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 .
Applicant’s amendment filed 11/21/2025 is acknowledged. Claims 2 and 10-16 are canceled.
All of the remaining amended claims filed on 11/21/2025, claims 1 and 3-9, are under examination on the merits.
Withdrawn Objections
The previous objections to claims 1-3, 7-8, 10, 14 and 15 are hereby withdrawn due to cancellation or amendment of the claims.
Withdrawn Rejections
The previous rejection of claims 2 and 10-16 under 35 U.S.C. §112(b) for being indefinite is withdrawn due to cancellation of the claims.
The previous rejection of claims 1 and 3-8 under 35 U.S.C. §102 is withdrawn due to amendment of the claims.
Maintained Rejections
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Previous Rejection Maintained in Part) Claims 1 and 3-9 are rejected under 35 U.S.C. 103 as being unpatentable over Hermens et al. (WO 2013036118 A1, published 3/14/2013; hereinafter referred to as “Hermens”) in view of Woods (supra). The rejection of claims 2 and 10-16 is withdrawn due to cancellation of the claims.
The claimed invention encompasses a method for separating larger viruses having a size of 45 nanometers or larger from smaller viruses smaller than 40 nanometers in size from a fluid, the method comprising (a) passing fluid containing viruses through a porous filter comprising a porous medium at a differential pressure of at least 20 pounds per square inch differential (psid) and obtaining viruses; (b) reducing the pressure to 3 psid or less; and, (c) passing additional fluid containing viruses through the porous filter comprising a medium at a pressure of at least 20 psid and obtaining additional viruses, as recited in claim 1. In different embodiments, the pressure in (b) is 0 psid, as recited in claim 3, is reduced for at least 2 minutes, as recited in claim 4, at least 5 minutes, as recited in claim 5, or is in the range of 2 minutes to 15 minutes, as recited in claim 6. In additional embodiments, the pressure in (a) and (c) is at least 30 psid, as recited in claim 7, or in the range of from 20 psid to 40 psid, as recited in claim 8. Alternatively, the obtained additional viruses are AAV, as recited in claim 9.
The Prior Art
Hermens teaches separation of viruses in a sample by filtration (Abstract). Hermens describes methods for removing contaminating viruses of a rod-like shape, such as baculovirus, from preparations of virus with an essentially spherical shape, such as adeno-associated viral gene therapy vectors (p. 1, lines 5-8; claims 1). Hermens specifically discloses that the diameter of the rod-like shaped virion and the essentially spherical shaped virion may differ less than 12 nm in size, or less than 5 nm in size (p. 14 printout, para. 2). Further, Hermens discloses that a filter may have a pore size of 30 nm to 70 nm (p. 14 printout, para. 4), and that a virus filter captures particles of certain sizes and lets smaller particles through (p. 15 printout, para. 2). Additionally, Hermens discloses filter membranes having a pore size which permits the removal of particles having a size of approximately 40-400 nm (p. 15 printout, para. 4). Hermens also discloses that rAAV has a diameter of approximately 25 nm (p. 3 printout, lines 27-28); and that baculoviridae are rod-shaped with a length of approximately 260 nm and a diameter of approximately 20 nm (pp. 3-4 printout, bridging para.).
However, Hermens does not teach a step of reducing the pressure to less than 3 psid during the filtration process.
Woods teaches that a temporary release in the transmembrane pressure can cause an approximately 10-fold increase in the phage concentration in the filtrate immediately after re-pressurization, with the phage concentration quickly decreasing to a value similar to that obtained in an experiment with a constant pressure (i.e., without any pressure release; p. 551, col. 1, para. 2). The reduction in pressure causes the “release” of some of the phage that were previously captured within the membrane, with these phage then migrating deeper into the pore structure when the filtration (the pressure is restored; p. 551, col. 1, para. 3). Woods discloses that a process disruption that causes a transient change in pressure can potentially compromise the overall virus removal from a liquid unless adequate in-process controls are in place (p. 551, cols. 1-2, bridging para). Woods specifically discloses passing bacteriophage XP071114096 through a filter at 210 kPa (30 psid), pausing to lower the pressure to 0 psi for 5 minutes, and then returning the pressure to the original value (p. 548, Figs. 2-3 & 5). Woods demonstrates that phage transmission increased immediately after a pressure release transiently by an order of magnitude immediately after a pressure release (Abstract).
It would have been obvious to one of ordinary skill in the art to modify the methods of Hermens to include a temporary pressure release where the pressure is reduced to 3 psid or less and then passing additional fluid containing viruses through the filter, as taught by Woods. Further, it would have been obvious to one of ordinary skill in the art to adapt Hermens’ methods to separate larger viruses having a size of 45 nanometers or larger from smaller viruses smaller than 40 nanometers in size, because Hermens discloses that rAAV has a diameter of approximately 25 nm (p. 3 printout, lines 27-28); and that baculoviridae are rod-shaped with a length of approximately 260 nm and a diameter of approximately 20 nm, filters may vary in size as needed, that the differences in size may be less than 12, or even 5 nm between viruses to be separated, and that filters may be employed to remove particles having a size of approximately 40-400 nm. One of ordinary skill in the art would have been motivated to increase the virus transmission into the filtrate, as taught by Woods. There would be a reasonable expectation of success because Hermens teaches use of filters to filter AAV from other viruses, and Woods teaches the method of passing fluid containing viruses through a filter at >20 psid, reducing the pressure to 3 psid or less, and then passing additional fluid through the filter at a pressure of >20 psid. Woods also teaches the additional limitations of the dependent claims, including the reduced pressure time range, and the pressures for passing fluid through the porous filter being at least 30 psid. Therefore, claims 1 and 3-9 were prima facie obvious before the priority date of the instant invention.
Response to arguments
Applicant presents the following arguments:
One of skill in the art would not be led to combine the teachings of Hermens and Woods in the manner set out by the Office, as there is no pointer leading one of skill in the art from the teachings of Hermens to the teachings of Woods.
Hermens teaches separating a population of parvoviral virions from a population of baculoviral virions using a filter through which only the parvoviral virions can pass. In view of this, since the parvoviral virions are separated from the baculoviral virions, one of skill in the art is not led to further complicate the method of Hermens by modifying it to utilize the pressure release taught by Woods.
Thus, a consideration of the factors set out in Graham v. John Deere Co., 383 US 1, 148 USPQ 459 (1996) indicates that the presently claimed aspect of the invention is unobvious to one of ordinary skill in the art at the relevant time in view of the combined disclosures of the cited references.
Since the independent claim is allowable for the reasons set forth above, the dependent claims are allowable as they depend from the novel and non-obvious independent claim.
Applicant’s arguments were carefully considered but are found unpersuasive:
Hermens is silent with regard to the pressure reduction required by the instant claims. However, we must consider, at the time of filing, what was the state of the art. One of ordinary skill in the art of separating different viruses based on size would be led to the teachings of Woods, because it is concerned with filtering viruses, which is recognized as a method of separating viruses. There is a unifying pointer between Hermens and Woods because that, and Woods contemplates commercially available filters, and discloses a benefit to a significant increase in virus through a number of commercial virus filters due to a temporary release in the transmembrane pressure.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671
/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671