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 .
Status of Application/Amendment/Claims
This Office action is in response to the communications filed on April 10, 2026 and April 15, 2026.
Currently, claims 1-26 are pending in the instant application. Claims 13-16 and 21-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Accordingly, claims 1-12 and 17-20 are under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
Terminal Disclaimer
The terminal disclaimer filed on April 10, 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Application Nos. 18/246,575; 18/246,578; and 18,858,540 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Response to Arguments/Declaration
Applicant’s arguments filed on April 10, 2026 and the §1.132 declaration filed on April 15, 2026 have been considered but are moot because they do not pertain to the new ground rejection necessitated by claim amendments as set forth hereinbelow. In addition, for applicant’s own edification, applicant’s attention is directed to the fact that post-filing data cannot be used to show that the instant specification itself describes the claimed subject matter as of the filing date sought. Note that the previous §112(a) rejection was a written description rejection, not an enablement rejection. Note that a written description inquiry occurs as of the filing date sought, not after the filing date. See Ariad Pharmaceuticals Inc. v. Eli Lilly & Co. 593 F3d 1336, 94 USPQ2d 1161 (Fed. Cir. 2010).
New Rejections Necessitated by Amendment
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.
Claims 1-12 and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Choi et al. (KR20170041363 A, of record) in view of Schmitt et al. (Gastroenterology, 2010, 139:999-1007, of record), Majowicz et al. (The Journal of Gene Medicine, 2013, 15:219-232, of record), and Gao et al. (US 2017/0166925 A1, of record).
Choi discloses making “a pharmaceutical composition for preventing or treating a neurological disease, comprising an AIMP2 mutant gene lacking exon 2 (AIMP2-DX2) or a vector containing the gene as an active ingredient.” See claim 1.
Choi teaches that the neurological disease is Parkinson’s disease and the vector is an “adenoassociated virus (AAV)” vector, wherein the “adeno-associated virus” vector comprising AIMP-DX2 is “introduced into nerve cells”. See claims 4 and 6; paragraph 0010.
Choi teaches that “Parkinson’s disease is known to be caused by the gradual loss of dopaminergic neurons distributed in the substantia nigra of the brain” and increased cell death in the substantia nigra, thereby “decreasing neurons” is the cause of Parkinson’s disease. See paragraphs 0002 and 0005.
Choi teaches that AIMP2-DX2 overexpression in N2A neuroblastoma cells reduces cell death such that “when DX2 was overexpressed, the level of cell death was restored to a level similar to (insignificant) when the original empty vector (PcDNA3.0) was inserted” and that “[T]his inhibition of N2A apoptosis by DX2 was also commonly confirmed in primary neurons.” (emphasis added). See paragraphs 0107 and 0111.
Choi discloses that “the AIMP2-DX2 gene has a base sequence represented by sequence number 1, and the AIMP2-DX2 polypeptide has an amino acid sequence represented by sequence number 2.” See paragraph 0026.
It is noted that the original KR publication discloses a 756-nt DNA sequence of SEQ ID NO:1 and a 251-amino acid long protein sequence of SEQ ID NO:2 (see pages 18-19), each of which is 100% identical to SEQ ID NO:1 and SEQ ID NO:2 claimed in the instant case, respectively.
Choi does not teach that the AIMP2-DX2-containing vector further comprises a miR-142 target nucleic acid for reducing off-target effects in hematopoietic cells. Choi also does not expressly disclose that the vector comprises an operably linked promoter.
Schmitt teaches making a transgene expression vector, wherein “an miRNA target sequence for the miR-142-3p (miR-142) is placed downstream of the therapeutic complementary DNA (cDNA). The miR-142 is specifically expressed in cells of the hematopoietic lineage, including antigen-presenting cells (APCs). After administration to mice, expression in APC is turned off because the miR-142 present in the cell will bind to its target sequence in the messenger RNA (mRNA) encoding the transgene. This will result in degradation of the mRNA if the target sequences perfectly matched to the miR-142 sequence.” (emphasis added). See page 1000.
Schmitt reports that “we show that addition of 4 copies of the miR-142 target sequences (miR-142T) to the cDNA encoding UGT1A1 allowed escape from the immune response and resulted in complete and definitive correction of Gunn rats after lentivirus delivery to adult animals with no induction of a cytotoxic immune response.” (emphasis added). See page 1000.
Schmitt discloses that the transgene of interest, UGT1A1, is transduced mostly in the liver such that “most of the transduction occurred in the liver”, which is the intended organ for UGT1A1 transgene expression for treating a human liver genetic disease, Crigler-Najjar type 1 (CN-I) caused by the absence of UGT1A1, when the transgene comprising miR-142 target sequences is “injected intraportally” via “intraportal vein injection” into the liver of animals. See pages 999-1001 and 1004.
Schmitt teaches, “Modification of the vector design is the most promising strategy to circumvent the immune response for future clinical application, particularly by exploiting the endogenous miRNA-mediated posttranscriptional pathway to induce degradation of vector-derived mRNA in APCs.” (emphasis added). See page 1005.
Consistent with Schmitt, Majowicz teaches that “the incorporation of specific miRNA target sequences after the transgene sequence can repress transgene expression in particular cell types. Transgene expression from vectors incorporating target sequences for mir-142-3p, which is the haematopoetic-specific miRNA, was shown to be effectively repressed in APCs.” (emphasis added). See page 228, left column.
Majowicz reports that “the incorporation of mir142-3p target sequences has the potential to reduce local, cellular immune responses, as previously noted by Boisgerault et al.” (emphasis added). See pages 228-229.
Majowicz teaches that a “very attractive target tissue for AAV vector-mediated gene therapy is muscle” and “the data obtained in the present study indicate that the rising humoral and cellular immune responses against OVA protein after intramuscular delivery can be efficiently reduced by use of mir-142-3p target sequences that prevent expression of OVA protein in APCs.” (emphasis added). See pages 226 and 230.
Gao teaches making a recombinant adeno-associated virus (rAAV) that “harbors a transgene engineered to express an RNA transcript that comprises a binding site of at least one immune-associated miRNA”, wherein the immune-related miRNA is “miR-142-3p” and the rAAV containing “two tandem” or “at least two” miRNA binding sites (BS) such as “miR-142BS” help “reduce immune response against rAAV-derived transgene products” by “reducing transgene expression in APCs, such as DCs”, wherein “immunotoxicity may result from inadvertent transduction of antigen presenting cells (APCs),” wherein the “inadvertent transduction may trigger host immunity towards transgene products.” (emphasis added). See paragraphs 0004, 0020, 0093, and 0095.
Gao demonstrates that “muscle injection” of the AAV vector encoding a transgene with miR-142 binding sites into the “target tissue (e.g., muscle tissue)” of mice, wherein “incorporating miR-142-3p binding sites inhibits transgene expression in antigen presenting cells, but not in muscle cells” when the AAV vector is “injected into mice intramuscularly”, thereby resulting in “AAV vectors maintained in the muscle cells.” (emphasis added). See paragraphs 0011, 0013-0014, 0057, and 0098.
Gao discloses that the sequence of miR-142-3p BS is 5’-TCCATAAAGTAGGAAACACTACA (SEQ ID NO:20), which is 100% identical to SEQ ID NO:5 claimed in the instant case. See Table 2.
Gao demonstrates that a vector that includes miR-142-3p binding sites reduces the transgene expression in dendritic cells (JAWS II) and macrophages (RAW264.7). See Figure 6B.
Gao teaches that the rAAV comprises a promoter operably linked to the transgene, wherein the promoter can be the “cytomegalovirus (CMV) promoter” or the “zinc-inducible sheep metallothionine (MT) promoter” See paragraphs 0035-0038.
It would have been obvious to one of ordinary skill in the art before the effective filing date to incorporate at least two miR-142-3p binding sites into the AIMP2-DX2-encoding vector of Choi. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to express AIMP2-DX2 in the target neurons or “nerve cells” by local (e.g., intracerebral injection) delivery of the AIMP-DX2-encoding vector without inducing unwanted immune responses against the transgene AIMP2-DX2 in the non-target hematopoietic cells and hematopoietic lineage cells including antigen-presenting cells (APCs), because making a vector encoding AIMP2-DX2 that is to be “introduced into nerve cells” for neuronal expression of AIMP2-DX2 for decreasing neuronal cell death in a neurological disease was an art-recognized goal as evidenced by Choi, and because incorporating miR-142-3p binding sites into a transgene-expressing viral vector was an art-recognized methodology for inducing therapeutic gene/protein expression in intended tissues/cells but not in the unintended target cells including hematopoietic cells when the viral vector is delivered to the intended tissues/cells via local delivery (e.g., intraportal vein injection, intramuscular injection) as amply evidenced by Schmitt, Majowicz, and Gao. That is, Choi’s teaching pertaining to the direct/local delivery of the AAV vector comprising AIMP-DX2 that is “introduced into nerve cells” would have been deemed to benefit from further “incorporating miR-142-3p binding sites” because such methodology pertaining to a vector encoding a transgene and miR-142-3p binding sites was deemed useful for expressing the transgene only in the intended target cells via local delivery, while inhibiting transgene expression in non-target hematopoietic lineage cells. Further, since use of a recombinant AAV vector comprising a CMV or MT promoter operably linked to a desired transgene further comprising miR-142-3p binding sites in the 3’ region was known in the art as taught by Gao, and since all necessary nucleotide/amino acid sequence information pertaining to SEQ ID NOs:1, 2, and 5 claimed in the instant case was available in the prior art as evidenced by Choi and Gao as explained above, one of ordinary skill in the art would have had a reasonable expectation of success in arriving at the claimed subject matter by merely assembling the necessary elements in an operable manner within the skills/techniques of an ordinarily skilled artisan in the relevant art. Furthermore, the newly recited limitation is a mere reflection of the art-recognized scientific principle as evidenced by the teachings of Schmitt, Majowicz, and Gao thus, there is no inventive feature or new discovery pertaining to the newly recited limitation.
Accordingly, claims 1-12 and 17-20 taken as a whole would have been prima facie obvious before the effective filing date.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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