
Therefore, claims 1-3, 5, 7, 11, 13, and 30-32 are rendered obvious by Meliani in view of Pan and Dane and are rejected under 35 U.S.C. 103.
The Supreme Court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation…103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions……the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) (emphasis added).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant has traversed the above rejection of the claims under 35 U.S.C. 103 as being unpatentable over Meliani in view of Pan and Dane. Applicant states that claim 1 has been amended to recite that the set interval of time to allow transduction is less than 16 hours. Applicant states that Meliani’s Figure 1 teaches a transduction step and then an incubation step of 16-24 hours, which Applicant states falls outside of the time range recited in the instant claims. Applicant states that the instant specification recites that the claimed invention allows for same-day or next-day/overnight determination of a sample’s inhibition titre, which Applicant states is not taught in the combination of Meliani, Pan, and Dane (remarks of 03/20/2026, pages 9-10). This argument has been fully considered but has not been found persuasive.
The Examiner notes that the instant claims are drawn to a method comprising a series of steps. The only time interval required in any of the instant claims regards the transduction step, which amended claim 1 recites must be less than 16 hours and dependent claims 2 and 30-32 limit further. Applicant’s claims recite no requirements about the overall length of time that the entire method takes. Meliani’s specifically taught step of transduction takes 30 minutes, and step (c) of claim 1 recites “waiting for a set interval of time to allow transduction to occur” (emphasis added). As such, Meliani waits for 30 minutes, which is less than any time range recited in instant claims 1-2 and 30-32, to allow transduction to occur. The amount of time required for any of Meliani’s other steps is not relevant to the instant claims, which do not limit the amount of time for any steps in the method other than the step of transduction. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Therefore, the Examiner has maintained the rejections presented above.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Erin M. Bowers, whose telephone number is (571)272-2897. The examiner can normally be reached Monday-Friday, 7:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau, can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Erin M. Bowers/Primary Examiner, Art Unit 1653 06/12/2026
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