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 .
Status of claims
Claims 2-12 as amended on 1/23/2026 are pending.
Claims 11-12 were withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/16/2025.
Claims 2-10 as amended on 1/23/2026 are under examination in the instant office action.
Claim Rejections - 35 USC § 103
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.
Claims 2-10 as amended are rejected under 35 U.S.C. 103 as being unpatentable over Andre et al (“In-line and real-time prediction of recombinant antibody titer by in situ Raman spectroscopy”. Analytica Chimica Acta, 892 (2015), pages 148-152).
The cited reference by Andre discloses a method for estimating a culture state and predicting titer of antibody by in situ Raman spectrometry, wherein the method comprises:
Emitting electromagnetic waves from a tip of a probe (see “immersion probe” on graphical abstract at page 148) for Raman spectroscopic analysis to cell suspension (which is inside “bioreactor”) and acquiring by the immersion probe spectral data (see “spectrum” on graphical abstract at page 148; see section 2.4 at page 149) by Raman spectrometer as intended for constructing a soft sensor (“chemometric model” for prediction, estimation and/or control),
Performing preprocessing on spectral data including spectral intensity values for each wavelength (figures 1-2) for constructing the soft sensor (prediction model in the cited reference);
Constructing the soft sensor or providing a software-based system for data analysis (see section 2.5 “chemometric data analysis” at page 150), which establish correlation between Raman spectra and the reference measurements (see first par. at section 3, page 150) , thereby, software “with machine learning using a plurality of combinations of the spectral data and the state data as training data” within the broadest reasonable meaning of the claims;
Consecutive step(s) of emitting electromagnetic waves from a tip of a probe for Raman spectroscopic analysis to cell suspension (which is inside “bioreactor”) and acquiring by the immersion probe spectral data for acquiring “state data” of the culture (reference and/or test cell culture measurements on figures 3-4); and
Extracting/inputting the spectral data acquired for a cell suspension which is being cultured in situ to the soft sensor (to software-based system for data analysis ) and predicting titer of antibody or “acquiring the state data output from the soft sensor” within the broadest reasonable meaning of last two steps of the claimed method of claim 2 as amended.
Thus, although the cited reference does not use the same terminology (for example: “soft sensor”, “state data”), the cited reference by Andre discloses substantially similar, if not the same, method as encompassed by claim 2 as directed to estimating a culture state and/or predicting cell culture titer of antibody by in situ Raman spectrometry.
Further as applied to claims 3, 4 and 6: in the method of the cited reference by Andre the computer-based analysis comprises “performing preprocessing” by selecting “important variable reflecting antibodies Raman shifts” (page 150, col. 2, par. 2), thereby, “selecting, from spectral intensity values for each wave number or wavelength included in the spectral data, a spectral intensity value used as the training data” within the broadest reasonable meaning of the claims. In the cited method “training data” are based on numbers of calibration tests collected from total 132 samples (page 150, section 2.5, second par.), the numbers fall within the claimed range 5-1000.
As applied to claim 5: in the method of the cited reference by Andre “the selection is performed by sparse modeling” meaning that they utilize only a small subset (only antibodies) of their potential parameters (cell density, metabolites, nutrients) to represent data.
As applied to claim 8: in the method of the cited reference by Andre the state data is data related to amount of antibody.
As applied to claim 9 and 10: Although in a particular embodiment of the cited reference by Andre the state data relate to antibodies, the cited reference by Andre clearly recognizes that Raman spectroscopy successfully applied to monitor metabolites, cells densities, nutrients, biomarkers in various cases of biotechnology (page 149, col.1, par. 3) to predict or to provide “state data output from the soft sensor” with regard to cell densities, cell numbers, culture medium components by the same or similar computer-based analyses of Raman spectral data as tough/suggested by Andre.
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to estimate or to predict or to provide “state data output from the soft sensor” with regard to cell culture and antibody production by the same or similar computer-based analyses of Raman spectral data as taught/suggested by Andre.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Claims 2-10 as amended are/remain rejected under 35 U.S.C. 103 as being unpatentable over Andre et al (“In-line and real-time prediction of recombinant antibody titer by in situ Raman spectroscopy”. Analytica Chimica Acta, 892 (2015), pages 148-152) as applied to claims 2-8, and further in view of WO 2019/071076 (Webster et al).
The cited reference by Andre is relied upon as explained above for a disclosure of a method for estimating a culture state (culture “state data”) and predicting titer of antibody by in situ Raman spectrometry by software and/or computer-based analyses (“soft sensor”) of Raman spectral data.
In particular, in the method of the cited reference by Andre the state data is data related to amount of antibody. However, the cited reference by Andre clearly recognizes that Raman spectroscopy is successfully applied to monitor metabolites, cells densities, nutrients, biomarkers in various cases of biotechnology (page 149, col.1, par. 3).
Further, as applied to claims 9-10, the cited WO 2019/071076 (Webster et al) teaches a method for monitoring and control of bioprocess using inline Raman probes to monitor changes and/or data related to amounts of components in the culture including media nutrients, cell metabolites and number of the cells or cell concentrations (see abstract). The method of estimating culture state of the cited WO 2019/071076 (Webster et al) in based on generation of calibrations model or “soft sensor” as encompassed by the pending claims.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
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 2-10 as amended remain rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
The claims recite a method for estimating a culture state by using “soft sensor” or software-based system for data analysis, wherein claimed “data” are a collection of spectral data in various combinations acquired by using Raman spectrometry.
The Raman spectroscopy has been successfully applied to monitor metabolites, cells densities, nutrients, biomarkers in various cases of biotechnology (see the reference by Andre (2015) at page 149, col. 1, par. 3). Therefore, step of acquiring spectral data by Raman spectrometry is a common, routine and conventional practice.
The core or the whole scope the claimed method is drawn the use of software, thereby, to mathematical concepts including algorithms, mathematical formulas, mathematical equations and mathematical calculations, all falling into category of abstract ideas. The final result of the claimed method is an acquisition of the “output from the soft sensor” which is a theoretical prediction of a culture state based on calibration of a plurality of combinations of spectral data derived from a culture solution during software based “preprocessing” and software “machine learning” of spectral data. Thus, the final result is a concept but not a product, the concept being an abstract idea.
This judicial exception is not integrated into a practical application because claimed elements in combination do not add a meaningful limitation or extra-solution to the claimed method, and the claimed method as a whole is nothing more than an attempt to generally link the claimed invention to a particular technological environment. A computer program-based prediction of a culture state can also be understood as a mental concept or a cognitive process that involves using existing in situ cell culture information (claimed “data”) to anticipate future outcomes.
With regard to limitation drawn to use of artificial intelligence and/or “machine learning” techniques (AI/ML), said recitation does not make the claim patent eligible, because said tools are utilized merely for data gathering and comparing, and are not utilized in express manipulation and control of functional aspects and/or hardware components/equipment of real-world processes and systems using output of AI models (e.g., manufacturing processes and equipment, medical treatments, communications processes and systems, logistics systems and hardware, interactive smart phone apps, etc.).
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because when considered separately and in combination, they do not add significantly more (also known as an “inventive concept”) to the exception.
Response to Arguments
Applicant's arguments filed on 1/23/2026 have been fully considered but they are not persuasive.
With regard to claim rejection under 35 USC § 103 Applicants’ main argument is that reference by Andre does not disclose “extracting spectral data that are highly correlated with state data” (response page 7, lines 1-2) and that Webster fails to cure the deficiencies of the teaching by Andre (response page 7, line 3).
This argument is not found persuasive because the cited reference by Andre clearly disclose providing (“extracting”) predictive data that are highly correlated with test culture “state data” (figure 3) as based on spectral analysis acquired by Raman spectrometry (entre document). The teaching by Webster further discloses the ability to generate calibration models for various cell culture parameters using inline Raman probes to monitor change in cell culture.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
With regard to claim rejection under 35 U.S.C. 101 Applicants argue that the claimed invention is not only based on an abstract idea and an algorithm but also uses some hardware components such as a probe (response page 5).
This argument is not found persuasive because a probe of Raman spectroscopy has been successfully applied to monitor metabolites, cells densities, nutrients, biomarkers in various cases of biotechnology (see the reference by Andre (2015) at page 149, col. 1, par. 3). Therefore, step of acquiring spectral data by a probe of Raman spectrometry equipment is a common, routine and conventional practice.
The core or the whole scope the claimed method is drawn the use of software, thereby, to mathematical concepts including algorithms, mathematical formulas, mathematical equations and mathematical calculations, all falling into category of abstract ideas. The final result is not a transformation of materials used (whether a probe as argued or a cell culture) but a mental or abstract conclusion based on “soft sensor” or software employing mathematical concepts including algorithms.
No claims are allowed.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VERA AFREMOVA whose telephone number is (571)272-0914. The examiner can normally be reached Monday-Friday: 8.30am-5pm EST.
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.
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.
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.
Vera Afremova
March 12, 2026
/VERA AFREMOVA/ Primary Examiner, Art Unit 1653