DETAILED ACTION
Election/Restrictions
Newly submitted claims 38-43 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: claims 38-43 are directed to a method of amplifying DNA, while the claims have previously been exclusively directed to a device for capturing DNA.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 38-43 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claims 1, 14, 16, 23 and 28-37 are rejected under 35 U.S.C. 103 as being unpatentable over Craighead (US 20140194313) in view of Southern (US 20090098541).
With respect to claims 1, 28, 35 and 36, Craighead discloses a microfluidic device (Figure 7:10) comprising a microchannel that includes a DNA capture array (Figure 1:40a,b) comprising a plurality of micropillars configured to immobilize genomic DNA. The DNA capture array terminates in a collection region (Figure 1:45) for collecting DNA amplification products. The whole genome amplification system further includes an input port (Figure 1:22) and an output reservoir (Figure 1:24). This is disclosed in at least paragraphs [0053]-[0063]. Paragraphs [0051] and [0109] teach that the micropillars have a diameter between 0.5 to 15 microns and that the spacing between micropillars narrows in a downstream manner (“a micropillar width of about 4 µm").
[AltContent: textbox (narrowed apex)][AltContent: arrow]
PNG
media_image1.png
245
534
media_image1.png
Greyscale
These micropillars are therefore dimensioned and arranged to physically entangle genomic DNA. See also paragraphs [0104] and [0111] (“Long strands of genomic DNA released from the cells become entangled in the array of microposts”). Sidewalls bordering the plurality of micropillars converge at an upstream end of the DNA capture array to form a narrowed apex. Again, see Fig. 1. Craighead states that the apex region functions as a cell capture site (Figure 1:41, see tapered region in Fig. 1), (“FIG. 3 provides a close view of multiple cells 60 (particularly hematopoietic stem-cells) immobilized by micropillars 41 of the micropillar array of one embodiment of a microfluidic device of the present invention. FIGS. 4-6, 11-13, and 15 include photomicrographs that show cells entrapped by the micropillars (by size exclusion)…the micropillar array includes micropillars that are spatially configured to entrap, by size exclusion, at least one cell”, see paragraphs [0058] and [0059]).
Craighead, however, does not expressly state that a plurality of these microchannels 30 originate from a single intake microchannel, or that the narrowed apex is a cell capture site configured to capture a single cell.
Southern discloses a microfluidic device comprising a solid substrate having one or more microfluidic channel systems therein. See at least Fig. 1. The microfluidic channel system includes a single intake microchannel (Figure 53:110) configured to receive a cell suspension comprising a plurality of cells. A plurality of cell segregation microchannels (Figure 53:115) extend from the single intake region, and a plurality of cell capture sites (Figure 54:120) are located downstream of each cell segregation microchannel and each include a narrowed apex for physically capturing a single cell and arresting any further movement of the single cell through the microfluidic channel system. This is disclosed in at least paragraphs [0029]-[0099], [0268] and [0269] (“Single cells are trapped, their contents are released, and the contents of individual cells are then analyzed along a channel containing suitable analytical components e.g. immobilized nucleic acid probes, immobilized antibodies, etc. Analysis of a single cell's genome, transcriptome, proteome, etc. thus becomes possible. Moreover, by arranging multiple channels on the same device, multiple cells can simultaneously be treated and analyzed in parallel, allowing individual cells within a population to be compared rapidly and conveniently. Where the multiple channels share a common input line, a population of cells can easily be separated into single cells, with one cell being associated with each channel”). Southern additionally states that a DNA capture array is positioned downstream from each cell capture site and that the array may include micropillars (Figure 36:60) (see paragraph [0082], “Preferred channels include a series of different immobilized nucleic acids for hybridizing to specific nucleic acids within a cell's contents”).
Before the effective filing date of the claimed invention, it would have been obvious to duplicate the Craighead microchannels 30 so that a plurality of identical cell segregation microchannels are split off from a common intake microchannel. Southern teaches that this is an effective way to simultaneously trap and lyse a plurality of individual cells in order to release intracellular analytes for further analysis using separate and independent downstream DNA capture arrays. The benefits of this configuration are described in paragraph [0009] and throughout the reference (“Single cells are trapped, their contents are released, and the contents of individual cells are then analyzed along a channel containing suitable analytical components e.g. immobilized nucleic acid probes, immobilized antibodies, etc. Analysis of a single cell's genome, transcriptome, proteome, etc. thus becomes possible. Moreover, by arranging multiple channels on the same device, multiple cells can simultaneously be treated and analyzed in parallel, allowing individual cells within a population to be compared rapidly and conveniently. Where the multiple channels share a common input line, a population of cells can easily be separated into single cells, with one cell being associated with each channel”).
With respect to claim 14, Craighead and Southern disclose combination as described above. Craighead additionally shows in Fig. 1 that the micropillars are arranged in a gradient so that the spacing between micropillars narrows in a downstream manner. This approach produces at least 2 distinct regions 40a,b. This is taught in at least paragraph [0060].
With respect to claim 16, Craighead and Southern disclose combination as described above. Southern teaches that the substrate and micropillars are made from PDMS, glass and/or plastics in at least paragraphs [0030]-[0032].
With respect to claims 23 and 37, Craighead and Southern disclose combination as described above. It would have been within the ability of one of ordinary skill in the art to optimize micropillar diameter to arrive at the most effective value (for example, 1.5-2 microns) through routine experimentation. Craighead does not specify a required micropillar diameter range, and the example diameter of 4 microns is close to the claimed range of 1.5-2 microns. A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05.
With respect to claim 29, Craighead and Southern disclose combination as described above. Southern shows at least 10 cell segregation microchannels extending from the single intake microchannel in at least Fig. 53.
With respect to claim 30, Craighead and Southern disclose combination as described above. Craighead and Southern each additionally teach the provision of at least one output reservoir.
With respect to claim 31, Craighead and Southern disclose combination as described above. Craighead and Southern do not discuss the use of mandatory valves. Craighead, in particular, indicates in paragraph [0117] that the device is valveless.
With respect to claims 32-34, Craighead and Southern disclose combination as described above. Southern additionally shows the state of the art regarding the use of a bypass channel to transport and expel non-arrested cells. Fig. 20 shows that the bypass channel removes cells that have not become trapped at cell capture sites. The bypass channel transports non-arrested cells directly to a waste location, thereby bypassing the DNA capture arrays.
[AltContent: textbox (Bypass channel)][AltContent: arrow][AltContent: oval][AltContent: textbox (Cell capture sites)][AltContent: arrow][AltContent: arrow][AltContent: arrow][AltContent: arrow][AltContent: arrow]
PNG
media_image2.png
1452
844
media_image2.png
Greyscale
Those of ordinary skill would have recognized that a plurality of bypass channels may be added to the Craighead device for the purpose of removing waste from first and second sides of the DNA capture array.
Response to Arguments
In response to Applicant’s amendment filed 26 June 2026, a new ground of rejection is made in view of the combination of Craighead with Southern.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached at (571) 272-1374. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NATHAN A BOWERS/Primary Examiner, Art Unit 1799
Prosecution Insights