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 .
Election/Restrictions
Applicant’s election without traverse of Invention I, claims 1-19 in the reply filed on 09/16/2025 is acknowledged.
Claim 20 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/16/2025.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China on 05/19/2022. It is noted, however, that applicant has not filed a certified copy of the CN202210557883.0 application as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement(s) (IDS) were submitted on:
01/16/2024
Accordingly, the information disclosure statement(s) are being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities:
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required:
Regarding claim 1, in lines 9 and 16; claim 2, in line 3; and, claim 4, in line 3; for the phrase “each pair of the first channel and the second channel”, the term “pair” is not in the instant written specification.
Regarding claim 1, in line 18, for the phrase “composed of”, this term is not in the instant written specification.
Regarding claim 19, in line 5, the phrase “cells engineered derived from” does not have the word “engineered” in the instant written specification. A similar phrase found in the instant specification is “normal cells with certain modifications” (instant specification, paragraph [0026]).
Regarding claim 8, in lines 1-2, the phrase “wherein each of the converging channels is composed of an inlet converging channel and an outlet converging channel”; however, the terms “composed of” is not the specification, and the limitation is also not present in the specification, as each singular converging channel would need to have two kinds of converging channels – an inlet one and an outlet one, when this is not the case in the drawings or the specification.
Regarding claim 19, in lines 5-6, the phrase “or cells engineered derived from the model of the normal cells” is phrased in the alternative “or”; in the instant specification, the phrase uses the term “and” instead (instant specification, paragraph [0026]). The limitations can be amended to include either or both, due to the presence of the limitation in the originally filed claims and the originally filed specification. Alternatively, these portions can be canceled.
Appropriate correction is required.
The use of the term “etaluma” (located in paragraphs [0081], [0083], and [0085] and should be Etaluma™), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 1, 3, 6, 9, 11, 13-14, 16, and 19 are objected to because of the following informalities:
Regarding claim 1, in lines 4-26, these lines should be indented to reflect the structure of the microfluidic chip claimed in line 3.
Regarding claim 3, in line 3, there should be a comma after the word “eight”.
Applicant is advised that should claim 1 be found allowable, claim 6 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Regarding claim 9, in line 3, the phrase “the most bottom” should be “a last level” or “a bottom level”.
Regarding claim 11, in line 5, the phrase “the last level” should be “a last level” or “a bottom level”.
Regarding claim 11, in line 9, the phrase “and lateral channels” should be “and the lateral channels”.
Regarding claim 12, in line 3, there should be an Oxford comma after the term “the first outlet”.
Regarding claim 12, in line 6, there should be an Oxford comma after the term “the second extension channel”.
Regarding claim 12, in line 11, there should be an Oxford comma after the term “the second channels”.
Regarding claim 12, in line 12, there should be an Oxford comma after the term “the second channels”.
Regarding claim 13, in lines 1-2, the phrase “the channel portions of the upper chip and those of the lower chip” should be “the upper channel portions and the lower channel portions”.
Regarding claim 14, in lines 1-2, the phrase “all the channel portions of the upper chip or that of the lower chip” should be “all the upper channel portions and the lower channel portions”.
Regarding claim 16, in line 2, the phrase “each of other channels than” should be “each channel other than”.
Regarding claim 19, in line 3, the phrase “immune cells and” should be “immune cells, and” to include an Oxford comma.
Regarding claim 19, in line 5, the phrase “macrophages or tumor-associated fibroblasts” should be “macrophages, tumor-associate fibroblasts” for clarity so the group of cells is better listed grammatically.
Regarding claim 19, in lines 2, 4, and 6, before each of the three phrases “and wherein”, it recommended to use a semicolon instead of a comma to denote three different lists within a single claim.
Appropriate correction is required.
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 1-19 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.
Regarding claim 1, in line 3, the claim recites the limitation “a microfluidic chip”; the limitation should read “at least one microfluidic chip” due to the dependency of claim 18, line 2, “a plurality of microfluidic chips”, as well as claim 6, line 2, “one microfluidic chip”. This claim becomes indefinite in later dependencies due to the singularity of microfluidic chip in claim 1, see below for claim 18.
Regarding claim 1, in line 8, the claim recites the limitation “two extension channels”; the limitation should read “a plurality of two extension channels”. This is because there are more than two extension channels mentioned later in claim 1, inherent to the plurality of the confined migration channels: “the two extension channels composed of a first extension channel and a second extension channel being respectively disposed at two opposite ends of each of the confined migration channels”. From the drawings at least, it would appear that the invention comprises a plurality confined migration channels and a plurality of pairs of the extension channels, wherein each pair of the extension channels comprises a first extension channel and a second extension channel.
Regarding claim 8, in lines 1-2, the phrase “wherein each of the converging channels is composed of an inlet converging channel and an outlet converging channel”; however, the limitation is worded incorrectly, as each singular converging channel would need to have two kinds of converging channels – an inlet one and an outlet one, when this is not the case in the drawings or the specification. Additionally, the closed language “composed of” limits further structure to the limitation of “the converging channels”, when further “comprising” language is used later in the claim. However, this claim limitation is being interpreted as “one of the converging channels comprise an inlet converging channel, and the other converging channels comprise an outlet converging channel”.
Regarding claim 9, in lines 1-4, the claim recites three instances of the term “a pyramid-like flow diverging structure”. The term “-like” in claim 9 is a relative term which renders the claim indefinite. The term “-like” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Regarding claim 10, in line 1, the claim recites the term “a pyramid-like flow diverging structure”. The term “-like” in claim 10 is a relative term which renders the claim indefinite. The term “-like” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. See explanation above.
Regarding claim 11, in lines 1-2, 6, and 8, the claim recites three instances of the term “a pyramid-like flow diverging structure”. The term “-like” in claim 11 is a relative term which renders the claim indefinite. The term “-like” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. See explanation above.
Regarding claim 12, in lines 5-6, the terms “the first channel”, “the second channel”, “the first extension channel”, “the second extension channel”, and “the confined migration channel” should be, respectively, “the first channels”, “the second channels”, “the first extension channels”, “the second extension channels”, and “the confined migration channels”. This claim is indefinite is due to the plurality of these channels in claim 1. There is insufficient antecedent basis for these limitations (“the first channel”, “the second channel”, and “the confined migration channel”) in the claim. Also, this is because there are more than two extension channels mentioned in claim 1, inherent to the plurality of the confined migration channels.
Regarding claim 12, in line 9, the term “the channels” should be “all channels” or describe exactly which channels are being bounded by the limitation, as it is unclear what is meant by “the channels” because there are multiple channels mentioned. This claim is indefinite is due to the plurality of these channels in claim 1. There is insufficient antecedent basis for this limitation (“the channels”) in the claim.
Regarding claim 13, in line 2, the term “the confined migration channel is” should be “each of the confined migration channels are”. This claim is indefinite is due to the plurality of these channels in claim 1. There is insufficient antecedent basis for this limitation (“the confined migration channel is”) in the claim.
Regarding claim 13, in line 3, the phrase “between the first extension channel and the second extension channel” should be “between each of their corresponding first extension channels and their corresponding second extension channels”. This claim is indefinite is due to the plurality of these channels in claim 1, see explanation above about the plurality of two extension channels. There is insufficient antecedent basis for this limitation (“between the first extension channel and the second extension channel”) in the claim.
Regarding claim 14, in lines 2-3, the phrase “the confined migration channel” should be “the confined migration channels”. This claim is indefinite is due to the plurality of these channels in claim 1. There is insufficient antecedent basis for this limitation (“the confined migration channel”) in the claim.
Regarding claim 14, in lines 3-4, the phrase “no channel is provided in a corresponding portion of the lower chip or a corresponding portion of the upper chip with respect to the confined migration channel” does not clearly describe the metes and bounds of the invention in a way that the examiner can understand. The limitation is indefinite and unclear because this configuration would result in no channel being present where any channel would be due to the depth of the confined migration channel being equal to the other channels and that there no channel with respect to the confined migration channel.
Regarding claim 14, in line 4, the phrase “the confined migration channel” should be “the confined migration channels”. This claim is indefinite is due to the plurality of these channels in claim 1. There is insufficient antecedent basis for this limitation (“the confined migration channel”) in the claim.
Regarding claim 15, in line 2, the phrase “the confined migration channel” should be “the confined migration channels”. This claim is indefinite is due to the plurality of these channels in claim 1. There is insufficient antecedent basis for this limitation (“the confined migration channel”) in the claim.
Regarding claim 15, in lines 3-4, the phrase “the confined migration channel” should be “the confined migration channels”. This claim is indefinite is due to the plurality of these channels in claim 1. There is insufficient antecedent basis for this limitation (“the confined migration channel”) in the claim.
Regarding claim 16, in lines 2-3, the phrase “the confined migration channel” should be “the confined migration channels”. This claim is indefinite is due to the plurality of these channels in claim 1. There is insufficient antecedent basis for this limitation (“the confined migration channel”) in the claim.
Regarding claim 16, in line 4, the phrase “the first extension channel” should be “the first extension channels”. This claim is indefinite is due to the plurality of these channels in claim 1, see above explanation about the plurality of two extension channels.
Regarding claim 16, in lines 4-5, the phrase “the second extension channel is” should be “the second extension channels are”. This claim is indefinite is due to the plurality of these channels in claim 1, see above explanation about the plurality of two extension channels.
Regarding claim 16, in line 5, the phrase “the confined migration channel is” should be “the confined migration channels are”. This claim is indefinite is due to the plurality of these channels in claim 1. There is insufficient antecedent basis for this limitation (“the confined migration channel”) in the claim.
Regarding claim 16, in line 6, the phrase “each of the confined migration channels has identical length, width, and a square cross-section with each other”, a square cross-section cannot be completed with the defined dimensions given in the confined migration channels in this claim. Therefore, the claim is indefinite and unclear.
Regarding claim 17, in line 2, the phrase “the channels” is undefined. Please define which channels are being considered. This claim is indefinite is due to the plurality of these channels in claim 1. There is insufficient antecedent basis for this limitation (“the channels”) in the claim.
Regarding claim 18, in line 2, the phrase “a plurality of the microfluidic chips”, there is a plurality of microfluidic chips mentioned, but only one is described in parent claim 1. It is unclear if the plurality of the microfluidic chips mentioned are duplicates of claim 1. A recommendation is to slightly rephrase claim 1, see above.
Regarding claim 19, in line 1, the phrase “the cells” should be “cells of the cell culture”. There is insufficient antecedent basis for this limitation (“the cells”) in the claim.
Regarding claim 19, in lines 2-4, the phrase is an improper Markush group. It includes open limitations using the term “comprises” as well as the term “and”. See below rejection for specifics.
Regarding claim 19, in lines 5-6, the term “a model of the disease cells are … cells engineered derived from the model of the normal cells”, the metes and bounds of this limitation are unclear and indefinite. Some engineered cells derived from the model of the normal cells may not meet the limitation of a “disease cell”. Others engineered cells may; however, engineered cells encompass both limitations, so the limitation indefinite as to its meaning.
Regarding claim 19, in lines 6-9, the phrase is an improper Markush group. It includes open limitations using the term “comprises” as well as the term “and”. See below rejection for specifics.
Regarding claim 19, in line 9, the parenthetical phrase “neuroendocrine tumor (cancer) cells and all other tumor cells associated therewith” is indefinite. The metes and bounds of the parenthetical limitation “(cancer)” are unknown, as not all tumor cells are cancerous. Also, some cancer cells do not generally form a tumor, e.g. leukemia. Although blood cells may not be considered neuroendocrine cells, differentiating the terms “tumor” and “cancer” is necessary. Also, the first indication in the phrase of “tumor” and the second indication in the phrase “all other tumor cells associated therewith” may be redundant once the term “(cancer)” is clarified.
Regarding claim 19, in line 9, the phrase “all other tumor cells associated therewith” is indefinite. The metes and bounds of the limitation are unknown, as the limitation is not explained.
Claim 19 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush groupings of:
“a model of the normal cells comprises kidney cells, lung, cells, digestive tract cells, brain cells, liver cells, fibroblasts, endothelial cells, immune cells, and macrophages” of claim 19; and,
“the tumor cells comprise gastric cancer cells, pancreatic cancer cells, colorectal cancer cells, liver cancer cells, bone cancer cells, lung cancer cells, kidney cancer cells, prostate cancer cells, breast cancer cells, brain cancer cells, neuroendocrine tumor (cancer) cells and all other tumor cells associated therewith” of claim 19
are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The term “comprising” and the term “and” force a grouping of alternatives to include all of the alternatives in an open limitation. This is a possible interpretation, however, it is confusing as it may not accurately reflect the invention in a proper Markush group. However, because the hypothetical proper Markush group is also not delineated in the instant specification, amending these groupings of alternatives into proper Markush groups would likely cause another rejection to occur. Applicant is notified that an amendment to this effect would likely result in at least one rejection under 35 U.S.C. § 112(a) for lack of written description and would constitute a new matter situation, as the originally filed application does not include the proper Markush group, even at the instant specification (see instant specification, paragraphs [0025]-[0027]).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Regarding the dependent claims 2-19, these claims are rejected for the same reason as the base claim upon which they depend.
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 1-11, 17, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Yoon (US 20190344270) (newly cited) in view of Qin (CN 111218401) (machine translation) (newly cited).
Regarding claim 1, Yoon discloses a confined migration microfluidic device (paragraph [0008] and [0081]) for cell culture and drug screening (paragraph [0093]), comprising:
a microfluidic chip (paragraph [0008]), the microfluidic chip comprising:
a plurality of first channels (paragraph [0008] “entrance channel”);
a plurality of second channels each being disposed in parallel with one of the first channels (paragraphs [0008] “exit channel” and [0068]-[0069] “parallel fluid channels”);
a plurality of confined migration channels (Fig. 1d-1e “Culture Chamber”, paragraph [0008]);
two extension channels (annotated Fig. 1);
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Yoon, Annotated Fig. 1
each pair of the first channel and the second channel being connected through the confined migration channels (annotated Fig. 1), each of the confined migration channel having a depth smaller than that of each of the first channels and second channels (paragraph [0069] the entrance and exit channels have a height of at least 5 times (e.g. at least 10 times) the height of the single cell chambers);
each of the first channels (paragraph [0008] “entrance channel”) being provided with a first inlet (annotated Fig. 3); and
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Yoon, Annotated Fig. 3
each of the second channels being provided with an outlet (annotated Fig. 3), respectively,
the plurality of confined migration channels between each pair of the first channel and the second channel being identical in terms of shape and dimension (paragraph [0110] “cell capture sites with 10 μm×10 μm opening area”);
the two extension channels composed of a first extension channel (annotated Fig. 1, top, inlet channel) and a second extension channel (annotated Fig. 1, bottom, outlet channel) being respectively disposed at two opposite ends of each of the confined migration channels (Fig. 1d-1e “Culture Chamber”, paragraph [0008]),
the first extension channel (annotated Fig. 1, top, inlet channel) communicating with the first channel (paragraph [0008] “entrance channel”) and the confined migration channel (Fig. 1d-1e “Culture Chamber”, paragraph [0008]);
the second extension channel (annotated Fig. 1, bottom, outlet channel) communicating with the second channel (paragraphs [0008] “exit channel”) and the confined migration channel (Fig. 1d-1e “Culture Chamber”, paragraph [0008]).
Yoon does not disclose:
the first channels being provided … an … outlet;
the second channels being provided with a second inlet; and,
each of the first extension channel and the second extension channel having a depth greater than that of the confined migration channel.
Regarding features 1 and 2, Qin discloses feature 1 (Fig. 1, element 4 “waste liquid tank” and paragraph [0033]) and feature 2 (Fig. 1, element 1 “inlet tank” and paragraph [0033]).
In the analogous art of tumor chips for neovascularization and drug evaluation methods, it would have been obvious to one skilled in the art before the effective filing date to modify the chip of Yoon with the inlets and outlets of Qin in order to provide a way to cause flow of media, cells, and drug candidates through the multiple microfluidic chip channels.
Regarding the limitation “each … outlet [… and] second inlet”, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). It would have been obvious to one skilled in the art before the effective filing date to modify Yoon’s microfluidic chip with multiple inlets and outlets of Qin in order to provide a way to cause flow of media, cells, and drug candidates through the multiple microfluidic chip channels.
Regarding feature 3, Yoon does not disclose this feature.
However, the limitation of the first extension channel and the second extension channel having a depth greater than that of the confined migration channel is a matter of relative dimensions. The claim limitation is obvious under MPEP § 2144.04(IV)(A), which states that “where the only difference between the prior art and the claims was a recitation of relative dimensions … [and the claimed device] would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device”. It would have been obvious to one skilled in the art before the effective filing date to modify the height or depth dimension of the first and second extension channels of Yoon to be greater than the confined migration channel in order to allow the cell to fluidically drawn towards the migration channel to present an opportunity for the cell to attempt or disregard migration through a conduit in response to a potential cancer drug candidate.
Regarding claim 2, Yoon discloses wherein the plurality of identical confined migration channels comprises 200 identical confined migration channels provided between each pair of the first channel and the second channel (paragraphs [0013] and [0105]).
Yoon does not disclose four to ten identical confined migration channels.
However, it would have been obvious to one skilled in the art before the effective filing date to modify the number of identical confined migration channels to be between four and ten in order to create a less intricate microfluidic chip that takes less time and resources to construct.
Also, the limitation is obvious as a matter of routine optimization, because the number of identical confined migration channels is a result-effective variable. The motivation for optimizing this result-effective variable is to create a less intricate microfluidic chip with fewer identical confined migration channels that takes less time and resources to construct. MPEP § 2144.05(II).
Additionally, regarding the limitation “four to ten identical confined migration channels”, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). It would have been obvious to one skilled in the art before the effective filing date to modify modified Yoon’s microfluidic chip in order to create a less intricate microfluidic chip with fewer identical confined migration channels that takes less time and resources to construct.
Regarding claim 3, Yoon discloses wherein the plurality of identical confined migration channels comprises 200 identical confined migration channels between each pair of the first channel and the second channel (paragraphs [0013] and [0105]).
Yoon does not disclose four, six, eight or ten identical confined migration channels.
However, it would have been obvious to one skilled in the art before the effective filing date to modify the number of identical confined migration channels to be between four and ten in order to create a less intricate microfluidic chip that takes less time and resources to construct.
Also, the limitation is obvious as a matter of routine optimization, because the number of identical confined migration channels is a result-effective variable. The motivation for optimizing this result-effective variable is to create a less intricate microfluidic chip with fewer identical confined migration channels that takes less time and resources to construct. MPEP § 2144.05(II).
Additionally, regarding the limitation “four, six, eight or ten identical confined migration channels”, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). It would have been obvious to one skilled in the art before the effective filing date to modify modified Yoon’s microfluidic chip in order to create a less intricate microfluidic chip with fewer identical confined migration channels that takes less time and resources to construct.
Regarding claim 4, Yoon does not disclose wherein each of the first extension channels has a depth identical to that of each of the first channels; each of the second extension channels has a depth identical to that of each of the second channel.
However, the limitation about the first extension channels and the second extension channels is a matter of relative dimensions. The claim limitation is obvious under MPEP § 2144.04(IV)(A), which states that “where the only difference between the prior art and the claims was a recitation of relative dimensions … [and the claimed device] would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device”. It would have been obvious to one skilled in the art before the effective filing date to modify the height or depth dimension of the first and second extension channels of Yoon to be as claimed in order to allow the cell to fluidically drawn towards the migration channel to present an opportunity for the cell to attempt or disregard migration through a conduit in response to a potential cancer drug candidate.
Regarding claim 5, Yoon does not disclose wherein the first extension channels and the second extension channels are identical to each other.
Qin discloses symmetrical channels that appear to be congruent (Fig. 1, element 8 and paragraphs [0034] and [0036]).
In the analogous art of tumor chips for neovascularization and drug evaluation methods, it would have been obvious to one skilled in the art before the effective filing date to modify the chip of Yoon with the first and second extension channels of Qin in order to provide a way to cause flow of media, cells, and drug candidates through the multiple microfluidic chip channels to test the drug candidates on cells for cell migration.
If it is deemed that modified Yoon does not teach the limitation, the limitation about the first extension channels and the second extension channels is a matter of relative dimensions, shape of parts, and duplication of parts. The claim limitation is obvious under MPEP § 2144.04(IV)(A), which states that “where the only difference between the prior art and the claims was a recitation of relative dimensions … [and the claimed device] would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device”. In addition, the claim limitation is obvious, as the configuration of the claimed shape is a matter of choice, absent persuasive evidence that the particular configuration is significant. MPEP § 2144.04(IV)(B). Additionally, regarding the limitation, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). Additionally, it would have been obvious to one skilled in the art before the effective filing date to modify the dimensions of the first and second extension channels of Yoon to be as claimed in order to allow the cell to fluidically drawn towards each of the migration channels to present an opportunity for the cell to attempt or disregard migration through a conduit in response to a potential cancer drug candidate.
Regarding claim 6, modified Yoon teaches wherein the plurality of the first channels and the plurality of the second channels are provided on one microfluidic chip (annotated Fig. 1), and wherein two opposite ends of each of the second channels are provided with a second inlet and a second outlet (see rejection to claim 1 under Yoon in view of Qin), respectively; two opposite ends of each of the first channels are provided with a first inlet and a first outlet, respectively (see rejection to claim 1 under Yoon in view of Qin).
Regarding claim 7, modified Yoon teaches further comprising converging channels (annotated Fig. 1a) provided on the microfluidic chip (paragraph [0013]), and the converging channels (annotated Fig. 1a) being disposed at two opposite ends of the microfluidic chip (paragraph [0013]); and configured to channelize all of the first channels (annotated Fig. 1a).
Yoon does not disclose the converging channels being disposed at two opposite ends of each of the first channels; however, modified Yoon teaches the ends of the first channels (see rejection to claim 1, Yoon in view of Qin, describing inlets and outlets).
It would have been obvious to one skilled in the art before the effective filing date to modify the converging channels already present in the microfluidic chip of Yoon with the opposite ends of each of the first channels in modified Yoon in order to collect the waste media and cells at an outlet.
Regarding claim 8, Yoon discloses wherein the converging channels (annotated Fig. 1a-1b), an inlet converging channel (annotated Fig. 1a-1b, left side inlet), and an outlet converging channel (annotated Fig. 1a-1b, right side outlet), and wherein the first inlet (annotated Fig. 1a-1b) connects to the inlet converging channel (annotated Fig. 1a-1b, left side) and the first outlet (annotated Fig. 3) connects to the outlet converging channel (annotated Fig. 1a-1b, right side), and wherein the microfluidic chip further comprises an outlet connection channel (annotated Fig. 1a-1b, right side, central channel in the middle) provided at a central part of the outlet converging channel (annotated Fig. 1a-1b); the outlet connection channel connects the first outlet and the outlet converging channel (annotated Fig. 1a-1b).
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Yoon, annotated Figs. 1a and 1b
Regarding the limitation, “each of the converging channels is composed of an inlet converging channel and an outlet converging channel”, this claim limitation is being interpreted as “one of the converging channels comprise an inlet converging channel, and the other converging channels comprise an outlet converging channel”. Nevertheless, each converging channel has an inlet and an outlet (Yoon, Figs. 1a-1b).
Regarding claim 9, Yoon discloses a pyramid-like flow diverging structure provided on the microfluidic chip, wherein the number of flow channels at the most bottom of the pyramid-like flow diverging structure is equal to the number of the first channels, and wherein a top end of the pyramid-like flow diverging structure connects to the first inlet (annotated Fig. 1a-1b and paragraph [0105]).
Regarding claim 10, Yoon discloses wherein the pyramid-like flow diverging structure is a gradient flow diverging structure, and wherein each subsequent gradient layer is added with double the flow channels with respect to a preceding layer (annotated Fig. 1a-1b).
Yoon does not disclose “added with one flow channel with respect to a preceding layer”.
However, this limitation is an obvious modification based on the shape of the pyramid-like flow diverting structure and its gradient flow diverting structure. The claim limitation is obvious, as the configuration of the claimed shape is a matter of choice, absent persuasive evidence that the particular configuration is significant. MPEP § 2144.04(IV)(B). It would have been obvious to one skilled in the art before the effective filing date to modify the shape of Yoon’s pyramid-like structure in order to mix the fluids with turbulent flow.
Regarding claim 11, Yoon discloses wherein the pyramid-like flow diverging structure (annotated Figs. 1a-1b and paragraph [0105]) comprises multiple levels of flow diverging channels (annotated Figs. 1a-1b), and each level of the flow diverging channels comprises a lateral channel (annotated Figs. 1a-1b, lateral to the flow across Yoon’s chip) and a longitudinal channel (annotated Figs. 1a-1b, inline to the flow across Yoon’s chip), wherein the longitudinal channel of a preceding level connects to the lateral channel of a subsequent level (annotated Figs. 1a-1b), and wherein the pyramid-like flow diverging structure has a top layer (annotated Figs. 1a-1b, channel at the point of the pyramid-like flow diverging structure of Yoon) comprising only a first longitudinal channel (annotated Figs. 1a-1b, channel at the point of the pyramid-like flow diverging structure of Yoon), and the first longitudinal channel (annotated Figs. 1a-1b, channel at the point of the pyramid-like flow diverging structure of Yoon) connects the first inlet (annotated Figs. 1a-1b, “an inlet”) and the lateral channel (annotated Figs. 1a-1b, lateral channel under the longitudinal channel under the point of the pyramid-like flow diverging structure of Yoon) of a second stage of the pyramid-like flow diverging structure (annotated Figs. 1a-1b), and wherein each of the longitudinal channels and lateral channels has a depth equal to that of the first channel (paragraph [0105] “100 μm” and [0124] “flow channel” was fabricated with several different embodiments of thicknesses, one of which is “100 μm”, see how Yoon’s device was manufactured in paragraph [0131]).
Yoon does not disclose wherein the lateral channel of the last level connects all the first channels.
However, this is an obvious change in the shape of parts. The claim limitation is obvious, as the configuration of the claimed shape is a matter of choice, absent persuasive evidence that the particular configuration is significant. MPEP § 2144.04(IV)(B). It would have been obvious to one skilled in the art before the effective filing date to modify the shape of the pyramid-like structure of Yoon with the lateral channel connecting all the first channels in order to create more mixing across the microfluidic chip.
Regarding claim 17, Yoon discloses a material that enhances cell adhesion and is incorporated into the channels, wherein the material is selected from fibronectin (paragraph [0080]).
Regarding the limitation “that enhances cell adhesion” the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Yoon would be fully capable of operating in this manner given the fibronectin coating and substrate surfaces of the Yoon device.
Regarding claim 19, Yoon discloses wherein the cells are normal cells or disease cells (paragraph [0010]), and wherein a model of the disease cells are tumor cells (paragraph [0010] “cancer cells (e.g., circulating tumor cells)”), tumor-associated macrophages or tumor-associated fibroblasts, or cells engineered derived from the model of the normal cells, and wherein the tumor cells comprise gastric cancer cells, pancreatic cancer cells, colorectal cancer cells, liver cancer cells, bone cancer cells, lung cancer cells, kidney cancer cells, prostate cancer cells, breast cancer cells, brain cancer cells, neuroendocrine tumor (cancer) cells and all other tumor cells associated therewith (paragraph [0010] “cancer cells (e.g., circulating tumor cells)”).
If it is deemed that Yoon does not disclose the tumor cells comprise gastric cancer cells, pancreatic cancer cells, colorectal cancer cells, liver cancer cells, bone cancer cells, lung cancer cells, kidney cancer cells, prostate cancer cells, breast cancer cells, brain cancer cells, neuroendocrine tumor (cancer) cells and all other tumor cells associated therewith; see below arguments about the MPEP § 2115.
Yoon does not disclose wherein a model of the normal cells comprises kidney cells, lung cells, digestive tract cells, brain cells, liver cells, fibroblasts, endothelial cells, immune cells and macrophages.
However, regarding this/these limitation(s), the material or article worked upon by the apparatus does not limit the apparatus claims. MPEP § 2115. This limitation is a manner of operating or intended use of a claimed apparatus and does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Yoon would be fully capable of operating in this manner given that the microfluidic chip already supports several cell types, such as suspension culture or adherent culture (see Yoon, paragraph [0080]). It would have been obvious to one skilled in the art before the effective filing date to modify the model of the normal cells of the microfluidic chip of modified Yoon to be that listed in order to adapt the microfluidic chip to different assays for suspension culture and adherent culture, co-culture assays, migration assays, and chemical/metabolite sensing assays (Yoon, paragraphs [0080]-[0081]).
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Yoon (US 20190344270) (newly cited) in view of Qin (CN 111218401) (machine translation) (newly cited) as applied to claim 1, Zhao (CN 210613744) (machine translation) (newly cited).
Regarding claim 18, Yoon does not disclose an accommodation structure capable of accommodating a plurality of the microfluidic chips, wherein the accommodation structure is provided with a plurality of microfluidic chip placement holes or slots each for accommodating one of the microfluidic chips, and wherein the microfluidic chip placement holes or slots are circular holes capable of accommodating the microfluidic chips to enable placing and removal of the microfluidic chips.
Zhao discloses an accommodation structure (abstract) capable of accommodating a plurality of the microfluidic chips (abstract and paragraphs [0008] and [0038]), wherein the accommodation structure is provided with a plurality of microfluidic chip placement holes or slots (paragraph [0038] element 5 “stepped surfaces”) each for accommodating one of the microfluidic chips (paragraphs [0038] and [0044]), and wherein the microfluidic chip placement holes or slots are holes capable of accommodating the microfluidic chips to enable placing and removal of the microfluidic chips (paragraphs [0041]-[0042]).
Modified Yoon does not teach wherein the microfluidic chip placement holes or slots are circular holes.
However, the claim limitation is obvious, as the configuration of the claimed shape is a matter of choice, absent persuasive evidence that the particular configuration is significant. MPEP § 2144.04(IV)(B). It would have been obvious to one skilled in the art before the effective filing date to modify the shape of a hole or slot of a microfluidic chip holder of modified Yoon to be circular in order to better fit a circular microfluidic chip or a differently shaped microfluidic chip such as one that is wider in the middle for multiple channels and tapered at the ends for fewer inlets or outlets.
Regarding the limitation “capable of accommodating the microfluidic chips to enable placing and removal of the microfluidic chips”, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Yoon would be fully capable of operating in this manner given the microfluidic chip of Yoon and the microfluidic chip holder of modified Yoon in view of Zhao.
Allowable Subject Matter
Claims 12-16 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Regarding claim 12, the closest prior art is Yoon (US 20190344270) (newly cited) in view of Qin (CN 111218401) (machine translation) (newly cited).
Regarding claim 12, modified Yoon teaches an upper chip and a lower chip, and one of the chips comprises channel portions (paragraph [0131] under “Device Fabrication”) provided therethrough with the first inlet (annotated Figs. 1a-1b), the second inlet (Yoon in view of Qin, see rejection to claim 1), the first outlet (Yoon in view of Qin, see rejection to claim 1) and the second outlet (annotated Figs. 1a-1b), and wherein the first channel, the second channel, the first extension channel, the second extension channel and the confined migration channel are formed between the upper chip and the lower chip (paragraph [0131] and Figs. 1a-1b); wherein the upper chip and the lower chip are associated with each other to form the microfluidic chip (paragraph [0131]);
Yoon does not disclose wherein the upper chip comprises upper channel portions; the lower chip comprises lower channel portions, and wherein the upper channel portions and the lower channel portions are combined to form the channels, and wherein the upper chip further comprises an upper set of the first channels, an upper set of the second channels and an upper set of the confined migration channels; the lower chip further comprises a lower set of the first channels, a lower set of the second channels and a lower set of the confined migration channels, and wherein a sum of a depth of each of the upper first channels and that of each of the lower first channels is equal to a sum of a depth of each of the first channels; a sum of a depth of each of the upper second channels and that of each of the lower second channels is equal to a sum of a depth of each of the second channels; a sum of a depth of each of the upper confined migration channels and that of each of the lower confined migration channels is equal to a sum of a depth of each of the confined migration channels.
Regarding the dependent claims 13-16, these claims contain allowable subject matter for the same reason as the base claim upon which they depend.
Additional Prior Art References
The prior art made of record and not relied upon is considered pertinent to Applicant’s disclosure.
Chen (“Single-cell Migration Chip for Chemotaxis-based Microfluidic Selection of Heterogeneous Cell Populations”) (cited from the IDS from 01/16/2024) – This non-patent literature describes a similar invention only with serpentine instead straight, parallel pathways.
Chen (CN 110713923) (machine translation) (newly cited, from related Chinese Office Action) – This prior art describes a microfluidic chip and its application for cancer cell migration analysis, with straight and not serpentine pathways.
Magdesian (US 20160186112) (newly cited) – This prior art describes a microfluidic cell culture system.
Wu (“Microfluidic cell culture systems for drug research”) (cited from the IDS from 01/16/2024) – This non-patent literature from the Information Disclosure Statement describes an invention with a pyramid-like distribution manifold on a microfluidic chip.
Sala (“Microfluidic Lab-on-a-Chip for Studies of Cell Migration under Spatial Confinement”) (cited from the IDS from 01/16/2024) – This non-patent literature from the Information Disclosure Statement contains a table (Table 1) for the size in microns of different types of channels.
Conclusion
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/N.G.E./Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799