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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/04/2025 has been entered.
Claims 1, 22 and 27 have been amended. No claims have been newly canceled or newly added.
Claims 1-5, 7, 21-32 are currently pending and have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-5, 7, 21-32 are rejected under 35 U.S.C. 103 as being unpatentable over Vulto et al (WO 2017/216113 A2) in view of Jain et al (WO 2015/102726 A2).
Regarding claims 1, 3, 7, 21-24, and 27-30, Vulto teach a system comprising a microfluidic device comprising a body and a microfluidic channel formed in the body (base), wherein the channel comprises a fluid inlet and a fluid outlet and a coating formed on the channel comprising a plurality of endothelial cells (wherein the endothelial cells line the microfluidic channel), specifically blood outgrowth endothelial cells, that have been isolated from a patient and which define an inner surface of the channel (page 29 lines 21-31, page 33 lines 9-24, page 34 lines 20-28, pages 61-62 claims 69-75). The endothelial cells are cultured for 1, 2 or 3 more days (page 50 lines 24-25) which allows for the culture media (growth media) to be present for at least 18 hours and also includes an embodiment wherein the fluid (such as the culture media/growth media) is induced in the microfluidic channel through use of a pump (page 29, lines 19-20).
Vulto disclose wherein the system further includes an imaging device configured to collect information pertaining to the plurality of endothelial cells (page 11, page 48 lines 9-24, Figure 33).
Vulto teach wherein the microfluidic channels are also lined with an extracellular matrix, which includes materials such as collagen, as an outer layer and along with the endothelial cells as an inner layer of the microfluidic channel (page 24 lines 24-34, page 33 lines 9-34, page 35 lines 4-10, pages 61-62 claims 69-75).
While Vulto does not explicitly state that the intended use of the system is for mimicking a blood vessel of a patient, Vulto does include all the components of the claimed system, including cells from a patient, and therefore is deemed suitable for such intended use.
Vulto do not specify a predefined period of time for perfusing the growth media, however, Vulto do indicate that the changing of the medium can be adjusted to avoid stressing the cells (page 52 lines 4-8). The length of the perfusion time is a result effective variable amenable to routine optimization and experimentation as the condition and viability of the cells are affected by this value.
Vulto do not include an embodiment with all the limitations of claims 1, 3, 7, 21-24, and 27-30 combined together in one system. However, the combination of these claimed features within the Vulto system would have been obvious because Jain teach that they all desirable in a microfluidic system and can be used to enhance hemostasis assessment and patient care in a subject (page 2 para 6).
Jain teach and suggest a microfluidic device that comprises a substrate (body) with microchannels formed therein and wherein the surface of the microchannels is treated with collagen and/or endothelial cells as a first or second treatment, and includes a fluid inlet and a fluid outlet (pages 31-32 para 77-78, pages 36-37 para 88-90). Including an imaging device to collect information is also taught and suggested as well (page 13 para 38, page 14 para 41, pages 18-19 para 50-51, page 27 para 71).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include all these claim limitations in one embodiment in the microfluidic device system of Vulto because Jain teach and suggest that these are suitable and beneficial features of a microfluidic device system to enhance and assess patient or subject care and also because Vulto also teach these limitations as well.
Vulto do not specifically describe wherein the plurality of BOECs are aligned with a flow axis of the microfluidic channel. However, they do indicate that it is desirable to provide a continuous flow of culture media into the microfluidic channels and that this flow can be induced in the channel through the use of a pump (page 29 lines 6-20).
Applicant’s disclosure indicates that the majority of BOECs will align with a flow axis in the microfluidic channel when culture medium is flowed continuously through the microchannel (Specification page 16 para 68, page 20 para 81).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to apply a continuous flow of culture medium to the microchannels of the microfluidic device of Vulto because Vulto teach and suggest that this is desirable and beneficial to do so. This process would have inherently provided wherein the cells lining the microchannel (BOECs) would then align with a flow axis in the microfluidic channel as evidenced by Applicant’s disclosure (Specification page16 para 68, page 20 para 81).
Vulto is silent regarding the specific type of flow of the growth media through the microfluidic channels or its effect on the alignment of the BOECs in the microchannel.
Jain teach and suggest that a microfluidic device containing a plurality of parallel microchannels that mimic blood vessels and permit real-time analysis of clotting dynamics will retain a laminar flow (page 13 para 39).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include a laminar flow within the microfluidic channels of the Vulto device because Jain teach and suggest that this is a suitable and beneficial feature of a microfluidic device system to enhance and assess patient or subject care and also because Vulto do not exclude a laminar flow type and Vulto also suggest the use of a pump to flow the culture media (growth media) through the microfluidic channels (page 29 lines 19-20). This laminar flow through the microfluidic channels would then inherently produce the alignment of the BOECs within 30 degrees of the flow axis of the microfluidic channel as evidenced by the fact that this is the type of flow that Applicant uses in their device to create the alignment of BOECs in the microchannel (Specification page 16 para 68, page 20 para 81).
Regarding claims 1, 2, 22, 27, While Vulto teach that their microfluidic device can be used with blood cells collected from a patient, such as blood outgrowth endothelial cells (page 34 lines 20-28), Vulto do not specifically describe using a pump configured to withdraw a blood sample from a patient from a fluid conduit connected to a fluid inlet of the channel and perfused through the channel to the outlet.
Jain teach that it is suitable and beneficial to include a pump configured to withdraw blood from a patient from a fluid conduit connected to a fluid inlet of the channel and perfused through the channel to the outlet (page 32 para 78, page 39 para 100).
One of ordinary skill in the art would have been motivated to include a pump configured to withdraw blood from a patient from a fluid conduit connected to a fluid inlet of the channel and perfused through the channel to the outlet in the microfluidic device system of Vulto because Jain teach and suggest that this is suitable and beneficial to do so. The addition of the pump would have provided the patient blood required for the Vulto system in a convenient, controllable and repeatable manner. One of ordinary skill in the art would have had a reasonable expectation of success because both Vulto and Jain are seeding microfluidic channels with endothelial cells from a patient and Vulto specifically state that they intend for their system to include modifications and variations as well (page 52 lines 25-30).
Regarding claims 1, 4, 22, 25, 27 and 31, Vulto do not specifically describe wherein their system includes a computer system for analysis of the endothelial cells in the microchannel.
Jain teach that it is suitable and beneficial to include a computer system configured to provide a readout comprising information associated with the function of the device and thus associated with the endothelial cells lining the channels of the device as well (pages 33-34 para 83-84). The computer system includes a controller including one or more processors for communicating information and a main memory and/or other dynamic storage device for storing information and instructions to be executed by the processor and further integrated with a pump operation and sensory data collection (page 33 para 83).
One of ordinary skill in the art would have been motivated to include a computer system including processors, storage devices and pumps for analysis and sensory data collection of the endothelial cells in the microchannel in the microfluidic device system of Vulto because Jain teach and suggest that this is suitable and beneficial to do so. One of ordinary skill in the art would have had a reasonable expectation of success because both Vulto and Jain are seeding microfluidic channels with endothelial cells from a patient and Vulto specifically state that they intend for their system to include modifications and variations as well (page 52 lines 25-30).
Regarding claims 5, 26 and 32, Vulto is silent with regard to the hydraulic diameter of their microfluidic channels.
Jain teach that it is suitable and beneficial to include microchannel diameters that mimic the diameter of blood vessels (page 13 para 39) and include a maximal hydraulic diameter between about 25 µm- 5mm (page 42 claim 5).
One of ordinary skill in the art would have been motivated to include microchannels that mimic the diameter of blood vessels and include a maximal hydraulic diameter between about 25 µm- 5mm in the microfluidic system of Vulto because Jain teach that it is suitable and beneficial to include microchannel diameters that mimic the diameter of blood vessels (page 13 para 39) and include a maximal hydraulic diameter between about 25 µm- 5mm (page 42 claim 5). This diameter range disclosed by Jain overlaps and thus renders obvious Applicant’s claimed range. One of ordinary skill in the art would have had a reasonable expectation of success because both Vulto and Jain are seeding microfluidic channels with endothelial cells from a patient and Vulto specifically state that they intend for their system to include modifications and variations as well (page 52 lines 25-30).
Regarding claim 27, Vulto is silent with regard to the shear rate of the flow of the culture media (growth media).
Jain teach and suggest that a shear rate of a microfluidic device containing endothelial cells is properly within the range of 75-2500 sec-1 (page 17 para 48 and page 18 para 50) which overlaps with the range of a shear rate that is less than 100 inverse seconds) and thus renders the claimed range obvious.
In the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art a prima facie case of obviousness exists. In re Wertheim (MPEP 2144.05).
Therefor one of ordinary skill in the art would have been motivated with a reasonable expectation of success to use a shear rate of 75-100 inverse seconds in the microfluidic device of Vulto because Jain teach and suggest that this is a suitable and beneficial feature of a microfluidic device system designed to enhance and assess patient or subject care.
Therefore, the teachings of Vulto et al and Jain et al render obvious Applicant’s invention as claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-5, 7-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending US Patent 12,387,622 (previously US Application No. 18/739567) in view of Vulto et al (WO 2017/216113 A2) and Jain et al (WO 2015/102726 A2).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of copending Application ‘567 are drawn to a microfluidic chip for modeling blood through a vein comprising a body comprising a microchannel coated with endothelial cells that form a vascular lumen, wherein the endothelial cells are coated over a layer of extracellular matrix, with a flow channel width between 25 µm and 200 µm.
Regarding claims 1, 3, and 7, While the copending claims do not recite wherein the endothelial cells are blood outgrowth endothelial cells (BOECs), it would have been obvious to substitute or add BOECs to the endothelial cells coating the channel because Vulto teach that BOECs are a suitable type of endothelial cell to line the surface of a microfluidic channel in a microfluidic device.
Regarding claims 1, 3, 7, 21-24, and 27-30, Vulto teach a system comprising a microfluidic device comprising a body and a microfluidic channel formed in the body (base), wherein the channel comprises a fluid inlet and a fluid outlet and a coating formed on the channel comprising a plurality of endothelial cells (wherein the endothelial cells line the microfluidic channel), specifically blood outgrowth endothelial cells, that have been isolated from a patient and which define an inner surface of the channel (page 29 lines 21-31, page 33 lines 9-24, page 34 lines 20-28, pages 61-62 claims 69-75). The endothelial cells are cultured for 1, 2 or 3 more days (page 50 lines 24-25) which allows for the culture media (growth media) to be present for at least 18 hours and also includes an embodiment wherein the fluid (such as the culture media/growth media) is induced in the microfluidic channel through use of a pump (page 29, lines 19-20).
While Vulto does not explicitly state that the intended use of the system is for mimicking a blood vessel of a patient, Vulto does include all the components of the claimed system and therefore is deemed suitable for such intended use.
Vulto disclose wherein the system further includes an imaging device configured to collect information pertaining to the plurality of endothelial cells (page 11, page 48 lines 9-24, Figure 33).
Vulto teach wherein the microfluidic channels are also lined with an extracellular matrix, which includes materials such as collagen, as an outer layer and along with the endothelial cells as an inner layer of the microfluidic channel (page 24 lines 24-34, page 33 lines 9-34, page 35 lines 4-10, pages 61-62 claims 69-75).
The combination of these claimed features would have been obvious because Jain teach that they all desirable in a microfluidic system and can be used to enhance hemostasis assessment and patient care in a subject (page 2 para 6).
Jain teach and suggest a microfluidic device that comprises a substrate (body) with microchannels formed therein and wherein the surface of the microchannels is treated with collagen and/or endothelial cells as a first or second treatment, and includes a fluid inlet and a fluid outlet (pages 31-32 para 77-78, pages 36-37 para 88-90). Including an imaging device to collect information is also taught and suggested as well (page 13 para 38, page 14 para 41, pages 18-19 para 50-51, page 27 para 71).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include all these claim limitations in one embodiment in the microfluidic device system of Vulto because Jain teach and suggest that these are suitable and beneficial features of a microfluidic device system to enhance and assess patient or subject care and also because Vulto also teach these limitations as well.
Vulto do not specifically describe wherein the plurality of BOECs are aligned with a flow axis of the microfluidic channel. However, they do indicate that it is desirable to provide a continuous flow of culture media into the microfluidic channels and that this flow can be induced in the channel through the use of a pump (page 29 lines 6-20).
Applicant’s disclosure indicates that the majority of BOECs will align with a flow axis in the microfluidic channel when culture medium is flowed continuously through the microchannel (Specification page 16 para 68, page 20 para 81).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to apply a continuous flow of culture medium to the microchannels of the microfluidic device of Vulto because Vulto teach and suggest that this is desirable and beneficial to do so. This process would have inherently provided wherein the cells lining the microchannel (BOECs) would then align with a flow axis in the microfluidic channel as evidenced by Applicant’s disclosure (Specification page16 para 68, page 20 para 81).
Vulto is silent regarding the specific type of flow of the growth media through the microfluidic channels or its effect on the alignment of the BOECs in the microchannel.
Jain teach and suggest that a microfluidic device containing a plurality of parallel microchannels that mimic blood vessels and permit real-time analysis of clotting dynamics will retain a laminar flow (page 13 para 39).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include a laminar flow within the microfluidic channels of the Vulto device because Jain teach and suggest that this is a suitable and beneficial feature of a microfluidic device system to enhance and assess patient or subject care and also because Vulto do not exclude a laminar flow type and Vulto also suggest the use of a pump to flow the culture media (growth media) through the microfluidic channels (page 29 lines 19-20). This laminar flow through the microfluidic channels would then inherently produce the alignment of the BOECs within 30 degrees of the flow axis of the microfluidic channel as evidenced by the fact that this is the type of flow that Applicant uses in their device to create the alignment of BOECs in the microchannel (Specification page 16 para 68, page 20 para 81).
Regarding claims 1, 2, 22, 27, While Vulto teach that their microfluidic device can be used with blood cells collected from a patient, such as blood outgrowth endothelial cells (page 34 lines 20-28), Vulto do not specifically describe using a pump configured to withdraw a blood sample from a patient from a fluid conduit connected to a fluid inlet of the channel and perfused through the channel to the outlet.
Jain teach that it is suitable and beneficial to include a pump configured to withdraw blood from a patient from a fluid conduit connected to a fluid inlet of the channel and perfused through the channel to the outlet (page 32 para 78, page 39 para 100).
One of ordinary skill in the art would have been motivated to include a pump configured to withdraw blood from a patient from a fluid conduit connected to a fluid inlet of the channel and perfused through the channel to the outlet in the microfluidic device system of Vulto because Jain teach and suggest that this is suitable and beneficial to do so. One of ordinary skill in the art would have had a reasonable expectation of success because both Vulto and Jain are seeding microfluidic channels with endothelial cells from a patient and Vulto specifically state that they intend for their system to include modifications and variations as well (page 52 lines 25-30).
Regarding claims 1, 4, 22, 25, 27 and 31, Vulto do not specifically describe wherein their system includes a computer system for analysis of the endothelial cells in the microchannel.
Jain teach that it is suitable and beneficial to include a computer system configured to provide a readout comprising information associated with the function of the device and thus associated with the endothelial cells lining the channels of the device as well (pages 33-34 para 83-84). The computer system includes a controller including one or more processors for communicating information and a main memory and/or other dynamic storage device for storing information and instructions to be executed by the processor and further integrated with a pump operation and sensory data collection (page 33 para 83).
One of ordinary skill in the art would have been motivated to include a computer system including processors, storage devices and pumps for analysis and sensory data collection of the endothelial cells in the microchannel in the microfluidic device system of Vulto because Jain teach and suggest that this is suitable and beneficial to do so. One of ordinary skill in the art would have had a reasonable expectation of success because both Vulto and Jain are seeding microfluidic channels with endothelial cells from a patient and Vulto specifically state that they intend for their system to include modifications and variations as well (page 52 lines 25-30).
One of ordinary skill in the art would have been motivated to include a computer system for analysis of the endothelial cells in the microchannel in a microfluidic device system because Jain teach and suggest that this is suitable and beneficial to do so. One of ordinary skill in the art would have had a reasonable expectation of success because both Vulto and Jain are seeding microfluidic channels with endothelial cells from a patient and Vulto specifically state that they intend for their system to include modifications and variations as well (page 52 lines 25-30).
Regarding claims 5, 26 and 32, Vulto is silent with regard to the hydraulic diameter of their microfluidic channels.
Jain teach that it is suitable and beneficial to include microchannel diameters that mimic the diameter of blood vessels (page 13 para 39) and include a maximal hydraulic diameter between about 25 µm- 5mm (page 42 claim 5).
One of ordinary skill in the art would have been motivated to include microchannels that mimic the diameter of blood vessels and include a maximal hydraulic diameter between about 25 µm- 5mm in a microfluidic device system because Jain teach that it is suitable and beneficial to include microchannel diameters that mimic the diameter of blood vessels (page 13 para 39) and include a maximal hydraulic diameter between about 25 µm- 5mm (page 42 claim 5). This diameter range disclosed by Jain overlaps and thus renders obvious Applicant’s claimed range. One of ordinary skill in the art would have had a reasonable expectation of success because both Vulto and Jain are seeding microfluidic channels with endothelial cells from a patient and Vulto specifically state that they intend for their system to include modifications and variations as well (page 52 lines 25-30).
Regarding claim 27, Vulto is silent with regard to the shear rate of the flow of the culture media (growth media).
Jain teach and suggest that a shear rate of an microfluidic device containing endothelial cells is properly within the range of 75-2500 sec-1 (page 17 para 48 and page 18 para 50) which overlaps with the range of a shear rate that is less than 100 inverse seconds) and thus renders the claimed range obvious.
In the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art a prima facie case of obviousness exists. In re Wertheim (MPEP 2144.05).
Therefor one of ordinary skill in the art would have been motivated with a reasonable expectation of success to use a shear rate of 75-100 inverse seconds in a microfluidic device containing endothelial cells because Jain teach and suggest that this is a suitable and beneficial feature of a microfluidic device system designed to enhance and assess patient or subject care.
Therefore, the teachings of the patent claims, Vulto et al and Jain et al render obvious Applicant’s invention as claimed.
Response to Arguments
Applicant's arguments filed 02/04/2026 have been fully considered but they are not fully persuasive.
Applicant argues that it would not have been obvious to modify the teachings of Vulto in view of the teachings of Jain to include perfusing a laminar flow of growth media continuously through the microfluidic channel 102 for a predefined period of time to align POECs within approximately 30 degrees of a flow axis. Applicant asserts that Jain does not describe perfusing a laminar flow of growth media because Jain teaches perfusing whole human blood and thus cannot teach perfusing growth media.
This is not found persuasive. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
In the current case, Vulto is silent with regard to the type of flow used to perfuse their growth media through their microchannels in the Vulto system. Jain teach and suggest that a microfluidic device containing a plurality of parallel microchannels that mimic blood vessels and permit real-time analysis of clotting dynamics will retain a laminar flow (page 13 para 39).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include a laminar flow within the microfluidic channels of the Vulto device because Jain teach and suggest that this is a suitable and beneficial feature of a microfluidic device system to enhance and assess patient or subject care and also because Vulto do not exclude a laminar flow type and Vulto also suggest the use of a pump to flow the culture media (growth media) through the microfluidic channels (page 29 lines 19-20). This laminar flow through the microfluidic channels would then inherently produce the alignment of the BOECs within 30 degrees of the flow axis of the microfluidic channel as evidenced by the fact that this is the type of flow that Applicant uses in their device to create the alignment of BOECs in the microchannel (Specification page 16 para 68, page 20 para 81).
Applicant argues that the Office Action improperly applies inherency analysis in asserting that the proposed combination of Vulto and Jain would inherently result in the features of claim 1 using Applicant’s own specification in support. Applicant points to PAR Pharmaceutical Inc v TWI Pharmaceuticals Inc as evidence of the lack of inherency as the cited references do not explicitly describe the claimed effects.
This is not found persuasive. Providing guidance on instances where the method steps of the prior art and instant claims are the same, Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) states “[T]hat since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims.”
Regarding the issue of inherency, see Persion Pharms. LLC v. Alvogen Malta Operations LTD., 945 F.3d 1184, 1191, 2019 USPQ2d 494084 (Fed. Cir. 2019), where the court stated that a proper finding of inherency does not require that all limitations are taught in a single reference, and that inherency may meet a missing claim limitation when the limitation is "the natural result of the combination of prior art elements." (emphasis in original). The court found that pharmacokinetic limitations of the asserted claims were inherently met by combining prior art references because the limitations were necessarily present in the prior art combination. Id. See also Hospira, Inc. v. Fresenius Kabi USA, LLC, 946 F.3d 1322, 1329-32, 2020 USPQ2d 6227 (Fed. Cir. 2020). (see MPEP 2112 (IV)).
In the current case, Applicant’s disclosure shows that a laminar flow through microfluidic channels produces the alignment of the BOECs within 30 degrees of the flow axis of the microfluidic channel (see Specification page 16 para 68, page 20 para 81). If this is not the case and there is something else required to provide the cell alignment within 30 degrees of the flow axis of the channel then it is not readily apparent from Applicant’s disclosure and it would appear that the claims are thus missing the steps or elements that provide these claimed features.
It is not necessary for the prior art to explicitly recognize that the effect of laminar fluid flow on the alignment of endothelial cells for this effect to be present. Behrens et al (Scientific Reports 2020) disclose that endothelial cells will align in a microfluidic channel under a laminar fluid shear stress (page 5).
Applicant argues that Vulto and Jain fail to teach or suggest a computer system comprising instructions that when executed by one or more processors to operate a pump to induce laminar flow of growth media and other limitations as recited in claim 22.
This is not found persuasive. Jain teach that it is suitable and beneficial to include a computer system configured to provide a readout comprising information associated with the function of the device and thus associated with the endothelial cells lining the channels of the device as well (pages 33-34 para 83-84). The computer system includes a controller including one or more processors for communicating information and a main memory and/or other dynamic storage device for storing information and instructions to be executed by the processor and further integrated with a pump operation and sensory data collection (page 33 para 83).
One of ordinary skill in the art would have been motivated to include a computer system including processors, storage devices and pumps for analysis and sensory data collection of the endothelial cells in the microchannel in the microfluidic device system of Vulto because Jain teach and suggest that this is suitable and beneficial to do SO. One of ordinary skill in the art would have had a reasonable expectation of success because both Vulto and Jain are seeding microfluidic channels with endothelial cells from a patient and Vulto specifically state that they intend for their system to include modifications and variations as well (page 52 lines 25-30).
Applicant argues that Jain does not describe how long the perfusion should take place given that it may depend on how long it is desired to observe the flow of the whole human blood.
This is not found persuasive. Vulto indicate that the changing of the medium can be adjusted to avoid stressing the cells (page 52 lines 4-8). The length of the perfusion time is a result effective variable amenable to routine optimization and experimentation as the condition of the cells are affected by this value.
Applicant argues that Vulto and Jain do not render obvious the invention of claims 27-32 for the same reason as described above.
This is not found persuasive for the same reasons as recited above.
Applicant argues that Vulto and Jain particularly fail to teach or suggest perfusing a laminar flow of growth media at a shear rate that is less than 100 inverse seconds.
This is not found persuasive. Jain teach and suggest that a shear rate of an microfluidic device containing endothelial cells is properly within the range of 75-2500 sec⁻¹ (page 17 para 48 and page 18 para 50) which overlaps with the range of a shear rate that is less than 100 inverse seconds) and thus renders the claimed range obvious.
In the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art a prima facie case of obviousness exists. In re Wertheim (MPEP 2144.05).
Therefor one of ordinary skill in the art would have been motivated with a reasonable expectation of success to use a shear rate of 75-100 inverse seconds in the microfluidic device of Vulto because Jain teach and suggest that this is a suitable and beneficial feature of a microfluidic device system designed to enhance and assess patient or subject care.
Applicant requests that the provisional rejection of claims 1-7 on the ground of nonstatutory double patenting over co-pending US Application 18/739567 in view of Vulto and Jain be held in abeyance until the rejections over the cited prior art have been overcome.
This is not found persuasive. The “provisional” double patenting rejection should continue to be made by the examiner in each application as long as there are conflicting claims in more than one application unless that “provisional” double patenting rejection is the only rejection remaining in one of the applications. See MPEP 822.01
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Van der Meer et al., " Three-dimensional co-cultures of human endothelial cells and embryonic stem cell-derived pericytes inside a microfluidic device", Lab Chip, 2013, 13, 3562–3568.
Shemesh et al., “Flow-induced stress on adherent cells in microfluidic devices”, Lab Chip,2015, Vol.15, pp. 4114-4127, 15 pages.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631