DETAILED ACTION
Applicant’s amendment and remarks filed September 26, 2025 are acknowledged and entered. Any prior objection or rejection that is not repeated or addressed below is either moot or withdrawn in view of Applicant’s amendment.
Claims Summary
Claim 1 is directed to a cell line derived from a Spodoptera frugiperda (S. frugiperda) organism or cell line that is contaminated with S. frugiperda rhabdovirus (Sf-rhabdovirus). The “derived from” limitation is a product-by-process limitation. The specification at paragraph [0044] indicates that “derived” means obtained from a source, directly or indirectly. (According to MPEP 2113, the patentability of a product does not depend on its method of production. The structure implied by the process steps should be considered, however, product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.) The specification discloses that a “cell line” means a population of cells that were expanded from one or a few common ancestor cell (see paragraph [0042]). The cell line is characterized by a lack of a persistent Sf-rhabdovirus infection and has no intact, assembled Sf-rhabdovirus genome in the transcriptome of the cell line. The cell line is structurally different from a S. frugiperda organism or cell line that is contaminated with Sf-rhabdovirus. The Sf-rhabdovirus-contaminated cell line comprises Sf-21 or Sf9 cells (claim 2). The cell line is characterized by a cell density, a doubling time, an average cell diameter, a morphology, and a N-glycosylation pattern that is the same or substantially the same as Sf9 cells when the cell line and the Sf9 cells are propagated under the same conditions (claim 3). The cell line is characterized by increased production of infectious recombinant baculovirus particles compared to production in Sf9 cells under the same conditions (claim 4), wherein the baculovirus particles are AcP(-)p6.9hEPO, or AcP(-)p6.9hSEAP (claim 14).
In a product-by-process limitation, the method by which the cell line is manufactured comprises (claim 5):
Isolating a cell from a Sf-rhabdovirus-contaminated organism or cell line by limiting dilution;
Combining the isolated cell with a cell culture media comprising an antiviral compound to form a first culture composition; the antiviral compound is a nucleoside analog (claim 7); wherein the antiviral compound is 6-azauridine (claim 8);
Incubating the first culture composition under conditions suitable for the cell to grow and divide, thereby generating a multiplicity of cells;
Removing a portion of the multiplicity of cells or the cell culture media and testing for the presence or absence of a virus; testing comprises RT-PCR, or RT-PCR and nested PCR, or quantitative RT-PCR, or an antibody-based detection technique (claims 6 and 8, respectively);
Combining at least some of the multiplicity of cells with cell culture media without an antiviral compound to form a second culture composition; and
Incubating the second culture composition under conditions suitable for the cells to grow and divide, thereby obtaining a virus free cell line.
Claim Rejections - 35 USC § 112
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.
Claim 14 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
It is apparent that baculoviruses AcP(-)p6.9hEPO and AcP(-)p6.9hSEAP are required to practice the claimed invention because they are a necessary limitation for the success of the invention as stated in the claims. As a required element it must be known and readily available to the public or obtainable by a repeatable method set forth in the specification, or otherwise readily available to the public. If it is not so obtainable or available, the enablement requirements of 35 U.S.C. § 112, first paragraph, may be satisfied by a deposit of baculoviruses AcP(-)p6.9hEPO and AcP(-)p6.9hSEAP. See 37 CFR 1.802. One cannot practice the claimed invention without the viruses that are required to show improved production. One cannot determine whether the claimed cell line has the necessary characteristics without access to the viruses. Therefore, access to baculoviruses AcP(-)p6.9hEPO and AcP(-)p6.9hSEAP is required to practice the invention. The specification does not provide a repeatable method for obtaining the viruses without access to them and they do not appear to be readily available material.
Deposit of baculoviruses AcP(-)p6.9hEPO and AcP(-)p6.9hSEAP in a recognized deposit facility would satisfy the enablement requirements of 35 U.S.C. 112, because the strains would be readily available to the public to practice the invention claimed, see 37 CFR 1.801- 37 CFR 1.809.
If a deposit is made under the terms of the Budapest Treaty, then an affidavit or declaration by applicants or someone associated with the patent owner who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the deposit has been made under the terms of the Budapest Treaty and that all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of a patent, would satisfy the deposit requirements. See 37 CFR 1.808.
If a deposit is not made under the terms of the Budapest Treaty, then an affidavit or declaration by applicants or someone associated with the patent owner who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the deposit has been made at an acceptable depository and that the following criteria have been met:
(a) during the pendency of this application, access to the invention will be afforded to one determined by the Commissioner to be entitled thereto;
(b) all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon granting of the patent;
(c) the deposit will be maintained for a term of at least thirty (30) years and at least five (5) years after the most recent request for the furnishing of a sample of the deposited material;
(d) a viability statement in accordance with the provisions of 37 CFR 1.807; and
(e) the deposit will be replaced should it become necessary due to inviability, contamination or loss of capability to function in the manner described in the specification.
In addition the identifying information set forth in 37 CFR 1.809(d) should be added to the specification. See 37 CFR 1.803 - 37 CFR 1.809 for additional explanation of these requirements.
Applicant’s arguments filed September 26, 2025 have been considered but fail to persuade. Applicant argues that the viruses “AcP(-)p6.9hEPO” and “AcP(-)p6.9hSEAP” are fully characterized in the literature such that a deposit is not required. Applicant points to the known nomenclature for AcP(-)p6.9hEPO and AcP(-)p6.9hSEAP, as well as known methods for producing viruses.
In response, the claims are directed to particular viruses, not a class of viruses having certain characteristics. “AcP(-)p6.9hEPO” and “AcP(-)p6.9hSEAP” are laboratory designations that indicate two particular viruses. Thus, the rejection is maintained because Applicant has not provided the viruses in the form of a deposit, or the complete genome of the those two particular viruses. If Applicant intends for those terms to describe features of two types of viruses, then appropriate language would be a description of the features of the viruses, not laboratory designations. For example, “wherein the infectious recombinant baculovirus particle is a AcMNPV having a deletion of the gene for the viral basic DNA-binding protein P6.9, having a p6.9 promoter that regulates expression of hEPO”, etc. If Applicant uses this type of description, please beware of introducing new matter.
Claims 5-8 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The specification is enabling for a cell line produced by a method comprising:
Isolating a cell from Sf-rhabdovirus contaminated S. frugiperda organism or cell line by limiting dilution;
Combining the isolated cell with a culture media comprising an antiviral to form a first culture composition;
Incubating the first culture composition under conditions suitable for the cell to grow and divide, thereby generating a multiplicity of cells;
Removing a portion of the multiplicity of cells or the cell culture media and testing for the presence or absence of a Sf-rhabdovirus [emphasis added];
Combining at least some of the multiplicity of cells with cell culture medium without an antiviral compound to form a second culture composition; and
Incubating the second culture composition under conditions suitable for the cells to grow and divide, thereby obtaining a Sf-rhabdovirus free S. frugiperda cell line.
The specification does not reasonably provide enablement for this method with any other type of virus. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The breadth of the claims encompasses a cell line free of every virus contamination. The nature of the invention is the manufacture of a Sf cell line that is not contaminated with Sf-rhabdovirus, resulting from a method that uses an antiviral during cell culture and subsequent culture in the absence of the antiviral. The specification envisions isolating single cells or small group of cells, which are then combined with a nucleoside analog, such as 6-azauridine (e.g., paragraph [0053]).
Example 2 of the specification demonstrates combining isolated Sf-rhabdovirus-infected Sf9 cells with medium containing the combination of ribavirin, 6-azauridine, and vidarabine to form a first culture composition; incubating the first culture composition under conditions suitable for the cell to grow and divide to generate a multiplicity of cells; testing the cells to determine the absence of Sf-rhabdovirus; combining at least a portion of the multiplicity of cells with cell culture medium without the antiviral compound to form a second culture composition, and incubating the second culture composition under conditions suitable for the cell to grow and divide. While the active steps of the rejected claims were carried out, the specification teaches that cells treated with the three antiviral compounds reverted back to Sf-rhabdovirus positive cells once the antiviral compounds were removed from the culture. Thus, the specification provides evidence of the unpredictability in this area, and the lack of enablement for the full scope of the claims.
Example 3 of the specification demonstrates isolating a Sf-rhabdovirus-infected Sf9 cell by limiting dilution; combining the isolated cell with medium containing the 6-azauridine to form a first culture composition; incubating the first culture composition under conditions suitable for the cell to grow and divide to generate a multiplicity of cells; testing the cells to determine the absence of Sf-rhabdovirus; combining at least a portion of the multiplicity of cells with cell culture medium without the antiviral compound to form a second culture composition, and incubating the second culture composition under conditions suitable for the cell to grow and divide. See also Fig. 2B. Example 5 demonstrates that the resulting Sf-RVN cell line is free of Sf-rhabdovirus.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability evidenced in Example 1, it would require undue experimentation to make the claimed cell line. Amendment of the claims (i.e., claim 5, lines 11 and 15) to specify that the virus is Sf-rhabdovirus and that the cell line is free of Sf-rhabdovirus would overcome this rejection.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vaughn et al. (In Vitro, 1977, 13(4):213-217, cited in the IDS filed 10/17/2022, “Vaughn”), evidenced by
Hashimoto et al. (PLoS ONE, 2017, 12(4):e0175633, 17 pages, “Hashimoto”). The claims are summarized above and correlated to the teachings of the prior art in bold font.
Vaughn discloses a primary culture from S. frugiperda (see abstract). Vaughn developed two cell lines from the primary culture, one of which was subsequently sequenced by Hashimoto et al. (PLoS ONE, 2017, 12(4):e0175633, 17 pages, “Hashimoto). Hashimoto reports that the cell line (ATCC CRL-1711 lot 5814 Sf9 cells) does not have an intact assembled Sf-rhabdovirus genome in the transcriptome of the cell line, rather, incomplete portions of Sf-rhabdovirus-like sequences (see page 4, “Results” section). Thus, Vaughn’s cell line reads on the claimed cell line because it is an Sf9 cell line that does not have an intact, assembled Sf-rhabdovirus genome in its transcriptome, nor is it persistently infected with Sf-rhabdovirus (claims 1 and 2). Vaughn’s cell line is structurally different from a Sf-rhabdovirus-contaminated S. frugiperda organism or from a Sf-rhabdovirus-contaminated S. frugiperda cell line because it does not have an intact assembled Sf-rhabdovirus genome in its transcriptome (claim 1). Although Vaughn does not teach that the cell line was derived from S. frugiperda contaminated with Sf-rhabdovirus, the presence of Sf-rhabdovirus-like sequences (as taught by Hashimoto) meets the structural implications of the product-by-process limitation regarding derivation from an S. frugiperda organism or cell line contaminated with Sf-rhabdovirus (claim 1).
Regarding claim 3, directed to a characterization limitation, Vaughn’s cell line is expected to have substantially the same morphology as Sf9 cells if propagated under the same conditions, since Vaughn’s cell line is an Sf9 cell line.
Regarding claim 4, directed to a characterization limitation, increased production of infectious recombinant baculovirus particles compared to production in Sf9 cells under the same conditions is expected since Vaughn’s cell line meets the structural limitations of the instantly claimed cell line. Therefore, the claims are anticipated by the prior art.
Regarding claims 5-8, directed to a process by which the cell line is obtained, Vaughn’s cell line reasonably falls within the scope of the claim because Vaughn’s cell line is virus-free in the sense that it does not comprise Sf-rhabdovirus (see page 4, “Results” section). Although Vaughn does not perform the method steps recited in claims 5-8, the structural implications of the process limitations are met by Vaughn’s cell line: no persistent Sf-rhabdovirus infection, structurally different from a Sf-rhabdovirus-contaminated S. frugiperda organism or from a Sf-rhabdovirus-contaminated S. frugiperda cell line because it does not have an intact assembled Sf-rhabdovirus genome in its transcriptome. Therefore, the claimed embodiments are anticipated by the prior art.
Applicant’s arguments filed September 26, 2025 have been carefully considered but fail to persuade. Applicant argues that the cell line analyzed in Hashimoto is not the same as the cell line established by Vaughn, rather, it is a subclone. Applicant reasons that since Hashimoto did not analyze the original cell line of Vaughn, no conclusions about the original cell line can be drawn.
Applicant’s claims are directed to a cell line derived from a Sf-rhabdovirus-contaminated Sf cell line. Applicant’s specification at paragraph [0044] indicates that “derived” means obtained from a source, directly or indirectly. The specification discloses that a “cell line” means a population of cells that were expanded from one or a few common ancestor cell (see paragraph [0042]). Hashimoto discloses analyzing Sf9 cell line CRL-1711 lot 5814, and references Vaughn. Since the cell line is broadly defined as “derived from”, and the claims do not recite any particular cell line as the point of derivation, nor do the claims recite any particular cell line other than structural features, Vaughn’s cell line or subclone meets the claim limitations. Regardless, recall that according to MPEP 2113, the patentability of a product does not depend on its method of production. The structure implied by the process steps should be considered, however, product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. In this instance, Vaughn’s cell line meets the limitations of the claims, being free of persistent Sf-rhabdovirus infection, differing structurally (genetically), and not having an intact, assembled Sf-rhabdovirus genome in the transcriptome of the cell.
Applicant also argues that Hashimoto’s analysis shows that the Sf9 cell line is indeed contaminated with Sf-rhabdovirus. Specifically, Applicant argues that Hashimoto’s total RNA isolation showed the presence of 99.1% of the Sf-rhabdovirus genome (not Sf-rhabdovirus-like endogenous viral elements), thus the cell line was contaminated with Sf-rhabdovirus. Pointing to Maghodia and Jarvis (Virology, 2017, 512:234-245), a reference that is not of record, Applicant argues that Hashimoto’s conclusion of no Sf-rhabdovirus contamination is incorrect.
In response, the reference relied upon, Maghodia and Jarvis, has not been considered since it has not been provided, nor is it of record. For the sake of argument, even if 99.1% of the Sf-rhabdovirus genome is present in the Sf9 cell line, and is not actually Sf-rhabdovirus-like endogenous viral elements, Vaughn’s cell line (or its subclone) still meets the limitations of the claims because it differs from a cell line contaminated with Sf-rhabdovirus. Having 99.1% of the genome is not the same as having 100% (intact, assembled) of the genome. Thus, Vaughn’s cell line, or its subclone, is structurally different from a cell line that is contaminated with Sf-rhabdovirus, and meets the limitations of the claims. Therefore, the rejection is maintained.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
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/STACY B CHEN/Primary Examiner, Art Unit 1672