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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. PCT/IB2021/058310, filed on 09/13/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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.
Claim(s) 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over Belhocine et al. (US20180216162A1) and Utharala et al. (US20180355407A1).
Regarding Claim 1, Belhocine et al. teaches a system for phenotypical profiling of at least one object and deterministic nanoliter-droplet encapsulation (See the Abstract, the microfluidic encapsulation systems, and the Claim(s) 1-30 in [0002]-[0437] in Fig. 1-31), the system (See in Fig. 1A-2, 27-28B, and 31) comprising:
sample supplying means comprising at least one sample reservoir configured to contain at least one object dispersed in a sample buffer (See how the microfluidic chip 104 comprises a plurality of reservoirs for the oil 101, polymeric or gel precursors 102 and cell or virus reagents 103 in [0130] in Fig. 1A-B);
buffer supplying means comprising at least one buffer reservoir configured to contain a primary reaction buffer (See how the microfluidic chip 123 comprises a plurality of reservoirs for the oil 121, cell beads 113 and barcode beads 122. The chip also includes additional reservoirs 127 and 128 that may be used to supply additional reagents such as, reagents for nucleic acid amplification, reagents that can degrade or dissolve cell beads 113 and/or barcode beads 122, or reagents that degrade linkages between barcodes and barcode beads 122, and etc. to phase 130 in [0132] in Fig. 1C);
a microfluidic chip (See in Fig. 1A-2, 27-28B, and 31) comprising: - a first imaging chamber (See how the channel structure can include channel segments 232, 234, 236 and 238 communicating at channel junction 240 where images can be derived in [0194] in Fig. 1D-2);
- a first microfluidic channel for transporting the at least one object from the sample supplying means to the first imaging chamber (See the first aqueous fluid 242 that includes suspended cell bead 244 in [0194] in Fig. 2);
- an oil inlet or introducing an oil that supports droplet formation in the microfluidic chip or a droplet forming substance inlet for introducing a droplet forming substance into the microfluidic chip (See how the second fluid 246 is immiscible with the aqueous fluid 242 and is delivered to the junction 240 from channel segments 234 and 236 to create discrete droplets 118 of the aqueous fluid including individual cell bead 244, flowing into channel segment 238 in [0194]-[0195] in Fig. 1D-2);
- an encapsulation area or structure in which the at least one object is encapsulated with a quantity of the primary reaction buffer by the formed droplet (See how the aqueous fluid comprising the cells and the polymer precursor material is flowed into channel junction 240, i.e. an encapsulation area, where it is partitioned into droplets 248 comprising the individual cells 244, through the flow of non-aqueous fluid 246 in [0197] in Fig. 2; Also see how the droplets 2711 comprising cell beads and polymeric or gel precursors are generated and flow away from the second intersection in a seventh channel 2712 in [0399] in Fig. 27-28B);
- a second microfluidic channel for transporting the primary reaction buffer from the buffer supplying means to the encapsulation area or structure (See the channel 2708 in [0398]-[0400] in Fig. 27);
- an oil supporting droplet formation microchannel or droplet forming substance microchannel connected to the encapsulation area to place the at least one object and the primary reaction buffer in direct contact with the oil that supports droplet formation or the droplet forming substance (See the channel 2709 and 2710 in [0398]-[0400], [0408]-[0409] in Fig. 27);
- a droplet microchannel or tubing for transporting the droplet (See the channel 2712 in [0398]-[0400], [0408]-[0409] in Fig. 27-28B);
detection means configured to detect the passage of the at least one object through the first imaging chamber (See the computer control systems in [0411]-[0422], [0423]-[0437] in Fig. 6);
a droplet deposition means configured to deposit the droplet in a well or in a well of a multi-well plate and comprising an outlet capillary connected to the droplet microchannel or the tubing (See how the channel segment 3108 may deliver the discrete droplets to an outlet reservoir fluidly coupled to the channel segment 3108, where they may be harvested in [0138] in Fig. 31 and in claim 16).
Belhocine et al. fails to explicitly teach that the system for phenotypical profiling of at least one object and deterministic nanoliter-droplet encapsulation, further comprises detection means configured to detect the passage of the at least one object through the first imaging chamber; at least one valve configured to stop the flow of the sample buffer when the detection means detect the passage of the at least one object through the first imaging chamber; phenotypical assessing means configured to assess the phenotype of the at least one object when the flow of the sample buffer is stopped by the at least one valve and the at least one object is at an object stopping site; a droplet deposition means configured to deposit the droplet in a well or in a well of a multi-well plate and comprising an outlet capillary connected to the droplet microchannel or the tubing.
However, in the analogous art of cell barcoding in microfluidics, Utharala et al. teaches a system for phenotypical profiling of at least one object and deterministic nanoliter-droplet encapsulation (See the Abstract, the microfluidic encapsulation, and the Claim(s) 1-15 in [0002]-[0140] in Fig. 1-6), the system (See in Fig. 2-3) comprising: a microfluidic chip (See Claim 15 and Fig. 1B) comprising:
detection means configured to detect the passage of the at least one object through the first imaging chamber (See the use of spectroscopy, cameras, and electrodes in [0041]-[0042], [0050]-[0053], [0115], [0122]-[0124] in Fig. 3);
at least one valve configured to stop the flow of the sample buffer when the detection means detect the passage of the at least one object through the first imaging chamber (See in [0005]-[0015], [0072]-[0074] in Fig. 5-6 and in claim(s) 1-2, 6, 9, and 15);
phenotypical assessing means configured to assess the phenotype of the at least one object when the flow of the sample buffer is stopped by the at least one valve and the at least one object is at an object stopping site (See in [0010]-[0012], [0050]-[0053], [0102] and claim(s) 3-4 and 13);
a droplet deposition means configured to deposit the droplet in a well or in a well of a multi-well plate and comprising an outlet capillary connected to the droplet microchannel or the tubing (See the collection and waste channels in [0062]-[0073], [0131] in Fig. 5-6).
Thus, it would be obvious to one with ordinary skills in the arts to modify or combine the system of Belhocine et al. by incorporating a detection means, at least one valve, a phenotypical assessing means , and a droplet deposition means (as taught by Utharala et al.) for the benefit of providing phenotypical profiling of at least one object that is droplet encapsulated using a microfluidic chip.
Regarding Claim(s) 2-3, The combination of Belhocine et al. and Utharala et al. teaches the system limitations of claim 1.
Belhocine et al. further teaches a system for phenotypical profiling of at least one object and deterministic nanoliter-droplet encapsulation (See the Abstract, the microfluidic encapsulation systems, and the Claim(s) 1-30 in [0002]-[0437] in Fig. 1-31), wherein the at least one object is a cell, a cellular entity or a cellular compartment (See claim 1 in [0006], [0225]-[0239]);
wherein the primary reaction buffer is configured to perform a first reaction and comprises an enzyme and/or a biochemistry of choice and/or a culture medium and/or growth matrices and/or a reverse transcriptase and/or a hyperactive transposase and/or a first molecular barcode such as a phenotype barcode (See in [0002]-[0059], [0060]-[0066]).
Regarding Claim(s) 4-7, The combination of Belhocine et al. and Utharala et al. teaches the system limitations of claim 1.
Belhocine et al. fails to explicitly teach that the buffer supplying means comprises at least one secondary buffer reservoir containing a placement buffer configured to instigate a biological reaction of the at least one object and/or enable an imaging-based assessment of the biological reaction; wherein the at least one object is positioned at the object stopping site by displacement of the sample buffer and/or the placement buffer and/or the primary reaction buffer; wherein the well or the wells of a multi-well plate are pre-loaded with stuffer droplets comprising the primary reaction buffer and/or a secondary reaction buffer to perform a secondary reaction inside the well or the wells of a multi-well plate, the stuffer droplets being configured to be merged with the droplet comprising the least one object and the primary buffer; wherein the well or the wells of a multi-well plate comprise a second molecular barcode, such as a well molecular barcode.
However, in the analogous art of cell barcoding in microfluidics, Utharala et al. further teaches a system for phenotypical profiling of at least one object and deterministic nanoliter-droplet encapsulation (See the Abstract, the microfluidic encapsulation, and the Claim(s) 1-15 in [0002]-[0140] in Fig. 1-6), wherein the buffer supplying means comprises at least one secondary buffer reservoir containing a placement buffer configured to instigate a biological reaction of the at least one object and/or enable an imaging-based assessment of the biological reaction (See the use of spectroscopy, cameras, and electrodes in [0041]-[0042], [0050]-[0053], [0115], [0122]-[0124] in Fig. 3);
wherein the at least one object is positioned at the object stopping site by displacement of the sample buffer and/or the placement buffer and/or the primary reaction buffer (See in [0010]-[0012], [0050]-[0053], [0102] and claim(s) 3-4 and 13);
wherein the well or the wells of a multi-well plate are pre-loaded with stuffer droplets comprising the primary reaction buffer and/or a secondary reaction buffer to perform a secondary reaction inside the well or the wells of a multi-well plate, the stuffer droplets being configured to be merged with the droplet comprising the least one object and the primary buffer; wherein the well or the wells of a multi-well plate comprise a second molecular barcode, such as a well molecular barcode (See in [0137]-[0140]).
Thus, it would be obvious to one with ordinary skills in the arts to modify or combine the system of Belhocine et al. by incorporating additional sample and reaction buffers, and barcodes (as taught by Utharala et al.) for the benefit of providing phenotypical profiling of at least one object that is droplet encapsulated using a microfluidic chip.
Regarding Claim(s) 8-11, The combination of Belhocine et al. and Utharala et al. teaches the system limitations of claim 1.
Belhocine et al. fails to explicitly teach that the system for phenotypical profiling of at least one object and deterministic nanoliter-droplet encapsulation, further comprises a second imaging chamber fluidically connected to the first imaging chamber, the second imaging chamber comprising an object stopping site; wherein the at least one valve is configured to be over-pressured to generate a leak flow of the sample buffer and/or the placement buffer and/or the primary reaction buffer until the at least one object reaches the object stopping site or the second imaging chamber; wherein the detection means and the phenotypical assessing means comprise a microscope comprising a dual-camera objective imaging and detection system, and/or an tunable lens to adjust the focal plane, and/or a laser excitation diode for epi- fluorescence imaging; the first and/or second imaging chambers and/or the encapsulation area and/or the inlets comprises rectangular channel structures and wherein an area around the at least one valve are non-rectangular channel structures.
However, in the analogous art of cell barcoding in microfluidics, Utharala et al. further teaches a system for phenotypical profiling of at least one object and deterministic nanoliter-droplet encapsulation (See the Abstract, the microfluidic encapsulation, and the Claim(s) 1-15 in [0002]-[0140] in Fig. 1-6), comprising a second imaging chamber fluidically connected to the first imaging chamber, the second imaging chamber comprising an object stopping site (See in [0010]-[0123] and claim(s) 3-4 and 13 in Fig. 3);
wherein the at least one valve is configured to be over-pressured to generate a leak flow of the sample buffer and/or the placement buffer and/or the primary reaction buffer until the at least one object reaches the object stopping site or the second imaging chamber (See in [0005]-[0015], [0072]-[0074] in Fig. 5-6 and in claim(s) 1-2, 6, 9, and 15);
wherein the detection means and the phenotypical assessing means comprise a microscope comprising a dual-camera objective imaging and detection system, and/or an tunable lens to adjust the focal plane, and/or a laser excitation diode for epi- fluorescence imaging (See the use of spectroscopy, cameras, and electrodes in [0041]-[0042], [0050]-[0053], [0115], [0122]-[0124] in Fig. 3);
the first and/or second imaging chambers and/or the encapsulation area and/or the inlets comprises rectangular channel structures and wherein an area around the at least one valve are non-rectangular channel structures (See claim 15 and Fig. 1-6).
Thus, it would be obvious to one with ordinary skills in the arts to modify or combine the system of Belhocine et al. by incorporating imaging chambers, a detection means, at least one valve, a phenotypical assessing means, and a droplet deposition means (as taught by Utharala et al.) for the benefit of providing phenotypical profiling of at least one object that is droplet encapsulated using a microfluidic chip.
Regarding Claim(s) 12-16, The combination of Belhocine et al. and Utharala et al. teaches the system limitations of claim 1.
Belhocine et al. further teaches a system for phenotypical profiling of at least one object and deterministic nanoliter-droplet encapsulation (See the Abstract, the microfluidic encapsulation systems, and the Claim(s) 1-30 in [0002]-[0437] in Fig. 1-31), wherein the sample supplying means comprise several reservoirs each containing at least one object dispersed in a sample buffer (See how the microfluidic chip 104 comprises a plurality of reservoirs for the oil 101, polymeric or gel precursors 102 and cell or virus reagents 103 in [0130] in Fig. 1A-B);
wherein the buffer supplying means comprise several reservoirs, containing several primary buffers having different compositions and/or phenotype barcode identifier (See how the microfluidic chip 123 comprises a plurality of reservoirs for the oil 121, cell beads 113 and barcode beads 122. The chip also includes additional reservoirs 127 and 128 that may be used to supply additional reagents such as, reagents for nucleic acid amplification, reagents that can degrade or dissolve cell beads 113 and/or barcode beads 122, or reagents that degrade linkages between barcodes and barcode beads 122, and etc. to phase 130 in [0132] in Fig. 1C);
wherein the droplet deposition means is configured to deposit the droplet in a specific well of a multi-well plate, the droplet deposition means comprising plate displacing means configured to displace horizontally and/or vertically the multi-well plate relative to the outlet capillary (See how the channel segment 3108 may deliver the discrete droplets to an outlet reservoir fluidly coupled to the channel segment 3108, where they may be harvested in [0138] in Fig. 31 and in claim 16);
wherein the system comprises a processor configured to obtain and digitally store detection and phenotype data of at least one object from the detection and phenotypical assessing means and to link the detection and phenotype data with the phenotype and/or molecular barcode identifier encapsulated with the at least one object and the well in which the droplet is deposited (See the computer control systems in [0411]-[0422], [0423]-[0437] in Fig. 6);
wherein the processor is further configured to operate an image-based selection process prior or previous to the at least one object encapsulation to deposit the droplet in a specific well depending on the phenotype of the encapsulated object and/or to discard the unwanted object or droplet comprising the unwanted object with a discarding valve configured to open to discard unwanted object (See the computer control systems in [0411]-[0422], [0423]-[0437] in Fig. 6).
Regarding Claim 17, The combination of Belhocine et al. and Utharala et al. teaches the system limitations of claim 1.
Belhocine et al. further teaches a method of operating a system for phenotypical profiling of at least one object and deterministic nanoliter- droplet encapsulation (See the Abstract, the microfluidic encapsulation systems, and the Claim(s) 1-30 in [0002]-[0437] in Fig. 1-31), the method comprising the steps of: - Introducing the at least one object from the sample supplying means into the first imaging chamber through the first microfluidic channel; - Introducing the primary reaction buffer from the buffer supplying means into the microfluidic chip through the second microfluidic channel; - Introducing the oil that supports droplet formation into the microfluidic chip or the droplet forming substance into the microfluidic chip through the oil inlet or the droplet forming substance inlet; - Transporting the at least one object and the primary reaction buffer to the encapsulation area or structure for encapsulation by the droplet; - Transporting the droplet to the droplet deposition means through the droplet microchannel or tubing for deposition of the droplet in a well or in a well of a multi-well plate (See in Claim(s) 1-30 in Fig. 1-31).
Belhocine et al. fails to explicitly teach that the method of operating a system further comprises the steps of: - Stopping the flow of the sample buffer when the detection means detect the passage of the at least one object through the first imaging chamber; - Assessing the phenotype of the at least one object when the flow of the sample buffer is stopped and the at least one object is at an object stopping site; - Transporting the at least one object and the primary reaction buffer to the encapsulation area or structure for encapsulation by the droplet.
However, in the analogous art of cell barcoding in microfluidics, Utharala et al. further teaches a method of operating a system for phenotypical profiling of at least one object and deterministic nanoliter- droplet encapsulation (See the Abstract, the microfluidic encapsulation, and the Claim(s) 1-15 in [0002]-[0140] in Fig. 1-6), the method comprising the steps of: - Stopping the flow of the sample buffer when the detection means detect the passage of the at least one object through the first imaging chamber; - Assessing the phenotype of the at least one object when the flow of the sample buffer is stopped and the at least one object is at an object stopping site; - Transporting the at least one object and the primary reaction buffer to the encapsulation area or structure for encapsulation by the droplet (See in Claim(s) 1-15 and in Fig. 1-6).
Thus, it would be obvious to one with ordinary skills in the arts to modify or combine the operating method of Belhocine et al. by incorporating the method steps of: stopping the flow, assessing the phenotype, and transporting (as taught by Utharala et al.) for the benefit of phenotypical profiling of at least one object that is droplet encapsulated using a microfluidic chip.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 18 is rejected under 35 U.S.C. 102(a)(1) based upon a public use or sale or other public availability of the invention. The instant invention is anticipated by Belhocine et al. (US20180216162A1).
Regarding Claim 18, Belhocine et al. teaches a defined group of droplets placed in one well, each containing at least one object, with each droplet containing one defined primary buffer and/or phenotype barcode identifier (See the Abstract, the microfluidic encapsulation systems, and the Claim(s) 1-30 in [0002]-[0437] in Fig. 1-31).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRITNEY N. WASHINGTON whose telephone number is (703)756-5959. The examiner can normally be reached Monday-Friday 9:00am - 5:30pm CT.
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/BRITNEY N. WASHINGTON/Examiner, Art Unit 1797
/JENNIFER WECKER/Primary Examiner, Art Unit 1797
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