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 .
Priority
Acknowledgement is made of Applicants’ claim for benefit to prior filed US Provisional application 63/123,570 (filed on 12/10/2020).
Election/Restriction
Applicant’s election without traverse of Group I, corresponding to claims 1-5, 20-22, 33-35, 37, 40, 42, and 43, in the reply filed on 04 February, 2026 is acknowledged. Claims 56, 61, 72, 77, 80, and 81 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 reply filed on 04 February, 2026.
Specification
The use of the term “T-Rex”, which is a trade name or a mark used in commerce, has 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.
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.
Claims 2-4, 20, and 42 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.
The term “preferably” in claims 2, 20, and 42 renders the claim indefinite because it is unclear whether the limitation(s) following the term are part of the claimed invention. See MPEP § 2173.05(d). The dependent claims do not add additional clarity, and therefore, are also indefinite.
The phrase “most preferably” in claims 2 and 20 renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The dependent claims do not add additional clarity, and therefore, are also indefinite.
The term “about” in claims 2-4 and 20 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The MOI, time after inoculation, and bioreactor volume are rendered indefinite by the use of the term “about”. The dependent claims do not add additional clarity, and therefore, are also indefinite.
The phrase “at least about” in claim 20 is a relative phrase which renders the claim indefinite. The phrase “at least about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The bioreactor volume is rendered indefinite by the use of the phrase “at least about”.
Claim 37 contains the trademark/trade name “T-Rex”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe HEK293 cells that stably express the tetracycline repressor protein and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 103
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.
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 1-3, 20, 22, 33-35, 37, 40, and 42-43 are rejected under 35 U.S.C. 103 as being unpatentable over Fedosyuk, et al. (Vaccine. 2019 Nov 8;37(47):6951-6961., NPL-IDS, filed, 5/30/2024, hereinafter “Fedosyuk”) in view of Fassit (Encyclopedia of Virology. 1999:1408–13).
Regarding claim 1, Fedosyuk teaches a method of producing an adenovirus for use in a vaccine (pg. 6951, Abstract), the method comprising: (a) adding adenovirus to a cell population in culture (pg. 6953, column 1); (b-c) culturing the cells under conditions that allow for infection and viral replication (pg. 6953, column 1 and Figure 1); and (d) harvesting the adenovirus (pg. 6954, column 2). Fedosyuk does not teach that adenovirus infection occurs at an MOI insufficient for infection of all the cells in culture.
However, Fassit teaches methods for propagating viruses including adenoviruses and further teaches that adenovirus preparations may contain up to 1000 defective particles per infectious virion and in order to generate as few defective particles as possible, adenovirus infection should occur at an MOI of 0.01 (1 infectious viral particle per 1000 cells) (pg. 1411, column 2).
It would have been prima facie obvious to one or ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Fedosyuk for a method of producing an adenovirus for use in a vaccine and the teachings of Fassit for infecting cells with a low MOI of adenovirus. Fassit provides motivation by teaching that adenovirus preparations may contain up to 1000 defective particles per infectious virion and in order to advantageously generate as few defective particles as possible, adenovirus infection should occur at an MOI of 0.01 (1 infectious viral particle per 1000 cells) (pg. 1411, column 2). One of ordinary skill would have had a reasonable expectation of success in combining Fedosyuk and Fassit because the both teach adenovirus propagation.
Regarding claim 2, Fassit teaches infecting cells with an MOI of 0.1 of adenovirus (pg. 1411, column 2).
Regarding claim 3, Fedosyuk teaches infecting cells immediately after cell seeding (pg. 6953, column 1).
Regarding claim 20, Fedosyuk teaches culturing the cells in a 3L bioreactor (pg. 6953, column 1).
Regarding claim 22, Fedosyuk teaches adding L-glutamine to the cell media (pg. 6952, column 2).
Regarding claims 33-35 and 37, Fedosyuk teaches that the cells are HEK293 T-rex cells (pg. 6952, column 2).
Regarding claims 40 and 43-43, Fedosyuk teaches that the virus is ChAdOx2 and ChAd63 (pg. 6952, column 2).
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially is absence of evidence to the contrary.
Claims 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Fedosyuk and Fassit as applied to claims 1-3, 20, 22, 33-35, 37, 40, and 42-43 above, and in further view of Adenovirus Production Protocol (Published by Genemedi in 2018 available at https://www.genemedi.net/pdf/Adenovirus%20production%20protocol-packaging%20concentration%20and%20purification-GeneMedi.pdf, hereinafter “Genemedi”).
As discussed above, claims 1-3, 20, 22, 33-35, 37, 40, and 42-43 were rendered prima facie obvious over Fedosyuk and Fassit.
Regarding claim 4, Fedosyuk and Fassit do not teach infecting cells 24 hours after cell seeding. However, routine optimization of the time between seeding and infection taught by Fedosyuk would have led to the claimed time period of 24 hours because Genemedi teaches that cell confluency should be 50-70% at the time of infection and that the time that takes and the number of cells seeded is a parameter that requires optimization to achieve the best results (pg. 9). The person of ordinary skill in the art would have found it obvious to optimize the time period between cell seeding and infection to achieve the desired cell density by starting at the time period taught by Fedosyuk because Genemedi teaches that cell confluency should be 50-70% at the time of infection and that the time that takes and the number of cells seeded is a parameter that requires optimization to achieve the best results (pg. 9).
It would have been further be obvious that the time period between cell seeding and viral infection is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal time period of between cell seeding and infection needed to achieve the desired results.
Regarding claim 5, Fedosyuk and Fassit teach a method of producing an adenovirus for use in vaccines (see claim 1). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to repeat the infection steps taught by Fedosyuk and Fassit after a first round of infection in order to obtain the same and predictable benefit of amplification of adenoviruses as taught by Genemedi (pg. 7).
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially is absence of evidence to the contrary.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Fedosyuk and Fassit as applied to claims 1-3, 20, 22, 33-35, 37, 40, and 42-43 above, and in further view of Genzel, et al. (Vaccine. 2006 Apr 12;24(16):3261-72., hereinafter “Genzel”).
As described above, claims 1-3, 20, 22, 33-35, 37, 40, and 42-43 were rendered prima facie obvious over Fedosyuk and Fassit.
Regarding claim 21, Fedosyuk and Fassit not teach not replacing the cell media or adding media to the cell culture. However, Genzel teaches methods of serum-free viral production to avoid washing steps and medium exchange and further teaches that not adding or replacing media during infection can simplify the infection process and reduced sterility issues during infection and cell culturing (Abstract).
It would have been prima facie obvious to one or ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Fedosyuk and Fassit for a method of producing an adenovirus for use in a vaccine and the teachings of Genzel for not replacing or adding cell media after infection. Genzel provides motivation by teaching that that not adding or replacing media during infection can simplify the infection process and reduced sterility issues during infection and cell culturing (Abstract). One of ordinary skill would have had a reasonable expectation of success in combining Fedosyuk, Fassit, and Genzel because the all teach viral propagation.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially is absence of evidence to the contrary.
Conclusion
NO CLAIMS ARE ALLOWED
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Cassandra Senn Grizer whose telephone number is (571)272-2292. The examiner can normally be reached M-Th 0630 - 1700 ET.
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/CASSANDRA SENN GRIZER/ Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672