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 .
Election/Restrictions
Applicants’ election without traverse of invention Group I in reply filed on 03/23/2026 is acknowledged. Claims 1-12 read on the elected group.
Claims Status
Claims 1-22 are pending.
Claims 13-22 are withdrawn.
Claims 1-12 have been examined on the merits.
Response to Arguments / Status of Rejections
RE: Objection to the Drawings submitted on 10/13/2023 without a granted petition for color images:
Applicants have amended drawings and submitted black and white figures on 07/31/2026.
Previous objection is withdrawn.
RE: Objection to claim 1
The amendment to the claim overcomes the basis of the prior objection of record.
The rejection is withdrawn.
RE: Rejection of claim 11 under 35 U.S.C. §112 (b):
Applicants traverse the rejection on the grounds that the calculation for oral bioavailability is a standard pharmacokinetic administration that would be understood by a person skilled in the art. Applicants further describes that in the context of the invention, a micro physiological system (MPS); concentrations of the compound are measured in the liver compartment over time after the administration of the intestinal compartment (oral dose) and when mixed into the cell culture media in the combined liver and gut basolateral compartment (IV dose). The AUC values are calculated as outlined in the formula of claim 11.
Applicants state that a skilled person would understand that area under the curve (AUC) oral refers to area under the plasma concentration time curve following oral administration of the treatment, which would correspond to the concentration time profile generated by the MPS (micro physiological systems); such that the oral dose refers to the administered oral dose in mass. Applicants also state that a skilled person would understand that AUC IV refers to the area under the plasma concentration time curve following direct IV administration of the treatment, which would correspond to the concentration time profile generated by the MPS; such that dose IV refers to the administered IV dose in mass.
These arguments are not found to be persuasive.
While the formula and calculation for oral bioavailability may be well known in the art for standard pharmacokinetic determination, in the context of the claimed invention it is not known nor clear how Applicants intend for the calculation to be determined based on the language of claim 11. The explanation provided by Applicants in the Remarks (See, p8) about how to use the MPS system to gather data needed to get AUC for oral and IV with the method of claim 11 includes a formula with variables not clearly defined in the claims 1, 7, and 10 (which claim 11 depends on), gives clarity on how to apply the formula in claim 11 to the method. Claims are required to have definiteness to ensure the scope of the claims is clear and to provide a clear measure of what the inventor regards as the invention (See, MPEP 2173). Provided there is sufficient support in the disclosed specification of the application to support the context and explanation of how to use the MPS of the claimed inventions to calculate oral bioavailability with the formula in claim 11 the inclusion of the necessary information would aid in the definiteness of the claim.
RE: Rejections of claims 1-10 and 12 under 35 U.S.C. § 103 over Shinohara et al (Scientific reports, 2021; as cited in IDS filed on 03/23/2026) and in view of Chen et al (Lab on chip, 2018):
Applicants traverse on the grounds that the MPS system taught in Shinohara et al does in fact teach the inclusion of epidermal growth factor (EGF) in the circulating medium of the co-culture and monoculture of the PBX cells and Chen et al does not remedy the deficiency of Shinohara et al because Chen et al also teaches the use of EGF in the co-culture medium.
This argument is found to be persuasive.
The inclusion of the EGF in the circulating medium of Shinohara et al was an oversight in the previous action. The initial circulating medium of the claimed invention does not include EGF, but it is added at a different point during the co-culture. This is sufficient to distinguish the claimed invention from those of the prior art, as both Shinohara et al and Chen et al, which teach similar systems both use EGF throughout.
Applicants traverse the rejections of claims 2 and 3 on the grounds that the interpretation of the MPS described in Shinohara et al does not read on the claimed invention. Specifically, Shinohara et al does not teach the second and third fluid paths that allow for independently recirculated within each chamber without fluid being passed between the chambers.
This argument is found to be persuasive.
The MPS detailed in Shinohara et al does not include fluid paths that allow for independent recirculation within each chamber without fluid being passed between the chambers. Applicants are encouraged to provide the context described in the Remarks to provide further clarity and definiteness to the claims. As claims 2 and 3 do not claim the second and third fluid paths allow for independent recirculation respectively, as the Applicants elaborated in the Remarks, this would provide the context necessary to distinguish the claimed invention from the prior art (See, p11).
Therefore, upon reconsideration Applicants arguments regarding claims 1-10 and 12 are found persuasive. Applicants provided evidence to distinguish the claimed invention from the prior art. The previous rejection of record is withdrawn.
RE: Rejections of claims 1-10 and 12 under 35 U.S.C. § 103 over Shinohara et al (Scientific reports, 2021; as cited in IDS filed on 03/23/2026) and Chen et al (Lab on chip, 2018), and in further view of Lau et al (Drug metabolism and disposition, 2004); evidenced by Bioavailability and Bioequivalence (EUPATI Open Classroom, 2021):
Applicants traverse this rejection that Lau et al does not teach the claimed configuration of compartmentalized growth factor control co-culture system of primary intestinal and hepatic cells under distinct microenvironmental conditions.
This argument is not found to be persuasive.
As Lau et al is not used for the configuration of the claimed system and the cell types co-cultured but it was used as motivation for calculating bioavailability from a co-culture system as described in Shinohara et al. Therefore, Lau et al does provide sufficient motivation to calculate oral bioavailability after co-culture.
Yet, as claim 11 is dependent on claim 1, and the obvious rejection over claim 1 is withdrawn, the rejection of claim 11 is withdrawn.
Maintained Grounds of Rejection
Claim Rejections - 35 USC § 112
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 11 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.
Claim 11 requires calculating oral bioavailability of at least one treatment using [the recited formula]. The formula references ‘area under the curve (oral) (IV)’ and ‘area under the curve (dose) (IV)’; however, it is not clear what curve is being referred to or how it is calculated. Therefore, there is insufficient antecedent basis for the limitations referring to ‘area(s) under the curve’. Overall, it is unclear what values are used for this calculation and therefore this claim is indefinite.
Appropriate action or clarification is required.
Allowable Subject Matter
Claims 1-10 and 12 are allowed.
An updated prior art search show the closest prior is Shinohara et al and it has been established that the circulating media includes EGF. Chen et al another close prior art, also uses EGF in the circulating media for the co-culture. The state of the art indicates that EGF is essential for culturing of primary hepatocytes and intestinal cells.
Claim 11 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
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 Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 4:30pm M-Th.
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/CAROLINE M LARA/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
