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 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) 1-4, 7, 9, 13-15, 18, 31, 32, 52 is/are rejected under 35 U.S.C. 103 as being unpatentable over Englehardt et al (US 20190083657 A1, of record) in view of Excoffon et al (PNAS, 2009, of record) and Wilschanski et al (Front in Pharm., 2012, of record.
Englehardt et al teach rAAV vectors characterized by a specific enhancer/promoter combination. Said rAAV vectors can be used in gene therapy to express transgenes such as CFTR. Englehardt et al teach the transcription enhancer sequence F5/tg83 wherein said sequence comprises instant SEQ ID NO: 14 (i.e., the F5 enhancer) as well as SEQ ID NO: 2 (i.e., the tg83 promoter) (see nucleotides 1-178 of SEQ ID NO: 27 of Englehardt et al). See AV2/2.F5tg83-fCFTRdeltaR, the abstract; ¶’s [0064]-[0066]). Said enhancer/promoter combination is operably linked to the CFTRdeltaR minigene and its use in gene therapy of CF, no matter the mutation, is envisaged (¶’s [0003], [0006]). Englehardt et al teach the packaging of the polynucleotide encoding the CFTRdeltaR into AAV1 or AAV2 capsids (Example 1) and describes rAAV vectors encoding the human CFTRdeltaR and its ability to transduce the lung of 1 month old ferrets (Example 2 and Fig 10). Englehardt et al teach the use of doxorubicin (an anthracycline) with administration of the rAAV (¶[0020]-[0021], Figs. 9, 10), considered to be “within about 48 hours” of rAAV administration (¶’s [0258], [0342] of the instant specification, US 20240115738 A1).
Englehardt et al does not teach the AV.TL65 capsid protein or a class I CFTR mutation.
Excoffon et al teach AAV2.5T (also known as AV.TL65) which is an evolved chimeric AAV capsid protein that mediates significantly improved apical airway transduction (Fig. 2, Fig. S1) for CF gene therapy purposes (abstract). The instant specification teaches (¶[0046], [0082], Table 1 of the published application, US 20240115738 A1) SEQ ID NO: 13 of the instant application is one and the same with the AV.TL65 capsid sequence of Excoffon et al. Further, Excoffon teaches AAV2.5T capsid as well as an rAAV comprising an AAV2.5T (i.e., AV.TL65 capsid) and a CMV promoter operably linked to a nucleic acid sequence encoding a CFTRdeltaR (Abstract; p3, column 1, paragraph2; p5, column 2, paragraphs 2-4; Figs 2-4).
Wilschanski et al teach Class I CFTR mutations include premature termination codons or nonsense codons. A nonsense mutation is a single point alteration in DNA that results in the inappropriate presence of a UAA, UAG, or UGA stop codon in the protein-coding region of the corresponding messenger RNA (mRNA) transcript. Such a stop codon causes premature cessation of translation, with protein truncation leading to loss of function and little to no functional CFTR. Nonsense mutations are responsible for about 10% of cystic fibrosis cases worldwide.
Thus, one of ordinary skill in the art, before the effective filing date of the claimed invention, would have been motivated to combine the teachings of Excoffon and Englehardt et al in order to have an rAAV comprising an AV.TL65 capsid protein known to significantly improve airway transduction with the F5-tg83 promoter enhancer combination driving expression of CFTRdeltaR in airway cells as taught by Englehardt et al. Likewise, the teachings of Excoffon, Wilschanski and Englehardt et al would motivate the skilled artisan to use the rAAV vectors in methods of CF gene therapy of class I mutations because Englehardt et al teaches the suitability of rAAV vectors for the treatment of any CF mutation, and Excoffon et al designed the AV.TL65 capsid for such CF applications. One would have had a reasonable expectation of success in combining said teachings due to both Excoffon, Wilschanski and Englehardt et al working in the field of gene therapy using AAV for the gene therapy treatment of CF.
Claim Objections
Applicant is advised that should claim 13 be found allowable, claim 14 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 14 recites the same limitations as claim 13 but in a different order. Thus, the claims do not differ in scope.
Conclusion
No claim is allowed.
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/MICHAEL D BURKHART/Primary Examiner, Art Unit 1638