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 .
The Examiner noted that the evidentiary reference cited in PTO892 on page 3 of office action mailed on 06/12/2026 was missing on PTO-892. Accordingly, this office action replaces the previous office action (mailed on 06/12/2026) and properly cited in PTO892 missing reference.
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 .
Claim Status
To expedite the compact prosecution, the Examiner is pursuing the amended claims dated 18 December 2024, in which applicant; amended claims 2-16. Therefore, claims 1-16 are pending in the application.
Priority
This application was filed 06/09/2024 and is a 371 application of PCT/GB2022/053136 filed on 12/08/2022, which claims benefit to the foreign application 2117844.7 filed on 12/09/2021. Thus, the earliest possible priority for the instant application is 12/09/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/18/2024 and 12/18/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner and the signed and initialed PTO Forms 1449 are mailed with this action.
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 1-2, 6, and 8-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Oh et al. (WO2019006390A1; cited in IDS filed 12/18/2024; hereinafter “Oh”) and evidentiary reference Millipore Inc. (Benzonase® Salt Tolerant Endonuclease; 23208979 Ver 1.0, Rev 05MAY2025; hereinafter “Millipore”).
Regarding claims 1-2, 13 and 14, Oh discloses a method for purifying an adeno-associated viral vector (AAV) vector particles comprising the step of lysing cells/particles harvested, treating the lysate to reduce nucleic acid contamination, optionally filtering the nucleic acid reduced lysate to produce a clarified lysate and subjecting said lysate to an cation exchange column (CEX) column chromatography to produce an eluate which is then subjected to an anion exchange column (AEX) chromatography, followed by size exclusion chromatography (SEC) and filtration (claim 1; [0121]). The sequence CEX[Wingdings font/0xE0]AEX[Wingdings font/0xE0]SEC can be inverted (claim 2; par [0122], [0134-0135]). Oh further discloses that the cation exchange column comprises a sulfonic acid cation exchanger (claim 46, [0049], [0127]) and the anion exchanger comprises a quaternary ammonium anion exchanger (claim 44, [0047], [0129]).
MPEP 2112.01(II) recites that if the composition is physically the same, it must have the same properties: "Products of identical chemical composition cannot have mutually exclusive properties. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Regarding the characteristics of claim 6 (some DNA is bound to the cation exchange column) of the claimed a cation exchange column have the same structure as the CEX column chromatography of Oh et al. and therefore would necessarily have the same characteristics, therefore, Oh anticipates the instant claims 6.
Regarding claim 8, Oh discloses that the flow-through from the cation exchange column is contacted directly with the anion exchanger (Fig. 1, [0068], [0144], [0151]).
MPEP 2112.01 state that “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established,” In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case regarding the claims 9-10, Oh discloses that the nuclease comprises benzonase (e.g., Final concentration, 2:50U/mL, such as 100U/mL [example 4, p. 41) is used to reducing contaminating nucleic acid (Claim 10, [0020], [0118]). Although Oh does not specifically mention that the benzonase is a salt active nuclease, however, evidentiary reference Millipore and google search teaches that the halotolerant endonuclease (often referred to as a Salt Active Nuclease or SAN) is a specialized enzyme that breaks down internal phosphodiester bonds within DNA and RNA, functioning optimally in environments with high salt concentrations (such as standard Benzonase). Therefore, POSITA at the time of the invention would not have expected that the method of purifying a viral vector preparation of Oh, wherein the viral vector eluate is treated using a halotolerant endonuclease (e.g., salt active nuclease Benzonase).
Regarding claims 11-12, Oh discloses that the SAN treated with the endonuclease, the viral vector eluate is filtered (p. 42 example 4 paragraph 2; [0118]) and the filtration is carried out by tangential flow filtration (TFF) (claim 6, [0154]).
Regarding claims 15 and 16, Oh discloses that the wherein the viral vector preparation is produced by culturing cells that produce the viral vector and harvesting a viral vector-containing supernatant from the cell culture (claim 1, [0156]), and the supernatant harvested from the cell culture is clarified (claim 1, Fig. 1).
Accordingly, Oh anticipates the instant claims 1-2, 6, and 8-16.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-2, 3-5, 6, 7 and 8-16 are rejected under 35 U.S.C. 103 as being unpatentable over Oh et al., (WO2019006390A1; cited in IDS filed 12/18/2024; hereinafter “Oh”) and evidentiary reference Millipore Inc. (Benzonase® Salt Tolerant Endonuclease; 23208979 Ver 1.0, Rev 05MAY2025; hereinafter “Millipore”), in view of Segura et al., (Biotechnology Advances 24 (2006) 321– 337, cited in PTO892; hereinafter “Segura”) and Klinker et al. (PloS one, 9(8), p.e104029, 2014; cited in PTO892; hereinafter “Klinker”)
As discussed previously, regarding claims 1-6, and 8-16, Oh discloses a method for purifying an adeno-associated viral vector (AAV) vector particles comprising the step of lysing cells/particles harvested, treating the lysate to reduce nucleic acid contamination, optionally filtering the nucleic acid reduced lysate to produce a clarified lysate and subjecting said lysate to an cation exchange column (CEX) column chromatography to produce an eluate which is then subjected to an anion exchange column (AEX) chromatography, followed by size exclusion chromatography (SEC) and filtration (claim 1; [0121] of Oh). The sequence CEX[Wingdings font/0xE0]AEX[Wingdings font/0xE0]SEC can be inverted (claim 2; par [0122], [0134-0135] of Oh). Oh further discloses that the cation exchange column comprises a sulfonic acid cation exchanger (claim 46, [0049], [0127] of Oh) and the anion exchanger comprises a quaternary ammonium anion exchanger (claim 44, [0047], [0129] of Oh).
Oh disclose the method of purifying adeno-associated viral vector preparation, however, regarding claims 3-5, Oh is silent to lentiviral vector is derived from a HIV-1. However, such was known in the prior art.
With respect to claims 3-5, Segura discloses an anion exchange chromatography exploits the negatively charged surface of retroviruses (i.e., HIV-1) for purification purposes. Ion exchange matrices show imperfect selectivity and high salt concentrations are required to elute retroviral particles (p. 332 “Ion-exchange chromatography” ¶).
MPEP 2143 (B) states that simple substitution of one known element for another to obtain predictable results. The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). Accordingly, it would have been obvious to practice the viral vector purifying method of Oh and substitute lentiviral vector that derived from a HIV-1 as taught by Segura with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Segura because ion exchange matrices show imperfect selectivity and high salt concentrations are required to elute retroviral particles. Consequently, in most cases further purification steps are required to eliminate similarly charged contaminants (i.e. DNA) and salt (p. 333 left col. 1st ¶). The POSITA would have had a reasonable expectation of success in combining the teachings of Oh and Segura because each of these teachings both successfully preparation viral vector using ion exchange column. Therefore, the products and method as taught by Oh et al. in view of Segura et al. would have been prima facie obvious over the products and method of the instant application. In regard to the reasonable expectation of success in doing so, substitute the lentiviral vector that derived from a HIV-1 in purifying method of Oh had a reasonable expectation of success since the steps thereof required no more than pipetting the appropriate HIV-1 concentration in ion exchange column and cell culture technology.
Regarding claim 7, Oh is silent to the viral vector preparation comprises histone and DNA.
With respect to claim 7, Klinker teaches a rapid DNA purification process using histones and cation exchange column (Fig. 1) and discloses that the histones carry a net positive charge at the pH of the buffer (pH 5.2), they bound to the cation exchange resin at low salt concentrations (p. 7 left hand col. 1st ¶). Therefore, histone could avoid DNA contaminations during filtering the solution through an anion exchange resin (p. 1 right col. 2nd ¶).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the 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 yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice the viral vector purifying method of Oh and include histone as taught by Klinker with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Klinker because histone could avoid DNA contaminations during filtering the solution through an anion exchange resin (p. 1 right col. 2nd ¶). The POSITA would have had a reasonable expectation of success in combining the teachings of Oh and Klinker because each of these teachings both successfully preparation DNA using ion exchange column. Therefore, the products and method as taught by Oh et al. in view of Klinker et al. would have been prima facie obvious over the products and method of the instant application. In regard to the reasonable expectation of success in doing so, include the histone in purifying method of Oh had a reasonable expectation of success since the steps thereof required no more than pipetting the appropriate histone concentration in ion exchange column and cell culture technology.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is 571-272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
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