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 .
Election/Restrictions
Applicant’s election without traverse of Group III (claims 17-22) in the reply filed on 3/2/2026 and the species of C228T in the supplemental response filed on 3/6/2026. Claim 18 was cancelled in the preliminary amendment filed on 4/8/2026 and therefore the species election pertaining to said claim has been withdrawn.
Claim Status
Claims 1-17 and 19-23 are pending.
Claims 1-16 and 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the replies filed on 3/2/2026 and 3/6/2026.
Claims 17 and 19-22 are being examined on the merits.
Drawings
The drawings are objected to because some of the figures are so pixelated that they are illegible. For example, please see Figures 3A, 3B, and 4. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Please see page 11, ln 20-21 and page 13, ln 3-5 in the specification.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located on page 7, line 22 (SEQ ID NO: 58). SEQ ID NO: 58 does not appear in the provided sequence listing.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Specification
The disclosure is objected to because of the following informalities: SEQ ID NO: 4 is improperly labeled as “C250T/C288T-hTERT promoter” in the Sequence Listing (Text File). It should be corrected to read “C250T/C228T-hTERT promoter” to properly reflect the nucleotide substitutions that are present in the sequence.
Appropriate correction is required.
Claim Objections
Claims 20 and 21 are objected to because of the following informalities:
Claim 20 reads “wherein the adenovirus has increased tumor killing ability compared to an adenovirus” and should read “wherein the oncolytic adenovirus has increased tumor killing ability compared to an adenovirus” to maintain consistent claim terminology and distinguish the oncolytic adenovirus with the mutated hTERT promoter from the adenovirus with the wild-type hTERT promoter.
Claim 21 reads “wherein the adenovirus has increased E1A expression compared to the adenovirus including the wild-type hTERT promoter” and should read “wherein the oncolytic adenovirus has increased E1A expression compared to the adenovirus including the wild-type hTERT promoter” for the same reason as provided above for claim 20.
Appropriate correction is required.
Claim Rejections - 35 USC § 112b - Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 17 and 19-22 are 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.
Claim 17 reads “An oncolytic adenovirus comprising a cancer cell-specific promoter in which a 228th nucleotide sequence of an hTERT promoter is substituted from C to T”. It is unclear if there is a separate cancer cell-specific promoter in addition to the hTERT promoter in this adenovirus or if the hTERT promoter itself is the cancer cell-specific promoter. For purposes of examination, the hTERT promoter with the substitution is interpreted to be the same as the cancer cell-specific promoter but clarification is required. To make this more clear, the claim could be amended to read “An oncolytic adenovirus comprising a cancer cell-specific promoter, wherein the cancer cell-specific promoter is an hTERT promoter in which a 228th nucleotide sequence of [[an]]the hTERT promoter is substituted from C to T”.
Claim 17 reads “a 228th nucleotide sequence of an hTERT promoter is substituted from C to T”. However, it is unclear how a single nucleotide corresponds to a “nucleotide sequence” which necessarily constitutes two or more nucleotides. The same error applies to “a 250th nucleotide sequence” in line 3 of the claim. For the purposes of examination this is interpreted as being a single nucleotide substitution at a singular position in the sequence. However, further clarification is required.
Claims 19-22 depend from claim 17, inherit these deficiencies, and are rejected on the same basis.
Claim 19 reads “a deletion of a 245th nucleotide sequence of the hTERT promoter”. However, it is unclear how a single nucleotide corresponds to a “nucleotide sequence” which necessarily constitutes two or more nucleotides. For the purposes of examination this is interpreted as being a single nucleotide deletion at a singular position in the sequence. However, further clarification is required.
Claims 19 and 22 are directed to the oncolytic adenovirus of claim 17 “wherein the promoter” is further limited. However, as discussed in the rejection of claim 17 above, there are two promoters defined in claim 17, therefore making it unclear which promoter is being further limited in claims 19 and 22 if they are in fact separate promoters within the same oncolytic adenovirus. For the purposes of examination, “the promoter” is being interpreted as specifically referring to the hTERT promoter as defined in claim 17. However, further clarification is required.
Claim Interpretation
The specification and the claims do not provide any specific genomic coordinates corresponding to “a 228th nucleotide sequence of an hTERT promoter”, “a 250th nucleotide sequence”, or “a 245th nucleotide sequence”. However, for purposes of examination, the art recognized C228 and C250 are being interpreted as corresponding to chromosome 5 positions 1,295,228 and 1,295,250, respectively (see Leao et al., 2018 - TERT promoter mutations; Huang et al., 2013 – Introduction). These positions also correspond to positions -124 and -146 upstream in relation to the transcription start site of the human TERT promoter (Leao et al., 2018 - TERT promoter mutations). Based on this art-recognized definition of these positions, it is being extrapolated that a 245th nucleotide sequence corresponds to chromosome 5 position 1,295,245, or -141 bp upstream from the transcription start site of the human TERT promoter, which is position 315 of SEQ ID NO: 1.
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.
Claims 17 and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Fujiwara (Fujiwara et al., US 2011/0044949 A1) in view of Huang (Huang et al., Molecular BioSystems 2017).
Fujiwara teaches an oncolytic adenovirus containing a cancer cell-specific promoter in the form of an hTERT promoter (relevant to claim 17; paragraph [0019-0020, 0033-0034, 0036], Figure 1). SEQ ID NO: 4 of Fujiwara shares 99.6% sequence identity with SEQ ID NO: 3 of the instant application (corresponding to the hTERT promoter with C228T substitution). The only base that differs is that of the C228T substitution, due to the fact that Fujiwara is using the wild-type version of the promoter. Fujiwara teaches that the oncolytic adenovirus with the hTERT promoter has tumor killing ability (relevant to claim 20; paragraph [0078]). Fujiwara teaches that the hTERT promoter is operably linked to E1A and E1B (relevant to claim 22; Figure 1, paragraph [0018]). Fujiwara teaches that E1A expression is increased in cancer cells compared to normal cells (relevant to claim 21; paragraph [0072]).
Fujiwara does not teach that the 228th nucleotide sequence of the hTERT promoter is substituted from C to T (claim 17). However, inclusion of the C228T substitution in the hTERT promoter is known in the art, as taught by Huang 2017.
Huang teaches a viral vector with a cancer-cell specific hTERT promoter that has been “enhanced” (Abstract and Introduction, paragraph 3). Huang teaches that the nucleotide corresponding to C228 has been substituted to T (see alignment below and Supplemental Table 1).
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The above CLUSTAL alignment is the enhanced hTERT promoter of Huang aligned with SEQ ID NO: 3 (C228T) of the instant application and SEQ ID NO: 1 (Wild-type hTERT) of the instant application. As indicated by the highlighted portion, the hTERT promoter of Huang contains the C228T substitution.
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Fujiwara with that of Huang to include the C228T substitution in the hTERT promoter. One would be motivated to do so given the teaching by Huang that this enhanced promoter maintains “tumor-specific features” and “enhance[s] hTERT expression compared with the wild-type hTERT promoter” (Introduction, paragraph 3). One would have a reasonable expectation of success given that Huang 2017 successfully integrates this promoter in a viral vector to cancer cell-specifically control the expression of an operably linked gene (Fig. 4).
With regard to claims 20 and 21, modification of the hTERT promoter according to the teachings of Huang (who teaches that hTERT expression is enhanced relative to the wild-type promoter) would lead to the predictable result of increasing E1A expression compared to the wild-type hTERT promoter (claim 21) and therefore lead to the predictable result of increasing the tumor killing ability compared to the adenovirus including a wild-type hTERT promoter (claim 20).
Double Patenting
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 17 and 20-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50-51 of copending Application No. 17/914,160 in view of Huang (Huang et al., Molecular BioSystems 2017).
The claims of ‘160 teach an anti-tumor adenovirus that includes a human telomerase promoter (hTERT) wherein this promoter is operably linked to E1A and E1B. The claims of ‘160 do not teach that the 228th nucleotide sequence of the hTERT promoter is substituted from C to T (claim 17). However, inclusion of the C228T substitution in the hTERT promoter is known in the art, as taught by Huang.
Huang teaches a viral vector with a cancer-cell specific hTERT promoter that has been “enhanced” (Abstract and Introduction, paragraph 3). Huang teaches that the nucleotide corresponding to C228 has been substituted to T (see alignment above in the 103 rejection and Supplemental Table 1). The above CLUSTAL alignment is the enhanced hTERT promoter of Huang aligned with SEQ ID NO: 3 (C228T) of the instant application and SEQ ID NO: 1 (Wild-type hTERT) of the instant application. As indicated by the highlighted portion, the hTERT promoter of Huang contains the C228T substitution.
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of ‘160 with that of Huang to include the C228T substitution in the hTERT promoter. One would be motivated to do so given the teaching by Huang that this enhanced promoter maintains “tumor-specific features” and “enhance[s] hTERT expression compared with the wild-type hTERT promoter” (Introduction, paragraph 3). One would have a reasonable expectation of success given that Huang successfully integrates this promoter in a viral vector to cancer cell-specifically control the expression of an operably linked gene (Fig. 4).
With regard to claims 20 and 21, modification of the hTERT promoter according to the teachings of Huang (who teaches that hTERT expression is enhanced relative to the wild-type promoter) would lead to the predictable result of increasing E1A expression compared to the wild-type hTERT promoter (claim 21) and therefore lead to the predictable result of increasing the tumor killing ability compared to the adenovirus including a wild-type hTERT promoter (claim 20).
This is a provisional nonstatutory double patenting rejection.
Claims 17 and 20-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7, 10, and 17 of copending Application No. 18/278,570 in view of Huang (Huang et al., Molecular BioSystems 2017) according to citations and rationales provided above.
This is a provisional nonstatutory double patenting rejection.
Claims 17 and 20-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 11 of copending Application No. 18/281,539 in view of Huang (Huang et al., Molecular BioSystems 2017) according to citations and rationales provided above.
This is a provisional nonstatutory double patenting rejection.
Claims 17 and 20-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 14, 17, and 22 of copending Application No. 18/723,312 in view of Huang (Huang et al., Molecular BioSystems 2017) according to citations and rationales provided above.
This is a provisional nonstatutory double patenting rejection.
Claims 17 and 20-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/843,814 in view of Huang (Huang et al., Molecular BioSystems 2017) according to citations and rationales provided above.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILEY E CASH whose telephone number is (571)272-0971. The examiner can normally be reached Monday-Friday 8:30am-6pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571)272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KAILEY ELIZABETH CASH/Examiner, Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
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