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 .
DETAILED ACTION
Status of Claims
Claims 31-50 are pending and have been examined.
Priority
This application, Serial No. 18/263,397 (PGPub: US2024/0084233) was filed 07/28/2023. This application is a 371 of PCT/CN2022/073892 filed 01/26/2022. This application claims priority to foreign application China 202110128093.6 filed 01/29/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)- (d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statements
The Information Disclosure Statements filed 07/28/2023 and 02/24/2025 have been considered by the Examiner.
Claim Objections
Claim 48 is objected to because of the following informalities:
Claim 48 at line 3 should be corrected to say “…is usable together with the main body.”.
Claim 48 at line 1 should be corrected to say “…comprising a main body and the microfluidic chip…of claim 31”.
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 45-47 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 45 is confusing because as currently recited it is unclear what the claims intended active method steps are. For example, the claim clearly recites steps of passing a diluted blood sample and introducing the blood sample from the primary sorting channel but the remaining limitations (“preliminarily aggregating…the white blood cells have not yet aggregated” and “the circulating tumor cells in the blood sample are aggregated…and the white blood cells are in a disordered motion state”) are unclear if they are intended to be functions of the two methods steps disclosed above or merely inherent properties of the sample components while being manipulated within the microfluidic chip. For examination purposes, only the active method steps described above will receive examination until further clarification is provided.
The term “preliminarily” in claim 45 is a relative term which renders the claim indefinite. The term “preliminarily” 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.
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.
Claim(s) 31-36, 43, 45 and 48-50 are rejected under 35 U.S.C. 103 as being unpatentable over Ying et al. (CN 105854967, 08/17/2016, IDS, translation attached) in view of Han et al. (US 2020/0171488, Pub Date: 06/04/2020).
Regarding claim 31, Ying teaches throughout the publication a microfluidic chip (see Figure 2), comprising a functional board (see Figure 4, board 10), a first side face of the functional board being provided with: a primary sorting channel (channel 2), which is in communication with a sample inlet (inlet 3); and a fine screening channel, which is in communication with the primary sorting channel (microchannel 1 connected to channel 2 and upstream of first turn).
However, Ying fails to teach that a deepened channel is dug on the side of the fine screening channel away from the aggregation of the circulating tumor cells, the deepened channel is arranged in an extension direction of the fine screening channel, and the deepened channel has a depth greater than that of the fine screening channel and that the microfluidic chip is configured for sorting and enriching circulating tumor cells and the primary sorting channel is configured to preliminarily aggregate circulating tumor cells and white blood cells in a sample.
Han teaches throughout the publication a microfluidic device (abstract) for sorting and filtering components of blood such as the separation of white blood cells and detection of circulating tumor cells (paragraph 0093). More specifically, Han teaches that one of the microchannels comprises a curved microchannel with a deeper side and a shallow side for focusing particles depending on their size (paragraph 0109).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to incorporate within the screening channel of Ying, a deepened channel as taught by Han and such that the device of Ying could be used for sorting circulating tumor cells away from white blood cells as taught by Han because it would have been desirable to integrate both concentration and separation functions into a single device without the need of additional sheath flow thereby providing better separation and providing use for a wider range of particle size (Han, paragraph 0044) and since using the device for enriching circulating tumor cells provides insight into numerous types of cancer (Han, paragraph 0128).
Regarding claim 32, Ying in view of Han teach the chip wherein the depth of the deepened channel is deeper (Han, paragraphs 0109 and 0113) with the channels having depths ranging from 20 to 200 micrometers (Han, paragraph 0119). While Ying in view of Han do not specifically teach the chip wherein the deeper channel is 50-200 micrometer greater than the depth of the fine screening channel or the depth of the deepened channel is 70-120 micrometers greater than the depth of the fine screening channel, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 32 are for any particular purpose or solve any stated problem, and the prior art teaches that channel parameters may be varied depending on the particle size and desired flow rate. Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the components disclosed by the prior art by normal optimization procedures known in the microfluidic art.
Regarding claim 33, although Ying in view of Han do not specifically teach the chip wherein the fine screening channel is designed such that a ratio of the size of the circulating tumor cells to a hydraulic diameter is less than or equal to 0.5; or the fine screening channel is designed such that the ratio of the size of the circulating tumor cells to the hydraulic diameter is less than or equal to 0.07; or the fine screening channel is designed such that the ratio of the size of the circulating tumor cells to the hydraulic diameter is 0.045 to 0.065; or the fine screening channel is designed such that the ratio of the size of the circulating tumor cells to the hydraulic diameter is 0.05 to 0.06, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 33 are for any particular purpose or solve any stated problem, and the prior art teaches that channel parameters may be varied depending on the particle size and desired flow rate. Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the components disclosed by the prior art by normal optimization procedures known in the microfluidic art.
Regarding claim 34, Ying in view of Han teach the chip wherein the first side face of the functional board is further provided with a first turning channel having a radius of curvature greater than that of the fine screening channel (Ying, Figure 2, first turning portion of microchannel 1) the first turning channel is in communication with the fine screening channel (See Ying, Figure 2), and the deepened channel correspondingly extends into the first turning channel and is located on the side away from the aggregation of the circulating tumor cells (Han, paragraphs 109-113).
Regarding claim 35, Ying in view of Han teach the chip wherein the first side face of the functional board is further provided with a removal channel, the removal channel is in communication with the end of the first turning channel away from the fine screening channel (portion of channel 1 downstream of the first turn but before the next turn), the deepened channel correspondingly extends into the removal channel and is located on the side away from the aggregation of the circulating tumor cells (Han, paragraphs 109-113). Although the references do not specifically teach that the removal channel is provided with a shunt hole penetrating a wall face of the removal channel, Ying teaches that there are various outlets throughout the device (see Figure 2) and Han teaches that the device can comprise additional components upstream, downstream or within the device such as collection reservoirs, or membranes for upstream/downstream analysis (paragraph 0131). Therefore, one skilled in the art would be motivated to incorporate an outlet shunt in the removal channel of Ying and Han because it would have been desirable to provide access to separated material for further analysis.
Regarding claim 36, Ying in view of Han teach the chip wherein the first side face of the functional board is further provided with a second turning channel having a radius of curvature greater than that of the removal channel, the second turning channel is in communication with the end of the removal channel away from the first turning channel(Ying, see Figure 2, see second turning portion of channel 1 on left side of figure), and the deepened channel correspondingly extends into the second turning channel and is located on the side away from the aggregation of the circulating tumor cells (Han, paragraphs 109-113).
Regarding claim 43, Ying in view of Han teach the chip wherein the fine screening channel and the removal channel are sinusoidal arc-shaped channels (Ying, see Figure 2, portions of channel 1 upstream and downstream of first turn after inlet 3 and channel 2).
Regarding claim 45, Ying teaches throughout the publication a microfluidic chip (see Figure 2), comprising a functional board (see Figure 4, board 10), a first side face of the functional board being provided with: a primary sorting channel (channel 2), which is in communication with a sample inlet (inlet 3); and a fine screening channel, which is in communication with the primary sorting channel (microchannel 1 connected to channel 2 and upstream of first turn).
However, Ying fails to teach that a deepened channel is dug on the side of the fine screening channel away from the aggregation of the circulating tumor cells, the deepened channel is arranged in an extension direction of the fine screening channel, and the deepened channel has a depth greater than that of the fine screening channel and that the microfluidic chip is configured for sorting and enriching circulating tumor cells and the primary sorting channel is configured to preliminarily aggregate circulating tumor cells and white blood cells in a sample.
Han teaches throughout the publication a microfluidic device (abstract) for sorting and filtering components of blood such as the separation of white blood cells and detection of circulating tumor cells (paragraph 0093). More specifically, Han teaches that one of the microchannels comprises a curved microchannel with a deeper side and a shallow side for focusing particles depending on their size (paragraph 0109).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to incorporate within the screening channel of Ying, a deepened channel as taught by Han and such that the device of Ying could be used for sorting circulating tumor cells away from white blood cells as taught by Han because it would have been desirable to integrate both concentration and separation functions into a single device without the need of additional sheath flow thereby providing better separation and providing use for a wider range of particle size (Han, paragraph 0044) and since using the device for enriching circulating tumor cells provides insight into numerous types of cancer (Han, paragraph 0128).
As such, Ying in view of Han additionally teaches a method for sorting and enriching circulating tumor cells (Han, paragraph 0128), comprising the steps of: passing a diluted blood sample into a sample inlet of a microfluidic chip (Han, paragraph 0192), and preliminarily aggregating circulating tumor cells and white blood cells of the blood sample (Han, paragraphs 0109-0113) after the blood sample passes through a primary sorting channel of a repeatedly folded structure (see Ying, Figure 2); and introducing the blood sample from the primary sorting channel into a fine screening channel (Ying, channel 2 to connecter portion of channel 1), wherein a deepened channel is dug on the side of the fine screening channel away from the aggregation of the circulating tumor cells, the circulating tumor cells in the blood sample are aggregated into a thin band and are close to the bottom of an inner wall of the fine screening channel (Han, paragraphs 0109-0113).
Regarding claim 48, Ying in view of Han teach an in vitro analysis diagnostic instrument, comprising a main body and a microfluidic chip for sorting and enriching circulating tumor cells of claim 31 (see above), wherein the microfluidic chip for sorting and enriching circulating tumor cells are usable together with the main body (Ying, translation page 3 and see Ying claims 8-10).
Regarding claim 49, Ying in view of Han teach the instrument wherein the main body is provided with a chip mounting position for mounting the microfluidic chip for sorting and enriching circulating tumor cells (Ying, Figure 4, adherence of both body substrate sides interpreted as mounted), a mixing chamber for mixing a sample (Ying, Figure 4, extracting device 13 connected to mixed liquid outlet 6) , a diluent and a lysate (Han, paragraph 0092), and a recovery chamber for recovering the circulating tumor cells, wherein the mixing chamber is capable of being in communication with a sample inlet of the microfluidic chip for sorting and enriching circulating tumor cells, and the recovery chamber is capable of being in communication with a recovery hole through which the circulating tumor cells flow out of the microfluidic chip for sorting and enriching circulating tumor cells (see Ying, Figure 2).
Regarding claim 50, Ying in view of Han teach the instrument further comprising a power system and a control system, wherein the control system is configured to control the power system to inject the sample, the diluent and the lysate into the mixing chamber (Han, paragraph 0131 and 0140). Although Ying in view of Han do not specifically teach that the power system is controlled to inject at a specific ratio and to pass the mixed liquid from the mixing chamber into the microfluidic chip for sorting and enriching circulating tumor cells at a flow velocity, such limitation is drawn to intended use of the instrument and thus the prior art only needs to be capable of performing the recited intended use. Ying in view of Han teach the same structural components comprising a computer processor and programmed pump (Han, paragraph 0140) and thus is seen as being capable of performing the recited intended use.
Allowable Subject Matter
Claims 37-42 and 44 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 46-47 are also free of the prior art but remain rejected as being dependent on indefinite claim 45.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M GIERE whose telephone number is (571)272-5084. The examiner can normally be reached M-F 8:30-4:30.
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/REBECCA M GIERE/Primary Examiner, Art Unit 1677