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 Status
Claims 1-27 are pending and under examination.
Claims 28-30 have been canceled.
Response to Amendment
The claim objection(s) previously set forth in the non-final rejection have been maintained.
In view of Applicant’s amended claims and remarks, the previous prior art rejection over Fava has been modified to address the claim amendments (see below).
The terminal disclaimer, filed 04/08/2026, has been accepted. Therefore, the double patenting rejection(s) have been withdrawn.
Claim Objections
Claim 3 is objected to because of the following informalities:
Claim 3 recites “the assay protocol is created using comprises…” which appears to be grammatically incorrect and should recite “the assay protocol comprises…”.
Appropriate correction is required.
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 and 6-11, 13-17 and 19-27 are rejected under 35 U.S.C. 103 as being unpatentable over Fava et al. (US 2002/0147515; already of record – hereinafter “Fava”), where CRS (A255 Robot Arm User Guide; already of record – hereinafter “CRS”) is used as supporting documentation, in view of Wang et al. (US 2015/0320022; already of record – hereinafter “Wang”), and further in view of Food and Drug Administration 21 CFR Part 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals; in effect on 01/01/2022; already of record – hereinafter “FDA 211”).
Regarding claim 1, Fava disclose an automated system for conducting a GMP-compliant assay (Fava; figs. 1-4, [0020]), comprising:
a computer system (Fava disclose a laboratory automation workcell system LAWS comprising a process control PC, data manager DM, laboratory information system LIS, Laboratory information system driver U, a graphical user interface GUI, and an automation managing system AMS; figs. 1 & 2, [0015, 0017]), wherein the computer system receives an assay protocol for a GMP-compliant assay, stores the assay protocol for the GMP-compliant assay (Fava disclose the laboratory automation workcell system (LAWS) may be configured to automate a specific assay or a number of assays. A user interface allows the creation of a protocol by a user to be stored in a protocol by a user to be stored in a protocol database and obtained by a process controller for executing the programs; [0031, 0037-0039, 0041-0042, 0044, 0073-0077]), and wherein the computer system is capable of collecting data associated with at least one sample subjected to the assay protocol (Fava disclose the process controller maintains the history and status of each plate processed through the system and communicates with the automated equipment while it creates a log file and data export files for the laboratory information system. Each plate has a local copy of its sample protocol with its associated execution status stored in the protocol database. The export file contains the data deriving from any plate reader and a number of meta-data that describe the experiment like data, time, operator name, protocol name, reader type, reader settings for positive control of e.g. correct settings of filters and measurement units; [0044-0045, 0077, 0083]), validating the collected data (Fava disclose when all test results are received the laboratory automation workcell system process controller takes a decision, depending on the result and the configured expert-system rules, to release the rules to the laboratory information system or to ask the operator intervention to validate the result. The rules and configuration parameters include automatic test re-execution, reflex testing, and mathematical calculations of derived results, or to view test results and eventually validate or schedule a re-execution of the tests that the internal laboratory automation workcell system data manager expert system does not handle automatically, or for diagnostic and troubleshooting reasons; [0023, 0027]), and producing a GMP-compliant dataset based on the collected data (The Food and Drug Administration 21 CFR Part 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals; in effect on 01/01/2022 states under § 211.68 Automatic, mechanical, and electronic equipment “(b) Appropriate controls shall be exercised over computer or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel. Input to and output from the computer or related system of formulas or other records or data shall be checked for accuracy. The degree and frequency of input/output verification shall be based on the complexity and reliability of the computer or related system. A backup file of data entered into the computer or related system shall be maintained except where certain data, such as calculations performed in connection with laboratory analysis, are eliminated by computerization or other automated processes. In such instances a written record of the program shall be maintained along with appropriate validation data. Hard copy or alternative systems, such as duplicates, tapes, or microfilm, designed to assure that backup data are exact and complete and that it is secure from alteration, inadvertent erasures, or loss shall be maintained.”. Fava disclose control over changes in master production and control records or other records are instituted only by authorized personnel; [0044-0045, 0076-0077]). Fava also disclose a backup file of data entered into the computer or related system shall be maintained; [0077, 0083]); and
at least one automated equipment capable of subjecting the at least one sample to the assay protocol, wherein the computer system causes automated operation of the at least one automated equipment (Fava disclose the laboratory automation workcell system automates all the pre-analytical, analytical and post analytical phases of sample assaying in a homogeneous, concurrent, reactive, dynamic and expert-system-rule based fashion using a process controller. The system equipment includes centrifuges, decappers, assaying devices, sample carrier devices, turntables, sample container handling devices, readers, storage carousels, tip rack carousels, dispensers, liquid handling robots, plate shakers, incubators, plate washers, and detectors [0017, 0020, 0031-0039, 0041-0042, 0044-0045, 0077, 0083, 0085]), wherein the computer system and the at least one automated equipment are qualified (Fava disclose user defined lines of script to perform processing steps by a processor using the automated equipment; [0027, 0031, 0043-0044, 0076]. Accordingly, the automated equipment would necessarily need to meet the requirements defined by the computer programming code to perform the steps. Fava further disclose a resource logic status that determines if a resource is ready, busy, in an error state, or task end state; [0029, 0052, 0054]. In the case of an error, the equipment is not able to execute the programming code and is thus not qualified), and
wherein the GMP-compliant dataset includes an audit trail of the dataset (The Food and Drug Administration 21 CFR Part 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals; in effect on 01/01/2022 states under § 211.68 Automatic, mechanical, and electronic equipment “(b) Appropriate controls shall be exercised over computer or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel. Input to and output from the computer or related system of formulas or other records or data shall be checked for accuracy. The degree and frequency of input/output verification shall be based on the complexity and reliability of the computer or related system. A backup file of data entered into the computer or related system shall be maintained except where certain data, such as calculations performed in connection with laboratory analysis, are eliminated by computerization or other automated processes. In such instances a written record of the program shall be maintained along with appropriate validation data. Hard copy or alternative systems, such as duplicates, tapes, or microfilm, designed to assure that backup data are exact and complete and that it is secure from alteration, inadvertent erasures, or loss shall be maintained.”. Fava disclose control over changes in master production and control records or other records are instituted only by authorized personnel; 0044-0045, 0076-0077]). Fava also disclose a backup file of data entered into the computer or related system shall be maintained; [0077, 0083]. The process controller maintains the history and status of each plate processed through the system and communicates with the automated equipment while it creates a log file and data export files for the laboratory information system. Each plate has a local copy of its sample protocol with its associated execution status stored in the protocol database. The export file contains the data deriving from any plate reader and a number of meta-data that describe the experiment like data, time, operator name, protocol name, reader type, reader settings for positive control of e.g. correct settings of filters and measurement units; [0044-0045, 0077, 0083]), identification of location data for the at least one sample throughout execution of the assay protocol (Fava; [0044-0045, 0077, 0083]), and a record of any changes to the assay protocol, software and at least one automated equipment controlled by the computer system (Fava; [0076]).
Fava does not teach the assay is for dupilumab, wherein the at least one sample comprises dupilumab, and the dataset is for dupilumab.
However, Wang disclose the analogous art of conducting an assay for dupilumab on at least one sample comprising dupilumab (Wang; [0193]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the assay performed by Fava with the assay for dupilumab, and to modify the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, because Wang teaches assay performed on the at least one sample comprising Dupilumab determines the neutralizing effect against IL-4 (Wang; [0193]). Further, it would have been obvious to make the dupilumab assay of Wang automated as in Fava for the advantage of increased reproducibility, higher throughput, and use of less personal, because automating the dupilumab assay of Wang is merely automating a manual activity which is not considered patentably distinguishable over the prior art. In re Venner, 262 F.2d 91, 95, 120 USPQ 193, 194 (CCPA 1958) (Appellant argued that claims to a permanent mold casting apparatus for molding trunk pistons were allowable over the prior art because the claimed invention combined "old permanent-mold structures together with a timer and solenoid which automatically actuates the known pressure valve system to release the inner core after a predetermined time has elapsed." The court held that broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art.). See MPEP 2144.04(III). The modification resulting in the dataset of Fava being for dupilumab. One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since Fava and Wang teach performing an assay on at least one sample.
If it is deemed that modified Fava does not teach the automated system is GMP-compliant for conducting a GMP-compliant assay, or the dataset being GMP-compliant, FDA 211 disclose the analogous art of collecting data associated with at least one sample subjected to an assay protocol (FDA 211, p. 27, “§ 211.194 Laboratory records”, subsection (a)), wherein the data collection is GMP-compliant for conducting a GMP-compliant assay (FDA 211, p. 27, “§ 211.194 Laboratory records”).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the automated system of modified Fava to be GMP-compliant, as directed by the FDA, because the GMP-compliant guidelines set forth by the Food and Drug Administration are used in drug product commercialization and distribution to humans or animals in which laboratory records of all tests, including assays, are required. The modification therefore comprising a GMP-compliant assay and GMP-compliant dataset. One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since modified Fava and FDA 211 both teach collecting data on an assay for a drug product.
Regarding claim 2, modified Fava teach the system of claim 1 above, wherein the GMP-compliant assay for dupilumab is a bioassay (The modification of the assay performed by Fava with the assay for dupilumab, and the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, and the modification of the automated system of modified Fava to be GMP-compliant, as directed by the FDA, have previously been discussed in claim 1 above. The in vitro IgE class-switching assay taught by Wang is a bioassay).
Regarding claim 3, modified Fava teach the system of claim 1 above, wherein the assay protocol is created using comprises workflow visualization, real-time control, monitoring, and error management on multiple devices in an integrated software platform (Fava disclose the laboratory automation workcell system may be configured to automate a specific assay or a number of assays, wherein creation of a protocol is performed by a user; fig. 1, [0015. 0031, 0037-0039, 0041-0059, 0061-0065, 0073-0084]).
Regarding claim 4, modified Fava teach the system of claim 1 above, wherein the assay protocol is optimized using data collected from the at least one sample comprising dupilumab subjected to the assay protocol (The modification of the assay performed by Fava with the assay for dupilumab, and the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, has previously been discussed in claim 1 above. Fava disclose optimizing the assay protocol using data from the at least one sample; [0026-0027, 0067, 0071-0072]).
Regarding claim 6, modified Fava teach the system of claim 1 above, wherein the assay protocol is subjected to quality control review between 1 and 31 times per month, between 1 and 10 times per month, between 1 and 7 times per week, 1 time per week, 2 times per week, or 3 times per week (Fava; [0080]. Additionally, the modification of the method of modified Fava to be GMP-compliant, as directed by the FDA, has previously been discussed in claim 1 above. Sections § 211.22 (a), § 211.100(a), and §211.160(a) of the guidelines direct a quality control unit to “review production records to assure that no errors have occurred … written procedures, including any changes, shall be drafted, review, and approved by the appropriate organizational units and revied and approved by the quality control unit … any specifications, standards, sampling plans, test procedures, or other laboratory control mechanism … shall be … reviewed and approved by the quality control unit”. Accordingly, a quality control review is required for GMP-compliance).
Note: “wherein the protocol is subjected to quality control review between 1 and 31 times per month, between 1 and 10 times per month, between 1 and 7 times per week, 1 time per week, 2 times per week, or 3 times per week” relates to function/intended use. However, functional language does not add any further structure to an apparatus beyond that of a capability. See MPEP 2114 and 2111.04. Apparatus claims must distinguish over the prior art in terms of structure rather than function. Therefore, if the prior art structure is capable of performing the function, then the prior art meets the limitation in the claims.
Regarding claim 7, modified Fava teach the system of claim 1 above, wherein the computer system causes automated operation of the at least one automated equipment using a scheduling software (Fava; [0004, 0026-0027, 0030, 0040, 0043, 0069]).
Regarding claim 8, modified Fava teach the system of claim 7 above, wherein the scheduling software comprises workflow visualization, real-time control, monitoring, and error management on multiple devices in an integrated software platform (Fava; fig. 1, [0015, 0041-0059, 0061-0065, 0073-0084]).
Regarding claim 9, modified Fava teach the system of claim 1 above, wherein the at least one automated equipment includes a robotic arm (Fava; [0032, 0059]).
Regarding claim 10, modified Fava teach the system of claim 9 above, wherein the robotic arm is configured to move in the x, y, and z axes (Fava disclose equipment includes a CRS Robotics A255 articulated robot 13 mounted on a 4.5 meter long Inpecto TR-10/4 air bearing track (a double pair of pincers are designed to transfer Microtiter plates and Tip Racks and Sample Tubes to and from all Resources in the LAWS; [0032, 0059]. CRS part 1, page 1, paragraph 1 and corresponding figure disclose a robotic arm configured to move in the x, y, and z axes).
Regarding claim 11, modified Fava teach the system of claim 1 above, wherein the at least one automated equipment includes at least one liquid handler and/or reagent dispenser (Fava; [0033]).
Regarding claim 13, modified Fava teach the system of claim 1 above, wherein the at least one sample comprising dupilumab is selected from a group consisting of cell culture fluid, harvested cell culture fluid, filtrate, chromatography eluate, drug substance, and drug product (The modification of the assay performed by Fava with the assay for dupilumab, and the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, has previously been discussed in claim 1 above. Dupilumab is a drug substance and a drug product).
Regarding claim 14, modified Fava teach the system of claim 1 above, wherein collecting data comprises subjecting the at least one sample comprising dupilumab to at least one measurement (The modification of the assay performed by Fava with the assay for dupilumab, and the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, has previously been discussed in claim 1 above. Fava; [0023, 0033-0036, 0042, 0084]).
Regarding claim 15, modified Fava teach the system of claim 14 above, wherein the at least one measurement is selected from a group consisting of spectrophotometry, ultraviolet detection, fluorescence detection, luminescence detection, radioactivity detection, Raman spectroscopy, mass spectrometry, biolayer interferometry, surface plasmon resonance, and absorbance detection (Fava; [0034-0037]).
Regarding claim 16, modified Fava teach the system of claim 1 above, wherein the at least one sample comprising dupilumab is contained in a microplate (The modification of the assay performed by Fava with the assay for dupilumab, and the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, has previously been discussed in claim 1 above. Fava; [0032, 0083]).
Regarding claim 17, modified Fava teach the system of claim 1 above, wherein collecting data includes using at least one data analysis software (Fava; [0023, 0027]).
Regarding claim 19, modified Fava teach the system of claim 1 above, wherein the GMP-compliant dataset of dupilumab includes a unique identifier for the at least one sample comprising dupilumab (The modification of the assay performed by Fava with the assay for dupilumab, and the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, and the modification of the automated system of modified Fava to be GMP-compliant, as directed by the FDA, have previously been discussed in claim 1 above. Fava disclose the dataset includes a unique identifier for the at least one sample; [0018, 0022, 0083-0085]).
Regarding claim 20, modified Fava teach the system of claim 1 above, wherein the GMP-compliant dataset of dupilumab includes a unique identifier for a container containing the at least one sample comprising dupilumab (The modification of the assay performed by Fava with the assay for dupilumab, and the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, and the modification of the automated system of modified Fava to be GMP-compliant, as directed by the FDA, have previously been discussed in claim 1 above. Fava disclose the dataset includes a unique identifier for a container containing the at least one sample; [0018, 0022, 0083-0085]).
Regarding claim 21, modified Fava teach the system of claim 20 above, wherein the unique identifier is a barcode (Fava; [0018, 0022, 0083-0085]).
Regarding claim 22, modified Fava teach the system of claim 21 above, wherein the barcode is generated using a label printer (Fava; [0018, 0022, 0083-0085]).
Regarding claim 23, modified Fava teach the system of claim 21 above, wherein the container is labeled with the barcode using a label printer (Fava; [0018, 0022, 0083-0085]).
Regarding claim 24, modified Fava teach the system of claim 21 above, wherein the automated operation comprises scanning the barcode at each step of subjecting the at least one sample comprising dupilumab to the assay protocol to generate location data for the at least one sample comprising dupilumab (The modification of the assay performed by Fava with the assay for dupilumab, and the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, has previously been discussed in claim 1 above. Fava disclose standard export files associated with the barcode of each plate that is updated each time the barcode is scanned during the assay process; [0044-0045, 0077, 0083]).
Regarding claim 25, modified Fava teach the system of claim 1 above, wherein the GMP-compliant assay for dupilumab is a cell-based assay (The modification of the assay performed by Fava with the assay for dupilumab, and the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, and the modification of the automated system of modified Fava to be GMP-compliant, as directed by the FDA, have previously been discussed in claim 1 above. Wang teach the assay is an in vitro IgE class-switching assay with primary B cells isolated from humanized IL-4Rα mice; [0193]).
Regarding claim 26, modified Fava teach the system of claim 1 above, further comprising a qualification system for qualifying the computer system and the at least one automated equipment (Fava disclose user defined lines of script to perform processing steps by a processor using the automated equipment; [0027, 0031, 0043-0044, 0076]. Accordingly, the automated equipment would necessarily need to meet the requirements defined by the computer programming code to perform the steps. Fava further disclose a resource logic status that determines if a resource is ready, busy, in an error state, or task end state; [0029, 0052, 0054]. In the case of an error, the equipment is not able to execute the programming code and is thus not qualified. Further, the modification of the assay performed by Fava with the assay for dupilumab, and the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, and the modification of the automated system of modified Fava to be GMP-compliant, as directed by the FDA, have previously been discussed in claim 1 above. Accordingly, the LAWS system of modified Fava comprising a qualification system for qualifying the computer system and the at least one automated equipment).
Regarding claim 27, modified Fava teach the system of claim 26 above, wherein the qualification system is capable of qualifying the performance of the computer system and the at least one automated equipment (Fava disclose user defined lines of script to perform processing steps by a processor using the automated equipment; [0027, 0031, 0043-0044, 0076]. Accordingly, the automated equipment would necessarily need to meet the requirements defined by the computer programming code to perform the steps. Fava further disclose a resource logic status that determines if a resource is ready, busy, in an error state, or task end state; [0029, 0052, 0054]. In the case of an error, the equipment is not able to execute the programming code and is thus not qualified. Further, the modification of the assay performed by Fava with the assay for dupilumab, and the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, and the modification of the automated system of modified Fava to be GMP-compliant, as directed by the FDA, have previously been discussed in claim 1 above. Accordingly, the LAWS system of modified Fava comprising a qualification system capable of qualifying the performance of the computer system and the at least one automated equipment).
Claim 3 and 8 are additionally rejected under 35 U.S.C. 103 as being unpatentable over Fava, where CRS is used as supporting documentation, in view of Wang, and further in view of Greka et al. (US 2021/0169827; already of record – hereinafter “Greka”), or alternatively over Fava, where CRS is used as supporting documentation, in view of Wang and FDA 211, and further in view of Greka.
Regarding claim 3, modified Fava teach the system of claim 1 above, comprising the assay protocol.
Modified Fava does not teach wherein the assay protocol is created using comprises workflow visualization, real-time control, monitoring, and error management on multiple devices in an integrated software platform.
However, Greka teaches the analogous art of an automated system comprising automated equipment, wherein the automated system uses Cellario (Greka; [0329]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the computer system of modified Fava to use Cellario for scheduling software, as taught by Greka, because Greka teaches Cellario software allows the automated equipment of the automated system to be choreograph so that the protocol may be performed.
NOTE: When the claimed invention and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, the prior art products necessarily possess the characteristics of the claimed product. See MPEP 2112.01. As stated in In re Best, 562 F.2d 1252, 1255 (CCPA 1977): Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. Whether the rejection is based on “inherency” under 35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO’s inability to manufacture products or to obtain and compare prior art products. See MPEP 2112. A review of applicant’s as-filed specification states “In a specific aspect, the scheduling software is Cellario”, see paragraphs [0013, 0031]. In this case, Greka disclose an identical product.
Regarding claim 8, modified Fava teach the system of claim 7 above, comprising the scheduling software.
Modified Fava does not teach wherein the scheduling software is comprises workflow visualization, real-time control, monitoring, and error management on multiple devices in an integrated software platform.
However, Greka teaches the analogous art of an automated system comprising automated equipment, wherein the automated system uses Cellario (Greka; [0329]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the computer system of modified Fava to use Cellario for scheduling software, as taught by Greka, because Greka teaches Cellario software allows the automated equipment of the automated system to be choreograph so that the protocol may be performed.
NOTE: When the claimed invention and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, the prior art products necessarily possess the characteristics of the claimed product. See MPEP 2112.01. As stated in In re Best, 562 F.2d 1252, 1255 (CCPA 1977): Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. Whether the rejection is based on “inherency” under 35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO’s inability to manufacture products or to obtain and compare prior art products. See MPEP 2112. A review of applicant’s as-filed specification states “In a specific aspect, the scheduling software is Cellario”, see paragraphs [0013, 0031]. In this case, Greka disclose an identical product.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Fava, where CRS is used as supporting documentation, in view of Wang, and further in view of Mishima et al. (US 2006/0190187; already of record – hereinafter “Mishima”) or alternatively over Fava, where CRS is used as supporting documentation, in view of Wang and FDA 211, and further in view of Mishima.
Regarding claim 5, modified Fava disclose the system of claim 1 above, comprising the assay protocol.
Modified Fava does not teach wherein the assay protocol is protected by a password.
However, Mishima teach the analogous art of an automated system (Mishima; figs. 1 & 2, [0053-0054]), wherein the automated system is protected by a password (Mishima; figs. 21-23, S2, [0110]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the automated system comprising the protocol of modified Fava with the password protected system, as in Mishima, because Mishima teach the password grands access to a user’s confirmation database for the application program stored on the hard disk, and authenticates the user by determining whether or not there is an account recording the logon ID and password, whether or not the account is valid, and whether or not the account expiration time has expired; Mishima; [0110]). One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since modified Fava and Mishima both teach systems that perform automated assays on samples.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Fava, where CRS is used as supporting documentation, in view of Wang, and further in view of Noggle et al. (US 2013/0345094; already of record – hereinafter “Noggle”) or alternatively over Fava, where CRS is used as supporting documentation, in view of Wang and FDA 211, and further in view of Noggle.
Regarding claim 12, modified Fava teach the system of claim 11 above, comprising the at least one liquid handler and/or reagent dispenser configured to dispense (Fava; [0033]).
Modified Fava does not teach wherein the at least one liquid handler and/or reagent dispenser is configured to dispense between 0.5 µL to 1000 µL per channel, monitor air displacement, and comprises dynamic positioning system, and capacitance and pressure sensors.
However, Noggle teach the analogous art of at least one liquid handler and/or reagent dispenser configured to dispense (Noggle; fig. 5A, #100, [0218]), wherein the at least one liquid handler and/or reagent dispenser is configured to dispense between 0.5 µL to 1000 µL per channel, monitor air displacement, and comprises dynamic positioning system, and capacitance and pressure sensors (Noggle teach a Hamilton STARlet liquid handling robot; [0218]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the at least one liquid handler and/or reagent dispenser configured to dispense of modified Fava with the Hamilton STARlet liquid handling robot, as taught by Noggle, because Noggle teach the Hamilton STARlet liquid handling robot can be controlled by programmable software on a PC and is equipped with a modular arm for 4/8/12 channel pipetting (Noggle; [0230]). One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since modified Fava and Noggle both teach laboratory automation with liquid handlers.
NOTE: When the claimed invention and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, the prior art products necessarily possess the characteristics of the claimed product. See MPEP 2112.01. As stated in In re Best, 562 F.2d 1252, 1255 (CCPA 1977): Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. Whether the rejection is based on “inherency” under 35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO’s inability to manufacture products or to obtain and compare prior art products. See MPEP 2112. A review of applicant’s as-filed specification states “In a specific aspect, the at least one liquid handler and/or reagent dispenser is a Hamilton STARlet”, see paragraphs [0015, 0033]. In this case, Noggle disclose an identical product.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Fava, where CRS is used as supporting documentation, in view of Wang, and further in view of XU (US 2021/0011033; already of record – hereinafter “XU”) or alternatively over Fava, where CRS is used as supporting documentation, in view of Wang and FDA 211, and further in view of XU.
Regarding claim 18, modified Fava teach the system of claim 17 above, comprising the at least one data analysis software (Fava; [0023, 0027]).
Modified Fava does not teach wherein the at least one data analysis software comprises pre-configured assay protocols, curve-fitting algorithms, cross-plate analysis, interpolation and automatic calculation metrics, data acquisition and visualization functions.
However, XU teach the analogous art of conducting an assay (XU; [0122]) and using at least one software comprising pre-configured assay protocols, curve-fitting algorithms, cross-plate analysis, interpolation and automatic calculation metrics, data acquisition and visualization functions to analyze data (XU teach using Softmax software to plot the standard curve of assay results; [0122]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the at least one data analysis software of modified Fava with Softmax software, as taught by XU, because XU teach Softmax software can be used to plot the standard curve for an assay (XU; [0122]). One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since modified Fava and XU both teach data analysis of an assay using software.
NOTE: When the claimed invention and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, the prior art products necessarily possess the characteristics of the claimed product. See MPEP 2112.01. As stated in In re Best, 562 F.2d 1252, 1255 (CCPA 1977): Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. Whether the rejection is based on “inherency” under 35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO’s inability to manufacture products or to obtain and compare prior art products. See MPEP 2112. A review of applicant’s as-filed specification states “In a specific aspect, the at least one data analysis software is SoftMax”, see paragraphs [0020, 0038]. In this case, XU disclose an identical product.
Response to Arguments
Applicant’s arguments and remarks, filed 04/08/2026, have been considered.
Applicant argues on page 1 of their remarks towards the 103 rejection over claim 1 that none of the prior art provides motivation or guidance for the validation of the collected data produced in the PMG-compliant dataset or the use of a qualified computer system and at least one qualified automated equipment.
The examiner respectfully disagrees. Fava disclose the laboratory automation workcell system automates all the pre-analytical, analytical and post analytical phases of sample assaying in a homogeneous, concurrent, reactive, dynamic and expert-system-rule based fashion using a process controller. The system equipment includes centrifuges, decappers, assaying devices, sample carrier devices, turntables, sample container handling devices, readers, storage carousels, tip rack carousels, dispensers, liquid handling robots, plate shakers, incubators, plate washers, and detectors [0017, 0020, 0031-0039, 0041-0042, 0044-0045, 0077, 0083, 0085]. User defined lines of script are programmed to perform processing steps by a processor using the automated equipment; [0027, 0031, 0043-0044, 0076]. Accordingly, the automated equipment would necessarily need to meet the requirements defined by the computer programming code to perform the steps. Fava further disclose a resource logic status that determines if a resource is ready, busy, in an error state, or task end state; [0029, 0052, 0054]. In the case of an error, the equipment is not able to execute the programming code and would thus not be qualified. Fava also disclose when all test results are received the laboratory automation workcell system process controller takes a decision, depending on the result and the configured expert-system rules, to release the rules to the laboratory information system or to ask the operator intervention to validate the result. The rules and configuration parameters include automatic test re-execution, reflex testing, and mathematical calculations of derived results, or to view test results and eventually validate or schedule a re-execution of the tests that the internal laboratory automation workcell system data manager expert system does not handle automatically, or for diagnostic and troubleshooting reasons; [0023, 0027].
Applicant argues on pages 4-5 of their remarks towards the 103 rejection over claim 1 that Fava does not teach or suggest that the automated system can be applied to at least one sample comprising dupilumab.
The examiner respectfully disagrees. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Fava disclose all of the claimed physical elements to perform an assay where Wang is relied upon for teach an assay for Dupilumab. Accordingly, Fava in view of Wang disclose the claimed features.
Applicant argues on pages 2-4 towards the 103 rejection over claims 1 and 30 that Fava does not teach an audit trail of the dataset including identification of location data for the at least one sample throughout execution of the protocol, a record of any modifications to the assay protocol, or software and equipment controlled by the computer. Applicant further argues that it would not have been obvious to modify the assay performed by Fava with the assay for dupilumab, as taught by Wang, because Wang does not teach or suggest that the manual assay is suitable for automation and that the claimed method goes beyond mere automation of the manual method by providing an unexpected advantage of the manual method by providing secure storage and validation of assay data, which in turn generates comprehensive, traceable audit trails thus significantly reducing the rate of invalid results.
The examiner respectfully disagrees. Fava disclose control over changes in master production and control records or other records are instituted only by authorized personnel; [0044-0045, 0076-0077]). Fava also disclose a backup file of data entered into the computer or related system shall be maintained; [0077, 0083]. Fava specifically disclose that data files and export logs are generated each time a barcode on a sample is scanned which include date, time, Operator name, protocol name, reader type, reader settings for positive control of e.g. correct settings of filters and measurement units, and that at any moment during protocol definition to modify, added, or deleted any line of script, the protocols are saved with a specific identification and version number so that they can be used in any future moment. See Fava paragraphs [0044-0045, 0076-0077, 0083]. Additionally, automating a manual activity is not considered patentably distinguishable over the prior art. In re Venner, 262 F.2d 91, 95, 120 USPQ 193, 194 (CCPA 1958) (Appellant argued that claims to a permanent mold casting apparatus for molding trunk pistons were allowable over the prior art because the claimed invention combined "old permanent-mold structures together with a timer and solenoid which automatically actuates the known pressure valve system to release the inner core after a predetermined time has elapsed." The court held that broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art.). See MPEP 2144.04(III). Applicant’s Example 2 concludes in paragraph [0152] of their printed publication that “these results demonstrated that the automated assay behaved in a manner consistent with or better than the manual assay.”. Fava discloses the automated system is designed for different assays (Fava; [0005, 0042]) and utilizes equivalent laboratory equipment including plates, tip racks, sample carrier devices, a turntable, container handling devices, a barcode reader, plate storage carousels, tip rack storage carousel, a plate sealer, liquid handlers and/or reagent dispensers, robotic arms, a plate shaker, an incubator, a plate washer, and assay devices for detection (Fava; [0032-0033]) for performing assay protocols in an automated manner, which would behave in a manner consistent with or better than the manual method of Wang. That being said, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the assay performed by Fava with the assay for dupilumab, and to modify the at least one sample with the at least one sample comprising dupilumab, as taught by Wang, because Wang teaches assay performed on the at least one sample comprising Dupilumab determines the neutralizing effect against IL-4 (Wang; [0193]).
Applicant argues on pages 5-6 of their remarks towards the combination of Fava in view of FDA that Fava lacks all necessary elements to meet GMP standards, including an audit trail, identification of location data, and a record of any modification to the assay protocol, software and equipment, and that a person skilled in the art would not look to FDA 211 in curing the deficiencies of Fava because the modification would amount to impermissible hindsight to identify motivation.
The examiner respectfully disagrees. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). That being said, GMP standards are established by the FDA and one of ordinary skill in the art would be required to look to FDA 211 in order to cure the deficiencies of Fava. In this case, The Food and Drug Administration 21 CFR Part 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals; in effect on 01/01/2022 states under § 211.68 Automatic, mechanical, and electronic equipment “(b) Appropriate controls shall be exercised over computer or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel. Input to and output from the computer or related system of formulas or other records or data shall be checked for accuracy. The degree and frequency of input/output verification shall be based on the complexity and reliability of the computer or related system. A backup file of data entered into the computer or related system shall be maintained except where certain data, such as calculations performed in connection with laboratory analysis, are eliminated by computerization or other automated processes. In such instances a written record of the program shall be maintained along with appropriate validation data. Hard copy or alternative systems, such as duplicates, tapes, or microfilm, designed to assure that backup data are exact and complete and that it is secure from alteration, inadvertent erasures, or loss shall be maintained.”. Fava disclose control over changes in master production and control records or other records are instituted only by authorized personnel (Fava; 0044, 0076-0077]). Fava also disclose a backup file of data entered into the computer or related system shall be maintained which include an audit trail comprising identification of location data, and a record of any modification to the assay protocol, software and equipment (Fava; [0044-0045, 0076-0077, 0083]).
In short, the system of Fava would satisfy many of the GMP guidelines but is absent to a specific teaching of the term “GMP-Compliant”. That said, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the automated system of modified Fava to be GMP-compliant, as directed by the FDA, because the GMP-compliant guidelines set forth by the Food and Drug Administration are used in drug product commercialization and distribution to humans or animals in which laboratory records of all tests, including assays, are required. The modification therefore comprising a GMP-compliant assay and GMP-compliant dataset. One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since modified Fava and FDA 211 both teach collecting data on an assay for a drug product.
Applicant’s arguments on pages 6-9 have been fully considered but are moot because the current grounds of rejection does not rely on any of the references for teaching the argued limitations.
Citations to art
In the above citations to documents in the art, an effort has been made to specifically cite representative passages, however rejections are in reference to the entirety of each document relied upon. Other passages, not specifically cited, may apply as well.
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 extension fee 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 date of this final action.
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/C.A.T./Examiner, Art Unit 1798
/BENJAMIN R WHATLEY/Primary Examiner, Art Unit 1798
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