CTNF 18/687,181 CTNF 87349 DETAILED ACTION 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 Objections 07-29-01 AIA Claim s 1-2 and 6 are objected to because of the following informalities: a) In claim 1 line 4-5, please change "detecting changes in one or more process parameters selected from the group consisting of pH" to -- detecting changes in one or more process parameters selected from a group consisting of pH--. b) In claim 1 lines 7-8, please change "spectrometry immediately before, during and directly after the exchange of one process fluid to another process fluid" to --spectrometry immediately before, during and directly after an exchange of one process fluid to another process fluid--. c) In claim 1 line 13, please change "determine the HETP value and asymmetry of said derivatized data" to: --determine a HETP (Height of Equivalent Theoretical Plate) value and asymmetry of said derivatized data--. d) In claim 2 lines 1-2, please change "wherein said curve smoothing calculation is the Savitzky-Golay smoothing filter" to --wherein said curve smoothing calculation is a Savitzky-Golay smoothing filter--. e) In claim 6 lines 1-2, please change "wherein said columns are selected from the group consisting of affinity" to: --wherein said columns are selected from a group consisting of affinity --. Appropriate correction is required. Claim Rejections - 35 USC § 112 07-30-02 AIA 3. 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 Claims 1-11 are 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. a) Claim 1 lines 15-16 recites the limitation "wherein, if the HETP values and asymmetry fall within said standardized values the column is used for another process run." There is ambiguity regarding the term "the HETP values" and "the column." The claim limitation here does not address the situation where there is only one column and only one HETP value, and thus multiple HETP values may lead to some ambiguity as to what the other HETP values are referring to when there is only one column. It is not clear if HETP values and asymmetry are looked at for "each column" to determine whether each column (as "the column") is used for another process run, or whether the HETP values and asymmetry from "all" of the one or more columns are looked at to determine whether just one column (as "the column") is used for another process run. In other words, it is not clear what "the column" is referring to, as there can be more than one column and it is not clear if each column is analyzed individually or whether the results of all of the columns are used to determine whether each column or one column continues another process run. Appropriate correction/clarification is requested. b) Claim 1 lines 15-16 recites the limitation "wherein, if the HETP values and asymmetry fall within said standardized values the column is used for another process run." It is not clear what is meant by another "process run," as the claim does not clearly define that a process run has occurred, or what steps constitute a "process run" that was run previously out of the continuous process mode. A process run could refer to some other undisclosed process, as the metes and bounds of a "process run" have not been clearly defined. Appropriate correction/clarification is requested. c) Claim 10 lines 1-2 recites the limitation "wherein, if the HETP values and asymmetry fall within said standardized values the column is regenerated." There is ambiguity regarding the term "the HETP values" and "the column." The claim limitation here does not address the situation where there is only one column and only one HETP value, and thus multiple HETP values may lead to some ambiguity as to what the other HETP values are referring to when there is only one column. It is not clear if HETP values and asymmetry are looked at for "each column" to determine whether each column ("the column") is regenerated, or whether the HETP values and asymmetry from "all" of the one or more columns are looked at to determine whether just one column ("the column") is regenerated. In other words, it is not clear what "the column" is referring to, as there can be more than one column and it is not clear if each column is analyzed individually or whether the results of all of the columns are used to determine whether each column or one column is regenerated. Appropriate correction/clarification is requested. 4. Dependent claims 2-11 depend from claim 1 and are rejected for at least the same reasons as given for claim 1. Claim Rejections - 35 USC § 103 07-20-aia AIA 5. 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. 07-23-aia AIA The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. 07-21-aia AIA 6. Claim s 1 and 3-11 are rejected under 35 U.S.C. 103 as being unpatentable over Mao et al. (US Pat. Pub. 2018/0113101, hereinafter "Mao") as modified by Hyckenberg et al. (US Pat. Pub. 2019/0346412, hereinafter "Hyckenberg") . In regards to claim 1, Mao teaches a method of monitoring one or more chromatography columns for efficiency and quality (Mao abstract, paragraph [0006], and paragraph [0054] teach a method for monitoring one or more chromatography columns for performance (efficiency) and integrity (quality)) , the method comprising: a) providing one or more chromatography columns (Mao Fig. 1 and paragraphs [0056]-[0057] teaching providing one or more chromatography columns 106) ; b) detecting changes in one or more process parameters selected from the group consisting of pH, conductivity, salt concentration, light absorption, fluorescence after excitation with light of a suitable wavelength, refractive index, electrochemical response and mass spectrometry immediately before, during and directly after the exchange of one process fluid to another process fluid that differ in the one or more process parameters to generate process data (Mao Fig. 3 and paragraphs [0065]-[0066] teach detecting chromatograph (or chromatographic) transitions (changes) in one or more process parameters of conductivity, pH, salt concentration, light absorption, fluorescence after excitation, refractive index, electrochemical response, and mass spectrometric analysis, from the response at the outlet of a column to a change in step at the column's inlet as one mobile phase (process fluid) is replaced (exchanged) with another) ; c) applying a curve smoothing filter to said process data to generate corrected process data (Mao paragraphs [0012], [0075]-[0076], and [0100] teach applying a curve smoothing filter to obtain noise reduced (corrected) process data) ; d) calculating the first derivative of said corrected process data to produce derivatized process data of said corrected process data (Mao paragraph [0104] teach performing one or more mathematical processes such as taking a first derivative on the processed (post noise reduction smoothed) data of the curve to produced derivatized process data) ; e) determine the HETP value and asymmetry of said derivatized data (Mao paragraph [0104] teaches determining the HETP value and asymmetry of the derivatized data) ; f) comparing the HETP value and asymmetry to standardized values (Mao paragraph [0104] teaches comparing the HETP value and asymmetry to standardized values from transition analysis parameters of prior representative chromatography data, in order to determine a column integrity or lack thereof) ; g) wherein, if the HETP values and asymmetry fall within said standardized values the column is used for another process run (Mao paragraphs [0108] and [0125] teach that if the HETP values and asymmetry fall within said standardized values (to pass an integrity check), allowing a chromatography process to continue) . Mao fails to expressly teach the one or more chromatography columns being operated in continuous process mode and the one or more chromatography columns used in continuous mode. Hyckenberg abstract teaches monitoring an operational status in a continuous chromatography process and identifying deviating behavior from a time trend analysis of at least one parameter. Hyckenberg paragraph [0009] teaches where continuous chromatography operation results in better utilization of chromatography resin, reduced processing time and reduced buffer requirements, all of which benefits process economy. It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Hyckenberg to specify where the one or more chromatography columns are operated in continuous process mode because continuous chromatography results in better utilization of chromatography resin, reduced processing time and reduced buffer requirements. Therefore, since Mao is directed to in-process monitoring and control of chromatography systems (see Mao paragraph [0002]), it would be logical to specify application in a known type of continuous chromatography process system having a process economy that benefits from the continuous processing. In regards to claim 3 , Mao teaches the method wherein said column or columns have been used continuously for multiple runs (Mao paragraph [0054] teaches where the chromatography column is monitored over multiple chromatography runs, and paragraph [0068] teaches three chromatography runs) . Mao fails to expressly teach between 2 and 200 runs. However it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to specify a user selected range such as between 2 and 200 runs, since it has been held that where the general conditions of a claim are disclosed in the prior art (see Mao paragraph [0083] teaching generating reports based on a desired number of plural prior chromatography runs), discovering the optimum or working ranges involves only routine skill in the art (see In re Aller, 105 USPQ 233 ). In regards to claim 4 , Mao teaches the method wherein said column or columns have been used continuously for multiple runs. Mao fails to expressly teach between 5 and 50 runs. However it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to specify a user selected range such as between 5 and 50 runs, since it has been held that where the general conditions of a claim are disclosed in the prior art (see Mao paragraph [0083] teaching generating reports based on a desired number of plural prior chromatography runs), discovering the optimum or working ranges involves only routine skill in the art (see In re Aller, 105 USPQ 233 ). In regards to claim 5 , Mao teaches the method as explained in the rejection of claim 1 above. Mao fails to expressly teach wherein said continuous process mode comprises at least two but not more than five different columns in sequence. Hyckenberg abstract teaches monitoring an operational status in a continuous chromatography process configured to operate with at least three columns. Hyckenberg paragraph [0008] teaches where in continuous chromatography, several identical columns are connected in an arrangement that allows columns to be operated in series and/or in parallel such that all columns can be run simultaneously but in sequence with slightly shifted method steps. It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Hyckenberg to specify where the chromatography columns are operated in continuous process mode because continuous chromatography results in better utilization of chromatography resin, reduced processing time and reduced buffer requirements. Therefore, since Mao is directed to in-process monitoring and control of chromatography systems (see Mao paragraph [0002]), it would be logical to specify application in a known continuous chromatography process system having a process economy that benefits from the continuous processing. It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Hyckenberg to specify at least two columns but no more than five columns since it has been held that where the general conditions of a claim are disclosed in the prior art (Mao abstract teaches at least three which falls between at least two and no more than five), discovering the optimum or working ranges involves only routine skill in the art (see In re Aller, 105 USPQ 233 ). In regards to claim 6 , Mao teaches the method wherein said columns are selected from the group consisting of affinity, ion exchange, size exclusion, reverse phase, chiral, frontal and hydrophobic (Mao paragraph [0057] teaches where the columns are chosen based on performing one of various types of chromatography, such as affinity, ion exchange, size exclusion, reverse phase, etc.) . In regards to claim 7 , Mao teaches wherein each column is monitored for efficiency and quality (Mao paragraphs [0006] and [0054]) . In regards to claim 8 , Mao teaches the method as explained in the rejection of claim 1 above. Mao fails to expressly teach wherein said continuous process mode comprises multiple process steps, comprises at least two but not more than ten process steps in sequence and at least one process step comprises a chromatography column. Hyckenberg abstract teaches monitoring an operational status in a continuous chromatography process on at least three columns. Hyckenberg paragraph [0008] teaches where several columns are connected in an arrangement that allows columns to be operated in series and/or in parallel such that all columns can be run simultaneously but with slightly shifted method steps. Hyckenberg paragraph [0008] teaches where the method steps include a number of consecutive steps involving a chromatography column such as: load the sample, wash, elution, strip, Clean-In-Place (CIP) and re-equilibration. It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Hyckenberg to specify where the chromatography columns are operated in continuous process mode because continuous chromatography results in better utilization of chromatography resin, reduced processing time and reduced buffer requirements. Therefore, since Mao is directed to in-process monitoring and control of chromatography systems (see Mao paragraph [0002]), it would be logical to specify application in a known continuous chromatography process system having a process economy that benefits from the continuous processing. It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Hyckenberg to specify where the continuous process steps comprise at least two but not more than ten chromatography column process steps in sequence, since it has been held that where the general conditions of a claim are disclosed in the prior art (Mao paragraph [0008] lists five process steps as an example), discovering the optimum or working ranges involves only routine skill in the art (see In re Aller, 105 USPQ 233 ). In regards to claim 9, Mao teaches the method wherein said standardized values are based on historic data using the same or substantially the same columns and process parameters (Mao paragraph [0104] teaches wherein the standardized values are from transition analysis parameters of prior (historic) representative chromatography data using the same columns and process parameters in order to carry out a comparison for determining column integrity or lack thereof) . In regards to claim 10 , Mao teaches the method as explained in the rejection of claim 1 above. Mao fails to expressly teach wherein if the HETP values and asymmetry do not fall within said standardized values the column is regenerated. Hyckenberg paragraph [0079] teaches where upon determination that action is needed to maintain performance of continuous chromatography, an additional step is performed in which the particular column is removed from the columns used by the continuous chromatography for continuous purification. Hyckenberg paragraph [0053] and [0055]-[0056] teach where the steps to remove columns involves non-loading steps such as elution and regeneration. It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Hyckenberg to specify carrying out an un-loading removal process involving regeneration when a performance value indicates that a maintenance action is needed. Therefore, it would only be a matter of ordinary skill to specify carrying out a known regeneration process on a column when a poor performance indication (such as when the HETP values and asymmetry falling outside the standardized values) is determined. In regards to claim 11 , Mao teaches the method wherein if the HETP values and asymmetry do not fall within said standardized values an operator is notified by an automatic system (Mao paragraph [0125] teaches notifying an operator by an automatic alert system on a screen when monitored data (including HETP values and asymmetry--see paragraph [0104]) do not fall within standardized values) . 07-22-aia AIA 7. Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Mao et al. (US Pat. Pub. 2018/0113101, hereinafter "Mao") as modified by Hyckenberg et al. (US Pat. Pub. 2019/0346412, hereinafter "Hyckenberg") as applied to claim 1 above, and further in view of Satulovsky (US Pat. Pub. 2010/0292957) . In regards to claim 2, Mao teaches the method as explained in the rejection of claim 1 above. Mao fails to expressly teach wherein said curve smoothing calculation is the Savitzky-Golay smoothing filter. Satulovsky paragraph [0065] teaches where a signal having an excessive noise level may be de-noised in a manner preserving first and second derivatives using a Savitzky-Golay filter for carrying out smoothing. It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Satulovsky because multiple types of smoothing filters are well known in the art. Therefore, it would only be a manner of ordinary skill to choose a smoothing filter such as a Satulovsky-Golay filter for carrying out de-noising while preserving first derivatives (which are calculated at a subsequent step). Pertinent Art 8. Applicants are directed to consider additional pertinent prior art included on the Notice of References Cited (PTOL 892) attached herewith. The Examiner has pointed out particular references contained in the prior art of record within the body of this action for the convenience of the Applicant. Although the specified citations are representative of the teachings in the art and are applied to the specific limitations within the individual claim, other passages and figures may apply. Applicant, in preparing the response, should consider fully the entire reference as potentially teaching all or part of the claimed invention, as well as the context of the of the passage as taught by the prior art or disclosed by the Examiner. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. B. Stafford (US Pat. No. 10,717,023) discloses a Method for Continuous Purification. C. Ganguly et al. (US Pat. Pub. 2010/0127860) discloses Systems and Methods for Evaluating Chromatography Column Performance. D. Cunnien et al. (US Pat. Pub. 2014/0067308) discloses Automated System and Method for Monitoring Chromatography Column Performance and Applications Thereof. E. Randolph (US Pat. Pub. 2019/0321752) discloses Transition Analysis Method for Chromatography Column Qualification. Conclusion 9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL D LEE whose telephone number is (571)270-1598. The examiner can normally be reached on M to F, 9:30 am to 6 pm. 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, Arleen Vazquez can be reached at 571-272-2619. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair- my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /PAUL D LEE/Primary Examiner, Art Unit 2857 5/29/2026 Application/Control Number: 18/687,181 Page 2 Art Unit: 2857 Application/Control Number: 18/687,181 Page 3 Art Unit: 2857 Application/Control Number: 18/687,181 Page 4 Art Unit: 2857 Application/Control Number: 18/687,181 Page 5 Art Unit: 2857 Application/Control Number: 18/687,181 Page 6 Art Unit: 2857 Application/Control Number: 18/687,181 Page 7 Art Unit: 2857 Application/Control Number: 18/687,181 Page 8 Art Unit: 2857 Application/Control Number: 18/687,181 Page 9 Art Unit: 2857 Application/Control Number: 18/687,181 Page 10 Art Unit: 2857 Application/Control Number: 18/687,181 Page 11 Art Unit: 2857 Application/Control Number: 18/687,181 Page 12 Art Unit: 2857 Application/Control Number: 18/687,181 Page 13 Art Unit: 2857 Application/Control Number: 18/687,181 Page 14 Art Unit: 2857
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