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
Applicant’s submission filed 10/28/2025 has been received and entered. Claim 27 has been
amended. Claims 1, 4, 6, 8, 10, 11, 13, 15, 17, 20-22, 28-30, 38 and 39 remain withdrawn as being directed to non-elected inventions. Accordingly, claims 27, 31 and 34 are pending and under current examination.
Status of Prior Rejection/Response to Arguments
The rejections of claims 27, 31 and 34 under U.S.C. §102(a)(1) and 102(a)(2) over Chin et al. is withdrawn:
Applicant’s amendment to claim 27 recites “a hTAZ isoform consisting of the amino acid sequence of SEQ ID NO: 2”, and asserts that Chin does not teach a method of treating Barth syndrome that comprises administering to a subject in need thereof an effective amount of a hTAZ isoform consisting of the amino acid sequence of SEQ ID NO: 2. Additionally, Chin does not teach a nucleic acid molecule, an rAAV, or a composition comprising a nucleic acid molecule or the rAAV. Therefore, Chin does not teach each and every element as set forth in the instant claims (Remarks, p1-2).
Applicant’s amendment to instant claims limits administering a hTAZ isoform consisting of the amino acid sequence of SEQ ID NO: 2 for the treatment of Barth syndrome. While Chin teaches treating Barth syndrome using a fusion protein comprising a tafazzin peptide and a cellular permeability peptide, which comprises a peptide comprising SEQ ID NO: 2 (human TAZ wild type lacking exon 5 [NCBI RefSeq no. NP_851828.1]) (parag 0058). Applicant’s amendment to instant claims excludes the presence of cellular permeability peptide in the fusion protein. Therefore Chin does not anticipate instant claims, the rejection is withdrawn.
New grounds of rejection are necessitated by Applicant’s amendment.
New 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.
Claims 27, 31 and 34 are newly rejected under 35 U.S.C. 103 as being unpatentable over Suzuki-Hatano et al. (Hum Gene Ther. 2019 Feb;30(2):139-154, as cited in IDS) in view of Chin et al. (US 20150203827 A1, as cited in IDS). The rejection is necessitated by Applicant’s amendment.
Suzuki-Hatano et al. teach a study designed to test and compare three different AAV2/9-TAZ vectors that each contain a different promoter to drive TAZ expression (p140, left column).
Regarding claim 27, Suzuki-Hatano et al. teach Barth syndrome (BTHS) is a rare mitochondrial disease that affects heart and skeletal muscle and has no curative treatment. It is caused by recessive mutations in the X-linked gene TAZ, which encodes tafazzin (Abstract). Recessive single gene
defect disorders such as BTHS are optimal targets for gene replacement strategies. The potential
for various gene delivery systems to correct TAZ deficiency has been demonstrated in Saccharomyces
cerevisiae, Drosophila melanogaster, Danio rerio, and in vitro iPSC BTHS models (p140, left column). Replacement of TAZ demonstrated improvement in the BTHS disease phenotypes (motor weakness, mitochondrial respiration, in vitro cardiomyocyte contractile function). These studies strongly support development of a clinically relevant gene therapy approach to treat BTHS (p140, left column). Suzuki-Hatano et al. teach AAV-TAZ vector (p143, figure 1) comprising promoter (CMV, Des or TAZ) drives expression of the full-length human TAZ transgene complementary DNA (cDNA) (CCDS14748.1) (p140, right column), which express full-length human tafazzin. Suzuki-Hatano et al. teach the AAVs (which expressing full-length human tafazzin) were administered to TazKD mice at a dose of 1 X 1013 vg/kg (p140, right column). TazKD mice are Tafazzin short hairpin RNA knockdown mice (see p140, right column). This teaching reads on “a method of treating Barth syndrome (BTHS), the method comprising administering to a subject in need thereof an effective amount of a hTAZ”. Suzuki-Hatano et al. do not teach using an AAV vector expressing a hTAZ isoform consisting of the amino acid sequence of SEQ ID NO:2. However, such was disclosed by Chin et al. at the time of instant invention.
Chin et al. teach fusion proteins comprising a tafazzin peptide and a cellular permeability peptide and methods of making and using the same (parag 0002).
Regarding claim 27, Chin et al. teach using fusion proteins comprising a tafazzin peptide and a cellular permeability peptide to treat a patient having a disorder associated with a tafazzin deficiency or a remodeled cardiolipin deficiency (e.g., Barth syndrome) (see parag 0002). Chin et al. teach in some embodiments, tafazzin can refer to full-length human tafazzin or human tafazzin lacking exon
5, both of which can exhibit transacylase activity (parag 0034). Chin et al. also teach the amino acid sequence of human TAZ wild type lacking exon 5 [NCBI RefSeq no. NP_851828.1] is SEQ ID NO: 2 (see parag 0058), herein the SEQ ID NO: 2 is 100% identical to the SEQ ID NO: 2 in instant claim.
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Regarding claim 34, following the discussion above, Suzuki-Hatano et al. the AAV- TAZ vector comprising the full-length human TAZ transgene complementary DNA (cDNA) (CCDS14748.1) which expresses full-length human tafazzin was administered to TazKD mice (see p140, right column). Chin et al. teach both of full-length human tafazzin or human tafazzin lacking exon 5 (with SEQ ID NO:2) can exhibit transacylase activity (parag 0034).
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 modify Suzuki-Hatano et al.’s method of administering AAV-TAZ which expressing full length human tafazzin to TazKD mice, and have the AAV-TAZ expressing a hTAZ isoform comprising SEQ ID NO:2, as taught by Chin et al.. The only difference between instant claims and Suzuki-Hatano et al.’s AAV-TAZ vector which expressing full length human tafazzin is instant claims have a hTAZ isoform comprising amino acid SEQ ID NO:2 (which is human tafazzin lacking exon 5). Given that Chin et al. teach both full-length human tafazzin or human tafazzin lacking exon 5 can exhibit transacylase activity (parag 0034), one of ordinary skill in the art would have substituted Suzuki-Hatano et al.’s AAV-TAZ vector expressing full-length human tafazzin, and use an AAV-TAZ vector expressing a hTAZ isoform lacking exon 5, depends on their research interest or with the consideration of decreasing the AAV vector size. This simple substitution of one known element (AAV vector expressing full-length human tafazzin) for another known element (AAV vector expressing a hTAZ isoform lacking exon 5) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Regarding claim 31, Suzuki-Hatano et al. teach the AAV-TAZ vectors with different promoters (CMV, Des or TAZ) were each administered to TazKD mice at a dose of 1 X 1013 vg/kg (see p140, right column) in order to test the effect of the promoters. However, Suzuki-Hatano et al. also teach the aim of the study is to identify a promoter able to provide robust expression to cardiac and skeletal muscle with simultaneous low expression in the liver and other organs not impacted by BTHS as this would improve the safety and effectiveness of noninvasive intravenous gene therapy administration into human BTHS patients, indicate this AAV-TAZ treatment can also be used at human subjects.
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 modify Suzuki-Hatano et al.’s method of administering AAV-TAZ vector which expressing full length human tafazzin to TazKD mice, and have the AAV-TAZ vector expressing a hTAZ isoform comprising SEQ ID NO:2, as taught by Chin et al., further administer the AAV-TAZ vector expressing the hTAZ isoform comprising SEQ ID NO:2 (which is human tafazzin lacking exon 5) to human for the treatment of Barth syndrome. The skilled artisan would have been motivated to administer the AAV-TAZ vector expressing a hTAZ isoform comprising SEQ ID NO:2 to human for the treatment of Barth syndrome, since Suzuki-Hatano et al. teach the AAV-TAZ vector addressed the complete pathophysiology of BTHS in mice study (see p152, left column), and no negative effects were observed (p153, left column). There would be a reasonable expectation of success of administering the AAV-TAZ vector expressing a hTAZ isoform comprising SEQ ID NO:2 to human for the treatment of Barth syndrome since Suzuki-Hatano et al. teach no negative effects were observed in any of the mice exposed to their therapeutic strategy. As a multitude of AAV-mediated gene delivery strategies are currently being evaluated for clinical efficacy in humans to treat a range of genetically inherited disorders (spinal muscular atrophy, hemophilia), a strong precedent exists for their strategy to be successfully implemented as a valid therapy (p153, left column).
Conclusion
No claim is 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.
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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699