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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/14/2025 has been entered.
Priority
Applicant’s claim to priority from PCT/US2019/048361 filed 08/27/2019 and Provisional application No. 62/723,233 filed 08/27/2018 is hereby acknowledged. This application is a National Stage entry under 35 U.S.C. § 371 of PCT/US2019/048361.
Application status
Applicant’s election of Group I (claims 1, 8-9 and 15 drawn to a method of inhibiting a viral infection) in the reply filed on 11/23/2023 was acknowledged and still in effect. Claims 10-14,16-20 are withdrawn from further consideration pursuant to 37 CFR.1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/27/2023.
Amendments to claims filed 11/14/2025 are hereby acknowledged. Claims 1 and 15 are currently amended and claims 2-8 are cancelled. Therefore, claims 1, 8-9 and 15 are under consideration in this office action.
Any objection or rejection not reiterated in this office action have been rendered moot by the amendments and are therefore withdrawn.
Drawings
Corrected drawing sheets filed 04/23/2024 are hereby acknowledged and are
acceptable. High definition copies are available in the supplement filed 04/23/2024.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 9 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 9 recites “wherein the compound is a nucleic acid”. Claim 9 depends on claim 1, however, claim 1 does not recite “a compound” any longer. It is also clear that a poly I:C is a nucleic acid, therefore claim 9 does not further limit claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
New rejections necessitated by Applicant’s amendments
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.
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 non-obviousness.
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 1, 8-9 and 15 are rejected under 35 U.S.C. § 103 as being
unpatentable over Pantelic (Pantelic, L. et al. Journal of Virology, Vol. 79, No.3 (Feb., 2005), pp:1753-1764; previously cited) in view of Mascarenhas (Mascarenhas, J.X. et al. Biotechnology and Bioengineering, Vol.114, No.3 (Mar., 2017), pp:576-588; previously cited), Adamson (Adamson, S.R. Dev. Biol. Stand. Basel, Karger, Vol. 93 (1998), pp: 89-96; previously cited), Huang (Huang, C.C. et al. "A pathway analysis of poly(I:C)-induced global gene expression change in human peripheral blood mononuclear cells". Physiol. Genomics, Vol. 26 (2006), pp: 125–133) and Choi (Choi, S.S. et al. Hepatology, Vol. 54 (2011), pp: 1580-1590; previously cited).
Regarding claims 1 and 15, Pantelic teaches "[D]ifferential induction of
antiviral effects against West Nile Virus in primary mouse macrophages ( ... ) by alpha/beta Interferon (IFN) and Poly (I-C)" (see title). Pantelic teaches effective pretreatment with Interferon alpha/beta inhibiting West Nile virus replication in primary macrophages from mice (see page 1755, right column, "Results" section, line 41). Pantelic also teaches the effect of Poly (I-C) on West Nile virus replication in primary macrophages (see page 1758, first column (left), line 6). Therefore, Pantelic teaches a method of inhibiting viral infection, administering IFN and poly (I-C) to the sample in an amount effective at decreasing the virus titer.
Pantelic does not teach CHO cells. Pantelic does not teach a biopharmaceutical process. Pantelic does not teach that Poly I:C is effective to suppress expression of Gfi1 in the CHO cells and activate expression of STAT1 in the CHO cells.
However, Adamson teaches that CHO cells are being used for biopharmaceutical process and that CHO cells can be infected by virus in spite of resistance to some retroviruses (see page 89-90, "[l]ntroduction" section).
Mascarenhas teaches a method of improving viral resistance to Minute Virus of
Mice in CHO cells. On page 578, second column (right), lines 22-24, Mascarenhas
discloses "[T]he Cosmc and Mgat1 knockouts also show significant inhibition of infection likely due to their effect on decreasing cell surface sialic acid." Therefore, Mascarenhas
teaches a different method of inhibiting viral infection in CHO cells. Mascarenhas uses
gene editing ( see page 579, first column (left) "ZFN-Mediated or CRISPR-Cas9 Gene
editing" section) to inhibit mouse minute virus adventitious contamination in CHO cells,
targeting specifically genes involved in sialic acid metabolism, since sialic acid is an
important part of cell surface receptor modification for virus entry. Mascarenhas uses
multiple compounds included in a CRISPR-Cas gene editing system, i.e. using a gRNA to specifically target genes of interest in glycosylation pathways in CHO cells. The
compounds elicit viral resistance by compromising virus entry into CHO cells.
Huang teaches that Poly I:C is capable of inducing STAT1 expression by a factor of 5.38 after 3hours stimulation of Peripheral blood mononuclear cells (PBMCs) and by a factor of 3.74 after 24hours (see Table 3). Therefore, Huang teaches that STAT1 is an early-to-late response genes to poly I:C stimulation.
Choi teaches a cell line that is not permissive to HCV viral infection, Huh7 cell line, in which Gli1 expression is suppressed, and compares to a cell line, Huh7.5 cell line, that is permissive to HCV viral infection, in which Gli1 expression is 30 times higher (see figure 1D). Choi teaches that using an antagonist of Hedgehog (Hh) pathway, cyclopamine, reduced HCV RNA and protein levels, as well as Gli1 expression level (see figure 2). Therefore, Choi teaches a compound that prevents, and inhibits viral infection that also suppresses Gli1 expression.
Therefore, it would be obvious to one with ordinary skills in the art, before the effective filing date of the claimed invention to have substituted the cell line in the method of inhibiting viral infection taught by Pantelic with CHO cells taught by Mascarenhas, as both disclosures are drawn to methods of inhibiting or preventing viral infections in cells. It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Pantelic, Adamson, Mascarenhas, Huang and Choi, and have treated the CHO cells with Poly I:C as taught by Pantelic and Huang to activate innate immune response. Treating the CHO cells with Poly I:C would increase the level of antiviral genes expressed in the cells, such as STAT1, as taught by Huang, and inhibit Gli1 expression correlated with viral infections as taught by Choi.
One with ordinary skills in the art could have performed this modification to inhibit or prevent adventitious viral infections in an industrial setting, with a reasonable expectation of success and arrived at the claimed invention.
Regarding claim 8, drawn to “the method of claim 1 wherein the virus is VSV,
EMCV REO, an RNA virus, or a DNA virus”, Pantelic teaches not only West Nile virus
inhibition, but also EMCV inhibition; See page 1754, second column (right), line 10, "[V]iruses" section. West Nile virus belonging to the Flaviridae family and Flavivirus
genus, is an RNA virus; see page 1753, first column (left), lines 1-6. EMCV (Encephalomyocarditis virus) is a picornavirus, also an RNA virus; see page 1762, first
column (left), "[D]iscussion" section, lines 9-14.
Regarding claim 9 reciting "wherein the com pound is a nucleic acid", Pantelic
teaches Poly I-C, which is a double stranded RNA. Pantelic discloses on page 1753, Abstract section, line 7 "[l]t was only the combined pretreatment with IFN-alpha/beta
and plC (Poly I-C) that elicited strong antiviral responses that completely prevented
flavivirus replication in macrophages from susceptible mice. Primary macrophages isolated from the blood of healthy human donors expressed a similar need for double stranded (dsRNA) cofactor in developing efficient antiviral responses against West Nile
virus."
Response to Arguments
Applicant's arguments filed 11/14/2025 have been fully considered but they are not persuasive.
Applicant argues in section IV “Claim rejections under 35 U.S.C.§ 103”, page 6 of Remarks filed 11/14/2025, that “neither reference—alone or in combination—discloses or suggests administering an effective amount of a poly I:C to a culture of CHO cells.”
In response, the new rejections necessitated by Applicant’s amendments are over the combination of Pantelic, Mascarenhas, Adamson, Huang and Choi. Pantelic and Huang both teach adding Poly I:C to cells in culture in an efficient amount to reduce viral infection in Pantelic (See abstract) and to provoke gene expression changes in the innate immune response in Huang (see abstract). 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 Pantelic and Mascarenhas teach methods of inhibiting or preventing a viral infection. Substituting the cells taught by Pantelic with the cells taught by Mascarenhas is obvious. Pantelic and Huang teach that the process of adding Poly I:C to cultured cells are not a novelty. Using Poly I:C to inhibit a viral infection is not new as taught by Pantelic. Increasing innate immune response gene expression by adding Poly I:C is not a new concept according to Huang. Using CHO cells for pharmaceutical recombinant proteins production is not new according to Adamson and other with reasonable skills in the art. The knowledge of CHO cells being susceptible to viral infection is a known problem according to Adamson and Mascarenhas. The detection of gene expression levels after adding a compound is not new either in the art. Huang teaches alteration of gene expression by Poly I:C, as well as STAT1 expression. Choi teaches alteration of GFi1 expression by virus infection and treatment.
Regarding Applicant’s statement “let alone the claimed effects of doing so” in same paragraph, Examiner would like to remind that the claimed effects on expression levels of STAT1 or Gli1 are end-results of the use of the method. In response to applicant's argument, 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 claim is allowed.
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/A.D./Examiner, Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636