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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/04/2019 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The abstract of the disclosure is objected to because the abstract contains more than 150 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Interpretation
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) is/are: “rinsing step” and “filtering steps” in claims 16-20.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/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 it/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 it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 103
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.
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.
Claims 1-4, 6-8, and 10-20 are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0148677 A1-Kudugunti et al (hereinafter “Kudugunti”), and further in view of US 2022/0088538 A1-Pavlik (hereinafter “Pavlik”, has an earlier effective filing date as of the provisional application.
Regarding claim 1, Kudugunti discloses a device arrangement for separating cells from a culture medium in a biopharmaceutical process (alternating tangential flow (ATF) has been used to perform filtration and separate cells from product, para. [0046], lines 1-2), comprising; a storage tank for the culture medium (medium and additives are introduced into the bioreactor 210, para. [0058], lines 1-2, Fig. 1); a filtration module being a hollow fiber module, having at least one membrane adapted to be overflowed (an ATF system with a hollow fiber porous membrane, para. [0056], lines 1-2; hollow fiber filter 224, para. [0057], line 8), an intake line (feed line 214, para. [0058], line 2, Fig. 1; connects to bioreactor 210, shown in Fig. 1) which connects the storage tank to an unfiltrate inlet (systems include a bioreactor including an inlet, para. [0017], line 3) of the filtration module for supplying the culture medium into the filtration module, a return line which connects a retentate-side outlet of the filtration module to the storage tank for returning retentate into the storage tank (the ATF device provides at an ATF outlet a liquid containing cell product and returns to the bioreactor, para. [0007], lines 16-17), a filtrate line (bioreactor 210 is connected via a drain tube 212 to an ATF 220, para. [0057], lines 3-4, Fig. 1) which is connected to a permeate-side outlet of the filtration module for discharging filtrate,
Kudugunti discloses a first pump (pump 216, para. [0058], lines 1-3, Fig. 1) for maintaining a recirculation circuit (the ATF device provides at an ATF outlet a liquid containing cell product and returns to the bioreactor culture medium, para. [0007], lines 16-18),
Kudugunti discloses a second pump (pump 222, para. [0057], line 8, Fig. 1) for conveying the rinsing liquid into the filtration module.
Regarding claim 1, Kudugunti teaches the invention discussed above. However, Kudugunti does not explicitly teach a backflush line.
For claim 1, Pavlik teaches an invention relating to relating generally to filtration systems, and more particularly to an alternating tangential flow filtration unit (para. [0002], lines 1-3) and Pavlik teaches when gas is drawn back through line 34, such as by a vacuum source, not shown, in the indicated exhaust direction, the diaphragm 32 is drawn towards the gas inlet (para. [0028], lines 24-28), which reads on the instant claim limitation of a backflush line.
It would have been obvious to one of ordinary skill, in the art at the time, to further include backflush line as taught by Pavlik, because Pavlik teaches his action repeats drawing fluid back and forth from the vessel 2, through the filter, and chamber 30 causing an alternating flow tangentially through the filter 18 (para. 0028], lines 34-37).
Regarding claim 2, Kudugunti discloses characterized in that the rinsing liquid is one of the following: buffer solution; water; or substrate (phosphate buffered saline, para. [0008], line 4).
Regarding claim 3, Kudugunti discloses characterized by a first valve (valve 216, para. [0058], line 3) in the return line
Regarding claim 4, Kudugunti discloses characterized by a second valve (product drain tube 230 has a harvest pump/valve 232 that controls withdrawal of the products that filter across the hollow fiber filter, para. [0058], lines 15-17) in the filtrate line for selectively blocking the discharge of the filtrate.
Regarding claim 6, Kudugunti discloses characterized in that the first pump is integrated into the intake line (medium and additives are introduced into the bio reactor 210 via a feed line 214 , which is controlled by a valve and/or pump 216, para. [0058], lines 1-2).
Regarding claim 7, Kudugunti discloses characterized by a substrate supply line for supplying substrate into the storage tank (medium and additives are introduced into the bioreactor 210 via a feed line 214 , which is controlled by a valve and/or pump 216, para. [0058], lines 1-2).
Regarding claim 8, Kudugunti teaches the invention discussed above in claim 7. Further, Kudugunti teaches a storage tank. However, Kudugunti does not explicitly teach a third pump is provided for conveying the substrate into the storage tank.
For claim 8, Pavlik teaches an invention relating to relating generally to filtration systems, and more particularly to an alternating tangential flow filtration unit (para. [0002], lines 1-3) and Pavlik teaches harvested liquid may be restored by a level control mechanism that activates an additional pump 47 to pump liquid into the vessel through line 51 (para. [0035], lines 10-13), which reads on the instant claim limitation of a third pump is provided for conveying the substrate into the storage tank.
It would have been obvious to one of ordinary skill, in the art at the time, to further include a third pump is provided for conveying the substrate into the storage tank as taught by Pavlik, because Pavlik suggest the additional pump allows for liquid to be pumped in to the vessel (para. [0035], lines 10-13).
Regarding claim 10, Kudugunti teaches the invention discussed above in claim 7. Further, Kudugunti teaches a substrate supply line, discussed above. However, Kudugunti does not explicitly teach a fourth valve in the substrate supply for selectively blocking the supply of a substrate.
For claim 10, Pavlik teaches an invention relating to relating generally to filtration systems, and more particularly to an alternating tangential flow filtration unit (para. [0002], lines 1-3) and Pavlik teaches valve 10 in piping 8 (para. [0034], lines 10-11, Fig. 1), which reads on the instant claim limitation of a fourth valve in the substrate supply for selectively blocking the supply of a substrate.
It would have been obvious to one of ordinary skill, in the art at the time, to further include a fourth valve in the substrate supply for selectively blocking the supply of a substrate, as taught by Pavlik, because Pavlik teaches the piping 8 can include appropriate valves 10 and 12 for selectively isolating, or allowing, flow between the vessel 2 (para. [0034], lines 10-13).
Regarding claim 11, Kudugunti teaches the invention discussed above in claim 9. However, Kudugunti does not explicitly teach a sterile filter integrated in the backflush line.
For claim 11, Pavlik teaches a backflush line with an integrated filter (inlet/exhaust line 34 is attached to pump 24 via a connector such that when the gas is passed through the line 34, it is injected into the first chamber 28 of the pump and fills the first chamber 28 with the gas expanding the chamber and flushing any fluid in the second chamber 30 in a direction toward and through the filter 18, para. [0028], lines 12-19), which reads on the instant claim limitation of a sterile filter integrated in the backflush line.
It would have been obvious to one of ordinary skill, in the art at the time, to further include a sterile filter integrated in the backflush line as taught by Pavlik, because Pavlik teaches a diaphragm pump 24 is used to move the fluid from the vessel 2 through the filter 18 in the filter containing compartment 4 into the pump 24 and then reversing the fluid flow from pump 24 back through the filter to vessel 2 (para. [0026], lines 1-5).
Regarding claim 12, Kudugunti teaches the invention discussed above in claim 1. Further, Kudugunti teaches a controller arranged and programed to carry out one or more of the methods described herein, either singly or in various combinations and subcombinations (para. [0017], lines 9-11). However, Kudugunti does not explicitly teach sensors for directly or indirectly determining and monitoring one or more of the following parameters: viscosity; electrical conductivity; recirculation flow and/or filtrate flow; or transmembrane pressure.
For claim 12, Pavlik teaches sensors and sensor assemblies integrated into bioprocessing systems (abstract; para. [0002], lines 1-4), which reads on the instant claim limitation of sensors for directly or indirectly determining and monitoring one or more of the following parameters: viscosity; electrical conductivity; recirculation flow and/or filtrate flow.
It would have been obvious to one of ordinary skill, in the art at the time, to further include sensors for directly or indirectly determining and monitoring one or more of the following parameters: viscosity; electrical conductivity; recirculation flow and/or filtrate flow as taught by Pavlik, because Pavlik teaches t is desirable to monitor certain process variables, such as temperature, pH, optical density or turbidity, and/or viable cell density (para. [0056], lines 1-4).
Regarding claim 13, Kudugunti discloses the invention discussed above in claim 1. Further, Kudugunti discloses a method of separating cells from a culture medium (the present disclosure includes methods of harvesting a cell product from a cell culture, para. [0007], lines 1-2), using a device arrangement (a cell culture system including a bioreactor connected to an alternating tangential flow (ATF) device, para. [0007], lines )
11-13), the method comprising steps of:
-cultivating cells in a culture medium in a bioreactor (bioreactor 210, para. [0057], line 2, Fig. 1);
-filtering the culture medium in a filtration module having at least one membrane, being a hollow fiber module (an ATF system with a hollow fiber porous membrane, para. [0056], lines 1-2; hollow fiber filter 224, para. [0057], line 8), the culture medium passing through a recirculation circuit (the ATF device provides at an ATF outlet a liquid containing cell product and returns to the bioreactor culture medium, para. [0007], lines 16-18);
-rinsing the membrane using a rinsing liquid during filtration, the rinsing liquid being a buffer solution or water or substrate (phosphate buffered saline, para. [0008], line 4), and rinsing liquid being introduced into the recirculation circuit by the rinsing (the fluid medium used to refill the bioreactor can be phosphate buffered saline (PBS), or cell culture medium, or any other liquid that can be used to maintain the cells alive, para. [0008], lines 3-6).
Regarding claim 14, Kudugunti discloses characterized in that the rinsing liquid is conveyed via a separate line into one or more permeate-side connection(s) of the filtration module (medium and additives are introduced into the bio reactor 210 via a feed line 214, para. [0058], lines 1-2).
Regarding claim 15, Kudugunti teaches the invention discussed above in claim 1. However, Kudugunti does not explicitly teach one or more of the following parameters are determined and monitored at least during filtration: viscosity; electrical conductivity; recirculation flow and/or filtrate flow; or transmembrane pressure; and in that a backflush is initiated and controlled depending on whether one or more predetermined limit values of said parameters are reached and a backflush line.
For claim 15, Pavlik teaches sensors and sensor assemblies integrated into bioprocessing systems (abstract; para. [0002], lines 1-4), which reads on the instant claim limitation of one or more of the following parameters are determined and monitored at least during filtration: viscosity; electrical conductivity; recirculation flow and/or filtrate flow; or transmembrane pressure; and in that a backflush is initiated and controlled depending on whether one or more predetermined limit values of said parameters are reached.
It would have been obvious to one of ordinary skill, in the art at the time, to further include sensors for directly or indirectly determining and monitoring one or more of the following parameters: viscosity; electrical conductivity; recirculation flow and/or filtrate flow as taught by Pavlik, because Pavlik teaches t is desirable to monitor certain process variables, such as temperature, pH, optical density or turbidity, and/or viable cell density (para. [0056], lines 1-4).
Additionally, for claim 15, Pavlik teaches an invention relating to relating generally to filtration systems, and more particularly to an alternating tangential flow filtration unit (para. [0002], lines 1-3) and Pavlik teaches when gas is drawn back through line 34, such as by a vacuum source, not shown, in the indicated exhaust direction, the diaphragm 32 is drawn towards the gas inlet (para. [0028], lines 24-28), which reads on the instant claim limitation of a backflush line.
It would have been obvious to one of ordinary skill, in the art at the time, to further include backflush line as taught by Pavlik, because Pavlik teaches his action repeats drawing fluid back and forth from the vessel 2, through the filter, and chamber 30 causing an alternating flow tangentially through the filter 18 (para. 0028], lines 34-37).
Regarding claim 16, Kudugunti discloses the rinsing step is carried out several times in succession (the harvesting drain process resumes at flux of approximately 15 LMH until the volume in the bioreactor 210 again drops to approximately 30 % . This cycle is repeated a third and fourth time, if desired or required, para. [0060], lines 16-20).
Regarding claim 17, Kudugunti discloses the rinsing step is repeated cyclically during filtration (the rapid harvest can be accomplished by cyclical removal of volume from the culture vessel and refilling (batch filtration, para. [0059], lines 5-7).
Regarding claim 18, Kudugunti discloses the repeated rinsing step is carried out with different rinsing liquids (the fluid medium used to refill the bioreactor can be phosphate buffered saline (PBS), or cell culture medium, or any other liquid that can be used to maintain the cells alive, para. [0008], lines 3-6).
Regarding claim 19, Kudugunti discloses characterized in that the cultivating and filtering steps are carried out one after the other (the draining step and the refilling step are performed sequentially, and/or the refilling step and draining step are performed two or more times, para. [0009], lines 5-7; the rapid harvest of a culture with ATF has utility in commercial processes as an economically advantageous way to obtain a clarified feed stream suitable for further processing in a single step, para. [0046], lines 9-12).
Regarding claim 20, Kudugunti discloses characterized in that the cultivating and filtering steps are carried out at least partially simultaneously (any two or more of the draining step, the extracting step, and the refilling step can occur simultaneously and at a first flow rate, para. [0013], lines 1-3; ATF10 bioreactors can be run simultaneously, para. [0094], line 1).
Allowable Subject Matter
Claims 5 and 9 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: for claim 5, the prior art fails to teach or fairly suggest a third valve in the backflush line for selectively blocking the supply of the rinsing liquid to the filtration module, where these limitations are in combination with the claim as a whole.
The closest prior art is US 2018/0148677 A1-Kudugunti and US 2022/0088538 A1-Pavlik. Kudugunti teaches methods and systems of harvesting a cell product from a cell culture by culturing cells in a fluid medium until the cells have produced a cell product at a harvest concentration are disclosed. The cells are cultured in a cell culture system including a bioreactor connected to an ATF device. Pavlik an invention relating to apparatuses and methods that integrate sensors into bioprocessing systems and, advantageously, do not require significant re-engineering of these systems. The disclosure describes an assembly for alternating tangential flow filtration. However, Kudugunti and Pavlik do not teach or fairly suggest a third valve in the backflush line for selectively blocking the supply of the rinsing liquid to the filtration module.
The following is a statement of reasons for the indication of allowable subject matter: for claim 9, the prior art fails to teach or fairly suggest characterized in that the substrate supply line and the backflush line open upstream of the second pump into a common supply line, which in turn opens into the permeate-side connection and/or into the permeate-side outlet of the filtration module, where these limitations are in combination with the claim as a whole.
The closest prior art is US 2018/0148677 A1-Kudugunti and US 2022/0088538 A1-Pavlik. Kudugunti teaches methods and systems of harvesting a cell product from a cell culture by culturing cells in a fluid medium until the cells have produced a cell product at a harvest concentration are disclosed. The cells are cultured in a cell culture system including a bioreactor connected to an ATF device. Pavlik an invention relating to apparatuses and methods that integrate sensors into bioprocessing systems and, advantageously, do not require significant re-engineering of these systems. The disclosure describes an assembly for alternating tangential flow filtration. However, Kudugunti and Pavlik do not teach or fairly suggest characterized in that the substrate supply line and the backflush line open upstream of the second pump into a common supply line, which in turn opens into the permeate-side connection and/or into the permeate-side outlet of the filtration module.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LENORA A. ABEL whose telephone number is (571)272-8270. The examiner can normally be reached Monday-Friday 7:00am-4:00pm.
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/L.A.A./Examiner, Art Unit 1799
/MICHAEL L HOBBS/Primary Examiner, Art Unit 1799
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