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 1-24 and 30 are pending and under examination.
Claims 25-29 have been canceled.
Response to Amendment
The 101 rejection(s) have been modified to address the amended claims.
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 received and approved. Therefore, the double patenting rejection has been withdrawn.
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 1-24 and 30 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 1: Claims 1 and 30 are directed toward a method.
Step 2A, Prong One: Identify the law of nature/natural phenomenon/abstract ideas.
Claim 1 recites the abstract idea “validating the collected data”, and “generating a GMP-compliant dataset of dupilumab from the collected data”. Claim 30 recites the abstract ideas “validating the collected data” and “generating a GMP-compliant dataset of dupilumab from the collected data”.
These abstract ideas are mental processes that could be performed by a human person by pen and paper or by a black box computer. The computer system in claims 1 and 30 are merely a general-purpose computer for which to apply the abstract ideas, but does not preclude the steps from being considered an abstract idea. See MPEP 2106.04(a)(2) subsection (III).
Step 2A, Prong Two: Has the abstract idea been integrated into a particular practical application?
No. These judicial exceptions are not integrated into a practical application because the additional elements recited in the claims do not impose any meaningful limits on practicing the abstract ideas. Upon developing the assay protocol and generating a dataset, no further action is performed, and therefore is not a particular practical application.
Claims 1 and 30 additionally recite (a) obtaining an assay protocol for a GMP-compliant assay for dupilumab, wherein the assay protocol includes any changes and record of associated usage data, wherein any change to the protocol is stored and tracked, (b) subjecting at least one sample comprising dupilumab to automated operation of the assay protocol executed by a first secure computer system and at least one automated equipment, (c) wherein the first secure computer system receives the assay protocol and causes automated operation of the assay, (d) wherein the first secure computer system and the at least one automated equipment associated with the automated operation of the assay protocol are qualified prior to the automated operation of the assay protocol, (e) wherein the automated operation of the assay protocol comprises collecting data associated with the at least one sample comprising dupilumab subjected to the assay protocol, (f) wherein the GMP-compliant dataset of dupilumab includes an audit trail of the GMP-compliant dataset of dupilumab, identification of location data for the at least one sample comprising dupilumab throughout execution of the assay protocol, and a record of any changes to the assay protocol, software and the at least one automated equipment controlled by the first secure computer system.
The first secure computer that receives and executes the assay protocol is just a general-purpose computer. However, use of conventional computer functions to apply the judicial exception(s) does not qualify as a particular machine (MPEP § 2106.05(b)(I), MPEP § 2106.05(b)(II) and MPEP § 2106.05(b)(III)).
Claim elements (a) “obtaining an assay protocol for a GMP-compliant assay for dupilumab, wherein the assay protocol includes any changes and record of associated usage data, wherein any change to the protocol is stored and tracked”, (c) “wherein the first secure computer system receives the assay protocol and causes automated operation of the assay”, (e) “wherein the automated operation of the assay protocol comprises collecting data associated with the at least one sample comprising dupilumab subjected to the assay protocol”, and (f) “wherein the GMP-compliant dataset of dupilumab includes an audit trail of the GMP-compliant dataset of dupilumab, identification of location data for the at least one sample comprising dupilumab throughout execution of the assay protocol, and a record of any changes to the assay protocol, software and the at least one automated equipment controlled by the first secure computer system” are interpreted as extra-solution activity incidental to the primary process as mere data gathering which is not considered significantly more than the abstract idea, and generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the judicial exception, but does not amount to significantly more than the exception itself and cannot integrate the judicial exception into a practical application. Further, automated operations and generating information based on the abstract idea provides nothing more than mere instructions to implement the abstract idea to the field of use (see MPEP § 2106.05(f), MPEP § 2106.05(g), and MPEP § 2106.05(h))
Claim elements (b) “subjecting at least one sample comprising dupilumab to automated operation of the assay protocol executed by a first secure computer system and at least one automated equipment” and (d) “wherein the first secure computer system and the at least one automated equipment associated with the automated operation of the assay protocol are qualified prior to the automated operation of the assay protocol” are interpreted as generally linking the use of the judicial exception to a particular technological environment or field of use, but does not add significantly more (see MPEP § 2106.05(h)).
Step 2B: Does the claim recite any elements which are significantly more than the abstract ideas?
Claims 1 and 30 recite the additional elements (a) obtaining an assay protocol for a GMP-compliant assay for dupilumab, wherein the assay protocol includes any changes and record of associated usage data, wherein any change to the protocol is stored and tracked, (b) subjecting at least one sample comprising dupilumab to automated operation of the assay protocol executed by a first secure computer system and at least one automated equipment, (c) wherein the first secure computer system receives the assay protocol and causes automated operation of the assay, (d) wherein the first secure computer system and the at least one automated equipment associated with the automated operation of the assay protocol are qualified prior to the automated operation of the assay protocol, (e) wherein the automated operation of the assay protocol comprises collecting data associated with the at least one sample comprising dupilumab subjected to the assay protocol, (f) wherein the GMP-compliant dataset of dupilumab includes an audit trail of the GMP-compliant dataset of dupilumab, identification of location data for the at least one sample comprising dupilumab throughout execution of the assay protocol, and a record of any changes to the assay protocol, software and the at least one automated equipment controlled by the first secure computer system.
These additional elements do not amount to significantly more as they are well-understood, routine, and conventional (WURC) in the art as evidenced by Fava et al. (US 2002/0147515; – hereinafter “Fava”), and Wang et al. (US 2015/0320022 – hereinafter “Wang”). Fava disclose (a) obtaining an assay protocol for a GMP-compliant assay, wherein the assay protocol includes any changes and record of associated usage data, wherein any change to the protocol is stored and tracked (Fava; [0031, 0037-0039, 0041-0042, 0044, 0073-0077]), (b) subjecting at least one sample to automated operation of the assay protocol executed by a first secure computer system and at least one automated equipment (Fava; [0017, 0020, 0031-0039, 0041-0042, 0044-0045, 0077, 0083, 0085]), (c) wherein the first secure computer system receives the assay protocol and causes automated operation of the assay (Fava; [0017, 0020, 0031-0039, 0041-0042, 0044-0045, 0077, 0083, 0085]), (d) wherein the first secure computer system and the at least one automated equipment associated with the automated operation of the assay protocol are qualified prior to the automated operation of the assay protocol (Fava; [0027, 0027, 0031, 0043-0044, 0052, 0054, 0076]), (e) wherein the automated operation of the assay protocol comprises collecting data associated with the at least one sample subjected to the assay protocol (Fava; [0044-0045, 0077, 0083]), (f) wherein the dataset of dupilumab includes an audit trail of the dataset (Fava; [0044-0045, 0076-0077]), identification of location data for the at least one sample comprising dupilumab throughout execution of the assay protocol (Fava; [0044-0045, 0077, 0083]), and a record of any changes to the assay protocol, software and the at least one automated equipment controlled by the first secure computer system (Fava; p0044, 0076, 0083]). Wang disclose the additional elements of a dupilumab assay protocol (Wang; [0193]).
Claim 2 further limits the assay to a bioassay. However, these additional elements are interpreted as generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the judicial exception, but do not provide significantly more and cannot integrate the judicial exception into a practical application. See MPEP §2106.05(h), Field of Use and Technological Environment.
Claim 3 recites the abstract idea of “optimizing the protocol” (step 2A prong 1), but does not integrate the exception under 2A prong 2 because using data collected from the sample subjected to the assay protocol is merely data gathering and generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the judicial exception, but does not integrate the judicial exception into a particular practical application because data gathering is merely insignificant extra-solution activity. See MPEP § 2106.05(g), Insignificant Extra-Solution Activity and § 2106.05(f), Mere Instructions To Apply an Exception.
Claim 4 further limits the protocol as being password protected. However, a machine that contributes only nominally or insignificantly to the execution of the claimed method would not integrate a judicial exception or provide significantly more. See MPEP § 2106.05(b)(III), MPEP § 2106.05(c), Particular Transformation, MPEP § 2106.05(d), Well-understood, Routine, Conventional Activity and MPEP § 2106.05(g), Insignificant Extra-Solution Activity.
Claim 5 recites the abstract idea “the assay protocol is subjected to quality control review” (step 2A prong 1), but does not integrate the exception under 2A prong 2 because these additional elements are do not effectively transform or reduce the system to a different state or thing such that the claims recite significantly more. See MPEP § 2106.05(b)(III), MPEP § 2106.05(c), Particular Transformation, MPEP § 2106.05(d), Well-understood, Routine, Conventional Activity and MPEP § 2106.05(g), Insignificant Extra-Solution Activity
Claim 6 recites the first computer system executes the assay protocol using a scheduling software. However, a general-purpose computer that applies the judicial exception by use of conventional computer functions does not qualify as a particular machine (MPEP § 2106(b)(I)), a machine that is merely an object on which the method operates does not integrate the exception into a practical application or provide significantly more (MPEP § 2106(b)(II)), and the use of a machine that contributes only nominally or insignificantly to the execution of the claimed method would not integrate a judicial exception or provide significantly more (MPEP § 2106.05(b)(III)).
Claim 7 further limits the scheduling software in claim 6. However, a general-purpose computer that applies the judicial exception by use of conventional computer functions does not qualify as a particular machine (MPEP § 2106(b)(I)), a machine that is merely an object on which the method operates does not integrate the exception into a practical application or provide significantly more (MPEP § 2106(b)(II)), and the use of a machine that contributes only nominally or insignificantly to the execution of the claimed method would not integrate a judicial exception or provide significantly more (MPEP § 2106.05(b)(III)).
Claim 8 recites the automated operation includes a robotic arm. However, these elements are interpreted as generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the exception. See MPEP §2106.05(h), Field of Use and Technological Environment. Further, these elements do not effectively transform or reduce the system to a different state or thing beyond such that the claims recite significantly more than well-understood, routine, and conventional activities previously known to the industry as evidenced by Fava (Fava; [0032, 0059]). See MPEP § 2106.05(c), Particular Transformation and MPEP § 2106.05(d), Well-Understood, Routine, Conventional Activity.
Claim 9 further limits the robotic arm as being configured to move in the x, y, z axes. However, these elements are interpreted as generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the exception. See MPEP §2106.05(h), Field of Use and Technological Environment. Further, these elements do not effectively transform or reduce the system to a different state or thing beyond such that the claims recite significantly more than well-understood, routine, and conventional activities previously known to the industry as evidenced by Fava (Fava; [0032, 0059]). See MPEP § 2106.05(c), Particular Transformation and MPEP § 2106.05(d), Well-Understood, Routine, Conventional Activity.
Claim 10 recites the automated operation as comprising a liquid handler and/or reagent dispenser. However, these elements are interpreted as generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the exception. See MPEP §2106.05(h), Field of Use and Technological Environment. Further, these elements do not effectively transform or reduce the system to a different state or thing beyond such that the claims recite significantly more than well-understood, routine, and conventional activities previously known to the industry as evidenced by Fava (Fava; [0032, 0059]). See MPEP § 2106.05(c), Particular Transformation and MPEP § 2106.05(d), Well-Understood, Routine, Conventional Activity.
Claim 11 further limits the liquid handler and/or reagent dispenser dispense between 0.5 and 1000 microliters per channel, monitor air displacement, and comprises dynamic positioning systems, and capacitance and pressure sensors. However, these elements are interpreted as generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the exception. See MPEP §2106.05(h), Field of Use and Technological Environment. Further, these elements do not effectively transform or reduce the system to a different state or thing beyond such that the claims recite significantly more than well-understood, routine, and conventional activities previously known to the industry as evidenced by Noggle et al. (US 2013/0345094 – hereinafter “Noggle”). Noggle teach a Hamilton STARlet liquid handling robot; [0218]. See MPEP § 2106.05(c), Particular Transformation and MPEP § 2106.05(d), Well-Understood, Routine, Conventional Activity.
Claim 12 recites the at least one sample is selected from a group consisting of cell culture fluid, harvested cell culture fluid, filtrate, chromatography eluate, drug substance, and drug product. However, these elements are interpreted as generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the exception. See MPEP §2106.05(h), Field of Use and Technological Environment. Further, these elements do not effectively transform or reduce the system to a different state or thing beyond such that the claims recite significantly more than well-understood, routine, and conventional activities previously known to the industry as evidenced by Wang (Wang; [0193]). See MPEP § 2106.05(c), Particular Transformation and MPEP § 2106.05(d), Well-Understood, Routine, Conventional Activity.
Claim 13 recites the collected data comprises subjecting the at least one sample comprising dupilumab to at least one measurement. However, data gathering and generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the judicial exception do not integrate the judicial exception into a particular practical application because data gathering is merely insignificant extra-solution activity. See MPEP § 2106.05(g), Insignificant Extra-Solution Activity and § 2106.05(f), Mere Instructions To Apply an Exception.
Claim 14 further limits the at least one measurement as being 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. However, these elements are interpreted as generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the exception. See MPEP §2106.05(h), Field of Use and Technological Environment. Further, these elements do not effectively transform or reduce the system to a different state or thing beyond such that the claims recite significantly more than well-understood, routine, and conventional activities previously known to the industry as evidenced by Fava (Fava; [0034-0037]). See MPEP § 2106.05(c), Particular Transformation and MPEP § 2106.05(d), Well-Understood, Routine, Conventional Activity.
Claim 15 further limits the sample as being contained in a microplate. However, these elements are interpreted as generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the exception. See MPEP §2106.05(h), Field of Use and Technological Environment. Further, these elements do not effectively transform or reduce the system to a different state or thing beyond such that the claims recite significantly more than well-understood, routine, and conventional activities previously known to the industry as evidenced by Fava (Fava; [0032, 0083]). See MPEP § 2106.05(c), Particular Transformation and MPEP § 2106.05(d), Well-Understood, Routine, Conventional Activity.
Claim 16 recites the collecting data includes using at least one data analysis software. However, a general-purpose computer that applies the judicial exception by use of conventional computer functions does not qualify as a particular machine (MPEP § 2106(b)(I)), a machine that is merely an object on which the method operates does not integrate the exception into a practical application or provide significantly more (MPEP § 2106(b)(II)), and the use of a machine that contributes only nominally or insignificantly to the execution of the claimed method would not integrate a judicial exception or provide significantly more (MPEP § 2106.05(b)(III)).
Claim 17 further limits the data analysis software of claim 16. However, a general-purpose computer that applies the judicial exception by use of conventional computer functions does not qualify as a particular machine (MPEP § 2106(b)(I)), a machine that is merely an object on which the method operates does not integrate the exception into a practical application or provide significantly more (MPEP § 2106(b)(II)), and the use of a machine that contributes only nominally or insignificantly to the execution of the claimed method would not integrate a judicial exception or provide significantly more (MPEP § 2106.05(b)(III)).
Claim 18 recites the data includes a unique identifier for the at least one sample. However, data gathering and generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the judicial exception do not integrate the judicial exception into a particular practical application because data gathering is merely insignificant extra-solution activity. See MPEP § 2106.05(g), Insignificant Extra-Solution Activity and § 2106.05(f), Mere Instructions To Apply an Exception.
Claim 19 recites the data includes a unique identifier for a container containing the sample. However, data gathering and generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the judicial exception do not integrate the judicial exception into a particular practical application because data gathering is merely insignificant extra-solution activity. See MPEP § 2106.05(g), Insignificant Extra-Solution Activity and § 2106.05(f), Mere Instructions To Apply an Exception.
Claim 20 recites generating a unique identifier for a container containing the sample. However, data gathering and generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the judicial exception do not integrate the judicial exception into a particular practical application because data gathering is merely insignificant extra-solution activity. See MPEP § 2106.05(g), Insignificant Extra-Solution Activity and § 2106.05(f), Mere Instructions To Apply an Exception.
Claim 21 further limits the unique identifier as a barcode. However, these elements are interpreted as generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the exception. See MPEP §2106.05(h), Field of Use and Technological Environment. Further, these elements do not effectively transform or reduce the system to a different state or thing beyond such that the claims recite significantly more than well-understood, routine, and conventional activities previously known to the industry as evidenced by Fava (Fava; [0018, 0022, 0083-0085]). See MPEP § 2106.05(c), Particular Transformation and MPEP § 2106.05(d), Well-Understood, Routine, Conventional Activity.
Claim 22 recites the barcode is generated using a label printer. However, these elements are interpreted as generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the exception. See MPEP §2106.05(h), Field of Use and Technological Environment. Further, these elements do not effectively transform or reduce the system to a different state or thing beyond such that the claims recite significantly more than well-understood, routine, and conventional activities previously known to the industry as evidenced by Fava (Fava; [0018, 0022, 0083-0085]). See MPEP § 2106.05(c), Particular Transformation and MPEP § 2106.05(d), Well-Understood, Routine, Conventional Activity.
Claim 23 recites the container is labeled with the barcode using a label printer. However, these elements are interpreted as generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the exception. See MPEP §2106.05(h), Field of Use and Technological Environment. Further, these elements do not effectively transform or reduce the system to a different state or thing beyond such that the claims recite significantly more than well-understood, routine, and conventional activities previously known to the industry as evidenced by Fava (Fava; [0018, 0022, 0083-0085]). See MPEP § 2106.05(c), Particular Transformation and MPEP § 2106.05(d), Well-Understood, Routine, Conventional Activity.
Claim 24 recites scanning the barcode at a critical step of subjecting the sample to the assay protocol to generate location data for the sample. However, data gathering and generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the judicial exception do not integrate the judicial exception into a particular practical application because data gathering is merely insignificant extra-solution activity. See MPEP § 2106.05(g), Insignificant Extra-Solution Activity and § 2106.05(f), Mere Instructions To Apply an Exception.
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 1-3, 5-10, 12-16, 18-24 and 30 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, and further in view of Wang et al. (US 2015/0320022; already of record – hereinafter “Wang”), or alternatively over Fava where CRS is used as supporting documentation, in view of 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 a method for conducting an automated GMP-compliant assay (Fava; figs. 1-4, [0020, 0032, 0085]), the method comprising:
obtaining an assay protocol for a 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 database and obtained by a process controller for executing the programs; [0031, 0037-0039, 0041-0042, 0044, 0073-0077]);
wherein the assay protocol to includes any changes and record of associated usage data, wherein any change to the protocol is stored and tracked (Fava disclose a protocol database for storing assay protocols created by a user. At any moment during creation or when recalling an earlier protocol, a user may modify, add or delete any line of script with a specific identification and version number; [0044, 0076]); and
subjecting at least one sample to automated operation of the assay protocol executed by a first secure computer system, and at least one automated equipment causes automated operation of the assay protocol (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 first secure computer system and the at least one automated equipment associated with the automated operation of the assay protocol are qualified prior to the automated operation of the assay protocol (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 automated operation of the assay protocol comprises collecting data associated with the 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 generating a GMP-compliant dataset from the collected data, wherein the GMP-compliant dataset includes an audit trail of the GMP-compliant 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]), 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/or equipment controlled by the first secure computer system (Fava; [0044, 0076, 0083]).
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, wherein the assay is 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 automated 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 method 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 method 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 method of claim 1 above, wherein the 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 5, modified Fava teach the method 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).
Regarding claim 6, modified Fava teach the method of claim 1 above, wherein the first secure computer system executes the assay protocol using a scheduling software (Fava; [0004, 0026-0027, 0030, 0040, 0043, 0069]).
Regarding claim 7, modified Fava teach the method of claim 6 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 8, modified Fava teach the method of claim 1 above, wherein the automated operation of the assay protocol includes a robotic arm (Fava; [0032, 0059]).
Regarding claim 9, modified Fava teach the method of claim 8 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 10, modified Fava teach the method of claim 1 above, wherein the automated operation of the assay protocol includes at least one liquid handler and/or reagent dispenser (Fava; [0033]).
Regarding claim 12, modified Fava teach the method 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 to modify 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 13, modified Fava teach the method 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 to modify 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 14, modified Fava teach the method of claim 13 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 15, modified Fava teach the method 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 to modify 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 16, modified Fava teach the method of claim 1 above, wherein collecting data includes using at least one data analysis software (Fava; [0023, 0027]).
Regarding claim 18, modified Fava teach the method 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; [0018, 0022, 0083-0085]).
Regarding claim 19, modified Fava teach the method 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; [0018, 0022, 0083-0085]).
Regarding claim 20, modified Fava teach the method of claim 1 above, further comprising generating 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, has previously been discussed in claim 1 above. Fava; [0018, 0022, 0083-0085]).
Regarding claim 21, modified Fava teach the method of claim 20 above, wherein the unique identifier is a barcode (Fava; [0018, 0022, 0083-0085]).
Regarding claim 22, modified Fava teach the method 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 method 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 method of claim 21 above, further comprising scanning the barcode at a critical step of subjecting the at least one sample comprising dupilumab to the assay protocol to generate the 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; [0044-0045, 0077]).
Regarding claim 30, Fava teach a method for conducting an automated GMP-compliant assay (Fava; figs. 1-4, [0020, 0032, 0085]), the method comprising:
(a) providing an assay protocol for a 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 database and obtained by a process controller for executing the programs; [0031, 0037-0039, 0041-0042, 0044, 0073-0077]);
(b) subjecting at least one sample to automated operation of the assay protocol executed by a secure computer system and 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 at least one automated equipment are qualified prior to the automated operation of the assay protocol (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 automated operation of the assay protocol comprises
collecting a first data associated with the 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, 0076-0077, 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 generating a GMP-compliant dataset from 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]);
(c) modifying the assay protocol based on the first data collected from the at least one sample subjected to the assay protocol, wherein the modifications to the assay protocol are stored and recorded (Fava; [0076]);
(d) subjecting at least one sample to automated operation of the modified assay protocol executed by the secure computer system and 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 secure computer system and at least one automated equipment are qualified prior to the automated operation of the modified assay protocol (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), wherein the automated operation of the modified assay protocol comprises collecting a second data associated with the at least one sample subjected to the modified 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 second 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 generating a second GMP-compliant dataset from the second 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
(e) repeating steps (c) to (d) until the automated operation of the assay protocol has been optimized based on the collected data (Fava; [0076]);
wherein the first and second GMP-compliant dataset includes an audit trail of the GMP-compliant dataset, identification of location data for the at least one sample throughout execution of the assay protocol, and a record of any modifications to the assay protocol, software and the at least one automated equipment controlled by the secure computer system (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]. Fava disclose the dataset includes a record of modifications to the assay protocol, software, and equipment; [0044-045, 0076-0077, 0083).
Fava does not teach the assay is for dupilumab, wherein the at least one sample comprises dupilumab, and the dataset is of dupilumab.
However, Wang disclose the analogous art of conducting an assay, wherein the assay is 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 method 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 method 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 products administered 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.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Fava, where CRS is used as supporting documentation, in view of Wang, in view of FDA 211, and further in view of Mishima et al. (US 2006/0190187; already of record – hereinafter “Mishima”).
Regarding claim 4, modified Fava teach the method of claim 1 above, comprising the protocol.
Modified Fava does not teach wherein the 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 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 11 is rejected under 35 U.S.C. 103 as being unpatentable over Fava, where CRS is used as supporting documentation, in view of Wang, in view of FDA 211, and further in view of Noggle et al. (US 2013/0345094; already of record – hereinafter “Noggle”).
Regarding claim 11, modified Fava teach the method of claim 10, wherein the at least one liquid handler and/or reagent dispenser is 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 prior art device is the same as a device described in the specification for carrying out the claimed method, it can be assumed the device will inherently perform the claimed process. See MPEP 2112.02. As stated in In re King, 801 F.2d 1324, 231 USPQ 136 (Fed. Cir. 1986): Where, as here, if a prior art device, in its normal and usual operation, would necessarily perform the method claimed, the PTO can require an applicant to prove that the prior art process does not necessarily or inherently possess the characteristics of his claimed process. 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 and would necessarily perform the method claimed.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Fava, where CRS is used as supporting documentation, in view of Wang, in view of FDA 211, and further in view of XU (US 2021/0011033; already of record – hereinafter “XU”).
Regarding claim 17, modified Fava teach the method of claim 16 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 prior art device is the same as a device described in the specification for carrying out the claimed method, it can be assumed the device will inherently perform the claimed process. See MPEP 2112.02. As stated in In re King, 801 F.2d 1324, 231 USPQ 136 (Fed. Cir. 1986): Where, as here, if a prior art device, in its normal and usual operation, would necessarily perform the method claimed, the PTO can require an applicant to prove that the prior art process does not necessarily or inherently possess the characteristics of his claimed process. 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]. 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 and would necessarily perform the method claimed.
Response to Arguments
Applicant’s arguments and remarks, filed 04/08/2026, have been considered.
Applicant argues, see page 1 of their remarks, toward the 101 rejection over claims 1 and 30, that the amends clarify that the claimed method is not directed to an abstract concept, but to physical steps for conducting an automated, GMP-compliant assay for dupilumab that cannot be performed as mental steps.
The examiner respectfully disagrees. Step 2A prong One is directed toward identifying the law of nature/natural phenomenon/abstract idea in the claims. Independent claims 1 and 20 recites the abstract idea(s) “validating the collected data”, and “generating a GMP-compliant dataset of dupilumab from the collected data”. The abstract idea(s) is/are of the type that is in the grouping of “mathematical concepts” and/or “mental process” (See MPEP 2106.04(a)(2) subsections (I) and (III)) because validating data and generating a dataset could be performed in the mind and/or by using a mathematical relationship between variable or numbers. Specifically, a user or laboratory technician could easily, in their mind or with pen and paper, look at collected data and determine if the data is valid for a set of rules or instructions, and whether the data fall within predetermined threshold value, then generate a new dataset from the collected data.
Applicant argues on pages 1-2 of their marks that claims 1 and 30 are patentable under Step 2A Prong Two of the 101 rejection because claims 1 and 30 reflect improvements including “an audit trail of the GMP-compliant dataset” thereby enhancing the integrity of the stored data through secure write paths, data logs, and security mechanism, thereby reducing corruption of data.
The examiner respectfully disagrees. The audit trail is an attribute of the generated dataset which is the abstract idea itself. However, the abstract idea (validating/generating) itself cannot be the alleged improvement in a particular technology. See MPEP 2106.05(a). Further, the audit trail is interpreted extra-solution activity incidental to the primary process as mere data gathering which is not considered significantly more than the abstract idea, and generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the judicial exception, but does not amount to significantly more than the exception itself and cannot integrate the judicial exception into a practical application. Further, generating information based on the abstract idea provides nothing more than mere instructions to implement the abstract idea to the field of use (see MPEP § 2106.05(f), MPEP § 2106.05(g), and MPEP § 2106.05(h)). The audit trail does not amount to significantly more than WURC in the art because Fava disclose a log file and data export file that captures barcode scans and records date, time, operator name, reader type, reader settings and saved both locally and to the Laboratory Information System network (Fava; [0044, 0083]).
Applicant argues on pages 2-4 of their marks that claims 1 and 30 are patentable under Step 2A Prong Two of the 101 rejection because claims 1 and 30 reflect improvements including overall efficiency and reliability of the assay, reducing the amount of analyst time and the operational cost required when read as a whole and in light of the written description’s disclosure, and that the physical processes cannot be performed as mental steps.
The examiner respectfully disagrees. The additional elements recited in the claims are interpreted as extra-solution activity incidental to the primary process as mere data gathering which is not considered significantly more than the abstract idea, and generally linking the use of a judicial exception to a particular technological environment or field of use in which to apply the judicial exception, but does not amount to significantly more than the exception itself and cannot integrate the judicial exception into a practical application. Further, generating a dataset based on the abstract idea provides nothing more than mere instructions to implement the abstract idea to the field of use (see MPEP § 2106.05(f), MPEP § 2106.05(g), and MPEP § 2106.05(h)). In summary, outside of the abstract idea, the claim is generally at least one automated equipment that performs an automated assay and a computer that records data where many conventional automatic analyzers would perform these processes. The alleged improvements including improving efficiency, reliability of the assay, and reducing the amount of analyst time and the operational cost alone do not lead to an alleged improvement because all automated analyzers would aim to improve efficiency, reliability, and reduce time and cost. For example, Fava specifically disclose “It is now quite sometimes that robotic systems are used to increase productivity, reduce production costs, eliminate human errors, remove human operations from dangerous environments or simply take over boring and frustrating tasks”, see paragraph [0002] and “On the contrary, thanks to the present invention, the In Vitro Diagnostic Laboratory Automation Workcell System that uses the Laboratory Automation Management System, automates all the pre-analytical, analytical, and post-analytical phases of Sample assaying in a homogenous, concurrent, reactive, dynamic and expert-system-rule-based fashion”, see paragraph [0020]. The physical processes of the at least one automated equipment and computer do not amount to significantly more as they are well-understood, routine, and conventional in the art. See Fava paragraphs [0031-0039].
Applicant argues on page 4 of their remarks towards the 103 rejection over claims 1 and 30 that none of the prior art provides motivation or guidance for a method that validates the collected data before producing 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 page 4 of their remarks towards the 103 rejection over claims 1 and 30 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 4-7 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 7-8 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 8-10 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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