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
This action is in response to the papers filed August 12, 2026.
Claim Amendments
Applicant’s amendment to the claims filed on 08/12/2026 is acknowledged.
Claims 2-19, 22-87, 89-91, 93, 95, 97, 99-101, 103-104, 107-108 have been cancelled.
Claims 109-117 are newly added.
Claims 88 and 106 are amended.
Claims 1, 20-21, 88, 92, 94, 96, 98, 102, 105-106, 109-117 are pending.
Claim 88, 92, 94, 96, 98, 102, 105 and 117 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 1, 20-21, 106, 109-116 are under examination.
Election/Restrictions
The following is a summary of the restriction/election requirements in the present application. See, the Requirement for Restriction/Election mailed 03/14/2025.
In the reply filed 05/14/2025, Applicant elected without traverse: Group 1, drawn to a recombinant transgene or viral vector comprising a polynucleotide encoding a delta-catenin protein; the delta-catenin protein according to SEQ ID NO: 21 (amino acid sequence) and encoded by the sequence of SEQ ID NO: 20 (nucleic acid sequence); the promoter of synapsin 1; and the additional therapy of GSK3β inhibitor. Please note that SEQ ID NO: 31 is identical to elected SEQ ID NO: 21, and, therefore, SEQ ID NO: 31 reads on the elected invention.
As stated in the prior Office action mailed 03/12/2026, prosecution has shifted to the non-elected invention of the delta-catenin protein according to SEQ ID NO: 27 (amino acid sequence) and encoded by the sequence of SEQ ID NO: 26 (nucleic acid sequence).
Claims 88, 92, 94, 96, 98, 102, 105 and 117 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. In particular, claims 88-89, 92, 94-102, and 105 are drawn to non-elected Group 2 (methods). Election was made without traverse in the reply filed on 05/14/2025.
Priority
The instant application 17/637,760 was filed on 02/23/2022. This application is a national stage of international application PCT/US2020/047655 filed 08/24/2020, claiming priority based on U.S. Provisional Application No. 62/890,710 filed 08/23/2019.
Effective filing dates:
Applicant asserts SEQ ID NO: 26, as instantly claimed, possesses sufficient written support in U.S. Provisional Application No. 62/890,710, and, therefore, the claims have an effective filing date of 08/23/2019 based on the filing date of the provisional application. In particular, applicant argues that page 51, paragraph 2, of the provisional application discloses: "[p]lasmid containing human δ-catenin (CTNND2, NM_ 001288717) open reading frame...," and this same statement is included in paragraph 198 of the present national phase entry application, U.S. Application No. 17/637,760. Thus, since a sequence alignment shows that the CTNND2 sequence provided by NM_ 001288717 is identical across all 5323 bp to the sequence set forth in SEQ ID NO:26, the provisional application provides written description for SEQ ID NO:26. See, applicant’s reply.
37 CFR 1.57(c), (d), and (e) state:
c) Except as provided in paragraphs (a) or (b) of this section, an incorporation by reference must be set forth in the specification and must:
(1) Express a clear intent to incorporate by reference by using the root words "incorporat(e)" and "reference" ( e.g. , "incorporate by reference"); and
(2) Clearly identify the referenced patent, application, or publication.
(d) "Essential material" may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference. "Essential material" is material that is necessary to:
(1) Provide a written description of the claimed 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 set forth the best mode contemplated by the inventor of carrying out the invention as required by 35 U.S.C. 112(a);
(2) Describe the claimed invention in terms that particularly point out and distinctly claim the invention as required by 35 U.S.C. 112(b); or
(3) Describe the structure, material, or acts that correspond to a claimed means or step for performing a specified function as required by 35 U.S.C. 112(f).
(e) Other material ("Nonessential material") may be incorporated by reference to U.S. patents, U.S. patent application publications, foreign patents, foreign published applications, prior and concurrently filed commonly owned U.S. applications, or non-patent publications. An incorporation by reference by hyperlink or other form of browser executable code is not permitted.
See also, MPEP 608.01(p).
In this case, the provisional application refers to a nucleotide sequence by a database accession number “NM_ 001288717” (page 51, paragraph 2, of the provisional application), which applicant asserts provides the sequence set forth in SEQ ID NO: 26 of the present national phase entry application, U.S. Application No. 17/637,760. The examiner found that SEQ ID NO: 26 is identical to the sequence provided by GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI). See, Alignments below.
Nonetheless, the provisional application is not found to provide sufficient written support for SEQ ID NO: 26 for at least the following reasons:
An incorporation by reference must express a clear intent to incorporate by reference by using the root words "incorporat(e)" and "reference" (e.g., "incorporate by reference"), as set forth by 37 CFR 1.57(c)(1). In this case, there is no clear intent to incorporate by reference, by using the root words "incorporat(e)" and "reference," the sequence disclosed by database accession number “NM_ 001288717” found in the specification of the provisional application.
An incorporation by reference in the specification must clearly identify the referenced patent, application or publication, as set forth by 37 CFR 1.57(c)(2). In this case, the specification of the provisional application only refers the database accession number “NM_ 001288717;” but the reference neither clearly identifies the particular database from which the accession number was obtained, nor the record version and/or publication date of the database entry. Moreover, even if applicant intended to refer to the GenBank sequence database (produced and maintained by the NCBI), the accession number “NM_ 001288717” had two different record versions (each corresponding to a different sequence) prior to the filing date of the provisional application, i.e., prior to 08/23/2019. In particular, the Revision History for GenBank accession number NM_ 001288717 shows that the sequence was updated from “version 1” (i.e., NM_ 001288717.1) to “version 2” (i.e., NM_ 001288717.2) on 05/19/2019. (A copy of the Revision History is submitted with this Office action and cited as: Revision History of GenBank, NCBI Reference Sequence: NM_001288717.2, National Library of Medicine (US), National Center for Biotechnology Information (NCBI), online webpage, accessed on 10-Mar-2026, 2 pages). Therefore, when the specification of the provisional application refers the database accession number “NM_ 001288717,” it is unclear whether the specification intends to reference the sequence according to “version 1” (i.e., NM_ 001288717.1) or “version 2” (i.e., NM_ 001288717.2) in the GenBank sequence database. For these reasons, the specification of the provisional application is not found to clearly identify the referenced publication, as required by 37 CFR 1.57(c)(2). (The examiner further notes that page 77 of the specification of the present national phase entry application, U.S. Application No. 17/637,760, describes SEQ ID NO: 26 by the database accession number “NM_001288717.1,” but SEQ ID NO: 26 is only identical to version 2 of NM_001288717, i.e., NM_001288717.2).
“Essential material” may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference, as set forth by 37 CFR 1.57(d). In this case, SEQ ID NO: 26, as claimed, is “essential material” as defined under 37 CFR 1.57(d)(1)-(3). However, the database accession number “NM_ 001288717” (i.e., the reference which applicant relies upon for describing “essential material” of SEQ ID NO: 26) is not a reference to a U.S. patent or U.S. patent application publication, as required by 37 CFR 1.57(d).
For at least these reasons, written support for SEQ ID NO: 26, as claimed, is not found in the provisional application.
In addition, the limitations of a non-viral delivery composition comprising the recombinant polynucleotide and a liposome, a nanocapsule, a microparticle, a microsphere, a lipid particle, or a vesicle, as claimed in claim 114, are also not found to possess sufficient written support in the provisional application.
Accordingly, the claims are found to have an effective filing date of 08/24/2020 based on the filing date of the international application, PCT/US2020/047655. See, MPEP 608.01(p).
Response to arguments: Applicant’s remarks filed 08/12/2026 have been carefully considered, but are not found persuasive.
(A) Applicant argues that the provisional application expressly identifies the CTNND2 sequence as instantly claimed. see, pg. 7 of the reply. The argument is not persuasive because the provisional application fails to expressly disclose SEQ ID NO: 26 (i.e., the CTNND2 sequence as instantly claimed). The sequence according to SEQ ID NO: 26 appears nowhere in the provisional application. Rather, the provisional application attempts to reference accession number “NM_ 001288717” on page 51, paragraph 2, of the provisional application ("[p]lasmid containing human δ-catenin (CTNND2, NM_ 001288717) open reading frame ..."). However, as explained to applicant above, the incorporation by reference is improper.
(B) Regarding the version history of NM_ 001288717 in GenBank, Applicant argues that one of ordinary skill in the art would have assumed that “NM_ 001288717” refers to the most recent version of the sequence relative to the filing date (i.e., version 2), and this conclusion is corroborated by SEQ ID NO: 26 itself, which is identical to version 2 of NM_ 001288717. The argument is not persuasive because the provisional application fails to provide neither the database (in this case, GenBank) nor the version number (in this case, version 2) for the disclosed “NM_ 001288717.” Applicant’s position that the conclusion is corroborated by SEQ ID NO: 26 itself is a false argument because SEQ ID NO: 26 itself was not disclosed in the provisional application but only in the national stage entry application, and, therefore, applicant’s position relies entirely on hindsight reasoning. There is no reason to assume that the accession number necessarily referred to (1) the GenBank database nor (2) record version 2 of the accession number solely based on the disclosure of “NM_ 001288717” at the time of filing the provisional application. This hindsight argumentation is even contradicted by the national stage entry application, U.S. Application No. 17/637,760, describing SEQ ID NO: 26 by the database accession number “NM_001288717.1” (page 77), which would refer to record version 1.
(C) Applicant argues that the provisional application does contain the a clear intent to incorporate by reference “NM_001288717” because page 64, second paragraph, discloses “All references cited herein are fully incorporated by reference, unless explicitly indicated otherwise.” The argument is not persuasive because there is no clear intent to incorporate by reference NM_001288717, specifically. Moreover, “NM_001288717” is not clearly identified because both the source database and record version are missing in the provisional application.
(D) Applicant argues that the requirement of 37 CFR 1.57(d), that “essential material” may be incorporated by reference only by reference to a U.S. patent or U.S. patent application publication, need not be satisfied, in this case, because the provisional application does not rely on “NM_001288717” to transform an otherwise generic disclosure of "delta-catenin" into
possession of a subsequently selected species, but rather the disclosure provides a means for one of ordinary skill in the art to identify the particular sequence used by the inventors in the provisional application. The argument is not pervasive because Applicant is, in fact, attempting to import otherwise undisclosed essential subject matter into an application solely through incorporation by reference. In this case, the particular sequence according to SEQ ID NO: 26 itself appears nowhere in the provisional application. Rather, Applicant is attempting to incorporate by reference the sequence according to SEQ ID NO: 26 from the GenBank database, accession number NM_001288717, record version 2. However, 37 CFR 1.57(d) requires that “essential material” may be incorporated by reference only by reference to a U.S. patent or U.S. patent application publication.
(E) Applicant argues that the Examiner is acting inconsistently by citing GenBank NM_001288717.2 in rejecting the claims under 35 U.S.C. 102 and 103 while simultaneously treating the provisional application’s identification of "CTNND2, NM_001288717" as incapable of conveying the identity of that same CTNND2 sequence to a skilled artisan. The argument is not persuasive because the Examiner, in fact, is not acting inconsistently in this matter. In this case, the national entry application discloses SEQ ID NO: 26, which enabled the Examiner to conduct a sequence search of SEQ ID NO: 26 and identity the sequence as being identical to GenBank NM_001288717.2. The Examiner would not have conducted this search based solely on the provisional application because SEQ ID NO: 26 does not appear anywhere in the provisional application. Again, Applicant’s position entirely relies on hindsight reasoning based on the fact that the sequence according to SEQ ID NO: 26, only later disclosed in the national entry application, is identical to GenBank NM_001288717.2, which is neither clearly identified nor properly incorporated by reference in the earlier provisional application.
Regarding the newly added claims, Applicant’s remarks do not provide any reasoning how the limitations of claim 114 find sufficient written support in the provisional application.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 03/12/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Claim Rejections - 35 USC § 112
Claim 110 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.
This rejection is newly applied, necessitated by amendment.
Claim 110 contains the trademark/trade name Lipofectamine® (U.S. Registration No. 3,643,468). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe transfection reagents and, accordingly, the identification/description is indefinite.
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.
Claims 1, 20, 106, 115-116 are rejected under 35 U.S.C. 103 as being unpatentable over Yeo et al. (12-Sep-2019) “Repurposing cell growth-regulating compounds identifies kenpaullone which ameliorates pathologic pain via normalization of inhibitory neurotransmission,” Pre-print on bioRxiv, version 1; in view of GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI).
This rejection is reiterated for the same reasons provided in the previous Office action with respect to claims 1, 106, 115-116. Regarding applicant’s remarks that the “Yeo” disclosure does not qualify as prior art, because the disclosure is preceded by applicant’s provisional application, please see the examiner’s remarks under the Priority section, above. The claims are found to have an effective filing date of 08/24/2020 based on the filing date of international application, PCT/US2020/047655.
Regarding claims 1, 106, 115-116, Yeo discloses a human delta-catenin transgene cloned onto an AAV9 viral vector and operably linked to a human synapsin I (hSyn) promoter. See Results: δ-cat spinal transgenesis is analgesic in nerve constriction injury, and Methods: δ-catenin DNA constructs, transgenesis vectors.
Yeo does not disclose that the polynucleotide comprises the sequence according to SEQ ID NO: 26.
GenBank, NCBI Reference Sequence: NM_001288717.2, is relevant prior art for providing the nucleic acid sequence of human catenin delta 2 (CTNND2), transcript variant 4. The reference sequence is identical to the sequence according to SEQ ID NO: 20. See Alignments below.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the viral vector of Yeo by including the nucleic acid sequence according to SEQ ID NO: 26, as found in the GenBank accession NM_001288717.2, with a reasonable expectation of success because Yeo teaches that the viral vector contains a nucleic acid sequence encoding human delta-catenin protein, and one of ordinary skill in the art would have sought a known, wild-type coding sequence of human delta-catenin for use in constructing Yeo’s viral vector, as disclosed by GenBank.
For these reasons, claims 1, 106, 115-116 would have been prima facie obvious over the prior art.
Regarding dependent claim 20, Yeo discloses a human delta-catenin transgene cloned onto an AAV9 vector. See Results: δ-cat spinal transgenesis is analgesic in nerve constriction injury, and Methods: δ-catenin DNA constructs, transgenesis vectors.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Yeo et al. (12-Sep-2019) “Repurposing cell growth-regulating compounds identifies kenpaullone which ameliorates pathologic pain via normalization of inhibitory neurotransmission,” Pre-print on bioRxiv, version 1; and GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI), as applied above; in further view of Gray et al. (2012) “Design and Construction of Functional AAV Vectors” In: Snyder, R., Moullier, P. (eds), Adeno-Associated Virus: Methods in Molecular Biology, vol. 807, Chapter 2, pg. 25-46, Springer Protocols, Humana Press.
This rejection is reiterated for the same reasons provided in the previous Office action with respect to claim 21.
Regarding dependent claim 21, Yeo does not expressly disclose that the AAV9 vector further comprises one or more of (a) an inverted terminal repeat sequence (ITR); (b) an intron; (c) transcription terminator; (d) a flanking inverted terminal repeat sequence (ITR); and (e) a polyA tail, as instantly claimed.
Gray is relevant prior art for teaching the basic design of an AAV vector is relatively simple, in that it consists of an appropriately sized expression cassette flanked by inverted terminal repeats (ITRs), which mediate the replication and packaging of the vector genome by the AAV replication protein Rep and associated factors in vector producer cells. Pg. 25-26, bridging paragraph.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the AAV9 vector of Yeo to further comprise an ITR sequence, as taught by Gray, with a reasonable expectation of success because ITRs are part of the basic design of AAV vectors, required to mediate the replication and packaging of the vector genome in vector producer cells.
Claims 106, 109-114 are rejected under 35 U.S.C. 103 as being unpatentable over by WO 00/47615 A2 to St. George-Hyslop et al.; in view of GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI).
This rejection is reiterated for the same reasons provided in the previous Office action with respect to claims 106 and 114, and this rejection is newly applied with respect to claims 109-113.
St. George-Hyslop discloses a gene therapy vector encoding human Neural Plakophilin Related Armadillo Protein (hNPRAP). See, e.g., Abstract. The hNPRAP gene is synonymous with the human CTNND2 gene, which encodes human delta-catenin. The gene therapy vector stimulates nerve growth and regeneration by contacting nerve cells with hNPRAP. See, e.g., Abstract.
St. George-Hyslop further discloses promoter sequences operably linked to the hNPRAP transgene. See, e.g., pg. 3, ll. 17-20; pg. 13, ll. 14-31.
For these reasons, St. George-Hyslop is found to teach or fairly suggest a recombinant gene therapy vector comprising a transgene encoding human delta-catenin operably linked to a promoter sequence.
St. George-Hyslop does not disclose that the coding sequence according to SEQ ID NO: 26, as instantly claimed.
GenBank, NCBI Reference Sequence: NM_001288717.2, is relevant prior art for providing the nucleic acid sequence of human catenin delta 2 (CTNND2), transcript variant 4. The reference sequence is identical to the sequence according to SEQ ID NO: 26. See Alignments below.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the gene therapy vector of St. George-Hyslop by including the nucleic acid sequence according to SEQ ID NO: 26, as found in the GenBank accession NM_001288717.2, with a reasonable expectation of success because St. George-Hyslop teaches that the viral vector contains a nucleic acid sequence encoding human delta-catenin protein, and one of ordinary skill in the art would have sought a known, wild-type coding sequence of human delta-catenin for use in constructing St. George-Hyslop’s gene therapy vector.
For these reasons, claim 106 would have been prima facie obvious over the prior art.
Regarding dependent claims 114, St. George-Hyslop discloses liposomes comprising a plasmid vector encoding human delta-catenin operably linked to a promoter sequence. See, pg. 14, ll. 2-18.
Regarding dependent claims 109-111, George-Hyslop discloses transfection via lipid coupling, liposome encapsulation or calcium phosphate (CaPO₄) precipitation. See, pg. 14, ll. 2-18. Prior to the effective filing date of the instantly claimed invention, Lipofectamine® was a well-known and common transfection reagent relying on the formation of liposomes, from cationic lipid subunits, around the transfection payload, facilitating membrane fusion and cellular entry. Official Notice taken, if necessary. Therefore, it would have been prima facie obvious to one of ordinary skill in the art to substitute transfection reagents, as taught by George-Hyslop, with Lipofectamine®, as previously known in the art, with a reasonable expectation of success because George-Hyslop teaches transfection via liposome encapsulation, and the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Regarding dependent claims 112-113, George-Hyslop further discloses a pharmaceutically acceptable carrier or excipient, wherein the pharmaceutically acceptable carrier or excipient is lecithin or polyethylene glycol (PEG). See, pg. 9, ll. 26, through pg. 10, ll. 4.
Response to arguments: Applicant’s remarks filed 08/12/2026 have been carefully considered, but are not found persuasive. In this case, Applicant argues that the cited references do not establish a sufficient reasons why a person of ordinary skill, starting with George-Hyslop, would have selected the sequence from GenBank. See, page 16 of the reply. The argument is not persuasive because the sufficient motivation has been provided in the rejection of record.
Claims 1, 106, 115-116 are rejected under 35 U.S.C. 103 as being unpatentable over by WO 00/47615 A2 to St. George-Hyslop et al.; in view of GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI); and Liu et al. (2008) "Viral vectors based on bidirectional cell-specific mammalian promoters and transcriptional amplification strategy for use in vitro and in vivo" BMC biotechnology 8:1-8.
This rejection is reiterated for the same reasons provided in the previous Office action with respect to claims 1, 106, 115-116.
St. George-Hyslop discloses a gene therapy vector encoding human Neural Plakophilin Related Armadillo Protein (hNPRAP). See, e.g., Abstract. The hNPRAP gene is synonymous with the human CTNND2 gene, which encodes human delta-catenin. The gene therapy vector stimulates nerve growth and regeneration by contacting nerve cells with hNPRAP. See, e.g., Abstract.
St. George-Hyslop further discloses that the gene therapy vector is a viral vector. See, e.g., pg. 6, ll. 5-8; pg. 12, ll. 18, to pg. 13, ll. 13.
St. George-Hyslop further discloses promoter sequences operably linked to the hNPRAP transgene. See, e.g., pg. 3, ll. 17-20; pg. 13, ll. 14-31.
For these reasons, St. George-Hyslop is found to teach or fairly suggest a recombinant viral vector comprising a transgene encoding human delta-catenin operably linked to a promoter sequence.
St. George-Hyslop does not disclose that the coding sequence according to SEQ ID NO: 26, as instantly claimed.
GenBank, NCBI Reference Sequence: NM_001288717.2, is relevant prior art for providing the nucleic acid sequence of human catenin delta 2 (CTNND2), transcript variant 4. The reference sequence is identical to the sequence according to SEQ ID NO: 26. See Alignments below.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the gene therapy vector of St. George-Hyslop by including the nucleic acid sequence according to SEQ ID NO: 26, as found in the GenBank accession NM_001288717.2, with a reasonable expectation of success because St. George-Hyslop teaches that the viral vector contains a nucleic acid sequence encoding human delta-catenin protein, and one of ordinary skill in the art would have sought a known, wild-type coding sequence of human delta-catenin for use in constructing St. George-Hyslop’s gene therapy vector.
St. George-Hyslop does not disclose the promoter is a synapsin I promoter, as instantly claimed.
Liu is relevant prior art for teaching cell-specific promoters are advantageous for gene therapy by restricting gene expression to particular cells. Failure to do so results in gene expression in non-target cells that confounds data interpretation and may lead to undesirable side effects. In addition, cell-type-specific promoters are advantageous since they are less likely to activate host cell defense machinery and are less sensitive to cytokine-induced promoter inactivation than viral promoters. As such, improved stability and longevity of gene expression can be expected. See, e.g., Abstract; pg. 1-2, joining paragraph.
Liu further teaches that the human synapsin-I (SYN) promoter provides cell-specific gene expression in neurons and glia in the central nervous system (CNS). See, e.g., Abstract; pg. 2, left column; Figures 1-2.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the gene therapy vector of St. George-Hyslop by using a synapsin-I promoter, as taught by Liu, with a reasonable expectation of success because the target cell type of St. George-Hyslop’s vector is neuronal cells, and the synapsin-I promoter is selectively active in the target neuronal cells. Failure to restrict gene expression results in expression in non-target cells that confounds data interpretation and may lead to undesirable side effects. In addition, cell-type-specific promoters are advantageous since they are less likely to activate host cell defense machinery and are less sensitive to cytokine-induced promoter inactivation than viral promoters. As such, improved stability and longevity of gene expression can be expected.
For these reasons, claims 1, 106, 115-116 would have been prima facie obvious over the prior art.
Response to arguments: Applicant’s remarks filed 08/12/2026 have been carefully considered, but are not found persuasive. In this case, Applicant argues that the cited references do not establish a sufficient reasons why a person of ordinary skill, starting with George-Hyslop, would have selected the sequence from GenBank and promoter from Liu. See, pages 16-17 of the reply. The argument is not persuasive because the sufficient motivation has been provided in the rejection of record.
Claims 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over by WO 00/47615 A2 to St. George-Hyslop et al.; GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI); and Liu et al. (2008) "Viral vectors based on bidirectional cell-specific mammalian promoters and transcriptional amplification strategy for use in vitro and in vivo" BMC biotechnology 8:1-8, as applied above; in further view of Foust et al. (2009) “Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes” Nature biotechnology, 27(1), 59-65.
This rejection is reiterated for the same reasons provided in the previous Office action with respect to claims 20-21.
Regarding dependent claim 20, St. George-Hyslop does not disclose that the viral vector is an adeno-associated viral (AAV) vector, as instantly claimed.
Foust is relevant prior art for teaching AAV9 vector is capable of bypassing the blood-brain barrier (BBB) and efficiently targets cells of the central nervous system (CNS), showing extensive transduction of dorsal root ganglia and motor neurons throughout the spinal cord and widespread transduction of neurons throughout the brain, including the neocortex, hippocampus and cerebellum. See, e.g., Abstract.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the gene therapy vector of St. George-Hyslop by using an AAV vector, as taught by Foust, with a reasonable expectation of success because the target cell type of St. George-Hyslop’s vector is neuronal cells, and the AAV9 vector has been shown to efficiently target neuronal cells.
Regarding dependent claim 21, Foust discloses the AAV vector comprises an inverted terminal repeat (ITR) sequence. See, e.g., pg. 63, Methods: Virus.
Alignments
SEQ ID NO: 26 (Qy) and NCBI Reference Sequence: NM_001288717.2 (Db)
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1009
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948
593
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1010
597
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1006
599
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1013
607
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657
613
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Conclusion
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 JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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, James D Schultz can be reached at (571)272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
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