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 .
Applicant’s amendment and response filed on 2/2/2026 has been received and entered into the case.
Claims 21-30 have been canceled, claims 14-20 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-13 have been considered on the merits. All arguments have been considered.
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) 1-4, 7 and 9-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Richard et al. (US 2021/0107948) in view of Ozdinler et al. (US 2022/0339265; published on 10/27/2022) and evidenced by Lipinski et al. (2013,
Richard et al. teach a recombinant adeno-associated virus (AAV) comprising a therapeutic gene/a gene of interest encoding a therapeutic protein (para. 56, 60) for a gene therapy for treating various diseases including hereditary paraplegia and exemplify CYP2U1 gene (para. 91, 96).
Regarding the newly added limitation directed to the CYP2U1 open reading frame encoding a mammalian CYP2U1 protein, Richard et al. do not particularly teach that the CYP2U1 gene involved in paraplegia encodes a mammalian CYP2U1. However, it would have been obvious to a person skilled in the art to produce a recombinant AAV to express a mammalian CYP2U1 protein as the intended purpose of the AAV of Richard et al. is to treat hereditary paraplegia in a patient or an individual (para. 91 and 96), and the intended patient or individual in the teachings of Richard et al. is directed to a mammal including a human (para. 117).
Richard et al. teach an AAV vector packaging a gene of interest and the AAV genome is flanked by two ITRs and the AAV vector can be derived from AAVs of different serotypes including AAV2 (para. 2 and 55). Richard et al. teach that the gene of interest is operatively linked to a ubiquitous, tissue-specific or inducible promoter and the gene of interest may be inserted in an expression cassette further comprising polyA sequences (para. 62).
Ozdinler et al. teach a composition for treating neurological diseases, disorders and injuries (para. 6) and the neurodegenerative disease or disorder includes hereditary spastic paraplegia (HSP) (para. 7).
Ozdinler et al. teach a therapeutic gene encoding a therapeutic gene product to correct a defective gene product including those implicated in a neurological disease or condition (para. 70), and the therapeutic gene may include genes involved in hereditary spastic paraplegia (HSP) (para. 71), and the table therein discloses CYP2U1 as one of HSP causative genes (Table at p.11). Ozdinler et al. teach recombinant viral vectors including AAV vectors of various serotypes including 2 and 9 (para. 64-66). Ozdinler et al. teach a promoter being used in the AAV vector includes EF1a promoter (para. 67; RE: claim 3), and polyadenylation signals (para. 67)..
Regarding claim 2 directed to the ITRs are in the inverse complement, while Richard et al. in view of Ozdinler et al. do not particularly teach the limitation, however, it is considered an inherent feature of AAV vector. In support, Lipinski et al. teach that AAV vector contains two IRTs in reverse orientation (see two ITR arrows in opposite direction in Fig.1, p.29, 2nd col.).
Regarding claim 4 directed to a human CYP2U1 protein, while Richard et al. in view of Ozdinler et al. are silent with regard to the CYP2U1 gene being human, however, it would have been obvious to a person skilled in the art to use human CYP2U1 gene to encode a human CYP2U1 protein in order to use the AAV vector in treating human patients having SPG56 with a reasonable expectation of success.
Regarding claim 9, Richard et al. teach that the rAAV is a plasmid (para. 130-132), and Ozdinler et al. also teach AAV is a plasmid (para. 173, 220).
Regarding claim 10, Richard et al. in view of Ozdinler et al. teach AAV2 as discussed above.
Regarding claim 11, Richard et al. teach the production of AAV by transfecting 3 plasmids (para. 132) and a recombinant AAV capsid protein for the AAV vector (Abstract; para. 12). Furthermore, Ozdinler et al. teach AAV vectors including an AAV trans-plasmid encoding AAV2 capsid; and adenovirus helper plasmid and an AAV shuttle plasmid expressing a gene of interest are transfected into HEK293 cells (para. 220), and the resulting AAV particle (para. 108) would include AAV capsid protein. Thus, these teachings meet the limitation of claim 11.
Regarding claim 12 directed to the capsids being from AAV9, Richard et al. teach that the capsid is a hybrid between AAV9 and AAVrh74 (para. 11), and thus, this teaching would meet the limitation. Furthermore, Ozdinler et al. teach AAV9 as an option for the AAV vector, and thus, it would meet the AAV9 capsid.
Regarding claim 13 directed to a pharmaceutical composition comprising the rAAV of claim 11 and a pharmaceutically acceptable carrier, Richard et al. teach the pharmaceutical composition comprising a pharmaceutically acceptable carrier and/or vehicle and AAV vector particles (para. 108 and 111), and Ozdinler et al. also teach the use of a pharmaceutically acceptable carriers (para. 75).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Richard et al. in view of Ozdinler et al. as applied to claim 1 above, and further in view of Homo sapiens CYP2U1, XM_005262717 (GenBank, dated 2/3/2014).
Regarding claim 5 directed to the encoded CYP2U1 protein being SEQ ID NO:1, Richard et al. in view of Ozdinler et al. do not teach the sequence. However, as discussed above, one skilled in the art would use a human CYP2U1 gene encoding a human CYP2U1 protein in a human patient, and thus, it would have been obvious to a person skilled in the art to use a human CYP2U1 gene known in GenBank database at the time of filing with a reasonable expectation of success. The amino acid sequence of CYP2U1 of XM_005262717 from GenBank has 100% identity with SEQ ID NO:1 (see alignment below).
Query Match 100.0%; Score 2973; DB 1; Length 562;
Best Local Similarity 100.0%;
Matches 562; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSSPGPSQPPAEDPPWPARLLRAPLGLLRLDPSGGALLLCGLVALLGWSWLRRRRARGIP 60
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Db 1 MSSPGPSQPPAEDPPWPARLLRAPLGLLRLDPSGGALLLCGLVALLGWSWLRRRRARGIP 60
Qy 61 PGPTPWPLVGNFGHVLLPPFLRRRSWLSSRTRAAGIDPSVIGPQVLLAHLARVYGSIFSF 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PGPTPWPLVGNFGHVLLPPFLRRRSWLSSRTRAAGIDPSVIGPQVLLAHLARVYGSIFSF 120
Qy 121 FIGHYLVVVLSDFHSVREALVQQAEVFSDRPRVPLISIVTKEKGEREVVGCGYADAADES 180
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Db 121 FIGHYLVVVLSDFHSVREALVQQAEVFSDRPRVPLISIVTKEKGEREVVGCGYADAADES 180
Qy 181 PGVVFAHYGPVWRQQRKFSHSTLRHFGLGKLSLEPKIIEEFKYVKAEMQKHGEDPFCPFS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 PGVVFAHYGPVWRQQRKFSHSTLRHFGLGKLSLEPKIIEEFKYVKAEMQKHGEDPFCPFS 240
Qy 241 IISNAVSNIICSLCFGQRFDYTNSEFKKMLGFMSRGLEICLNSQVLLVNICPWLYYLPFG 300
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Db 241 IISNAVSNIICSLCFGQRFDYTNSEFKKMLGFMSRGLEICLNSQVLLVNICPWLYYLPFG 300
Qy 301 PFKELRQIEKDITSFLKKIIKDHQESLDRENPQDFIDMYLLHMEEERKNNSNSSFDEEYL 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 PFKELRQIEKDITSFLKKIIKDHQESLDRENPQDFIDMYLLHMEEERKNNSNSSFDEEYL 360
Qy 361 FYIIGDLFIAGTDTTTNSLLWCLLYMSLNPDVQEKVHEEIERVIGANRAPSLTDKAQMPY 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 FYIIGDLFIAGTDTTTNSLLWCLLYMSLNPDVQEKVHEEIERVIGANRAPSLTDKAQMPY 420
Qy 421 TEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPAIWEKPEDF 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 TEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPAIWEKPEDF 480
Qy 481 YPNRFLDDQGQLIKKETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPEDSKKP 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 YPNRFLDDQGQLIKKETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPEDSKKP 540
Qy 541 LLTGRFGLTLAPHPFNITISRR 562
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Db 541 LLTGRFGLTLAPHPFNITISRR 562
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Richard et al. in view of Ozdinler et al. as applied to claim 1 above, and further in view of Parodi et al. (2022, J. Bio-X. Res.; Published online 8/17/2022) and Pirozzi et al. (2006, J. Clin. Inv.).
Regarding claim 6, Richard et al. in view of Ozdinler et al. do not teach the CYP2U1 ORF encoding a murine CYP2U1 protein.
However, Parodi et al. teach an animal model of hereditary spastic paraplegia type 56, i.e. SPG56-HSP mouse model (Abstract), and the mice lack Cyp2u1 gene (i.e. Cyp2u1-/- mouse).
It would have been obvious to a person skilled in the art to use the AAV vector of Richard et al. in view of Ozdinler et al. in order to test if a mouse WT Cyp2u1 gene expressed by the AAV vector of Richard et al. in view of Ozdinler et al. would rescue the phenotype of the Cyp2u1-/- mouse. A person of ordinary skilled in the art would have been motivated to do so because the rescue of gene deficiency by using mouse gene in a knockout mouse of HSP model is known in the art. For example, Pirozzi et al. teach that the mouse model of hereditary spastic paraplegia caused by Spg7 gene mutation (i.e. Spg7-/- mouse model) was rescued by delivery of AAV2/2-Spg7 expressing mouse Spg7 cDNA (p.203, Results). Thus, one skilled in the art would utilize a mouse Cyp2u1 gene to be expressed by the AAV vector of Richard et al. in view of Ozdinler et al. for the rescue of the mouse model of SPG56 (Cyp2u1-/- mouse) taught by Parodi et al. with a reasonable expectation of success.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Allowable Subject Matter
Claim 8 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.
Response to Arguments
Applicant's arguments filed 2/2/2026 have been fully considered but they are not persuasive.
Applicant asserted that Richard et al. teach more than 4 pages of genes for treating at least 15 categories of neuromuscular diseases, and CYP2U1 is one of them, and Richard et al. lack the necessary guidance to select among these many options. Applicant further argued that Richard provides data only for the expression of luciferase in the new hybrid AAV vector, and no data for use of the vector for any therapeutic application. Based on these, applicant alleged that Richard fails to provide a reasonable expectation of success that an AAV vector encoding CYP2U1 with any utility for treating any particular hereditary paraplegia, let alone SPG56. The Examiner respectfully disagrees with the applicant’s argument.
The claimed invention is directed an AAV replicon, i.e. AAV vector encoding CYP2U1, not the method of using the AAV for treating any disease. Thus, the structure of the claimed product matters in determining the patentability, and therefore, there is no requirement that Richard shows any therapeutic effect in treating hereditary paraplegia using the AAV vector encoding CYP2U1 for the product claims. Even if the claims disclose any intended purpose or use, as discussed above, the patentability of the product claims would be determined based on the structure, and the obviousness rejection does not require absolute evidence for the therapeutic efficacy.
As Richard teaches the AAV vector for gene therapy to express a gene of interest and the gene of interest includes large number of species, it would have been obvious to a person skilled in the art that any one of the listed species can be used as a gene of interest to be expressed by the AAV vector of Richard et al. Introducing a nucleic acid encoding any gene of interest into the AAV vector is extremely well known in the art. Therefore, a person skilled in the art would have reasonable expectation of success in generating an AAV vector to encode a gene encoding mammalian CYP2U1 for gene therapy treating hereditary paraplegia according to Richard.
Regarding the teaching Ozdinler, applicant argued that Ozdinler mentions CYP2U1 in a laundry list of genes and no data whatsoever on its use. For the same reason as discussed above with the teaching of Richard, it is the Examiner’s position that the teaching of Ozdinler renders the claimed product obvious.
The Examiner has identified an allowable subject matter, i.e. SEQ ID NOs disclosed in claim 8. Applicant is advised to incorporate the subject matter of claim 8 into claim 1 in order to overcome the rejections.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631
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