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 .
Priority
This application is a continuation-in-part of application no. 16/948,734. Application no. 16/948,734 contains support for a number of limitations in the current set of claims, including limitations drawn to an organ plate comprising at least three wells, multiple loops and bridge channels. See paragraphs [0266]-[0269] and Figs. 8-11, for example.
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Application no. 16/948,734, however, does not appear to support the limitation “the at least one fluid stops at an expansion channel after the bridge channels”. No teaching regarding an “expansion channel” is found in the parent application. Although application no. 16/948,734 generally discusses in paragraph [0311] the culture of epithelial and endothelial cells to create a blood-retinal barrier model, application no. 16/948,734 does not specifically disclose “endothelial and epithelial regions connected by bridge channels….whereas a co-culture of at least one modeled organ is cultured in at least one of the bridge channels”. Rather, application no. 16/948,734 discusses embodiments comprising bridge channels and embodiments contemplating an iBRB separately without instruction on how the two embodiments may be used together.
Furthermore, limitations found in claim 20 relating to a robotic arm and a moving plate grabber are not disclosed in parent application no. 16/948,734.
For these reasons, each and every limitation set forth in independent claims 1 and 20 is not supported by the disclosure of application no. 16/948,734. The instant claims therefore do not receive the priority date of the parent application, and the effective filing date for the filed claims is 29 September 2023. See MPEP 2152.01 (“If the application is a continuation-in-part of an earlier U.S. application or international application, any claims in the new application not supported by the specification and claims of the parent application have an effective filing date equal to the actual filing date of the new application”).
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.
Claims 1-20 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Independent claims 1 and 20 recite the limitation “expansion channel”, however it is unclear what is meant by this term. It is unclear if “expansion” refers to an expanding cell population, an expanding geometrical configuration of the channel, or something else. Paragraph [0119] of the specification mentions that “gels, liquids, fluids, cells and/or cell mixtures may be delivered into one or more ports of the epithelial region and may stop at the expansion channel area 118A adjacent to the bridges 115A”, however this does not provide insight into exactly what is contemplated by the term “expansion channel” or indicate what kind of channels are and are not “expansion channels”.
Claim 15 is indefinite because it requires “a plurality of organ plate devices” when independent claim 1 is drawn to “an organ plate device”. It is unclear how a single device (i.e., the subject matter of claim 1) can be further limited by a recitation requiring multiple copies of that same device.
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.
Claims 1-9 and 14-19 are rejected under 35 U.S.C. 103 as being unpatentable over Collins (US 20210095235) in view of Kang (US 20230332079), Mukesh (US 20240101943) and Ponomarenko (US 20180141047).
With respect to claim 1, Collins discloses an organ plate device comprising at least three wells (Figure 10B:1000) that contain a volume of media. Multiple loops (Figure 10A:1001 and Figure 10A:1002 and Figure 10A:1003) are provided in series or parallel and are connected to the wells in order to form fluidic paths. The loops are connected using bridge channels (Figure 11B:1101a) and may contain a fluid comprising a gel, liquid, cells and cell mixtures. This is discussed in paragraphs [0268]-[0270].
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Paragraphs [0310] and [0311] state that endothelial and epithelial regions are developed to create a co-culture of at least one modeled organ. Collins, however, does not expressly teach that the modeled organ is cultured in at least one bridge channel or that fluid stops at an expansion channel after the bridge channels.
Kang discloses an organ plate comprising at least three wells connected by a series of parallel fluid paths. Bridge channels (Figure 2:220, 320, 420, 620, 720) and an expansion channel (Figure 2:210, 310, 610, 710) are used to create a modeled organ using a co-culture of epithelial cells and endothelial cells. See paragraphs [0099]-[0110] (“each of the first cell C1, the second cell C2, and the third cell C3 may be a specific cell of an endometrium. In more detail, the first cell C1 may be a uterine vascular endothelial cell, the second cell C2 may be an endometrial stromal fibroblast, and the third cell C3 may be an endometrial epithelial cell”).
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Mukesh discloses an organ plate comprising at least three wells (Figure 1A:108) connected by a series of fluid paths (Figure 1A:113) that create a plurality of parallel loops. Bridge channels (Figure 1A:117) and an expansion channel (Figure 1A:115) are used to create co-culture cells and create a modeled organ. See paragraphs [0053]-[0057].
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Ponomarenko discloses an organ plate comprising at least three wells (Figure 1:12, 21, 22, 32) connected by a series of parallel fluid paths that communicate via central chamber (Figure 3:3) configured as an expansion channel. Ponomarenko teaches that epithelial cells and endothelial cells are co-cultured to create a modeled organ. See paragraphs [0040]-[0041].
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Before the effective filing date of the claimed invention, it would have been obvious to ensure that the Collins organ plate includes an expansion channel configured to regulate fluid flow in a desired manner and enhance the co-culture of endothelial and epithelial cells. Kang, Mukesh and Ponomarenko all disclose organ plate systems in which cell media is delivered to a confluence of channels that creates an expansion channel region suitable for three-dimensional co-culture. It is well within the ability of one of ordinary skill to optimize the fluid flow circuitry of Collins in order to produce a channel pattern most conducive to the creation of a particular modeled organ (heart, blood barrier, lung, etc.).
With respect to claim 2, Collins, Kang, Mukesh and Ponomarenko disclose the combination as described above. Mukesh further teaches in paragraphs [0056]-[0057] that micropillars are used to separate fluid channels and enable communication between adjacent fluid channels (“the growth barriers 120 partially block a given channel while still allowing fluid to flow therethrough…the growth barriers 120 can be formed as one or more pillars”). Kang discloses the use of a similar plurality of micropillars 500 (“The posts 500 may be arranged at preset gaps to define the boundaries between the chambers, and thus set gaps or patterns of cells cultured in the chambers”).
With respect to claims 3 and 4, Collins, Kang, Mukesh and Ponomarenko disclose the combination as described above. Kang teaches that a hydrophobic material is applied to the bridge channels to regulate fluid flow and contain the extracellular matrix. Ponomarenko likewise discloses the hydrophobic materials are applied to a channel surface to trap a scaffolding substance that facilitates three-dimensional cell culture (“a further preferred embodiment the microfluidic device according to the present invention is characterized in that at least the wall end of the wall of the body is of a hydrophobic material. Accordingly, the scaffolding substance may be a droplet of a hydrophilic material, such as a hydrophilic liquid, particularly water suitable for cell culture, which is maintained in the culture chamber between the hydrophobic wall ends”).
With respect to claims 5 and 6, Collins, Kang, Mukesh and Ponomarenko disclose the combination as described above. As previously discussed, Kang and Ponomarenko teach the co-culture of endothelial cells and epithelial cells. The references further teach the culture of stromal cells and immune cells, as well as the production of brain, kidney, lung, liver, intestinal, heart, skin and muscle organ models.
With respect to claim 7, Collins, Kang, Mukesh and Ponomarenko disclose the combination as described above. Collins further teaches in paragraph [0261] that a transwell insert (Figure 4A:503) is disposed in at least one well.
With respect to claims 8 and 9, Collins, Kang, Mukesh and Ponomarenko disclose the combination as described above. Collins indicates in at least paragraphs [0256]-[0263] that a fluidic lid is used to connect wells to each other and to external input and output devices. The cited references further teach the state of the art regarding mixing reservoirs and external reservoirs configured to prepare a cell culture medium.
With respect to claims 14 and 15, Collins, Kang, Mukesh and Ponomarenko disclose the combination as described above. Collins teaches in paragraphs [0252]-[0261] that medium recirculation across a plurality of organ plate devices is accomplished by tilting corners of the organ plates and using gravity-driven flow.
With respect to claim 16, Collins, Kang, Mukesh and Ponomarenko disclose the combination as described above. Collins discloses in paragraphs [0062] and [0277] that the organ plate is sealed to create a sterile closed system using a hinge and latch arrangement.
With respect to claims 17-19, Collins, Kang, Mukesh and Ponomarenko disclose the combination as described above. The cited prior art teaches a variety of measurement systems configured to monitor key parameters relevant to cell culture, including oxygen, pH, temperature and humidity sensors. Collins discusses the provision of both optical and electrical (e.g., field potential sensors, TEER sensors) devices in paragraph [0091].
Claims 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Collins (US 20210095235) in view of Kang (US 20230332079), Mukesh (US 20240101943) and Ponomarenko (US 20180141047) as applied to claim 1, and further in view of Ingber (US 20110250585).
Collins, Kang, Mukesh and Ponomarenko disclose the combination as described above, however do not appear to teach that the organ plate includes a vacuum pump and a stretching membrane.
Ingber discloses an organ plate device comprising a plurality of wells and channels (see Figs. 2A and 2B). A stretching membrane (Figure 3A:208) is actuated in order to apply a force to barrier cells and proteins disposed on surfaces of the membrane. See paragraphs [0041]-[0049] and Fig. 7C. The stretching effect is created using vacuum channels (Figure 3A:252) in communication with a vacuum pump (Figure 1:118). Epithelial and endothelial cells are cultured on the flexing membrane in order to simulate the activity of muscle, lung and/or skin organs. See paragraphs [0045] and [0132]-[0139].
Before the effective filing date of the claimed invention, it would have been obvious to provide the Collins organ plate with a well comprising a stretching membrane activated by a vacuum pressure source. Ingber teaches that this is an effective way to simulate a variety of organ systems, including muscle, lung and/or skin tissues. Indeed, Ingber directly states that “one can recreate any of these tissues in the cell culture device as described by plating applicable cell types on the porous membranes and applying applicable vacuum to provide physiological or artificial mechanical force on the cells to mimic physiological forces, such as tension on skin or mechanical strain on lung”. Ingber teaches many organ systems may be replicated when one side of the membrane is coated with epithelial cells and the other side is coated with endothelial cells.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Collins (US 20210095235) in view of Kang (US 20230332079), Mukesh (US 20240101943), Ponomarenko (US 20180141047) and Gilligan (US 20220011331).
Collins discloses an organ plate system comprising an organ plate having at least three wells (Figure 10B:1000) that contain a volume of media. Multiple loops (Figure 10A:1001 and Figure 10A:1002 and Figure 10A:1003) are provided in series or parallel and are connected to the wells in order to form fluidic paths. The loops are connected using bridge channels (Figure 11B:1101a) and may contain a fluid comprising a gel, liquid, cells and cell mixtures. This is discussed in paragraphs [0268]-[0270].
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Paragraphs [0310] and [0311] state that endothelial and epithelial regions are developed to create a co-culture of at least one modeled organ. Collins, however, does not expressly teach that the modeled organ is cultured in at least one bridge channel or that fluid stops at an expansion channel after the bridge channels.
Kang discloses an organ plate comprising at least three wells connected by a series of parallel fluid paths. Bridge channels (Figure 2:220, 320, 420, 620, 720) and an expansion channel (Figure 2:210, 310, 610, 710) are used to create a modeled organ using a co-culture of epithelial cells and endothelial cells. See paragraphs [0099]-[0110] (“each of the first cell C1, the second cell C2, and the third cell C3 may be a specific cell of an endometrium. In more detail, the first cell C1 may be a uterine vascular endothelial cell, the second cell C2 may be an endometrial stromal fibroblast, and the third cell C3 may be an endometrial epithelial cell”).
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Mukesh discloses an organ plate comprising at least three wells (Figure 1A:108) connected by a series of fluid paths (Figure 1A:113) that create a plurality of parallel loops. Bridge channels (Figure 1A:117) and an expansion channel (Figure 1A:115) are used to create co-culture cells and create a modeled organ. See paragraphs [0053]-[0057].
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Ponomarenko discloses an organ plate comprising at least three wells (Figure 1:12, 21, 22, 32) connected by a series of parallel fluid paths that communicate via central chamber (Figure 3:3) configured as an expansion channel. Ponomarenko teaches that epithelial cells and endothelial cells are co-cultured to create a modeled organ. See paragraphs [0040]-[0041].
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Before the effective filing date of the claimed invention, it would have been obvious to ensure that the Collins organ plate includes an expansion channel configured to regulate fluid flow in a desired manner and enhance the co-culture of endothelial and epithelial cells. Kang, Mukesh and Ponomarenko all disclose organ plate systems in which cell media is delivered to a confluence of channels that creates an expansion channel region suitable for three-dimensional co-culture. It is well within the ability of one of ordinary skill to optimize the fluid flow circuitry of Collins in order to produce a channel pattern most conducive to the creation of a particular modeled organ (heart, blood barrier, lung, etc.).
Collins additionally teaches in paragraphs [0252]-[0261] that the organ plate is processed by a system comprising a gravity-assisted recirculation device in the form of table (see Fig. 2C) configured to tilt individual corners of the organ plate. Paragraph [0053] further states that the system includes a reagent processing platform comprising orbital mixers and spinning well plates. Collins, Kang, Mukesh and Ponomarenko additionally teach a variety of dispensing and media changing devices, as well as measurement systems configured to monitor key parameters relevant to cell culture, including oxygen, pH, temperature and humidity sensors. Collins discusses the provision of optical, electrical (e.g., field potential sensors, TEER sensors) and imaging devices in paragraph [0091]. Collins, however, does not appear to teach that the system includes a robotic arm or a moving plate grabber.
Gilligan discloses an automated cell culture processing system comprising a plurality of cell culture plates that are manipulated using a robotic arm (Figure 2:164), a recirculation device, a spinning platform (Figure 16:108), a moving plate grabber (Figure 2:162), a media change dispenser (Figure 16:340) and an imaging device. This is described in paragraphs [0178]-[0181].
Before the effective filing date of the claimed invention, it would have been obvious to ensure that a robotic arm and a moving plate grabber are utilized when operating the Collins organ plate system. Gilligan shows how these features are typically used to automatically move cell culture plates between liquid addition, incubation and detection locations. Those of ordinary skill would have found it desirable to achieve additional efficiency gains by further automating the fluid handling and plate transport operations required by Collins.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The Mokhtari (US 20220238042), Hagiwara (US 20220169970), Bobrow (US 20210062128), Jeon (US 20110244567), McKim (US 20150267158), Reiserer (US 20220135925) and Cuiffi (US 20140030752) references teach the state of the art regarding organ plates.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm.
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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/NATHAN A BOWERS/ Primary Examiner, Art Unit 1799