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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/11/2025 has been entered.
Claims 1, 3-14, and 16-21 are pending.
Claims 5-12 and 16-21 were previously withdrawn from examination.
Claims 1, 3, 4, 13, and 14 are pending and under examination.
Claim Rejections - 35 USC § 103- Maintained
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, 3, 4, 13, and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Trono (US20030138954A1, published 07/24/2003) and further in view of Shenzhen (CN108707627A, published 10/26/2018; Foreign Document Cite No. 2 of IDS submitted 10/15/2021).
Regarding claims 1 and 3, Trono teaches a lentiviral vector, comprising a hEF1-alpha promoter (i.e., promoter promotes detectable transcription of the transgene in a human cell, including in human hematopoietic progenitor cells [0016]; availability of the human genome sequence should greatly facilitate identification of such elements that are contemplated as part of the present invention [0021]; [0100]) and CYBB that are organized in tandem [0112; Fig. 5A shows example of promoter and transgene organized in tandem), and the CYBB (i.e., gp91-phox) comprising the amino acid sequence of instant SEQ ID NO: 2 (shares 100% identity with SEQ ID NO: 19 of Trono) ([0195]; pg. 38-40; claims 1, 17, 21, 41, 42). Further, Trono teaches instant SEQ ID NO: 3 (shares 100% identity with SEQ ID NO: 18 of Trono) (claim 3) ([0195]; pg. 35-38)
Trono is silent on the specific sequence of the recited hEF1-alpha promoter.
Shenzhen teaches a lentivirus vector comprising an ARSA gene and a hEF1-alpha promoter comprising the nucleic acid sequence of instant SEQ ID NO: 1 (shares 100% identity with nts 7 through 1542 of SEQ ID NO: 3 of Shenzhen, which represents a human ARSA gene/EF1 alpha gene promoter DNA construct) (Abstract; pg. 8; [400]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to substitute the hEF1-alpha promoter taught by Trono with the hEF1-alpha promoter and its sequence taught by Shenzhen with a reasonable expectation for success. An artisan would have a reasonable expectation of success because 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. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).” M.P.E.P. §2144.06.
Further, replacing a sequence with another has long been done in the molecular biology art and would be routine. One would be motivated to replace the hEF1-alpha promoter in the lentiviral vector taught by Trono because as taught by Shenzhen, the hEF1-alpha promoter effectively identifies and expresses the transgene (i.e., ARSA) (pg. 8).
Regarding claim 4, Trono teaches discloses a lentivirus comprising the lentiviral vector (i.e., lentiviruses can be prepared by co-transfection of a lentiviral vector plasmid and packaging plasmids into a cell to assemble a lentivirus, as described on pg. 5 of the instant specification) [0066].
Regarding claims 13 and 14, Trono teaches a pharmaceutical composition comprising the lentiviral vector, further comprising a pharmaceutically acceptable carrier, excipient, and/or diluent [0153-0157].
Response to Arguments
Applicant's arguments filed 07/11/2025 have been fully considered but they are not persuasive.
The applicant argues that Trono does not disclose or suggest the specific hEFla promoter sequence of SEQ ID NO: 1, nor does it suggest using such sequence to drive CYBB expression. The Applicant elaborates that based on the teachings of Trono, a skilled person in the art would not be motivated to replace the gp91-phox (most preferred) promoter with a long EF la promoter for the expression of the gp91-phox gene.
This argument is not persuasive. First, the examiner stated in the 103 rejection that Trono does not teach instant SEQ ID NO: 1. However, Trono does suggest that hER1a is a preferred promoter for the lentiviral vector, as recited in [0017], as cited by the applicant. The suggestion of Trono that the gp91-phox promoter is the most preferred does not mean the hF1a promoter taught by Trono would not work. The teachings of Trono demonstrate that the art recognizes hEF1a promoter to work in a lentiviral vector also comprising CYBB. There is no evidence that the hEF1a promoter does not work (i.e., Trono does not teach away from using the hEF1a promoter).
Additionally, while Trono does teach a short form of the EF1a promoter (lacks an intron) in [0171] and Fig. 5A, Trono does not specify the use of the short form of the EF1a promoter elsewhere, such as in [0017] and [0058].
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See 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), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, both Trono and Shenzhen teach a lentiviral vector comprising an hEF1a promoter and a transgene. While Trono is silent on the exact promoter sequence that may be used, Trono still teaches the hEF1a promoter to be a preferred promoter in the vector. As stated above, M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).” M.P.E.P. §2144.06.
The Applicant also argues that the vector taught by Shenzhen is differs from the claimed vector. This argument is not persuasive because Shenzhen was not relied upon to teach a vector; Shenzhen was reference to teach the sequence of the hEF1a promoter. The Applicant fails to provide evidence for why the promoter sequence taught by Shenzhen would not work in the vector taught by Trono.
Additionally, the Applicant argues that the promoter sequence in Shenzhen “is not identical to SEQ ID NO: 1-the terminal 9 base pairs differ suggesting functional divergence. Specifically, the hEFla sequence of the present invention is 1545 bp in length, and the terminal 9 bp sequence differs from the EFla promoter in Shenzhen.” This argument is not persuasive because SEQ ID NO: 3 of Shenzhen does teach instant SEQ ID NO: 1; SEQ ID NO: 3 of Shenzhen comprises 100% of instant SEQ ID NO: 1. The claim language does not exclude sequences larger/comprising more nucleotides than instant SEQ ID NO: 1. The examiner also notes that instant SEQ ID NO: 1 is 1536 bps in length, and nts 7-1542 of SEQ ID NO: 3 (Shenzhen) share 100% identity with the entirety (nts 1-1536) of instant SEQ ID NO: 1. Additionally, even if the claim language required a sequence with no nts more or less than the claimed sequence SEQ ID NO: 1 (e.g., “consisting of”), the Applicant fails to distinctly point out how the few additional bps of Shenzhen’s sequence suggest “functional divergence” from the claimed hEF1a promoter.
In response to applicant's argument that “the present invention achieves efficient and stable expression of the CYBB gene in patients' monocytes and neutrophils, resulting in significantly elevated oxidase activity and a long-lasting therapeutic effect. These results represent a marked improvement over prior approaches and demonstrate unexpected technical effects that are not disclosed or suggested by the cited art.”, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Conclusion
No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 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 MARIE JOHNSON/Examiner, Art Unit 1638 /ROBERT M KELLY/Primary Examiner, Art Unit 1638