Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Status
Claims 1, 3-6, and 8, 10-25 are pending. Claims 10-19 are withdrawn.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3-6, and 8 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over A High Capacity Strong Cation Exchange Resin for the Chromatographic Purification of Monoclonal Antibodies and Other Proteins by O’Donnell et al. (O’Donnell) in view of U.S. Patent No. 7901581 by Bryntesson et al. (Bryntesson); U.S. Patent No. 7901581 was previously published as WO2008/153472 on December 18, 2008
In regard to claim 1, O’Donnell teaches a method for determining binding capacities of a chromatography column (slide 6, “dynamic binding capacity”). O’Donnell teaches detecting a feed signal representative of a composition of a feed material provided to an inlet of the column (slides 4 and 6; Figure; the feed signal is represented on the Figure on slide 6 at the zero coordinate). O’Donnell teaches detecting an effluent signal representative of the composition of the effluent from the column (slides 4 and 6; Figure; effluent signal is represented on the Figure on slide 6 at all points past the zero coordinate). O’Donnell teaches using the feed signal and the effluent signal to monitory binding capacities of the column (slide 6). It is inherent that in order to monitor a binding capacity that there would be a feed and effluent signal, representative of a feed signal, at an inlet of a feed line, and an effluent signal, at an outlet of a chromatography column, in order to compare the compositions to one another in order to determine a breakthrough. O’Donnell teaches continuously determining the binding capacities of the column during the chromatography process (slide 6); O’Donnell teaches continuous determining of the binding capacities is independent of a feed concentration of the feed material (slide 6).
O’Donnell teaches disposing a feed material in an inlet of one of the at least two chromatography columns (slide 4).
O’Donnell does not specifically teach that when a certain breakthrough or saturation point level has been reached a control system controls the chromatography system to proceed to a next process step. O’Donnell does not specifically teach simulated moving bed (SMB). O’Donnell does not teach the method comprises detecting the pH, conductivity, light scattering, fluorescence, IR, or visible light in the feed material and an effluent.
Further, Bryntesson teaches a method of binding a component to an adsorbent and determining a breakthrough (abstract; C7/L14-19). Bryntesson teaches generating a feed signal at an inlet of a chromatography column (Figure 5, UV between C1 and C2; C10/L29-37). Bryntesson teaches a feed signal detector (Figure 5, UV between C1 and C2; C10/L29-37). Bryntesson teaches the feed signal detector is upstream of at least two chromatography columns (Figure 5, UV between C1 and C2; C10/L29-37; upstream of both C2 and C3). Bryntesson teaches the feed signal detector is directly connected to a determining unit (Figure 5, PC; C10/L18-37). The detector is used to determine the breakthrough (C7/L14-19). Bryntesson teaches a detector generating an effluent signal at the outlet of a chromatography column (Figure 5; UV between C2 and C3; C10/L29-37). It would have been obvious to one of ordinary skill in the art at the time of the invention to have incorporated the step of measuring a feed signal, at an inlet of the first column, and an effluent signal, at an outlet of the first column, as taught by Bryntesson, into the method of O’Donnell in order to determine the breakthrough based on comparison of feed and effluent concentrations. Bryntesson teaches that it is known in the art of chromatography to control a process based on system characteristics, such as purity or recovery (C2/L27-41). Bryntesson teaches controlling flow rate to adjust liquid streams and process productivity (C9/LL30-39). Bryntesson teaches detecting an effluent signal for each chromatography column in a periodic counter current system (C1/L34-38; C4/L46-50; C3/L34-36). Bryntesson teaches that continuous chromatography allows for adjustments in series or parallel and can be operated simultaneously (C1/L34-38). Byntesson teaches simulated moving bed (abstract; C1/L34-50). Bryntesson also teaches that continuous chromatography results in a better utilization of chromatography resin, reduced processing time, and reduced buffer requirements, which benefits process economy (C1/L46-50). Bryntesson teaches adjusting flow rate of the stream in a desired manner to improve productivity (C9/L16-29). Bryntesson teaches when a certain breakthrough or saturation point level has been reached a control system controls the chromatography system to proceed to a next process step (C6/L65 to C7/L41; C9/L30-39; C3/L1-10; C2/L27-41). Bryntesson teaches the method comprises detecting the pH, conductivity, or light scattering in the feed material and an effluent (C8/L15-20; C10/L29-33; C9/L1-7).
It would have been obvious to one of ordinary skill in the art at the time of the invention to have incorporated the method of monitoring binding capacities, as taught by O’Donnell, into the simulated moving bed system which comprises multiple columns, taught by Bryntesson, in order to better utilize chromatography resin, reduce processing time, reduce buffer requirements, and benefit process economy. It would be obvious to one of ordinary skill in the art at the time of the invention to compensate for a difference in properties of at least two columns of a chromatography system, as taught by Bryntesson, in the method of O’Donnell in order to achieve desired chromatography results in a continuous process with chromatography columns connected in series and to improve productivity.
Bryntesson teaches detecting an effluent signal for each chromatography column in a system (C1/L34-38; C4/L46-50; C3/L34-36). Bryntesson teaches that continuous chromatography allows for adjustments in series or parallel and can be operated simultaneously (C1/L34-38). Bryntesson also teaches that continuous chromatography results in a better utilization of chromatography resin, reduced processing time, and reduced buffer requirements, which benefits process economy (C1/L46-50). Bryntesson teaches adjusting flow rate of the stream in a desired manner to improve productivity (C9/L16-29).
In regard to claim 3, O’Donnell teaches detecting the feed signal and the effluent signal using the same type of detector (slide 6).
In regard to claims 4-5, O’Donnell teaches the difference between the feed signal and the effluent signal is the delta signal. The delta signal is calculated to be defined as the feed signal chosen from any signals measured between the second given time reduced by the predetermined delay time and the first given time minus the effluent signal measured at the first given time. The predetermined delay time is a time for a nonbinding compound in the sample to travel from the first detector to the second detector.
In regard to claim 6, O’Donnell teaches using the deltasignal to determine a breakthrough point (c) and/or a saturation point (d) of the column (slide 6, slide 8). O’Donnell teaches breakthrough point and saturation point being calculated as a respective certain predefined percentage of the deltasignalmax (slide 6, slide 8).
In regard to claim 8, O’Donnell teaches detecting the UV absorbance in the feed material and effluent (slide 6).
Claims 20-25 are rejected under pre-AIA 35 U.S.C. 103(a) as obvious over A High Capacity Strong Cation Exchange Resin for the Chromatographic Purification of Monoclonal Antibodies and Other Proteins by O’Donnell et al. (O’Donnell) in view of U.S. Patent No. 7901581 by Bryntesson et al. (Bryntesson), as noted above, and additionally as evidenced by AKTAprime Plus Operating Instructions by General Electric (General Electric); U.S. Patent No. 7901581 was previously published as WO2008/153472 on December 18, 2008.
In regard to claim 20, modified O’Donnell teaches all the limitations as noted above. O’Donnell teaches a method for use with a chromatography system conducting a chromatography process (slide 6). O’Donnell teaches a method for determining binding capacities of a chromatography column (slide 6, “dynamic binding capacity”). O’Donnell teaches automatically and continuously determining a breakthrough point of at least one column (slide 6, chart). O’Donnell teaches the method is performed with an AKTAprime system (slide 4). General Electric provides evidence that the AKTAprime system has a control system (page 16, page 38). O’Donnell teaches multiple columns with non-identical properties (slide 2).
O’Donnell teaches determining binding capacities of the at least one chromatography column according to claim 1 (see rejection of claim 1 above).
O’Donnell controlling the start and stop of the different chromatography process steps according to the determined binding capacities (slide 6, slide 8). O’Donnell teaches dynamically controlling the process in real-time by stopping the process shortly after 10% breakthrough (slide 6, slide 8); controlling the process would result in controlling a feed to a column.
In regard to claim 21, modified O’Donnell teaches all the limitations as noted above.
Bryntesson teaches detecting an effluent signal for each chromatography column in a periodic counter current system (C1/L34-38; C4/L46-50; C3/L34-36). O’Donnell teaches continuously determining the binding capacities of the column during the chromatography process (slide 6). The binding capacity is determined continuously as the UV detection is measured throughout the process as seen by the continuous nature of the lines on the Figure (slide 6).
O’Donnell controlling the start and stop of the different chromatography process steps according to the determined binding capacities (slide 6, slide 8). O’Donnell teaches dynamically controlling the process in real-time by stopping the process shortly after 10% breakthrough (slide 6, slide 8); controlling the process would result in controlling a feed to a column.
In regard to claim 22, modified O’Donnell teaches all the limitations as noted above. Bryntesson teaches a method for controlling a simulated moving bed system comprising at least two column (abstract, C1/L34-38; C4/L46-50; C3/L34-36).
O’Donnell teaches a method for determining binding capacities of a chromatography column (slide 6, “dynamic binding capacity”). O’Donnell teaches detecting a feed signal representative of a composition of a feed material provided to the inlet of the column (slides 4 and 6; Figure; the feed signal is represented on the Figure on slide 6 at the zero coordinate). O’Donnell teaches detecting an effluent signal representative of the composition of the effluent from the column (slides 4 and 6; Figure; effluent signal is represented on the Figure on slide 6 at all points past the zero coordinate). O’Donnell teaches using the feed signal and the effluent signal to determine binding capacities of the column (slide 6). It is inherent that in order to determine a binding capacity that there would be a feed and effluent signal, representative of a feed signal, at an inlet of a feed line, and an effluent signal, at an outlet of a chromatography column, in order to compare the compositions to one another in order to determine a breakthrough.
Further, Bryntesson teaches a method of binding a component to an adsorbent and determining a breakthrough (abstract; C7/L14-19). Bryntesson teaches generating a feed single at an inlet of a chromatography column (Figure 5, UV between C1 and C2; C10/L29-37). The detector is used to determine the breakthrough (C7/L14-19). Bryntesson teaches a detector generating an effluent signal at the outlet of a chromatography column (Figure 5; UV between C2 and C3; C10/L29-37). It would have been obvious to one of ordinary skill in the art at the time of the invention to have incorporated the step of measuring a feed signal, at an inlet of the first column, and an effluent signal, at an outlet of the first column, as taught by Bryntesson, into the method of O’Donnell in order to determine the breakthrough based on comparison of feed and effluent concentrations. Bryntesson teaches that it is known in the art of chromatography to control a process based on system characteristics, such as purity or recovery (C2/L27-41). Bryntesson teaches controlling flow rate to adjust liquid streams and process productivity (C9/LL30-39). Bryntesson teaches detecting an effluent signal for each chromatography column in a periodic counter current system (C1/L34-38; C4/L46-50; C3/L34-36). Bryntesson teaches that continuous chromatography allows for adjustments in series or parallel and can be operated simultaneously (C1/L34-38). Bryntesson also teaches that continuous chromatography results in a better utilization of chromatography resin, reduced processing time, and reduced buffer requirements, which benefits process economy (C1/L46-50). Bryntesson teaches adjusting flow rate of the stream in a desired manner to improve productivity (C9/L16-29).
It would have been obvious to one of ordinary skill in the art at the time of the invention to have incorporated the method of determining binding capacities, as taught by O’Donnell, into the periodic counter current system which comprises multiple columns, taught by Bryntesson, in order to better utilize chromatography resin, reduce processing time, reduce buffer requirements, and benefit process economy. It would be obvious to one of ordinary skill in the art at the time of the invention to compensate for a difference in properties of at least two columns of a chromatography system, as taught by Bryntesson, in the method of O’Donnell in order to achieve desired chromatography results in a continuous process with chromatography columns connected in series and to improve productivity.
O’Donnell teaches dynamically controlling the process in real-time by stopping the process shortly after 10% breakthrough (slide 6, slide 8); controlling the process would result in controlling a feed to a column.
In regard to claim 23, modified O’Donnell teaches all the limitations as noted above. O’Donnell teaches continuously determining the binding capacities of the column during the chromatography process (slide 6). The binding capacity is determined continuously as the UV detection is measured throughout the process as seen by the continuous nature of the lines on the Figure (slide 6).
O’Donnell controlling the start and stop of the different chromatography process steps according to the determined binding capacities (slide 6, slide 8). O’Donnell teaches dynamically controlling the process in real-time by stopping the process shortly after 10% breakthrough (slide 6, slide 8); controlling the process would result in controlling a feed to a column.
In regard to claim 24, modified O’Donnell teaches all the limitations as noted above.
O’Donnell controlling the start and stop of the different chromatography process steps according to the determined binding capacities (slide 6, slide 8). O’Donnell teaches dynamically controlling the process in real-time by stopping the process shortly after 10% breakthrough (slide 6, slide 8); controlling the process would result in controlling a feed to a column. Bryntesson teaches pumps (C10/L18-37).
In regard to claim 25, modified O’Donnell teaches all the limitations as noted above.
O’Donnell teaches compensating for any differences in the different column properties and/or flow rates by adjusting for how long, and in which position, different columns should be in the loading zone according to the determined binding capacities (slide 6, slide 8).
Claim Rejections - 35 USC § 101
Claims 1, 3-6, 8 and 20-25 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon consideration of all of the relevant factors with respect to the claims as a whole, claims 1, 3-6, 8 and 20-26 are determined to be directed to an abstract idea. The claimed invention is directed to an abstract idea without significantly more. The claims recite a mathematical relationship involving the feed signal, effluent signal, and binding capacity; further, the monitoring of binding capacity is also considered a mental process. This judicial exception is not integrated into a particular practical application because the additional recited elements are directed to generic simulated moving bed chromatography method steps and do not add a meaningful limitation to the abstract idea. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The rationale for this determination is further explained below:
The claims fall within the statutory class of a process; however, the claims are directed to an abstract idea. The abstract idea of these claims is a mathematical relationship between binding capacity and the feed and effluent signals.
There are no other limitations in the claim that show a patent-eligible application of the abstract idea itself. The steps of “providing the simulated moving bed system, wherein the simulated moving bed system comprises at least two chromatography columns”; “disposing a feed material in an inlet of one of the at least two chromatography columns”; “detecting with a feed signal a feed signal representative of a composition of the feed material provided to the inlet of one of the at least two chromatography columns of the simulated moving bed system”, “detecting with an effluent signal detector an effluent signal from each chromatography column in the simulated moving bed, SMB, system, wherein the feed signal detector is upstream of the at least two chromatography columns, the effluent signal detector is downstream of one or more of the at least two chromatography columns, and the feed signal detector and the effluent signal detector are directly connected to a determining unit”; “wherein when a certain breakthrough or saturation point level has been reached a control system controls the chromatography system to proceed to a next process step”; and “wherein the method comprises detecting the UV absorbance, pH, conductivity, light scattering, fluorescence, IR, or visible light in the feed material and an effluent” do not significantly amount to anything more than measuring a feed signal and measuring an effluent signal in a PCC system and extra-solution activity. The limitation “wherein when a certain breakthrough or saturation point level has been reached a control system controls the chromatography system to proceed to a next process step, wherein the determining unit is configured to use the feed signal and the effluent signals to determine the breakthrough or saturation point level” appears to be nothing more than a generic statement of post solution activity generically applying the abstract idea.
These steps are routine and conventional steps of composition measurement. Measuring a signal and relating the signal to a composition is a fundamental principal of absorbance measurement. The fact that the claim requires measuring signals does not result in anything significantly more than the abstract idea, because this is a basic principle of spectroscopy. See MPEP §2106.
In essence the claims as a whole are directed to an abstract idea as both the intended use limitation and conventional data gathering do not contribute significantly more to the claim.
The courts have recognized that performing repetitive calculations, electronic record keeping, and storing and receiving information in memory as well‐understood, routine, and conventional functions when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. Performing repetitive calculations, Flook, 437 U.S. at 594, 198 USPQ2d at 199 (recomputing or readjusting alarm limit values); Bancorp Services v. Sun Life, 687 F.3d 1266, 1278, 103 USPQ2d 1425, 1433 (Fed. Cir. 2012) ("The computer required by some of Bancorp’s claims is employed only for its most basic function, the performance of repetitive calculations, and as such does not impose meaningful limits on the scope of those claims."). Electronic recordkeeping, Alice Corp., 134 S. Ct. at 2359, 110 USPQ2d at 1984 (creating and maintaining "shadow accounts"); Ultramercial, 772 F.3d at 716, 112 USPQ2d at 1755 (updating an activity log). Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93. See MPEP 2106.05(d),II.
The courts have held computer‐implemented processes not to be significantly more than an abstract idea (and thus ineligible) where the claim as a whole amounts to nothing more than generic computer functions merely used to implement an abstract idea, such as an idea that could be done by a human analog (i.e., by hand or by merely thinking). On the other hand, courts have held computer-implemented processes to be significantly more than an abstract idea (and thus eligible), where generic computer components are able in combination to perform functions that are not merely generic. DDR Holdings, LLC v. Hotels.com, L.P., 773 F.3d 1245, 1257-59, 113 USPQ2d 1097, 1105-07 (Fed. Cir. 2014). An abstract idea is present in the claim and the claim does not amount to significantly more than the abstract idea itself. See MPEP 2106.
In essence the claims as a whole are directed to an abstract idea as all of the limitations noted above do not contribute significantly more to the claim.
Additionally, see Parker v. Flook found in Federal Register, Vol. 79, No. 241, Tuesday, December 16, 2014 which is similar to this situation. A process is not unpatentable simply because it contains a law of nature or mathematical algorithm. The claim as a whole must be analyzed to determine what additional elements are recited in the claim.
As the claim is directed to a broad concept of controlling operation of a chromatography system and appears to be merely post solution activity directed by the generic solution, the claim is not directed to patent eligible subject matter and does not comply with 25 U.S.C. 101.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive. The updated rejection above incorporates citations for the added limitations.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/KARA M PEO/Primary Examiner, Art Unit 1777
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