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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 September 22, 2025 has been entered.
Status of Claims/Rejections
Claims 1-26 are currently 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 Claims 13-16 and 21-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim.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.
Any rejections not repeated in this Office action are withdrawn, and the following objections/rejections are the only objections/rejections applied in this application.
Specification
The disclosure is objected to because of the following informalities: The specification contains sequence rule non-compliant subject matter. See paragraph 0156 reproduced below.
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Appropriate correction is required as instructed below.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide sequences appearing in the specification, see paragraph 0156, are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-12 and 17-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-12 and 17-20 are now amended to require that “the AIMP-DX2 gene is selectively expressed in a neuron.”
It is noted that the instant specification fails to describe that the claimed vector has the function of selectively expressing the AIMP-DX2 gene in a neuron only as claimed.
For instance, “AAV-DX2-miR142 target seq” administration into mice resulted in an increased expression level of DX2 mRNA in PBMC of mice compared to control as shown in Figure 3 of the instant application. In addition, it is noted that the results shown in Figure 3 pertain exclusively to intracranial/intraparenchymal injection of the vector, which is deliberately intended to be delivered to the brain cells as such injection route is a direct delivery to the brain. Indeed, “AAV-DX2” without the “miR142 target seq” also provided DX2 mRNA expression in the brain tissue of mice at a similar level to “AAV-DX2-miR142 target seq” with no significant statistical difference. Hence, it is clear that the brain-directed delivery route intentionally used by the instant co-inventors is responsible for the high level of DX2 in the brain tissue compared to other tissues in mice. For completeness of the record, Figure 3 is reproduced below.
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Most importantly, the “brain” delivery shown in Figure 3 does not whatsoever describe that the “AAV-DX2-miR142 target seq” construct expresses the AIMP-DX2 gene only in a “neuron” as claimed because the “brain” tissue is not comprised exclusively of neurons. That is, the “brain” tissue in Figure 3 is not synonymous with the “neuron” cell type as it is art-recognized knowledge as well as a scientific fact that the brain tissue also comprises non-neuron cells such as microglia, astrocytes, oligodendrocytes, oligodendrocyte precursor cells, neural endothelial cells, and neural stem cells as evidenced by Simard et al. (US 2010/0092469 A1, of record) and further evidenced by Duyckaerts et al. (Acta Neuropathologica, 2009, 118:5-36, applicant’s citation), McKenzie et al. (Scientific Reports, 2018, 8:8868), and Shao et al. (Frontiers in Molecular Neuroscience, 2018, 11:48). Since Figure 3 does not differentiate neurons from non-neuron cells in the brain tissue, there is no adequate support that the claimed vector selectively expresses AIMP-DX2 in only neurons as opposed to other cells in the brain tissue.
The instant specification also discloses in vitro experimental results pertaining to AIMP-DX2 expression in a neuroblastoma cell line (SH-SY5Y) versus a leukemic monocyte cell line (THP-1). As an initial matter, it is noted that a “neuroblastoma” is not a neuron. That is, a neuron is a fully differentiated cell, whereas a neuroblastoma is an undifferentiated cell that has a potential to be differentiated into a neuron thus is a neural progenitor cell, not a neuron, and furthermore, a neuroblastoma is a cancer that occurs in infancy. See Salimi et al. (Journal of Cellular Biochemistry, 2018, 119:6482-6491) and Tibullo et al. (Molecular Neurobiology, 2017, 55:3344-3350). In addition, even if the neuroblastoma cell line should represent a fully differentiated, mature neuron for the sake of argument, the comparison between the blastoma cell line and the monocytic cell line as disclosed in the instant application does not and cannot support that AIMP-DX2 is expressed only selectively in neurons as evidenced by the fact that AIMP-DX2 is also expressed in the monocytic cell line, THP-1 as shown in Figure 2. Moreover, even if Figure 2 showed a complete lack of DX2 expression (zero expression) in “THP-1” cells (see the black bar) in miR-142-3p-containing vector for the sake of argument, the data in Figure 2 fails to show that DX2 is not expressed in non-monocytic cells such as PBMC, astrocytes, and neural endothelial cells. That is, the in vitro experimental design disclosed in the instant application is not inclusive of all cell types thus cannot show that the claimed vector expresses the claimed gene only selectively in neurons while not be expressed in all non-neuron cells, wherein the monocytic cells of THP-1 (even if there was zero DX2 expression) is not representative of all cell types of other than the neuron.
In the remarks filed on September 22, 2025, applicant points out paragraph 0149 of the published application as providing “explicit written description support” for the amended claims. It is noted that the paragraph number is identical in the instant specification filed on May 2, 2023. For discussion purpose, the paragraph of the instant specification is reproduced below.
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As shown above, the paragraph pointed out by applicant at best discloses the reason/purpose for the instant co-inventors to make the claimed recombinant vector: “in order to induce specific expression of the AIMP2 splicing variant only in neuron”. However, this paragraph is far from adequately supporting that the instant specification describes that the claimed vector provides AIMP-DX2 expression only selectively in a neuron but not any other cells for the reasons stated above.
Applicant also argues that the “neuron-selective expression” is shown in “EXHIBITS 1 and 2” that were submitted on April 30, 2025. It is noted that “EXHIBIT 1” (Lee et al., 2024) does not show any evidence that DX2 is expressed only selectively in neurons in the substantia nigra of the brain intracranially injected with the vector as brain cell types expressing DX2 were not analyzed. Further, “EXHIBIT 2” (Kook et al., 2022) appears to demonstrate that DX2 is co-localized with GFP in cells in the spinal cord having expression markers for “NeuN” (neuron), “GFAP” (astrocyte), “Olig2” (oligodendrocyte), and Iba1 (microglia) in mice intrathecally injected with the vector as shown in Figure 5D, which is reproduced below.
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Further, Figure 6B of “EXHIBIT 2” shows that the intrathecal injection of the vector expresses DX2 in both microglia and astrocytes in the spinal cord of the mice injected with the vector so as to allow the function of DX2 in the non-neuron cells: microglia and astrocytes. See Figure 6B reproduced below.
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As such, it is clear on the record as evidenced by the post-filing reference of Kook et al. (2022) that it was not known or predictable that the claimed vector would selectively express AIMP-DX2 only in a neuron such that it is not expressed in any other brain cells or non-brain cells including PBMC and THP-1. Note that the Kook reference (“EXHIBIT 2”) expressly contradict the instantly claimed “wherein” limitation as now presented.
In view of the foregoing, it is concluded that the instant specification fails to adequately describe the instantly claimed structure-function correlation for the claimed vector that is now required to express the claimed gene only selectively in a neuron. Therefore, the specification fails to reasonably convey that the instant co-inventors had possession of the claimed subject matter as of the filing date sought in the instant application.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-12 and 17-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12, 15, and 20-28 of copending Application No. 18/246,575.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the recombinant vector comprising AIMP2-DX2 gene further comprising miR-142 target sequences recited in the method claims of the ‘575 application. Since all structural limitations of the recombinant vector used in the ‘575 claims are patentably indistinct from those recited in the instant claims, it necessarily follows that the recombinant vector that is used in the ‘575 claims would inherently possess the function of “wherein” clause recited in the instant claims, absent objective evidence to the contrary.
Claims 1-12 and 17-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4 and 12-20 of copending Application No. 18/246,578.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the recombinant vector comprising AIMP2-DX2 gene further comprising miR-142 target sequences recited in the method claims of the ‘578 application. Since all structural limitations of the recombinant vector used in the ‘578 claims are patentably indistinct from those recited in the instant claims, it necessarily follows that the recombinant vector that is used in the ‘578 claims would inherently possess the function of “wherein” clause recited in the instant claims, absent objective evidence to the contrary.
Claims 1-12 and 17-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5, 8, and 13-21 of copending Application No. 18/858,540.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the recombinant vector comprising AIMP2-DX2 gene further comprising miR-142 target sequences recited in the method claims of the ‘540 application. Since all structural limitations of the recombinant vector used in the ‘540 claims are patentably indistinct from those recited in the instant claims, it necessarily follows that the recombinant vector that is used in the ‘540 claims would inherently possess the function of “wherein” clause recited in the instant claims, absent objective evidence to the contrary.
Conclusion
No claim is allowed.
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