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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/12/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election with traverse of Group I, claims 1-2, 5, 9, 14, 17, 20-21, 23, 28-29, 41, 44-45, 52, 54-55, 57, 60, 65 and 68-69 in the reply filed on 03/09/2026 is acknowledged. The traversal is on the ground(s) that claims 1-2, 5, 9, 14, 17, 20-21, 23, 28-29, 41, 44-45, 52, 54-55, 57, 60, 65, and 68-69 (Group I) and claims 132 (Group III) being related as a product and a process that requires such product, respectively. This is not found persuasive because MPEP § 806.05(e) states that an apparatus and process for its practice are distinct if it can be shown that either: (1) the process as claimed can be practiced by another and materially different apparatus or by hand, or (2) the apparatus as claimed can be used to practice another and materially different process. As disclosed in the previous office action, the apparatus as claimed can be used with a process that does not require expanding cells in a cell culture fluid in a bioreactor as required by the method.
As to applicant’s remarks regarding MPEP § 821.04(b), it appears that applicant has conflated a restriction traversal with that of a request for rejoinder. A rejoinder is only applicable to examined claims that have been found to be allowable. Since none of the claims (elected invention) of the instant application have received a first action on the merits and are in condition for allowance, a request for rejoinder at this stage is moot. Further, it is noted that MPEP § 821.04(b) states Where claims directed to a product and to a process of making and/or using the product are presented in the same application, applicant may be called upon under 35 U.S.C. 121 to elect claims to either the product or a process.
The requirement is still deemed proper and is therefore made FINAL.
Claims 76 and 132 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 03/09/2026.
Claim Rejections - 35 USC § 112
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.
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 65 is 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.
Regarding claim 65, it is unclear what the accuracy requirement corresponds to. Therefore, the scope of the claim cannot be determined. Is the accuracy requirement representative of a retentate yield, a permeate yield, a flow rate, etc.?
Claim 65 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, for failing to further limit the subject matter of the claim upon which it depends. Claim 65 does not further limit the structure of the bioreactor system of claim 1. 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 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.
Claims 1-2, 5, 9, 14, 17, 20, 21, 23, 28, 29, 41, 44, 45, 52, 54, 55, 57, 60, 68, and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Castillo et al. (hereinafter Castillo) US 2020/0318060.
Regarding claim 1, Castillo discloses a bioreactor system, comprising: (a) a bioreactor (bioreactor 1) including an input port and an output port as shown in Fig. 4 reproduced below; (b) a feed stream conduit operably connected to the output port and an inlet of a Hollow Fiber (HF) filter (concentrator 2) [0046, 0081 and 0086], wherein the feed stream conduit is operable to carry fluid from the bioreactor to the HF filter, as shown in Fig. 4 reproduced below; (c) a retentate stream conduit operably connected to the input port of the bioreactor and an outlet of the HF filter, wherein the retentate stream conduit is operable to carry fluid to the bioreactor from the HF filter, [0043 and 0072], as shown in Fig. 4 reproduced below; and (d) a multi-purpose assembly operably connected to the HF filter, wherein the multi-purpose assembly includes including a first flow path and a second flow path, wherein the first flowpath includes a first pump (pump 5) operable to draw fluid from the HF filter and a first flow meter operable to measure flow rate of fluid in the first flowpath (In an embodiment, the conduits of the system comprise pumps, valves and flow meters or sensors to control and monitor the flow of liquid from, for example, the concentrator to the bioreactor and/or intermediate vessel. [0040]); wherein the second flowpath includes a second pump (pump 5) operable to draw fluid from the HF filter (The system may comprise one or more decontamination vessels and may be adapted with suitable conduits such as an output conduit line from the concentrator to the decontamination vessel(s) in order to discard the permeate. In some embodiments, the system comprises at least 1, 2, 3, 4, 5, 6, 8, 10, or more decontamination vessels, [0049]. In an embodiment, the conduits of the system comprise pumps, valves and flow meters or sensors to control and monitor the flow of liquid from, for example, the concentrator to the bioreactor and/or intermediate vessel, [0040].). Therefore, Castillo discloses a second flowpath including a second pump. Also see whole document.
Alternatively, it would have been prima facie obvious to one of ordinary skill in the art to provide a second flowpath including a second pump, since it has been held that mere duplication of the essential working parts of a device involves only routine skill in the art. See MPEP §2144.04 (VI-B).
Castillo does not expressly state that the first pump and the second pump are configured to have different pump capacities. However, Castillo does disclose in [0045] that the conduits of the system are fitted with one or more pumps to provide directional liquid flow and to allow control or induce differential pressure between different parts of the system. In a further embodiment, the pumps can operate both forward and backwards. Castillo further discloses in [0053] the process flow from the bioreactor to the concentrator is controlled by a process controller or process control device. The controller controls and operates bioreactor parameters as well as process flow parameters and monitors and records data from one or more sensors described above (pH, temperature and/or DO). Preferably, liquid flow is managed by the controller in the system by controlling the functioning of the pumps and or valves present therein. In an embodiment the process control device provides automated control of the system’s process flow. Therefore, absent unexpected results, it would have been obvious to one of ordinary skill in the art to configure the one or more pumps of Castillo to operate at different pump capacities in order to optimize the production and purification of biomolecules resulting in a high yield of the biomolecules, thereby significantly reducing the cost of goods as well as capital expenditures.
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Regarding claim 2, Castillo discloses wherein the HF filter is operable for tangential flow [0086].
Regarding claim 5, Castillo discloses one or more clarification filter(s) in the first flow path and/or second flow path (In an embodiment, the system is provided with a pre-filter which is positioned between the bioreactor and the concentrator. In some embodiments, the system includes at least 1, 2, 3, 4, 5, 6, 8, 10, or more pre-filters, [0047 and 0050].).
Regarding claim 9, as to the intended use limitations (…wherein the retentate stream conduit is operable to carry cell culture fluid to the bioreactor from the HF filter, wherein the first flowpath includes including the first pump operable to draw fluid from the HF filter and is operable to draw a perfusion permeate stream fluid from the HF filter, and wherein the second flowpath includes including the second pump operable to draw fluid from the HF filter and is operable to draw a harvest permeate stream fluid from the HF filter.), the device disclosed by Castillo is structurally the same as the instantly claimed. Thus, in the absence of further positively recited structure the device of Castillo is capable of providing the operating conditions as listed in the intended use section of the claim in view of paragraphs [0005-0006, 0022-0023, 0040 and 0049].
Further, it is noted that apparatus claims cover what a device is, not what a device does or how it is to be used. A claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim. See MPEP § 2114.
Regarding claims 14, 17, 20, 21, 23, 28, 54, 55, 57 and 60, Castillo does not expressly disclose the claimed operating parameters (e.g., a feed flow rate, a flow rate and a flux rate) of the first and second pump. However, Castillo does disclose in [0045] that the conduits of the system are fitted with one or more pumps to provide directional liquid flow and to allow control or induce differential pressure between different parts of the system. In a further embodiment, the pumps can operate both forward and backwards. Castillo further discloses in [0053] the process flow from the bioreactor to the concentrator is controlled by a process controller or process control device. The controller controls and operates bioreactor parameters as well as process flow parameters and monitors and records data from one or more sensors described above (pH, temperature and/or DO). Preferably, liquid flow is managed by the controller in the system by controlling the functioning of the pumps and or valves present therein. In an embodiment the process control device provides automated control of the system’s process flow. Therefore, absent unexpected results, it would have been obvious to one of ordinary skill in the art to configure the one or more pumps of Castillo to operate under the claimed conditions in order to optimize the production and purification of biomolecules resulting in a high yield of the biomolecules, thereby significantly reducing the cost of goods as well as capital expenditures.
Alternatively, the device disclosed by Castillo is structurally the same as the instantly claimed. Thus, in the absence of further positively recited structure the device of Castillo is capable of providing the operating conditions as listed in the intended use section of the claim in view of paragraphs [0045, 0053, 0092 and 0117].
Further, it is noted that apparatus claims cover what a device is, not what a device does or how it is to be used. A claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim. See MPEP § 2114.
Regarding claim 29, Castillo discloses wherein the first pump is operable to draw fluid from the HF filter while maintaining a shear rate (s-1) of less than about 5,000 s-1 [0091].
Regarding claim 41, Castillo discloses wherein the bioreactor system is capable of operating in a perfusion process, an in-between perfusion and harvest process, and a harvest process [0037-0038, 0041 and 0087].
Regarding claim 44, Castillo discloses wherein the bioreactor system is capable of operating in a continuous harvest process [0034 and 0038].
Regarding claim 45, Castillo discloses a human machine interface (HMI) control unit (computer), wherein the HMI control unit is programmed and can display (touch screen 29) perfusion process controls, in-between perfusion and harvest process controls, or harvest process controls [0053-0054 and 0093].
Regarding claim 52, Castillo discloses a second flow meter operable to measure flow rate of fluid in the second flowpath (The system may comprise one or more decontamination vessels and may be adapted with suitable conduits such as an output conduit line from the concentrator to the decontamination vessel(s) in order to discard the permeate. In some embodiments, the system comprises at least 1, 2, 3, 4, 5, 6, 8, 10, or more decontamination vessels, [0049]. In an embodiment, the conduits of the system comprise pumps, valves and flow meters or sensors to control and monitor the flow of liquid from, for example, the concentrator to the bioreactor and/or intermediate vessel, [0040].). Therefore, Castillo discloses a second flow meter.
Alternatively, it would have been prima facie obvious to one of ordinary skill in the art to provide a second flow meter, since it has been held that mere duplication of the essential working parts of a device involves only routine skill in the art. See MPEP §2144.04 (VI-B).
As to accurately monitoring a flow rate of about 0 to about 10 LPM. Castillo discloses in [0040] the conduits of the system comprise pumps, valves and flow meters or sensors to control and monitor the flow of liquid from, for example, the concentrator to the bioreactor and/or intermediate vessel. Castillo further discloses in [0053] the process flow from the bioreactor to the concentrator is controlled by a process controller or process control device. The controller controls and operates bioreactor parameters as well as process flow parameters and monitors and records data from one or more sensors described above (pH, temperature and/or DO). Preferably, liquid flow is managed by the controller in the system by controlling the functioning of the pumps and or valves present therein. In an embodiment the process control device provides automated control of the system’s process flow. Therefore, absent unexpected results, it would have been obvious to one of ordinary skill in the art to configure the second flow meter of Castillo to accurately monitor a flow rate of about 0 to about 10 LPM in order to optimize the production and purification of biomolecules resulting in a high yield of the biomolecules, thereby significantly reducing the cost of goods as well as capital expenditures.
Regarding claim 68, Castillo does not explicitly disclose wherein the HF filter comprises isotropic pore structure and/or pores with an average lumen diameter of about 0.65 µm to about 8 µm.
Castillo discloses that the tangential flow filtration device (TFF) may be provided with at least one hollow fiber having pores with a specific porosity, e.g. a porosity sufficient to retain practically all of the target biomolecules in the retentate, while permitting smaller contaminants such as growth medium and solutes to end up in the permeate [0086]. Also see [0043 and 0072].
Therefore absent unexpected results, it would have been obvious to one of ordinary skill in the art to modify the hollow fiber with an isotropic pore structure and/or pores with an average lumen diameter of about 0.65 µm to about 8 µm, since 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. See MPEP §2144.05 (II-A).
Regarding claim 69, Castillo discloses wherein the bioreactor system is operable for use with shear sensitive cells and/or operable for use with cells for the production of a biologic [0005-0006, 0018 and 0022-0023].
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Shevitz US 2013/0059371 and Steen US 10,350,518 represent analogous art since Shevitz and Steen are reasonably pertinent to the problem being solved, namely filtering a liquid feed through a tangential flow filtration (TFF) system.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYDIA EDWARDS whose telephone number is (571)270-3242. The examiner can normally be reached on Monday-Wednesday 08:00-18:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Curtis Mayes can be reached on 571-272-1234. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LYDIA EDWARDS/Primary Examiner, Art Unit 1796
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