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 instant application is in response to the papers filed on February 7, 2025. Claims 105-125 are currently pending. Claims 1-104 have been cancelled and claims 105-125 are newly filed in Applicant’s amendment filed on February 7, 2025.
Therefore, claims 105-125 are currently 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 the International Application No. PCT/US2023/061702, filed January 31, 2023. Applicant’s claim for the benefit of a prior-filed parent provisional application 63/312,480 filed on February 22, 2022 and 63/304,960 filed on January 31, 2022 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 January 31, 2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on: July 18, 2024, September 16, 2024, November 14, 2024, March 17, 2025, May 14, 2025, June 23, 2025, July 31, 2025, November 19, 2025, February 26, 2026, and May 28, 2026 were filed. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 105, 108, 111, 112, 114, and 115 are objected to because the recited abbreviations should be spelled out at the first encounter in the claims:
Claim 108 recites “UTR” in line 2. Claim 111 recites “CMV” in line 2. Claim 112 recites “hSyn” in line 1. Claim 114 recites “WPREx” in line 2. Claim 115 recites “hGH” in line 2.
Claims 105 is objected to for the use of parentheses for the SEQ ID NOs recited. The claim should be amended to recite the nucleotide sequences without the parentheses. Appropriate corrections are required.
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 are 110, 117, 118, and 121-125 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 110 is indefinite because the location of the 5' untranslated region (UTR) and intron are not clear, particularly which elements they are situated between. It is recommended to use the same language of claim 109 wherein the location of the intron is specified based on being between two different elements. The dependent claims 117 and 118 are rejected for not resolving the indefinite issues set forth in claim 110.
Claims 121, and 123-125 recitation of “according to” renders the claims indefinite as it is unclear in what instances the claimed elements comprise the respective SEQ ID NOs. The use of “according to” introduces ambiguity as to whether the claimed SEQ ID No(s) are a constant limitation or rather a conditional limitation. Examples of suitable language are the following:
“comprising the polynucleotide sequence as set forth in SEQ ID NO: _”
“comprising the amino acid sequence as set forth in SEQ ID NO: _”
The dependent claim 122 is rejected for not resolving the indefinite issues set forth in claim 121.
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 105-107 are rejected under 35 U.S.C. 102(a)(1)(2) as being anticipated by Greenberg (US 2019/0161529 A1; shared assignee: Trames Bio, Inc.).
Regarding claim 105, Greenberg teaches a recombinant nucleic acid comprising an expression cassette comprising, in 5' to 3' order, one or more of: a 5’ enhancer, a promoter, a transgene encoding a ligand-gated ion channel (LGIC), a 3’ enhancer, and a polyadenylation sequence (“Examples of cis-acting sequences that regulate the expression of polynucleotide sequences and that may be operably linked to the polynucleotides of the present disclosure to regulate the expression of the subject engineered receptors are well known in the art and include such elements as promoter sequences …, enhancers, posttranscriptional regulatory elements…, and polyadenylation sequences.” (par 0141; 0152)). In relation to the transgene, Greenberg teaches SEQ ID NO: 32 that is 100% identical to instant SEQ ID NO: 32 (Result #1) [nucleic acid sequence that encodes instant SEQ ID NO: 33] and teaches SEQ ID NO: 33 that is 100% identical to instant SEQ ID NO: 33 (Result #1). Furthermore, in relation to the claimed domains of the transgene, Greenberg teaches SEQ ID NO: 16 that is 100% identical to amino acids 23-220 of instant SEQ ID NO: 25 (Result #9) and teaches SEQ ID NO: 17 that is 100% identical to amino acids 255-457 of instant SEQ ID NO: 26 (Result #2; all results are provided with this Office Action). Lastly, Greenberg teaches the LGIC as having a Cys-loop domain derived from a human Glycine receptor (par 0021). As stated above, Greenberg’s teaching of the claimed composition with only one of the claimed elements is sufficient for anticipating the claimed invention due to the language of “one or more of:”.
Regarding claims 106-107, both dependent on claim 105, Greenberg teaches SEQ ID NO: 33 that is 100% identical to instant SEQ ID NO: 33 (Result #1).
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.
Claims 105-117, 119-120 are rejected under 35 U.S.C. 103 as being unpatentable over Greenberg (US 2019/0161529 A1; shared assignee: Trames Bio, Inc.) as applied to claims 105-107 above, and further in view of Sacramento et al. (US 2023/0174994 A1).
The rejection of Greenberg is discussed supra.
Regarding claims 108-110, Greenberg teaches the claimed recombinant nucleic acid comprising an expression cassette that comprises a transgene encoding a ligand-gated ion channel that is delivered to neuronal cells for expression (par 0157), stating “In some aspects of the present disclosure, a method is provided of treating a neurological disorder in a subject in need thereof comprising administering to said subject a polynucleotide encoding an engineered ligand-gated ion channel (LGIC) receptor” (par 0035). Greenberg further teaches the expression cassette may comprise a promoter (e.g. CMV, hSYN, Actin promoters) enhancers, introns, and polyadenylation sequences (par 139-141, 279).
Greenberg does not teach the particular structure of cassette wherein each element is in the claimed order as set forth in the claims, and furthermore the claimed sequences (not including the transgene sequence).
Sacramento teaches an expression cassette in 5’ to 3’ order comprising a 5’ enhancer (e.g. CMV enhancer (par 0301)), a promoter (e.g. Syn, Chicken beta-actin (Table 3)), a 5’ UTR (e.g. 5’ hSyn UTR (Table 4)), intron (par 0302, 0305; Fig. 9), a transgene, a 3’ enhancer (e.g. WPRE (Table 5)), a 3’ UTR (e.g. 3’UTR(globin) (Table 5), a polyadenylation signal (e.g. rβglobin, hGh (Table 6)), and wherein the transgene is operably linked to the promoter (par 0008; Figs 2-9, 14-17). Sacramento describes the recombinant nucleic acid comprising an expression cassette as being delivered, and subsequently expressed in neurons (Example 5; Example 6, par 0480-481).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the expression cassette taught by Greenberg to include the transgene taught by Sacramento because it would have been obvious to substitute one known element for another to obtain predictable results. Substituting the transgene taught by Sacramento for the transgene taught by Greenberg, e.g. a transgene encoding a ligand-gated ion channel, would have led to predictable results with a reasonable expectation of success because the expression cassette taught by Sacramento showed gene expression in neuron cells, and similarly Greenberg taught the transgene can be delivered and expressed in neurons for the treatment of neurological disorders. Therefore, it would be expected that the transgene encoded receptor would be expressed in neurons when included in the Sacramento expression cassette. Secondly, there is clear motivation in substituting because the claimed transgene is taught by Greenberg as being used in the treatment of a neurological disorder, and moreover Sacramento teaching the expression cassette allows for transgene expression in neuronal cells.
Regarding claim 111, dependent on claim 105, Sacramento teaches wherein the 5' enhancer is a CMV 5' enhancer comprising a polynucleotide sequence having at least 90% sequence identity with SEQ ID NO: 37 as seen in teaching SEQ ID NO: 35 that is greater than 95% identical to such sequence.
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460
527
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Regarding claim 112, dependent on claim 105, Sacramento teaches wherein the promoter is a hSyn promoter comprising a polynucleotide sequence having at least 90% sequence identity with SEQ ID NO: 48 as seen in teaching SEQ ID NO: 33 that is 100% identical to such sequence.
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636
534
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Regarding claim 113, dependent on claim 105, Sacramento teaches wherein the promoter is a chicken β-actin (cβactin) promoter comprising a polynucleotide sequence having at least 90% sequence identity with SEQ ID NO: 41 as seen in teaching SEQ ID NO: 30 that is 99% identical to such sequence.
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447
523
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Regarding claim 114, dependent on claim 105, Sacramento teaches wherein the 3' enhancer is a WPREx 3' enhancer comprising a polynucleotide sequence having at least 90% sequence identity with SEQ ID NO: 64 as seen in teaching SEQ ID NO: 43 that is 99% identical to such sequence.
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979
514
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Regarding claim 115, dependent on claim 105, Sacramento teaches wherein the poly A sequence is a hGH poly A comprising a polynucleotide sequence having at least 90% sequence identity with SEQ ID NO: 68 as seen in teaching SEQ ID NO: 52 that is 100% identical to such sequence.
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379
523
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Regarding claim 116, dependent on claim 108, Sacramento teaches wherein the 3' UTR sequence is a Globin 3' UTR sequence comprising a polynucleotide sequence having at least 90% sequence identity with SEQ ID NO: 66 as seen in teaching SEQ ID NO: 48 that is 100% identical to such sequence.
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246
514
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Regarding claim 117, dependent on claim 110, Sacramento teaches wherein the 5' UTR sequence is a hSyn 5' UTR comprising a polynucleotide sequence having at least 90% sequence identity with SEQ ID NO: 54 as seen in teaching SEQ ID NO: 38 that is 100% identical to such sequence.
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308
524
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Regarding claim 119, dependent on claim 105, Sacramento teaches the recombinant nucleic acid further comprising (i) a 5' inverted terminal repeat (ITR) sequence flanking the 5' end of the expression cassette and comprising a polynucleotide sequence having at least 90% sequence identity with SEQ ID NO: 94 as seen in teaching SEQ ID NO: 26 that is 100% identical to such sequence.
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309
517
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Regarding claim 120, dependent on claim 105, Sacramento teaches wherein the AA V vector comprises a capsid protein having at least 95% sequence identity with SEQ IDNO: 8 as seen in teaching SEQ ID NO: 60 that is 100% identical to such sequence.
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971
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Subject Matter Free of the Prior Art
Claim 118 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
SEQ ID NO: 59, which encodes a hSyn intron, is free of the prior art as the closest sequence similarity is below the claimed 90% sequence identity.
Conclusion
Claims 105-125 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
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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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/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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