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 .
Claim Status
2. Claims 3-5, 7-14, 17, 19, 23-30, 33, 36-39, 43-51, 54, 56, and 58 are canceled.
Claims 1-2, 6, 15-16, 18, 20-22, 31-32, 34-35, 40, 42, 52-53, 55, and 57 are currently under consideration.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on 29 June 2026 was filed after the mailing date of the Non-Final Office Action mailed 29 December 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Objections Withdrawn
Specification
4. The objection to the specification for nucleotide and/or amino acid sequence disclosure is withdrawn in view of Applicant’s amendments.
5. The objection to the specification for trade names or marks used in commerce are withdrawn in view of Applicant’s amendments.
Claim Objections
6. The objection to claims 1, 8, 16, 21, 32, and 57 for informalities are withdrawn in view of Applicant’s amendments.
Rejections Withdrawn
Claim Rejections - 35 USC § 112
7. The rejections of claims 1-2, 6, 8-9, 15-16, 18, 20-22, 31-32, 34-35, 40, 42, 52-53, 55, and 57 are under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite are withdrawn in view of Applicant’s amendments.
Rejections Maintained
8. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 103
9. Claims 1-2, 6, 16, 18, 20-22, 31-32, 34-35, 40, 42, 52-53, 55 and 57 remain rejected under 35 U.S.C. 103 as being unpatentable over Grieger (Mol. Ther., February 2016, 24(2): 287-297) (See IDS filed 15 June 2023) in view of Panteli (WO 2018208960 A1; published 15 November 2018) (See IDS filed 15 June 2023).
Applicant’s Arguments: Applicant states that the claimed method provides a novel and inventive approach for lowering the cost of recombinant virus production by increasing virus yield, a known challenge when increasing bioreactor volume. Applicant also argues that Grieger, Panteli, nor their combination would have led a skilled person to reasonably expect success of multiple transfection mixtures in a large scale AAV production method. Applicant argues that Grieger teaches away from increasing the volume of mixture as it resulted in a negative effect on total titer, and that Panteli agrees. Applicant further argues that Panteli does not show working examples for multiple transfection mixtures, but rather provides a hypothesized approach. In addition, Applicant argues that Panteli’s method only uses “mild” mixing and provides insufficient guidance with respect to the transfer method.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive.
Applicant argues that the method provided lowers cost of production by increasing virus yield in large scale suspension culture. However, Applicant fails to argue or establish unexpected results. No data, statistical significance, or comparison to the closest prior art is provided. If Applicant is arguing a long felt need, MPEP 716.04 makes clear that Applicant has not met the criteria for this argument. Establishing long-felt need requires objective evidence that an art recognized problem existed in the art for a long period of time without solution. The relevance of long-felt need and the failure of others to the issue of obviousness depends on several factors. First, the need must have been a persistent one that was recognized by those of ordinary skill in the art. In re Gershon, 372 F.2d 535, 539, 152 USPQ 602, 605 (CCPA 1967). Second, the long-felt need must not have been satisfied by another before the invention by applicant. Newell Companies v. Kenney Mfg. Co., 864 F.2d 757, 768, 9 USPQ2d 1417, 1426 (Fed. Cir. 1988) ("[O]nce another supplied the key element, there was no long-felt need or, indeed, a problem to be solved".) Third, the invention must in fact satisfy the long-felt need. In re Cavanagh, 436 F.2d 491, 168 USPQ 466 (CCPA 1971). Applicant is not solving a problem that would not solvable using a different method. It is noted that the prior art of record in the 103 rejection shows methods of producing recombinant virus particles for example. In regards to providing evidence, there appears to be none. Further, the drawings do not seem to support the claim that the split transfection resulted in an increase in viral titer compared to single dose transfections. Notably, Figure 9’s split transfection does not appear to be significantly higher than some of the single transfections and Figure 12 does not compare split vs. single transfection between the same volumes of culture and thus the effect of the split transfection is unclear. Regarding the “mild” mixing of Panteli, the mechanical rocking was sufficient to “reach a steady state concentration of DNA within the transfection master mix” and was incubated after (¶ [0006]). It is noted that any showing of unexpected results should be a comparison with the closest prior art and practically and statistically significant. At least here, no statistically significant surprising result is put forth.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Regarding claim 57, it was noted in the Non-Final Office Action mailed 29 December 2025 on page 12 that the intended result of having twice as many rAAV particles produced was not given patentable weight. The claimed reference method is similar to those in the prior art and all method steps are provided in the obvious method and thus any result would be inherent. MPEP 2112(II) states that no requirement that one of ordinary skill would have recognized the inherent property at the time of invention or before for art to be anticipatory. Therefore, the fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). For the same reasons as discussed supra, Grieger and Panteli do not teach away from the claimed invention as they make the claims obvious. Even if a negative effect were seen in Grieger this is not equivalent to a teaching that the method does not work. In fact, it teaches functionality just a different efficiency. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). The same argument is made for the discussion by Applicant of teaching away in Panteli.
The lack of working examples of Panteli is irrelevant since no working example is required for enablement and the teachings of Panteli do teach sufficiently the structures required for rAAV production as discussed on page 12 of the previous action.
Taken all together, this rejection stands.
10. Claim 15 remains rejected under 35 U.S.C. 103 as being unpatentable over Grieger (Supra) and Panteli (Supra) as applied to claims 1-2, 6, 16, 18, 20-22, 31-32, 34-35, 40, 42, 52-53, and 55 above, and further in view of Hu (US 20110212526 A1; 01 September 2011) (See PTO-892 mailed 29 December 2025).
Applicant’s Arguments: Applicant argues that Grieger, Panteli, and Hu do not teach or suggest every element of the claimed method, nor have a reason to use an inline mixer.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive.
Hu teaches a device that comprises the growth substrate means that can function as a static mixer to cultivate rAAV(¶ [0006]). A static mixer is a type of inline mixer. Therefore, as stated previously, it would have been obvious to one of ordinary skill to simply substitute the rocking device of Panteli with an inline mixer.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Double Patenting
11. Claims 1-2, 6, 15-16, 18, 20-22, 31-32, 34-35, 40, 42, 52-53, 55, and 57 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4, 20-21, 30-31, 33, 38, and 44-45 of copending Application No. 18/261,551 in view of Grieger (Mol. Ther., February 2016, 24(2): 287-297) (See IDS filed 15 June 2023), Panteli (WO 2018208960 A1; published 15 November 2018) (See IDS filed 15 June 2023), and Hu (US 20110212526 A1; 01 September 2011) (See PTO-892 mailed 29 December 2025).
Applicant’s Arguments: Applicant argues that the Instant claims are not obvious in view of the copending ‘551 application in view of Grieger, Panteli, and Hu because ‘551 does not teach forming at least two separate compositions comprising polynucleotide:transfection reagent complexes and transferring them to the suspension cell culture to transfect the cells and Grieger, Panteli, and Hu do not remedy the deficiencies of the recited claims as traversed supra.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive.
The “comprising” language of claim 4 of ‘551 and the Instant Claims allows for additional steps. Therefore, claims 4, 30-31, 33, 38, and 44-45, of ‘551 in view of Grieger, Panteli, and Hu make the Instant Claims obvious for reasons discussed supra.
This is a provisional nonstatutory double patenting rejection.
New Objections
Claim Objections
12. Claims 1, 34, and 52 are objected to because of the following informalities:
Regarding claim 1, the word “of” in line 2 should be deleted for grammatical clarity.
Regarding claim 34, “viable cell” should be plural for grammatical clarity.
Regarding claim 52, “one or more polynucleotide” should be plural for grammatical clarity.
Appropriate correction is required.
Conclusion
13. 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 KRISTINA E LY whose telephone number is (571)272-5169. The examiner can normally be reached Monday - Thursday, 8:00 am - 5:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KRISTINA E. LY/Examiner, Art Unit 1671
/Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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