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 .
Election/Restrictions
Claims 56, 69, 104, 105 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/12/2025.
Applicant’s election without traverse of Group I, and election of species SEQ ID NO: 13, representing a 4R tau isoform sequence (4R isoform 2N4R), and species SEQ ID NO: 14, representing a 3R tau isoform sequence (3R isoform 2N3R) in the reply filed on 12/12/2025 is acknowledged.
Claims 1-28, 56, 69, 83, and 102-105 are pending.
Claims 19-22 (drawn to non-elected 4R isoform 1N4R, which reads on SEQ ID NOs: 23, 27, and 31, and 3R isoform 1N3R, which reads on SEQ ID NOs: 24, 28, 32, and 49; see [0011] of specification), 56, 69, 104, and 105 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 1-18, 23-28, 83, 102, and 103 are under consideration.
Priority
The claims of the instant case are entitled to the priority date of provisional application 63/309,055, filed 02/11/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/27/2023 and 12/12/2025 are considered by the examiner.
Claim Objections
Applicant is advised that should claims 1 and 28 be found allowable, claims 102 and 103 respectively 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 Rejections - 35 USC § 112(b)
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.
Claim 18 is 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 the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 18 recites the phrase “the sequence set forth in SEQ ID NO(s)”.
As a first matter, the Directors Technology Center 1600 Memorandum, Nucleic Acid and Peptide Claim Interpretation: “A” and “The” (December 29, 2005) informs the TC1600 Examiners that the phrase “A nucleic acid comprising a nucleotide sequence of SEQ ID NO:1” encompasses nucleic acids that comprise any portion of SEQ ID NO:1; whereas, the phrase “A nucleic acid comprising the nucleotide sequence of SEQ ID NO:1” is directed only to nucleic acids that comprise the full length of SEQ ID NO:1.
English has two articles: ‘the’, and ‘a/an’.
‘the’ is a definite article, referring to a specific or particular noun; whereas, ‘a/an’ is an indefinite article, modifying non-specific or non-particular nouns.
As a second matter, the claims recite the phrase “the sequence set forth in”, which renders the claims indefinite because the reference SEQ ID NO is composed of a plurality of amino acid subsequences or nucleotide subsequences, respectively, and it is unclear to which subsequence “set forth in” the reference SEQ ID NO Applicant refers.
The preposition “in”, per “set forth in”, does not have the same meaning as the preposition “of”. For example, “in” indicates a location or position within a limit or reference, e.g. a fragment or some portion of the referenced SEQ ID NO.
The house is in Tippecanoe county.
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Three cows are grazing in the field.
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The preposition “of” indicates possession of the reference, characteristic, or trait, that is to say, the entirety of the referenced SEQ ID NO.
To the extent that Applicant is referring to the entirety of the referenced SEQ ID NO, then replacing the phrase “the sequence set forth in” with the phrase “the sequence of SEQ ID NO:” would render the rejection moot.
As a third matter, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claims recite the broad recitation “set forth in SEQ ID NO: 13”, and the claim also recites “SEQ ID NO: 13”, for example, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-7, 12-18, 23-27, 83, and 102 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Woerman (WO2017172764A1, published 10/05/2017; cited in IDS filed 06/27/2023).
Regarding claims 1-4, 27, 83, and 102, Woerman discloses a cell (and a population of cells comprising a plurality of cells – claim 27, and composition – claim 83) comprising a first nucleic acid comprising a coding sequence for the 4R tau isoform and a coding sequence for the first reporter protein (e.g., mCherry or YFP) and a second nucleic acid comprising a coding sequence for the 3R tau isoform and a coding sequence for the second reporter protein (e.g., mCherry or YFP), wherein the cell expresses the 4R tau isoform, the 3R tau isoform, the first reporter protein, and the second reporter protein (Fig. 1, 15a, 16a; [0022]).
Regarding claims 5 and 6, Woerman discloses the coding sequence for the 4R tau isoform and the coding sequence for the first reporter protein are separated by a coding sequence for a first 2A (e.g., P2A- claim 6) peptide, and the coding sequence for the 3R tau isoform and the coding sequence for the second reporter protein are separated by a coding sequence for a second 2A peptide (e.g., P2A- claim 6) (Fig. 15a, 16a).
Regarding claim 7, Woerman discloses the first nucleic acid and the second nucleic acid being integrated into the genome of the cell (i.e., transfected) (claims 1, 2, 5, 6 of Woerman).
Regarding claims 12 and 13, Woerman discloses the first reporter protein being eYFP (a first fluorescent reporter protein), and the second reporter protein being mCherry (a second fluorescent report protein) [0036] (claim 9 of Woerman).
Regarding claim 14, Woerman discloses the 4R tau isoform and the 3R tau isoform being human [0026, 0028],
Regarding claims 15-17, Woerman discloses the 4R tau isoform being a 2N4R tau isoform and the 3R tau isoform being a 2N3R tau isoform (i.e., constructs encoding the RD of 4R tau (amino acids 243-375 corresponding to 2N4R tau) containing the mutations P301L and V337M, and the RD of 3R tau (amino acids 243-274; 306-375) containing the mutations L266V and V337M) [0077-0078].
Regarding claim 18, Woerman discloses the 4R tau isoform comprising the sequence set forth in SEQ ID NO: 13 (SEQ ID NO: 4 of Woerman), and the 3R tau isoform comprising the sequence set forth in SEQ ID NO: 14 (SEQ ID NO: 7 of Woerman).
Regarding claims 23-26, Woerman discloses the cell being a HEK293 cell (i.e., a mammalian, human, immortalized cell) [0037-0038].
Claim Rejections - 35 USC § 103
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.
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) 8-11, 28, and 103 is/are rejected under 35 U.S.C. 103 as being unpatentable over Woerman as applied to claims 1-7, 13-18, 23-28, 83, and 102 above, and further in view of Xu (Xu, Cheng, et al. "Co-expression of three wild-type 3R-tau isoforms induces memory deficit via oxidation-related DNA damage and cell death: A promising model for tauopathies." Journal of Alzheimer’s Disease 73.3 (2020): 1105-1123.).
Woerman does not teach the cell comprising a viral vector (lentiviral or AAV – claim 9) comprising the first nucleic acid and the second nucleic acid (claim 8) [0077-0078].
Wierman does not teach the cell comprising a first viral vector comprising the first nucleic acid and a second viral vector comprising the second nucleic acid (claim 10) (lentiviral or AAV – claim 11) (i.e., constructs were introduced separately) [0078].
Woerman does not teach a non-human animal comprising a four-repeat (4R) tau isoform linked to a first reporter protein and a three-repeat (3R) tau isoform linked to a second reporter protein that is different from the first reporter protein (and a non-human animal comprising the cell) (claims 28 and 103).
Woerman teaches a vector comprising the first nucleic acid and the second nucleic acid (e.g., pIRESpuro3 vector or the pIRESblaS vector), and that the nucleic acids may be separately introduced or tandemly connected [0077-0078].
Xu teaches the plasmids pEGFP-tau-0N3R, pEGFP-tau-1N3R, and pEGFP-tau-2N3R, encoding different isoforms of human 3R-tau, which were used to construct virus AAV-CMV-eGFP-tau-0N3R, AAV-CMV-eGFP-tau-1N3R, AAV-CMV-eGFP-tau-2N3R, AAV-CMV-eGFP-tau-0N4 R, AAV-CMV-eGFP-tau-1N4 R, and AAV-CMV-eGFP-tau-2N4 R (pg. 1106-1107, “Plasmids, viruses, regents, and antibodies”). These vectors were used to establish a mouse model co-expressing three isoforms of human 3R-tau isoforms (AAV-eGFP-tau-0N3R, AAV-eGFP-tau-1N3R, and AAV-eGFP-tau-2N3R; 1 : 1:1) by infusing a mixture of the three into the dorsal hippocampal CA3 of mice (pg. 1109-1110, “Co-expressing three 3R-tau isoforms in vitro and in vivo and the identification”; Fig. 1). Xu confirmed that the three isoforms of tau proteins were indeed co-expressed in a same cell, we further conducted in vitro experiment by co-transfection of HEK293T cells or primary hippocampal neurons (7 div) with three isoforms of tau plasmids (0N3R-eGFP, 1N3R-DsRed, and 2N3R-flag) (pg. 1111, col 1, para 2).
Resolving the level of ordinary skill in the pertinent art.
People of the ordinary skill in the art will be highly educated individuals such as medical doctors, scientists, or engineers possessing advanced degrees, including M.D.'s and Ph.D.'s. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, nucleic acid delivery vehicles, and methods of making lipid nanoparticles. Therefore, the level of ordinary skill in this art is high.
"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at ___, 82 USPQ2d at 1396.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
It would have been obvious to an artisan before the effective filing date of the current invention to apply the teaching of using plasmids/vectors comprising tau isoforms linked to reporter proteins to create AAV viral vectors and non-human animals overexpressing tau isoforms by Xu to the vectors taught by Woerman to arrive at the claimed invention. One would have a reasonable expectation of success because the plasmids/vectors taught by Xu comprise a 3R or 4R isoform and reporter protein. Absent evidence to the contrary, there is nothing to suggest that an AAV vector would be unable to comprise a vector/plasmid comprising both 3R and 4R isoforms, such as in Woerman. One would be motivated to combine the teachings of Woerman and Xu to arrive at the claimed invention because as taught by Xu, the resulting cells comprising AAV viral vector(s) comprising the first nucleic acid and the second nucleic acid, and non-human animals comprising the first nucleic acid and the second nucleic acid (e.g., overexpressing 3R and 4R isoforms) can be used as in vitro and in vivo models for drug development of tauopathies (pg. 1120, col 1, para 3).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M JOHNSON whose telephone number is (703)756-1396. The examiner can normally be reached Monday-Friday 9am-5pm.
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ALLISON M. JOHNSON
Examiner
Art Unit 1638
/ALLISON MARIE JOHNSON/ Examiner, Art Unit 1638
/KEVIN K HILL/ Primary Examiner, Art Unit 1638