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 .
Response to Amendment
This is an office action in response to Applicant’s arguments and remarks filed on 25 June 2026. Claims 32-40 are currently pending. Claims 1-31 have been previously canceled. Claims 32-40 are being examined herein.
Response to Amendment
The objections to claim 1 is withdrawn in view of amendments.
The rejections to claims 32-40 under 35 U.S.C. 112(b) are withdrawn in view of amendments.
The rejections to claims 32-40 under 35 U.S.C. 103 in view of Burgess, et. al. (US 20100221838 A1) in view of Flieg, et. al. (US 20150320924 A1) and Babcock, et. al. (US 20070205155 A1) are withdrawn in view of arguments.
Response to Arguments
Applicant's arguments filed 25 June 2026 have been fully considered but they are not persuasive.
First, Applicant argues Flieg is not analogous art (remarks, pg. 7, par. 02 - pg. 9, par. 02). Specifically, applicant argues Flieg does not relate to "diffusion-based evaluation of drug release from a dosage form."
Examiner respectfully disagrees. Dialysis is a type of filtration, and Flieg teaches a filtration device (Abstract) wherein an active substance (like a drug dosage form) is within the hollow fibers and the device is used for "medical, chemical, and/or biotechnological applications" (par. 0001). Ultimately, Burgess and Flieg and the instant applicant are monitoring the movement of an analyte of interest across a membrane and therefore are analogous art. Further, motivation to combine and modify prior art does not need to match the motivation and objective of the present application. Flieg teaches the use of hollow fibers allows for high productivity and selectivity in filtration (Flieg, par. 0002-0004) and these motivations are important in the field of biotechnology. However, Applicant point out the vast size difference between the apparatus of the present application and the apparatus as taught by Flieg.
Applicant’s arguments, see remarks, pg. 7, par. 02 - pg. 9, par. 02, filed 25 June 2026, with respect to the rejection of claims 32-40 have been fully considered and are persuasive. The rejection under 35 U.S.C. 103 of claim 32-40 has been withdrawn.
Regarding the vast differences in membrane surface area (remarks, pg. 8, par. 03 - pg. 9, par. 01), Examiner reiterates motivation to combine and modify prior art does not need to match the motivation and objective of the present application.
Examiner notes, the size of the hollow fiber module as taught by Flieg is significantly larger than the size of the hollow fiber module of the present application. With the new rejection, provided below, Examiner brings the prior art of Flieg in to teach the modification in the functional limitation wherein an active substance (drug dosage) can be deposited within a permeate chamber with diffuse into the hollow fibers of the retentate chamber and wherein the circulated medium is only that of the hollow fiber interior.
Applicant's arguments filed 25 June 2026 have been fully considered but they are not persuasive.
Applicant argues membrane surface area, volume, flow rate, concentration, solubility, and related parameters cannot be taught by routine optimization (remarks, pg. 9, par. 02 - pg. 11, par. 04).
Examiner has presented new art (see below) for membrane surface area, volume processing, flow rate, and membrane area-to-volume ratio.
However, Examiner maintains the use of Babcock to teach the limitation of the sample loading parameter as recited in claim 33. a chamber is defined by its volume and a sampling load by is mass. These measurements are unrelated as they have no common units. The size (volume) of a substance can greatly vary depending on the density of the substance. For example, a more concentrated drug dosage will require less mass of the sample to reach the same amount of a drug dosage that is less concentrated. Further, it is unclear if the volume of the permeate chamber holding this sample load is entirely filled or partially empty. Ultimately, several factors go in to whether or not the sample chamber can accommodate the recited sample load; the surface area of the hollow fiber membranes, volume, time, flow rate, solubility factors, concentration of active substance in the permeate chamber, and more go in to determine the effectiveness of the hollow fiber module [Babcock, par. 0048]. The goal is to optimize each element of the device in order to closely mimic in vivo absorption rates [Babcock, par. 0006-0007]. Therefore, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to have the concentration of the active substance applied to the permeate chamber to have an equivalent sampling load of about 1.2 to 1.4 grams.
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.
Claims 33 and 34 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.
The term “about” in claims 33 and 34 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As for claim 33, it is unclear of how close the sampling load should be between 1.2 to 1.4 gram. As for claim 34, it is unclear how close the total surface area of the hollow-fiber microtubular membranes should be to 20 cm2.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 32 and 34-40 are rejected under 35 U.S.C. 103 as being unpatentable over Burgess, et. al. (US 20100221838 A1) in view of Love, et. al. (US 20190070564 A1) and Flieg, et. al. (US 20150320924 A1).
Regarding claim 32, Burgess teaches a dialysis adapter cell [Abstract] for in vitro release testing of colloidal dispersion systems [par. 0007] (A system for in-vitro release testing of a drug from a dosage form). Burgess teaches a system for in vitro release testing of drugs comprising a medium reservoir 102 that consists of a container to hold the dissolution medium (a media reservoir configured to hold dissolution media) that has the ability to be closed or open configuration, a pump 104 to move the fluid from the medium reservoir through a flow through cell with a dialysis adapter and back to the reservoir (a pump connected to the media reservoir and configured to pump dissolution media from the media reservoir) (wherein the retentate medium is returned… to the media reservoir) [Fig. 5; par. 0037]. Burgess also teaches the dissolution medium can be heated via a water bath when moving from the medium reservoir to the dialysis cell [par. 0039] (at least one temperature-controlling unit in thermal contact with either the media reservoir or a retentate flow path). Burgess teaches a long, cylindrical dialysis adapter cell holding a dialysis membrane is placed in a standard USP dissolution apparatus 4 where the analyte of interest is disposed; the dialysis membrane used can change depending on type of dialysis being performed and type of analyte being tested [par. 0030, 0033, 0042] (wherein the system is compatible with a United States Pharmacopeia (USP) Type-4 dissolution apparatus without immersing the dosage form in bulk dissolution media).
Burgess is silent to Burgess is silent to a hollow-fiber module comprising: (i) a closed permeate chamber configured to hold the dosage form; and (ii) a retentate chamber comprising a plurality of hollow-fiber microtubular membranes with a total surface area of between 5 to 92 cm2 and a retentate medium volume processing ability of between 20-1000 ml; wherein the pump is configured to circulate the dissolution medium only through the retentate chamber of the hollow-fiber module while the permeate chamber remains closed; and wherein drug released from the dosage form diffuses through the hollow-fiber membranes into the circulating dissolution medium, to form the retentate medium.
Love teaches a filtration system comprising a filter bundle of hollow fibers for analyzing pharmaceutical products [Abstract]. Love teaches the hollow fiber probe 100 comprises a structured segment 150 (a hollow-fiber module comprising) with spacing elements 130A, 130B on either size wherein within the structured segment is a plurality of hollow fibers 110 (a retentate chamber comprising a plurality of hollow-fiber microtubular membranes) with an interior central shaft 120 (a closed permeate chamber) [Fig. 1; par. 0053]. Love teaches the hollow fibers can have a total surface area between 20 cm2 to 100 cm2 within the structured segment [par. 0089] (with a total surface area of between 5 to 92 cm2). While Love does not teach an inner volume of the hollow fibers directly, Love does teach the hollow fibers can have a plurality of lengths within the structured segment (one length being between 10 mm and 500 mm) [par. 0086], each hollow fiber can have a plurality of inner diameters (an inner diameter of at least about 1 mm) [par. 0068], and there can be a plurality of number of fibers within a bundle (at least about 100 fibers) [par. 0066]; all of these coming together to create a total inner volume of the hollow fiber bundle of 39 mL (a retentate medium volume processing ability of between 20-1000 mL). Love teaches the use of a hollow fiber bundle as compared to a single-membrane filter allows for increased effective surface area for a similar sized filter, higher flow rates, and promotes interior circulation between fibers when spaced correctly which prevents fouling [par. 0049-0050].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the dialysis membrane of Burgess to instead be a bundle of hollow fibers (a hollow-fiber module) as taught by Love because hollow fibers allow for increased effective surface area for a similar sized filter, higher flow rates, and promote interior circulation between fibers when spaced correctly which prevents fouling [Love, par. 0049-0050] with reasonable expectation of success. MPEP 2143(I)(G).
Modified Burgess is silent to the permeate chamber being configured to hold the dosage form; wherein the pump is configured to circulate the dissolution medium only through the retentate chamber of the hollow-fiber module while the permeate chamber remains closed; and wherein drug released from the dosage form diffuses through the hollow-fiber membranes into the circulating dissolution medium, to form the retentate medium.
Flieg teaches a hollow fiber filtration device for medical, chemical and biotechnical applications wherein the filtrate space is filled with "with particles of a chemically or physically active substance" [Abstract]. Flieg teaches a hollow fiber membrane module filtration device (a hollow-fiber module) comprising a housing 2 holding a plurality of hollow fibers 3 and surrounded by a filtrate space 4. Flieg teaches the fluid to be treated inter the housing through inlet 7b, moves through the hollow fibers 3 (a retentate chamber comprising a plurality of hollow-fiber microtubular membranes), interacts with the particulate material (active substance) in the filtrate space 4 (a closed permeate chamber configured to hold the dosage form), and exits the hollow fibers 3 through outlet 8 [Fig. 2, 10; par. 0023]. Flieg teaches the inner space of the hollow fibers and the filtrate space are not required to be interconnected through respective inlets 7b, 7a and outlets 8, 9, meaning the filtrate space (permeate chamber) can be effectively closed off from the inner space of the hollow fibers (retentate chamber) keeping the active/treatment media entirely separate from the media to be treated except for what moves across the hollow fiber membranes [par. 0012] (wherein drug released from the dosage form diffuses through the hollow-fiber membranes into the circulating diffusion medium to form a retentate medium). Flieg teaches the use of hollow fiber membranes as a filter for monitoring medically active compounds because hollow fibers allow fluids to interact with a target substance with high productivity and selectivity [par. 0002-0004].
Putting the devices of modified Burgess and Flieg together, specifically the pump 104 of modified Burgess [Burgess, Fig. 5; par. 0037] and the hollow fiber module of Love [Love, ], and the hollow fiber module configuration of Flieg [Flieg, Fig. 2; par. 0023], the pump is designed to only pump the dissolution media through the retentate chamber of the hollow fiber module and return it the media reservoir where it is recirculated (wherein the pump is configured to circulate the dissolution medium only through the retentate chamber of the hollow-fiber module while the permeate chamber remains closed) (wherein the retentate medium is returned from the hollow- fiber module to the media reservoir).
Examiner notes, the size of the hollow fiber module as taught by Flieg is significantly larger than the size of the hollow fiber module of modified Burgess in view of Love (as described above). Examiner brings the prior art of Flieg in to teach the modification how where an active substance (drug dosage) can be deposited within a permeate chamber with diffuse into the hollow fibers of the retentate chamber and wherein the circulated medium is only that of the hollow fiber interior.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the hollow fiber module of modified Burgess to have the membrane be a hollow fiber module configuration as taught by Flieg because
hollow fibers provide a filtration device capable of high productivity and selectivity with reasonable expectation of success. MPEP 2143 (I)(G).
Regarding claim 34, modified Burgess in view of Love teaches the hollow fibers can have a total surface area of at least about 20 cm2 within the structured segment [Love, par. 0089] (wherein the total surface area of the plurality of hollow-fiber microtubular membranes is about 20 cm2).
Regarding claim 35, modified Burgess in view of Love teaches the hollow fibers can be made of polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), and polyethersulfone (PES) and other polysulfones [Love, par. 0091] (wherein the plurality of hollow-fiber membranes are polysulfone, polyethersulfone… or polyethylene-based membranes).
Regarding claim 36, modified Burgess in view of Love teaches the hollow fibers have a molecular weight cut-off pore size of at least about 1kDa to of at least about 100 kDa [Love, par. 0071] (wherein the hollow-fiber module is an ultrafiltration module).
Regarding claim 37, modified Burgess teaches wherein in one example, ophthalmic suspension of dexamethasone was analyzed [Burgess, par. 0043] (wherein the system is configured to evaluate ophthalmic suspensions).
Regarding claim 38, modified Burgess teaches the pump having flow rates of 4, 8, and 16 mL/min [Burgess, par. 0039] (wherein the retentate medium is recirculated at a flow rate between 4 to 32 ml/min).
Regarding claim 39, modified Burgess in view of Love teaches the hollow fibers extend linearly within the structured segment 150 between spacing elements 130A, 130B wherein the spacing elements 130A, 130B provide spacing between the hollow fibers 110 [Love, Fig. 1; par. 0053] (wherein the plurality of hollow-fiber membranes are arranged linearly to maintain consistent mass-transfer area).
Regarding claim 40, modified Burgess in view of Love teaches the hollow fibers can have a total surface area between about 20 cm2 to 100 cm2 within the structured segment [Love, par. 0089] and the structured segment (comprising the permeate chamber, therefore the volumes are equivalent) has lengths between 10 mm to 500 mm [Love, par. 0086] and a diameter between 5 mm to 50 mm [Love, par. 0088]. Putting these limitations together, the structured segment which comprising the permeate chamber in full can have an approximate membrane area-to-volume (MAV) ratio of 15 cm2/mL if the 20 cm2 hollow fiber surface area is used and the structured segment has a length of 500 mm and a diameter of 5 mm (wherein the permeate chamber volume and membrane surface areas define a membrane area-to-volume (MAV) ratio of approximately 14-17 cm2/mL).
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Burgess, et. al. (US 20100221838 A1) in view of Love, et. al. (US 20190070564 A1) and Flieg, et. al. (US 20150320924 A1) as applied to claim 32 above, and further in view of Babcock, et. al. (US 20070205155 A1).
Regarding claim 33, modified Burgess teaches the limitation as applied to claim 32 (see above).
Modified Burgess is silent to wherein the permeate chamber has a sampling load of about 1.2 to 1.4 grams.
Babcock teaches a membrane-permeation test and microporous membrane for evaluating pharmaceutical compositions [Abstract]. Babcock teaches an embodiment of the microporous membrane system comprising a plurality of hollow-fiber membranes within a housing [Fig. 7; par. 0035]. Babcock teaches the dosage in the feed solution is on the outside surface and moves into the inner area of the membrane to be collected [par. 0026-0027].
Babcock further teaches a plurality of factors define how the filtration device operate. Specifically, Babcock teaches wherein the surface area of the hollow fiber membranes, volume, time, flow rate, solubility factors, concentration of active substance in the permeate chamber, and more go in to determine the effectiveness of the hollow fiber module [Babcock, par. 0048]. Therefore, the goal is to optimize each element of the device in order to closely mimic in vivo absorption rates [Babcock, par. 0006-0007]. Since this particular parameter is recognized as a result-effective variable (i.e. a variable which achieves a recognized result), the determination of the optimum or workable ranges of said variable can be characterized as routine experimentation. See MPEP 2144.05 (II)(A). Therefore, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to have the concentration of the active substance applied to the permeate chamber to have an equivalent sampling load of about 1.2 to 1.4 grams.
Examiner notes this is drawn to a functional limitation of the permeate chamber of the apparatus. Further, a chamber is defined by its volume and a sampling load by is mass. These measurements are unrelated as they have no common units. The permeate chamber of modified Burgess as described above is more than capable of holding an amount of a sampling load of about 1.2 to 1.4 grams.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MADISON T HERBERT whose telephone number is (571)270-1448. The examiner can normally be reached Monday-Friday 8:30a-5:00p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached at (571) 270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/M.T.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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