DETAILED ACTION
This application is a Continuation-In-Part (CIP) of Application No. 15/893,336, filed 09 February 2018.
The Applicant’s response, received 08 July 2025 has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 08 July 2025 has been entered.
Status of the Claims
Claims 1-16 and 21-23 are pending.
Claims 1-16 and 21-23 are rejected.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The Applicant’s claim for the benefit of a prior-filed application:
U.S. Non-Provisional Application No. 15/893,336, filed 09 February 2018; and
Provisional Application Nos.: 62/736,115, filed 25 September 2018; 62/736,125, filed 25 September 2018; 62/736,130, filed 25 September 2018; 62/736,120, filed 25 September 2018; 62/736,144, filed 25 September 2018; 62/736,154, filed 25 September 2018; and 62/736,143, filed 25 September 2018;
under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c), is acknowledged.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 15/893,336, filed 09 February 2018, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Claims 1-16 and 21-23 are not given the benefit of priority to U.S. Patent Application No. 15/893,336, filed 09 February 2018, because there is not support for first and second target environments in a bioreactor vessel for first and second incubation periods, respectively, or support for a third target environment in a second bioreactor vessel for a third incubation period.
Claims 1-16 and 21-23 are given the benefit of priority to Provisional Application No. 62/736,143, filed 9/25/2018.
Therefore, the effective filing date of the claimed invention is 25 September 2018.
Information Disclosure Statement
The information disclosure statements (IDS) received on 20 May 2025 and 27 August 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Claim Interpretation
The amendment received 08 July 2025 has been fully considered, however after further consideration the claim limitations being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, in the Office action mailed 10 April 2025 are maintained in view of the amendment.
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) are:
first module, in claims 1, 12, and 22;
second module(s), in claims 1, 12, and 22; and
third module, in claims 22 and 23.
Because these claim limitation(s) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, they are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
The written description discloses a corresponding structure for:
first module, at Figures 1 and 2; and ¶¶ [000102] & [000110] of the specification (subsystems; and may be a modified version of a Sefia Cell Processing System);
second module(s), at Figures 1, 2, & 3-77; and ¶¶ [000102], [000112], & [000216] of the specification (subsystems; system (400) including bioreactor vessels); and
third module, at Figures 1 and 2; and ¶ [000111] of the specification (may be a modified version of a Sefia Cell Processing System).
If applicant does not intend to have these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Response to Arguments
The Applicant states on page 7 (para. 2) that the claimed modules do not recite any elements in means plus function format. The Applicant further states (para. 3) that there is no legal/regulatory basis for this limitation, and that the claims do not recite “means for,” nor “module for” and the Examiner fails to provide any law or rule that supports the conclusion that the claims are in means plus function format. The Applicant further states that the Office action references MPEP 2181 Section A, however this section of the MPEP does not support the position taken in the Office action. The Applicant further states on page 8 (para. 1) that it must be recognized that the present claims do not recite any of the terms from the list of non-structural terms, and that the claims do not recite “module for”, but instead recite “a single first module” and “a plurality of second modules” that carry out various tasks, and that the Office action fails to cite any law or rule that supports the conclusion that these claim limitations are in means plus function format.
These arguments are not persuasive, because first, the MPEP at 2181 subsection I.(A) notes that there is no fixed list of generic placeholders that always result in 35 U.S.C. 112(f) interpretation, and likewise there is no fixed list of words that always avoid 35 U.S.C. 112(f) interpretation. Every case will turn on its own unique set of facts. Second, for a term to be considered a substitute for "means," and lack sufficient structure for performing the function, it must serve as a generic placeholder and thus not limit the scope of the claim to any specific manner or structure for performing the claimed function. It is important to remember that there are no absolutes in the determination of terms used as a substitute for "means" that serve as generic placeholders (MPEP 2181 subsection I.(A)). Third, with respect to MPEP 2181 subsection I.(B), it must be clear that the element in the claims is set forth, at least in part, by the function it performs as opposed to the specific structure, material, or acts that perform the function. A function must be recited within the claim limitation, but it is not necessary that a particular format be used. Typically, the claim limitation will use the linking word "for" to associate "means" or a generic placeholder with the function. However, other linking words may be used, such as "so that" or "configured to", provided it is clear that the claim element is reciting a function. In certain circumstances, it is also not necessary to use a linking word if other words used with "means", or the generic placeholder, convey the function. Fourth, with respect to MPEP 2181 subsection I.(C), the term "means" or "step" or the generic placeholder recited in the claim must not be modified by sufficiently definite structure, material, or acts for achieving the specified function.
Claim Objections
The objections to claims 21 and 22 in the Office action mailed 10 April 2025 are withdrawn in view of the amendment received 08 July 2025.
Claim Rejections - 35 USC § 112
The rejection of claim 23 in the Office action mailed 10 April 2025 is withdrawn in view of the amendment received 08 July 2025.
The amendment received 08 July 2025 has been fully considered, however after further consideration new grounds for rejection are raised in view of the amendment.
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.
Claim 1-16 and 21 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.
Claims 1 and 12 are indefinite for reciting “in a single first module, carry out enrichment and isolation of a first apheresis product from a first patient, and carry out enrichment and isolation of a second apheresis product from a second patient, the enrichment and isolation of the first apheresis product and second apheresis product occurring asynchronously” and further reciting “in a plurality of second modules, carry out genetic modification and expansion of cells from the first patient and the second patient simultaneously” because it is not clear as to whether the “cells from the first patient and the second patient” in the plurality of second modules are the “first apheresis product from a first patient” and “second apheresis product from a second patient” in a single first module. The final wherein clause implies that the cells must be from the apheresis products, which raises confusion as to whether the cells are required to be from the apheresis products or not.
Claims 2-11, 13-16, and 21 are indefinite for depending from either claim 1 or claim 12 and for failing to remedy the indefiniteness of claim 1 or claim 12.
Claims 1 and 12 are indefinite for reciting “wherein for each second module of the plurality of second modules, the controller is configured to maintain a first target environment in a bioreactor vessel…” because it is not clear as to whether the limitation “each second module” is reciting the same structure as “a bioreactor vessel…” or else if “each second module” is not “a bioreactor vessel…” and therefore the claim is referring to two different structures. The limitation reciting “each second module” is interpreted to be the same structure as “a bioreactor vessel.”
Claims 2-11, 13-16, and 21 are indefinite for depending from either claim 1 or claim 12 and for failing to remedy the indefiniteness of claim 1 or claim 12.
Claims 1 and 12 are indefinite for reciting “wherein the first module is configured to be utilized in conjunction with the plurality of second modules, and the controller is configured to use the first module and the plurality of second modules to provide for parallel and asynchronous processing of the first apheresis product and the second apheresis product” because it is not clear as to whether the processing relationship between the first module and the plurality of second modules is asynchronous or parallel.
Claims 2-11, 13-16, and 21 are indefinite for depending from either claim 1 or claim 12 and for failing to remedy the indefiniteness of claim 1 or claim 12.
Claim 16 recites the limitation “the second bioreactor vessel” in line three. There is insufficient antecedent basis for this limitation in the claim.
Claim 21 is indefinite for reciting “The non-transitory computer readable medium of claim 15, wherein: the first bioreactor vessel and the second bioreactor vessel are part of a functionally closed system” because the computer readable medium (CRM) comprises instructions that configure a controller (e.g. processor) to control some bioreactor, however the claim does not recite any limitations relating to the CRM (e.g. instructions configured to…), and therefore it is not clear as to the limiting effect of the wherein clause on the CRM (does “closed system” have some meaning with the instructions or is this just defining the system the controller is intended to operate on (i.e., an intended use of the CRM). This claim is interpreted to recite an intended use of the computer readable medium.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 21 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 21 does not recite any limitations that further limit the computer readable medium comprising instructions configured to adapt a controller, and therefore the claim fails to further limit the subject matter of claim 12, and as noted above, the claim is interpreted as reciting an intended use of the computer readable medium.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The rejection of claims 1-16, and 21-23 under 35 U.S.C. 103 as being unpatentable over Davis et al. in view of Hollyman et al. in view of Vunjak-Novakovic et al. in view of Molleryd et al. in view of Barringer, Jr. in view of Murthy in the Office action mailed 10 April 2025 is withdrawn in view of the amendment received 08 July 2025.
The amendment received 08 July 2025 has been fully considered, however after further consideration, new grounds of rejection are raised in view of the amendment.
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.
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.
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.
Claims 1-8, 10, 12, 13, 15, 16, and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Hauwaerts et al. (WO 2018/015561, newly cited) in view of Ghouze et al. (WO 2016/012459, newly cited).
Regarding independent claims 1, 12, and 22, Hauwaerts et al. shows a method and apparatus for automated independent parallel batch-processing of cells (Title; and Figure 1):
the cell processing device is suitable for performing independent concurrent processing of a plurality of cell preparations using a plurality of cell processing modules, wherein each of the plurality of cell processing modules comprises discrete processing compartments defined within, the processing compartments comprising
(i) a reagent pack, the reagent pack comprising one or more reagent vessels; and
(ii) one or more fluidic cartridges, each fluidic cartridge comprising one or more cell processing compartments and a cell incubation compartment, wherein each of the processing compartments is in fluid communication with each other (Abstract);
the device is configured such that each of the plurality of cell preparations are physically and/or temporally separated throughout processing (page 3, lines 19-20);
two or more cellular processing methods can be performed on different samples on the same device, independent of each other, but essentially concurrent (i.e., at least partially overlapping in time), thus, a method on a new cellular sample can be initiated on the same device (in a different cell processing module) prior to the processing method of the previous sample being finished (page 22, lines 12-21);
each of the plurality of cell processing modules comprises a closed environment, typically provided within the reagent pack and/or the fluidic cartridge (page 3, lines 21-24);
a fluidic cartridge may comprise at least one input port, a separation chamber, an activation chamber, a transduction chamber, a cell culture chamber, and at least one output port (page 3, lines 25-28);
the cell processing of each cell preparation is spatially and/or temporally separated from each other cell preparation (page 7, lines 11-12);
cellular samples include blood, apheresis, or leukapheresis product (page 21, line 27);
the cells are T cells and the genetic modification is a genetic modification with a chimeric antigen receptor (CAR) (page 7, lines 30-32);
a typical procedure for the preparation of CAR-T cells (Example 3; and pages 23-27);
the device can accommodate two or more cell processing modules at the same time (page 12, lines 1-3); and
a central processing unit (CPU) and a main control system including an embedded controller and Program Logic Controller (PLC) (page 12, lines 13-14).
Hauwaerts et al. shows that a considerable portion of the overall manufacturing time involves cells in the incubation operations, and that during this incubation time most of the fluid handling and cell handling technologies are inactive (page 12, lines 28-32); however Hauwaerts et al. does not explicitly show, in a plurality of second modules, carrying out genetic modification and expansion of cells from the first patient and the second patient simultaneously.
Regarding independent claims 1, 12, and 22, Ghouse et al. shows methods and systems for parallel processing of biological cellular samples in a space and time efficient fashion, and with particular utility in processing patient samples for use in cell therapy (Title; and Abstract). Ghouse et al. further shows:
the numbers of processing stations in each unit may be tailored to provide the optimum efficiency and throughput to the facility by having a larger number of stations in units where the processing step has a long duration and a smaller number of stations in units with short process steps (e.g., a small number of stations in the sample isolation unit; and a larger number of stations in the cell expansion unit); and
segregation of processing stations by function enables the provision of the optimum environment (lighting, electrical power and other services, temperature control, etc.) required for processing stations within a common unit (page 16, lines 3-10).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method shown by Hauwaerts et al. by incorporating methods for scaling the number of processing stations in each unit according to the duration of the different processing steps, as shown by Ghouse et al. and discussed above. One of ordinary skill in the art would have been motivated to combined the methods of Hauwaerts et al. with the methods of Ghouse et al. because Ghouse et al. shows parallel processing of cellular material that addresses the problem of optimizing processing biological cellular samples, e.g., patient samples, in a scalable format which provides economies of scale. This modification would have had a reasonable expectation of success given that both Hauwaerts et al. and Ghouse et al. show methods for parallel processing of biological cellular samples for use in cell therapies.
Regarding dependent claim 2, Hauwaerts et al. further shows a cell processing device that is an automated fluid handling system that consists of peristaltic pumps, valves, and a bag mixer for the processing bag, and also includes pressure and fluid sensors, and the fluidic movements are managed by the computer-controlled system in the cell processing device, which synchronizes pumps and valves to achieve the designated tasks (page 37, lines 33-35 through page 38, lines 1-5); and at each manufacturing step, cells (provided either as apheresis product at the start of the process or as the in-process cultured cells during the process) are transferred automatically from cell containers (inlet) to the cell processing bag, and for cultured cells, the connection from the cell container to the cell processing bag comprises a series of tube elbows and consecutive tubing diameter changes (page 38, liens 19-25).
Regarding dependent claim 3, Hauwaerts et al. further shows syphon tubes are used to add and remove material and also to rinse the chamber for better cell recovery (page31, lines 24-25); and further shows that retentate flow is returned to the processing chamber where a defined volume of media is introduced (page 33, lines 36-37).
Regarding dependent claim 4, Hauwaerts et al. further shows different fluidic vessels used at each step by the cell processing device (page 40, Table 3.1) and further shows that the seeded culture vessels were maintained at 37°C and 5% CO2 (page 40, line 3); thermal management equipment for heating and cooling (page 12, line 16); heating supply plumbed to the individual cell processing module enclosures to provide the requisite temperature environment (page 14, lines 23-25); and a range of sensors to monitor a variety of different parameters, e.g., temperature (page 16, lines 5-10).
Regarding dependent claim 5, Hauwaerts et al. further shows alternative methods, including using cell culture bags with rocking (page 26, line 30).
Regarding dependent claim 6, Hauwaerts et al. further shows genetic modification of cells using standard procedures for implementing the genetic modification step (page 25, lines 10-36 through page 26, lines 1-16).
Regarding dependent claim 7, Hauwaerts et al. further shows that effluent waste collected within the waste vessel may be voided to a sealed waste storage chamber, and that cellular material comprised within the retentate flow is returned to the processing chamber where a defined volume of media is introduced from the reagent vessels (page 33, lines 35-38).
Regarding dependent claim 8, Hauwaerts et al. further shows that fluidic movements are managed by the computer-controlled system which synchronizes pumps and valves to achieve the designated task (page 37, line 35 through page 38, lines 1-4).
Regarding dependent claim 13, Hauwaerts et al. further shows a cell processing device that is an automated fluid handling system that consists of peristaltic pumps, valves, and a bag mixer for the processing bag, and also includes pressure and fluid sensors, and the fluidic movements are managed by the computer-controlled system in the cell processing device, which synchronizes pumps and valves to achieve the designated tasks (page 37, lines 33-35 through page 38, lines 1-5); and at each manufacturing step, cells (provided either as apheresis product at the start of the process or as the in-process cultured cells during the process) are transferred automatically from cell containers (inlet) to the cell processing bag, and for cultured cells, the connection from the cell container to the cell processing bag comprises a series of tube elbows and consecutive tubing diameter changes (page 38, liens 19-25); and automated cell processing methods typically comprise one or more steps selected from: selection and/or enrichment of the cells of interest; activation of cells; genetic modification of cells, e.g., by transduction; expansion of the cells; concentration of the cells; and/or formulation of the cells, wherein the formulation is for preservation (including cryopreservation) and/or direct injection; and that in between these steps, cells will typically be washed with appropriate buffer to remove the excess reagents, or in order to change media (page 22, lines 35-56 through page 23, lines 1-9).
Regarding dependent claim 15, Hauwaerts et al. further shows transferring transduced cell product to and from processing chambers (page 35, lines 23-33).
Regarding dependent claim 21, Hauwaerts et al. further shows the cell processing module comprises a closed, substantially aseptic environment for cell processing (page 3, lines 22-23).
Regarding dependent claim 23, Hauwaerts et al. further shows steps of periodic harvest of cells following the expansion step (page 36, lines 23-27).
Hauwaerts et al. shows independent regulation of environmental conditions for the extended periods of time that may be necessary, i.e., incubation, for the activation step to be completed, however, Hauwaerts et al. does not explicitly show the bioreactor vessel is a first bioreactor vessel; and wherein the instructions are configured to adapt the controller to maintain a third target environment in a second bioreactor vessel for a third incubation period to activate the population of cells, and to initiate a transfer of the activated population of cells to the first bioreactor vessel for genetic modification of the population of cells for the first incubation period (claim 10); or maintaining a third target environment in the second bioreactor vessel for a third incubation period to produce an expanded population of genetically modified cells (claim 16).
Regarding dependent claims 10 and 16, Ghouse et al. shows a system that is readily scalable by increasing the number of processing stations in each unit and the numbers of processing stations in each unit may be tailored to provide the optimum efficiency and throughput by having a larger number of stations in units where the processing step has a long duration and a smaller number of stations in units with short processing steps, (e.g., a small number of stations in the sample isolation unit, and a larger number of stations in the cell expansion unit), and that segregation of processing stations by function enables the provision of the optimum environment (lighting, electrical power and other services, temperature control, etc.) required for the processing stations within a common unit (page 16, lines 7-10).
Therefore, it would have been further obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method shown by Hauwaerts et al. by incorporating methods for maintaining different environments in a modular bioreactor system, as shown by Ghouse et al. and discussed above. One of ordinary skill in the art would have been motivated to combined the methods of Hauwaerts et al. with the methods of Ghouse et al. because Ghouse et al. shows parallel processing of cellular material with the number of processing stations scaled according to the duration of the processing step, and that the segregation of the processing stations by function enables the provision of the optimum environment required for a particular processing station. This modification would have had a reasonable expectation of success given that both Hauwaerts et al. and Ghouse et al. show methods for parallel processing of biological cellular samples using modular bioreactor systems.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, and further in view of Berteau et al. (WO 2015/003012, newly cited).
Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, does not show the instructions are further configured to adapt the controller to receive data from at least one load cell indicating a weight of at least one of the bioreactor vessel, the waste bag and/or a media source bag and control at least one of the first pump and/or the second pump in dependence on the data (claim 9).
Regarding dependent claim 9, Berteau et al. shows a distributed perfusion bioreactor system for continuous culture of biological cells (Title) in which a plurality of modular bioreactors are operated in parallel to produce and maintain a biological cell culture (Abstract); the bioreactor may include one or more sensors or probes for detecting one or more operational parameters in real-time, e.g., a cell culture weight sensor (page 15, lines 12-25) such as a load cell (Figures 2, 9A, 9B, 9C, 9D, and 9E); and various types of device controllers (Figure 12), e.g., to automatically open/close one or more outlet ports at a bioreactor and to control flow rates at the outlet ports (page 30, lines 11-21).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method shown by Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, by incorporating methods for measuring the weight of a bioreactor vessel and its contents for monitoring and controlling various processes, e.g., feeding and/or removing waste, as shown by Berteau et al. and discussed above. One of ordinary skill in the art would have been motivated to combined the methods of Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, with the methods of Berteau et al. because Berteau et al. shows using load cells and various automated device controllers for monitoring and controlling various cell culturing processes in a bioreactor vessel, e.g., feeding and waste removal. This modification would have had a reasonable expectation of success given that both Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, and Berteau et al. disclose methods for operating modular bioreactors in parallel to produce and maintain biological cell cultures.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, and further in view of Vunjak-Novakovic et al. (US 2011/0136225, newly cited).
Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, further shows that at any point in the process, the process may be paused (page 34, lines 4-15).
Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, does not show the instructions are configured to adapt the controller to prompt a user to collect a sample from the bioreactor vessel (claim 11).
Regarding claim 11, Vunjak-Novakovic et al. shows that medium can be withdrawn for sample collection and medium exchange at the outlet port (so that the cartridge contents are sampled) using a syringe (para. [0069]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method shown by Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, by incorporating methods for performing manual sample collection, as shown by Vunjak-Novakovic et al., and discussed above. One of ordinary skill in the art would have been motivated to combined the methods of Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, with the methods of Vunjak-Novakovic et al. because Vunjak-Novakovic et al. shows methods for collecting a sample using an outlet port and a syringe. This modification would have had a reasonable expectation of success given that both Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, and Vunjak-Novakovic et al. disclose systems with cell processing units/cell culture chambers with at least one output port.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, and further in view of Murthy (WO 2017/079674, newly cited).
Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, does not show washing the cells is carried out via filterless perfusion (claim 14).
Regarding dependent claim 14, Murthy shows devices, systems, and methods for the automated production of cells and immunotherapeutic products within a closed system (Abstract) comprising a series of modules arranged in parallel that can process samples ranging from 1-10 to 100s of samples (page 3, lines 7-23); and further shows fluidic systems that provide at least one cell generation module that can culture cells using a filterless construction, whereby maintaining the fluid flow rate below the sedimentation rate, cells remain within the culture chamber because of their mass, thus sinking towards the bottom of the cell culture chamber and therefore remaining in the cell culture chamber without requiring a filter (page 15, lines 30-34 through page 16, lines 1-3).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method shown by Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, by incorporating methods for culturing cells using a filterless system, as shown Murthy and discussed above. One of ordinary skill in the art would have been motivated to combined the methods of Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, with the methods of Murthy because Murthy shows that a filterless system will not suffer clogged filters or require that a filter be replaced. This modification would have had a reasonable expectation of success given that both Hauwaerts et al. in view of Ghouze et al. as applied to claims 1-8, 10, 12, 13, 15, 16, and 21-23 above, and Murthy disclose methods for culturing cells using modular bioreactors operating in parallel.
Response to Arguments
The Applicant’s arguments/remarks received 08 July 2025 have been fully considered, however they are not persuasive.
The Applicant states on page 8 (bottom) of the Remarks that neither Davis, Hollyman, Vunjak-Novakovic, Molleryd, Barringer, nor Murthy, either alone or in combination, teach or suggest each recitation of claims 1, 12, and 22 as currently amended.
This argument is not persuasive, because a new combination of references is used in the above rejection which does not rely on the same references used in the Office action mailed 10 April 2025.
The Applicant states on page 9 (paras. 1-2) of the Remarks that independent claims 1 and 12 have been amended to more particularly and specifically recite aspects of the invention, specifically, that the first module is configured to be utilized in conjunction with the plurality of second modules to provide for parallel and asynchronous processing of the first apheresis product and the second apheresis product. The Applicant further states that, similarly, independent claim 22 has been amended to recite that the first module is configured to be utilized in conjunction with the plurality of second modules, and that as disclosed therein, the utilization of first and second modules (and a third module as recited in claim 22) allows enrichment and isolation of target cells from different patients to be carried out sequentially (and not at the same time), and then transferred to a plurality of second modules where genetic modification and expansion of the different populations of cells can be carried out simultaneously. The Applicant further states that this is critical, as it allows the first module to be freed-up during genetic modification/expansion, the longest duration part of the entire process, so that it can again be used for enrichment and isolation of cells from a different patient, and moreover, as recited in claim 22, the third module is utilized to harvest the different populations of expanded cells from different patients (one at a time), asynchronously. The Applicant further states that as discussed in the specification, in this manner, first and third modules can be used to carry out enrichment/isolation and harvest, respectively, of many different cell populations, while the multiple second modules can be used for the longest part of the process (which frees up the first and third modules for use on different cells/patients), and thus, this particular workflow (asynchronous enrichment and isolation, parallel (i.e., synchronous/simultaneous) genetic modification/expansion, and asynchronous harvest) provides for a level of processing efficiency heretofore not seen in the art.
These arguments are not persuasive, because a new combination of references is used in the above rejection which does not rely on the same references used in the Office action mailed 10 April 2025.
The Applicant states on page 9 (bottom) of the Remarks that the Applicant has reviewed the references of record and can find no disclosure or teaching of this configuration or functionality, specifically, the cited references do not describe or suggest the first module being configured to be utilized in conjunction with the plurality of second modules, and further, the cited references do not describe or suggest the controller being configured to use the first module and the plurality of second modules to provide for parallel and asynchronous processing of the first apheresis product and the second apheresis product. The Applicant further summarizes (Remarks, page 10) the references of record used in the rejection in the Office action mailed 10 April 2025.
These arguments are not persuasive, because a new combination of references is used in the above rejection which does not rely on the same references used in the Office action mailed 10 April 2025.
The Applicant states on page 10 (bottom) of the Remarks that as a final matter, the Applicant notes that a combination of six prior art references has been cited to reject independent claims 1, 12, and 22, despite the present invention not being overly complex, and that accordingly, the Applicant submits that the Examiner’s rejection in this regard is the result of impermissible hindsight reconstruction of the Applicant’s invention, using the Applicant’s own specification as a roadmap through the prior art. The Applicant further states (page 11, para. 1) that the large number of references, combined with the deficiencies of the references and the gaps that remain even with the proposed combinations, does weigh against obviousness.
These arguments are not persuasive, because a new combination of references is used in the above rejection which does not rely on the same references used in the Office action mailed 10 April 2025.
Conclusion
No claims are allowed.
This Office action is a Non-Final action. A shortened statutory period for reply to this action is set to expire THREE MONTHS from the mailing date of this application.
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/S.W.B./Examiner, Art Unit 1687
/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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