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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 13 April 2026 has been entered.
Response to Amendments
Applicant’s amendments filed 06 April 2026 have been entered.
Claim 1 has been amended; Claims 2, 3, 8, 9, and 13 were canceled; and Claims 15-19 are withdrawn. Overall, Claims 1, 4-7, 10-12, and 14-19 are pending.
Applicant’s amendments to Claim 1 with respect to the rejections of Claims 1, 4-7, 10-12, and 14 under 35 U.S.C. 103 as being unpatentable over NAUGHTON et al. (US Patent 6,395,538) in view of SKUDAS et al. (US PGPub 2013/0280788 A1) are unpersuasive. The grounds of rejection have been sustained.
Response to Arguments
Applicant’s arguments filed 06 April 2026 have been fully considered but are not persuasive.
Applicant argues that as-amended Claim 1 is not disclosed or suggested by NAUGHTON (pg. 7, par. 2), i.e., NAUGHTON fails to disclose or suggest “controlling the bioprocess purification system based on the identified deviation” wherein the “identified deviation comprises a loading volume or a concentration of the target product that is greater than or less than an expected level” (pg. 7, par. 3). Because of this, Applicant argues that the claims are not prima facie obvious over the cited art (pg. 7, par. 4).
The Examiner respectfully disagrees.
Initially, it is noted that the as-amended limitation to Claim 1 does not change the scope of the claim. Even further, the instant limitation has already been addressed in previous rejections.
In the prior art rejection of the Office action dated 06 December 2026 (pg. 4, par. 1), NAUGHTON clearly identifies protein concentration as part of the fingerprinting analysis that is used to determine an appropriate response to control the purification process. Briefly, NAUGHTON describes identifying a deviation in biomolecule concentration (col. 15, lines 13-16) and subsequently determining an appropriate response, i.e., initiating “control steps” if deviations are determined (col. 15, lines 54-60). Overall, NAUGHTON discloses, especially in col. 23, lines 1-5 (and more broadly, lines 1-19) that the taught process enables the skilled artisan to “sharpen the peak” and improve the resolution via IR spectroscopic monitoring to “markedly [improve] the quality of the purification” (lines 14-19). Thus, the prior art of record does indeed read upon the as-amended limitation “controlling the bioprocess purification system based on the identified deviation” based on “the identified deviation comprises a loading volume or a concentration of the target product that is greater than or less than an expected level”.
Priority
Applicant’s claim for the benefit of a prior-filed application (371 of PCT/EP2017/084495 filed 22 December 2017) under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Acknowledgment is made of applicant’s claim for foreign priority (GB1622343 filed 29 December 2016) under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4-7, 10-12, and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over NAUGHTON et al. (US Patent 6,395,538) in view of SKUDAS et al. (US PGPub 2013/0280788 A1).
Regarding Claim 1, NAUGHTON discloses a method for controlling and monitoring a biomanufacturing process using infrared spectroscopic monitoring and fingerprinting of a biomolecule to produce a desired biomolecule having appropriate characteristics (abstract; c2/20-25; c2/30-33); such purification techniques involve chromatographic separations (i.e., a method for controlling a continuous bioprocess purification system comprising a… chromatography process… wherein the continuous purification is performed on a sample comprising a target product having desired characteristics; c21/13-24).
The process is designed to optimize the production of the biomolecule with adjustments during the process (c18/44-49), e.g., the biomolecule of interest is separated from other molecules and purified to homogeneity or inactive biomolecules are monitored (i.e., (a) detecting at least one parameter indicative of target characteristics of the target product; (b) controlling the continuous bioprocess purification system to meet the desired characteristics based on the detected at least one parameter; c21/15-17).
NAUGHTON further discloses that fingerprinting includes comparing the recorded biomolecule spectra to a reference spectrum (c14/58-63) and monitoring includes determining quantitative information about the biomolecule, i.e., including the amount of biomolecule purified (c15/5-12) and the biomolecule concentration (i.e., at least one parameter indicative of target characteristics; c18/29-31), and about inactive biomolecules in the analyzed sample (i.e., wherein impurities in the target product after the sample has been processed in the continuous chromatography is detected in step a); c15/41-42).
More specifically, NAUGHTON discloses the use of multiple chromatography columns in series to purify a biomolecule, i.e., a first cation exchange column, followed in sequence by an anion exchange column, a hydroxyapatite column, then gel filtration chromatography, wherein the collected eluted fractions from previous columns are filtered in a subsequent column (i.e., a continuous chromatography process configured to operate with at least three columns; c31/20-c/32/51). NAUGHTON further discloses that if the biomolecule solution contains an excess concentration/proportion of an unwanted product (e.g., inactive biomolecules), the solution is “shunted back for reprocessing” (i.e., wherein the target characteristics are within a pre-determined range; step b) comprises reprocessing the target product with the detected impurities; c32/1-4; concentration: c31/44-47). While a specific example is provided, NAUGHTON further discloses the number and type of chromatography steps used in the purification of a biomolecule is dependent on the nature of the biomolecule, the source material, and the level purity/yield required (c21/52-57).
NAUGHTON further discloses real time process control based on the IR fingerprinting of the biomolecules (c12/54-62). The spectra collected during fingerprinting is further analyzed and “fed” to a process model to determine expected parameters (e.g., concentrations, tolerances) (i.e., wherein the method further comprises performing real time trend analysis of each detected at least one parameter to identify a deviation from the desired characteristics of the target product before step b); trend analysis: c15/5-12; identify a deviation: c15/13-16; concentrations: c25/45-58, c26/35-39) to determine the appropriate response to control the separation/purification process to achieve the desired outcome (c15/13-40; c15/54-60), i.e., adjustments are made to elution buffer so that the biomolecule purification can be optimized (i.e., the identified deviation comprises a loading volume or a concentration of the target product that is greater than or less than an expected level; c22/24-31; c22/39-49; c22/59-62). Such a purification involves separating the biomolecule of interest from “unwanted material” to improve the resolution (i.e., controlling the bioprocess purification system based on the identified deviation; c23/1-5).
NAUGHTON is deficient in explicitly disclosing the chromatography process is a continuous chromatography process configured for continuous purification in a cyclic operation or that the continuous chromatography process comprises loading, elution, and cleaning steps of each column.
However, such configurations are well known in chromatography, especially for biomolecules used for pharmaceutical purposes. For instance, SKUDAS discloses a continuous chromatography process for the purification of biopharmaceutical molecules (p0001; p0008). In the disclosed process, at least three columns are connected in series such that continuous purification is achieved, wherein each column is generally subjected to load, wash, elute, and regenerate steps in staggered sequence, and the operation is repeated one or more times (i.e., a continuous chromatography process… configured for continuous purification in a cyclic operation; wherein the continuous chromatography process comprises loading, elution, and cleaning steps of each column; p0137). Such a continuous operation advantageously yields better utilization of resins, reduces processing time, and reduces buffer requirements compared with conventional, non-continuous chromatography (p0008). Thus, prior to the effective filing date of the invention, one of ordinary skill in the art would have found it obvious to utilize a continuous chromatography process configured for continuous purification in a cyclic operation as suggested by SKUDAS for the biomolecule purification process of NAUGHTON. Furthermore, one of ordinary skill in the art prior to the effective filing date of the invention would have a reasonable expectation of success in adapting this continuous chromatography process with cyclic operation as disclosed by SKUDAS in the method of NAUGHTON because SKUDAS discloses such a method is suitable for use in biomanufacturing and with affinity and ion exchange media (p0137).
Regarding Claim 4, modified NAUGHTON makes obvious the control method of Claim 1. SKUDAS further discloses that after being subjected to continuous separation, a target molecule is subjected to virus inactivation and subsequent chromatography purification (i.e., a viral inactivation step after the continuous chromatography process; FIG. 15; p0183). Advantageously, viral inactivation renders viruses inactive and thereby, the purified product safe for therapeutic use (p0184). Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to subject the target product to viral inactivation as suggested by SKUDAS for the method disclosed by NAUGHTON.
Furthermore, the limitation “further comprises processing the purified target product with the detected impurities through another viral inactivation step” is directed to a duplication of process steps. The mere duplication of parts or process steps has no patentable significance unless a new and unexpected result is produced (In re Harza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960); MPEP §2144.04). The mere duplication of the essential working parts of a device involves only routine skill in the art (St. Regis Paper Co. v. Bemis Co., 193 USPQ 8). As explained by Applicant, the additional viral inactivation step has no other expected result other than to further remove or inactivate any viruses present in solution (pg. 13, lines 12-17).
Regarding Claim 5, modified NAUGHTON makes obvious the control method of Claim 1. NAUGHTON further discloses the IR spectroscopy step is initially practiced to determine an initial sample spectra (c14/47-57) and that the fingerprint of the biomolecule itself is monitored to detect the initial level of production in the sample (i.e., step b) controls an upstream process in the continuous bioprocess purification system; c19/41-46).
Regarding Claim 6, modified NAUGHTON makes obvious the control method of Claim 5. NAUGHTON further discloses that the monitoring of the spectra includes determining quantitative information about the biomolecule, i.e., including the biomolecule concentration (i.e., controlling the concentration of the target product in the sample being fed into the continuous chromatography process; c18/29-31).
Regarding Claim 7, modified NAUGHTON makes obvious the control method of Claim 5. NAUGHTON further discloses that the biomolecules are expressed from cell culture flasks or bioreactors and fermentation cultures (i.e., wherein the continuous bioprocess purification system comprises a cell culture process; c16/7-9; c17/1-3). NAUGHTON further discloses adaptation of the process for a fermentation process (i.e., step b) comprises controlling the cell culture process to adjust the composition of the sample being fed into the continuous chromatography process; c17/27-35; c18/29-49).
Regarding Claim 10, modified NAUGHTON makes obvious the control method of Claim 1. NAUGHTON further discloses a subsequent formulation step after purification, wherein the purified biomolecule is resuspended in a final solution containing physiologically acceptable excipients, lyophilizing, and aseptic processing (i.e., the continuous bioprocess purification system comprises a polish step; c23/20-29). NAUGHTON further discloses the biomolecule spectra are compared with a reference and a calibration curve to verify the validity of the detected biomolecule spectra (i.e., defining a target product fingerprint; c14/58-63). Fingerprinting as such is performed throughout the process, i.e., at biological production, at recovery and purification, and at bulk formulation (i.e., in step a), obtaining at least one fingerprint after the sample has been processed in the continuous chromatography process; c12/16-29). NAUGHTON discloses comparing biomolecule spectra with a reference to verify validity of the detected spectra (c14/58-63) and to determine whether purification is further required based on a degree of tolerance (i.e., comparing the target product fingerprint with the at least one fingerprint of the sample to identify deviations; c15/5-12). Finally, NAUGHTON discloses in situ real-time monitoring and control of the purification process during which the spectra of the biomolecule solution are compared before and after each chromatographic separation (i.e., comparing the target product fingerprint with the at least one fingerprint of the sample to identify deviations; adjusting the polish step in response to the identified deviations; c23/42-45; c22/24-31).
Regarding Claim 11, modified NAUGHTON makes obvious the control method of Claim 10. NAUGHTON further discloses the biomolecule spectra are compared with a reference and calibration curve to verify the validity of the detected biomolecule spectra (i.e., wherein the target product fingerprint is defined by the composition of the target product and/or detected impurities in the target product; c14/58-63).
Regarding Claim 12, modified NAUGHTON makes obvious the control method of Claim 10. NAUGHTON further discloses infrared spectrometry (i.e., wherein the at least one fingerprint is obtained by spectrometry; c14/10).
Regarding Claim 14, modified NAUGHTON makes obvious the control method of Claim 13. NAUGHTON further discloses determining quantitative information about the biomolecule, i.e., including the amount of biomolecule purified (i.e., step a) further comprises measuring a purified amount of the target product; c15/5-12).
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 RYAN B HUANG whose telephone number is (571)270-0327. The examiner can normally be reached 9 am-5 pm EST.
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, In Suk Bullock can be reached on 571-272-5954. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Ryan B Huang/Primary Examiner, Art Unit 1777
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