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 Arguments
Applicant's arguments filed 05/12/2026 have been fully considered but they are not persuasive.
Applicant has argued that the “middle channel” disclosed by Uzel et al. (Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units) does not read on the claimed neuron supply part because Applicant alleges that it contains gel and not neurons. In response to applicant’s argument, the Examiner asserts that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Neurons are not a positively recited structural component of the claimed chip; rather, the claim recites culturing neurons as an intended use of the chip (“the neuron chamber stores, fixes, and cultures therein a mixture of neurons and an auxiliary component supplied through the neuron inlet and serves as a culture container in which the fixed neurons are cultured”). The “middle channel” disclosed by Uzel et al. is structurally the same as the claimed neuron supply part, as discussed in the prior Office Action, and Applicant has not pointed to any specific structural features that are present in the claimed neuron supply part as opposed to the prior art. In this case, the prior art neuron chamber (chamber of “middle channel”) is fully capable of performing the intended use as it comprises a 0.5 mm wide chamber that is structurally capable of storing, fixing, and culturing a mixture of neurons and an auxiliary component (see p. 3 col. 2 para. 2-p. 4 col. 2 para. 1, p. 9 col. 1 para. 4 and Figs. 3-4; in fact, Uzel et al. discloses a portion of a neuron extends into the chamber during operation, see axonal outgrowth in Figs. 3-4). For example, a user could pipette neurons into the chamber of the “middle channel” of the device disclosed by Uzel et al., wait for a time period (“stores” as claimed), fix the neurons using a hydrogel or other fixing solution (“fixes” as claimed), add an auxiliary component through the neuron inlet, and culture the neurons therein (“cultures therein a mixture of neurons and an auxiliary component” as claimed), thus allowing the chamber of “middle channel” to serve as a culture container in which fixed neurons are cultured. Whether or not Uzel et al. discloses use of different hydrogels and/or cell types within the channels during operation of the device does not preclude Uzel et al. from anticipating the structural features of the device according to claim 1, as the underlying prior art device comprises the same structural features as those claimed.
In the prior Office Action, the Examiner acknowledged that while Uzel et al. discloses the micro-post structures, Uzel et al. is silent as to them having “a vertically long hexagonal shape”; however, this feature is obvious in view of the teachings of Novak et al. as previously discussed. Applicant has argued that Novak et al. discloses circularly arranged micro-posts. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As discussed in the prior Office Action, Uzel et al. already discloses a linear arrangement of micro-post structures in the direction of extension of channels and chambers (see prior Office Action and Figs. 3-4 of Uzel et al.). The secondary reference Novak et al. was merely relied upon for the particular teaching of the shape of the individual micro-post structures. Therefore, Applicant’s argument is unpersuasive.
The claim amendments dated 05/12/2026 have necessitated a new grounds of rejection.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-5, 7, and 11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the astrocyte supply parts" in the 7th-to-last line. There is insufficient antecedent basis for this limitation in the claim. The prior lines of the claim recite “(b) astrocyte supply part” (singular) rather than a plurality of astrocyte supply parts.
Claim 1 recites the limitation “the culture medium supply parts” in the 5th-to-last line. There is insufficient antecedent basis for this limitation in the claim. The prior lines of the claim recite “(a) a culture medium supply part” (singular) rather than a plurality of culture medium supply parts.
For the purpose of examination on the merits, the Examiner will interpret the claim as defining a device comprising two astrocyte supply parts, each astrocyte supply part comprising the structure defined in part (b) of the claim, and two culture medium supply parts, each culture medium supply part comprising the structure defined in part (a) of the claim.
Regarding claim 3, the phrase “wherein the culture medium channels serve as main flow passage” is unclear and the metes and bounds of the claim therefore cannot be discerned. It is unclear if this phrase recites that the culture medium channels each serve as separate main flow passages, or whether they collectively serve as a single main flow passage.
Claim 3 recites the limitation “the two culture medium storage chambers” in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 3 depends, has been interpreted as reciting two culture medium supply parts, each comprising two culture medium storage chambers, as discussed above, and thus the device comprises a total of four culture medium storage chambers. It is unclear which two of the four are being referred to in claim 3.
Claim 5 recites the limitation “the astrocyte inlet” in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 5 depends, has been interpreted as reciting two of the astrocyte supply parts, each comprising an astrocyte inlet, as discussed above, and thus the device comprises a total of two astrocyte inlets. It is unclear which of the two is being referred to in claim 5.
Claim 7 recites the limitation “the auxiliary component” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 5, from which claim 7 depends, recites “an auxiliary component supplied through the astrocyte inlet”; however, claim 1, from which claim 7 also ultimately depends, recites “an auxiliary component supplied through the neuron inlet”. It is unclear which auxiliary component is being referred to in claim 7.
Claim 11 recites the limitation “the portion of the culture medium channels” in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 11 depends, has been interpreted as reciting two culture medium supply parts, each comprising a portion, as discussed above, and therefore antecedent basis for a single portion of both culture medium channels is not present.
Claim 11 recites the limitation “the portion of the astrocyte chambers” in lines 3-4. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 11 depends, has been interpreted as reciting two astrocyte supply parts, each comprising a portion, as discussed above, and therefore antecedent basis for a single portion of both astrocyte channels is not present.
Dependent claims are rejected for the same reason(s) as the base claim(s) upon which they depend.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3, 5, 7, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Uzel et al. (Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units) (already of record) in view of Novak et al. (US Patent Application Publication 2017/0022464) (already of record).
Regarding claim 1, Uzel et al. discloses a biomimetic nerve chip (Abstract) (Fig. 3, p. 4) for evaluating a drug response (p. 4 col. 2 para. 1-p. 5 col. 1 para. 1) (thus, the device is fully capable of evaluating efficacy and toxicity of a drug), the biomimetic nerve chip comprising:
a culture medium supply part (p. 3 col. 2 para. 2, p. 9 col. 1 para. 4) (Fig. 3, p. 4), comprising:
two culture medium storage chambers (p. 3 col. 2 para. 2, p. 9 col. 1 para. 4) (Fig. 3, p. 4), and
a culture medium channel communicating with each of the chambers (p. 3 col. 2 para. 2, p. 9 col. 1 para. 4) (Fig. 3, p. 4);
a cell supply part (p. 3 col. 2 para. 2-p. 4 col. 2 para. 1, p. 9 col. 1 para. 4) (Fig. 3, p. 4) (reads on an astrocyte supply part as will be discussed below), comprising:
a cell inlet, cell outlet, and cell chamber (see “leftmost channel” and two ports at either end thereof, p. 3 col. 2 para. 2-p. 4 col. 2 para. 1, p. 9 col. 1 para. 4) (Figs. 3-4, pp. 4-5) (note: the cell chamber is a 0.5 mm channel that receives neurospheres therein via the ports, see p. 3 col. 2 para. 2, and thus the aforementioned structures are fully capable of operating as an astrocyte inlet, astrocyte outlet, and astrocyte chamber, and will hereinafter be referred to as such),
wherein the astrocyte chamber has two ends (Figs. 3-4, pp. 4-5),
wherein the astrocyte inlet is provided at one end of the astrocyte chamber (Figs. 3-4, pp. 4-5),
wherein the astrocyte outlet is provided at the other end of the chamber (Figs. 3-4, pp. 4-5),
wherein the astrocyte chamber is provided between the astrocyte inlet and the astrocyte outlet and extended in the same direction as the culture medium channel to be joined with a portion of the culture medium channel (p. 3 col. 2 para. 2-p. 4 col. 2 para. 1) (Figs. 3-4, pp. 4-5), wherein a first mixing region for cross-communication of the a culture medium is formed in a joining portion between the astrocyte chamber and the culture medium channel (p. 3 col. 2 para. 2-p. 4 col. 2 para. 1) (Figs. 3-4, pp. 4-5), and
astrocyte channels provided to communicate between one end of the astrocyte chamber and the astrocyte inlet and between the other end of the astrocyte chamber and the astrocyte outlet, respectively (see channels communicating between each of the two ports and the 0.5 mm channel, Figs. 3-4, pp. 4-5); and
a neuron supply part (comprising “middle channel”; receives portion of neurons and thus reads on a neuron supply part) (channel (p. 3 col. 2 para. 2-p. 5 col. 1 para. 1) (Figs. 3-4, pp. 4-5), comprising:
a neuron inlet, a neuron outlet, and a neuron outlet (see “middle channel” and two ports at either end thereof, p. 3 col. 2 para. 2-p. 4 col. 2 para. 1, p. 9 col. 1 para. 4) (Figs. 3-4, pp. 4-5) (note: the two ports read on a neuron inlet and neuron outlet, respectively, as they are ports communicating with a region receiving a portion of a neuron as discussed above),
wherein the neuron chamber has two ends (Figs. 3-4, pp. 4-5),
wherein the neuron inlet is provided at one end of the neuron chamber (Figs. 3-4, pp. 4-5),
wherein the neuron outlet is provided at the other end of the neuron chamber (Figs. 3-4, pp. 4-5),
wherein the neuron chamber is provided between the neuron inlet and the neuron outlet and extended in the same direction as the astrocyte chamber to be joined with a portion of the astrocyte chamber (p. 3 col. 2 para. 2-p. 5 col. 1 para. 1) (Figs. 3-4, pp. 4-5), wherein a second mixing region for cross-communication of a culture medium is formed in a joining portion between the neuron chamber and the astrocyte chamber (p. 3 col. 2 para. 2-p. 5 col. 1 para. 1) (Figs. 3-4, pp. 4-5), and
neuron channels provided to communicate between one end of the neuron chamber and the neuron inlet and between the other end of the neuron chamber and the neuron outlet (see channels communicating between each of the two ports and the main region of the middle channel comprising the neuron portion, Figs. 3-4, pp. 4-5); wherein the first mixing region is composed of a portion of the culture medium channel, a portion of the astrocyte chamber joined with the portion of the culture medium channel, and partial block members (called posts) formed in the joining portion (p. 3 col. 2 para. 2-p. 5 col. 1 para. 1) (Figs. 3-4, pp. 4-5);
wherein the second mixing region is composed of a portion of the astrocyte chamber, a portion of the neuron chamber joined with the portion of the astrocyte chamber, and partial block members (called posts) formed in the joining portion (p. 3 col. 2 para. 2-p. 5 col. 1 para. 1) (Figs. 3-4, pp. 4-5);
wherein the partial block members are micro-post structures separated from each other and arranged in a line (“row of posts”) in a direction of extension of the culture medium channel, the astrocyte chamber, and the neuron chamber (p. 3 col. 2 para. 2-p. 5 col. 1 para. 1) (Figs. 3-4, pp. 4-5), wherein the arrangement of micro-post structures forms bottleneck-structured movement passages between the culture medium channel, the astrocyte chamber, and the neuron chamber (p. 3 col. 2 para. 2-p. 5 col. 1 para. 1) (Figs. 3-4, pp. 4-5),
wherein two sets of astrocyte supply parts are respectively provided above and below the neuron supply part (see the first astrocyte supply part discussed above and additionally the “right channel”; thus two parts are provided on either side of the “middle” neuron channel which fulfills the claim limitation of “above and below the neuron supply part” depending on the orientation of the device; each of the left and right channels read on being an astrocyte supply part as each of the left and right channels are at least 0.5 mm wide cell channels which would be fully capable of receiving astrocytes, see p. 3 col. 2 para. 2-p. 5 col. 1 para. 1 and Figs. 3-4, pp. 4-5); and
wherein two sets of culture medium supply parts are respectively provided so as to “flank” the “left”, “middle”, and “right” cell channels (reads on two sets of culture medium supply parts being provided respectively “above” the astrocyte supply part provided “above” the neuron supply part and “below” the astrocyte supply part provided “below” the neuron supply part) (p. 3 col. 2 para. 2-p. 5 col. 1 para. 1) (Figs. 3-4, pp. 4-5).
As to the limitation “wherein the neuron chamber stores, fixes, and cultures therein a mixture of neurons and an auxiliary component supplied through the neuron inlet and serves as a culture container in which the fixed neurons are cultured”, this is a recitation of intended use of the neuron chamber and has been given appropriate patentable weight. It is well established that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In this case, the prior art neuron chamber (chamber of “middle channel”) is fully capable of performing the intended use as it comprises a 0.5 mm wide chamber that is structurally capable of storing, fixing, and culturing a mixture of neurons and an auxiliary component (see p. 3 col. 2 para. 2-p. 4 col. 2 para. 1, p. 9 col. 1 para. 4 and Figs. 3-4; in fact, Uzel et al. discloses a portion of a neuron extends into the chamber during operation, see axonal outgrowth in Figs. 3-4). For example, a user could pipette neurons into the chamber of the “middle channel” of the device disclosed by Uzel et al., wait for a time period (“stores” as claimed), fix the neurons using a hydrogel or other fixing solution (“fixes” as claimed), add an auxiliary component through the neuron inlet, and culture the neurons therein (“cultures therein a mixture of neurons and an auxiliary component” as claimed), thus allowing the chamber of “middle channel” to serve as a culture container in which fixed neurons are cultured.
Uzel et al. is silent as to wherein the micro-post structures have a vertically long hexagonal shape; however Uzel et al. discloses that during use the micro-post structures may be used to constrain a gel while allowing cell-cell signaling and nutrient supply (p. 4 col. 1 para. 1).
Novak et al. discloses a biomimetic chip (para. 55-56) comprising a first chamber (130) and a second chamber (132) divided by an arrangement of spaced apart micro-posts (124) (para. 68-69) (Figs. 1a-1c) such that the micro-posts constrain a fluid such as a gel within one or more of the chambers (para. 73, 81). Novak et al. further discloses forming the micro-post structures so as to have a hexagonal shape because “it has been found that the shape of a hexagon provides better contact angles for surface tension of fluids (e.g., liquids, gels, etc.) to constrain the fluids by the posts” (para. 73). Additionally, Novak et al. discloses that each micro-post structure is taller than it is wide (para. 70, 73), and that the arrangement of micro-posts forms bottleneck-structured movement passages between the chambers (Fig. 1c, sheet 2 of 16).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the micro-post arrangement disclosed by Uzel et al. such that the micro-post structure are a vertically long (i.e., each micro-post is taller than it is wide) hexagonal shape wherein the arrangement of hexagonal micro-post structures forms bottleneck-structured movement passages between the chambers and the channels, as Novak et al. discloses that this particular shape and arrangement was known in the art to be effective for constraining a gel within a chamber on a biomimetic chip, and the skilled artisan would have been motivated to select a particular configuration recognized in the art to be effective for confining gel regions, as envisioned by Uzel et al.
Regarding claim 2, Uzel et al. discloses wherein the culture medium storage chambers store therein a culture medium to be supplied to the astrocyte chambers and the neuron chamber through the first and second mixing regions and serve to supply the stored culture medium to neurons through the culture medium channels and the astrocytes chamber (p. 3 col. 2 para. 2-p. 5 col. 1 para. 1) (Figs. 3-4, pp. 4-5).
Regarding claim 3, Uzel et al. discloses wherein the culture medium channels serves as a main flow passage of a culture medium wherein the culture medium flows between the two culture medium storage chambers (p. 3 col. 2 para. 2) (Figs. 3-4, pp. 4-5).
Regarding claim 5, Uzel et al. discloses wherein the astrocyte chambers store, fix, and culture therein a mixture of cells and Matrigel (reads on an auxiliary component supplied through the astrocyte inlet (p. 3 col. 2 para. 2, p. 6 col. 1 para. 1) (Figs. 3-4, pp. 4-5), serve as culture containers in which the fixed cells are cultured (Abstract, p. 3 col. 2 para. 2, p. 6 col. 1 para. 1) (Figs. 3-4, pp. 4-5), and serves as a passage through which culture medium introduced through the culture medium channels is delivered to neurons fixed in the neuron chamber and various metabolites and wastes secreted from the neurons are drained to the outside of the neuron chamber (Abstract, p. 3 col. 2 para. 2-p. 6 col. 1 para. 1) (Figs. 3-4, pp. 4-5).
As to the limitation of the cells being astrocytes, this is a recitation of intended use of the chip and has therefore been given appropriate patentable weight (see MPEP 2114). The structure disclosed by Uzel et al. is fully capable of operating such that the cells are astrocytes, as discussed in the rejection of claim 1, above, and therefore this limitation does not introduce a patentable distinction over the prior art.
Regarding claim 7, Uzel et al. discloses wherein the auxiliary component is Matrigel, as set forth above.
Regarding claim 11, Uzel et al. discloses wherein the micro-post structures allow cross-communication of a culture medium, through the separated regions thereof, between the portion of the culture medium channels and the portion of the astrocyte chambers joining with the portion of the culture medium channels and between the portion of the astrocyte chambers and the portion of the neuron chamber joining with the portion of the astrocyte chamber (p. 3 col. 2 para. 2-p. 6 col. 1 para. 1) (Figs. 3-4, pp. 4-5).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Uzel et al. (Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units) (already of record) in view of Novak et al. (US Patent Application Publication 2017/0022464) (already of record) as applied to claim 1, above, and in further view of Osaki et al. (Crosstalk between developing vasculature and optogenetically engineered skeletal muscle improves muscle contraction and angiogenesis) (already of record).
Regarding claim 4, Uzel et al. discloses the culture medium channels, as set forth above, and further discloses wherein the culture medium channels communicate with neighboring channels, such as a channel containing muscle cells (p. 3 col. 2 para. 2-p. 4 col. 1 para. 1) (Figs. 3-4, pp. 4-5).
Uzel et al. is silent as to wherein an inner surface of the culture medium channels are coated with vascular endothelial cells.
Osaki et al. discloses that crosstalk between vasculature and muscle is important to the physiological function of muscle (Title, abstract) and to this end Osaki et al. discloses providing vascular endothelial cells and muscle cells within a microfluidic device to study their interaction (p. 66 col. 1 para. 3-col. 2 para. 2, p. 73 col. 1 last paragraph) (Fig. 1, p. 66).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the culture medium channels disclosed by Uzel et al. to be coated with vascular endothelial cells, based on the teachings of Osaki et al., to provide for crosstalk between vascular endothelial cells and other cell types within the device to improve physiological modeling.
Conclusion
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 HOLLY KIPOUROS whose telephone number is (571)272-0658. The examiner can normally be reached M-F 8.30-5PM.
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/HOLLY KIPOUROS/Primary Examiner, Art Unit 1799
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