DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
The amendments filed on 06/29/2026 have been entered. Claims 1, 22, and 24 have been amended; claims 5, 7, and 8 have been canceled. Accordingly, claims 1-4, 6, and 9-24 are pending and under consideration.
Response to Arguments
Applicant's arguments filed 06/29/2026 have been fully considered but they are not persuasive.
Regarding Applicant’s remarks stating that “Notably, the Office Action cites Nosrati in order to teach the fluid and gas transfer units modularly combined in a housing. However, the cited references teach coupling independent extracorporeal devices rather than creating a monolithic blood treatment module via components that would be integrated within the housing. Notably, none of the references alone or in combination disclose, teach, or suggest the single circuit aspect of Applicant's claimed device because while the cited art may generally disclose oxygenation, ultrafiltration, pressure regulation, or microfluidic channels, the cited art admittedly does not teach the claimed integration of these features into a single fluidly connected blood circuit using common manifolds within the housing as claimed. Structurally, the defined circuit is not taught or suggested by the cited references, and the modular aspect of Nosrati does not contemplate this integration as there are considerations addressed by Applicant's system that would not make the parts obviously combinable” on page 11 and “The Office Action alleges that the claimed invention would be an obvious modification of Nosrati, however Applicant respectfully submits that the proposed combination of modules in Nosrati fundamentally changes the architecture disclosed by Nosrati. Although Nosrati broadly contemplates using multiple functional chipsets within a treatment system, each chipset remains a discrete functional component that is separately connected without any common manifolds or integration between units. The claimed limitations are directed to a fundamentally different structural architecture in which the blood flow path for each of the types of transfer units is internal to a single monolithic microfluidic structure. Rather than directing blood from one extracorporeal device through external tubing into a second extracorporeal device (i.e., the modular approach of Nosrati), the present claims are directed to a structure in which blood enters the housing into one integrated device and exits via a common manifold after both oxygenation and fluid management have been performed” on page 11 of Applicant’s remarks, Examiner acknowledged the remarks, but respectfully disagrees. In response to Applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., creating a single monolithic blood treatment module via components that would be integrated within the housing) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In addition, Kniazeva is relied upon for teachings of the common manifolds, rather than Nosrati.
Regarding Applicant’s remarks stating that “Neither Nosrati nor any of the other cited references teach or suggest replacing externally interconnected oxygenation and filtration devices with an internally integrated microfluidic blood circuit, and the Office Action identifies no reason why one of ordinary skill would have fundamentally redesigned Nosrati's modular architecture in this manner. Because the cited references externally connect the modules, the fundamental differences in hydraulic architectures for fluid flow would not make it obvious to combine the architectures to operate as a single blood circuit because the external design has different implications on shear and does not contemplate the changes in viscosity after partial treatment” on page 12 and “Applicant further submits that the Office Action relies on impermissible hindsight reasoning in order to modify Nosrati, as well as to combine Nosrati with the other cited references. Notably, the Office Action uses Applicant's disclosure as a roadmap by extracting isolated features from the references directed to different extracorporeal technologies and assembling them into the claimed invention. While the cited art may generally disclose oxygenation, ultrafiltration, pressure regulation, or microfluidic channels, the cited art admittedly does not teach the claimed integration of these features into a single fluidly connected blood circuit using common manifolds. The motivation to eliminate the external connections between independent oxygenation and filtration devices and instead redesign them into a unified extracorporeal module arises only from Applicant's disclosure, where the motivations are set forth in Applicant's Specification at pages 5-7, setting forth the complexities of modular approaches. Absent impermissible hindsight reasoning using Applicant's specification, there is no articulated reasoning supported by the prior art that would have led one of ordinary skill to fundamentally redesign Nosrati's modular system into Applicant's integrated architecture, let alone with a reasonable expectation of success. In fact, the Office Action's alleged combination of systems based on the cited art would be an externally connected modular system, which is distinguishable from an integrated structure as claimed” on page 13 of Applicant’s remarks, Examiner acknowledged the remarks, but respectfully disagrees. Examiner remains highly unsure of Applicant’s traversal regarding the internal versus external blood circuit of the combination of references. Channels of Nosrati are interpreted to be an internal circuit because they are within the housing 114 (Fig. 7 of Nosrati; see rejection of claims below). Par. 151 of Nosrati also discusses a system with a plurality of microfluidic units arranged in series configuration, which one of ordinary skill in the art would have reasonably understood that the channels have to be fluidly connected to each other in the system. Furthermore, at least Figs. 4A-4B, and Fig. 12A of Nosrati show “internal”/”integrated” channels into the chips 104, 106; see also Par. 40 of Nosrati, “Microfluidics uses photolithography to build very large and dense networks of micro-channels 110a-d with essentially the same ease as making a single channel.” Thus, Nosrati reads on the claimed limitations.
Regarding Applicant’s remarks stating that “Applicant further respectfully submits that the combination of elements recited in the Office Action is based on impermissible hindsight because Nosrati does not merely omit a claimed feature; rather, Nosrati describes different chipsets as function-specific modules designed to perform different physiological operations. Nosrati's oxygenation chipset is directed to gas transfer across a gas-permeable membrane, whereas the claimed fluid transfer unit is directed to ultrafiltration across a fluid-permeable membrane with transmembrane pressure monitoring and pump-based control. The Office Action treats these different functional units as freely interchangeable building blocks, but Nosrati does not teach or suggest physically unifying the blood circuits or adhering a fluid transfer unit to a gas transfer unit within a common housing with common manifolds in the claimed manner. Instead, the rejection reconstructs Applicant's integrated blood treatment module only after using Applicant's disclosure as a roadmap” on page 13-14 of Applicant’s remarks, Examiner acknowledged the remarks, but respectfully disagrees. Nosrati does discuss a modular and scalable microfluidic unit that each that utilizes different and various principles of microfluidics for performing different processes on blood and plasma. These processes include but not limited to filtration, ultrafiltration, diafiltration, various forms of dialysis, hemoperfusion, plasma separation and etc. (Par. 145). Par. 74 further listed 18 units/modules that can be used for a combination of many of these modules. Thus, one of ordinary skill in the art would have had the technological capability to select the appropriate treatment modules from the disclosure of Nosrati to form a desired blood treatment system.
Regarding Applicant’s remarks stating that “Applicant further submits that the proposed modification set forth in the Office Action as well as the general assertion of combinability stated by the Office Action would require more than routine combination of parts because the gas transfer unit and the fluid transfer unit are designed around materially different pressure regimes, in addition to the differing hydraulics discussed above, and there is no explanation of how one of ordinary skill would accommodate these factors. As set forth in Applicant's Specification, the flow factors considered for oxygenation and fluid removal are unique. Thus, the claimed architecture is not a simple aggregation of known oxygenation and filtration components. The combination would require reconciling competing flow-related and pressure-related objectives-minimizing pressure drop for gas exchange while generating and controlling transmembrane pressure for ultrafiltration-which is not taught or suggested by Nosrati or other references, or even contemplated within their combination. Accordingly, Applicant's overall architecture and structural components addresses objectives that would not be addressed by a routine combination of parts” and “Applicant further notes that combining units as suggested by the Office Action would result in changes in the properties of blood flowing through the modules, including hematocrit and viscosity. These changes directly affect the factors addressed by Applicant's claimed structure and components. Nosrati's oxygenation architecture is premised on biomimetic microfluidic flow and controlled gas exchange, but Nosrati does not teach or suggest modifying its oxygenation units to operate in a laminated structure in which ultrafiltration changes blood rheology during the same treatment process. Thus, the Office Action's proposed modification is not a predictable use of prior-art elements according to their established functions, but would require substantial redesign of Nosrati's modules" on page 14 of Applicant’s remarks, Examiner acknowledged, but respectfully disagrees. In response to Applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., pressure regimes, differing hydraulics) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In this instant case, all the structures are disclosed by the combination of references (see rejection of claims below. For the sake of compact prosecution, Par. 235-243 of Nosrati does discuss the variations in the unit channels and semipermeable membranes to accommodate different types of flow. This, in fact, suggests that Nosrati, or one of ordinary skill in the art, would have had the technological capability to contemplate flow characteristics within the chipsets to construct/engineer an appropriate system. See also Par. 243 of Nosrati, “By changing the characteristics and permeability of the membrane one can achieve different types of capillaries for engineered tissue and organ.”
Regarding Applicant’s remarks stating that “Applicant additionally submits that the rejection improperly treats gas-side pressure regulation and filtration-side transmembrane pressure control as independent features. In the claimed module, the gas outlet pressure regulator and the pump-controlled fluid transfer unit operate in the same extracorporeal blood treatment module, such that gas-channel pressure, blood- channel pressure, filtrate pressure, and transmembrane pressure are interrelated. Adjusting pump draw rate affects blood-side and filtrate-side pressures, while gas pressure regulation affects the pressure environment of the gas transfer units. The cited art does not teach or suggest this integrated pressure-management architecture. At most, the references disclose separate pressure- control concepts in separate devices or contexts, which does not render obvious the claimed module having both regulated gas transfer and feedback-controlled ultrafiltration within a common integrated structure” on page 15 of Applicant’s remarks, Examiner acknowledged the remarks, but respectfully disagrees. In response to Applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., gas-channel pressure, blood-channel pressure, filtrate pressure, and transmembrane pressure are interrelated) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). See rejection of claims below.
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.
Claims 1-4, 6, 9-12, and 20-24 are rejected under 35 U.S.C. 103 as being unpatentable over Nosrati US 2017/0252701 A1 (previously cited, hereinafter Nosrati), as cited in the IDS, and further in view of Kniazeva et al., “Performance and scaling effects in a multilayer microfluidic extracorporeal lung oxygenation device” (previously cited, hereinafter Kniazeva), Borenstein et al. US 2019/0184342 A1 (previously cited, hereinafter Borenstein), Gremel US 5,788,287 A (previously cited, hereinafter Gremel), and Charest et al. US 2016/0158428 A1 (previously cited, hereinafter Charest).
Regarding claim 1, Nosrati discloses an extracorporeal blood treatment module 100 (Fig. 1) comprising:
a fluid transfer unit 102a (Fig. 4B – microfluidic chip unit 102a, and Par. 74 describes a variety of functional options for the microfluidic chip unit, i.e. hemodialysis function, ultrafiltration function, etc.), the fluid transfer unit 102a (Fig. 4B) including:
(i) a third polymer layer 106 (Fig. 4B and Par. 224 – “microfluidic unit 102 fabricated from any biocompatible polymer”) having a plurality of fluid collection channels 110c-d (Fig. 4A and Par. 234 – “micro-channels 110 for carrying dialysate”) defined therein, the plurality of fluid collection channels 110c-d (Fig. 4A) having a first depth (Fig. 4A; Examiner notes that a channel inherently has a depth),
(ii) a fourth polymer layer 104 (Fig. 4B and Par. 224 – “microfluidic unit 102 fabricated from any biocompatible polymer”) having a plurality of blood channels 110a-b (Fig. 4A and Par. 234 – “micro-channels 110 for carrying blood”) defined therein, and
(iii) a fluid permeable membrane 108 (Fig. 4B and Par. 228 – “the semipermeable membrane 108 enables passage of toxins, water…”) disposed between the plurality of fluid collection channels 110c-d (Fig. 4A) and the plurality of blood channels 110a-b (Fig. 4A – membrane 108 is sandwiched between layer 104 and layer 106) and providing for the transport of fluid from the plurality of blood channels 110a-b (Fig. 4B) into the plurality of fluid collection channels 110c-d (Fig. 4B and Par. 228 – “the semipermeable membrane 108 enables passage of toxins, water…”, thus indicating mass transfer across the membrane 108 between the fluid channels and the blood channels) while preventing transport of blood cells from the plurality of blood channels 110a-b (Fig. 4B) into the plurality of fluid collection channels 110c-d (Fig. 4B and (Par. 228 – “…form a permeable barrier between the blood and the dialysate”);
a housing 114 (Fig. 7 – microfluidic housing 114) containing the fluid transfer unit 102a (Fig. 7 – microfluidic chipset 102a is within the housing 114).
However, Nosrati, in the same embodiment, does not explicitly disclose a plurality of gas transfer units, each of the gas transfer units including a first polymer layer having a plurality of gas channels, a second polymer layer having a plurality of blood channels, and a gas permeable membrane disposed between the plurality of gas channels and the plurality of blood channels and providing for the transport of gas between the plurality of gas channels and the plurality of blood channels, a gas outlet manifold defined in the first polymer layer and fluidically coupled to each of the plurality of gas channels; a fluid transfer unit adhered to at least one of the plurality of gas transfer units, wherein the first depth of the plurality of fluid collection channels is at least twice a second depth of the plurality of blood channels, wherein the plurality of blood channels of the fluid transfer unit are fluidly coupled to the plurality of blood channels of the at least one gas transfer unit to define a bonded internal circuit extending through the plurality of gas transfer units and the fluid transfer unit; the fluid transfer unit comprising a transmembrane pressure sensor configured to measure a transmembrane pressure across the fluid permeable membrane; and a housing containing the plurality of gas transfer units, such that, within the housing, the plurality of gas transfer units and the fluid transfer unit collectively define a single extracorporeal bonded blood circuit via common entry and exit manifolds; and a gas outlet of the housing coupled to the gas outlet manifold of each of the plurality of gas transfer units, the gas outlet comprising a pressure regulator to maintain a target gas pressure in the plurality of gas channels of each of the plurality of gas transfer units, the gas outlet configured to ventilate gas from the plurality of gas transfer units via a vent; a pump coupled to a fluid outlet manifold of the fluid transfer unit and configured to control a rate at which fluid is drawn from the plurality of fluid collection channels of the fluid transfer unit; and a controller configured to: receive a transmembrane pressure measurement across the fluid permeable membrane from the transmembrane pressure sensor, and adjust, based on the transmembrane pressure measurement, a rate at which the pump draws fluid from the plurality of fluid collection channels to maintain a target transmembrane pressure across the fluid permeable membrane during a blood filtration process.
Nosrati, in another embodiment, teaches a plurality of gas transfer units 102b-d (Fig. 4B, Fig. 7 – multiple units 102b-d, and Par. 74 describes a variety of functional options for the microfluidic chip unit, including oxygenation – “The O Chipset (Oxygenation) in formation of this any type of ECMO membrane will be used”, which is known in the art as a gas-blood interface), each of the gas transfer units 102b-d (Fig. 7 and Par. 41 – “multiple types of microfluidic chip units 102a-d may be used…”) including:
a first polymer layer 106 (Fig. 4B and Par. 224 – “microfluidic unit 102 fabricated from any biocompatible polymer”) having a plurality of gas channels 110c-d (Fig. 4A and Par. 234; since it is established above by Par. 74 that the chip units are now the O Chipset, i.e., oxygenation, channels 110c-d are now understood by one of ordinary skill in the art to be the gas channels),
a second polymer layer 104 (Fig. 4B and Par. 224 – “microfluidic unit 102 fabricated from any biocompatible polymer”) having a plurality of blood channels 110a-b (Fig. 4A and Par. 234 – “micro-channels 110 for carrying blood”),
a gas permeable membrane 108 (Fig. 4B and Par. 74-75 – the Oxygenation unit will receive an ECMO membrane to allow manipulation of gases) disposed between the plurality of gas channels 110c-d (Fig. 4A) and the plurality of blood channels 110a-b (Fig. 4A) and providing for the transport of gas (Par. 75 – “Each chipset module utilizes a specific semipermeable membrane to allow manipulation of gases”) between the plurality of gas channels 110c-d (Fig. 4A) and the plurality of blood channels 110a-b (Fig. 4A);
a fluid transfer unit 102a (Fig. 7) adhered to at least one of the plurality of gas transfer units 102b-d (Fig. 7 – stacking of microfluidic units 102);
wherein the plurality of blood channels of the fluid transfer unit 102a (Fig. 7) are fluidly coupled to the plurality of blood channels of the at least one gas transfer unit 102b-d (Fig. 7) to define a bonded internal circuit (Fig. 7 – the chipsets are stacked to form a circuit, Par. 145 – “The present invention is directed to a modular and scalable microfluidic unit that each that utilizes different and various principles of microfluidics for performing different processes on blood and plasma. These processes includes but not limited to filtration, ultrafiltration, diafiltration, various forms of dialysis, hemoperfusion, plasma separation and etc. of any fluid, such as blood, plasma and lymph”, Par. 148-151 – “a modular microfluidic dialysis system, comprises: a plurality of microfluidic units, the plurality of microfluidic units configured to enable any one of different forms of blood filtration, ultrafiltration, diafiltration, plasma separation and dialysis of blood, the plurality of microfluidic basic building block units can be arranged in modular configuration in parallel or in series for enabling scalability, the plurality of microfluidic units at least partially fabricated from inert and biocompatible polymers commonly used in microfluidic such as a polymeric organosilicon compound…”; thus indicating that blood channels are fluidly connected throughout the device) extending through the plurality of gas transfer units 102b-d (Fig. 7) and the fluid transfer unit 102a (Fig. 7); and
a housing 114 (Fig. 7 – microfluidic housing 114) containing the plurality of gas transfer units 102b-d (Fig. 7) and the fluid transfer unit 102a (Fig. 7), such that, within the housing 114 (Fig. 7), the plurality of gas transfer units 102b-d (Fig. 7) and the fluid transfer unit 102a (Fig.7) collectively define a single extracorporeal bonded blood circuit (Fig. 7, Par. 85 – “The Combined microfluidic-based kidney and Liver dialysis device can be made in a compact form to be used for many different types of Multi-System/Multi-Organ Dysfunctions”, and Par. 104 – “This device utilizes a plurality of various microfluidic-based chipset units/modules/segments”; thus indicating that multiple units form a blood processing device).
Examiner strongly notes that each microfluidic unit of Nosrati comprises a fundamental build of three layers as shown in Fig. 4B, and the difference between an oxygenation and other fluid units relies on the functioning membrane utilized (Par. 74 and Par. 75). Thus, it allows creators to combine many microfluidic units that function as various organs/tissues and scale the treatment system (Par. 76).
Nosrati, in another embodiment for the microchannels, teaches an outlet manifold (see annotated Fig. 12C below – “outlet manifold” is the primary branch on the left) and fluidically coupled to each of the plurality of channels (see annotated Fig. 12C below – the “outlet manifold” branches into smaller channels).
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Annotated Fig. 12C of Nosrati
Kniazeva, in the same field of endeavor of microfluidic extracorporeal lung oxygenation device (Title), teaches common entry and exit manifolds (see annotated Fig. 1 below); a gas outlet of the housing (see annotated Fig. 1 below – “gas outlet of the housing” can be seen as the gas outlet of the device) coupled to the gas outlet manifold of each of the plurality of gas transfer units (see annotated Fig. 1 below – the annotated port fluidly communicates with every outlet manifold at each gas unit of the stack).
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Annotated Fig. 1 of Kniazeva
Borenstein, in the same field of endeavor of microfluidic device (Title), teaches a pressure regulator 110 (Fig. 1A – pressure regulator 110) to maintain a target gas pressure in the plurality of gas channels of each of the plurality of gas transfer units (Par. 27 – “one or more pressure regulators 110 to regulate the pressure within the pressure vessel 104 and maintain a predetermined pressure within the pressure vessel 104”; Examiner also notes that the pressure within the pressure vessel 104 directly relates to the pressure of the plurality of gas channels, as discussed in Par. 26 – “…gas channels of the microfluidic device 102 are open and exposed to the ambient, atmospheric conditions created within the pressure vessel 104…”; therefore, the pressure regulator 110 does in fact regulates the pressure of the gas channels).
Gremel, in the same field of endeavor of devices for removing gases from blood (Col. 1, line 6-7), teaches the gas outlet 12 (Fig. 2 – outlet connector 12) configured to ventilate gas (Col. 3, line 14-16 – “Hole 18 vents the interior hollow passage of the outlet connector 12, and consequently the interior of the oxygenator 2, to ambient pressure”) from the plurality of gas transfer units 4 (Fig. 1 – fiber bundle 4) via a vent 18 (Fig. 2 – vent holes 18).
Charest, in the same field of endeavor of extracorporeal microfluidic device (Abstract), teaches a pump (Fig. 5B, and Par. 95 – outflow pump 517) coupled to a fluid outlet manifold 116 (Fig. 1A – filtrate outlet manifold 116 for exemplary demonstration; Par. 95 – “The device 513 also includes an outflow pump 517 in-line with the filtrate channel 502”; Fig. 5B shows the outer loop of channel 502) of the fluid transfer unit 513 (Fig. 5B – microfluidic convective clearance device 513, and Par. 81 – “Each of the devices described in relation to FIGS. 5A, 5B, 6A-10, and 13 can form a layer 102 of the device illustrated in FIG. 1A”, thus there can be a stack of layers 500 to form a device like Fig. 1A with a fluid outlet manifold like 116 and channels 502) and configured to control a rate at which fluid is drawn from the plurality of fluid collection channels 502 (Fig. 5B – filtrate channel 502) of the fluid transfer unit 513 (Fig. 5B and Par. 95 – “The outflow pump 517 is configured to draw filtrate out of the filtrate channel 502”; Examiner also notes that pumps inherently controls a rate of fluid flow in any given channel); and
Charest, in another embodiment, teaches the fluid transfer unit 300 (Fig. 3) comprising a transmembrane pressure sensor 304 (Fig. 3 – pressure sensor 304, and Par. 73 – “Pressure sensors 304 and flow sensors 306 can be placed inside the blood channel”, and Par. 142 – “the control system receives pressure measurements from pressure sensors placed along the length of any of the filtrate, blood, and infusate channels”) configured to measure a transmembrane pressure across the fluid permeable membrane (Par. 143 – “The control system can receive pressure measurement from the pressure sensors placed along the length of the blood and filtrate channels to ensure that the pressure difference remains below a critical transmembrane pressure along the length of the device”);
a controller 300 (Fig. 3 – control system 300) configured to:
receive a transmembrane pressure measurement across the fluid permeable membrane from the transmembrane pressure sensor 304 (Fig. 3, and Par. 143 – “The control system can receive pressure measurement from the pressure sensors placed along the length of the blood and filtrate channels to ensure that the pressure difference remains below a critical transmembrane pressure along the length of the device”), and
adjust, based on the transmembrane pressure measurement, a rate at which the pump draws fluid from the plurality of fluid collection channels to maintain a target transmembrane pressure across the fluid permeable membrane during a blood filtration process (Par. 6 – “the control system is configured to modify the state of the first controllable flow control device responsive to an output of the at least one pressure sensor. In some implementations, the first controllable flow control device is… an outflow pump”; and Par. 5 – “the control system is configured to control the first controllable flow control device to maintain a pressure difference between a pressure of a first fluid flowing through the blood channel and a pressure of a second fluid flowing through the filtrate channel that is below a critical transmembrane pressure”).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the blood treatment module of Nosrati that has a fluid transfer unit to further include a plurality of gas transfer units, also as taught by Nosrati, in order to produce a microfluidic-based system that mimics properties of multiple human organs and tissues (Abstract of Nosrati). In other words, by combining various functioning modules, these building blocks can simultaneously perform various functions that otherwise would have existed individually in individual dialysis device and organ support systems, such as albumin/lipid dialysis, water purification, bioreactors, kidney support, lung support, etc. (Abstract and Par. 462). Once the combination is made, a plurality of gas transfer units and a fluid transfer unit will be stacked and located inside a housing as seen in Fig. 7 of Nosrati.
It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the gas transfer unit of Nosrati to have the microchannels in a configuration such that there a manifold fluidically coupled to each of the plurality of channels also as taught by Nosrati, in order to improve flow control (Par. 26 of Nosrati) as “biomimetic designs can encompass surface treatments that mimic physiological processes or use biological principles to enhance performance through geometric optimization” (Par. 25 of Nosrati). Once the modification is made as discussed, each gas channel 110c-d of the gas transfer units 102b-d of Nosrati will be coupled to a gas outlet manifold as taught by the microchannel embodiment of Nosrati, which connects all channels toward a larger channel as seen in Fig. 12C of Nosrati.
It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the depth channels, such that the first depth of the plurality of fluid collection channels is at least twice a second depth of the plurality of blood channels, in order to fit the particular procedure being done since this claimed dimension of the channels does not change the fluid transfer unit ability to perform mass exchange in blood treatment. Since applicant has not given any criticality to why the dimension disclosed has any importance to the function of the claimed device (Par. 69 of Applicant’s PG-Pub), the Federal Circuit held that, where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device. In Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777. Moreover, Nosrati also allows for varying heights of microchannels (Par. 396 of Nosrati), in order to maximize diffusion and convection of the desirable substances, such as blood, dialysate, fluids, etc. (Par. 396 of Nosrati).
Furthermore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Nosrati to further include a gas outlet of the housing as taught by Kniazeva, as it is known in the art that a gas outlet is used to deliver the waste gas out of the system and maintain the established flow within the device.
It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the gas outlet of Nosrati in view of Kniazeva to include a pressure regulator as taught by Borenstein, in order to regulate the pressure within the pressure vessel and maintain a predetermined pressure (Par. 27 of Borenstein) in the gas channels.
It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the gas outlet of Nosrati in view of Kniazeva in view of Borenstein to further include an external vent as taught by Gremel, in order to vent the interior hollow passage of the gas outlet, and consequently the interior of the oxygenator/gas unit, to ambient pressure (Col. 3, line 14-21 of Gremel).
Lastly, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of the combination to further incorporate a pump at the fluid outflow as taught by Charest, in order to draw filtrate out of the device (Par. 95 of Charest). Furthermore, having a pump also means maintain and controlling the hematocrit level within the blood device (Par. 97 of Charest). It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of the combination to further incorporate a transmembrane pressure and a controller as taught by Charest, since both components help maintain a predetermined pressure difference between the channels (Par. 143 of Charest). These electronic components ensure that the patient’s blood remains healthy (Par. 72 of Charest).
Regarding claim 2, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 1. The combination further discloses a blood inlet manifold (Par. 233 of Nosrati – inflow tubing attached to a manifold for dividing blood) having channels (Fig. 12C of Nosrati – channels branching from manifolds) fluidically coupled to each of the plurality of blood channels 110a-b (Fig. 12C of Nosrati) in both the plurality of gas transfer units 102b-d (Fig. 7 of Nosrati) and the fluid transfer unit 102a (Fig. 7 of Nosrati and Par. 233 of Nosrati).
Once the combination is made as discussed in claim 1, both gas transfer units and the fluid transfer unit of Nosrati will have a plurality of blood channels 110a-b in layer 104, thus the blood inlet manifold will deliver blood into said plurality of blood channels 110a-b in layer 104 of each unit 102. Thus, the limitation is met.
Regarding claim 3, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 2. The combination further discloses a blood exit manifold (Par. 233 of Nosrati – outflow tubing attached to a manifold for dividing blood) having channels (Fig. 12C of Nosrati – channels branching from manifolds) fluidically coupled to each of the plurality of blood channels 110a-b (Fig. 12C of Nosrati) in both the plurality of gas transfer units 102b-d (Fig. 7 of Nosrati) and the fluid transfer unit 102a (Fig. 7 of Nosrati and Par. 233 of Nosrati).
Once the combination is made as discussed in claim 2, both gas transfer units and the fluid transfer unit of Nosrati will have a plurality of blood channels 110a-b in layer 104, thus the blood outlet manifold will collect blood from said plurality of blood channels 110a-b in layer 104 of each unit 102. Thus, the limitation is met.
Regarding claim 4, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 3. The combination further discloses wherein further comprising a fluid exit manifold (Par. 233 of Nosrati – outflow tubing attached to a manifold for dividing dialysate to each microfluidic chip 106) is fluidically coupled to each of the plurality of fluid collection channels 110c-d (Fig. 4B of Nosrati) in the fluid transfer unit 102a (Fig. 7 of Nosrati and Par. 233 of Nosrati).
Once the combination is made as discussed in claim 3, the fluid transfer unit 102a of Nosrati will have a plurality of fluid collection channels 110c-d in layer 106, thus the fluid exit manifold will collect fluid from said plurality of fluid collection channels 110c-d in layer 106 of each unit 102a.
Regarding claim 6, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 4. The combination further discloses a pressure regulator 154 (Par. 233 of Nosrati – micro-valve 154) configured to maintain the transmembrane pressure at the target transmembrane pressure (Par. 233 of Nosrati – “factors such as pressure dictate the position of the micro-valve 154”; Examiner notes that the position of a valve, i.e. closed or open or partially open, is known to affect flow rate and pressure).
However, the combination does not explicitly disclose a pressure regulator fluidly is coupled to the pump and the fluid exit manifold. Examiner notes that the current pressure regulator 154 of Nosrati is placed at the blood inlet manifold (Fig. 15).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have rearranged the location of the pressure regulator/valve of the combination to so it was at the fluid exit manifold and fluidly coupled to the pump, since this claimed position of the pressure regulator does not change the valve ability to regulate fluid flow through the microfluidic channels and manifold that ultimately affects transmembrane. Since applicant has not given any criticality to why the position of the pressure regulator disclosed has any importance to the function of the claimed device (Applicant’s Page 15-16), the Federal Circuit held that, where the only difference between the prior art and the claims was the position of a claimed element and altering the position of that claimed element would not have modified the operation of the device, the claimed device was not patentably distinct from the prior art device because it merely involved the rearrangement of parts. See MPEP 2144. In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950). Therefore, one of ordinary skill in the art would have been motivated to rearrange the valve of the combination in the claimed manner in order to determine the mode of movement for fluid (Par. 233 of Nosrati) and halt the fluid flow if the layers are not properly aligned (Par. 233 of Nosrati), which can potentially lead to inefficient ultrafiltration within the machine.
Regarding claim 9, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 1. However, the combination does not disclose an upper surface of the third polymer layer is bonded to a lower surface of the second polymer layer of one of the plurality of gas transfer units.
According to the current configuration of each Nosrati’s unit, the current device of Nosrati demonstrates a lower surface of the third polymer layer 106 (Fig. 7; third polymer layer 106 belongs to the fluid transfer unit 102a) is bonded to an upper surface of the second polymer layer 104 (Fig. 4B) of one 102b of the plurality of gas transfer units 102b-d (Fig. 4B and Fig. 7), which is opposite of the claimed limitation.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have rearranged the position of the fluid transfer unit 102a so it was at the bottom of the device, below the gas transfer unit 102d in Fig. 7 of Nosrati (see annotated Fig. 7 below), since this claimed position of the polymer layers does not change the polymer layer’s ability to receive fluids, including blood, and treat the blood by flowing blood through the permeable membrane. Since applicant has not given any criticality to why the position of the polymer layers disclosed has any importance to the function of the claimed device, the Federal Circuit held that, where the only difference between the prior art and the claims was the position of a claimed element and altering the position of that claimed element would not have modified the operation of the device, the claimed device was not patentably distinct from the prior art device because it merely involved the rearrangement of parts. See MPEP 2144. In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950). Therefore, one of ordinary skill in the art would have been motivated to make such an arrangement, not only because the new arrangement will still perform the blood treating function, but also because having the fluid transfer unit at the bottom is more optimal in machine stabilization. More specifically, one of ordinary skill in the art would recognize that the weight of both blood and fluid removed at the bottom are likely to provide better stabilization for the machine, as opposed to when the weight is at the top. Furthermore, blood can proceed to gas exchange with less weight going into the gas transfer units given the fluid removed, i.e. water removed.
Furthermore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have rearranged the position of layers from both the gas transfer units and the fluid transfer unit of Nosrati so that the polymer layer 104 is at the bottom and the polymer layer 106 is at the top (see annotated Fig. 7 below), since the mere swapped position of polymer layers 104 and 106 does not change the polymer layer’s ability to form micro-channels of blood and fluid/gas. Since applicant has not given any criticality to why the position of the polymer layers disclosed has any importance to the function of the claimed device, the Federal Circuit held that, where the only difference between the prior art and the claims was the position of a claimed element and altering the position of that claimed element would not have modified the operation of the device, the claimed device was not patentably distinct from the prior art device because it merely involved the rearrangement of parts. See MPEP 2144. In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950). Therefore, one of ordinary skill in the art would have been motivated to make such an arrangement, not only because the new rearrangement will still perform the blood treating function, but also because the rearrangement will relieve the permeable membrane of the downward pressure of blood as flowing blood is now putting its weight onto the channels 104 instead. Given this rearrangement, the integrity of permeable membrane can be maintained for prolonged operation of the machine. Once the rearrangement is made as discussed, the third polymer layer 106 now has an upper outer surface, and the second polymer layer 104 now has a lower outer surface; when stacked upon each other, “an upper surface of the third polymer layer 106 (see annotated Fig. 7 below; third polymer 106 belongs to the fluid transfer unit 102a) is bonded to a lower surface of the second polymer layer 104 (see annotated Fig. 7 below) of one 102d of the plurality of gas transfer units 102b-d (see annotated Fig. 7 below)”. Thus, the limitation is met.
Regarding claim 10, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 9. The combination further discloses the one of the plurality of gas transfer units 102d (see annotated Fig. 7 below of Nosrati) is at an end of a stack of the plurality of gas transfer units 102b-d (see annotated Fig. 7 below of Nosrati – gas transfer unit 102d is at the bottom end of the stack). Examiner notes that once the rearrangement is made as discussed in claim 9, the stack of gas transfer units will be position on top of a single fluid transfer unit as claimed. Thus, the limitation is met.
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Annotated Fig. 7 of Nosrati (modified as discussed in claim 9)
Regarding claim 11, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 1. However, the combination does not disclose a lower surface of the fourth polymer layer is bonded to an upper surface of the first polymer layer of one of the plurality of gas transfer units.
According to the current configuration of each Nosrati’s unit, the current device of Nosrati demonstrates the fourth polymer layer 104 (Fig. 7; fourth polymer layer 104 belongs to the fluid transfer unit 102a) is not bonded to any surface since said layer 104 of unit 102a is at the very top of the system (Fig. 4B and Fig. 7).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have rearranged the position of layers from both the gas transfer units and the fluid transfer unit of Nosrati so that the polymer layer 104 is at the bottom and the polymer layer 106 is at the top (see annotated Fig. 7' of Nosrati below), since the mere swapped position of the polymer layers 104 and 106 does not change the polymer layer’s ability to form micro-channels of blood and fluid/gas. Since applicant has not given any criticality to why the position of the polymer layers disclosed has any importance to the function of the claimed device, the Federal Circuit held that, where the only difference between the prior art and the claims was the position of a claimed element and altering the position of that claimed element would not have modified the operation of the device, the claimed device was not patentably distinct from the prior art device because it merely involved the rearrangement of parts. See MPEP 2144. In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950). Therefore, one of ordinary skill in the art would have been motivated to make such an arrangement, not only because the new rearrangement will still perform the blood treating function, but also because the rearrangement will relieve the permeable membrane of the downward pressure of blood as flowing blood is now putting its weight onto the channels 104 instead. Given this rearrangement, the integrity of permeable membrane can be maintained for prolonged operation of the machine. Once the rearrangement is made as discussed, the fourth polymer layer 104 now has a lower surface, and the first polymer layer 106 now has an upper surface; when stacked upon each other, “a lower surface of the fourth polymer layer 104 (see annotated Fig. 7’ of Nosrati below; fourth polymer layer 104 belongs to the fluid transfer unit 102a) is bonded to an upper surface of the first polymer layer 106 (see annotated Fig. 7’ of Nosrati below) of one 102b of the plurality of gas transfer units 102b-d (see annotated Fig. 7’ of Nosrati below).” Thus, the limitation is met.
Regarding claim 12, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 11. The combination further discloses that the one of the plurality of gas transfer units 102b (see annotated Fig. 7’ below of Nosrati) is at an end of a stack of the plurality of gas transfer units 102b-d (see annotated Fig. 7’ below of Nosrati; gas transfer unit 102b is at the top end of the stack). Examiner notes that once the rearrangement is made as discussed in claim 11, the stack of gas transfer units will be position below a single fluid transfer unit as claimed. Thus, the limitation is met.
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Annotated Fig. 7’ of Nosrati (modified as discussed in claim 11)
Regarding claim 20, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 1. However, the combination does not explicitly disclose the blood channels of the plurality of gas transfer units are substantially identical in size and shape to the blood channels of the fluid transfer unit.
While Nosrati does not explicitly disclose the specific size of the blood channels in both units, it would have been obvious to one of ordinary skill in the art at the time of the invention to have changed the size of the blood channels of the combination so that blood channels in both units are substantially identical, since such a modification would have involved a mere change in the size (or dimension) of a component. A change in size (dimension) is generally recognized as being within the level of ordinary skill in the art. In re Rose, 220 F.2d 459, 105 USPQ 237 (CCPA 1955). Where the only difference between the prior art and the claims is a recitation of relative dimensions of the claimed device, and the device having the claimed dimensions would not perform differently than the prior art device, the claimed device is not patentably distinct from the prior art device, Gardner v. TEC Systems, Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 USPQ 232 (1984). Thus, the limitation of “the blood channels of the plurality of gas transfer units are substantially identical in size to the blood channels of the fluid transfer unit” is met.
Furthermore, it is well known in the art that the channels can have a variety of shapes of configurations, including circular, rectangular, trapezoidal, etc. (as evidenced by Par. 33 of Nosrati). Therefore, it would have been obvious to one having ordinary skill in the art at the time the invention was made to have modified the device of the combination to have substantially identical in shape for the blood channels, whether they are circular, rectangular, etc., as such modification would involve a mere change in configuration. It has been held that a change in configuration of shape of a device is obvious, absent persuasive evidence that a particular configuration is significant. In re Dailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966). Therefore, one of ordinary skill in the art would have been motivated to have substantially identical in shape for the blood channels not only because it requires a mere change in shapes, but also because identical shapes will maintain a consistent flow profile throughout the machine. Thus, the limitation of “the blood channels of the plurality of gas transfer units are substantially identical in size and shape to the blood channels of the fluid transfer unit” is met.
Regarding claim 21, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 1. However, the combination does not disclose the gas channels of the plurality of gas transfer units are substantially identical in size and shape to the fluid collection channels of the fluid transfer unit.
While Nosrati does not explicitly disclose the specific size of the gas/fluid channels in both units, it would have been obvious to one of ordinary skill in the art at the time of the invention to have changed the size of the blood channels of the combination so that gas/fluid channels in both units are substantially identical, since such a modification would have involved a mere change in the size (or dimension) of a component. A change in size (dimension) is generally recognized as being within the level of ordinary skill in the art. In re Rose, 220 F.2d 459, 105 USPQ 237 (CCPA 1955). Where the only difference between the prior art and the claims is a recitation of relative dimensions of the claimed device, and the device having the claimed dimensions would not perform differently than the prior art device, the claimed device is not patentably distinct from the prior art device, Gardner v. TEC Systems, Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 USPQ 232 (1984). Thus, the limitation of “the gas channels of the plurality of gas transfer units are substantially identical in size to the fluid collection channels of the fluid transfer unit.” is met.
Furthermore, it is well known in the art that the channels can have a variety of shapes of configurations, including circular, rectangular, trapezoidal, etc. (as evidenced by Par. 33 of Nosrati). Therefore, it would have been obvious to one having ordinary skill in the art at the time the invention was made to have modified the device of the combination to have substantially identical in shape for the gas/fluid channels, whether they are circular, rectangular, etc., as such modification would involve a mere change in configuration. It has been held that a change in configuration of shape of a device is obvious, absent persuasive evidence that a particular configuration is significant. In re Dailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966). Therefore, one of ordinary skill in the art would have been motivated to have substantially identical in shape for the blood channels not only because it requires a mere change in shapes, but also because identical shapes will maintain a consistent flow profile throughout the machine. Thus, the limitation of “the gas channels of the plurality of gas transfer units are substantially identical in size and shape to the fluid collection channels of the fluid transfer unit.” is met.
Regarding claim 22, Nosrati discloses a blood treatment module 100 (Fig. 1) comprising:
a first plurality of polymer layers 104 (Fig. 4B and Fig. 7 – a plurality of units 102, each unit 102 comprises a polymer layer 104, hence the plurality of polymer layers 104) each having a plurality of blood channels 110a-b (Fig. 4A and Par. Par. 234 – “micro-channels 110 for carrying blood”) having a first depth (Fig. 4A; Examiner notes that a channel inherently has a depth);
a second plurality of polymer layers 106 (Fig. 4B and Fig. 7 – a plurality of units 102, each unit 102 comprises a polymer layer 106, hence the plurality of polymer layers 106) each having one of a plurality of gas channels or fluid collection channels 110c-d (Fig. 4A and Par. 234 – “micro-channels 110 for carrying dialysate”; Examiner contends that channels 110c-d are also capable of delivering gas since gas is also a fluid), each of the first plurality of polymer layers 104 (Fig. 4B) secured to at least one of the second plurality of polymer layers 106 (Fig. 4B) with a membrane 108 (Fig. 4B – layer 104 and layer 106 are assembled with a membrane 108 therebetween), at least one of the membranes 108 (Fig. 4B) being a fluid permeable membrane 108 (Fig. 4B and Par. 228 – “the semipermeable membrane 108 enables passage of toxins, water…”), wherein at least one layer of the second plurality of polymer layers 106 (Fig. 4A) having fluid collection channels 110c-d (Fig. 4A) has a second depth (Examiner notes that a channel inherently has a depth); and
a housing containing 114 (Fig. 7 – microfluidic housing 114) the first plurality of polymer layers 104 (Fig. 4B) and the second plurality of polymer layers 106 (Fig. 4B and Fig. 7 – each unit 102 comprises a layer 104 and a layer 106; thus, the housing 114 contains layers 104 and 106) such that the blood channels 110a-b (Fig. 4A), gas channels 110c-d (Fig. 4A), and fluid collection channels 110c-d (Fig. 4A) collectively define a single extracorporeal bonded circuit (Fig. 7, Par. 85 – “The Combined microfluidic-based kidney and Liver dialysis device can be made in a compact form to be used for many different types of Multi-System/Multi-Organ Dysfunctions”, and Par. 104 – “This device utilizes a plurality of various microfluidic-based chipset units/modules/segments”; thus indicating that multiple units form a blood processing device).
However, Nosrati does not explicitly disclose a plurality of the membranes being gas permeable membranes, a second depth is at least twice the first depth of the plurality of blood channels, wherein each of at least two layers of the second plurality of polymer layers comprises a gas outlet manifold fluidically coupled to the plurality of gas channels; and with the first plurality of polymer layers fluidly connected via a common entry manifold, the housing comprising a gas outlet coupled to the gas outlet manifold of each of the at least two layers, the gas outlet comprising a pressure regulator to maintain a target gas pressure in the at least two layers, the gas outlet configured to ventilate gas from the at least two layers via a vent; a pump coupled to a fluid outlet manifold of the fluid collection channels and configured to control a rate at which fluid is drawn from the fluid collection channels; and a controller configured to: receive a transmembrane pressure measurement across the fluid permeable membrane from a transmembrane pressure sensor, and adjust, based on the transmembrane pressure measurement, a rate at which the pump draws fluid from the plurality of fluid collection channels to maintain a target transmembrane pressure across the fluid permeable membrane during a blood filtration process.
Nosrati, in another embodiment, teaches a plurality of the membranes being gas permeable membranes (Par. 74-75 – the Oxygenation unit will receive a specific or various semipermeable ECMO membrane to allow manipulation of gases).
Nosrati, in another embodiment for the microchannels, teaches the polymer layer (Par. 211 – “micro-channels fabricated… on a microfluidic chip”) comprises an outlet manifold (see annotated Fig. 12C above – “outlet manifold” is the primary branch on the left) and fluidically coupled to each of the plurality of channels (see annotated Fig. 12C above – the “outlet manifold” branches into smaller channels).
Kniazeva, in the same field of endeavor of microfluidic extracorporeal lung oxygenation device (Title), teaches with the first plurality of polymer layers (Fig. 1 – stacked layers with vascular channels) fluidly connected via a common entry manifold (see annotated Fig. 1 above), the housing (see annotated Fig. 1 above – “…of the housing” can be seen as the device) comprising a gas outlet (see annotated Fig. 1 below – “gas outlet of the housing”) coupled to the gas outlet manifold of each of the at least two layers (see annotated Fig. 1 below – the annotated port fluidly communicates with every outlet manifold at each gas unit of the stack).
Borenstein, in the same field of endeavor of microfluidic device (Title), teaches a pressure regulator 110 (Fig. 1A – pressure regulator 110) to maintain a target gas pressure in the at least two layers (Par. 27 – “one or more pressure regulators 110 to regulate the pressure within the pressure vessel 104 and maintain a predetermined pressure within the pressure vessel 104”; Examiner also notes that the pressure within the pressure vessel 104 directly relates to the pressure of the plurality of gas channels, as discussed in Par. 26 – “…gas channels of the microfluidic device 102 are open and exposed to the ambient, atmospheric conditions created within the pressure vessel 104…”; therefore, the pressure regulator 110 does in fact regulates the pressure of all the gas channels).
Gremel, in the same field of endeavor of devices for removing gases from blood (Col. 1, line 6-7), teaches the gas outlet 12 (Fig. 2 – outlet connector 12) configured to ventilate gas (Col. 3, line 14-16 – “Hole 18 vents the interior hollow passage of the outlet connector 12, and consequently the interior of the oxygenator 2, to ambient pressure”) from the layers 4 (Fig. 1 – fiber bundle 4) via a vent 18 (Fig. 2 – vent holes 18).
Charest, in the same field of endeavor of extracorporeal microfluidic device (Abstract), teaches a pump (Fig. 5B, and Par. 95 – outflow pump 517) coupled to a fluid outlet manifold 116 (Fig. 1A – filtrate outlet manifold 116 for exemplary demonstration; Par. 95 – “The device 513 also includes an outflow pump 517 in-line with the filtrate channel 502”; Fig. 5B shows the outer loop of channel 502) of the fluid collection channels 502 (Fig. 5B – filtrate channel 502, and Par. 81 – “Each of the devices described in relation to FIGS. 5A, 5B, 6A-10, and 13 can form a layer 102 of the device illustrated in FIG. 1A”, thus there can be a stack of layers 500 to form a device like Fig. 1A with a fluid outlet manifold like 116 and multiple channels 502) and configured to control a rate at which fluid is drawn from the fluid collection channels 502 (Fig. 5B and Par. 95 – “The outflow pump 517 is configured to draw filtrate out of the filtrate channel 502”; Examiner also notes that pumps inherently controls a rate of fluid flow in any given channel); and
Charest, in another embodiment, teaches a controller 300 (Fig. 3 – control system 300) configured to:
receive a transmembrane pressure measurement across the fluid permeable membrane from a transmembrane pressure sensor 304 (Fig. 3 – pressure sensor 304, and Par. 143 – “The control system can receive pressure measurement from the pressure sensors placed along the length of the blood and filtrate channels to ensure that the pressure difference remains below a critical transmembrane pressure along the length of the device”), and
adjust, based on the transmembrane pressure measurement, a rate at which the pump draws fluid from the plurality of fluid collection channels to maintain a target transmembrane pressure across the fluid permeable membrane during a blood filtration process (Par. 6 – “the control system is configured to modify the state of the first controllable flow control device responsive to an output of the at least one pressure sensor. In some implementations, the first controllable flow control device is… an outflow pump”; and Par. 5 – “the control system is configured to control the first controllable flow control device to maintain a pressure difference between a pressure of a first fluid flowing through the blood channel and a pressure of a second fluid flowing through the filtrate channel that is below a critical transmembrane pressure”).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the blood treatment module of Nosrati to further include gas permeable membranes, also as taught by Nosrati, in order to produce a microfluidic-based system that mimics properties of multiple human organs and tissues (Abstract of Nosrati), in this instant case, blood/fluid exchange for toxins removal similar to the kidney and blood/gas exchange for carbon dioxide removal similar to the lung. By combining various functioning modules, these building blocks can simultaneously perform various functions that otherwise would have existed individually in individual dialysis device and organ support systems, such as albumin/lipid dialysis, water purification, bioreactors, kidney support, lung support, etc. (Abstract and Par. 462).
It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the second plurality of polymer layers of Nosrati to have the microchannels in a configuration such that there a manifold fluidically coupled to each of the plurality of channels also as taught by Nosrati, in order to improve flow control (Par. 26 of Nosrati) as “biomimetic designs can encompass surface treatments that mimic physiological processes or use biological principles to enhance performance through geometric optimization” (Par. 25 of Nosrati). Once the modification is made as discussed, each gas channel 110c-d of the polymer layers 106 of Nosrati will be coupled to a gas outlet manifold as taught by the microchannel embodiment of Nosrati, which connects all channels toward a larger channel as seen in Fig. 12C of Nosrati.
It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the depth channels, such that the first depth of the plurality of fluid collection channels is at least twice a second depth of the plurality of blood channels, in order to fit the particular procedure being done since this claimed dimension of the channels does not change the fluid transfer unit ability to perform mass exchange in blood treatment. Since applicant has not given any criticality to why the dimension disclosed has any importance to the function of the claimed device (Par. 69 of Applicant’s PG-Pub), the Federal Circuit held that, where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device. In Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777. Moreover, Nosrati also allows for varying heights of microchannels (Par. 396 of Nosrati), in order to maximize diffusion and convection of the desirable substances, such as blood, dialysate, fluids, etc. (Par. 396 of Nosrati).
Furthermore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Nosrati to further include a gas outlet of the housing as taught by Kniazeva, as it is known in the art that a gas outlet is used to deliver the waste gas out of the system and maintain the established flow within the device.
It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the gas outlet of Nosrati in view of Kniazeva to include a pressure regulator as taught by Borenstein, in order to regulate the pressure within the pressure vessel and maintain a predetermined pressure (Par. 27 of Borenstein) in the gas channels.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the gas outlet of Nosrati in view of Kniazeva in view of Borenstein to further include an external vent as taught by Gremel, in order to vent the interior hollow passage of the gas outlet, and consequently the interior of the oxygenator/gas unit, to ambient pressure (Col. 3, line 14-21 of Gremel).
Lastly, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of the combination to further incorporate a pump at the fluid outflow as taught by Charest, in order to draw filtrate out of the device (Par. 95 of Charest). Furthermore, having a pump also means maintain and controlling the hematocrit level within the blood device (Par. 97 of Charest). It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of the combination to further incorporate a transmembrane pressure and a controller as taught by Charest, since both components help maintain a predetermined pressure difference between the channels (Par. 143 of Charest). These electronic components ensure that the patient’s blood remains healthy (Par. 72 of Charest).
Regarding claim 23, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 22. The combination further discloses the fluid permeable membrane 108 (Fig. 4B of Nosrati) is an ultrafiltration membrane (Par. 228 of Nosrati – membrane 108 enables passage of water, and Par. 74 – ultrafiltration membrane).
Regarding claim 24, Nosrati discloses a method of treating blood (Par. 221), the method comprising passing the blood 134 (Fig. 1) through a blood treatment module 100 (Fig. 1) to undergo gas transfer (Par. 74 – O Chipset (Oxygenation)) and fluid transfer (Par. 74 – UF Chipset (Ultrafiltration)) while remaining within a single bonded circuit (Fig. 7 – the chipsets are stacked to form a circuit, Par. 145 – “The present invention is directed to a modular and scalable microfluidic unit that each that utilizes different and various principles of microfluidics for performing different processes on blood and plasma. These processes includes but not limited to filtration, ultrafiltration, diafiltration, various forms of dialysis, hemoperfusion, plasma separation and etc. of any fluid, such as blood, plasma and lymph”, Par. 148-151 – “a modular microfluidic dialysis system, comprises: a plurality of microfluidic units, the plurality of microfluidic units configured to enable any one of different forms of blood filtration, ultrafiltration, diafiltration, plasma separation and dialysis of blood, the plurality of microfluidic basic building block units can be arranged in modular configuration in parallel or in series for enabling scalability, the plurality of microfluidic units at least partially fabricated from inert and biocompatible polymers commonly used in microfluidic such as a polymeric organosilicon compound…”; thus indicating a circuit throughout the module) of the blood treatment module 100 (Fig. 1), the blood treatment module 100 (Fig. 1) comprising:
a fluid transfer unit 102a (Fig. 4B – microfluidic chip unit 102a, and Par. 74 describes a variety of functional options for the microfluidic chip unit, i.e. hemodialysis function, ultrafiltration function, etc.), the fluid transfer unit 102a (Fig. 4B) including:
(i) a third polymer layer 106 (Fig. 4B and Par. 224 – “microfluidic unit 102 fabricated from any biocompatible polymer”) having a plurality of fluid collection channels 110c-d (Fig. 4A and Par. 234 – “micro-channels 110 for carrying dialysate”) defined therein, the plurality of fluid collection channels 110c-d (Fig. 4A) having a first depth (Fig. 4A; Examiner notes that a channel inherently has a depth),
(ii) a fourth polymer layer 104 (Fig. 4B and Par. 224 – “microfluidic unit 102 fabricated from any biocompatible polymer”) having a plurality of blood channels 110a-b (Fig. 4A and Par. 234 – “micro-channels 110 for carrying blood”) defined therein, and
(iii) a fluid permeable membrane 108 (Fig. 4B and Par. 228 – “the semipermeable membrane 108 enables passage of toxins, water…”) disposed between the plurality of fluid collection channels 110c-d (Fig. 4A) and the plurality of blood channels 110a-b (Fig. 4A – membrane 108 is sandwiched between layer 104 and layer 106) and providing for the transport of fluid from the plurality of blood channels 110a-b (Fig. 4B) into the plurality of fluid collection channels 110c-d (Fig. 4B and Par. 228 – “the semipermeable membrane 108 enables passage of toxins, water…”, thus indicating mass transfer across the membrane 108 between the fluid channels and the blood channels) while preventing transport of blood cells from the plurality of blood channels 110a-b (Fig. 4B) into the plurality of fluid collection channels 110c-d (Fig. 4B and (Par. 228 – “…form a permeable barrier between the blood and the dialysate”); and
a housing 114 (Fig. 7 – microfluidic housing 114) containing the fluid transfer unit 102a (Fig. 7 – microfluidic chipset 102a is within the housing 114).
However, Nosrati, in the same embodiment, does not explicitly disclose a plurality of gas transfer units, each of the plurality of gas transfer units including a first polymer layer having a plurality of gas channels, a second polymer layer having a plurality of blood channels, and a gas permeable membrane disposed between the plurality of gas channels and the plurality of blood channels and providing for the transport of gas between the plurality of gas channels and the plurality of blood channels, a gas outlet manifold fluidically coupled to each of the plurality of gas channels; a fluid transfer unit adhered to at least one of the plurality of gas transfer units, the fluid transfer unit comprising a transmembrane pressure sensor configured to measure a transmembrane pressure across the fluid permeable membrane; a housing containing the plurality of gas transfer units, such that, within the housing, the plurality of blood channels of the fluid transfer unit are fluidly coupled to the plurality of blood channels of the at least one gas transfer unit to define the single bonded circuit extending through the plurality of gas transfer units and the fluid transfer unit via a common blood entry manifold; and a gas outlet of the housing coupled to the gas outlet manifold of each of the plurality of gas transfer units, the gas outlet comprising a pressure regulator to maintain a target gas pressure in the plurality of gas channels of each of the plurality of gas transfer units, the gas outlet configured to ventilate gas from the plurality of gas transfer units via a vent; and a pump coupled to a fluid outlet manifold of the fluid transfer unit and configured to control a rate at which fluid is drawn from the plurality of fluid collection channels of the fluid transfer unit; and a controller configured to: receive transmembrane pressure measurement across the fluid permeable membrane from the transmembrane pressure sensor, and adjust, based on the transmembrane pressure measurement, a rate at which the pump draws fluid from the plurality of fluid collection channels to maintain a target transmembrane pressure across the fluid permeable membrane while passing the blood through the blood treatment module.
Nosrati, in another embodiment, teaches a plurality of gas transfer units 102b-d (Fig. 4B and Fig. 7 – multiple units 102b-d, and Par. 74 describes a variety of functional options for the microfluidic chip unit, i.e. oxygenation, etc.), each of the gas transfer units 102b-d (Fig. 7 and Par. 41 – “multiple types of microfluidic chip units 102a-d may be used…”) including:
a first polymer layer 106 (Fig. 4B and Par. 224 – “microfluidic unit 102 fabricated from any biocompatible polymer”) having a plurality of gas channels 110c-d (Fig. 4A and Par. 234 – “micro-channels 110 for carrying dialysate”; Examiner notes that channels 110 is capable of receiving types of fluids, which encompasses gas),
a second polymer layer 104 (Fig. 4B and Par. 224 – “microfluidic unit 102 fabricated from any biocompatible polymer”) having a plurality of blood channels 110a-b (Fig. 4A and Par. 234 – “micro-channels 110 for carrying blood”),
a gas permeable membrane 108 (Fig. 4B and Par. 74-75 – the Oxygenation unit will receive an ECMO membrane to allow manipulation of gases) disposed between the plurality of gas channels 110c-d (Fig. 4A) and the plurality of blood channels 110a-b (Fig. 4A) and providing for the transport of gas (Par. 75 – “Each chipset module utilizes a specific semipermeable membrane to allow manipulation of gases”) between the plurality of gas channels 110c-d (Fig. 4A) and the plurality of blood channels 110a-b (Fig. 4A);
a fluid transfer unit 102a (Fig. 7) adhered to at least one of the plurality of gas transfer units 102b-d (Fig. 7 – stacking of microfluidic units 102); and
a housing 114 (Fig. 7 – microfluidic housing 114) containing the plurality of gas transfer units 102b-d (Fig. 7) and the fluid transfer unit 102a (Fig. 7) such that, within the housing 114 (Fig. 7), the plurality of blood channels of the fluid transfer unit 102a (Fig. 7) are fluidly coupled to the plurality of blood channels of the at least one gas transfer unit 102b-d (Fig. 7) to define the single bonded circuit (Fig. 7 – the chipsets are stacked to form a circuit, Par. 145 – “The present invention is directed to a modular and scalable microfluidic unit that each that utilizes different and various principles of microfluidics for performing different processes on blood and plasma. These processes includes but not limited to filtration, ultrafiltration, diafiltration, various forms of dialysis, hemoperfusion, plasma separation and etc. of any fluid, such as blood, plasma and lymph”, Par. 148-151 – “a modular microfluidic dialysis system, comprises: a plurality of microfluidic units, the plurality of microfluidic units configured to enable any one of different forms of blood filtration, ultrafiltration, diafiltration, plasma separation and dialysis of blood, the plurality of microfluidic basic building block units can be arranged in modular configuration in parallel or in series for enabling scalability, the plurality of microfluidic units at least partially fabricated from inert and biocompatible polymers commonly used in microfluidic such as a polymeric organosilicon compound…”; thus indicating that blood channels are fluidly connected throughout the device) extending through the plurality of gas transfer units 102b-d (Fig. 7) and the fluid transfer unit 102a (Fig. 7).
Examiner strongly notes that each microfluidic unit of Nosrati comprises a fundamental build of three layers as shown in Fig. 4B, and the difference between an oxygenation and other fluid units relies on the functioning membrane utilized (Par. 74 and Par. 75). Thus, it allows creators to combine many microfluidic units that function as various organs/tissues and scale the treatment system (Par. 76).
Nosrati, in another embodiment for the microchannels, teaches an outlet manifold (see annotated Fig. 12C below – “outlet manifold” is the primary branch on the left) and fluidically coupled to each of the plurality of channels (see annotated Fig. 12C below – the “outlet manifold” branches into smaller channels).
Kniazeva, in the same field of endeavor of microfluidic extracorporeal lung oxygenation device (Title), teaches via a common blood entry manifold (see annotated Fig. 1 above), a gas outlet of the housing (see annotated Fig. 1 below – “gas outlet of the housing” can be seen as the gas outlet of the device) coupled to the gas outlet manifold of each of the plurality of gas transfer units (see annotated Fig. 1 below – the annotated port fluidly communicates with every outlet manifold at each gas unit of the stack).
Borenstein, in the same field of endeavor of microfluidic device (Title), teaches a pressure regulator 110 (Fig. 1A – pressure regulator 110) to maintain a target gas pressure in the plurality of gas channels of each of the plurality of gas transfer units (Par. 27 – “one or more pressure regulators 110 to regulate the pressure within the pressure vessel 104 and maintain a predetermined pressure within the pressure vessel 104”; Examiner also notes that the pressure within the pressure vessel 104 directly relates to the pressure of the plurality of gas channels, as discussed in Par. 26 – “…gas channels of the microfluidic device 102 are open and exposed to the ambient, atmospheric conditions created within the pressure vessel 104…”; therefore, the pressure regulator 110 does in fact regulates the pressure of the gas channels).
Gremel, in the same field of endeavor of devices for removing gases from blood (Col. 1, line 6-7), teaches the gas outlet 12 (Fig. 2 – outlet connector 12) configured to ventilate gas (Col. 3, line 14-16 – “Hole 18 vents the interior hollow passage of the outlet connector 12, and consequently the interior of the oxygenator 2, to ambient pressure”) from the plurality of gas transfer units 4 (Fig. 1 – fiber bundle 4) via a vent 18 (Fig. 2 – vent holes 18).
Charest, in the same field of endeavor of extracorporeal microfluidic device (Abstract), teaches a pump (Fig. 5B, and Par. 95 – outflow pump 517) coupled to a fluid outlet manifold 116 (Fig. 1A – filtrate outlet manifold 116 for exemplary demonstration; Par. 95 – “The device 513 also includes an outflow pump 517 in-line with the filtrate channel 502”; Fig. 5B shows the outer loop of channel 502) of the fluid transfer unit 513 (Fig. 5B – microfluidic convective clearance device 513, and Par. 81 – “Each of the devices described in relation to FIGS. 5A, 5B, 6A-10, and 13 can form a layer 102 of the device illustrated in FIG. 1A”, thus there can be a stack of layers 500 to form a device like Fig. 1A with a fluid outlet manifold like 116 and channels 502) and configured to control a rate at which fluid is drawn from the plurality of fluid collection channels 502 (Fig. 5B – filtrate channel 502) of the fluid transfer unit 513 (Fig. 5B and Par. 95 – “The outflow pump 517 is configured to draw filtrate out of the filtrate channel 502”; Examiner also notes that pumps inherently controls a rate of fluid flow in any given channel); and
Charest, in another embodiment, teaches the fluid transfer unit 300 (Fig. 3) comprising a transmembrane pressure sensor 304 (Fig. 3 – pressure sensor 304, and Par. 73 – “Pressure sensors 304 and flow sensors 306 can be placed inside the blood channel”, and Par. 142 – “the control system receives pressure measurements from pressure sensors placed along the length of any of the filtrate, blood, and infusate channels”) configured to measure a transmembrane pressure across the fluid permeable membrane (Par. 143 – “The control system can receive pressure measurement from the pressure sensors placed along the length of the blood and filtrate channels to ensure that the pressure difference remains below a critical transmembrane pressure along the length of the device”);
a controller 300 (Fig. 3 – control system 300) configured to:
receive transmembrane pressure measurement across the fluid permeable membrane from the transmembrane pressure sensor 304 (Fig. 3, and Par. 143 – “The control system can receive pressure measurement from the pressure sensors placed along the length of the blood and filtrate channels to ensure that the pressure difference remains below a critical transmembrane pressure along the length of the device”), and
adjust, based on the transmembrane pressure measurement, a rate at which the pump draws fluid from the plurality of fluid collection channels to maintain a target transmembrane pressure across the fluid permeable membrane during a blood filtration process (Par. 6 – “the control system is configured to modify the state of the first controllable flow control device responsive to an output of the at least one pressure sensor. In some implementations, the first controllable flow control device is… an outflow pump”; and Par. 5 – “the control system is configured to control the first controllable flow control device to maintain a pressure difference between a pressure of a first fluid flowing through the blood channel and a pressure of a second fluid flowing through the filtrate channel that is below a critical transmembrane pressure”).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the blood treatment module of Nosrati that has a fluid transfer unit to further include a plurality of gas transfer units, also as taught by Nosrati, in order to produce a microfluidic-based system that mimics properties of multiple human organs and tissues (Abstract of Nosrati). In other words, by combining various functioning modules, these building blocks can simultaneously perform various functions that otherwise would have existed individually in individual dialysis device and organ support systems, such as albumin/lipid dialysis, water purification, bioreactors, kidney support, lung support, etc. (Abstract and Par. 462). Once the combination is made, a plurality of gas transfer units and a fluid transfer unit will be adhered/stacked and located inside a housing as seen in Fig. 7 of Nosrati. Thus, the limitation of “a fluid transfer unit adhered to at least one of the plurality of gas transfer units; and a housing containing the plurality of gas transfer units” is met.
It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the gas transfer unit of Nosrati to have the microchannels in a configuration such that there a manifold fluidically coupled to each of the plurality of channels also as taught by Nosrati, in order to improve flow control (Par. 26 of Nosrati) as “biomimetic designs can encompass surface treatments that mimic physiological processes or use biological principles to enhance performance through geometric optimization” (Par. 25 of Nosrati). Once the modification is made as discussed, each gas channel 110c-d of the gas transfer units 102b-d of Nosrati will be coupled to a gas outlet manifold as taught by the microchannel embodiment of Nosrati, which connects all channels toward a larger channel as seen in Fig. 12C of Nosrati.
It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the depth channels, such that the first depth of the plurality of fluid collection channels is at least twice a second depth of the plurality of blood channels, in order to fit the particular procedure being done since this claimed dimension of the channels does not change the fluid transfer unit ability to perform mass exchange in blood treatment. Since applicant has not given any criticality to why the dimension disclosed has any importance to the function of the claimed device (Par. 69 of Applicant’s PG-Pub), the Federal Circuit held that, where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device. In Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777. Moreover, Nosrati also allows for varying heights of microchannels (Par. 396 of Nosrati), in order to maximize diffusion and convection of the desirable substances, such as blood, dialysate, fluids, etc. (Par. 396 of Nosrati).
Furthermore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Nosrati to further include a gas outlet of the housing as taught by Kniazeva, as it is known in the art that a gas outlet is used to deliver the waste gas out of the system and maintain the established flow within the device.
It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the gas outlet of Nosrati in view of Kniazeva to include a pressure regulator as taught by Borenstein, in order to regulate the pressure within the pressure vessel and maintain a predetermined pressure (Par. 27 of Borenstein) in the gas channels.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the gas outlet of Nosrati in view of Kniazeva in view of Borenstein to further include an external vent as taught by Gremel, in order to vent the interior hollow passage of the gas outlet, and consequently the interior of the oxygenator/gas unit, to ambient pressure (Col. 3, line 14-21 of Gremel).
Lastly, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of the combination to further incorporate a pump at the fluid outflow as taught by Charest, in order to draw filtrate out of the device (Par. 95 of Charest). Furthermore, having a pump also means maintain and controlling the hematocrit level within the blood device (Par. 97 of Charest). It also would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of the combination to further incorporate a transmembrane pressure and a controller as taught by Charest, since both components help maintain a predetermined pressure difference between the channels (Par. 143 of Charest). These electronic components ensure that the patient’s blood remains healthy (Par. 72 of Charest).
Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest as applied to claim 1 above, and evidenced by Jovanovic et al. US 2012/0292246 A1 (previously cited, hereinafter Jovanovic).
Regarding claim 13, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 1. However, the combination does not explicitly disclose the plurality of blood channels in each of the plurality of gas transfer units are oriented perpendicular to the plurality of gas channels.
While Nosrati does not explicitly disclose the perpendicular flow within the gas transfer units, Par. 241 of Nosrati teaches the plurality of dialysate channels in a fluid transfer unit 102a, particularly in polymer layer 106, are oriented perpendicular (90 degrees) to the [blood] flow in the other layer 104.
Given gas is also a type of fluid, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined system and incorporated the perpendicular flow configuration between the blood channels and the fluid channels as taught by Nosrati, into the gas transfer unit, in order to provide a uniform gradient across the microfluidic (Par. 241 of Nosrati). It is also known in the art that fluid flow inside extracorporeal membrane has mainly three optimal options: 0 degree (co-current), 90 degrees, and 180 degrees (counter-current) (Par. 241 of Nosrati). Therefore, it is within the technical capability of one of ordinary skill in the art to have chosen the perpendicular option for fluid flow, as evidenced by Fig. 4D and Par. 47 of Jovanovic – “perpendicular orientation decreases the compressibility of the membrane, resulting in higher permeability”. Thus, the limitation of “the plurality of blood channels in each of the plurality of gas transfer units are oriented perpendicular to the plurality of gas channels” is met.
Regarding claim 14, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 1. The combination of Nosrati, Kniazeva, Borenstein, and Gremel in view of Charest further discloses the plurality of blood channels 110a-b (Fig. 4A of Nosrati) in the fluid transfer unit 102a are oriented perpendicular (Par. 241 of Nosrati – 90 degrees; further evidenced by Fig. 4D of Jovanovic) to the plurality of fluid collection channels 110c-d (Fig. 4A of Nosrati and Par. 241 of Nosrati – the angle of flow in the dialysate channels vs the [blood] flow in the other layer could range from 0-180 degrees; 90 degrees option for dialysate flow).
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest as applied to claim 1 above, and further in view of Borenstein et al. US 2014/0193799 A1 (previously cited, hereinafter Borenstein ‘799), and further evidenced by Sudusinghe et al. “Increased risk of dialysis circuit clotting in hemodialysis patients with COVID-19 is associated with elevated FVIII, fibrinogen and D-dimers” (previously cited, hereinafter Sudusinghe).
Regarding claim 15, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 1. However, the combination does not disclose surfaces of the blood channels in each of the plurality of gas transfer units and in the fluid transfer unit are coated with an anticoagulant.
Borenstein ‘799, in the same field of endeavor of artificial lung assist device (Title), teaches surfaces of the blood channels in each of the plurality of gas transfer units and in the fluid transfer unit (Par. 58 – channels that form a microvascular network in the polymer layer) are coated with an anticoagulant (Par. 58 – channels of microvascular network coated with an anti-coagulant).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the blood channels in both gas transfer units and the fluid transfer unit of the combination to include an anti-coagulant coating as taught by Borenstein, in order to reduce blood clotting (Par. 58 of Borenstein) that might occur when blood is extracorporeally delivered to the device. It is also known in the art that the shear stress, or turbulent blood flow, etc. are common causes for blood clotting in extracorporeal blood treatment, evidenced by the Introduction section of Susdusinghe. Therefore, anti-coagulants in the blood channels ensure that safe and un-clotted treated blood will return to the patient and reduce device malfunction.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest as applied to claim 1 above, and further in view of Spearman et al. US 2020/0179586 A1 (previously cited, hereinafter Spearman).
Regarding claim 16, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 1. However, the combination does not explicitly disclose the blood treatment module configured to treat up to seven liters of blood per minute in the plurality of gas transfer units.
Spearman, in the same field of endeavor of systems for treating blood (Abstract), teaches the blood treatment 100 (Par. 74) configured to treat up to seven liters of blood per minute (Par. 74 – blood flow rate to be between 4 to 7 liters per minute) in the plurality of gas transfer units 114 (Par. 74 –blood can be flowing through oxygenator 114).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of the combination to treat blood via gas exchange at a rate of less or equal than 7 liters per minute taught by Spearman, since administering oxygen at said workable range assists healthy cells and facilitate killing of unhealthy cells, such as cancer cells or other cells deleterious to the body (Par. 71 of Spearman).
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest in view of Spearman as applied to claim 16 above, and further in view of Haghiri et al. US 2021/0380920 A1 (previously cited, hereinafter Haghiri).
Regarding claim 17, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest in view of Spearman discloses the invention of claim 16. However, the combination does not explicitly disclose the blood treatment module configured to raise O2sat of blood passing through the plurality of gas transfer units from 75% or lower to 95% or higher in a single pass.
Haghiri, in the same field of endeavor of microfluidic gas exchange device (Title), teaches the blood treatment configured to raise O2sat of blood passing through the plurality of gas transfer units (Par. 39 – blood flow through an artificial lung) from 75% or lower to 95% or higher in a single pass (Par. 39 – 70% saturation input to 95% saturation output).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of the combination to perform gas exchange such that the oxygen saturation goes from 70% to 95% after flowing through the artificial lung as taught by Haghiri, since it is known in the art that it is critical to maintain blood oxygen at about 95% saturation for normal and healthy function of blood cells. Raising blood oxygen level to the workable range as taught by Haghiri will ensure efficient blood treatment for patients having decreased lung function.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest as applied to claim 1 above, and further in view of Moghaddam US 2021/0113753 A1 (previously cited, hereinafter Moghaddam).
Regarding claim 18, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest discloses the invention of claim 1. However, the combination does not explicitly disclose the blood treatment module configured to treat up to 100 mL of blood per minute in the fluid transfer unit.
Moghaddam, in the same field of endeavor of microfluidic membrane module (Abstract), teaches the blood treatment module configured to treat less than 100 mL of blood per minute (Par. 64 – flow rate of <100 mL/min) in the fluid transfer unit (Moghaddam’s disclosure directs to a device replacing kidney functions, hence it is understood to be fluid transfer unit as seen in Fig. 6).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of the combination to incorporate the blood treatment rate as taught by Moghaddam, since the small size of the microfluidic membrane module along with the workable flow rate greatly enhances the reliability and safety of dialysis (Par. 64 of Moghaddam). Furthermore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the working range of less than 100mL/minute of Moghaddam by making the blood flow rate through the fluid transfer unit be up to 100mL/minute, in order words, less than or equal to 100mL/minute, as a matter of routine optimization, since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, one of ordinary skill in the art would have been motivated to optimize the working range to the claimed value in order to provide an option for patients who require higher filtration need, so that the machine can accommodate a higher blood volume being treated. Thus, the limitation of “up to 100 mL of blood per minute” is met.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest in view of Moghaddam as applied to claim 18 above, and further in view of Matson et al. US 2004/0199099 A1 (previously cited, hereinafter Matson).
Regarding claim 19, Nosrati in view of Kniazeva in view of Borenstein in view of Gremel in view of Charest in view of Moghaddam discloses the invention of claim 18. However, the combination does not explicitly disclose the blood treatment module configured to remove up to seven liters of fluid per day from blood passing through the fluid transfer unit.
Matson, in the same field of endeavor of hemofiltration system (Abstract), teaches disclose the blood treatment module configured to remove 2 to 6 liters of fluid per day (Par. 27 – ultrafiltrate discarded) from blood passing through the fluid transfer unit (Matson’s disclosure directs to a device replacing kidney functions, hence it is understood to be fluid transfer unit as seen in Fig. 5A-5C).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of the combination to incorporate the fluid removal volume as taught by Matson, since said range of fluid removal can accommodate patients with edema (over hydration) (Par. 64 of Matson). Furthermore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the working range of 2-6 liters per day of Matson by making the fluid removal volume through the fluid transfer unit be up to 7 liters, in order words, less than or equal to 7 liters per day as a matter of routine optimization, since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, one of ordinary skill in the art would have been motivated to optimize the working range to the claimed value in order to provide an option for patients who require higher filtration need, so that the machine can accommodate a higher blood volume being treated and remove a higher volume of waste fluid for better efficiency. Thus, the limitation of “up to 7 liters of fluid per day” is met.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Stroock et al. US 8,663,625 B2 teaches monolithic biomaterial with embedded microfluidic channels.
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 QUYNH DAO LE whose telephone number is (571)272-7198. The examiner can normally be reached Monday - Friday 8:30 am - 5:30 pm.
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/QUYNH DAO LE/Examiner, Art Unit 3781
/JESSICA ARBLE/Primary Examiner, Art Unit 3781
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