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 .
Claim Objections
The claims are objected to because of the following informalities:
Claims 1-25 fail to comply with 37 CFR 1.121(c) and are required to have a status identifier of ‘Cancelled’ since the claims as originally filed have been cancelled.
Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. The status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
Appropriate correction is required.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/6/23 is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group II, claims 26, 31, and 32 (a method for controlling pH) in the reply filed on 6/3/26 is acknowledged.
Claims 1, 2, 4, 6, 7, 8, 9, 11, 14, 15, 19, 21, 23, and 33 are withdrawn from
further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected
inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/3/26.
Claim Status
Claims 26, 31, 32, and new claims 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, and 45 are pending and are examined. Claims 1-25 and 33 are cancelled.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 26, 31, 32, and 34-45 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
The claimed invention is directed to a method for controlling pH without significantly more. The claims recite(s) “initiating pH control”, “comparing the measured pH”, and “determining a volume of the pH”. These limitations under its broadest reasonable interpretation cover performance for the limitation in the mind but for the recitation of generic components. That is, other than reciting “culture wells” and “microplate”, nothing in the claim precludes the step from practically being performed in the mind. For example, the context of this claim encompasses the user manually handling a pH meter.
Similarly, the limitation of comparing first and second items of “comparing the measured pH” is a process that, under its broadest reasonable interpretation, covers performance of the limitation in the mind. For example, the context of this claim encompasses the user evaluating a difference between information.
Similarly, the limitation of “determining whether the measured pH deviates from the predetermined pH” is a process that under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic components. That is, other than reciting “culture wells” and “microplate” nothing in the claim precludes the step from practically being performed in the mind. For example, the context of this claim encompasses the user evaluating what is acceptable based on stored information (“predetermined pH”).
Similarly, the limitation of “determining a volume of the pH” is a process that under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic components. That is, other than reciting “culture wells” and “microplate” nothing in the claim precludes the step from practically being performed in the mind. For example, the context of this claim encompasses the user evaluating what is acceptable based on the user evaluating a difference between information.
This judicial exception is not integrated into a practical application because there is no structure or device recited to perform these steps of initiating, comparing, and determining.
Claim 26 does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the method only lists the step without the actual structures required to perform these steps. Specifically, the other elements of the claims other than the abstract idea and determine are not beyond what is well understood, routine, and conventional within the prior art. Thus, claim 26 is not deemed patent eligible.
Claims 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, and 45 are rejected as being dependent on independent claim 26.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 26, 31, 32, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, and 45 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Klein (US Pub 2005/0176155).
Regarding Claim 26, Klein teaches a method for controlling pH in parallel culture wells ([0039] FIGS. 1 and 2 illustrate a top perspective view and a top plan view of a well plate 100 in accordance with one embodiment of the present invention. Well plate 100 is illustrated as having a top surface 102 and a plurality of wells 110. [0041] pH control for each well.),
the method comprising:
measuring pH in a culture well of a plurality of culture wells contained in a microplate ([0046] each well 110 includes one or more sensors to measure the dissolved oxygen and/or the pH level. The measurement of dissolved oxygen and/or pH level in each well 110); and
initiating pH control for the culture well before measuring pH in at least one or more other culture wells of the plurality of culture wells ([0089] The processor 390 controls the solenoid 308 to provide the appropriate amount of gas to the well 110 to produce the desired pH level. The detection and control of the dissolved oxygen content is controlled in a similar manner.),
wherein the pH control comprises: comparing the measured pH in the culture well to a predetermined pH for the culture well; based on the comparison, determining whether the measured pH deviates from the predetermined pH; and in response to a determination that the measured pH deviates from the predetermined pH ([0046] In addition, each well 110 includes one or more sensors to measure the dissolved oxygen and/or the pH level. The measurement of dissolved oxygen and/or pH level in each well 110 may be used to control the control the supply of gas to the well 110, e.g., in a feedback loop.)
adjusting the pH in the culture well to correct the deviation; wherein adjusting the pH in the culture well to correct the deviation comprises dosing the culture well with pH adjusting fluid, wherein the method further comprises determining a volume of the pH adjusting fluid to dose the culture well with based on a computed correcting variable; and wherein the method further comprises computing the correcting variable based on a difference between the predetermined pH and the measured pH, a proportional factor of a proportional component, and a proportional factor of an integral component ([0097] The drip valves 570 are coupled to a supply 572, which provides the desired liquid to the drip valves 570 to adjust the pH level in the contents of the well 560, such as dilute NaOH or acid. The drip valves are coupled to and controlled by the processor 390. The detection heads 251 associated with each well 560 provide information to the processor 390 regarding the pH level of individual wells. In response the processor 390 controls the flow of liquid into the wells 570 to adjust the pH level to the desired level. The drip valves 570 may be, e.g., peristaltic or syringe pumps or a micro valve. If control over the dissolved oxygen is desired, a gas supply may be provided to the well, e.g., through an aperture in the bottom of the well, as described above.).
Regarding Claim 31, Klein teaches the method of claim 26, wherein the pH is one process parameter measured in the culture well, and the method further comprises: measuring one or more additional process parameters in the culture well before measuring the pH in the at least one or more other culture wells of the plurality of culture wells, the one or more additional process parameters including at least one of dissolved oxygen, biomass, and fluorescence intensity ([0046] each well 110 includes one or more sensors to measure the dissolved oxygen and/or the pH level. The measurement of dissolved oxygen and/or pH level in each well 110 may be used to control the control the supply of gas to the well 110, e.g., in a feedback loop.).
Regarding Claim 32, Klein teaches the method of claim 26, further comprising: determining whether the deviation of the measured pH from the predetermined pH meets a threshold value, wherein the pH in the culture well is only adjusted if the threshold value is met ([0046] The measurement of dissolved oxygen and/or pH level in each well 110 may be used to control the control the supply of gas to the well 110, e.g., in a feedback loop).
Regarding Claim 35, Klein teaches the method of claim 26, wherein measuring pH comprises using an optical sensor device that includes an optical source and a sensor, and a pH optode immobilized in one or more culture wells of the plurality of culture wells ([0059] Figs. 8 and 9. An optical plate 250 is positioned below the support plate 201 and includes optical devices that are used to measure the dissolved oxygen and/or pH level using the sensors 140 and 142. Below the optical plate 250 is a gas manifold 300, which is illustrated schematically in FIGS. 8 and 9. Manifold 300 is used to control the flow of gas to the individual wells 110 in the well plate 100.).
Regarding Claim 36, Klein teaches the method of claim 26, wherein dosing the culture well with pH adjusting fluid comprises conveying the pH adjusting fluid from a fluid source to each of the plurality of culture wells via a fluidics device ([0080] Figs. 8 and 9 As illustrated in FIG. 9, within the manifold 300, separate gas lines 304a, 304b, 304c (collectively 304) are routed from the gas inputs 302 to valves 306a, 306b, and 306c (collectively 306). It should be understood that, although FIG. 9 illustrates the lines overlapping in sections, the gas lines 304a, 304b, and 304c are all separate lines.).
Regarding Claim 37, Klein teaches the method of claim 36, wherein the fluidics device is integrated with the microplate and includes: a plurality of channels connecting the fluid source to each of the plurality of culture wells; anda plurality of valves controlling flow of the pH adjusting fluid between the fluid source and the plurality of culture wells via the plurality of channels; wherein the fluidics device is a microfluidic chip comprising the plurality of channels and the plurality of valves, and wherein the microplate further includes a plurality of reservoir wells as the fluid source containing the pH adjusting fluid, the plurality of reservoir wells positioned above the plurality of valves ([0080] Referring back to FIGS. 8 and 9, gas is supplied to the wells 110 of the well plate 100 through a manifold 300. The manifold includes gas inputs 302a, 302b, and 302c (collectively 302), through which the desired gas is supplied to the manifold 300. As illustrated in FIG. 9, within the manifold 300, separate gas lines 304a, 304b, 304c (collectively 304) are routed from the gas inputs 302 to valves 306a, 306b, and 306c (collectively 306). It should be understood that, although FIG. 9 illustrates the lines overlapping in sections, the gas lines 304a, 304b, and 304c are all separate lines. The valves 306 are operated by solenoids 308a, 308b, and 308c (collectively 308)).
Regarding Claim 38, Klein teaches the method of claim 37, wherein the plurality of channels are disposed planarly underneath a bottom surface of the microplate to allow the pH adjusting fluid to be conveyed from the fluid source to each of the plurality of culture wells via an opening in a bottom surface of each of the plurality of culture wells ([0041] FIG. 3A is a view of the interior bottom surface of one well 110. As can be seen in FIGS. 2 and 3A, each well 110 includes a plurality of apertures. The apertures in the bottom surface of each well 110 provide access for temperature measurement and control and the dissolved oxygen and pH control for each well. [0042] In one embodiment, a plurality of apertures 112 are located in the approximate center of the each well 110 and are used provide a gas to the well 110.).
Regarding Claim 39, Klein teaches the method of claim 37, wherein the microplate includes a cover and the plurality of channels are included in the cover to allow the pH adjusting fluid to be conveyed from the fluid source to each of the plurality of culture wells via an opening in a top surface of each of the plurality of culture wells ([0080] Referring back to FIGS. 8 and 9, gas is supplied to the wells 110 of the well plate 100 through a manifold 300. The manifold includes gas inputs 302a, 302b, and 302c (collectively 302), through which the desired gas is supplied to the manifold 300. As illustrated in FIG. 9, within the manifold 300, separate gas lines 304a, 304b, 304c (collectively 304) are routed from the gas inputs 302 to valves 306a, 306b, and 306c (collectively 306). It should be understood that, although FIG. 9 illustrates the lines overlapping in sections, the gas lines 304a, 304b, and 304c are all separate lines. The valves 306 are operated by solenoids 308a, 308b, and 308c (collectively 308). [0092] Fig. 19 the lid 502 of the well plate 100 and are inserted into the media in the wells 110 when the lid is placed on the well plate 100.).
Regarding Claim 40, Klein teaches the method of claim 36, wherein (i) a top surface of each of the plurality of culture wells includes one or more apertures and the pH adjusting fluid is conveyed to each of the plurality of culture wells via the one or more apertures using an automated pipetting system; or (ii) dosing the culture well with the pH adjusting fluid comprises dosing the culture well with a particular volume of the pH adjusting fluid, the particular volume based on the correcting variable ([0041] FIG. 3A is a view of the interior bottom surface of one well 110. As can be seen in FIGS. 2 and 3A, each well 110 includes a plurality of apertures. The apertures in the bottom surface of each well 110 provide access for temperature measurement and control and the dissolved oxygen and pH control for each well.).
Regarding Claim 41, Klein teaches the method of claim 26, further comprising: receiving, from an application executing on a computing device, a protocol generated based on user input; and storing the protocol in a memory ([0089] in FIG. 16, a detection head on the optics plate 250 is coupled to a processor 390 that is also coupled to a solenoid 308. The pH level in the contents of the well 110, as measured by the sensor 142 and detection head, is determined by the processor 390. The processor 390 controls the solenoid 308 to provide the appropriate amount of gas to the well 110 to produce the desired pH level. The detection and control of the dissolved oxygen content is controlled in a similar manner.).
Regarding Claim 42, Klein teaches the method of claim 41, wherein the predetermined pH for the culture well is obtained from the protocol, the protocol including pH profiles corresponding to the plurality of culture wells, wherein the pH profiles include expected pH values for the plurality of culture wells; and wherein at least one of (i) at least two of the pH profiles corresponding to the plurality of culture wells are different from one another; (ii) a pH profile for at least one of the plurality of culture wells includes a plurality of expected pH values, each of the plurality of expected pH values corresponding to a time period; and (iii) the method further comprises: receiving an instruction corresponding to a user input for modifying a portion of the protocol as an experiment is being run in accordance with the protocol; and causing, in response to the received instruction, the portion of the protocol to be modified based on the received instruction as the experiment is being run, the portion of the protocol modified including at least one pH profile of one of the plurality of culture wells ([0089] The gas supply and sensors may be linked together in a feedback loop. FIG. 16 schematically illustrates a feedback loop for one well 110. As illustrated, in FIG. 16, a detection head on the optics plate 250 is coupled to a processor 390 that is also coupled to a solenoid 308. The pH level in the contents of the well 110, as measured by the sensor 142 and detection head, is determined by the processor 390. The processor 390 controls the solenoid 308 to provide the appropriate amount of gas to the well 110 to produce the desired pH level. The detection and control of the dissolved oxygen content is controlled in a similar manner.).
Regarding Claim 43, Klein teaches the method of claim 42, wherein at least one of (i) the pH of the plurality of culture wells is one process parameter defined by the protocol for measurement, and the protocol further defines one or more additional process parameters for measurement, the one or more additional process parameters including at least one of dissolved oxygen, biomass, and fluorescence intensity; and (ii) the protocol defines a time interval between successive measurements of pH for the plurality of culture wells ([0059] Figs. 8 and 9. An optical plate 250 is positioned below the support plate 201 and includes optical devices that are used to measure the dissolved oxygen and/or pH level using the sensors 140 and 142. Below the optical plate 250 is a gas manifold 300, which is illustrated schematically in FIGS. 8 and 9. Manifold 300 is used to control the flow of gas to the individual wells 110 in the well plate 100.).
Regarding Claim 44, Klein teaches the method of claim 26, further comprising: positioning a pH measurement device from culture well to culture well to successively measure pH for each of the plurality of culture wells; and, after measuring pH for the culture well, repositioning the pH measurement device to a next culture well of the plurality of culture wells for which pH is to be measured ([0065] FIG. 11 is a top plan view of the optics plate 250. Optics plate 250 includes a plurality of detection heads 251 that are used in conjunction with the sensors 140 and 142 to measure the dissolved oxygen and pH level of the contents in a well.).
Regarding Claim 45, Klein teaches the method of claim 26, wherein measuring pH comprises successively measuring pH for each of the plurality of culture wells in a predefined pattern; and wherein the predefined pattern is (i) a serpentine pattern; or (ii) a raster pattern (Fig. 2 Well plate 100 is illustrated as having a top surface 102 and a plurality of wells 110, e.g., 24, 48, 96 or any other desired number of wells that extend generally downward from the top surface 102. Note the rastor pattern which is a grid pattern).
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.
Claim 34 is rejected under 35 U.S.C. 103 as being unpatentable over Klein (US Pub 2005/0176155), in view of Zhang (US Pub 2006/0199260).
Regarding Claim 34, Klein teaches the method of claim 26.
Klein is silent to further comprising: inserting the microplate into a bioreactor.
Zhang teaches in the related art of [0010] In certain aspects of the invention the microscale bioreactors include means for controlling the temperature and/or pHin the culture vessel. [0101] Fig. 1 Robotics may be used, for example, to interface microfermentors or microfermentor arrays with, for example, a microtiter plate from which materials may be transferred into the fermentor or into which samples may be placed.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of inserting the microplate into a bioreactor, as taught by Zhang, in the method, as taught by Klein, to allow for microscale bioreactors (microfermentors) and microscale bioreactor arrays for use in culturing cells, as taught by, Zhang, in the Abstract.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACQUELINE BRAZIN whose telephone number is (571)270-1457. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Charles Capozzi can be reached at 571-270-3638. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JB/
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
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