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 .
Detail Action
Claims 1-14 submitted on 9/27/2024 are pending.
Applicants’ election on 7/30/2026 without traverse of group I (claims 1-12) directed to a production method for a product, comprising: culturing cells in a culture container, wherein the culturing is a perfusion culture method, Expressions (1) to (5) are satisfied in a production period of a product after reaching a target viable cell density, a variation of VCD during the production period is ±20% or less with respect to an average viable cell density during the production period, and a variation of VCV during the production period is ±20% or less with respect to an average value of the VCV during the production period,
0 ≤ Gln-C ≤ 2.5 Expression (1) 0.5 ≤ Gluc-C ≤ 8.0 Expression (2) 1.0 ≤ NH4-C ≤ 8.0 Expression (3)
50 ≤ VCD ≤ 300 Expression (4) 0.6 × 105 ≤ VCV ≤ 4.0 × 105 Expression (5) in the expressions, Gln-C indicates a glutamine concentration [mmol/L] in a culture solution, Gluc-C indicates a glucose concentration [g/L] in the culture solution, NH4-C indicates an ammonia concentration [mmol/L] in the culture solution, VCD indicates a viable cell density [×106 cells/mL], VCV indicates VCD × π/6 × Cd3 [×106 μm3/mL], and Cd indicates an average diameter [μm] of viable cells.
in their response against the restriction requirement of 6/11/2026 is acknowledged. Claims 12-14 comprise non elected subject matters are withdrawn. Claims 1-12 are for examination. Election made final.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/7/2025 and 12/16/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the examiner has considered the IDS statement.
Claim Rejections: 35 USC § 112(b)
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.
Claim 7 and 12 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
Claim 7 is indefinite in reciting “ Expression (6)” because it lack antecedent basis..
claim 7 depends on claim 1 and claim 1 does not recite Expression (6).
Claim 12 is indefinite in reciting Expressions (2B)” because it lack antecedent basis..
claim 12 depends on claim 1 and claim 1 does not recite Expressions (2B).
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) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
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(a) 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.
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.
According to MPEP 2143:"Exemplary rationales that may support a conclusion of obviousness include:(A) Combining prior art elements according to known methods to yield predictable results;(B) Simple substitution of one known element for another to obtain predictableresults;(C) Use of known technique to improve similar devices (methods, or products) in the same way;(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel."
Claims 1-12 are rejected under 35 U.S.C. 103(a) as being unpatentable over D1: JP 2020-005511 A (HITACHI LTD) 16 January 2020 (2020-01-16, pp 1-22, IDS) in view of D2: DOWNEY,B. J. etal. (PROG. 2014, vol. 30, no. 2, PP. 479-48, IDS) and D3: US 2020/0255785 A1, claims 1-29 & WO 2019/055796 A1 ( Attached herewith)
Document 1 discloses (JP 2020-005511 A (claims 1-10, paragraphs [0017], [0031], [0034], [0036], [0040]-[0055], [0091]-[0094], fig. 2-3, 5, table 2) an invention relating to a culture method wherein cells are continuously cultured while continuously supplying a culture medium to a culture tank and continuously discharging the culture medium (refer to claims 1-10, paragraph [0009] etc.), and indicates that when doing so, one or more of the concentration of glucose, the concentration of glutamine, the concentration of lactic acid, and the concentration of ammonia in the culture tank is adjusted by controlling the supply flow rate of the culture medium (refer to claim 4 etc.). CHO cells are cited as an example of test cells (refer to paragraph [0031] etc.). It is further indicated that the concentration of glucose during a production phase is adjusted to less than 0.4 g/L. (refer to paragraph [0034], fig. 2 etc.), the concentration of glutamine during the production phase is configured to be at least 0.4 but less than 1.5 mM from the point of view of maintaining a relatively high production rate (refer to paragraph [0036], fig. 3 etc.), and the concentration of ammonia during the production phase is configured to be more than 2.0 mM but at most 20 mM from the point of view of maintaining a high survival rate of approximately 90% or more (refer to paragraph [0040], fig. 5 etc.), and it is indicated that taking into consideration the relationship between the concentration of glucose and the concentration of glutamine and the relationship between the concentration of glucose and the concentration of ammonia, the concentration of glucose during the production phase is configured to be less than 1.5 g/L (refer to paragraphs [0041]-[0055], table 2 etc.). In addition, the feature of also monitoring cell count density, specific growth rate, and survival rate is disclosed (refer to paragraphs [0091]-[0094] etc.), and a capacitance method is cited as an example of a means of doing so (paragraph [0092]).
Document 2 (abstract) indicates that online measurement of living cell volume (VCV) is essential to the monitoring and control of bioprocesses. Document 2 (p. 481, left column, line 28 to p. 481, right column, line 10) also indicates that viable cell volume (VCV) can be calculated from the viable cell density (VCD) and average viable cell diameter.
Document 3 discloses an invention relating to a method for controlling the perfursion rate in a perfusion bioreactor (claims 1-29), and discloses the feature of measuring viable cell density using a biomass capacitance probe (claim 1). If the invention as in claim 1 and the invention disclosed in document 1 are compared, said inventions coincide with respect to the feature of relating to a method for producing a product, said method including culturing cells in a culture vessel using a perfusion culture method in which the glutamine concentration, glucose concentration, ammonia concentration in a culture medium, and viable cell density during the production period of the product each satisfy specified conditions, but differ in that in the former, fluctuations in VCV during the production period are ±20% or less with respect to the average value of VCV during the production period, whereas the latter does not specify such a feature. Meanwhile, as indicated in document 2, it was already known that VCV is also an important factor for monitoring bioprocesses. Furthermore, there is a high probability, to begin with, that if CHO cells are maintained in a preferable culture condition, measured VCV values also fall within a prescribed numerical range. Accordingly, referring to the disclosures in document 2, a person skilled in the art could easily have conceived of also using VCV to monitor bioprocesses in the method disclosed in document 1 and confirming whether said measured values are maintained in a prescribed numerical range.
Furthermore, the feature of monitoring VCD using a capacitance method is disclosed in document D3. the technical field of which coincides with documents 1 and 2 with respect to the feature of relating to the monitoring of bioprocesses, and said feature is also exemplified in document 1 (paragraph [0092]). Accordingly, a person skilled in the art could also have monitored VCD using a capacitance method as necessary and appropriate. The same is the case for claims 2-12.
Therefore it would have been obvious to a person of ordinary skill in the art, at the time of the instant invention is filled to combine the teaching of over D1: JP 2020-005511 A (HITACHI LTD) in view of D2: DOWNEY, et al. and D3: (US 2020/0255785 A1, also WO 2019/055796 A1 ) in the method of D1 modify using the process of D2 and D3 to come applicants invention of claim 1-12.
Conclusion
Claims 1-12 are rejected and no claim is allowable.
Any inquiry concerning this communication or earlier communications from the
examiner should be directed to Mohammad Meah whose telephone number is 571-272-
1261. The examiner can normally be reached on 8:30-5PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
supervisor, Robert Mondesi can be reached on 4089187584. The fax phone number
for the organization where this application or proceeding is assigned is 571-273-8300.
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/MOHAMMAD Y MEAH/Examiner, Art Unit 1652
