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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 22APR2026 has been entered.
Response to Arguments
The Amendment filed 23MAR2026 has been entered. No new matter has been entered. Applicant's arguments filed 23MAR2026 have been fully considered but they are not persuasive.
Regarding the combination of CHERUBINI and BELLAMY, the Applicant argues that CHERUBINI and BELLAMY disclose systems used for entirely different purposes and they would not be combined by a POSA. This is not found persuasive, because both references are in the technological environment of centrifugal separations. CHERUBINI discloses a method using a rotatable vessel for processing particles for sedimentation and resuspension of the particles of interest (abstract) including washing (C5/L7). CHERUBINI is also concerned with improving automation such that manual steps may be avoided (C2/L3-5; C3/L16-17). BELLAMY discloses a method and apparatus for the centrifugal washing of particles in a closed system (title). BELLAMY is also concerned with avoiding difficult and time-consuming techniques (C1/L43-46). One having ordinary skill in the art would understand that simultaneously adding/removing material (via e.g. a conduit) while rotating a vessel would improve throughput and automation while decreasing reliance on manual steps (such as a manual pipette). One having ordinary skill in the art may rely on the broad spectrum of prior arts for improvement in their technological field. An obviousness rejection may rely on analogous arts either from the same field of endeavor as the claimed invention (even if it addresses a different problem) or the reference is reasonably pertinent to the problem of the inventor (even if it is not in the same field of endeavor as the claimed invention). MPEP 2141.01(a). Both CHERUBINI and BELLAMY are reasonably pertinent to the claimed invention and are analogous arts.
Furthermore the Applicant argues incompatible mechanical systems. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
The point of BELLAMY is not the mechanical system itself, but a method of withdrawing liquid while continuing rotation of the vessel.
For the similar reasons as described above, the combination of CHERUBINI and SCHLUTZ are also analogous arts and obvious. SCHLUTZ discloses a centrifuge separation and washing device and method (title). SCHLUTZ is also concerned with improving the low throughput per unit time of batch operation (C2/L20-22,52-65). Furthermore, there is a clear disadvantage to stopping rotation in terms of automation efficiency and throughput and thus one having ordinary skill in the art would be motivated to look for alternative solutions. Clearly a conduit is a simple obvious choice of removing material, whereas a burst valve only works under certain conditions (e.g. high pressure).
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.
Claim(s) 16-17,19-24,27,33-35,40 are rejected under 35 U.S.C. 103 as being unpatentable over CHERUBINI (WO 2016016345) in view of BELLAMY (US 3347454).
Regarding claim 16, CHERUBINI teaches an automated system for processing particles (title, Figs.) including a method of washing cells from a sample including cells suspended in a liquid (P14/L9; P17/L19), the method comprising:
a) dispensing (introducing) the sample into a vessel (e.g. Figs. 1A-2A #200) including a body defining a pocket (Fig. 2A #206), and a cavity (inner space; Fig. 2A #202) positioned below the pocket, the pocket defined by a first inner surface portion (Fig. 2A #206) of the inner surface disposed between and radially outward relative to a second inner surface portion (Fig. 2A #207) and a third inner surface portion of the inner surface (Fig. 2A #205);
b) rotating the vessel about an axis of the vessel at a first speed (P30/L7-8) using an actuating device (P3/L11-13);
c) displacing the cells into the pocket (P30/L7-11);
d) sedimenting the cells within the pocket (P30/L7-11); and
e) withdrawing at least part of the liquid (P30/L19-20).
CHERUBINI teaches improving automation such that manual steps may be avoided (C2/L3-5; C3/L16-17). CHERUBINI does not teach withdrawing the liquid through a conduit while continuing rotation of the vessel. However, BELLAMY teaches a method and apparatus for the centrifugal washing of particles in a closed system (title, Figs.) in which the particles are maintained in the washing field by centrifugal force (C1/L15-16). BELLAMY teaches withdrawing liquid through a conduit (e.g, via outlet tube, Fig. 1 # 15) while continuing rotation of the vessel provides for quickly and adequately washing impurities from particles such as cells (C1/L36,47-48,58-59,65-66) while avoiding difficult and time-consuming techniques (C1/L43-46).
Therefore, before the effective filing date of the invention, it would have been obvious to one of ordinary skill in the art to modify the method of CHERUBINI to include withdrawing liquid through a conduit while continuing rotation of the vessel as taught by BELLAMY in order to quickly and adequately wash impurities from particles and improve automation. The references are combinable, because they are in the same technological environment of centrifugal separations. See MPEP 2141 III (A) and (G).
Regarding claim 17, CHERUBINI’s modified method teaches washed cells are formed after step e) (see CHERUBINI Fig. 7 and P36/L21-23,28-29; particularly P38/L3-8) and wherein the step of displacing includes:
adding a first aliquot of a wash liquid through a conduit, and wherein the step of withdrawing includes aspirating through the conduit (fluid handling including a pipettor, Fig. 1B #910 of CHERUBINI and a pump for driving liquid in and out of the vessel; P12/L16-18); and,
a conduit extending into the vessel and terminating at the bottom (and thus below the pocket; see conduit of e.g. BELLAMY Fig. 1 #15).
While BELLAMY appears to show two conduits (one for an inlet, Fig. 1 #14 and one for an outlet, Fig. 1 #15), it is known in the art to use a single conduit for both influent and effluent (see CHERUBINI P7/L4-5,10-12). It is an obvious engineering design choice to one having ordinary skill in the art to provide for the same conduit both influent and effluent.
Regarding claim 19, CHERUBINI teaches resuspending the washed cells (see e.g. the Example on P55 including step #9 of resuspension after washing).
Regarding claim 20, CHERUBINI teaches the step of resuspending includes adding a resuspension liquid to the vessel and stopping rotating (see e.g. P33/L1-4).
Regarding claim 21, CHERUBINI teaches the step of resuspending includes reversing a direction of rotation of the vessel (P31/L13-26; particularly P31/L21-23).
Regarding claim 22-23, CHERUBINI teaches the cavity has a volume (e.g. Fig. 2A #202; in this example about 1mL) below the pocket, and the sample has a sample volume less than the volume below the pocket (in the example of P55; the sample volume is 100 μl; step 2), which is less than about 0.7 times the volume below the pocket (100 μl is less than 700 μl).
Regarding claim 24, CHERUBINI teaches the resuspension liquid has a resuspension volume (e.g. 400 μl of PBS at step 12) less than the sample volume (100 μl of whole blood + 800 μl of RBC lysis buffer = about 900 μl of sample volume).
Regarding claim 27, CHERUBINI teaches a centrifugal force of e.g. 1,000 g during a sedimentation step (P52/L7-8), anticipating the claimed range of at least about 100 x g.
Regarding claims 33-35, CHERUBINI’s modified device teaches adding a rinse liquid (wash buffer; P13/L3) into the vessel using a dispense probe terminating within the vessel (pipettor; P3/L16-19; P7/L4-5; see also e.g. BELLAMY Fig. 1 #14 as a “dispense probe”) and aspirating the rinse liquid using an aspiration probe terminating within the vessel at a lower point than the dispense probe (e.g. BELLAMY outlet tube, Fig. 1 #15 as an “aspiration probe”).
Regarding claim 40, CHERUBINI teaches the pocket has a length to depth ratio. The ratio range of “at least about 2:1 length to depth” appears to be either satisfied or obvious in view of Fig. 2C as optimizing the desired volume of the pocket. See also P19/L30-31.
The length to depth ratio has not been established to provide any criticality or to provide any unexpected result/benefit over the prior art of record. It has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233. Further, it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USP 215 (CCPA 1980).
Claim(s) 32 is rejected under 35 U.S.C. 103 as being unpatentable over CHERUBINI (WO 2016016345) in view of BELLAMY (US 3347454) and ZURCHER (US 6001087).
Regarding claim 32, CHERUBINI teaches liquid biological samples containing particles such as blood cells (P2/L28-30), but does not teach EDTA. However, ZURCHER teaches a collection assembly with a reservoir (title, Figs.) and that blood is typically mixed with anticoagulants such has EDTA to prevent clotting or coagulation (C1/L27-35; C3/L20-24).
Therefore, at the time the invention was filed, it would have been obvious to one of ordinary skill in the art to combine the method of CHERUBINI with EDTA as taught by ZURCHER in order to prevent clotting or coagulation. The references are combinable, because they are in the same technological environment of treating biological liquids. See MPEP 2141 III (A) and (G).
Differences in concentration […] will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration […] is critical (MPEP 2144.05.II.A. The concentration has not been established to provide any criticality or to provide any unexpected result/benefit over the prior art of record. It has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233. Further, it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USP 215 (CCPA 1980).
Claim(s) 16,25-26, are rejected under 35 U.S.C. 103 as being unpatentable over CHERUBINI (WO 2016016345) in view of SCHLUTZ (US 3982691).
Regarding claim 16, CHERUBINI teaches an automated system for processing particles (title, Figs.) including a method of washing cells from a sample including cells suspended in a liquid (P14/L9; P17/L19), the method comprising:
a) dispensing (introducing) the sample into a vessel (e.g. Figs. 1A-2A #200) including a body defining a pocket (Fig. 2A #206), and a cavity (inner space; Fig. 2A #202) positioned below the pocket, the pocket defined by a first inner surface portion (Fig. 2A #206) of the inner surface disposed between and radially outward relative to a second inner surface portion (Fig. 2A #207) and a third inner surface portion of the inner surface (Fig. 2A #205);
b) rotating the vessel about an axis of the vessel at a first speed (P30/L7-8) using an actuating device (P3/L11-13);
c) displacing the cells into the pocket (P30/L7-11);
d) sedimenting the cells within the pocket (P30/L7-11); and
e) withdrawing at least part of the liquid (P30/L19-20).
CHERUBINI teaches improving automation such that manual steps may be avoided (C2/L3-5; C3/L16-17). CHERUBINI does not teach withdrawing the liquid through a conduit while continuing rotation of the vessel. However, SCHLUTZ teaches centrifuge separation and washing device and method (title, Figs.) in which liquid is withdrawn through a conduit (e.g, Fig. 5 #52,76) while continuing rotation of the vessel to provide a continuous separation and/or washing operation achieving a high throughput of finely-divided solid particulate material suspended in a liquid (e.g. biological material such as cells; C1/L6-7,14-15,49; C2/L20-22,52-65; C3/L3-4; C5/L35-41).
Therefore, before the effective filing date of the invention, it would have been obvious to one of ordinary skill in the art to modify the method of CHERUBINI to include withdrawing liquid through a conduit while continuing rotation of the vessel as taught by SCHLUTZ in order to wash cells continuously with a high throughput. The references are combinable, because they are in the same technological environment of centrifugal separations. See MPEP 2141 III (A) and (G).
Regarding claim 25, CHERUBINI’s modified method teaches rotating the vessel at a second speed during the withdrawing step, wherein the second speed is less than the first speed (C5/L47-49).
Regarding claim 26, SCHLUTZ teaches the second speed in terms of RPM (400 RPM; C5/L47-49) and for a 12 in diameter rotor (15 cm radius; C4/L56) equates to about 27 x g, which anticipates the claimed range of at least 25 x g. (formula: RCF = (RPM)2 × 1.118 × 10-5 × r).
Claim(s) 18,28-29, are rejected under 35 U.S.C. 103 as being unpatentable over CHERUBINI (WO 2016016345) in view of BELLAMY (US 3347454) and REEDER (US 4668214).
Regarding claim 18,28, CHERUBINI teaches f) adding a second aliquot of the wash liquid through the conduit (see P31/L27-P32/L2 for repetition of steps; see also the Example on P55 where the wash buffer PBS was added twice in steps 8,12; see also generally P12/L31-32).
CHERUBINI does not teach adding a second aliquot of the wash liquid at a slower dispense rate than the first aliquot of wash liquid. However, REEDER teaches a method of washing red blood cells (title, Figs.) including dispensing a washing solution in an alternating high flow rate/low flow rate sequence for optimal cleaning of cells (abstract; see also Fig. 6 showing a second aliquot of the wash liquid at a slower dispense rate than a first aliquot of wash liquid). Note that many variables of flow rates and time durations will provide an effective wash (C6/L53-54).
Therefore, at the time the invention was filed, it would have been obvious to one of ordinary skill in the art to modify the method of CHERUBINI to include a second aliquot of the wash liquid at a slower dispense rate as taught by REEDER in order to wash cells with an improve cleaning. The references are combinable, because they are in the same technological environment of centrifugal separations. See MPEP 2141 III (A) and (G).
Regarding claim 29, CHERUBINI teaches g) cleaning the vessel (P12/L33-P13/L1).
Claim(s) 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over CHERUBINI (WO 2016016345) in view of BELLAMY (US 3347454), REEDER (US 4668214) and KELLEY (US 3880592).
Regarding claim 30, CHERUBINI teaches step g) includes:
i. adding a rinse liquid (P13/L3).
CHERUBINI does not teach:
ii. rotating the vessel at a third speed; and
iii. aspirating the rinse liquid through the conduit.
However, KELLEY teaches a blood analysis system including a plasma separator (title, Figs.) and a cleaning step including:
i. adding a rinse liquid (C7/L23-25);
ii. rotating the vessel at a third speed (C7/L28-31); and
iii. aspirating the rinse liquid through the conduit (C7/L26-27).
Therefore, at the time the invention was filed, it would have been obvious to one of ordinary skill in the art to combine/modify the method of CHERUBINI with the cleaning steps as taught by KELLEY in order to prepare for introduction of the next sample. The references are combinable, because they are in the same technological environment of centrifuging cells. See MPEP 2141 III (A) and (G).
Regarding claim 31, KELLEY teaches varying a speed of rotation while filling the centrifuge to allow equal distribution of fluid (C6/L46-52). It is obvious to one having ordinary skill in the art to apply a similar concept to aspirating the rinse liquid for the purpose of avoiding dead zone when withdrawing fluids.
Claim(s) 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over CHERUBINI (WO 2016016345) in view of BELLAMY (US 3347454) and BROWN (US 4940543).
Regarding claims 41-42, CHERUBINI teaches does not teach the conduit remains stationary while the vessel rotates and the conduit extends within the vessel parallel to and offset from the axis of the vessel. However, BROWN teaches a plasma collection set (title, Figs.) including a rotating centrifuge (Fig. 1 #12) and a stationary conduit (Fig. 1 #46) that extends within the vessel parallel to and offset from the axis of the vessel for the purpose of withdrawing/collecting separated components as desired without using rotating seals (C2/L3-5).
Therefore, at the time the invention was filed, it would have been obvious to one of ordinary skill in the art to combine/modify the method of CHERUBINI with the offset conduit as taught by BROWN in order to provide for withdrawing/collecting separated components as desired without using rotating seals. The references are combinable, because they are in the same technological environment of centrifuging cells. See MPEP 2141 III (A) and (G).
Telephonic Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIAM A ROYCE whose telephone number is (571)270-0352. The examiner can normally be reached M-F ~08:00~15:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Benjamin Lebron can be reached at (571)272-0475. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Liam Royce/Primary Examiner, Art Unit 1777
LIAM A. ROYCE
Primary Examiner
Art Unit 1777
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