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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/01/2026 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Claims 5-12 and 16-21 were previously withdrawn from examination.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, updated in view of amendments
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. Additionally, Trono does not teach the lentiviral vector being a TYF lentiviral vector.
Shenzhen teaches a TYF 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 and TYF lentiviral vector backbone taught by Trono with the hEF1-alpha promoter sequence and HIV-based lentiviral 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).
Additionally, one would have a reasonable expectation of success to substitute for the TYF lentiviral vector because the TYF lentiviral vector is HIV-based, and Trono teaches using HIV-derived viruses to express CYBB (Abstract). Trono notes that HIV-derived lentivectors which are safe, highly efficient, and very potent for expressing transgenes for human gene therapy, especially, in human hematopoietic progenitor cells as well as in all other blood cell derivatives (Abstract). Trono teaches improvements to HIV-based lentiviral vectors such as a including mutated self-inactivating 3’ inverted repeats (e.g., ITRs, LTRs) (e.g., [0071, 0170]), primer binding sites (e.g., [0068]), lentiviral packaging signals (psi) (e.g., [0068]), a polypurine track (PPT) (e.g., [0019]), and bovine growth hormone polyA signals (e.g., [0111]), all of which are structural components of TYF lentiviral vectors (see instant specification pg. 8, Remarks pg. 1 filed 5/1/2026). One would be motivated to use a TYF lentiviral vector because as taught by Shenzhen, the TYF lentiviral vector no longer has pathogenicity, which makes the HIV virus lose its self-replication function, thus greatly improving the safety performance of the lentiviral vector itself used in gene therapy (pg. 3).
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 05/01/2025 have been fully considered but they are not persuasive.
The applicant argues that Shenzhen provides no basis for predicting how the hEF1alpha promoter sequence would perform in the context of a TYF vector driving CYBB expression in hematopoietic stem cells.
This argument is not persuasive. First, Shenzhen teaches a TYF lentiviral vector comprising the hEF1alpha promoter. As discussed in the 103 rejection above, Trono also teaches HIV-derived lentiviral vectors comprising an hEF1alpha promoter driving CYBB expression in hematopoietic stem cells. The teachings of Trono demonstrate that the art recognizes hEF1a promoter to work in a lentiviral vector also comprising CYBB. The Applicant fails to provide evidence that the hEF1alpha promoter sequence of Shenzhen would be unable to drive CYBB expression.
Additionally, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., expressing in hematopoietic stem cells) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In response to applicant's argument that Shenzhen is directed to a different therapeutic application than the present invention, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
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.
In response to applicant's argument that “the present invention achieves efficient and stable expression of the CYBB gene in both differentiated and undifferentiated hematopoietic stem cells”, 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). Further, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
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
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