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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8/25/2026 has been entered.
Claim Rejections - 35 USC § 103
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.
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.
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.
Claim(s) 1, 3-6, 8, 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Herzog et al (US 11,883,506, efd 8/7/2020) as evidenced by Chamberlain et al (Curr. Opin. Cardiol., 2017) in view of Holzmeister et al (WO 2021/038291,3/4/2021, cited by applicants) as evidenced by Rickelt (Cell Tissue Res., 2012). This rejection is maintained for reasons made of record in the Office Actions dated 8/27/2025, 2/25/2026 and for reasons set forth below.
Herzog et al teach plakophilin-2 (PKP2) gene therapy for treatment of cardiomyopathies such as ARVC, ACM, and other cardiomyopathies by delivery of a viral vector encoding PKP2 to cardiomyocytes. See the abstract, col. 1 lines 41-60, col. 7, lines 36-40, Fig. 9, claim 1. The term “haploinsufficient” is taken to mean when one copy (or allele) of a gene is inactivated or deleted and the remaining functional copy cannot completely replace the inactivated allele. The therapy of Herzog et al restores PKP2 mRNA or protein levels in the desmosome due to deletion or other insufficiencies caused by autosomal dominant variation (col. 1, lines 38-50). As evidence by Chamberlain et al, such haploinsufficiencies are found in common cardiomyopathies including those due to PKP2 insufficiency (“Inherited Cardiomyopathies” p.276, Table 1). Desmosomal expression of PKP2 was increased upon transduction of induced cardiomyocytes with the AAV vectors of Herzog et al, considered to be in sufficient amounts to meet the “1.5-fold” limitation of instant claim 1. See Figs 5A, 5B and relevant legends; col. 3 line 64 – col. 4 line 31; col. 42, lines 39-42. Herzog et al teaches that PKP2 localizes to desmosomes and nuclei, binds to desmoplakins and plakoglobin facilitating cell-to-cell contact, and controls transcription processes (col 8, lines 7-14). Rickelt teaches that PKP2 is a regulatory component in cytoplasmic junctions, such as desmosomes, and regulates the normal distribution of desmoplakin in cardiomyocyte junctions (abstract, Discussion ¶ linking first and second cols, p. 289). Thus it appears that “increasing” desmoplakin or plakoglobin expression is a natural feature, or inherent property, of PKP2 by increasing the ability of such to form cellular junctions.
Further, the desmosomal expression increase of PKP2 limitations are intended results limitations and are not required, positive method steps of the claimed methods. Such limitations are given little patentable weight as they describe a result of a process, not a method step. See MPEP 2111.04:
However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003))
The viral vector may be AAV6 (col. 3, lines 28-29-56) and a cardiac-specific promoter may be used (col. 2 lines 1-2). An intron may follow the promoter, considered to be “immediately downstream” of the promoter, and are considered chimeric with respect to the AAV vector, or promoter, and one such intron (Table 4) is labeled “chimeric intron sequence”. See Fig. 11, Table 4, col. 37, line 61-col. 38, line 45. The methods of Herzog et al were effective to produce production of PKP2 (see above) and at levels sufficient to alleviate symptoms of ARVC (e.g. Figs 6-9). Human subjects are taught in col. 3, line 58, and intracoronary administration in the abstract and claim 1.
Herzog et al do not teach perfusion of the vector into a closed coronary circuit.
Holzmeister et al teaches the use of device to form a closed coronary circuit in a heart of a patient as a means for perfusing gene therapy vectors to the heart in order to reduce immune reactions to doses with viral gene therapy vectors, such as AAV. See the abstract, ¶’s [0007]-[0011], [0019], Fig 1A, 1B.
The claimed method of treating cardiomyopathy is essentially disclosed by Herzog et al with the exception of the closed coronary circuit limitation. The ordinary skilled artisan, seeking a method to treat cardiomyopathy with AAV vectors, would have been motivated to use the closed coronary circuit device of Holzmeister et al with the methods of Herzog et al because Herzog et al teaches intracoronary delivery of the AAV vector, and Holzmeister et al teaches an efficient means for such delivery. It would have been obvious for the skilled artisan to do this because of the known benefit of administration of AAV vectors for gene therapy as taught by Herzog and Holzmeister et al. Given the teachings of the cited references and the level of skill of the ordinary skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Response to Arguments
Applicant's arguments filed 8/25/2026 have been fully considered but they are not persuasive. Applicants essentially assert that: 1) the claims have been amended to recite affirmative method steps, not merely intended results; 2) Herzog and Rickelt et al do not provide evidence of inherency; 3) the specification confirms the recited results are not inherent.
Regarding 1), the claims have always recited both affirmative method steps, e.g. “perfusing”, and intended results, e.g. “increasing ….expression”. The instant amendments merely change the phrasing and order of language but the premise remains the same. That is, by performing the “perfusing” step, the methods lead to the intended result of “increasing ….expression”. The fact remains that “increasing….expression” is not an active method step performed by the skilled artisan, i.e. the skilled artisan cannot themselves increase PKP2 expression in desmosomes; and, the limitation does not add any further structure to the claimed gene therapy vector. Thus, the claims are properly interpreted as reciting an intended result, the limitations of which have been addressed above in the record. It is noted that applicant’s also address these limitations as “…the claimed biological result.” See the most recent response, page 5, second full ¶.
Regarding 2), the teachings of Herzog and Rickelt et al stand. It was not alleged that Herzog or Rickelt et al taught quantification or titration of desmosomal expression of the recited proteins, only that PKP2 inherently increases proper desmoplakin or plakoglobin expression in order to form cellular junctions. That Rickelt et al use an animal model rather than humans is deemed irrelevant as the function of PKP2 across the species is the same, absent evidence to the contrary.
Regarding 3), reporting results not found in the prior art does not remove an inherency or intended result argument. This is the basis of such arguments: discovery of a new property possessed by a composition taught by the prior art does not render the prior art composition novel or non-obvious.
Double Patenting
The rejection of the claims over copending Application No. 17/761,677 is withdrawn due to amendment of the claims in that application to no longer recite methods of treatment.
The rejection of the claims over copending Application No. 19/023,648 is withdrawn due to amendment of the instant claims, as the features of the instant viral vector and closed circuit limitations are not claimed in the ‘648 application.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
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/MICHAEL D BURKHART/Primary Examiner, Art Unit 1638
