CTNF 18/555,205 CTNF 101527 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Claim Rejections - 35 USC § 112 07-30-02 AIA The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. 07-34-01 Claim 17 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The term ‘NovaFlex device’ and ‘a Raman Probe’ in claim 17 renders the scope of the claim unclear which renders the claim indefinite. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite device and/or technology, and one of ordinary skill in the art would not be reasonably apprised of the invention and therefore the metes and bounds of the claim, as it is not clear if the applicant is referring to a brand name, a generic instrument or a specific instrument and/or component of an instrument, or if the instrument must merely be capable of functioning as a Novaflex device or Raman probe. Claim Rejections - 35 USC § 101 07-04-01 AIA 07-04 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 1-20 and 21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (abstract idea) without significantly more. The claim(s) recite(s) a method of controlling nutrient feed in a cell culture process: receiving a sample from a bioreactor, measuring residual nutrients, determining viable cell density (VCD), calculating cell growth rates, predicting a VCD, integrating a predicted VCD, and integrating these predicted variables to further calculate necessary nutrients for future timepoints, for feeding said nutrients, based on the prior calculations. The judicial exception is not integrated into a practical application because the mental steps of measuring, determining, calculating, integrating, and/or predicting are mathematical concepts, which are performed in the human mind, including an observation, evaluation, judgement, and/or opinion, which corresponds to the method steps of receiving a sample from the bioreactor and feeding nutrients to said bioreactor. In instant case, the assessment step(s) is not defined as anything more than reviewing measurements, provided by automated instrumentation followed by informing the bioreactor, based on predictions calculated through mathematical interpretations, to make judgements regarding nutrient feed—all of which may be done mathematically and/or mentally. With regards to Step 1, Claim 1 and dependent claims 2-20 and 21 are considered to be in a statutory category of process. With regards to Step 2A, prong 1, claim 1 and dependent claims 2-20 and 21, the claims as a whole are directed towards assessing the culture state within the bioreactor, based on data gathering, which constitutes an abstract idea. Specifically, under the 2019 Revised Patent Subject Matter Eligibility Guidance (PEG), it falls into the grouping of mathematical concepts (mathematical relationships, mathematical formulas, or equations, and mathematical calculations). In instant case, the assessment step is not defined as anything more than measuring nutrients and/or VCD in a sample and calculating and/or predicting future nutrients and VCD and making a judgement, regarding optimization of future culture conditions within a bioreactor, all of which may be done mathematically and/or mentally. With regards to Step 2A, prong 2, regarding claim 1 and dependent claims 2-20 and 21, in addition to the recitation of measuring and predicting steps the claims are directed to fine-tuning culture conditions which includes nutrients, residual nutrients, by-products, and/or VCD monitoring, which are mere data gathering steps in order to accomplish the assessment steps, of measuring and predicting future culture conditions. The step of feeding nutrient/glucose to the bioreactor amounts to a mere instruction to apply the exception, as a general instruction to control the outcome. See MPEP 2106.05(f). As such, there is no additional element in claims 1-20 and 21 that applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to incorporating measurements into calculations to predict future culture conditions. Therefore, this is insignificant extra solution activity regarding selection of a particular data type for additional operational steps. Accordingly, the claims do not recite additional elements that alone or together amount to significantly more than the judicial exception itself. With regards to Step 2B: in claim 1, inline and offline measurements gathered through automated systems, regarding nutrients, residual nutrients, by-products, and/or VCD are acquired using methods that are recited in a generic manner and are routine conventional in the prior art as evidenced by Webster, et al., (US20190137338A1, published 2019-05-09). As such, the claims do not recite additional elements that alone or together amount to significantly more than the judicial exception itself. Regarding claims 2,4,5,7,8,10,11,15, and 16 the dependent claims merely recite additional details regarding the underlying calculations and mental processes set forth in the independent claims. These limitations do not integrate the abstract idea into a practical application, but instead further define the abstract calculations themselves. Regarding claims 3,6,9,12-14 and 17-20 the dependent claims further recite additional elements (non-transitory storage medium, nutrient type, nutrient measurement device, bioreactor type, cell type) that are well-understood, routine, and conventional in the relevant field. These elements do not meaningfully limit the abstract idea or transform it into patent-eligible subject matter. For the forgoing reasons, the claims are not deemed to encompass patent eligible subject matter under 35 USC § 101. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – 07-08-aia AIA (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. 07-15 AIA Claim s 1-21 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Webster, T. et al., (US20190137338A1, published 2019-05-09) . Regarding claims 1, 13, 14 and 21 , Webster et al., discloses a method for an automated sampling and monitoring system for cell culture, with a bioreactor, measuring residual nutrients inline (non-invasive) using Raman spectroscopy monitoring/analysis system coupled to a controller to determine concentration of the parameters and providing nutrients to cells in the bioreactor, based on measurements collected for minutes, hours and days (paragraphs 0084-0085) and batch processing of cells from 2 days to 28 days (page 2, paragraph 0013). Nutrients and bi-product measurements include: glucose , lactate, and/or glutamate ( claims 13 and 14 ) concentrations while the controller of the system adjusts nutrient feed to the bioreactor based on said measurements (page 6, 0087). Webster et al., further discloses culture conditions, over time, and modifying nutrients based on statistical analysis or preprocessing prior to determining parameter concentrations, these measurements are then used for predicative modelling ( page 6, paragraphs 0089-0090). Predictive models are programmed into the controller to predict future concentrations to said parameters (page 7, 0094) and designed based on experiments with desired parameters (including VCD) using Raman spectral/imaging data and/or offline data collection from additional methods/instruments, (page 7, paragraph 0095). Regarding claim 2 , Webster et al., disclose determining a VCD on a current day, predicting VCD for a next day, or calculating a nutrient target based on complied predications of VCD (page 2, paragraphs 0013-0014). Regarding claims 3, 6, 9, and 12, Webster, et al., teaches cell density was measured using offline and inline instrumentation that includes non-transitory storage medium to further recall and assess VCD from multiple time points ( claim 3 ) which includes: integrated VCD for a current day ( claim 6 ), integrated VCD from a previous day ( claim 9 ) and empirically determined nutrients ( claim 12 ) --(page 8, paragraphs 0105-0106). Regarding claims 4, 5, 7, 8, 10, and 11, Webster et al., previously discloses collecting inline measurements using a programmable controller that is able to simultaneously collect multiple parameters, some of which includes VCD, total cell concentration, nutrients, and waste for time periods of minutes, hours, and days. Additionally, Webster et al., further discloses using these measurements with statistical analysis methods to build predictive models that were integrated into the controller system, resulting in adjustments to said parameters based on the predictive inputs. The upstream analyses of the predictive models include assessing multiple cell lines, nutrients, and cell products other than the cell line(s) and parameters used for calibration, followed by comparisons of the predictive model statistics with offline data collection from multiple other instruments, for predictive model validation and further for scalability. Webster et al., discloses the following regarding the claims with predictive models: Claim 4 : VCD for next day predicted based on calculated cell growth rate and VCD on current day (page 7, paragraph 0096); Claim 5 : predicted viable cell density based on current day data, including integrated viable cell density data collected for a current day (page 7, paragraphs 0094-0095); Claim 7 : Predicted nutrient consumption rate relative to consumption over previous day(s)/current day(s), calculations of nutrient targets (page 7, paragraph 0096); Claim 8 : The nutrient consumption rate relative to cellular growth rate and based on periods of current and integrated VCD from a previous day (page 7, paragraph 0094 and 0101); Claim 10 : Predicted models of nutrient consumption based on specified daily consumption and viable cell density parameters for a current day (page 7, 0096-0097); Claim 11 : A nutrient calculated based on a predicted nutrient and an empirically determined nutrient to maintain value (page 8, paragraph 0109; claim 3). Regarding claims 15-20 , Webster et al., teaches methods of collecting inline (page 8, paragraph 0106) and offline (page 8, paragraph 0105) measurements ( claim 16 ) of viable cell (VCC) and total cell (TCC) concentrations of CHO-K1SV (GS-KO™) cells (page 8, paragraph 0103), a mammalian CHO cell line ( claims 19 and 20 ), along with residual nutrients measurements (glucose, lactate, and ammonium) from a 5L bioreactor (page 8, paragraph 0109), ( claims 15 and 18 ). Measurements are taken from cells and nutrients, using a Novak Bioprofile and Raman probes with spectra analysis (page 8, paragraph 0105) ( claim 17 ). Correspondence Information Any inquiry concerning this communication or earlier communications from the examiner should be directed to ENUSHA KARUNASENA whose telephone number is (571)272-3972. The examiner can normally be reached Monday-Friday 7:30am-5pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at 571-272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /ENUSHA KARUNASENA/Examiner, Art Unit 1653 /SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653 Application/Control Number: 18/555,205 Page 2 Art Unit: 1653 Application/Control Number: 18/555,205 Page 3 Art Unit: 1653 Application/Control Number: 18/555,205 Page 4 Art Unit: 1653 Application/Control Number: 18/555,205 Page 5 Art Unit: 1653 Application/Control Number: 18/555,205 Page 6 Art Unit: 1653 Application/Control Number: 18/555,205 Page 7 Art Unit: 1653 Application/Control Number: 18/555,205 Page 8 Art Unit: 1653
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