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 .
1. Original claims 1-15 are pending and under examination.
Claim Rejections - 35 USC § 103
2. 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 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.
3. Claims 1 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Paul et al. (J. Neurosci Res., 2005, 81: 706-719), in view of both Titeux et al. (Mol. Ther., 2010, 18: 1509-1518) and Skalamera et al. (PLOS ONE, 2012, 7: 1-15). Paul and Titeux are of record in the parent application 15/565,065.
Paul et al. teach an adenoviral vector encoding the mouse NPC1 from the CMV promoter, wherein the vector is suitable to deliver NPC1 in vivo for analyzing its cellular localization, movement, and functional properties. (see Abstract; p. 707, column 2, first paragraph; p. 717, paragraph bridging columns 1 and 2).
Paul et al. do not teach do not teach a minimal EF1[Symbol font/0x61] promoter (claim 1). Titeux et al. teach the minimal EF1[Symbol font/0x61] promoter having a length of 237 bp, which ensures high levels of transgene expression (see p. 1510, column 1, first full paragraph and paragraph bridging columns 1 and 2; p. 1516, column 1, third paragraph). Skalamera et al. teach that the EF1[Symbol font/0x61] promoter is superior to the CMV promoter because it is less prone to silencing; as opposed to the CMV promoter, the EF1[Symbol font/0x61] promoter provides stable long term expression and provides a valuable resource for the analysis of the human genes (see Abstract; p. 9, column 1, first full paragraph; p. 12, column 2, second paragraph). Based on these teachings, one of skill in the art would have found obvious to replace the CMV promoter with the minimal EF1[Symbol font/0x61] promoter taught by Titeux et al., to achieve the predictable result of obtaining an vector capable of sustained long-term transgene NPC1 expression for analyzing its cellular its localization, movement, and functional properties.
With respect to claim 5, the recited SEQ ID NO: 8 is the sequence of the nucleic acid encoding the minimal EF1[Symbol font/0x61] promoter (see the specification, [0050]). While it is not clear whether the minimal promoter taught by Titeux et al. and the minimal promoter encoded by SEQ ID NO: 8 are identical, MPEP § 716.02 states that “[a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).” In the instant case, it is noted that there no evidence on the record that specifically using the minimal promoter encoded by SEQ ID NO: 8 imparts an unexpected property.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
4. Claims 1, 2, 5, 6, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Paul et al. taken with both Titeux et al. and Skalamera et al., in further view of both Wang et al. (Gene Ther., 1999, 6: 667-675) and Carstea et al. (Science, 1997, 277: 228-231). Wang and Carstea are of record in the parent application 15/565,065.
The teachings of Paul et al., Titeux et al., and Skalamera et al. are applied as above for claims 1 and 5. Paul et al., Titeux et al., and Skalamera et al. do not teach an AAV (claim 2). However, Paul et al. teach that AAV vectors could be used instead of adenoviral vectors (see p. 717, paragraph bridging columns 1 and 2). Wang et al. teach that, as opposed to adenoviral vectors, AAV vectors are nonpathogenic and have the ability to integrate into chromosomes to provide sustained long-term transgene expression (see paragraph bridging p. 667 and 668). Thus, expressing NPC1 from an AAV vector would have been obvious to one of skill in the art.
While Paul et al. teach the mouse NPC1 cDNA which is 5.8 kb, Wang et al. teach that the packaging limit for AAV is 5 kb. However, Carstea et al. teach that the human NPC1 protein has a length of 1278 amino acids (i.e., encoded by a cDNA of about 3.8 kb). Based on these teachings, one of skill in the art would have found obvious to replace the mouse NPC1 cDNA with the 3.8 kb human NPC1 cDNA, with the reasonable expectation that doing so would enable NPC1 cDNA packaging into AAV vectors (claim 2).
With respect to claim 6, it is noted that SEQ ID NO: 7 is the sequence of an AAV vector encoding NCP1 from the minimal EF1[Symbol font/0x61] promoter (see the instant specification, [0017]-[0019]; [0031]). There is no evidence on the record that the vector backbone results in a construct exhibiting an unexpected property. The essential components (i.e., the expression cassette comprising the minimal EF1[Symbol font/0x61] promoter and the NCP1 gene) and a vector comprising all these essential elements are taught by the combined art above. The difference between the claimed vector and the vector taught by the cited prior art is the vector backbone. The backbone is not significant if it does not provide a novel feature.
With respect to claim 8, the human NPC1 cDNA is codon-optimized for expression in humans.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
5. Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Paul et al. taken with all Titeux et al., Skalamera et al., Wang et al., and Carstea et al., in further view of de Jesus et al. (EMBO Mol. Med., 2012, 4: 691-704). de Jesus et al. is of record in the parent application 17/033,166.
The teachings of Paul et al., Titeux et al., Skalamera et al., and Wang et al., Carstea et al. are applied as above for claims 1, 2, 5, 6, and 8. Paul et al., Titeux et al., Skalamera et al., Wang et al., and Carstea et al. do not specifically teach AAV9 (claims 3 and 4). de Jesus et al. teach that AAV vectors comprising the AAV2 LTRs and the AAV9 capsid (AAV2/9) mediate efficient and stable transduction in a broad range of tissues (p. 692, paragraph bridging columns 1 and 2 and column 2, first full paragraph; p 701, paragraph bridging columns 1 and 2). Using AAV2/9 as the AAV vector would have been obvious to one of skill in the art with the reasonable expectation that doing so would result in efficient and stable NCP1 expression
With respect to claims 7 and 9-15, Wang et al teach an ITR-only AAV having ITRs (145 bp each), short promoters, and a short TK polyA (65 bp); the ITR-only AAV allows for the incorporation of 4.7 kb inserts (see p. 668, paragraph bridging columns 1 and 2; column 2, first paragraph; paragraph bridging p. 668 and 669; p. 669, column 1, last paragraph). One of skill in the art would have found obvious to extrapolate the teachings of Wang et al. to the AAV2/9 taught by the cited prior art, to achieve the predictable result of efficiently packaging the human NPC1 cDNA into the AAV2/9 vector. By doing so, one of skill in the art would have obtained a 4.39 kb AAV genome comprising a first AAV ITR (145 bp), the minimal EF1[Symbol font/0x61] promoter (237 bp) operably linked to the human NPC1 cDNA (3.8 kb), a TK polyA (63 bp), and a second AAV ITR (145 bp). A 4.39 kb genome is below the AAV packaging limit (claims 7 and 14).
While Wang et al. do not specifically teach 130 bp AAV2 ITRs (claim 9), as per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, there is no evidence of record indicating that using 130 bp ITRs leads to unexpected results over 145 ITRs.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
5. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633
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