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 .
DETAILED ACTION
Applicant’s response filed dated 01/05/2026 is duly acknowledged.
Claims 1-15 as currently presented are pending in this application.
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1-13; directed to “A method of simulating gastrointestinal dissolution and permeation of a substance…”) in the reply filed on 01/05/2026 (see REM, p. 6) is acknowledged.
Accordingly, claims 14 and 15 (drawn to non-elected invention of “A gastrointestinal tract simulation system…” and use thereof; taken as a device/apparatus) have been withdrawn from further considerations.
Claims 1-13 (elected invention of Group I, without traverse; directed to “A method of simulating gastrointestinal dissolution and permeation of a substance…”) have been examined on their merits in this action hereinafter.
Priority
This application is a 371 of PCT/EP2021/087117 (filed on 12/21/2021), which claims foreign priority from European applications EP 20216750.8 (filed on 12/22/2020) and EP 21154616.3 (filed on 02/01/2021).
Claim Objections
1. Claim 1 (as presented) is objected to because of the following informalities: Claim 1 recites the limitations of step d) “sampling the fluid of the first compartment and of inner the inner vessel of the second compartment to assess the dissolution of said substance…”, which should be amended to recite “sampling the fluid of the first compartment and of . Appropriate correction is required.
2. Claim 8 is objected to because of the following informalities: claim 8 (line ) recites the limitations “0-50 vol%/min waste sink from the outer vessel of the second compartment to a waste sink reservoir”, which should be amended to recite “0-50 vol%/min waste sink solution from the outer vessel of the second compartment to a waste sink reservoir” (see instant specification, p. 10, last paragraph, for instance). Appropriate correction is required.
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.
1. Claims 1-13 (as currently presented) 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.
Claims 1 and 2 as presented have been reproduced below:
“1. (Original) A method of simulating the gastrointestinal dissolution and intestinal permeation of a substance, comprising the steps of:
a) providing a dynamic gastrointestinal tract simulation system comprising at least two consecutive compartments of which a first compartment simulates at least part of the stomach and a second compartment simulates at least part of the small intestine, said second compartment comprising an outer vessel and an inner vessel mounted inside the outer vessel, said inner vessel having a wall comprising a grid structure and a semi-permeable membrane mounted around said grid structure;
b) introducing the substance in the first compartment;
c) operating the gastrointestinal tract simulation system, further comprising a fluid transfer system for transferring fluids into and from said at least two consecutive compartments, to transfer the substance from the first compartment into said inner vessel and to allow permeation of said substance in a dissolved state through the membrane; and
d) sampling the fluid of the first compartment and of inner the inner vessel of the second compartment to assess the dissolution of said substance and/or sampling fluid from the outer vessel of the second compartment to assess the permeation of said substance through the membrane.”
“2. (Previously Presented) The method of claim 1, wherein the gastrointestinal tract simulation system is operated fully dynamic.”
At the outset, it is to be noted that applicant has not specifically defined the term “dynamic” in terms of “a gastrointestinal tract simulation system” per se (see specification, p. 5, reproduced below; and see also p. 3, 1st paragraph, for instance):
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Is to be noted that the term “dynamic” as known to a person of ordinary skill in the art may mean variously, including “continuous and productive activity or change”, or being energetic or forceful (see term “dynamic” as defined by Merriam-Webster online dictionary; cited as ref. [U] on PTO 892 form), or may also relate to periodic changes, etc. Thus, the recitation of “a dynamic gastrointestinal tract simulation system” renders the claim ambiguous as the metes and bounds of the claimed process employing such a “gastrointestinal tract simulation system” cannot be properly defined. No specific structural elements and/or features have been recited and/or defined in instant claim 1, that would render or configure said system into a “dynamic” gastrointestinal tract simulation system per se. Thus, the process as claimed is deemed indefinite for failing to clearly recite the process steps and/or components as required by the method as claimed.
Similarly, instant claim 2 recites the limitation “wherein the gastrointestinal tract simulation system is operated fully dynamic”, which is ambiguous and confusing because it is not clear as to how the gastrointestinal tract simulation system is operated in a fully dynamic manner, or if there are other configuration or means required in order for the process to be “fully dynamic”? Since, it is unclear as to what exactly the term “fully dynamic” would encompass to an artisan in the art, the metes and bounds of the claimed process does not appear to be properly defined.
The instant specification disclosure of record, as well as the dependent claims as presented do not clarify this ambiguity, and therefore, the dependent claims 3-13 are also rejected as being indefinite for the same reasons, as discussed above. Appropriate correction and/or explanation is required.
For the prior art purposes herein, any method using a system/device that simulates and/or mimics gastrointestinal tract physiology for a given substance, has been taken as “a dynamic gastrointestinal tract simulation system” using the plain meaning of the term consistent with the instant disclosure of record.
NOTE: 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 (i.e., changing from AIA to pre-AIA ) 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.
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.
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.
1. Claims 1-13 (as currently presented) are rejected under 35 U.S.C. 103 as being unpatentable over LEE (US 2021/0011038 A1; US-PGPUB cited as ref. [A] on PTO 892 form) taken with AUGUSTIJNS et al (WO 2018/108942 A1; FOR cited as ref. [N] on PTO 892 form).
Claim 1 has been reproduced as follows:
“1. (Original) A method of simulating the gastrointestinal dissolution and intestinal permeation of a substance, comprising the steps of:
a) providing a dynamic gastrointestinal tract simulation system comprising at least two consecutive compartments of which a first compartment simulates at least part of the stomach and a second compartment simulates at least part of the small intestine, said second compartment comprising an outer vessel and an inner vessel mounted inside the outer vessel, said inner vessel having a wall comprising a grid structure and a semi-permeable membrane mounted around said grid structure;
b) introducing the substance in the first compartment;
c) operating the gastrointestinal tract simulation system, further comprising a fluid transfer system for transferring fluids into and from said at least two consecutive compartments, to transfer the substance from the first compartment into said inner vessel and to allow permeation of said substance in a dissolved state through the membrane; and
d) sampling the fluid of the first compartment and of inner the inner vessel of the second compartment to assess the dissolution of said substance and/or sampling fluid from the outer vessel of the second compartment to assess the permeation of said substance through the membrane.” (see also the 112b rejection discussed above. It is noted that instant claim 1 does not require “a substance” to be a pharmaceutical substance per se)
See also limitations of dependent claims 2-13 as currently presented.
Lee (2021), while teaching an automated dissolution/permeation testing system for pharmaceutical products or drugs (see title, Abstract, and Claims), disclose (regarding instant claims 1-2) the method for performing both dissolution testing and permeation testing of the pharmaceutical product through a membrane employing an automated testing apparatus in which, for the permeation testing, “the system recreates flow of release of a pharmaceutical from the stomach to the intestines using a man-made intestinal membrane” and also allows for “quantification of dynamic permeation of the pharmaceutical through the intestinal wall via
UV or HPLC systems” (see Lee, [0001]-[0002], for instance); wherein “flow of release of a pharmaceutical from the stomach to the intestines is recreated using a man-made intestinal membrane, while at the same time, dissolution testing of the pharmaceutical product can be performed” (see Lee, [0012], for instance); wherein (regarding instant claims 3-4) said “testing apparatus includes temperature-controllable testing cell units arranged on a housing frame. Each testing cell unit includes a donor chamber receivable of dissolution media, a receptor chamber receivable of bodily fluid, gaskets that retain a membrane between the two chambers, and controllable mixers that mix the fluid in the receptor chamber. A flow control arrangement operatively circulates dissolution media through the donor chamber and enables sampling of the dissolution media. Another flow control arrangement operatively circulates bodily fluid through the receptor chamber. An analysis unit analyzes dissolution media removed from the donor chamber and bodily fluid removed from the receptor chamber to provide data about dissolution of a pharmaceutical product dissolved in the dissolution media and permeation of the pharmaceutical product through the membrane into the bodily fluid” (see Abstract; [0038]-[0042], [0045], Figures 6-9, for instance); wherein “mixing device may be any type of mixing device used to mix fluid, such as a stirrer” (see [0042], [0045], for instance); wherein said “membrane represents, for example, an intestinal wall. That is the membrane may be any type of membrane that has properties which are the same as or similar to an intestinal wall or other body part for which permeation testing is undertaken. Preferably, the membrane is PERMEFILMTM...” (see Lee, [0041], for instance), which is held using annular gaskets on each side of the testing cells/units (see Lee, [0020], [0072], for instance); wherein (regarding instant claim 8, partly) the testing system comprises multiple compartments, including suitable reservoirs for sample as well as waste collections (see Lee, [0084], [0104], Figures 7 and 11, for instance) interconnected via conduit systems configured for secure fluid flow between compartments/vessels; wherein (regarding instant claim 9) the system is operated so as to control in each compartments, one or more of the parameters such as liquid flow, temperature, pH, for instances (see Lee, [0038]-[0040], [0051], [0055], for instances); wherein (regarding instant claim 10) a plurality of said gastrointestinal tract simulation systems can be operated simultaneously and identically, i.e. employing multiple testing stations (see Lee, [0038], [0082]-[0084], [0107]-[0108], Figure 11, for instance); wherein (regarding instant claim 11) the system comprises vessels having an top opening or a cover or lid system for providing access to multiple passageways for fluid flow via fluid transfer tubes (see Lee, [0038], [0048], [0052], Figures 7, 9 and 11, for instance); and wherein (regarding instant claim 12) “the dissolution sampling pump arrangement and the permeation sampling pump arrangement may each comprise a syringe pump arrangement, a peristaltic pump arrangement or a ceramic pump arrangement” (see Lee, [0038], [0088], [0104], for instance).
However, a method of simulating the gastrointestinal dissolution and intestinal permeation of a pharmaceutical product or substance with a GI tract simulation system- that comprises a semi-permeable membrane mounted on a grid structure (see instant claim 1, step-a); wherein the pharmaceutical product or substance belongs to Biopharmaceutics Classification System (BCS) Class I, Class II, Class III, or Class IV (see instant claims 5 and 6) ; and wherein the gastrointestinal tract simulation system is operated to transfer simulated gastric fluid and simulated duodenal fluid (see instant claim 7), have not been explicitly disclosed by Lee, as discussed above.
Although, Lee discloses an artificial intestinal membrane structure used for automated dissolution/permeation testing system (disclosed as PERMEFILMTM; see Lee, [0041], [0051], [0064]-[0065], [0071], for instances), however does not explicitly provide for the molecular weight cut offs for the membrane per se. Also, Lee discloses the use of flow control arrangements that circulate media simulating an “intestinal fluid or other bodily fluids” (see Lee, Abstract, [0023], [0046], [0078], [0089], [0099], for instances), however, does not specifically disclose simulated gastric or duodenal fluids per se.
Augustijns et al (2018), while teaching permeability model (see Title, Abstract, and Claims), disclose a “method for assessing the intestinal absorption of a compound comprising measuring in function of time the permeation of said compound dissolved or suspended in a simulated intestinal fluid (SIF) as a first liquid through a regenerated cellulose membrane into a second liquid, wherein said membrane has a molecular weight cutoff between 1.0 kDa and 5.0 kDa” (i.e. a “semi-permeable” membrane; see Abstract); wherein the compound is pharmaceutical drug(s) belonging to BCS Class II and Class IV (see entire disclosure on p. 4, p. 7; p. 8, 1st and 3rd paragraphs; and Example 9, for instance), and wherein the membrane is a regenerated cellulose membrane insert system (see Summary of the Invention” on p. 4, claims 1, 7-8, for instance); wherein the simulated intestinal fluids used in the method employing a two-stage dissolution assessment combined with the AMI-system containing said cellulose membrane includes a simulated gastric fluids and a simulated duodenal fluids in respective compartments (see p. 6, 2nd paragraph, Fig. 14; p. 9, 2nd paragraph; p. 11-12, section “Assessment of the permeation potential of itraconazole after two-stage dilution of an oral solution”; and Examples 7-9, for instance). Augustijns et al also disclose the art-known fact that BCS II/IV class of pharmaceutical products or compounds are known to suffer from “low aqueous solubility, limiting intestinal concentrations and fraction absorbed” (see p.1, lines 20-21, for instance), and therefore require special formulations, attesting to the importance of such dissolution-permeability studies as disclosed in pharmaceutical drug development areas (see p. 2, lines 17-19, for instance).
Thus, given the detailed disclosure and demonstration for the use of semi-permeable membrane insert system for successfully testing the permeability of Class II/IV drugs or pharmaceutical compounds using suitable compartments and simulated fluids (including gastric and duodenal fluids) as taught by Augustijns et al, it would have been obvious to an artisan of ordinary skill in the art to employ such semi-permeable membrane structure as disclosed by Augustijns et al for testing of pharmaceutical products from BCS Class II/IV using the simulated intestinal fluids, as specifically taught by Augustijns et al in the method of Lee (see detailed teachings/suggestions above) such that the method provides superior and efficient automated dissolution-permeability assessment for said class of drugs as already suggested by the teachings of Augustijns et al. Since, Augustijns et al already suggest the reasons for testing such drugs having low solubility with limiting intestinal concentrations/absorption, etc., an artisan in the art would have been motivated and would have had a reasonable expectation of success in modifying the method of Lee in order to employ the specific semi-permeable membrane insert system, at least for the BCS Class II/IV of pharmaceutical products or drugs that require such dissolution-permeability testing, assessment and/or evaluation, etc.
Given the detailed disclosure for multiple vessels that can be fluidically interconnected with one another for testing plurality of drugs or compounds as disclosed by Lee (when taken with Augustijns et al, as discussed above), the limitations of providing empty gastrointestinal tract simulation system comprising empty compartments, filling said compartments with simulating fluids mimicking physiological fluids (see instant claim 3), would have been deemed obvious and fully contemplated by an artisan of ordinary skill in the art as being part of the process of assembling and performing the testing apparatus already disclosed in the cited prior art. Similarly, the limitations of employing control test systems that do not have the drug that is being tested (i.e. akin to control samples; see instant claim 10) would have been obvious to an artisan in the art given the disclosure from Lee for the use of plurality of connected vessels that can be employed and operated in an automated mode for testing and/or evaluation of drugs for their dissolution rates and permeability assessments. Since, the instant claims do not recite the specific components, conditions, and/or configurations (other than being interconnected vessels and/or compartments) that “simulate” jejunum or ileum per se, the limitations of instant claim 13 would have also been deemed obvious and fully contemplated by an artisan in the art given the combined teachings and/or suggestions from the cited prior art of Lee taken with Augustijns et al, as discussed above.
It is noted that instant claim 1 does not require any molecular weight cut off for the “semi-permeable” membrane used in the process, and in addition does not recite specific components of the simulated “gastric” or “duodenal” fluids (see instant claims 1 and 7), and therefore, the disclosure provided in the cited prior art of Lee when taken with the teachings from Augustijns et al, as discussed above, would have made it obvious to an artisan of ordinary skill in the art to modify the process of simulating the gastrointestinal dissolution and intestinal permeation of a pharmaceutical substance/drug, as currently required by the claims, unless evidence and/or data provided on record to the contrary (which is currently lacking on record; see instant specification, Figures 5-7, 9-10, 12-13, for instance).
Thus, the claim as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention as claimed.
As per MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. In re American Academy of Science Tech Center, F.3d, 2004 WL 1067528 (Fed. Cir. May 13, 2004)(The USPTO uses a different standard for construing claims than that used by district courts; during examination the USPTO must give claims their broadest reasonable interpretation.). This means that the words of the claim must be given their plain meaning unless applicant has provided a clear definition in the specification. In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989).
Conclusion
NO claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SATYENDRA K. SINGH whose telephone number is (571)272-8790. The examiner can normally be reached M-F 8:00- 5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, LOUISE W HUMPHREY can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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SATYENDRA K. SINGH
Primary Examiner
Art Unit 1657
/SATYENDRA K SINGH/Primary Examiner, Art Unit 1657