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 .
DETAILED ACTION
The Examiner for this Application has changed. Please direct all future correspondence to Katriel Kasayan, AU 1634. Additional contact information can be found at the end of this paper.
This action is in response to the papers filed on September 17, 2025. A response to the restriction requirement filed on September 17, 2025 is acknowledged.
Claims 1-6, 10-17, 19-22 and 26-27 are currently pending. Claims 10-17 and 19 have been amended and withdrawn by Applicants’ amendment filed on 9/17/2025. No claims were canceled by Applicants’ amendment filed on 9/17/2025. Applicants' election of Group 1 directed to an expression cassette, e.g., claims 1-6 is acknowledged.
Claims 10-17, 19-22, 26 and 27 are withdrawn from further consideration, pursuant to 37 CFR l. l 42(b ), as being drawn to non-elected invention, there being no allowable generic or linking claim. The restriction requirement is deemed proper, maintained and made FINAL.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election was treated as an election without traverse (MPEP § 818.03(a)).
Therefore, claims 1-6 are under examination to which the following grounds of rejection are applicable.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2021/040238, filed July 2, 2021. Applicant’s claim for the benefit of a prior-filed parent provisional application 63/048,405, filed on July 6, 2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is July 6, 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 2/14/2023, 07/24/2024, 12/09/2024, and 09/17/2025 were filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-6 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 1, 2 and 5 are indefinite in their recitation of “a sequence as set forth” . It is unclear if the quoted phase refer to the full length of the claimed sequence of a domain of the claimed sequence. Amending the claims to recite “a sequence comprising the amino acid of SEQ ID NOS:4 or 8”in claims 1 and 5, “a sequence comprising the nucleotide sequence of SEQ ID NO:3 or SEQ ID NO:7 in claim 2 would obviate the rejection.
Claims 3, 4 and 6 are rejected insofar as they depend on claim 1.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 2 are rejected under 35 U.S.C. 102(a(1))(a(2)) as being anticipated by Julien et al. [Cited in IDS filed 2/14/2023; citations are from US Pub. Pub. 2016/0091504].
Regarding claim 1, Julien teaches an expression cassette [para 0059, "The present invention also relates to an expression cassette comprising the sequence of TDP-43WT. TDP-43A315T or TDP-43G348C"] comprising one or more polynucleotides encoding a polypeptide at least 95% identical to a sequence as set forth in SEQ ID NO: 8 [SEQ ID NO: 1 amino acids 275-414 of Julien exhibit 100% identity to claimed SEQ ID NO: 8 (See alignment of claimed amino acid sequence of SEQ ID NO: 8 and of Julien’ SEQ ID NO: 1 below)]; para 0097 "TDP-43 polypeptides as well as polynucleotides are well known in the art. For example, see NM_007375.3, Gene Bank AK222754.1 or UniProt 013148 Representative polypeptide sequence (SEQ ID NO:1)"].
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Regarding claim 2, Julien teaches the expression cassette of claim 1, wherein the one or more polynucleotides comprise a sequence at least 95% identical to a sequence as set forth in SEQ ID NO: 3 [SEQ ID NO: 2 nucleic acids 859-1314 of Julien exhibit 100% identity to claimed SEQ ID NO: 3; See alignment of claimed nucleotide sequence of SEQ ID NO: 3 and of Julien’ SEQ ID NO: 2 below].
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Thus, by teaching all the claimed limitations, Julien et al., anticipates claims 1 and 2.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Julien et al. [Cited in IDS filed 2/14/2023; citations are from US Pub. Pub. 2016/0091504], in view of Foglieni et al. [Cited in IDS filed 2/14/2023].
With regard to instant claims 1 and 2, the teachings of the expression cassette render obvious the claimed product, as iterated in the 102 rejection the content of which is incorporated herein, in its entirety. Moreover, Julien discloses expression cassettes functionally linked to promoters and other translational regulatory control elements (para [0174], “’expression cassette’ as used herein refers to the combination of promoter elements with other transcriptional and translational regulatory control elements which are operably linked”).
Regarding claim 3, Julien discloses the expression cassette of claim 1, further comprising a polynucleotide encoding a promoter [para 0167, “the expression “human TDP-43 genomic fragment operably linked to a human TDP-43 promoter” refers to a TDP-43 nucleic acid sequence fragment comprising TDP-43 coding sequence, the introns, the 3′ sequence autoregulating TDP-43 synthesis…[and] the human TDP-43 promoter] and a second expression cassette comprising polynucleotide encoding a fluorescent protein [para 0211, "We used TDP-43wt; GFAP-luc double transgenic mice because the reporter luciferase (luc) allowed the longitudinal and non-invasive biophotonic imaging with CCD camera of the GFAP promoter activity which is a target of activated NF-kB"].
However, Julien does not explicitly teach that a single expression cassette is comprised of a polynucleotide encoding a promoter and a polynucleotide encoding a fluorescent protein.
It would have been obvious for someone of ordinary skill in the art to combine the polynucleotides encoding SEQ ID NO: 8 into a single expression cassette containing a fluorescent protein and a promoter to detect protein expression by translational regulatory control elements in the promoter. Such expression of the fluorescent protein would allow for non-invasive imaging of GFAP promoter activity. A skilled artisan would have had a reasonable expectation of success as controlling gene vector expression encoding a polynucleotide of interest using activation of promoters by transcription factors was known in the before the effective filing date of the claimed invention.
A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
Regarding claim 4, Julien makes obvious the expression cassette of claim 3, yet Julien does not teach the expression cassette comprising a polynucleotide encoding a linker sequence.
However, Foglieni teaches expression cassettes comprising a polynucleotide encoding for a linker sequence. Foglieni discloses the parallel implementation of two split GFP technologies, the GFP bimolecular and trimolecular fluorescence complementation (biFC and triFC) in the context of TDP-43 self-assembly [page 1 para 1], comprising a polynucleotide encoding a linker sequence [page 2, para 3 - Fig. 1 A and C "For both tagged variants, the S11 beta-strand of GFP was spaced from Tau by a relatively short, nine amino acid-long linker"]. Furthermore, Foglieni teaches that a linker sequence can be “engineered to carry a short antibody epitope, in order to facilitate the independent analysis of fusion constructs” [page 6 para 1 “The presence of noth TDP-43 forms in the same cells was confirmed by immune staining…specific for the epitopes inserted in the respective linkers”]. Foglieni also teaches that “Expression of the two TDP-43 tagged variants with GFP 1-10 also resulted in a nuclear signal produced by the T 11β1-TDP-43/GFP 1_10 biFC complex” (page 3, last paragraph).
With the aim of understanding TDP-43 assembly, it would have been obvious to modify the expression cassette rendered obvious by Julien to incorporate a linker sequence carrying an epitope linking a small GFP fragment, with a TDP variant to arrive at the claimed invention. The incorporation of Foglieni’s linker sequence allows for the visualization of successful fusion constructs within living cells, containing the TDP variant. Furthermore, due to the oligomeric structure of TDP-43, it would have been obvious to incorporate small fragment tags such as T10-11 to visualize the direct protein interactions with inner protein domains. A skilled artisan would have had a reasonable expectation of success as localization of nuclear TDP-43 using two TDP-43 tagged variants with GFP 1-10 resulting in a nuclear signal produced by the T 11β 1-TDP-43/GFP 1_10 biFC complex (Fig. 2D) was known in the before the effective filing date of the claimed invention.
The rationale to support a conclusion that the claim would have been obvious is that a method of enhancing a particular class of devices (methods, or products) has been made part of the ordinary capabilities of one skilled in the art based upon the teaching of such improvement in other situations. One of ordinary skill in the art would have been capable of applying this known method of enhancement to a "base" device (method, or product) in the prior art and the results would have been predictable to one of ordinary skill in the art. See Intel Corp. v. PACT XPP Schweiz AG, 61 F.4th 1373, 1380-81, 2023 USPQ2d 297 (Fed. Cir. 2023). See also MPEP 2143(I)(C).
Regarding claim 5, the combined teachings of Julien and Foglieni render obvious the expression cassette of claim 1, 3 and 4. Moreover, Foglieni teaches the linker sequence is present between the polynucleotide encoding the fluorescent protein (page 2 para 3 , "For both tagged variants, the S11 beta-strand of GFP was spaced from Tau by a relatively short, nine amino acid-long linker"). Foglieni teaches that parental plasmids each encoding for one of the two C-terminal consecutive β strands T10 and T11 of GFP22 followed by a peptide linker was used to subclone of cDNAs encoding a protein of interest (page 2, last paragraph).
Regarding claim 6, Julien renders obvious the expression cassette of claims 1 and 3. Moreover, Foglieni teaches that the fluorescent protein is a fluorescent donor protein or a fluorescent acceptor protein of a proximity detection protein pair (page 1 para 2, "Fluorescent sensors are applied to determine protein interactions in cells. One prominent example is FRET from donor to acceptor fluorophores coupled to binding partners"). See Legend Fig 2. C. “Dimerization of the tagged TDP-43 proteins steers T10 and T11 in an orientation and distance allowing triFC”
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A skilled artisan would have been motivated to utilize FRET donor to acceptor fluorophores to determine protein interactions within cells. Thus, it would have been obvious to modify Julien’s construct to select a GFP 1-10 to dimerize tagged TDP-43 proteins and nuclear colocalization in triFC with a reasonable expectation of success
Conclusion
Claims 1-6 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Katriel B Kasayan whose telephone number is (571)272-1402. The examiner can normally be reached 10-4p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATRIEL BARCELLANO KASAYAN/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634