DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election without traverse of Group I, claims 1-12 in the reply filed on 09 March 2026 is acknowledged. Claims 13-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-12 are under consideration.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on 02 November 2023 was filed after the mailing date of the Instant Application on 19 July 2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
4. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
5. The drawings are objected to because Figures 1A and 1B are difficult to read. 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
6. 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:
7. 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 in Table 2, Figure 1A and Figure 5A.
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.
8. Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
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 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.
Specification
9. The use of the terms “Gene Pulser XCell electroporation system” (¶ [0094]), “QuantStudio”
(¶ [0095]), and “Breathe-Easy” (¶ [0097]), which are trade names or marks used in commerce, have been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Note that “Gene Pulser XCell electroporation system”, “QuantStudio”, and “Breathe-Easy” are merely examples and all improper uses of trademarks in the specification should be identified by Applicant and properly addressed.
Claim Objections
10. Claims 1, 3, and 7 are objected to because of the following informalities:
Regarding claim 1, the phrase “wherein the producer cell line expresses a SARS-CoV-2 ORF3 gene and a SARS-CoV-2 Envelope gene” is repetitive and should be deleted.
Regarding claim 3, "a SARS-CoV-2 Envelope gene" should be "the SARS-CoV-2 Envelope gene".
Regarding claim 7, "a ORF3 gene" should be "the ORF3 gene".
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
11. 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.
12. Claims 5 and 8-9 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.
Regarding claim 5, “a nucleic acid sequence of” could read on the full length sequence or a fragment thereof, and therefore there are multiple structural interpretations. It is suggested to change “a” to “the”. See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) ("[R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite.").
Claims 8-9 recite the limitation "the envelope gene". There is insufficient antecedent basis for this limitation in these claims.
Claim Rejections - 35 USC § 112(a) – Enablement
13. 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.
In making a determination as to whether an application has met the requirements forenablement under 35 U.S.C. 112 ¶ 1, the courts have put forth a series of factors. See, In reWands, 8 USPQ2d 1400, at 1404 (CAFC 1988). The factors considered include: (1) the breadth of the claims, (2) the nature of the invention, (3) the relative skill of those in the art, (4) the presence or absence of working examples, (5) the amount of direction or guidance provided, (6) the state of the prior art, (7) the level of predictability in the art, and (8) the quantity of experimentation necessary.
14. Claims 7-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for isolated vectors and cells, does not reasonably provide enablement for unisolated vectors and cells. 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/or use the invention commensurate in scope with these claims.
The claims recite “producer cell”, which includes transgenic animals since they are not isolated.
The nature of the invention is a trans-complementation system.
The level of skill of one of ordinary skill in this art is high.
The specification does not give definitions for “isolated” or indicate that the “producer cell” is isolated or made in vitro. Therefore, these words will be given their broadest reasonable interpretation to one of ordinary skill in the art as discussed above. With respect to transgenes within animals and transgenic animals themselves, none were made here.
With respect to the unisolated host cells, the state of the art at the time of filing was such that one of skill could not predict the phenotype of transgenics. The art of transgenic animals has for many years stated that the unpredictability lies, in part, with the site or sites of transgene integration into the target genome and that "the position effect" as well as unidentified control elements are recognized to cause aberrant expression of a transgene (Wall et Al., Theriogenology, 1996, 45: 57-68).
The elements of the particular construct used to make transgenic animals are also held to be critical, and they must be designed case by case without general rules to obtain good expression of a transgene; e.g., specific promoters, presence or absence of introns, etc. (Houdebine et Al., J. Biotechnol., 1994, 34: 269- 287). Furthermore, transgenic animals are regarded to have within their cells, cellular mechanisms that prevent expression of the transgene, such as methylation or deletion from the genome (Kappell et Al., Current Opinions in Biotechnology, 1992, 3: 548-553). Houdebine (Comparative Immunology, Microbiology, and Infectious Diseases, 2009, 32: 107-121) teaches progress has been made in the field of transgenic animals for production of foreign proteins (Abstract); however, constructing an efficient expression vector to produce a therapeutic protein is not a standard operation (Pg. 116, Paragraph, second). Therefore, undue experimentation is required to make and use a transgene and transgenic animal to produce the antibody and antibody fragments of the instant claims.
The Examiner notes here, in addition to these issues, even assuming arguendo PHOSITA could make a host organism with functional transgene that encodes the instantly recited antibody, there is no predictability that the host will survive its expression. The transgene depends on the host for function and harm to the host, including death, renders the transgene nonfunctional and thus not enabled.
The art is well-aware of side effects caused by therapeutic antibodies such as the one instantly recited. In a transgenic cell or animal that expresses the same, the antibody will exert any possible side effect it can. It is not administered but chronically present and so such side effects are chronic and potentially more serious than any from an administered antibody. Hansel (Nat. Rev. Drug. Discov., 2010, 9: 325-337) teaches in their table 1 on page 328 numerous exemplary side effects from licensed monoclonal antibodies to include: increased bleeding risk, infection, heart failure, cancer, thyroid disorder, autoimmune reactions, and cytokine release syndrome (CRS) to name only a few. One or more such effects, or similar, may occur with the therapeutic antibody instantly recited when administered and indeed be exacerbated by chronic exposure due to internal expression. The instantly encoded antibody may very well target related or unrelated proteins in the transgenic host, leading to such side effects. For all these reasons, transgenes in transgenic animals and the animals themselves are not enabled.
At the time of filing, the phenotype of a transgene and transgenic cell contained within any animal was unpredictable. The claims as written, encompassing a transgene and cell in a transgenic animal, is not adequately described in the specification as to prevent excessive experimentation by the public to generate and use the invention. Applicants can obviate the instant rejection by amending the claim to recite the term "isolated" or “in vitro” before the recitation "producer cell". Applicant may consider using purified in such claims if description is appropriate for such a term and it is not redefined away from standard meaning. Method claims using these products should also carry the appropriate adjectives above.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by Applicant, and the absence of working examples, undue experimentation would be required to make and use functional transgenes and transgenic animals encompassed by the instant claims.
Claim Rejections - 35 USC § 101
15. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
16. Claims 7-9 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). The term “producer cell” can be interpreted to be a human or other organism. The producer cell “comprises at least one heterologous nucleic acid encoding a ORF3 gene and/or SARS-CoV-2 gene” could read on a human or other animal getting infected with SARS-CoV-2. The ORF3 and envelope genes of SARS-CoV-2 are encoded the same nucleic acid and different nucleic acids at different points during viral replication. Zhang (Front Microbiol, 9 March 2022, 9(13): 854567) teaches during replication, the full-length +gRNA is used as a template to generate a full-length -gRNA (SARS-CoV-2 Infectious Life Cycle), which would have both genes on the same nucleic acid. The +gRNA is used as a template to produce a nested set of -sgRNAs, which would then be used to produce nested +sgRNAs (SARS-CoV-2 Infectious Life Cycle). These nested +sgRNAs would have the ORF3 and envelope genes separately. See also Figures 1 and 2:
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A human or animal getting infected with SARS-CoV-2 is not patentable.
Furthermore, even if the cells were isolated, this still would not overcome this rejection as they would be structurally identical to naturally infected cells. They would not be incorporated into a practical application because the claimed invention is not used to provide a particular treatment or prophylaxis for a disease or medical condition. Further, the claimed invention does not apply or use the judicial exception in a meaningful way and there is no inventive concept in the claims. Therefore, the instant claims do not recite any additional elements that integrate the exception into a practical application.
Claim Rejections - 35 USC § 102
17. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
18. Claims 7-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hu (06 October 2020, Nature Reviews Microbiol., 19: 141-154) (See IDS filed 02 November 2023).
Regarding claims 7-9. The term “producer cell” can be interpreted to be a human or other organism. The producer cell “comprises at least one heterologous nucleic acid encoding a ORF3 gene and/or SARS-CoV-2 gene” could read on a human or other animal getting infected with SARS-CoV-2. Hu teaches the emergence and spread of SARS-CoV-2 in humans in late December 2019 through most of 2020 (Emergence and spread). The ORF3 and envelope genes of SARS-CoV-2 are encoded the same nucleic acid and different nucleic acids at different points during viral replication. Zhang (Front Microbiol, 9 March 2022, 9(13): 854567) teaches during replication, the full-length +gRNA is used as a template to generate a full-length -gRNA (SARS-CoV-2 Infectious Life Cycle), which would have both genes on the same nucleic acid. The +gRNA is used as a template to produce a nested set of -sgRNAs, which would then be used to produce nested +sgRNAs (SARS-CoV-2 Infectious Life Cycle). These nested +sgRNAs would have the ORF3 and envelope genes separately. See also Figures 1 and 2:
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Therefore, the natural infection and spread of SARS-CoV-2 in humans anticipates the claims.
Claim Rejections - 35 USC § 103
19. 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 nonobviousness.
20. Claims 1-2 and 4-10 are rejected under 35 U.S.C. 103 as being unpatentable over Baric (US 20060240530 A1; 26 October 2006) (See IDS filed 02 November 2023) in view of Castano-Rodriguez (22 May 2018, mBio, 9(3): e02325-17) (See IDS filed 02 November 2023) and Hatmal (08 December 2020, Cells, 9(12): 2638).
Regarding claims 1, 4, and 7-9, Baric teaches “the present invention provides a helper cell for producing an infectious, multiplication-defective, coronavirus particle, comprising: (a) a SARS coronavirus replicon RNA comprising a coronavirus packaging signal and a heterologous RNA sequence, wherein said replicon RNA lacks a sequence encoding at least one coronavirus structural protein; and/or (b) at least one separate helper RNA encoding the at least one coronavirus structural protein absent from the replicon RNA, said helper RNA lacking a coronavirus packaging signal; wherein the combined expression of the replicon RNA and the helper RNA produces an infectious, multiplication-defective coronavirus particle.” (¶ [0023]), wherein the “structural protein” can include the E gene (¶ [0034]) and “The present invention further provides a cDNA of a SARS coronavirus, wherein all or part of a nucleotide sequence of the cDNA is deleted and wherein the nucleotide sequence is selected from the group consisting of a nucleotide sequence encoding… ORF3a, ORF3b…” (¶ [0052]). Therefore, Baric teaches a system with SARS-CoV RNA with genes deleted, as well as a helper cell with at least one helper RNA that encodes the deleted genes. Therefore, there could be more than one helper RNA within the helper cell and it would be obvious to separate the selected genes onto two separate RNAs. While Baric teaches that the ORF3 and E genes can be selected from a list, they do not provide a reason for choosing this combination of genes.
However, Castano-Rodriguez teaches regarding SARS-CoV: “The Δ3a and ΔE mutants grew to lower titers than the parental wild-type (wt) virus (Fig. 1A). However, while the ΔE mutant showed 100-fold-lower titers (around 8 105 PFU/ml), Δ3a titers decreased slightly (3-fold) (3 107 PFU/ml). These results show that both proteins were required for optimal virus replication in cell culture.” (Page 3, ¶ 2). Castano-Rodriguez also teaches “Collectively, these results demonstrate key roles for the ion channel and PBM domains in optimal virus replication and pathogenesis and suggest that the viral viroporins and PBMs are suitable targets for antiviral therapy and for mutation in attenuated SARS-CoV vaccines” (Abstract, ¶ 2), wherein ORF3 and E are viroporins. Since the ORF3 and E genes are required for optimal virus replication in SARS-CoV, it would have been obvious to one of ordinary skill before the filing date to delete these two genes when making a replication-deficient virus. This is important because replication-deficient, or attenuated, viruses are used in vaccines for their safety and ability to elicit an immune response without being able to replicate or spread disease in the recipient. A rationale to support a conclusion that a claim would have been obvious is that there is some teaching, suggestion, or motivation in the prior art or in the knowledge generally available to one of ordinary skill in the art to modify the reference or combine reference teachings, and the modification or combination would have a reasonable expectation of success. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, G. and 2143.02).
Neither Baric nor Castano-Rodriguez teach using this method for SARS-CoV-2. However, Hatmal teaches that SARS-CoV and SARS-CoV-2 have very similar structure, as seen below in Figure 1A:
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Since the structure of both coronaviruses are very similar, it would have been obvious to one of ordinary skill before the time of filing to use the method made obvious by Baric and Castano-Rodriguez and substitute the SARS-CoV used in the method for SARS-CoV-2 with a reasonable expectation of success due to the structural similarity between SARS-CoV viruses. The same benefits from the deletions above would be expected in both viruses by a person of ordinary skill in the art. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
Regarding claims 2 and 6, Baric further teaches “SARS Vector Replicon Design: First, a determination will be carried out regarding whether any of the group specific ORFs (X1-X5) can be deleted and replaced with either luciferase or GFP. […] The overall goal is to identify a group specific ORF that can be deleted and replaced with an indicator gene that allows for easy visualization of replication and gene expression.” (¶ [0052]).
Regarding claim 5, Baric further teaches “Mutations were introduced to the TRS site by utilizing the `no see'm` strategy. […] This resulted in Amplicon 1 (TRS2), by PCR, with three mutations (CCGGAT) in the TRS site…” (¶ [0191]).
Regarding claim 10, Baric further teaches “A further embodiment of this invention is a method of making infectious, multiplication-defective, coronavirus particles, comprising: a) providing the helper cells of this invention: and b) producing coronavirus particles in the helper cell. Optionally, the particles can be collected from the cells.” (¶ [0121]) and “the helper cell can be provided by introducing the replicon RNA and/or the helper RNA into the helper cell by electroporation.” (¶ [0122]).
21. Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Baric (Supra), Castano-Rodriguez (Supra), and Hatmal (Supra) as applied to claims 1-2 and 4-10 above, and further in view of Chang (October 2010, Virol. Sin., 25(5): 361-368).
Regarding claim 3, Baric, Castano-Rodriguez, and Hatmal make claim 1 obvious as seen supra. All discussions thereon above incorporated here. Baric further teaches “The DNAs of this invention can further comprise a promoter to direct the transcription of the helper RNA and the replicon RNA, respectively, in the helper cell.” (¶ [0120]) and later uses the CMV promoter in the working examples
(¶ [0144]). Baric does not specifically discuss an inducible promoter.
However, Chang teaches “The Tet-On gene expression systems is a regulated, high-level gene expression system. Maximal expression levels in Tet-On systems are very high and compare favourably with the maximal levels obtainable from strong, constitutive mammalian promoters such as CMV. In this study, we established a series of double stable SARS-CoV nucleocapsid protein-expressing cell lines derived from BHK-21, and the expression was tightly regulated in response to induce doxycycline in a precise and dose-dependent manner.” (Page 362, ¶ 3).
Therefore, it would have been obvious to one of ordinary skill before the time of filing to take the system made obvious by Baric, Castano-Rodriguez, and Hatmal and further include a Tet-on inducible promoter as it performs comparably to the CMV promoter but is able to be controlled. A rationale to support a conclusion that a claim would have been obvious is that there is some teaching, suggestion, or motivation in the prior art or in the knowledge generally available to one of ordinary skill in the art to modify the reference or combine reference teachings, and the modification or combination would have a reasonable expectation of success. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, G. and 2143.02).
22. Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Baric (Supra), Castano-Rodriguez (Supra), Hatmal (Supra), and Chang (Supra) as applied to claim 3 above, and further in view of Gammell (WO 2008015662 A1; 07 February 2008).
Regarding claims 11-12, a replication defective genome and a producer cell line that complements the genome is made obvious supra by Baric, Castano-Rodriguez, Hatmal, and Chang. All discussions thereon above incorporated here. None of these references teach adding the products to a kit.
However, Gammell teaches “The invention also provides a kit useful for producing recombinant biological products, the kit comprising: (a) a mammalian producer cell line; (b) means for transfecting the cells with a miRNA molecule of Table 1 ; and/or (c) means for transfecting the cells with an inhibitor of one of the miRNA molecules of Table 1.” (Page 8, line 30 to page 9, line 2).
Therefore, it would have been obvious to one of ordinary skill before the time of filing to add both of the obvious product to a kit. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
Conclusion
23. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA E LY whose telephone number is (571)272-5169. The examiner can normally be reached Monday - Thursday, 8:00 am - 5:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KRISTINA E. LY/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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