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 .
Claim Status
1. The amendment filed 08/05/2025 has been entered. Claims 1 – 15 remain pending and new claim 16 is pending. Claims 1 – 16 are under consideration.
Priority
2. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. FR1860401, filed on 11/09/2018.
3. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Claim Interpretation
4. For the purpose of applying prior art, the terms “defining” in claim 1, “defined” in claim 4, and “defines” in claim 6 are interpreted as “comprising”, “comprised”, and “comprises”, respectively such that the claims are given their broadest reasonable interpretation.
Maintained Claim Rejections
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.
5. Claim(s) 1 – 3 and 11 – 15 remain rejected under 35 U.S.C. 103 as being unpatentable over Inal (Inal, Sahika, et al. Advanced Biosystems 1.6 (2017): 1700052; previously cited), hereinafter Inal as evidenced by Wan (Wan, Alwin Ming-Doug, et al. Journal of Materials Chemistry B 3.25 (2015): 5040-5048; previously cited), hereinafter Wan in view of Huang (Huang, Jen‐Huang, et al. Advanced Materials 21.35 (2009): 3567-3571; previously cited), hereinafter Huang.
Regarding claim 1, Inal teaches a device body comprising a culture chamber for cell culture having a transparent optical window (polystyrene cuvette), a fluid inlet, a fluid outlet where the fluid inlet and outlet are in fluid communication with the culture chamber and a porous three-dimensional culture scaffold disposed in the culture chamber where fluid flows from the fluid inlet to the fluid outlet traverses the scaffold and the chamber (cuvette) is arranged around the scaffold and the scaffold comprises a skin layer on top of the scaffold and a first and second surface of the scaffold faces the transparent optical window (Figure 1 where Figure 1a is shown below; page 2, right col. last paragraph; page 3, right col.; page 4, left col.; page 7, right col. paragraph 2; page 8, left col. paragraph 1 – 2). Inal does not teach “a network of micro-channels configured to deliver a homogenous flow rate within 10%, on each of its outlets” or the scaffold is “situated in series with the network of micro-channels”.
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Regarding claim 2, Inal teaches fluid flow through the fluidic tube into the scaffold where the media perfusion tubes were integrated where the opening of the tube corresponds approximately to the center of the scaffold (page 3, right col.). Inal does not teach “network of micro-channels”.
Regarding claim 3, Inal teaches the cuvette is used to contain media where the media is shown above the surface of the scaffold in Figure 1a and 1c along with the fluid outlet (page 3, right col.; page 4, left col.; page 8, left col. paragraph 1 – 2).
Regarding claim 11, Inal teaches the cuvettes were modified such that a plastic tubing was incorporated where the opening of the tube corresponds approximately to the center of the scaffold (page 3, right col.; page 8, left col. paragraph 1; Figure 1). Inal does not teach “network of micro-channels”.
Regarding claim 12, Inal teaches the perfusion tubes were fixed on the cuvettes and the cuvettes were placed with a medical glue on top of gold coated glass substrates (page 8, left col. paragraph 1). Inal does not teach “network of micro-channels”.
Regarding claim 13, Inal teaches the scaffold was prepared by ice-templating of PEDOT:PSS followed by sublimation (page 2, right col. last paragraph) where a solution is frozen with confinement of solute particles in the regions between dendrites of solvent crystals and as ice is removed through sublimation, a 3D network of macropores is formed in the spaces that were once occupied by the solvent crystals as evidenced by Wan (page 5041, right col. paragraph 2; Figure 1 shown below).
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Inal does not teach “a network of micro-channels configured to deliver a homogenous flow rate within 10%, on each of its outlets” or the scaffold is “situated in series with the network of micro-channels”. However, Inal teaches due to the challenge of maintaining a homogenous distribution and viability of cells inside a relatively large structure and to maximize the cell density and homogenize their attachment, media perfusion tubes were integrated where the opening of the tube corresponds approximately to the center of the scaffold (page 3, right col.). Inal teaches the tubes were used for cell seeding throughout the entire scaffold and for media changes (page 4, left col.). Inal teaches perfusion aided homogenous population of the volume of the scaffold with cells rather than cells accumulating only at the surface (page 4, left col.). Inal teaches a simple perfusion system ensured homogenous growth of cells throughout the scaffold and extensive tissue formation was clear at multiple days after seeding (page 7, right col. paragraph 2). Inal teaches multiple flow rates for perfusion including a weak flow for seeding cells and higher flows for media perfusion and to cell dissociation (page 8, right col. paragraph 1 – 3). Inal teaches microfluidics have gained favor for perfusion, reduction in reagent volumes and flow-induced stress can enhance differentiation such that trends have seen the integration of fluidics into 3D cultures (page 2, left col. paragraph 1). Inal teaches what is missing with integrating microfluidics with 3D cultures are techniques for evaluation of tissues (page 2, left col. paragraph 1). Inal teaches optical techniques for monitoring cells cultured in 3D can be challenging due to difficulties in imaging through the scaffolds (page 2, left col. paragraph 1). Inal teaches the device allows for live-cell monitoring (Abstract).
Regarding “a network of micro-channels configured to deliver a homogenous flow rate within 10%, on each of its outlets” or the scaffold is “situated in series with the network of micro-channels” of claim 1 and “network of micro-channels” of claims 2, 11, 12, and claims 14, 15, Huang teaches a network of micro-channels formed inside plastic materials (claim 2, 11, 12) that may help enable production of tissue scaffolds containing embedded vasculature (page 3567, left col. paragraph 1 and right col. paragraph 2; Figure 1). Huang teaches the network of micro-channels has at least second order rotational symmetry and comprises multiple stages of multiple branches (claims 14, 15) (page 3567, right col. paragraph 2; Figure 1; Figure 2, shown below; Figure 3; page 3568, right col. paragraph 2). Huang teaches the microchannels mimic many attributes of naturally occurring vasculature (page 3569, right col. paragraph 2). Huang teaches the micro-channel network is a new tool to embed vascular networks in tissue scaffold materials so they can support cell culture (page 3570, right col. paragraph 2). Huang teaches the ability to mimic natural vascular networks in vitro would be immensely beneficial in the field of tissue engineering where diffusion limitations generally restrict the maximum thickness of constructs (page 3567, left col. paragraph 1).
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It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Inal regarding a device comprising a culture chamber for cell culture having a transparent optical window, a fluid inlet, a fluid outlet where the fluid inlet and outlet are in fluid communication with the culture chamber and a porous three-dimensional culture scaffold disposed in the culture chamber with the teachings of Huang regarding a network of micro-channels embedded in plastic to arrive at the claimed device comprising a network of micro-channels configured to deliver a homogenous flow rate within 10% on each of its outlets situated in series with the 3D scaffold. One would have been motivated to combine the teachings of Inal and Huang in a device for 3D tissue engineering studies as Inal teaches trends have seen the integration of fluidics into 3D cultures but what is missing are techniques for evaluation of tissues and Huang teaches the ability to mimic natural vascular networks in vitro would be immensely beneficial in the field of tissue engineering where diffusion limitations generally restrict the maximum thickness of constructs. One would have a reasonable expectation of success in combining the teachings as Inal teaches the device comprises fluidics in the plastic cuvette and Huang teaches the network of micro-channels are formed inside plastic materials, and Inal teaches the device allows for live-cell monitoring.
6. Claim(s) 4 and 5 remain rejected under 35 U.S.C. 103 as being unpatentable over Inal (Inal, Sahika, et al. Advanced Biosystems 1.6 (2017): 1700052; previously cited), hereinafter Inal as evidenced by Wan (Wan, Alwin Ming-Doug, et al. Journal of Materials Chemistry B 3.25 (2015): 5040-5048; previously cited), hereinafter Wan in view of Huang (Huang, Jen‐Huang, et al. Advanced Materials 21.35 (2009): 3567-3571; previously cited), hereinafter Huang as applied to claims 1 – 3 and 11 – 15 above, and further in view of Wan in view of Hung (US-20120003732-A1; Filed 01/21/2011; Published 01/05/2012; previously cited), hereinafter Hung.
Inal as evidenced by Wan in view of Huang make obvious the limitations of claim 1 as set forth above. Inal and Huang do not teach claim 4 or 5. However, Inal teaches a semi-micro cuvette which comprises the optical window is mounted on gold coated glass slides and the PEDOT:PSS scaffolds are formed in situ to perform electrical measurements during cell culture (page 2, right col. paragraph 2). Inal teaches detaching the scaffold from the glass for characterization (page 8, left col. paragraph 3). (Figure 1a; page 8, left col. paragraph 1).
Regarding claim 4, Hung teaches a microfluidic cell culture device in multi-well plates comprising imaging windows that can be used for 3D cell culture (page 2, 0052; page 7, 0124 – 0125 and 0128; page 9, 0148; Figure 11A – D; Figure 20A). Hung teaches in Figure 4A and 4B a standard well frame is mounted onto fluidic ports, microfluidics, and a glass slide. Hung teaches imaging of cells grown in the multi-well microfluidic plates in Figure 24 and optical images of 3D perfusion culture cells grown in the multi-well microfluidic plates in Figures 17. Hung teaches design features of the microfluidic multi-well plates include the ability to maintain long-term continuous perfusion cell culture and cellular observation wells or culture wells of the microfluidic plate (page 2, 0053). Hung teaches cell assays can be performed directly on the microfluidic cel culture using standard optically based reagent kits where the reagents can be introduced into the cells via the microfluidic channels (page 11, 0165).
Regarding claim 5, Wan teaches placing PEDOT:PSS scaffolds in wells of a 12-well plate (page 5042, right col. last paragraph; page 5046, right col. paragraph 1; page 5047, left col. paragraph 2; Figure 1B). Wan teaches the scaffolds support the growth of cells for 7 days, the cells successfully invaded the scaffold and adhered (Abstract; page 5042, right col. last paragraph; Figure 3; page 5043, left col.).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to substitute the cuvette of Inal with a multi-well plate of Hung to arrive at the claimed device where the optical window is defined by a plate directly mounted on the device body and the culture scaffold is removably received in the multi-well plate. One would have been motivated to make such a substitution to obtain multiple devices for 3D tissue engineering studies because Hung teaches in Figure 4A that each device comprises 3 wells and therefore a multi-well plate could comprise multiple devices compared to a single cuvette. One would have a reasonable expectation of success in carrying out the substitution as both Inal and Hung teach attaching the plastic component in which cells are cultured to glass slides and Wan teaches the scaffolds removable received in multi-well plates supported cell growth for 7 days.
7. Claim(s) 6 – 10 remain rejected under 35 U.S.C. 103 as being unpatentable over Inal (Inal, Sahika, et al. Advanced Biosystems 1.6 (2017): 1700052; previously cited), hereinafter Inal as evidenced by Wan (Wan, Alwin Ming-Doug, et al. Journal of Materials Chemistry B 3.25 (2015): 5040-5048; previously cited), hereinafter Wan in view of Huang (Huang, Jen‐Huang, et al. Advanced Materials 21.35 (2009): 3567-3571; previously cited), hereinafter Huang as applied to claims 1 – 3 and 11 – 15 above, and further in view of Frerich (US-20110091926-A1; Filed 03/25/2008, Published 04/21/2011; previously cited) hereinafter Frerich.
Inal as evidenced by Wan in view of Huang make obvious the limitations of claim 1 as set forth above. Inal and Huang do not teach claims 6 – 10.
Frerich teaches a device perfusable bioreactor comprising a 3D scaffold and living cells (page 1, 0001 – 0003). Frerich teaches in Figure 4A the device comprises a cavity for the tissue (21 in Figure 4A) and an insert (25 in Figure 4A) screwed into the cavity that closes the cavity (claim 6). Frerich teaches the screw comprises the top of the device (18.1 in Figure 4A) and Inal teaches the culture medium collects in the top of the device (claim 7). Frerich teaches in Figure 4A the insert comprises an end lip engaged on the seal having a radially outer surface with respect to an axis of symmetry (claim 8, 9). Frerich teaches the end of the device comprises a central opening (23 in Figure 4A) but does not teach the screw (25 in Figure 4A) has a central opening (claim 10). However, Frerich teaches the device can comprise functional monitoring by means of a probe system which monitors physical and chemical variables such as oxygen, pH, and temperature where monitoring contributes to regulating the growth conditions (page 2, 0034). Frerich teaches there is a need for bioreactors in which supplying blood vessels can be cultivated in conjunction with any tissue and that moreover satisfy the physical/mechanical requirements of soft-tissue and/or vascular/microvascular engineering (page 1, 0006).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Inal regarding a device comprising a culture chamber for cell culture having a transparent optical window, a fluid inlet, a fluid outlet where the fluid inlet and outlet are in fluid communication with the culture chamber and a porous three-dimensional culture scaffold disposed in the culture chamber with the teachings of Huang regarding a network of micro-channels embedded in plastic with the teachings of Frerich regarding a screw insert into a bioreactor perfusion device to arrive at the claimed device comprising an insert being screwed into the cavity of the device body wherein the insert has a central opening configured to receive an end fitting configured to connect a tubing for the fluid outlet. One would have been motivated to combine the teachings of Inal, Huang, and Frerich in a device for 3D tissue engineering studies as Huang teaches the ability to mimic natural vascular networks in vitro would be immensely beneficial in the field of tissue engineering where diffusion limitations generally restrict the maximum thickness of constructs and Frerich teaches there is a need for bioreactors in which supplying blood vessels can be cultivated in conjunction with any tissue and that moreover satisfy the physical/mechanical requirements of soft-tissue and/or vascular/microvascular engineering. One would have a reasonable expectation of success in combining the teachings as Inal teaches the device allows for live-cell monitoring and Frerich teaches the device can comprise functional monitoring by means of a probe system which monitors physical and chemical variables such as oxygen, pH, and temperature where monitoring contributes to regulating the growth conditions.
New Claim Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 103
8. Claim(s) 16 is rejected under 35 U.S.C. 103 as being unpatentable over Inal (Inal, Sahika, et al. Advanced Biosystems 1.6 (2017): 1700052; previously cited), hereinafter Inal as evidenced by Wan (Wan, Alwin Ming-Doug, et al. Journal of Materials Chemistry B 3.25 (2015): 5040-5048; previously cited), hereinafter Wan in view of Huang (Huang, Jen‐Huang, et al. Advanced Materials 21.35 (2009): 3567-3571; previously cited), hereinafter Huang as applied to claims 1 – 3 and 11 – 15 above, and further in view of McFetridge (US-9599604-B2; Filed 12/07/2012, Published 03/21/2017) hereinafter McFetridge.
Inal as evidenced by Wan in view of Huang make obvious the limitations of claim 1 as set forth above. Inal teaches in Figure 1, images of taken from different parts of the scaffold showing cells within the scaffold but shows the fluidic tube traverses the scaffold (Figure 1c; page 4, left col.). Inal and Huang do not teach the fluid inlet and fluid outlet are on the same side of the culture chamber of claim 16. However, Inal teaches integration of media perfusion tube inside the scaffold enables homogenous cell spreading and fluid transport throughout the scaffold, ensuring long term cell viability and also allows for co-culture of multiple cell types inside the scaffold (Abstract). Inal teaches multilayer 3D tissue models hold a lot of promise for certain applications but cannot be easily applied for more complex tissue or organ constructs including vasculature (page 1, right col.). Inal teaches a challenge of 3D culture is associated with the difficulty of oxygenation of tissues in the absence of vasculature (page 1, right col.). Inal teaches microfluidics have gained favor because of inclusion of perfusion, reduction in reagent volumes, and the fact that flow induced stress is known to enhance differentiation via mecahnotransduction and encourage intercellular/organ communication (page 1, right col.; page 2, left col. para. 1). Inal teaches what is lacking in the integration of fluidics into 3D cultures is techniques for evaluation of tissues because optical techniques can be challenging to apply in 3D due to difficulties in imaging through the scaffolds (page 2, left col. para. 1). Huang teaches microchannels produced by electrostatic discharge mimic many attributes of naturally occurring vasculature (page 3569, right col. para. 2). Huang teaches the method of forming these microchannels that resemble anatomical vasculature provides a convenient platform to study transport and flow in branched 3D microfluidic networks and introduce the exciting possibility of harnessing the method as a new tool to embed vascular networks in tissue scaffold materials so they can support cell culture (page 3570, right col. para. 2).
McFetridge teaches in Figure 1, 2, and 7 a device comprising fluid inlet and outlet ports on the same side of the culture chamber (12 in Figure 1 and HUV scaffold in Figure 2 and Flow Channel in Figure 7) (col. 2, lines 16 – 37; col. 3, lines 17 – 28; col. 6, lines 44 – 50). McFetridge teaches the device comprises a viewing window for high-magnification fluorescence microscopy imaging where the viewing window can be disposed adjacent the flow channel to view the sample in real time as the sample is exposed to fluid (col. 2, lines 21 – 23 and 33 – 35; col. 7, lines 1 – 4). McFetridge teaches the flow channel (12 in Figure 1) includes a sample such as a scaffold material that can be made of a synthetic material or a biological material or a combination of both (col. 7, lines 18 – 31). McFetridge teaches the inlet and exit ports can be controlled manually and/or with a control device to regulate the flow of fluid into the flow channel (col. 6, lines 58 – 60). McFetridge teaches a decellularized human umbilical vein scaffold is sliced open and spread out to create a tightly sealed channel that can be imaged through the viewing window (col. 2, lines 25 – 35; Figure 8; col. 3, lines 29 – 39; col. 7, lines 41 – 52; col. 9, lines 49 – 63). McFetridge teaches endothelial cells are seeded on the scaffold and shear stress is applied by the controlled flow of culture media with pumps (col. 2, lines 38 – 46; Figure 3 and 9; col. 3, lines 40 – 52). McFetridge teaches the device can be used to view cell interactions on biological or synthetic membranes or used for screening drugs or other molecules or cells to monitor and observe in real time the interactions with the cells or scaffold material (col. 6, lines 31 – 37 and lines 61 – 67; col. 8, lines 16 – 28). McFetridge teaches in Example 1 a device for seeding and conditioning of an endothelium under defined shear conditions on a decellularized vascular surface and live imaging of interactions between the scaffold and fluorescently labeled blood cells (col. 9, lines 5 – 47). McFetridge teaches endothelialization of vascular grafts is used to minimize unfavorable host responses that lead to graft failure but assessment of vascular grafts require high volumes of whole blood and only end-point assessment is possible due to the closed vascular geometry (col. 8, lines 63 – 67; col. 9, lines 1 – 5). McFetridge teaches details of the microenvironment in which endothelial cells reside are critical to their behavior (col. 9, lines 65 – 67). McFetridge teaches the device provides an environment more reminiscent of the vascular intima and permits live visualization of cultured cells under flow (col. 10, lines 6 – 10). McFetridge teaches the device has been successfully tested with human umbilical vein and human amniotic membrane and can be adapted for a wide range of other conduit biomaterials (col. 10, lines 10 – 13). McFetridge teaches cell interactions at the surface of implantable vascular grafts can only be assessed terminally after perfusion due to opacity of these materials (col. 10, lines 23 – 42; col. 11, lines 22 – 41). McFetridge teaches in Example 2 the device for real-time analysis of blood-biomaterial interactions under flow with 3D imaging (col. 10, lines 23 – 42; col. 11, lines 22 – 41; col. 14, lines 37 – 54; Figure 11). McFetridge teaches the device can be used for preliminary assessment of clinically relevant biomaterials before implantation (col. 10, lines 37 – 42).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Inal regarding a device for perfusing and imaging a 3D living tissue with the teachings of Huang regarding a method of creating a network of microchannels resembling anatomical vasculature to study transport and flow in branched 3D microfluidic networks with the teachings of McFetridge regarding a device for viewing cell interactions on a scaffold where the fluid inlet and fluid outlet are on the same side of the chamber housing the scaffold to arrive at the claimed device where the fluid inlet and the fluid outlet are on the same side of the culture chamber. One would have been motivated to combine the teachings of Inal, Huang, and McFetridge in a device to monitor cell interactions because Inal’s device comprises fluid inlet and outlet that traverses the scaffold thus interfering with imaging, Inal teaches 3D tissue models hold a lot of promise for certain applications but cannot be easily applied for more complex tissue or organ constructs including vasculature and a challenge of 3D culture is the difficulty of oxygenation of tissues in the absence of vasculature and Inal teaches what is lacking in the integration of fluidics into 3D cultures is techniques for evaluation of tissues because optical techniques can be challenging to apply in 3D due to difficulties in imaging through the scaffolds, Huang teaches the method of forming these microchannels that resemble anatomical vasculature provides a convenient platform to study transport and flow in branched 3D microfluidic networks and introduce the exciting possibility of harnessing the method as a new tool to embed vascular networks in tissue scaffold materials so they can support cell culture, and McFetridge teaches the device can be used for preliminary assessment of clinically relevant biomaterials before implantation. One would have a reasonable expectation of success in combining the teachings as McFetridge teaches the device provides an environment more reminiscent of the vascular intima and permits live visualization of cultured cells under flow and the device has been successfully tested with human umbilical vein and human amniotic membrane and can be adapted for a wide range of other conduit biomaterials and teaches in Example 2 the device for real-time analysis of blood-biomaterial interactions under flow with 3D imaging.
Applicant’s Arguments/ Response to Arguments
9. Applicant Argues: On page 5, paragraph 4, Applicant asserts the cited art does not teach “ a seal arranged around the culture scaffold” as recited in independent claim 1.
Response to Arguments: Inal teaches that the scaffold was prepared in situ inside disposable cuvettes fixed on gold-coated substrates (page 2, right col. last para and Figure 1a, both previously cited). Therefore the culture chamber (disposable cuvette) is also the seal around the culture scaffold. Should the Applicant amend the claim to recite that the culture chamber further comprises a seal, the rejection may be overcome.
Applicant Argues: On page 6 and page 7, paragraph 1, Applicant asserts the cited art does not teach “ a network of micro-channels configured to deliver a homogenous flow rate within 10% , on each of its outlets” as recited in independent claim 1 and that Huang does not teach which of the openings are inlets and outlets or the distribution of flow between multiple outlets .
Response to Arguments: Inal teaches one micro-channel composed of plastic tubing with a fluid inlet and fluid outlet in fluid communication with the polystyrene cuvette culture chamber (fluidic tube in Figure 1a) and control of the flow rate of media using a pump (page 4, left col.; page 8, right col. para. 1 – 2 as previously cited). Therefore, Inal teaches a homogenous flow rate and this flow rate can be a weak flow (1.6 µL/min) or a higher flow rate (10 µL/min) when using a pump. Inal does not teach a network of micro-channels. However, , Huang teaches a network of micro-channels formed inside plastic materials that may help enable production of tissue scaffolds containing embedded vasculature (page 3567, left col. paragraph 1 and right col. paragraph 2; Figure 1 as previously cited). Huang teaches the microchannels mimic many attributes of naturally occurring vasculature (page 3569, right col. paragraph 2). Huang teaches the micro-channel network is a new tool to embed vascular networks in tissue scaffold materials so they can support cell culture (page 3570, right col. paragraph 2). Huang teaches the ability to mimic natural vascular networks in vitro would be immensely beneficial in the field of tissue engineering where diffusion limitations generally restrict the maximum thickness of constructs (page 3567, left col. paragraph 1). Therefore, the combination of Inal and Huang would make obvious the claimed device comprising a network of micro-channels configured to deliver a homogenous flow rate within 10% on each of its outlets. One would have been motivated to combine the teaching sof Inal and Huang in a device for 3D tissue engineering studies as Inal teaches trends have seen the integration of fluidics into 3D cultures but what is missing are techniques for evaluation of tissues and Huang teaches the ability to mimic natural vascular networks in vitro would be immensely beneficial in the field of tissue engineering where diffusion limitations generally restrict the maximum thickness of constructs. One would have a reasonable expectation of success in combining the teachings as Inal teaches the device comprises fluidics in the plastic cuvette and Huang teaches the network of micro-channels are formed inside plastic materials, and Inal teaches the device allows for live-cell monitoring. Should the Applicant amend the claim to further define “configured to” or explain how the network of micro-channels are configured to deliver a homogenous flow rate, the rejection may be overcome.
Regarding inlets and outlets of Huang, Huang teaches in Figure 2 (previously cited) the direction of flow in through the network of channels and flow out of the network of channels in Figure 2a. Thus combining Inal and Huang would provide a homogenous flow using the pump to control the flow rate of media as described by Inal though the fluid inlet described by Inal throughout the network of microchannels comprising multiple outlets as shown in Figure 2a of Huang and out the fluid outlet described by Inal.
Applicant Argues: On page 7, paragraph 2, Applicant asserts that the claimed device is in no way a reproduction of a vascular system and that the device of claim 1 has a symmetrical fractal-type design in order to enable homogenous and centripetal distribution of the culture medium at the scaffold input and that the claimed channels are not biomimetic at all, i.e. they do not simulate a vascular function.
Response to Arguments: Applicant’s specification discloses that the culture scaffold may be transplanted or implanted (page 3, lines 6 – 7) and that the invention may be used within the scope of understanding the biology of bones with the aim notably of optimizing the production of living bone grafts (page 3, lines 17 – 20). Applicant’s specification discloses that the invention also offers the possibility of having available bone models as a standard platform for screening molecules, notably osteo-active or anti-cancerous molecules, as a replacement for animal models (page 3, lines 21 – 23). Therefore, because claim 1 does not recite the geometry of the network of micro-channels configured to deliver a homogeneous flow and Applicant’s specification contemplates the device for generating bone grafts and screening molecules, it is plausible to use a network of micro-channels that simulates vasculature to deliver a homogenous flow rate controlled by a pump. Should applicant amend claim 1 to recite the geometry of the network of microchannels that enables homogenous and centripetal distribution of the culture medium at the scaffold input, the rejection may be overcome.
Conclusion
No claims allowed.
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 ZANNA M BEHARRY whose telephone number is (571)270-0411. The examiner can normally be reached Monday - Friday 8:45 am - 5:45 pm.
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/Z.M.B./Examiner, Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632