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
Claims 6-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/2/2026.
Response to Amendment
The amendment filed June 2, 2026 has been entered.
Claims 1-14 remain pending in the application, with claims 1-5 and 14 being examined, and claims 6-13 deemed withdrawn.
Applicant’s amendments to the Specification and Claims have overcome each and every drawing objection, claim objection, and 112(b) rejection previously set forth in the Non-Final Office Action mailed April 9, 2026. However, new 112(b) rejections are outstanding, as detailed in the Claim Rejections-35 USC 112 section of this instant Office Action.
Based on Applicant’s amendments and remarks, the previous prior art rejection has been modified to address the claim amendments.
Drawings
Applicant’s amendments to the Specification received 6/2/2026 have overcome the objection to the Drawings made in the Non-Final Office Action mailed 4/9/2026.
Claim Interpretation
For the limitation “A quasi in vivo (QIV) test” as it appears in instant claim 14, the term “quasi in vivo (QIV)” has been examined as defined according to Pg. 15 Lns. 19-22 of the instant Specification, i.e. “a condition or system that stimulates or comes close to the conditions of a living organism but is not truly within a living entity…a model or experimental system that attempts to closely mimic the in vivo environment without actually being in a living organism.”
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 1-5 and 14 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.
Regarding claim 1, 2nd to Last Ln. to Last Ln. recite “a miniaturized microscope probe positioned above the substrate surface”. However, it is unclear if this miniaturized microscope probe is the same as or different from the miniaturized microscope probe previously recited in Claim 1, particularly as the miniaturized microscope probe was previously recited as being “positioned at the substrate surface”, while the miniaturized microscope probe in the 2nd to Last Ln. to Last Ln. was recited as, “positioned above the substrate surface”. Further clarification is needed. For purposes of compact prosecution, the above limitation has been examined as, “the miniaturized microscope probe”, and the miniaturized microscope probe has been examined as being positioned above the substrate surface in both instances, in accordance with Fig. 1 of the instant Drawings and Pg. 4 Ln. 29-Pg. 5 Ln. 12 of the instant Specification.
Claims 2-5 and 14 are rejected at least for depending on a rejected claim.
Regarding claim 5, Ln. 2 recites, “the external reservoir”. However, it is unclear if this external reservoir is the same as or different from the one or more external reservoir chambers previously recited in claim 1. Further clarification is needed. For purposes of compact prosecution, the above limitation has been examined as, “an external reservoir chamber of the one or more external reservoir chambers”.
Further regarding claim 5, Ln. 3 recites, “the medical device”. There is insufficient antecedent basis for this limitation in the claim. For purposes of compact prosecution, the above limitation has been examined as, “a medical device”.
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 1-3 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Gevaert et al. (US Pub. No. 2016/0244717; hereinafter Gevaert; already of record) in view of Vellinger et al. (US Pat. No. 7,198,940; hereinafter Vellinger; already of record) and Yamamoto et al. (US Pub. No. 2004/0152188; hereinafter Yamamoto).
Regarding claim 1, Gevaert discloses a system ([0051]-[0060], see Fig. 2 at two cell culture chambers 10 separated by membrane 23). The system comprises:
a first chamber containing an adjustable substrate support ([0051]-[0060], see Fig. 2 at , top cell culture chamber 10, [0079], see Fig. 2 at discrete scaffolds 15 in the two cell culture chambers. The discrete scaffolds can be used to attach a model medical device. Further, the discrete scaffolds are movable and are therefore adjustable).
An interlocked second chamber fluidly connected to the first chamber ([0051]-[0060], [0069], see Fig. 2 at bottom cell culture chamber 10 can be considered a cell seeding chamber, and is separated from the top cell culture chamber 10 by membrane 23).
A cell selective porous membrane completely separating the first and second chamber ([0051]-[0060], [0069], see Fig. 2 at membrane 23).
An influx tube positioned between the substrate and the porous membrane in the first chamber ([0051]-[0060], [0069], see Fig. 2 at inlet 8, which is between some of the scaffolds 15 and membrane 23 in a vertical direction. See also [0077]).
Inlet and outlet tubing valve flow control ports connected to the first and second chambers ([0077], inlet 8 and outlet 9 can be connected to medium perfusion tubing via stopcock valves).
One or more external reservoir chambers ([0080], see Fig. 3 at pump 17 and media container 19).
One or more analyte probes interfaced with the chambers ([0086]).
An external flow control pump ([0080]).
A temperature regulator ([0091]).
Gevaert fails to explicitly disclose:
that the system is a flow cell surface deposition test system;
the one or more analysis probes are multiparameter adjustable analyte probes;
an adjustable miniaturized microscope probe positioned above the substrate surface; and
wherein a cell suspension in an external reservoir is pumped into the second chamber for timed periods at selected temperature and flow rates and wherein changes over time on the surface of a test substrate in the first chamber caused by cells migrating through the cell selective porous membrane are measured with the miniaturized microscope probe positioned above the substrate surface.
However, Vellinger is in the analogous field of bioreactor apparatuses (Vellinger Col. 1 Lns. 11-13). Vellinger teaches multiparameter adjustable analyte probes (Vellinger Col. 3 Lns. 5-11, the probes can measure both pH and oxygen and therefore have an adjustable function). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the apparatus of Gevaert with the teachings of Vellinger so that the one or more analysis probes are multiparameter adjustable analyte probes, as providing multiparameter adjustable analyte probes will enhance the versatility of the probes and allow them to detect multiple properties within the system simultaneously, providing more comprehensive data of the system.
Modified Gevaert fails to explicitly disclose:
that the system is a flow cell surface deposition test system;
an adjustable miniaturized microscope probe positioned above the substrate surface; and
wherein a cell suspension in an external reservoir is pumped into the second chamber for timed periods at selected temperature and flow rates and wherein changes over time on the surface of a test substrate in the first chamber caused by cells migrating through the cell selective porous membrane are measured with the miniaturized microscope probe positioned above the substrate surface.
Yamamoto is in the analogous field of incubators for sample culture (Yamamoto [0001]). Yamamoto teaches an adjustable miniaturized microscope probe positioned above the substrate surface (Yamamoto; [0009]-[0012], see Fig. 3 at camera 7, and Fig. 16 at camera drive mechanism 71 for driving camera 7 along two axes). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the system of modified Gevaert with the teachings of Yamamoto so that an adjustable miniaturized microscope probe is positioned above the substrate surface, in order to observe samples in the system without exposing the system to the atmosphere, so that interior ambient conditions of the system are not altered (Yamamoto; [0005], [0009]-[0012], see Fig. 3).
Further, with regards to the limitation where a cell suspension in an external reservoir is pumped into the second chamber for timed periods at selected temperature and flow rates and wherein changes over time on the surface of a test substrate in the first chamber caused by cells migrating through the cell selective porous membrane are measured with the miniaturized microscope probe positioned above the substrate surface, this limitation is drawn to functional language. As the system of modified Gevaert is identical to the instantly claimed system, it is therefore capable of performing the claimed limitation. See MPEP 2114.
Further, with regards to the system being a flow cell surface deposition test system, see MPEP 2111.02, which states that, “if the body of a claim fully and intrinsically sets forth all the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.”
Note: The instant Claims contain a large amount of functional language (ex: “wherein a cell suspension in an external reservoir is pumped into the second chamber…”, “to passage selected cell types…”, etc.). However, functional language does not add any further structure to an apparatus beyond a capability. Apparatus claims must distinguish over the prior art in terms of structure rather than function (see MPEP 2114). Therefore, if the prior art structure is capable of performing the function, then the prior art meets the limitation in the claims.
Regarding claim 2, modified Gevaert discloses the surface deposition test system of claim 1. Modified Gevaert further discloses that the porous membrane has a pore size to passage selected cell types from the cell seeding chamber into the fluidly connected cell bioreactor chamber (Gevaert [0142], which states that the membrane may have pores of 0.45 micron size, and Pg. 8 Lns. 16-25 of the instant Specification, which states that lymphocytes may go through pores as small as 0.3 µm).
Regarding claim 3, modified Gevaert discloses the surface deposition test system of claim 2. Modified Gevaert further discloses that the selected cell types are fibroblast, macrophage, epithelial, or lymphocyte cells (Gevaert [0142], which states that the membrane may have pores of 0.45 micron size, and Pg. 8 Lns. 16-25 of the instant Specification, which states that lymphocytes may go through pores as small as 0.3 µm).
Regarding claim 5, modified Gevaert discloses the surface deposition test system of claim 1. Modified Gevaert further discloses that S. aureus cells from the cell suspension pumped in from an external reservoir chamber of the one or more external reservoir chambers form a biofilm on the surface of a medical device after 14 days (the apparatus of modified Gevaert is identical to the instantly claimed invention, and is therefore capable of performing the claimed function).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Gevaert in view of Vellinger and Yamamoto as applied to claims 1-3 and 5 above, and further in view of Tokonami et al. (US Pub. No. 2020/0182770; hereinafter Tokonami; already of record).
Regarding claim 4, modified Gevaert discloses the surface deposition test system of claim 1. Modified Gevaert further discloses that a cell suspension of S. aureus cells from the second chamber pass through the porous membrane into the first chamber (Gevaert [0142], which states that the membrane may have pores of 0.45 micron size, and Pg. 8 Lns. 16-25 of the instant Specification, which states that lymphocytes, which have a diameter of 10 µm may go through pores as small as 0.3 µm. Further, see [0055] of Tokonami, which states that the diameter of S. aureus is about 0.8 µm. Therefore, as the membrane of Gevaert has already been shown to be capable of permitting cells to pass that are significantly larger than S. aureus, i.e. lymphocytes having a diameter of 10 µm, the membrane of Gevaert is capable of permitting S. aureus cells to pass through).
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Gevaert in view of Vellinger and Yamamoto as applied to claims 1-3 and 5 above, and further in view of El-Azizi et al. (US Pub. No. 2008/0076147; hereinafter El-Azizi; already of record) and Zhong (US Pat. No. 6,468,649; already of record).
Regarding claim 14, modified Gevaert discloses the flow test deposition system of claim 1.
Modified Gevaert fails to explicitly disclose a quasi in vivo (QIV) test comprising the flow test deposition system of claim 1, wherein the substrate is an implantable medical device, and wherein the test data from cells deposited on the substrate surface over measured time periods are used to compare changes on the medical device surface over time to other medical device surfaces that are unaffected in the same test conditions.
El-Azizi is in the analogous field of simulation of in vivo conditions for medical devices (El-Azizi [0001]). El-Azizi teaches a quasi in vivo (QIV) test comprising a system using a substrate that is an implantable medical device (El-Azizi; [0018], [0040]-[0041], see Fig. 1 at fluid flow conduit 3, which may be a catheter, endotracheal tube, or other medical device, which is placed in a sampling apparatus that has fluid pumped therethrough via feed line 15 and outlet line 25 to simulate an in vivo condition, where biofilm formation on the fluid flow conduit is measured). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the flow test deposition system of modified Gevaert with the teachings of El-Azizi to provide a quasi in vivo (QIV) test comprising the flow test deposition system, wherein the substrate is an implantable medical device. The motivation would have been to determine whether a biofilm forms in the medical device prior to implantation in the simulated in vivo environment, in order to determine whether a biofilm will form on the medical device upon implantation, which would be harmful to a patient (El-Azizi; [0002], [0018], [0040]-[0041], see Fig. 1). Further, as the apparatus of El-Azizi is used to simulate in vivo conditions (El-Azizi [0040]), a person having ordinary skill in the art before the effective filing date of the invention would have been motivated to use the system of modified Gevaert instead of the apparatus of El-Azizi with a reasonable expectation of success, as the device of modified Gevaert is used to simulate in vivo systems (Gevaert [0047]).
Modified Gevaert fails to explicitly disclose that the test data from cells deposited on the substrate surface over measured time periods are used to compare changes on the medical device surface over time to other medical device surfaces that are unaffected in the same test conditions.
Zhong is in the analogous field of placing test samples in environments that simulate in vivo conditions (Zhong; Col. 10 Ln. 64-Col. 12 Ln. 9, Col. 12 Lns. 41-47, see Table below Col. 12 Ln. 47). Zhong teaches test data from cells deposited on a substrate surface over measured time periods are used to compare changes on a medical device surface over time to other medical device surfaces that are unaffected in the same test conditions (Zhong; Col. 10 Ln. 64-Col. 12 Ln. 9, Col. 12 Lns. 41-47, see Table below Col. 12 Ln. 47, which shows that that an uncoated 6 French EVA stent has biofilm detected after 1 day, while the coated stents from Examples 2 and 3 do not have biofilm present even after 5 days). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Gevaert with the teachings of Zhong so that the test data from cells deposited on the substrate surface over measured time periods are used to compare changes on the medical device surface over time to other medical device surfaces that are unaffected in the same test conditions, in order to identify medical device surfaces that do not form a biofilm under specific conditions (Zhong; Col. 10 Ln. 64-Col. 12 Ln. 9, Col. 12 Lns. 41-47, see Table below Col. 12 Ln. 47), particularly as biofilms that form on implanted medical devices can cause serious or fatal infections in patients (Zhong Col. 1 Lns. 30-42).
Response to Arguments
Applicant's arguments filed June 2, 2026 have been fully considered but they are not persuasive.
Applicant argues on Pgs. 10-12 of their Remarks that the prior art of record does not teach a miniaturized microscope probe located inside a chamber holding a substrate on which a film is deposited. While the Examiner agrees with this assessment, this limitation has been rejected using the Yamamoto reference. For a more detailed explanation, please see the rejection of Claim 1 in the Claim Rejections-35 USC 103 section of this instant Office Action. Applicant’s amendments necessitated the new grounds of rejection.
Applicant further argues on Pg. 12 of their Remarks that the apparatus of Gevaert as modified by Vellinger is not capable of forming a biofilm on the surface of a medical device from pumped-in S. aureus cells after 14 days. The Examiner respectfully disagrees. The limitation in question is drawn to functional language. However, functional language does not add any further structure to an apparatus beyond a capability. Apparatus claims must distinguish over the prior art in terms of structure rather than function (see MPEP 2114). Therefore, if the prior art structure is capable of performing the function, then the prior art meets the limitation in the claims. As the system of modified Gevaert is identical to the instantly claimed system, the system of modified Gevaert is capable of promoting biofilm formation from pumped-in S. aureus cells, absent persuasive evidence to the contrary.
Applicant further argues on Pg. 13 of their Remarks that claim 4 is allowable over the prior art, as the prior art does not suggest a miniaturized microscope probe and inlet/outlet configuration that introduces selected cells into a membrane to test migration onto a substrate surface. The Examiner respectfully disagrees, as the above limitations have been taught by Gevaert in view of Vellinger, Yamamoto, and Tokonami. Tokonami is relied upon as a reference to evidence that S. aureus cells would pass through the porous membrane.
Applicant further argues on Pgs. 13-14 that the prior art of record does not disclose the limitations as in amended claim 1, and that claim 14 should therefore be allowed as depending from claim 1. The Examiner respectfully disagrees, as Claim 1 has been rejected under 35 U.S.C. 103 over Gevaert in view of Vellinger and Yamamoto. For a more detailed explanation, please see the rejection of Claim 1 in the Claim Rejections-35 USC 103 section of this instant Office Action.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 John McGuirk whose telephone number is (571)272-1949. The examiner can normally be reached M-F 8am-530pm.
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/JOHN MCGUIRK/Examiner, Art Unit 1798
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