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 OFFICE ACTION
This Office Action is in response to the papers filed on 06 November 2025.
CLAIMS UNDER EXAMINATION
Claims 1-3, 5-8 and 10 are pending and have been examined on their merits.
PRIORITY
The Applicant claims priority to Provisional Application 61613239, filed on 20 March 2012. A search of the Provisional Application does not appear to provide support for a step of separating whole blood in a second collection cycle to obtain a second quantity of MNCs while simultaneously photoactivating the first quantity of MNCs to obtain a first quantity of treated MNCs. The Provisional Applicant provides support for one or more cycles, but it does not mention separating whole blood in a second collection cycle to obtain a second quantity of MNCs while simultaneously photoactivating the first quantity of MNCs to obtain a first quantity of treated MNCs. A search of CIP Application 13/760774 does not appear to provide support for simultaneously photoactivating the first quantity of MNCs to obtain a first quantity of treated MNCs. Support is found in Application 16360725, filed on 21 March 2019. Therefore claim 1 has a benefit of priority to the 16360725 Non-Provisional Application.
WITHDRAWN REJECTIONS
The Terminal Disclaimer filed on 06 November 2025 has been approved. The rejection of claims 1-3, 5-8 and 10 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-8 of US Patent 11571504 (07 February 2023) is withdrawn.
REJECTIONS
Step e) of claim 1 has been amended to require combining the first quantity of treated MNCs with a cryopreservation medium during the second collection cycle. The rejections have been modified to address the limitation.
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.
Claims 1 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Radwanski et al. (previously cited; Methods and Systems For Collecting Mononuclear Cells. US2016/0114095. 2016) in view of Radwanski (previously cited; Cryopreserved ECP-Treated Lymphocytes Maintain Apoptotic Response and Anti-Proliferative Effect. Journal of Clinical Apheresis 30:154–161 2015).
Radwanksi teaches a method of collecting mononuclear cells (Abstract). Whole blood is withdrawn from a patient ([0024]). Mononuclear cells are separated ([0024]). Mononuclear cells are collected in container “68” ([0027]). A crystalloid solution (preferably saline) is added to obtain the desired hematocrit for UV-A irradiation (typically around 150-200 mL of saline is added to achieve a hematocrit of 2% or less) ([0036]). As the plasma content in the overall product represents typically 25% or less of the total volume, the effect of elevated plasma protein or lipid levels on UV-A dose delivered to MNCs is reduced ([0036]). Cells are photoactivated ([0037]-[0039]).
The art teaches collection in a batch process ([0035]). The art teaches more than one cycle can be performed to achieve the desired yield of MNCs to be treated ([0036]). It is noted the art teaches separated MNCs may be separated from whole blood, chemically treated with a light-activated agent, such as 8-methoxypsoralen exposed to ultraviolet light, and returned to the patient to produce an anti-tumor action ([0003]). Other components separated from the whole blood, such as red blood cells and platelets may be returned to the patient ([0024]). It is of note Radwanksi teaches the blood processing set includes an inlet needle for collecting patient blood and a return needle for returning blood components ([0030]).
Radwanksi teaches the apheresis device includes a programmable controller ([0034]). The art teaches the following:
A user/operator may select a particular processing protocol to achieve a desired outcome or objective. The controller can separate blood into its various components, as well as operate one or more pumps to move blood, blood components and/or solutions through the various openable valves and tubing segments of a processing set ([0034]).
This may include, for example, initiating and causing the separation of mononuclear cells from whole blood in the separation chamber and combining a crystalloid solution to the MNCs. The various processing steps performed by the pre-programmed automated apheresis device may occur separately, in series, simultaneously or any combination of these ([0034]).
Therefore the art teaches the processing steps can be performed separately, in series or simultaneously. The art teaches multiple cycles of whole blood processing.
Radwanksi does not explicitly teach beginning a second collection cycle after achieving a target hematocrit for a first quantity of MNCs. The art does not teach separating additional whole blood in a second collection cycle while simultaneously photoactivating the first quantity of MNCs.
Radwanski (2015) teaches the ability to cryopreserve a portion of the cells treated during extracorporeal photopheresis (ECP) would improve therapy logistics, particularly for pediatric patients, by allowing multiple therapeutic doses to be collected from a single apheresis session. Radwanski cryopreserves ECP treated cells using a cryoprotectant (see Figure 1). The art teaches cryopreservation did not impair the apoptotic response or anti-proliferative effect of ECP-treated lymphocytes (see first sentence of Conclusion section on right column page 160). The art teaches apoptosis increases in fresh ECP-treated cells over time (see page 157, right column, “Lymphocyte Apoptosis” section; see Figure 2).
It would have been obvious to combine the first, treated MNCs with a cryopreservation medium as claimed. One would have been motivated to do so to store collect and store multiple aliquots of cells for later use, as taught by Radwanski (2015). The skilled artisan would do so during the second collection cycle since Radwanksi (2015) teaches apoptosis of fresh cells increases over time. The skilled artisan would add cryopreservative for cryopreservation during the second cycle to decrease apoptosis of fresh cells collected in the first cycle. One would have had a reasonable expectation of success adding a cryopreservative since Radwanski (2015) teaches cells treated with photopheresis can be cryopreserved. One would have expected similar results since both Radwanski references are directed to cells treated with extracorporeal photopheresis. Because the use of cryopreservative and cryopreservation are rendered obvious, one would expect the cells to exhibit an apoptosis trend that is not significantly affected upon thawing as claimed.
It would have been obvious to begin a second blood collection cycle after achieving a target hematocrit for MNCs obtained from a first cycle. Radwanski teaches adjusting the hematocrit prior to delivering a UV-A dose. The skilled artisan would wait to process a second collection cycle of whole blood to prevent elevating plasma protein or lipid levels, since Radwanski teaches plasma and lipid to have a negative effect on UV-A treatment. One would have had a reasonable expectation of success performing the steps in this order since the art teaches the disclosed steps can be performed sequentially.
It would have been obvious to separate blood in a second collection cycle while simultaneously photoactivating the first quantity of MNCs. Radwanksi teaches the system comprises an inlet needle for collecting blood, and a return needle for returning treated components to the patient. The skilled artisan would simultaneously separate a second cycle of blood while photoactivating the first MNCs to continuously collect and return treated blood components to a patient. One would have had a reasonable expectation of success since Radwanski collecting and photoactivating blood in cycles and teaches the steps can be performed simultaneously.
Therefore claim 1 is rendered obvious.
Radwanski teaches UVA exposure of approximately 1.5-2.0 J/cm2 per lymphocyte ([0041]). Therefore claim 10 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 2-3 and 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over Radwanski in view of Radwanksi (2015) as applied to claim 1 above, and further in view of Min et al. (previously cited; incorporated by Radwanski; Patent 6027657 and US20130197419).
Claim 1 is rejected on the grounds set forth above. The teachings of Radwanski are reiterated. Radwanski collects and separates whole blood to obtain mononuclear cells. Hematocrit is adjusted using saline. The cells are photoactivated.
The art discloses a system comprising a separation component and an irradiation component ([0022]). The art teaches “it will be appreciated that the methods described herein may also be used with devices having integrated separation and irradiation components” ([0022]). Radwanski teaches a system comprising a disposable fluid circuit includes a network of tubing and pre-connected containers for establishing flow communication with the patient and for processing and collecting fluids and blood and blood components ([0026]).
Examiner notes that while Radwanski does not explicitly teach the separation steps and containers as recited in claim 2, Radwanski teaches a separation system as described in US20130197419 (Min ‘419) and the use of an Amicus Separator as described in US Patent 6027657 (Min‘657). Radwanski states both Min references are incorporated in the disclosure..
Min et al. (‘419) disclose systems and methods for performing online extracorporeal photopheresis of mononuclear cells (Abstract). Whole blood is removed from a patient and introduced through a processing set into a separation chamber to separate the desired cell population from the blood. (Abstract). Min teaches a “disposable fluid circuit” comprising a processing chamber for separating whole blood into one or more components including mononuclear cells and at least one storage container adapted to receive mononuclear cells ([0016]). Therefore the art taches a disposable fluid circuit having a separation chamber. Whole blood is withdrawn from a patient ([0025]). Min teaches the following at [0027]:
Apparatus useful in the collection (and washing) of mononuclear cells include the Amicus® Separator made and sold by Fenwal, Inc., of Lake Zurich, Ill. Mononuclear cell collections using a device such as the Amicus® are described in greater detail in U.S. Pat. No. 6,027,657, the contents of which is incorporated by reference herein in its entirety. Preferably, the apparatus used for the harvesting, collection and reinfusion of mononuclear cells in accordance with the apparatus and methods described herein is a “multifunctional” automated apheresis device, as is the case with the Amicus® Separator. In other words, it is preferable that the separation component 10 be an multifunctional automated apparatus that can perform various collection protocols and/or serve multiple purposes, as may be needed by a particular hospital or facility, such that it can be used not only in the systems and methods for performing photopheresis treatment of MNC as described herein, but can also be used for other purposes including the collection of blood and blood components including platelets, plasma, red blood cells, granulocytes and/or perform plasma/RBC exchange, among other functions required by the hospital or medical facility. One benefit of the systems and described herein, in which a fluid processing circuit engages both a multifunctional apheresis device and an irradiation device, is that a “dedicated” photopheresis device that is designed only to perform ECP treatment, but which does not perform any other functions, is not required.
As set forth above, the art discloses the use of a multifunctional apheresis device that can collect components including platelets, plasma and red blood cells. Examiner notes the art teaches a container for collecting plasma ([0028]), a container for collecting mononuclear cells ([0028]) and a container with red blood cells ([0030]). The art teaches a blood processing container defining a separation chamber suitable for harvesting mononuclear cells (MNC) from whole blood ([0028]). The separated target cell population, e.g., mononuclear cells, is then treated and irradiated in treatment component ([0026]). The method comprises the steps of providing a disposable fluid circuit comprising a processing chamber for separating whole blood into one or more components including mononuclear cells and at least one treatment container adapted to receive mononuclear cells ([0017]). Effective treatment of the mononuclear cells with light may require that the amount of collected mononuclear cells have a suitable hematocrit. Thus, it may be desired or even necessary to dilute the mononuclear cells with a diluting solution such as plasma or saline, as shown in step 33. In the example described above, approximately 15 ml of MNC may be diluted in about 200 ml of plasma ([0038]). The art teaches the diluted mononuclear cells (in container 68) are then combined with the suitable photoactivation agent in step 34. Alternatively, the desired volume of the agent may be pre-added to the container ([0038]). As noted above, the mononuclear cells collected in accordance with the mononuclear cell collection process described above may be collected in container 68 that is suitable for irradiation by light of a selected wavelength. By “suitable” it is meant that the walls of the container are sufficiently transparent to light of the selected wavelength to activate the photoactive agent. In treatments using UVA light, for example, container walls made of ethylene vinyl acetate (EVA) are suitable. Accordingly, container 68 in which the mononuclear cells are collected may serve both as the collection container and the irradiation container ([0040]).
Min teaches collection of the mononuclear cells may proceed in one or more cycles. The number of processing cycles conducted in a given therapeutic procedure will depend upon the total volume of MNC to be collected. For example, in a representative procedure, five collection cycles may be performed sequentially.
Examiner notes Min teaches the use of the Amicus Separator, which is identified as a multifunctional automated apheresis device ([0027]). Radwanski teaches the use of the Amicus Separator device for cell separation as Patent 6027657 (Min ‘657), which is incorporated by reference ([0027]).
Min (‘657 Patent) teaches a preprocessing priming cycle with primes the fluid circuit (column 10, lines 48-50).
It would have been obvious to combine the teachings of the prior art to perform the separation and collection steps recited in claim 2. One would have been motivated to do so since Min teaches a method of separating and photoactivating MNCs and Min (incorporated by Radwanksi) teaches performing each of the claimed separation and collection steps to separate the components of whole blood to produce MNCs. One would have expected success since Radwanski teaches these steps can be used to separate blood and photoactivate cells. One would have expected similar results since each refence collects MNCs. As set forth above, Radwanski teaches multiple collection cycles can be performed and teaches steps can be performed simultaneously. One would have expected similar results since Min and Radwanski are both directed to techniques for collecting and treating MNCs from whole blood. Therefore claim 2 is rendered obvious as claimed.
Radwanski teaches the use of one or more containers for collecting mononuclear cells ([0013]). Examiner notes the art teaches the valves leading to the product container can be closed (hence, sealed) ([0035]). The art teaches the disposable fluid circuit includes a network of tubing and pre-connected containers for establishing flow communication with the patient and for processing and collecting fluids and blood and blood components ([0026]).The art teaches the use of an illumination container (hence, a treatment container that is pre-attached to the disposable set ([0028]). Examiner notes the second collection cycle recited in claim 3 are the same as the first collection cycle recited in claim 2. As set forth above, Radwanski teaches multiple cycles can be performed. Therefore performing the same steps in the first and second cycles is rendered obvious. Therefore claim 3 is included in this rejection.
As set forth above, Min teaches the diluted mononuclear cells (in container 68) are then combined with the suitable photoactivation agent in step 34. Alternatively, the desired volume of the agent may be pre-added to the container. The art teachings treating with UVA (supra). As set forth above, Min teaches reinfusion to a patient. Therefore claim 5 is included in this rejection.
Min teaches a disposable fluid circuit comprising a processing chamber for separating whole blood into one or more components including mononuclear cells and at least one storage container adapted to receive mononuclear cells ([0016]). As set forth above, Min teaches the diluted mononuclear cells (in container 68) are then combined with the suitable photoactivation agent in step 34. Alternatively, the desired volume of the agent may be pre-added to the container. The art teachings treating with UVA (supra). Therefore claim 6 is included in this rejection.
Radwanski teaches the following at [0034] and [0035]
the apheresis device may include a programmable controller that is pre-programmed with one or more selectable protocols. A user/operator may select a particular processing protocol to achieve a desired outcome or objective. The pre-programmed selectable protocol(s) may be based on one or more fixed and/or adjustable parameters. During a particular processing procedure, the pre-programmed controller may operate the centrifuge and processing chamber associated therewith to separate blood into its various components, as well as operate one or more pumps to move blood, blood components and/or solutions through the various openable valves and tubing segments of a processing set, such as such as processing set 14 illustrated in FIG. 3. This may include, for example, initiating and causing the centrifugal separation of mononuclear cells from whole blood in the separation chamber 16, removing plasma from mononuclear cells (i.e., pumping the removed plasma to a storage or waste bag) to obtain MNC concentrate, purging or flushing the tubing segments to collect additional MNCs that may reside or remain in the tubing during or after processing, and combining a crystalloid solution to the concentrated MNCs…
In accordance with the present disclosure, an automated apheresis device may be used to perform MNC collection in a batch process in which MNCs continuously collect in the chamber 16 until the target cycle volume is reached. As the MNCs are transferred out of the chamber 16, they pass through an optical sensor which detects the presence of cells in the tubing line to determine the start and end of the MNC harvest (i.e. when to open and close the valves leading to the product container). After MNC harvest is complete, the remaining cells in the line are flushed into the product container with a predetermined volume of plasma known as the “plasma flush”.
Said plasma flush is interpreted to read on a plasma purge. The art teaches the use of an RBC line for conveying red blood cells through the system. This is interpreted to read on an RBC push. Therefore claims 7-8 are included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 06 November 2025. The arguments state Radwanski (‘095) does not teach adding a cryopreservative to the first quantity of treated MNCs during the second collection cycle.
Response to argument: New grounds of rejection have been set forth above.
CONCLUSION
No Claims Are Allowed
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653