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 .
DETAILED ACTION
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119€ or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The earliest possible effective filing date for the instant claims is 12/10/2020 based on the filing date of the provisional application 63/123,564.
Status of Claims
Claims 1-5, 12, 19, 21, 27, 32-33, 40, 42-46, 54, 56-60, 63-66 were pending.
Claims 1, 4, and 58 are amended.
Claims 57, 64-66 are cancelled.
Claims 1-5, 12, 19, 21, 27, 32-33, 40, 42-46, 54, 56, 58-60, 63 are under consideration.
Specification
(previous objection, withdrawn) The disclosure is objected to because of the following informalities:
The use of the term T-RExTM, Millistak+®HC, Millipore Express®, Mustang®, Sartobind®, Fractogel®, to name a few 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.
Appropriate correction is required.
Applicant contends: A replacement specification is submitted concurrently herewith, including appropriate reference to trade names and generic. Reconsideration and withdrawal of the objections is requested.
Office response: The replacement specification is acknowledged. The objection is withdrawn.
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.
(previous rejection, withdrawn) Claims 1-5, 12, 19, 21, 27, 32-33, 40, 42-46, 54, 56-60, 63, 64, 66 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.
a. (amended) Claims 1, 4 contain the language “at least about…” which is an unclear threshold. To remedy, remove the phrase “at least about” (for example, “a cell density of at least 4x106”). The dependent claims do not add additional clarity and, therefore, are also indefinite.
b. (amended) Claim 44 contains language “greater than or equal to about 2.4x106 ifu/ml” which is unclear. To remedy, remove word “about” to better define the threshold.
c. (cancelled) Claim 57 (amended) Claim 58 contain 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 cells and, accordingly, the identification/description is indefinite.
d. (amended) Claim 58 also recites “consists of mammalian cells, e.g. T-REx cells. Regarding claim 58, the phrase "such as" (e.g.) renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. As a result, claim 58 is broadly interpreted as “The method of claim 1 wherein the host cell population consists of mammalian cells” (See MPEP § 2173.05(d)).
e. (cancelled) Claim 64 recites the method of claim 1 wherein the adenovirus encodes nCov-19 spike protein. However, an adenovirus itself does not encode a protein. However, an adenovirus vector can be made in such a way as to express an nCov-19 spike protein. It is also unclear if the inventor means the entire nCov-19 spike protein or a fragment of the nCov-19 spike protein.
f. (cancelled) Claim 66 recites a drug substance obtainable by or obtained by the method of claim 1. However, claim 46 recites the method of claim 1 wherein the method further comprises subjecting the TFF product or formulated product to sterile filtration to provide a drug substance which is consistent with what is written in the specification. As a result, it is unclear what is meant by “drug substance” in claim 66.
See claims 1-5, 12, 19, 21, 27, 32-33, 40, 42-46, 54, 56, 58-60, 63 as submitted 03/27/2026
Applicant contends: Applicant traverses the rejection. However, in an effort to advance prosecution, the present claims have been amended, rendering each of the objections moot. Reconsideration and withdrawal of the rejections under 112 for indefiniteness and improper dependency is thus respectfully requested.
Applicant cancelled claims 57, 64-66.
Office response:
Applicant’s traversal of the rejections is acknowledged.
The applicant’s amendments and cancellations are acknowledged. And as a result of the amendments and cancellation, the rejections are withdrawn.
Claim Rejections - 35 USC § 101
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.
(previous rejection; withdrawn) Claims 65, 66 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. This judicial exception is not integrated into a practical application and claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below. See MPEP § 2106.04 for analysis parameters.
Applicant contends: Rejection is rendered moot in view of cancelled claims 65 and 66.
Office response: Cancellation of claims 65 and 66 are acknowledged. Accordingly, the claim 65 and 66 rejections are withdrawn.
Claim Rejections - 35 USC §§ 102/103
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 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.
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.
(previous rejection; withdrawn as necessitated by cancellation of claims) Claims 65 and 66 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Duffy et al. (Duffy) (See PTO-892 Notice of References Cited).
Applicant contends: Rejection is rendered moot in view of cancelled claims 65 and 66.
Office response: Applicant’s cancellation of claims 65 and 66 is acknowledged. Accordingly, the rejections for claims 65 and 66 are withdrawn.
(previous rejection, withdrawn as necessitated by amendment as to claims 1, 3, 5, 12, 27, 32, 40, 43, 54, 56, 58, 59) Claims 1, 3, 5, 12, 27, 32, 40, 43, 54, 56, 58, 59 are rejected under 35 U.S.C. 103 as being unpatentable over Weggeman et al. (Weggeman) (See IDS submitted 5/30/2024) in view of Leo de Vocht (Leo de Vocht)(US8470585B2)(See PTO-892: Notice of References Cited).
(previous rejection; withdrawn as necessitated by amendment to claim 1) Claims 2 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Weggeman in view of Leo de Vocht as applied to claim 1 above, and further in view of Shen et al. (Shen) (See PTO-892: Notice of References Cited) and in view of Altaras et al. (Altaras) (See IDS submitted 5/30/2024).
(previous rejection; withdrawn as necessitated by amendment to claim 1) Claims 19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Weggeman in view of Leo de Vocht as applied to claim 1 above, and further in view of Cherradi et al. (Cherradi) (See PTO-892 Notice of References Cited).
(previous rejection; withdrawn as necessitated by amendment to claim 1) Claims 33 is rejected under 35 U.S.C. 103 as being unpatentable over Weggeman in view of Leo de Vocht as applied to claim 1 above, and further in view of Keszey et al. (Keszey)(WO2020200980A1) (See PTO-892 Notice of References Cited).
(previous rejection; withdrawn as necessitated by amendment to claim 1) Claims 45 and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Weggeman in view of Leo de Vocht as applied to claim 1 above, and further in view of Adriaansen et al. (Adriaansen)(WO2015040234A1) (See PTO-892 Notice of References Cited).
(previous rejection; withdrawn as necessitated by cancellation) Claims 57 is rejected under 35 U.S.C. 103 as being unpatentable over Weggeman in view of Leo de Vocht as applied to claim 1 above, and further in view of Cates et al. (Cates)(US20050124067) (See PTO-892 Notice of References Cited).
(previous rejection; withdrawn as necessitated by amendment to claim 1) Claims 60,63 are rejected under 35 U.S.C. 103 as being unpatentable over Weggeman in view of Leo de Vocht as applied to claim 1 above, and further in view of Morris et al. (Morris) (See PTO-892 Notice of References Cited).
(previous rejection; withdrawn as necessitated by claim cancellation) Claim 64 is rejected under 35 U.S.C. 103 as being unpatentable over Weggeman in view of Leo de Vocht as applied to claim 1 above, and further in view of Fernandez-Garcia et al. (Fernandez-Garcia)(See PTO-892 Notice of References Cited).
RESPONSE TO ARGUMENTS
Applicant contends:
Applicant respectfully traverses the rejections under 103. In the interest of brevity and in view of each of the rejections reliance primarily on Weggeman, the rejections are addressed collectively.
Weggeman (US 2009/0123989 A1) teaches purification by ultrafiltration/diafiltration (UF/DF) conducted under permeate back-pressure to improve recovery and purity. It expressly contemplates a filtration-only route in which anion-exchange chromatography (AEX) may be omitted; however, where AEX is included, it is performed only after UF/DF and not immediately post-clarification. Thus, Weggeman neither discloses nor suggests, the method order "clarification -- AEX -> TFF" recited in the pending claims. Rather, Weggeman specifically teaches away from use of AEX, particularly as used in the instant claims.
De Vocht (US 8,470,585 B2) addresses high-cell-density harvests by combining selective host-cell-DNA precipitation with tangential-flow filtration (TFF) as the clarification step and reports that direct TFF clarification fails at high density without the precipitation step. Its core teaching is to place TFF up front, before any capture step. Thus, like Weggeman, De Vocht also teaches away from use of an AEX-first capture route following clarification as claimed in the present methods.
A person of ordinary skill would have no reasoned motivation to remove the pre-AEX TFF step that both references rely upon (indeed, the teachings caution against due to fouling and/or pressure issues absent such front-end TFF). Neither disclosure would motivate one to insert AEX directly after clarification particularly at the scales and loads contemplated in the present application. Any proposal to re-order the steps as "clarification -- AEX -> TFF" can only be based on impermissible hindsight and contradict the express teachings and process rationales of Weggeman and De Vocht.
None of Cherradi et al., Keszey et al., Adriaansen et al., Cates et al., Morris et al., or Fernandez-Gracia et al., whether alone or in any combination, remedy the deficiencies of Weggeman and De Vocht. As such, none of the asserted rejections support a prima facie case of obviousness. Reconsideration and withdrawal of the obviousness rejections are thus respectfully requested.
Even assuming arguendo one would contemplate to re-order the prior-art steps, the
results achieved could not have been anticipated in view of the disclosures or knowledge of one skilled in the art. The present application provides evidence that eliminating pre-AEX TFF yields unforeseen advantages over the disclosures cited: a materially shorter cycle time (the removal of the intervening TFF step shortened processing by approximately one day), reduced raw-material consumption and waste, and drug-substance meeting the specified quality attributes. These results run counter to the prior art's expectation that upstream TFF is a necessary step to protect capture and achieve purity. The results were unexpected over any disclosure of Weggeman, De Vocht, or any of the secondary references, whether alone or collectively. As such, even in view of such disclosures, the provided methods are non-obvious and patentable over the express teachings and process rationales of Weggeman, De Vocht, Cherradi et al., Keszey et al., Adriaansen et al., Cates et al., Morris et al., and Fernandez-Gracia et al., whether alone or in any combination. Reconsideration and withdrawal of the rejections under 103 is respectfully requested.
Office Response
Applicant cancelled claims 57 and 64 and so rejection is moot.
Applicant amended the claim with “wherein the clarified sample is processed without any intervening concentration step, ultrafiltration, diafiltration, or tangential-flow filtration prior to step (b).
Support for the amendment can be found in the specification (submitted 06/08/2023) on page 15: The methods of the present invention are characterized in that the clarified sample (e.g. clarified lysate) is processed by anion exchange chromatography without any intervening concentration steps such as TFF. Elimination of an intervening concentration step (e.g. TFF) results in significant process simplification and reduced raw material consumption and
eliminates a large volume of waste stream. The elimination of an intervening concentration step (e.g. TFF) between clarification and anion exchange chromatography can drastically reduce processing time; in the methods of the present invention, removal of this step shortened processing time by one day. Thus, the methods of the present invention have improved scalability and throughput but still provide acceptable product quality (as shown in
Example 3). Therefore no new matter has been added.
Applicant' s arguments, see pages 7-9 filed 03/27/2026 with respect to claims Claims 1, 3, 5, 12, 27, 32, 40, 43, 54, 56, 58, 59 have been fully considered and are persuasive but only with respect to the Weggeman (20090123989) reference teachings. Initially, latitude was afforded to the order of steps based on claim language. For example, reference claim 1 recites “said method comprising: a step of ultrafiltration”…and reference claim 11. “The method according to claim 7, said method further comprising a step of further purifying the recombinant adenovirus with at least one chromatography step” where in reference claim 11, “the recombinant adenovirus” is used rather than, for example, “the retentate” from the ultrafiltration process. However, on further review of both the claims and the specification, it appears more likely that an order is implied with anion exchange chromatography occurring after the ultrafiltration step.
Thus, the previous rejection of Claims 1-5, 12, 19, 21, 27, 32-33, 40, 42-46, 54, 56, 58-60, 63 has been withdrawn.
(new, necessitated by amendment to claim 1) Claims 1, 3, 5, 12, 27, 32, 40, 43, 54, 56, 58, 59 are rejected under 35 U.S.C. 103 as being unpatentable over Weggeman et al. (Weggeman 2005)(WO2005080556A2) in view of (Leo de Vocht)(US8470585B2)(See PTO-892: Notice of References Cited).
See claims 1, 3, 5, 12, 27, 32, 40, 43, 54, 56, 58, 59 as submitted 03/27/2026.
Regarding claim 1, 3, Weggeman 2005 teaches reference claim 1, A method for the purification of a virus from a host cell, said method comprising in the given order the steps of: a) culturing host cells that are infected with a virus, e.g., as stated in reference claim 4, a recombinant adenovirus. Weggeman 2005 teaches reference claim 2, A method according to claim 1, said method further comprising: d) clarification of the lysate and reference claim 8, A method according to any one of claims 2-7, wherein step d) comprises depth filtration and membrane filtration. Weggeman 2005 teaches reference claim 3, A method according to claim 1 or claim 2, said method further comprising: e) further purifying the virus with at least one chromatography step and reference claim 12, A method according to any one of claims 4-11, wherein step e) comprises anion exchange chromatography. Weggeman 2005 teaches in the specification, UF/DF can be used to concentrate and/or buffer exchange the virus suspensions according to the present invention in different stadia of the purification process, e.g. the lysate and/or further purified virus suspensions such as those that have undergone chromatography (p. 23). Thus, in an embodiment, Weggeman 2005 suggests a method of clarification of the lysate (reference claim 2) followed by anion exchange chromatography (reference claims 3 and 12) followed by UF/DF.
Regarding claim 5, 12, Weggeman 2005 teaches claim 1, A method for the purification of a virus from a host cell, said method comprising in the given order the steps of: a) culturing host cells that are infected with a virus, b) adding nuclease to the cell culture, and c) lysing said host cells to provide a lysate comprising the virus.
Regarding claim 27, Weggeman 2005 teaches in addition to anion exchange columns, anion exchange membrane chromatography products such as those produced by Pall (e.g. Mustang™ series) and Sartorius (e.g. Sartobind series) are suitable (p. 26).
Regarding claim 32, Weggeman 2005, teaches any clarification approach including dead-end filtration, microfiltration, centrifugation, or body feed of filter aids (e.g. diatomaceous earth) in combination with dead-end or depth filtration, which provides a filtrate of suitable clarity to not foul the membrane and/or resins in the subsequent steps, will be acceptable to use in the clarification step of the present invention (p. 20).
Regarding claim 40, Weggeman 2005 teaches Diafiltration (DF) , or buffer exchange, using ultrafilters is an ideal way for removal and exchange of salts, sugars, non- aqueous solvents separation of free from bound species, removal of material of low molecular weight, or rapid change of ionic and/or pH environments…In one embodiment according to the invention, the lysate is concentrated by UF/DF 5-fold, and the resulting concentrated virus suspension is buffer exchanged with 6 diafiltration volumes (DFV) of a buffer comprising 1 M NaCl, using a constant volume diafiltration method (p. 23).
Regarding claim 43, Weggeman 2005 teaches In another aspect, the invention provides a batch of recombinant adenovirus comprising a transgene chosen from the group consisting of: an Ebolavirus nucleoprotein, an Ebolavirus glycoprotein, a Plasmodium falciparum circumsporozoite gene, and measles virus hemagglutinin, said batch characterized in that it contains less than 0.1 ng host cell DNA per 1E11 viral particles (p. 6).
Regarding claims 54 and 58, Weggeman 2005 teaches Examples of other useful mammalian cell lines that may be used directly as host cells for propagating viruses or converted into complementing host cells for replication deficient virus are Vero and HeLa cells and cell lines of Chinese hamster ovary, W138, BHK, COS-7, HepG2, 3T3, RIN and MDCK cells, as known to the person skilled in the art (p. 8).
Weggeman 2005 does not teach does not teach the host cell population density of at least 4x106 cells per ml, HEK cells, or specifically state replication deficient adenoviruses.
Regarding claims 1 – preamble, 56, and 59, Leo de Vocht, however, teaches claim 1(b) lysing with a detergent, cells within the host cell suspension having a cell density between 5x10⁶ and 150x10⁶ cells/mL (as recited in claim 1 preamble); propagation of E1-deficient rAd35, specific producer cells that express E1B-55K of Ad35 can be constructed, for instance based on existing producer cells that express E1A and E1B of Ad5 such as PER.C6 or HEK293 cells (as recited in claim 56); and the replication-deficient adenoviral vector can be generated by using any species, strain, subtype, or mixture of species, strains, or subtypes, of an adenovirus or a chimeric adenovirus as the source of vector DNA (as recited in claim 59).
One of ordinary skill in the art would have been motivated to combine the teachings of Weggeman 2005, e.g. with respect to purifying adenoviruses with a clarifying step, followed by an anion exchange step, and further followed by a TFF (UF/DF) step and the teachings of Leo de Vocht, e.g. a suggested host cell suspension cell density, host cell population cells, a replication deficient adenovirus to arrive at the current invention in order to improve the adenovirus purification process in order to increase efficiency, yield and purity of product (See MPEP 2143 Rationale A. Combining prior art elements according to known methods to yield predictable results and Rationale G. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
One of ordinary skill in the art would have had a reasonable expectation of success using known purification steps as taught by Weggeman 2005 using details such as a starting cell density, cell types, and a replication deficient adenovirus as taught by Leo de Vocht to devise the method of purifying adenovirus from an adenovirus-containing sample. There would have been a reasonable expectation of success given the underlying materials and methods are known within the adenovirus, adenovirus vector fields, gene therapy fields, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
(new, necessitated by amendment to claim 1) Claims 2 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Weggeman 2005 in view of Leo de Vocht as applied to claims 1, 3, 5, 12, 27, 32, 40, 43, 54, 56, 58, 59 above, and further in view of Shen et al. (Shen) (See PTO-892: Notice of References Cited) and Altaras et al. (Altaras) (See IDS submitted 5/30/2024).
See claims 2 and 4 as submitted 03/27/2026
Weggeman and Leo de Vocht teach the method of claim 1.
Weggeman and Leo de Vocht do not teach wherein the anion exchange product is processed in a further step by mixed mode size exclusion chromatography to provide a mixed mode size exclusion product and wherein the mixed mode exclusion product is processed by TFF of step (c).
However, Shen teaches an IEX column pre-equilibrated with 300 mM NaCl in Buffer A (50 mM HEPES, 2 mM MgCl2, 2% sucrose, pH 7.5), and then was washed with the equilibrating buffer followed by consecutive steps of 450 mM NaCl in Buffer A, 600 mM NaCl in Buffer A and 1 M NaCl in Buffer A. The IEX purified adenovirus eluate was collected, diluted with Buffer A to reach ∼0.5 M NaCl in Buffer A, filtered through a 0.45 μm CA membrane and loaded onto a 74 mL Capto Core 700 multimodal chromatography column previously equilibrated with 0.5 M NaCl in Buffer A for polishing. The flow through pool was collected (p. 3382).
In the specification, the inventors clarify that the mixed mode size exclusion chromatography can be performed with mixed mode size exclusion resins including but not limited to Capto Core 700(Cytiva), Capto Core 400 (Cytiva) and Monomix Core 60 (Sepax Technologies).
Altaras teaches Table 1 which summarizes different companies’ adenovirus cultivation examples. In the column for Canji, Altaras reports an infection cell density of 5 x 106 to 1 x 107 cells/mL)(p. 213)(as recited in claim 4).
One of ordinary skill in the art would have been motivated to start with a host cell population of 1x107 as taught by Altaras, proceed with lysis, clarification and chromatography and then take the anion exchange product and run it through the Capto Core 700 multimodal chromatography column as taught by Shen in order to advantageously remove cellular proteins and improve purity of the product (See MPEP 2143, Rationale A: Combining prior art elements according to known methods to yield predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success for processing the product through an additional Capto Core 700 multimodal chromatography column step as taught by Shen. There would have been a reasonable expectation of success given the underlying materials and methods are known within the field of protein purification, vaccinology, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
(new, necessitated by amendment to claim 1) Claims 19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Weggeman 2005 in view of Leo de Vocht as applied to claims 1, 3, 5, 12, 27, 32, 40, 43, 54, 56, 58, 59 above, and further in view of Cherradi et al. (Cherradi) (See PTO-892 Notice of References Cited).
Claims 19 and 21 as submitted 03/27/2026.
Weggeman 2005 and Leo de Vocht teach claim 1.
Weggeman 2005 and Leo de Vocht do not teach wherein the depth filtration in step (a) comprises using a single type of depth filter (as recited in claim 19) nor wherein the depth filtration in step (a) comprises using at least two different depth filters in series (as recited in claim 21).
However, Cherradi teaches there are several types of depth filters available, including conventional, graded density, and newer synthetic products. For clarification, they have nominal pore sizing of 0.1–60 µm and are often multilayer. Depth filter devices are available in a wide range of sizes to accommodate process development scale (1–10 L) through commercial manufacturing scales (200 L to >2,000 L), and individual devices can be stacked together in a non-product contact holder to provide linear scalability. Depth filters are thus true “plug-and-play” solutions, as these single-use devices require no clean-in-place solution (p. 2, third paragraph).
One of ordinary skill in the art would have been motivated to use either a single type of depth filter from a variety of options or at least two different depth filters in series as taught by Cherradi to improve clarification of the adenovirus-containing sample. While best known for size exclusion, the depth filters are also beneficial for retaining larger contaminants and also physically adsorbing some contaminants, too (See MPEP 2143, Rationale A: Combining prior art elements according to known methods to yield predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success with either a single type of depth filter or at least two different depth filters in series as taught by Cherradi. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
(new, necessitated by amendment to claim 1) Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Weggeman 2005 in view of Leo de Vocht as applied to claims 1, 3, 5, 12, 27, 32, 40, 43, 54, 56, 58, 59 above, and further in view of Keszey et al. (Keszey)(WO2020200980A1) (See PTO-892 Notice of References Cited).
Claims 33 as submitted 03/27/2026.
Weggeman 2005 and Leo de Vocht teach claim 1.
Weggeman 2005 and Leo de Vocht do not teach that the anion exchange product undergoes microfiltration.
However, Keszey teaches a microfiltration step post anion exchange for purifying immunoglobulins in order to remove a microbial contaminant. Keszey also teaches the microfiltration step prior to a tangential flow filtration (TFF) comprising ultrafiltration and diafiltration (See Figure 3) which is consistent with the steps claim 1(b), followed by 1(c) in the instant application.
One of ordinary skill in the art would have been motivated to add an extra microfiltration step as taught by Keszey post anion exchange chromatography in order to advantageously reduce the microbial load of and improve the purity of an adenovirus product (See MPEP 2143, Rationale A: Combining prior art elements according to known methods to yield predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success with adding a microfiltration step with the intent of reducing microbial contaminants as taught by Keszey. There would have been a reasonable expectation of success given the underlying materials and methods are known in the context of the adenovirus and adenovirus vector, immunoglobulin, and in general protein purification fields, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
(new, necessitated by amendment to claim 1) Claims 45 and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Weggeman 2005 in view of Leo de Vocht as applied to claims 1, 3, 5, 12, 27, 32, 40, 43, 54, 56, 58, 59 above, and further in view of Adriaansen et al. (Adriaansen)(WO2015040234A1) (See PTO-892 Notice of References Cited).
Claims 45 and 46 as submitted 03/27/2026.
Weggeman 2005 and Leo de Vocht teach claim 1.
Weggeman 2005 and Leo de Vocht do not teach wherein the method further comprises formulating the TFF product to provide a formulated product nor wherein the method further comprises subjecting the TFF product or formulated product to sterile filtration to provide a drug substance.
However, Adriaansen teaches adenovirus formulations and related pharmaceutical products for use in e.g. gene therapy and/or vaccine applications. In particular, liquid formulations for adenoviruses are disclosed herein, which improve the adenoviral stability by preserving quantity, potency (infectivity) and quality of the contained adenovirus when stored in about the 2-8°C range or higher while also being compatible with parenteral administration [Field of Invention](as recited in claim 45).
In Example 1, Per formulation, 12 columns were used; eluates were pooled, sterile filtrated and stored at 2-8 °C in a glass bottle. Samples were taken for viral titer determination by vp- QPCR and all titers were adjusted with the appropriate buffer to 1.7xlOn vp/mL (as recited in claim 46).
One of ordinary skill in the art would have been motivated to use adenovirus formulations and sterile filtration as taught by Adriaansen to advantageously stabilize the composition and further remove impurities to improve its safety for administration to subjects (See MPEP 2143, Rationale A: Combining prior art elements according to known methods to yield predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success with the adenovirus formulations and sterile filtration as taught by Adriaansen. There would have been a reasonable expectation of success given the underlying materials and methods are known in the context of the adenovirus and adenovirus vector fields and vaccinology, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
(new, necessitated by amendment to claim 1) Claims 60, 63 are rejected under 35 U.S.C. 103 as being unpatentable over Weggeman 2005 in view of Leo de Vocht as applied to claims 1, 3, 5, 12, 27, 32, 40, 43, 54, 56, 58, 59 above, and further in view of Morris et al. (Morris) (See PTO-892 Notice of References Cited).
Claims 60 and 63 as submitted 03/27/2026.
Weggeman 2005 and Leo de Vocht teach claim 1.
Weggeman 2005 and Leo de Vocht do not teach wherein the adenovirus is a simian adenovirus (as recited in claim 60) nor wherein the adenovirus is not a human adenovirus (as recited in claim 63).
However, Morris teaches adenovirus vaccine development has focused on simian-derived adenoviral vectors, which have the desirable vector characteristics of HAdV-C5 but with negligible seroprevalence in the human population (Abstract, p. 649). Key considerations in the design of SAd vectors for use as vaccines are similar to those for HAdV-C5. Leading nonhuman adenovirus candidates include vectors derived from simian adenoviruses (SAds) and in particular those derived from chimpanzee adenoviruses (termed ChAds or AdCs). The vaccine vector must be nonreplicating and unlike adenovirus gene therapy vectors have negligible immune modulatory activity (p. 649).
One of ordinary skill in the art would have been motivated to use simian adenoviruses as taught by Morris to advantageously overcome the human adenovirus seroprevalence seen in human populations (See MPEP 2143, Rationale A: Combining prior art elements according to known methods to yield predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success with simian adenoviruses as taught by Morris. There would have been a reasonable expectation of success given the underlying materials and methods are known in the context of the adenovirus and adenovirus vector fields, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
Allowable Subject Matter
Claims 42 and 44 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/C.C./Examiner, Art Unit 1672
/M FRANCO G SALVOZA/Primary Examiner, Art Unit 1672
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