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
Applicant's election with traverse of Group 1, Claims 1-10 in the reply filed on 4/9/26 is acknowledged. The traversal is on the ground(s) that lack of unity has not been established because it hasn’t established a lack of inventive step with full discussion and citations. This is not found persuasive because the requirement found the common technical feature (the apparatus of claim 1) was not a special technical contribution over the references cited. The requirement further cited prior art references that met the claimed limitations, plus how and why one of ordinary skill in the art would’ve combined the prior art to arrive at the claimed invention. Therefore, the common technical feature does not meet the standards to be a special technical feature and the claims lack unity as per PCT Rule 13.2. As further evidence the claimed common technical feature did not contribute over the prior art, see the 35 USC 103 rejection below which provides detailed analysis and citations for each claimed limitation.
The requirement is still deemed proper and is therefore made FINAL.
Claims 11-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 4/9/26.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/2/22 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/024795, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claims 5 and 6 lack support in the provisional application as it does not disclose the claimed stimulator current frequency range of 40-250 cycles per minute or claimed mechanical pressure range of 0-300mmHg.
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 5-6, 10 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 claims 5-6, 10 these claims depend from claim 2 in which various components are listed as alternative limitations. While the components of claims 5-6, 10 are included in that list, they not are not recited as positively required components of the system in either claim 2 or 5/6/10 respectively. Therefore, it is unclear if these components are required in the claim invention as the limitations of claim 2 can be met by a system without the electrical stimulator or mechanical pressure which would render claims 5 & 6 & 10 lacking in antecedent basis. Applicant should consider positively reciting these elements at least in claims 5 , 6 and 10 respectively, in order to overcome this issue.
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 1-2, 7-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over ALLBRITTON (WO2019/222333) as cited by applicant on the IDS dated 11/2/22 in view of WIKSWO (US 20180326417), and SETHU (WO 2020/154658) and CLEMENTS (US 2015/0362476)
Regarding claim 1, ALLBRITTON discloses an apparatus comprising:
A base 120 comprising a fluid chamber which is open at a top surface of the base (inside of 120 (Fig 1j-1k; pg. 50, line 70- pg. 51, line 4);
a middle section positioned on the base (440; Fig 1J-1K; pg. 50, In 17 - pg. 51, In 4), wherein the middle section comprises:
i) a media chamber which is open at a bottom surface of the middle section (Box VIII) (inside of 440; Fig 1J-1K; pg. 50, In 17 pg. 51, In 4); 440 comprises a membrane 170, which is porous and, therefore open (fluid chamber of the base and the media chamber of the middle section are separated by a flexible membrane (pg. 44, In 26-31,);
and
ii) an upper section (portion of 460 below cover flange 162; Fig 1J-1K; pg. 50, In 17 - pg. 51, In 4) comprising at least one pair of open slots which extend from a top surface of the upper section and through the upper section and which open at a bottom surface of the upper section (slots wherein 472, 474 and 476 extend through; Fig 1J-1K; pg. 50, In 17 - pg. 51, In 4);
a top (162; Fig 1J-1K; pg. 50, In 17 - pg. 51, In 4) comprising a top upper surface (top surface of 162; Fig 1J-1K; pg. 50, In 17 - pg. 51, In 4) and a top bottom surface (bottom surface of 162; Fig 1J-1K; pg. 50, In 17 - pg. 51, In 4), wherein the top comprises at least two electrodes extending from the top upper surface, through the top and out from the top bottom surface (472, 474, 476 collectively; Fig 1J-1K; pg. 50, In 17 pg. 51, In 4; pg. 48, In 29-33 further teaches wherein the sensors can be electrodes), wherein the at least two electrodes are configured to be received by the at least one pair of open slots in the upper section (Fig 1J-1K; pg. 50, In 17 - pg. 51, In 4);
ALLBRITTON discloses the elements of claim 1, expect the recessed culture wells in a top surface of the middle section, the wells having inserts positioned therein in which the inserts comprise two posts configured to support a tissue and an electrode circuit board to engage the electrodes.
ALLBRITTON does not disclose recessed culture wells in a top surface of a middle section above a flexible membrane forming a media chamber. However, WIKSWO discloses a multicompartment microfluidic bioreactor in which there are a plurality of wells formed in a top surface of a section above a flexible membrane creating a separate chamber (Fig 6a, 0147-148).
It would have been obvious to one of ordinary skill in the art at the time of the filing of the invention to modify the well section of ALLBRITTON to include one or more tissue culture wells recessed into a top surface of the section above a flexible membrane allowing fluid communication with a lower fluid chamber as taught by WIKSWO because it can support more than two cell types and is able to use electrical recordings in situ (0017, 0021).
ALLBRITTON does not disclose the wells having inserts positioned therein in which the inserts comprise two posts configured to support a tissue. However, SETHU discloses a culture chamber well 12 with posts 14 (inserts) extending upwardly within the well, the posts upper ends configured to support a tissue 16 (Fig 3, 0047-0048, 0057-58). It would have been obvious to one of ordinary skill in the art at the time of the filing of the invention to modify the wells of ALLBRITTON to include the insert posts of SETHU because it allows for accurate recreation of physiologically relevant stresses on a heart tissue (0064).
ALLBRITTON does not disclose the electrodes are connected to an electrode circuit board configured to electrically engage with the electrodes. However, CLEMENTS discloses a multiwell microelectrode array comprising the electrodes printed on a substrate that can be a printed circuit board (circuit board configured to electrically engage) (0040, 0043, Fig 6). It would have been obvious to one of ordinary skill in the art at the time of the filing of the invention to modify the system of ALLBRITTON to include the electrodes being in electrical engagement with an electrode circuit board as taught by CLEMENTS because it allows for creating an integrated multiwell microelectrode array that does not interfere with visibility of well contents (0043).
Regarding claim 2, ALLBRITTON discloses the system can comprise a second apparatus with a second reservoir that is fluidically connected to the first system (reservoir for culture medium) (Fig 13 A-B). Additionally, WIKSWO discloses the system can have a perfusion controller with a pump 1506 (pumping system) that circulates culture medium from a reservoir 1502, 1509 (0164-165, Fig 15A-C). It would have been obvious to one of ordinary skill in the art at the time of the filing of the invention to modify the system of ALLBRITTON to include the reservoir with pumping system as taught by WIKSWO to allow for fluid recirculation which allows for maximum nutrient usage of the media (0164).
Regarding claim 7-8, ALLBRITTON does not explicitly disclose a computerized monitoring system nor a continuous monitoring system.
However, WIKSWO discloses the bioreactor system may be under computer control (0173) that allows real-time measurement (continuous monitoring) (0117-0120). t would have been obvious to one of ordinary skill in the art at the time of the filing of the invention to modify the system of ALLBRITTON to include the computerized monitoring system that is a continuous monitoring system of WIKSWO because it allows for precise monitoring and control to allow for maintaining specific experimental protocols without the risk of human error. Additionally, it has been held that broadly providing a mechanical or automatic means to replace manual activity which has accomplished the same result involves only routine skill in the art. MPEP 2144.04.
Claim(s) 3-6, 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over ALLBRITTON (WO2019/222333) as cited by applicant on the IDS dated 11/2/22 in view of WIKSWO (US 20180326417), and SETHU (WO 2020/154658) and CLEMENTS (US 2015/0362476) as applied above and further in view of VARGAS (MX 2017004364) ) as cited by applicant on the IDS dated 11/2/22 all rejections cited to the English Translation being provided herewith.
Regarding claim 3, modified ALLBRITTON does not explicitly disclose the system further comprising a force transducer.
However, VARGAS teaches a bioreactor system for tissue engineering (lines 5-6) comprising a bioreactor 6 made of a base and multiple sections thereon including a culture chamber 60 (tissue culture well) (Fig 3B), the system further including a mechanical stimulation subsystem with an actuator 61 (force transducer) that exerts a compressive force on a membrane 64 located below the construct to induce stimulation through direct contact with the cellular scaffold (Fig 3B, lines 288-312). It would have been obvious to one of ordinary skill in the art at the time of the filing of the invention to modify the system of ALLBRITTON to include the mechanical stimulation subsystem (force transducer) of VARGAS because mechanical stimuli can increase cellular maturation and contraction to enhance protein expression in cells and yield a tissue with potential to replaced damaged tissue (line 49-55) and constructs subjected to mechanical stimulation demonstrated greater contractile force and aligned cells properly (lines 90-92).
Regarding claim 4, It is noted that neither the manner of operating a disclosed device nor material or article worked upon further limit an apparatus claim. Said limitations do not differentiate apparatus claims from prior art. See MPEP 2114 and 2115. The limitation regarding the type of tissue sample placed in the system is considered a material worked upon by the system and therefore has been given the appropriate weight.
ALLBRITTON discloses the tissue can be heart (pg. 28, ln 5-14) and that various kinds of sensors can be used to monitor the tissue (pg. 48, ln 5-pg 49, ln 35) but does not explicitly disclose the system further comprises an ECG and strain gauge.
However, VARGAS discloses the tissue can be cardiomyocytes (heart) (line 42-54) and that previous researches had recorded contractile force and contraction amplitude (line 79-97) and that the bioreactor has multiple sensors which collect data related to stimulator current (ECG) or force applied by the actuator (strain gauge) (line 324-348). It would have been obvious to one of ordinary skill in the art at the time of the filing of the invention to modify the system of ALLBRITTON to include the sensors for electrical signals and contractile function of the tissue as taught by VARGAS because they provide valuable information on the health and function of the cultured cells (lines 79-97).
Regarding claims 5-6, ALLBRITTON discloses the tissue can be heart (pg. 28, ln 5-14) but does not explicitly disclose an electrical stimulator or mechanical pressure source as claimed.
However, VARGAS discloses the tissue can be cardiomyocytes (heart) (line 42-54) and that the system can include an electrical stimulation subsystem with electrodes 70 connected to a stimulator 8 that delivers pulses at frequencies lower than 3 Hz, which is 180 or less cycles per minute (overlaps claimed frequency range of 40-250 cycles/ min) (line 288-301) and a mechanical stimulation subsystem 61 (pneumatic driver configured to exert mechanical pressure across membrane) in which the motor provides variable speed motion (cyclical) controlled via control means (302-312). It would have been obvious to one of ordinary skill in the art at the time of the filing of the invention to modify the system of ALLBRITTON to include the electrical stimulator or mechanical pressure means as taught by VARGAS they can increase cellular maturation and contraction to enhance protein expression in cells and yield a tissue with potential to replaced damaged tissue (line 49-55) and constructs subjected to mechanical stimulation demonstrated greater contractile force and aligned cells properly (lines 90-92).
It is noted that the current frequency of the stimulator of 40-250 cycles per minute and the pressures from 0-300 mmHg are considered intended uses of the claimed system and as such do not further limit the claimed structures. It is further noted that a recitation directed to the manner in which a claimed apparatus is intended to be used does not distinguish the claimed apparatus from the prior art, if the prior art has the capability to so perform. MPEP 2114-2115. As the system of modified ALLBRITTON with VARGAS discloses the structural components as claimed they are considered capable of operating at the claimed frequencies and pressures.
Regarding claim 9, ALLBRITTON and WIKSWO above discloses the computerized monitoring system but does not explicitly disclose it monitors one or both of the contractile function signal or ECG of each well.
However, VARGAS teaches a bioreactor system for tissue engineering (lines 5-6) comprising a bioreactor in which the system also comprises a computer to process data obtained by sensors (monitoring system) (line 347-348), that previous researches had recorded contractile force and contraction amplitude (line 79-97) and that the bioreactor has multiple sensors which collect data related to stimulator current (ECG) or force applied by the actuator (contractile function signal) (line 324-348). It would have been obvious to one of ordinary skill in the art at the time of the filing of the invention to modify the system of modified ALLBRITTON to include the monitoring system monitors one or both of the data from sensors for electrical signals and contractile function of the tissue as taught by VARGAS because they provide valuable information on the health and function of the cultured cells (lines 79-97).
Regarding claim 10, It is noted that the current frequency of the stimulator of 72 cycles per minute and the pressures from 0-125 mmHg are considered intended uses of the claimed system and as such do not further limit the claimed structures. It is further noted that a recitation directed to the manner in which a claimed apparatus is intended to be used does not distinguish the claimed apparatus from the prior art, if the prior art has the capability to so perform. MPEP 2114-2115. As the system of modified ALLBRITTON with VARGAS discloses the structural components as claimed they are considered capable of operating at the claimed frequencies and pressures, especially since VARGAS discloses frequencies lower than 3 Hz, which is 180 or less cycles per minute (overlaps claimed frequency range of 40-250 cycles/ min) (line 288-301).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The additional references cited on the attached PTO 892 represent the state of the art of applicant’s invention.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIELLE B HENKEL whose telephone number is (571)270-5505. The examiner can normally be reached M-Th 11-7 EST, Alt. Fridays.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached at 571-272-1374. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANIELLE B HENKEL/Examiner, Art Unit 1799
/William H. Beisner/Primary Examiner, Art Unit 1799
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