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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/05/2026 has been entered.
Claims 1-5 and 9-21 are pending. Claim 1 is an independent claim. Applicant amended claims 1 and 9 by amendment filed on 03/05/2026. Claims 6-8 were previously cancelled by amendment filed 06/27/2025.
Therefore, claims 1-5 and 9-21 are currently under examination to which the following grounds of rejection are applicable.
Priority
This application is a CON of PCT/US2020/056130 filed on 10/16/2020, which claims benefit to PRO 62/916,095 filed on 10/16/2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/05/2026, was filed before the mailing date of this office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections/Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112(a)
In view of Applicants’ amendments, the rejection of claims 1-5 and 9-21 under 35 U.S.C. 112(a) as containing new matter has been withdrawn.
New rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112
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.
Claim 9 is 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 9 recites the limitation "The virus of claim 1, wherein the at least one viral gene…" at line 1. Claim 1 has been amended to delete the recitation of “at least one viral gene”. Therefore, there is insufficient antecedent basis for this limitation in the instant claim 9.
Maintained and modified rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
Claim(s) 1-5 and 10-16 remain rejected and claim 9 is newly rejected under 35 U.S.C. 103 as being unpatentable over Falkner et al. (US 6,352,856 Bl, IDS) in view of Kirn et al. (US 20120276053 A1, IDS) as evidenced by Holzer et al. (Holzer, G.W. et al. Methods in Molecular Medicine™, 2003).
Note: The rejection is modified for consideration of the amendments filed 9/29/2025, but the claims remain rejected under 35 USC § 103.
Regarding Claims 1 and 9, Falkner teaches the use of the poxvirus (Abstract), and specifically the vaccinia virus (Pg. 11, Column 4, Lines 10-16; Pg. 14, Example 1.) Falkner teaches their virus vector to encode for an env (retroviral envelope), a foreign gene contained within the viral transfer portion of the vector, and the packaging component to encode for gag (retroviral structural protein) (Figure 1A). The foreign gene may include non-retroviral proteins such as, tumor therapy proteins (Pg. 11, Column 3, Final Paragraph). Falkner teaches the insertion of a retroviral vector genome at the thymidine kinase locus (Fig 1;Column 10, Lines 48-60). This specific method of insertional mutation causes a disruption of the TK gene rendering it deficient, as evidenced by the teachings of Holzer et al., who describes that after insertion the selection of recombinants is performed for TK negative phenotypes (Pg. 4, Section 1.2 of Holzer).
Although Falkner describes both replicating and non-replicating virus (Column 5, Lines 45-59), they do not expressly demonstrate use of a replicating virus.
Kirn expressly teaches the use of a replication competent oncolytic vaccinia virus comprising mutation or deletion of viral gene. Specifically, Kirn teaches an oncolytic vaccinia virus (JX594 & JX963) comprising a viral backbone mutation having deletion of thymidine kinase (TK) gene and the viral particles further expressed GM-CSF, a modification that promotes T-cell response (Abstract; Fig.1-3, Fig.5; Example 4, Example 6; Pg. 30-31, Paragraph [0299]-[0307]; Pg. 38, Paragraph [0433]).
Kirn further teaches that deletion of B18R (for instant claim 9) anti-interferon alpha/Beta product also leads to enhanced viral sensitivity to IFN-mediated clearance, reduced titers in normal tissues and reduced virulence; BBR and A35R share these properties (Pg. 7, Paragraph [0086]; Pg. 8, Paragraph [0091]). Kirn also teaches mutation or deletion of A34R, B5R, or A56R (Pg. 11, Paragraph [0113]; Pg. 11-12, Paragraph [0118)]).
It would have been obvious for one of ordinary skill in the art at the time of the invention to have modified the teachings of Falkner by employing the retroviral producer-virus components of their teachings into the TK-deleted replication-competent oncolytic vaccinia backbone containing at least one of the viral gene deletions, such as B18R, as taught by Kirn.
One would have been motivated to delete or mutate specific viral genes, such as thymidine kinase (TK) (promotes T-cell response) and BI8R (enhanced viral sensitivity to IFN-mediated clearance, reduced titers in normal tissues and reduced virulence) as this would provide advantageous characteristics, increasing the therapeutic potential of an oncolytic virus. Further, one having ordinary skill in the art would reasonably contemplate that the combination of Kirn’s tumor-selective vaccinia replication with Falkner’s localized production of replication-defective therapeutic retroviral particles would increase production for the therapeutic particles in tumor tissue while reducing productive viral replication in normal tissue.
There would have been reasonable expectations of success in combining these teachings as both Falkner and Kirn teach successful integration of genetic elements into viral genomes, with Kirn specifically demonstrating that B18R deletion enhances viral selectivity by making the virus more susceptible to immune clearance in normal tissues, TK deletion increases tumor specificity, and A34R, B5R, A56R deletions facilitate improved viral spread and immune evasion, supporting their use in developing a more effective and tumor-selective oncolytic virus.
Regarding Claim 2, Falkner teaches the packaging, transfer, and envelope constructs are located at different locations on the gene (Figure 1A).
Regarding Claim 3, Falkner teaches the envelope construct to contain a retroviral envelope gene (env) encoding for a retroviral envelope protein and the packaging construct to contain a retroviral structural protein gene (gag) encoding for a retroviral structural protein.
Regarding Claims 4-5, Falkner teaches the sequences of both env and gag can be under the control of early promoters (Pg. 12, Column 6, Line 27) and further the constructs are under the control of two separate promotes (a first and second) (Figure 1A.).
Regarding Claims 10-11, Falkner teaches the foreign gene may include non-retroviral proteins such as, tumor therapy proteins (Pg. 11, Column 3, Final Paragraph). Falkner further teaches “The foreign protein may be any desired protein, a protein for substitution therapy or tumor therapy being, however, particularly preferred. Proteins suitable for substitution therapy may be plasma proteins, such as, e.g., factor II, factor V, factor VII, factor VIII, factor IX, factor X, factor 65, XI, factor XIII, protein C, protein S, von Willebrand factor or erythropoietin. Proteins suitable for tumor therapy are tumor suppressor proteins, such as p53 or p73, or "suicidal genes", such as HSY TK, immunostimulators, such as B7.”( Pg. 11, Column 3, Final Paragraph and leading into Column 4). Therefore, these teachings cover therapeutic proteins (for claim 10), and specifically multiple claimed therapeutic proteins of the instant application (for claim 11), including blood factors, immunostimulatory agents, hormones, anticoagulant.
Regarding Claims 12-16, Falkner teaches the following regarding origin of the packaging constructs (components):
“Within the present invention, by "packaging component" any genes necessary for forming a retroviral vector, such as gag-pol and env, of a retrovirus are understood. For the construction of the chimeric poxviruses of the invention (so-called Retro Vac vectors), simple retroviruses, such as MLV (for claim 12 and 15 of gamma retrovirus, and claim 16 Moloney murine Leukemia Virus), just as well as complex retroviruses, e.g., human immunodeficiency virus (HIV) (for claims 12-13 of lentivirus and claim 14 of HIV) can be used. (Pg. 11, Column 4, Line 53-59).
Response to Applicants’ Arguments as they apply to the rejection of 1-5 and 9-16 under 35 U.S.C. 103 as being unpatentable over Falkner et al. (US 6,352,856 Bl, IDS) in view of Kirn et al. (US 20120276053 A1, IDS)
At pages 7-8 of the remarks filed on 03/05/2026, applicants argue that the rejection of claims be withdrawn as “Claim 1 is amended to incorporate the aspect of Claim 9, thymidine kinase (TK) gene." Claim 9 is recognized by the Office as non-obvious. As such, the incorporation of the subject matter of claim 9 into claim 1 renders the obviousness rejection to
independent claim 1 and rejected dependent claims therefrom no longer relevant.”
Applicants’ arguments have been considered, but have not been found persuasive.
The office has not recognized claim 9 as non-obvious. In the claims filed 06/27/2025, claim 9 was improperly dependent on cancelled claim 8. Further, reconsideration of the art has demonstrated that amended claim 1, including the limitations from claim 9 previously not considered, are indeed rendered obvious as discussed in the 103 rejection above.
Claims 17-21 are rejected under 35 U.S.C. 103 as being unpatentable over Falkner et al. (US 6,352,856 Bl, IDS) in view of Kirn et al. (US 20120276053 A1, IDS) as applied to claims 1-5 and 9-16 above and in view of Borkotoky et. al (Borkotoky S, Int J Biol Macromol., 2018, of record).
This rejection has been modified in response to applicants’ amendments, but remains rejected under 103.
With regard to instant claim 1 above, Falkner and Kirn render obvious the claimed virus as iterated above in the 103 rejection, the content of which is incorporated herein, in its entirety.
Falkner and Kirn together do not specifically teach the virus to contain an exogenous nucleic acid sequence encoding a nucleic acid polymerase for claim 17. Falkner and Kirn together do not teach the nucleic acid to be selected from the group consisting of a T7 RNA polymerase, T3 RNA polymerase and SP6 RNA polymerase, an RNA polymerase variant, and a DNA polymerase mutant for claim 18. Falkner and Kirn together do not teach the virus of claim 1, comprising an exogenous nucleic acid sequence that codes for a bacteriophage polymerase for claim 19. Falkner and Kirn together do not teach a bacteriophage polymerase selected from the group consisting of a T3 bacteriophage, a T7 bacteriophage, and an SP6 bacteriophage for claim 20. Falkner does not teach a T3 bacteriophage polymerase is expressed with a T3 bacteriophage promoter, a T7 bacteriophage polymerase is expressed with a T7 bacteriophage promoter, and an SP6 bacteriophage polymerase is expressed with an SP6 bacteriophage promoter for claim 21.
Borkotoky cures the deficiencies of Falkner and Kirn as Borkotoky teaches the use of a T7 polymerase that is incorporated within a vaccinia virus and under the control of a T7 promoter. Specifically, they teach “Vaccinia virus, a linear double-stranded DNA virus, was advantageous for developing it as eukaryotic expression vector. The advantages of T7RNAP (T7 RNA polymerase) include its ability to encode an entire transcription system including RNA polymerase, capping/methylating enzymes and poly (A) polymerase, large capacity for foreign DNA, genome stability, and wide vertebrate host range. To test whether T7 RNA polymerase made under control of vaccinia virus can function in mammalian cells, Fuerst and colleagues constructed vaccinia/T7 hybrid systems containing target genes such as E. coli β-galactosidase gene (lacZ) and the CAT gene (cat) derived from the Tn9 transposon flanked by T7 promoter and termination regulatory elements. When compared, the synthesis of β -galactosidase and CAT by the hybrid system was found to be 15 to 20 fold more efficient than the straight vaccinia system and 400 to 600 fold more efficient than the conventional transient-expression system. Recombinant vaccinia virus expressing bacteriophage T7 RNA polymerase has also been used for studies on processing of i) HCV polyproteins [14], ii) editing mRNA of Ebola virus and iii) recovering infectious viruses from their full-size cDNA clones of negative-strand RNA viruses like vesicular stomatitis virus, rabies virus, bunya virus, respiratory syncytial virus, and sendai virus.” The teachings by Borkotoky of the T7RNAP within the vaccinia virus fully encompasses the instant application claims 17-20 and the use of the T7 promoter within this system encompasses the instant application claim 21.
It would have been obvious for one of ordinary skill in the art at the time of the invention to have modified the viral system taught by Falkner and Kirn to incorporate an exogenous nucleic acid sequence encoding a T7 polymerase, as taught by Borkotoky, to develop an improved viral vector with enhanced transcriptional efficiency.
One would have also been motivated to include the T7 polymerase within the viral system to leverage its highly efficient RNA transcription capabilities as taught by Borkotoky above, thereby improving gene expression and expanding the utility of the virus for various applications, including recombinant protein production and viral rescue systems.
There would have been reasonable expectations of success in the inclusion of a T7 polymerase within the viral backbone, as Falkner, Kirn, and Borkotoky teach successful integration of genetic elements into viral genomes, with Borkotoky specifically demonstrating the functionality of a vaccinia virus-T7 polymerase system in mammalian cells, with the resulting virus having significantly increased transcription efficiency.
Response to Applicants’ Arguments as they apply to the rejection of claim(s) 17-21 which remain rejected under 35 U.S.C. 103
At pages 8 of the remarks filed on 03/05/2026, applicants argue that the rejection of claims be withdrawn as “Claim 1 is amended to incorporate the aspect of Claim 9, thymidine kinase (TK) gene." Claim 9 is recognized by the Office as non-obvious. As such, the incorporation of the subject matter of claim 9 into claim 1 renders the obviousness rejection to
independent claim 1 and rejected dependent claims therefrom no longer relevant.”
Applicants’ arguments have been considered, but have not been found persuasive.
The office has not recognized claim 9 as non-obvious. In the claims filed 06/27/2025, claim 9 was improperly dependent on cancelled claim 8. Further, reconsideration of the art has demonstrated that amended claim 1, including the limitations from claim 9 previously not considered, are indeed rendered obvious as discussed in the 103 rejection above.
Conclusion
No claims are allowed.
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/KODYE LEE ABBOTT/Examiner, Art Unit 1634
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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