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 .
Claim Rejections - 35 USC §§ 102 | 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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 1-3, 9-10, and 21-22 are rejected under 35 U.S.C. §§ 102(a)(1) and 102(a)(2) as anticipated by Pant (US 20150377861) (previously disclosed); or, in the alternative, under 35 U.S.C. 103 as obvious over Pant (US 20150377861) (previously disclosed) in view of Golway (US 20190330583) (previously disclosed).
Regarding claim 1, Pant discloses a device comprising:
a bio-assembly (paragraphs [0068]-[0075]; Figs. 10A-11) comprising:
a substrate (paragraph [0069]; Fig. 10A, element 132 “substrate”), and
a plate (paragraph [0069]; Fig. 10A, element 133 “well plate”) comprising a plurality of partitions (paragraph [0070]; Fig. 10A, elements 138 “one or more wells”), and
a plurality (paragraph [0126] “the chambers can include collagen or Matrigel or other gelatinous cell culture scaffold material”) of bio-scaffolds (paragraph [0065]) affixed (paragraph [0069] “affixed, combined, integrated, or otherwise joined together”) to the substrate (paragraph [0069]; Fig. 10A, element 132 “substrate”) and disposed within the plurality of partitions (paragraph [0070]; Fig. 10A, elements 138 “one or more wells”); and
a loader (paragraph [0069]; Figs. 10A-10B, element 134 “manifold”) comprising:
a plurality of loader inlets (paragraph [0073], Fig. 10A, elements 136a and 137a “Each inlet manifold channel”),
a plurality of loader outlets (paragraph [0073], Fig. 10A, elements 136b and 137b “Each outlet manifold channel”),
a fluid inlet channel (paragraph [0074] “a plurality of linked wells or assay regions can receive a single fluid inlet”), and
a fluid outlet channel (paragraph [0074] “a plurality of linked wells or assay regions can receive a single fluid inlet or a single fluid outlet”),
wherein the plurality (paragraph [0126] “the chambers can include collagen or matrigel or other gelatinous cell culture scaffold material”) of bio-scaffolds (paragraph [0065]) comprises a plurality of vascular components (paragraph [0029]) having a plurality of vascular inlets (paragraph [0054]) and a plurality of vascular outlets (paragraph [0054]),
wherein the plurality of vascular inlets is in fluid communication with the plurality of loader inlets (paragraphs [0054] and [0059]) and the plurality of vascular outlets is in fluid communication with the plurality of loader outlets (paragraphs [0054] and [0059]),
wherein the fluid inlet channel (paragraph [0074] “a plurality of linked wells or assay regions can receive a single fluid inlet”) is in fluid communication with the plurality of loader inlets (paragraph [0073], Fig. 10A, elements 136a and 137a “Each inlet manifold channel”), and
wherein the fluid outlet channel (paragraph [0074] “a plurality of linked wells or assay regions can receive a single fluid inlet or a single fluid outlet”) is in fluid communication with the plurality of loader outlets (paragraph [0073], Fig. 10A, elements 136b and 137b “Each outlet manifold channel”).
While Pant does not teach that their invention is “a kit” as stated in the claimed preamble, a preamble merely indicates the intended use of the apparatus and does not add structural limitations to the claims. MPEP § 2111.02(II). Because the apparatus taught by Pant teaches all the structural limitations claimed, it would be capable of being used as “a kit”. Applicant is also reminded that the intended use of or manner of operating a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II).
If it is deemed that Pant does not disclose a plurality of bio-scaffolds … disposed within the plurality of partitions, Golway discloses a plurality of bio-scaffolds (paragraphs [0091]-[0094] “3-D matrix” or “gel”) … disposed within the plurality of partitions (paragraphs [0091] and [0094] “a well of a 24-well plate” and “microfluidic chamber (defined by the well walls)”).
In the analogous art of vascularized in vitro perfusion devices, it would have been obvious to one skilled in the art before the effective filing date to modify Pant with the plurality of bio-scaffolds disposed within the plurality of partitions of Golway in order to perfuse different cell lines in different partitions to flow from one cell culture to another in series or in parallel (Golway, paragraph [0071] “Liver IPM to a Kidney IPM”).
Regarding claim 2, Pant discloses further comprising a fluid mixture configured to be injected into one or more of the plurality of the bio-scaffolds (paragraph [0067] “inject the precise volume into a microfluidic chip may be used to convey fluid from one or more reservoirs to each chip”).
Regarding claim 3, Pant discloses wherein one or more of the plurality of the bio-scaffolds comprises a hydrogel (paragraph [0126] “the chambers can include collagen or matrigel or other gelatinous cell culture scaffold material” and paragraph [0065]).
Regarding claim 9, Pant discloses wherein one or more of the plurality of the bio-scaffolds comprises a void (paragraph [0096], internal portion of a channel, lumen, or tissue space), the void comprising a perfusable or injectable space with one or more inlets and one or more outlets (paragraphs [0091] and [0096]).
Regarding claim 10, Pant discloses wherein the fluid mixture is configured to be combined with live cells, the combination being injectable into the void (paragraphs [0091] and [0096] “Cells at a concentration of 1×105/ml-5×107/ml are pumped into the network inlets” and “cells in the lumen of the tissue space”).
Regarding claim 21, Pant discloses wherein the fluid inlet channel is in fluid communication with the plurality of loader inlets in series or parallel (paragraph [0074] “a plurality of linked wells or assay regions can receive a single fluid inlet”; inherently, the fluid path must be linked in series and/or in parallel).
If it is deemed that Path does not disclose this limitation, Golway discloses wherein a fluid inlet channel is in fluid communication with a plurality of inlets in series or parallel (paragraphs [0018] and [0071]-[0072]; Figs. 1-8 and 11A-12C for parallel flow; Figs. 9-10 for serial flow).
In the analogous art of vascularized in vitro perfusion devices, it would have been obvious to one skilled in the art before the effective filing date to modify Pant with the plurality of bio-scaffolds disposed within the plurality of partitions of Golway in order to perfuse different cell lines in different partitions to flow from one cell culture to another in series or in parallel (Golway, paragraph [0071] “Liver IPM to a Kidney IPM”).
Regarding claim 22, Pant discloses wherein the fluid outlet channel is in fluid communication with the plurality of loader outlets in series or parallel (paragraph [0074] “a plurality of linked wells or assay regions can receive a single fluid inlet or a single fluid outlet”; inherently, the fluid path must be linked in series and/or in parallel).
If it is deemed that Path does not disclose this limitation, Golway discloses wherein a fluid inlet channel is in fluid communication with a plurality of inlets in series or parallel (paragraphs [0018] and [0071]-[0072]; Figs. 1-8 and 11A-12C for parallel flow; Figs. 9-10 for serial flow).
In the analogous art of vascularized in vitro perfusion devices, it would have been obvious to one skilled in the art before the effective filing date to modify Pant with the plurality of bio-scaffolds disposed within the plurality of partitions of Golway in order to perfuse different cell lines in different partitions to flow from one cell culture to another in series or in parallel (Golway, paragraph [0071] “Liver IPM to a Kidney IPM”).
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 8 is rejected under 35 U.S.C. 103 as being unpatentable over Pant (US 20150377861) (previously disclosed) as applied to claim 1, in view of Nath (US 20180066220) (previously disclosed) and Sharei (US 20140287509) (previously disclosed); or, in the alternative, under 35 U.S.C. 103 as obvious over Pant (US 20150377861) (previously disclosed) in view of Golway (US 20190330583) (previously disclosed) as applied to claim 1, further in view of Nath (US 20180066220) (previously disclosed) and Sharei (US 20140287509) (previously disclosed).
Regarding claim 8, Pant discloses the bio-assembly (paragraphs [0068]-[0075]; Figs. 10A-11) and loader (paragraph [0069]; Figs. 10A-10B, element 134 “manifold”).
Pant does not disclose wherein the bio-assembly and loader fluid communication are mediated by a tapered constriction in the bio-assembly and provides a fluidic seal at a normal operating fluid pressure.
Nath teaches wherein a bio-assembly (claim 1 “microfluidic device”; paragraphs [0006], [0043], and [0047]; Fig. 2C) and loader (Fig. 1B, paragraph [0046]) fluid communication are mediated by a connection in the bio-assembly (Fig. 1C of Nath) and provides a fluidic seal at a normal operating fluid pressure (paragraphs [0046]-[0047], Fig. 1C, elements 18 and 11 the two side chambers are sealed to fit the inlet and outlet of the partition and the two side chambers fluidly communicate to a constricted flow path to the numerous hollow fibers of the bio-assembly, all sealed together with adhesives such as adhesive transfer tape or other means of lamination, as well as medical grade silicone glue).
It would have been obvious to one skilled in the art before the effective filing date to modify the bio-assembly and loader of Pant or modified Pant with the connection of Nath in order to create a fluidic connection in channels so that fluidically sealed laminar flow is ensured through the bio-assembly.
Additionally, Sharei discloses a tapered constriction (Figs. 1A-6; paragraph [0234]).
In the analogous art of intracellular delivery apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify the geometry of the channels of the bio-assembly and loader of modified Pant to have a tapered constriction as in Sharei in order to create a fluidic connection in channels so that fluidically sealed laminar flow is ensured through the bio-assembly. Additionally, depending on the geometry of the tapered constriction, the tapered constriction of Sharei would provide for a vector-free microfluidic platform for direct-to-cytosol intracellular delivery of materials, e.g., a compound or composition, to a eukaryotic cell (Sharei, paragraph [0005]).
Additional Prior Art References
The prior art made of record and not relied upon is considered pertinent to the Applicant’s disclosure.
Nozawa (JP 2014/233275) (machine translation) (previously disclosed) – This invention is a culture vessel with engaging parts to be connected to another culture vessel, similar to puzzle pieces.
Banaeiyan (US 2019/0062686) (newly disclosed) – This invention is a microfluidic device for culturing cells.
Response to Arguments
Applicant’s arguments filed 02/25/2026 have been fully considered but they are not persuasive.
Regarding pgs. 6 to 8 of 14 of Applicant arguments, arguments are given against the rejections under anticipation, or alternatively, obviousness of claims 1-3, 9-10, and 21-22. Pant is summarized with its abstract and Pant’s Fig. 10A. Applicant argues that Pant does not disclose bio-scaffolds but instead comprise well channels. However, Pant discloses bio-scaffolds as currently claimed in the claim set; Pant discloses in paragraph [0065]:
The channels forming SMNs, IMNs, bifurcations, and the luminal surfaces of tissue spaces may be coated with native or recombinant proteins, glycoproteins, proteoglycans, or other substrate molecules to assay for associations with particles or to facilitate the growth of cells on the inner surfaces of the channels. Examples of substrate molecules include collagen, gelatin, laminin, and fibronectin. Other materials such as matrigel, puramatrix, alginate beads, or others that can be used, such as a monolayer substrate or a 3-D gel can be used. The channels may also be coated with adhesion molecules such as P-selectin, E-selectin, ICAM-1, or other receptors to facilitate adhesion of specific cell types or particles such as lipisomes or drug encapsulating or targeting agents.
-- Pant, paragraph [0065]
The paragraph above shows that the bio-scaffold of Pant comprises the same materials as the instant claim 3, which claims one or more of the plurality of bio-scaffolds comprises a hydrogel (see specifically, “matrigel, puramatrix, alginate beads, or others that can be used, such as a monolayer substrate or a 3-D gel can be used”). Additionally, the vascular components comprising a plurality of vascular inlets and a plurality of vascular outlets are also present as claimed in claim 1, according to Pant (Pant, Figs. 1, 2A, and 11; and, paragraph [0054] “Other embodiments may have more than one inlet and/or outlet”). Also, in accordance with Pant, the vascular components are called “cell culture scaffold material” (paragraph [0126]).
Regarding affixing the components (Pant, paragraph [0069] “a substrate 132, a well plate 133, and a manifold 134 coupled together. These components can be affixed, combined, integrated, or otherwise joined together as separate parts or formed from a unitary member.”) together, this either already present in Pant, or alternatively, is an obvious integration of parts. The substrate is shown to include the microfluidic chips that are vascular networks with or without extravascular spaces, which constitute bio-scaffolds (Pant, paragraphs [0029], [0054], [0065], [0070] and [0126] “cell culture scaffold material”). Alternatively, integration of parts would have been obvious to one of ordinary skill in the art as a matter of obvious engineering choice. MPEP § 2144.04(V)(B).
Regarding Pant paragraph [0054], Pant discloses inlets and outlets to the microfluidic chips, which comprise cell culture scaffold material, see the following excerpts:
A microfluidic chip comprising the synthetic microvascular network (SMN) 12 and a tissue space 13 is illustrated in FIG. 2A. The SMN 12 comprises a plurality of interconnected, nonlinear flow channels 14, in fluid communication with an inlet port 10 and an outlet port 11…
The inlet port 10 and the outlet port 11 each have two lobes in this embodiment to facilitate easy connections to reservoirs and the inlet and outlet ports may have single lobes and/or other shapes as well…
Other embodiments may have more than one inlet and/or outlet.
-- Pant, paragraph [0054]
Therefore, the inlets and outlets of the microfluidic chips containing synthetic microvascular networks of Pant anticipate “a plurality of vascular inlets and a plurality of vascular outlets” as claimed in claim 1. Arguments about the inlets and outlets of the microfluidic chips of Pant being part of a manifold or a microfluidic chip are moot. Whether or not the flow channels are integrally connected to a manifold, the flow channels read upon the claim limitation. Additionally, the vascular networks are present and affixed to the substrate as described in instant claim 1, see above arguments about Pant’s disclosure of optional integration of parts, or the obvious integration of parts under MPEP § 2144.04.
Regarding Golway, in pg. 9 of 14, the motivation for combining Pant in view of Golway is questioned. The Applicant relies on an accusation of hindsight reasoning, substantial reconstruction and redesign of the prior art, and a change in the basic principles under which the prior art is designed to rebut the obviousness-based rejection.
First, if Pant discloses that a system of two or more cell cultures is present, it would be deemed that Golway is in the field of analogous prior art. Motivation to combine should not be difficult under the terms of substantial reconstruction and redesign or a change in the basic principles of the prior art as the two prior art inventions are similar in nature and disclose vasculature in a gel bio-scaffold. Additionally, upon further inspection, the motivation statement given:
… to modify Pant with the plurality of bio-scaffolds disposed within the plurality of partitions of Golway in order to perfuse different cell lines in different partitions to flow from one cell culture to another in series or in parallel (Golway, paragraph [0071] “Liver IPM to a Kidney IPM”).
-- Office Action
The plurality of cell cultures can be different cell cultures, with each bio-scaffold comprising a cell culture in a different partition (see Golway, paragraph [0071]), similarly to Pant (see Pant, paragraph [0120]). Motivation to combine these features is apparent because both prior art use these features and rendering one’s design or operation useful to another would be obvious. Evidence of the record has been given (upholding motivation for obviousness), and need not require reading into the prior art teachings of the invention at issue (rejecting hindsight bias).
Furthermore, it is apparent that a “plurality of partitions” is obvious under MPEP § 2144.04, and despite not being part of the rejection, Applicant should be made aware that there is a section of the MPEP that states that mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B).
In view of these prior art and the MPEP, it should be clear that the only feature that Golway was cited for its disclosure, “a plurality of bio-scaffolds … disposed within the plurality of partitions” is obvious.
Second, in Golway’s Fig. 1 and Pant’s Fig. 1A, it is unsubstantiated that the inlet ports and outlet ports of Pant and Golway are incompatible. Golway’s 3D printed perfusion module could be incorporated into well-plates (Golway, paragraphs [0072], [0091], and [0094] “well plate”) such as those used by Pant (Pant, paragraph [0070]; Fig. 10A, elements 138 “one or more wells”).
Third, Applicant argues, “Golway does not provide a singular plate comprising a plurality of partitions”. This is irrelevant as Golway is not the primary reference, and the quotation is not present in the Office Action.
However, for the sake of compact prosecution, Pant’s and Golway’s inventions can both used in singular and the plural (see Pant paragraph [0167]; and, Golway paragraph [0071]). Pant specifically describes a singular plate (Figs. 10A-10B and paragraphs [0068]-[0069]), and Golway describes a singular plate (Figs. 11A-12C and paragraphs [0032]-[0033]).
Regarding the dependent claims, these claims are rejected as the independent claim is still rejected and no further arguments were made regarding the dependent claims.
Conclusion
THIS ACTION IS MADE FINAL. 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 NATHAN G ESPERON whose telephone number is 571-272-9807, and whose fax number is 571-273-8464. The examiner can normally be reached 9 am - 6 pm Monday through Thursday, and 9 am - 6 pm every other Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, Applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached at 571-272-1374. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/N.G.E./
Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799
Prosecution Insights