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 .
Application Status
This action is written in response to applicant’s correspondence received on 3/12/2026. Claims 1, 16, and 18-32 are pending. Claim 16 has been amended. Claims 2-15 and 17 are cancelled. Claims 1 and 27-31 are withdrawn. Claims 16, 18-26, and 32 are currently under examination.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow. This Office Action is Final.
Election/Restrictions
Applicant’s election without traverse of Group II in the reply filed on 11/7/2025 is acknowledged. Group II reads on claims 16, 18-26, and 32.
Regarding the election of the invention group, the Applicant has elected a promoter with structure “-CTGCACGTA-S20-CTGCACGTA-S20-CTGCACGTA-S20- CTGCACGTA-S20-CTGCACGTA- S20-CTGCACGTA-S59-CMV-MP,” where Sx denotes a spacer with “X” number of bases/nucleotides.” This election reads on SEQ ID NO: 82 of claim 16. SEQ ID NO: 82 was found to be free of the art. The search was expanded to include SEQ ID NO: 84 recited in claim 16. The remaining sequences in claim 16 (85-87) have not been searched because SEQ ID NO: 84 was found to be obvious in view of the teachings of the art (see 103 rejection).
Claim Rejections - 35 USC § 112 – Maintained
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the 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 shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the 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 shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 21 and 22-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 21, claim 21 recites a cell comprising the hypoxia-inducible promoter of claim 16. This claim language is problematic because it broadly encompasses any cell type, where furthermore the claim language is recited with functional language in the sense that the promoter must be ‘hypoxia-inducible” within the cell, per claim 16 and 21. However, as discussed further below, the genus of “cell” is unpredictable with regards to whether or not the recited promoters would be “hypoxia-inducible” in a given “cell,” where the Applicant has not identified a structure/function relationship which would reliably predict cells in which the recited promoter would function as being hypoxia-inducible.
With regards to the guidance provided in the specification, the applicant has designed and reduced to practice five hypoxia-inducible promoters (RTV-015, HYBT, RTV-016, SYNP-HYP-001, and HV3C, see Examples 5-7 and Figures 13-17). The Applicant alleges that “results seem to validate our design principals with the strength of the promoters correlating to their theoretical relative strength,” (page 87, paragraph 4). However, the exact rationale behind the design of the spacer elements and promoters does not appear to be discussed in the specification; the Applicant has not identified any core structure-function relationship between the recited promoters and a reliable way of predicting their functionality across different cells. Furthermore, the Applicant has tested the promoters in HEK cells and CHO cells, but has not reduced to practice and shown functionality in other cell types such as bacterial cells, where the claim limitations require that the promoter is “hypoxia-inducible.” Such functional language is unpredictable across cell types including bacterial cells (see state of the art, below).
With regards to the state of the art, it is known that different cell types rely upon different transcription factors which recognize variable transcription factor motifs within a promoter, where such motifs dictate the functionality of the promoter across cell types. For instance, the teachings of Schultheis (of record) teache that:
“Of note, human and mouse are some of the most studied models in terms of TF binding, but for most other organisms, the rate of TFs with known motifs is considerably lower (JASPAR CORE vertebrates: 14% non-human),” (Introduction, first paragraph).
Thus, Schultheis teaches that transcription factor DNA motifs and how transcription factors are predicted to bind to such motifs are largely uncharacterized and unknown even in highly studied organisms like humans and mice (Abstract and Introduction). Such known DNA motifs are even less characterized in non-humans (14%, above). Thus, the genus of “cell”” includes cells with uncharacterized transcription factor binding motifs, where the “hypoxia-inducible promoters” may not function as hypoxia-inducible promoters across uncharacterized cell types which rely upon different TF binding motifs for regulation. It is entirely unknown if such promoters are functional across cell types (e.g., yeast and bacteria) given that other organisms and their transcription networks are largely undefined (Schultheis, Abstract and Introduction).
Claims 23-25 depend from claim 21 and do not resolve this 112(a) issue and are therefore also rejected.
Response to Arguments
The Applicant’s Remarks filed 3/12/2026 have been considered but are not persuasive. The Applicant argues that the amendments to the claims obviates the 112(a) rejection concerning the genus of “spacer” and “hypoxia-inducible promoter.” This argument is persuasive, and this portion of the original 112(a) rejection is withdrawn. The Applicant has substantially amended the claims, which are now drawn to five specific sequences without any undefined residues.
The Applicant argues that the present claims recite specifically defined promoters. This argument is persuasive. However, the Applicant further argues that the specification is sufficient to show possession across cell types because they have tested mammalian cell lines, arguing that the cell lines tested are “sufficient representative examples” to show possession of the genus “cell.” This argument is persuasive with respect to the rejection of claim 22; the office acknowledges that the Applicant has shown possession of mammalian cells with specific functional limitations recited in claim 21 regarding the promoter (i..e, that the promoter is hypoxia-inducible). However, as previously stated and reiterated in the present 112(a) rejection, the Applicant has not shown that such promoters are “hypoxia-inducible” within non-mammalian cells such as yeast and bacteria, which rely on completely different and uncharacterized transcriptional machinery. For instance, the claims encompass hypoxic responses in cells such as fungal and archaeal cells, which were not tested. While not every cell type must be exhaustively tested, the Applicant must still show representative species of the claimed genus, where it is not reasonable to say that testing a mammalian cells is a representation of yeast cells, archaeal cells, or bacterial cells. Thus, the Applicant did not demonstrate possession of the genus “cell” coupled with the functional requirements of being a hypoxia-inducible promoter within the cell.
Claim Rejections - 35 USC § 103 – Maintained/Updated in Response to Amendment
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 16, 18-26, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Qi (WO 2021/158658, published as a WIPO document 8/12/2021 with effective filing date of 2/4/2020 with US designation, which makes Qi prior art).
Regarding claims 16, as an initial matter, Qi – while having a publication date after the effective filing date of the present application, nonetheless has an earlier effective filing date of 2/4/2020 and therefore qualifies as prior art. Qi teaches hypoxia inducible promoters (e.g., paragraph 115). Qi teaches that the hypoxia-inducible promoter can comprise SEQ ID NO: 11, where an alignment to SEQ ID NO: 84 is shown below (paragraph 115):
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Thus, the only difference between SEQ ID NO:11 of Qi and SEQ ID NO: 84 (recited in dependent claim 17 and thus reads on claim 16 of the present claim set) is that SEQ ID NO: 84 has one extra “C” nucleotide in the final spacer region (“S17”). Thus, the only difference between SEQ ID NO:84 and SEQ ID NO: 11 appears to be the addition of a single base in a spacer region of SEQ ID NO: 11, where such an addition does not appear to have any overall effect as both promoters retains their capacity of “hypoxia inducible” promoters.
It would have been obvious to a person of ordinary skill in the art before the time of the effective filing date to arrive at SEQ ID NO: 84 from SEQ ID NO: 11 by making a minor base addition in the spacer region, as this region appears to be only a spacer region between HREs and a core minimal promoter, where such an addition of a single base does not appear to have an overall affect. As such, the sequence of instant SEQ ID NO: 84 could be arrived at from SEQ ID NO: 11 by routine laboratory optimization of a promoter sequence, where furthermore the addition of this single base in the spacer region does not appear to have any effect on the overall promoter functionality. Thus, absent evidence to the contrary, the results are predictable, as Qi teaches that SEQ ID NO: 11 is a known hypoxia-inducible promoter, where the addition of a single base from a variable spacer region is not predicted, and does not appear to have, significant effects.
Regarding claims 18-19, Qi teaches that the promoter is part of an expression cassette to express a transgene, and specifically a therapeutic (e.g., Figure 14A, paragraph 295).
Regarding claim 20, Qi teaches that the promoter can be in a vector (paragraph 145).
Regarding claims 21-25, Qi teaches that a cell can comprise the hypoxia inducible promoter, where the cell is a human cell (e.g., Figure 14A, claims 21-22). Qi teaches HEK293 cells (paragraph 295, claim 22). Regarding claims 23-25, Qi teaches culturing cells in media to support growth, which reasonably includes a vessel and a population of cells (e.g., paragraph 303).
Regarding claim 26, Qi teaches that the vector can manufacture a product of interest (e.g., paragraph 70, Figure 14).
Regarding claim 32, Qi teaches that the product can be a Cas product, which can reasonably be interpreted to be a therapeutic given the teachings of Qi in Figure 14, which identifies the activation of a therapeutic response (paragraph 70, Figure 14).
Response to Arguments
The Applicant’s arguments filed 3/12/2026 have been considered but are not persuasive. As an initial matter, the Applicant argues that SEQ ID NO: 82 should be searched, as it is drawn to the elected species. SEQ ID NO: 82 has been searched and found to be free of the art. However, claim 16 recites SEQ ID NO: 84. SEQ ID NO: 84 is not considered to be inventive, as SEQ ID NO: 11 of Qi is an exact match of the sequence with the exception that SEQ ID NOL 82 comprises one additional “C” base in the spacer region. This addition does not appear to have any unpredictable effects, where a practitioner starting from SEQ ID NO: 11 could arrive at such an addition by routine laboratory optimatization of a sequence. Furthermore, absent any evidence to the contrary, the results of the addition of the C baes relative to Qi’s SEQ ID NO: 11 does not appear to have any effect on the promoter, and is therefore only a minor, insignificant change to a known hypoxia-inducible promoter (i.e., SEQ ID NO: 11 of Qi).
Double Patenting – Maintained/Updated in Response to Amendment
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 16, 18-26 and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 15, and 51 of copending Application No. 17/907,232 (‘232, reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 16, claim 1 of ‘232 recites the inducible promoter sequence SEQ ID NO: 1, which is identical to instant SEQ ID NO: 82, which reads on claims 16 and 17.
Regarding claims 18-19 and 26, Claim 51 of ‘232 recites a method of culturing cells comprising the promoter, to produce viral particles (i.e., an expression cassette for a transgene/therapeutic/product of interest, claims 18-19 and 26),
Regarding claims 20, claim 15 of ‘232 recites the nucleic acid is in a vector (a nucleic acid construct, claims 1 and 15 of ‘232), where such a construct can be considered a bioprocessing vector.
Regarding claims 21-25, claims 15 and 51 of ‘232 recites that the vector is in a cell (claim 21), where the cell is a CHO cell (claim 22), where method claim 51 of ‘232 recites culturing cells of claim 15 of ‘232, which reasonably includes a population of cells (claim 23) in a medium for growth (claim 24) within a vessel (claim 25).
Regarding claim 32, claim 51 of ‘232 recites a method of producing viral particles, which can be interpreted to be a therapeutic.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
The Applicant’s arguments filed 3/12/2026 have been considered but are not persuasive. Applicant requests that the double patenting rejection over co-pending application ‘232 be held in abeyance. A request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an OBJECTION or REQUIREMENTS AS TO FORM (see 37 CFR 1.111(b) and MPEP §714.02). Thus, the double patenting rejections of record have been maintained as no response to these rejections has been filled by applicant at this time.
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 DOUGLAS CHARLES RYAN whose telephone number is (571)272-8406. The examiner can normally be reached M-F 8AM - 5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at (571)-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.C.R./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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