Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Arguments
Applicant's arguments filed 08/20/2026 have been fully considered but they are not persuasive. Starting on page 8 applicant argues that Watanabe in view of Zhang does not teach “using quantitative image features”. The Examiner respectfully disagrees. First the claim gives the options of what the features are for example so therefore only one of these must be addressed. At least one of them has been addressed by Watanabe and these points the applicant does not argue with this point. As for small molecule factors and growth factor differences not being taught. As Zhang teaches, “growth of organoids was observed” in ¶[0144] and then further, ¶[0073] teaches growth factors, and by having this analysis from image to image this would be the differentiation. All of the molecules are “small” and the growth factor is clearly being taught by having the gradient growth factor. As there are no specifics on what is being or what the growth factor is spatial concentration variation would be the growth factor, as the limitation before states “an organoid area” therefore closed to gradient growth factor than growth factor on its own. Small molecule factors is also not defined in the speciation, and only by the system in Zhang running this is a differentiation by having that observation. For these reasons the same rejection applies.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Watanabe (US 2020/0165653) in view of Zhang (US 2023/0174909).
As per claims 1 and 11, Zhang teaches, a system and method for analyzing a plurality of organoids, the system comprising: an imaging device configured to collect a plurality of images for an organoid of the plurality of organoids (Watanabe, ¶[0037] “FIG. 4 shows examples of images of objects being detected in an embodiment of the present invention. [0038] FIG. 5 shows micrographs illustrating forskolin-induced swelling of a human intestinal organoid stimulated with forskolin.” This shows being configured to collect images for an organoid from a plurality of organoids and ¶[0044] FIG. 11 verified human intestinal organoid swelling induced by six different types of endogenous mediator related to anion/fluid secretion” Showing organoid from a plurality of organoid images); and a non-transitory medium comprising instructions causing a computer to implement an organoid analysis platform, wherein the organoid analysis platform is configured to:
determine a plurality of features from the plurality of images, wherein the plurality of features comprise a plurality of an organoid area, a total image area (Watanabe, ¶ Organoids were seeded into a 96-well plate for 3D-scanning with 2 μl of Matrigel and 100 μl of complete culture medium. After the passage of a preliminary culture process of leaving for 24 hours after seeding, scanning was then performed both before and 30 min after the addition of the reagent subject to analysis. An image was acquired during scanning in auto-focus (AF) mode. The analysis parameters summarized in following Table 1 were set and the cross-sectional area of recognized organoids measured automatically.” Applicant has written the limitations with “or” limitation and only of these must be addressed, however here we have a way of detection “the cross-sectional area of recognized organoids measured automatically” therefore represents organoid area), a percentage of the image covered by organoid (Watanabe, ¶ [0065] “The “allowable object's maximum area” is a threshold value for the size of an object up to which the object will be taken as being an organoid-derived object, expressed as a percentage of well area.” This represents percentage of the image covered by organoid ), a total intensity of organoid, a total intensity of organoid-by-organoid area, or a total intensity of organoid by total image area (Watanabe, ¶ [0014] “For example, when pixel intensity values are expressed as on an 8 bit display as is employed for ordinary image analysis, then the pixel intensity values are represented by a gray-scale with a pixel intensity value 0 representing black and a pixel intensity value 255 representing white. Under such assumptions setting a difference in pixel intensity value from the background of 7.8% or above as edge-candidate pixels is equivalent to there being a difference in pixel intensity value of 20 or greater thereto. Similarly, setting a difference in pixel intensity value from the background of 29.2% or more as the confirmed-edge pixels is equivalent a different in pixel intensity value of 75 or greater thereto. Namely, in such a case, when a closed shape is obtained enclosed by “points” that are pixels having a pixel intensity value from the background of 75 or greater, and by “lines” that are pixels between these “points” having a pixel intensity value from the background of 20 or greater, then such a closed shaped is detected as an object.” This would represent different types of intensity value, on a pixel by pixel basis); determine, using the plurality of features from the plurality of images, one or more differentiation factors between the plurality of images (Watanabe, ¶[0024] “In the present aspect a multi-well plate may, for example, be employed as the culture receptacle, and so different types and different concentrations of reagent may be introduced into each well, enabling rapid imaging thereof for each well.” This represents differentiation factors between the plurality of images, since the different types of concentrations would create a different image and creating different factors and different features thereof).
Watanabe doesn’t clearly teach, wherein the one or more differentiation factors comprise small molecule factors and growth factors.
However, Zhang teaches, wherein the one or more differentiation factors comprise small molecule factors and growth factors (Zhang, ¶[0144] “Interestingly, accelerated growth of organoids was observed after perfusion was established on day 5.” This represents growth factors of the organoids, and ¶[0073 ]” b) illustration for generating a gradient of growth factors/morphogens, ions, or chemical molecules to mimic controlled morphogenesis of cells in organ development;” this would then represent the small molecule factors differentiation as well as growth factors differentiation).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention was made to combine the teachings of Watanabe with those of Zhang to be able to be able to tell the growth factor and molecule factor differentiation.
The motivation would have been to improve testing and development as taught by Zhang in ¶[004] “In the case of both drug testing and therapeutic implantation, a perfusable cell culture device containing self-assembled vasculature networks is needed to address the required demands.”.
As per claims 2 and 12, Watanabe in view of Zhang teaches, the system of claim 1, wherein the image collected by the imaging device is a microscopic image or a fluorescent image (Watanabe, ¶ [0004] “Thus an object of the present invention is to enable the fluid secretion function of epithelial cells have a fluid secretion function, such as intestinal epithelial cells, to be evaluated simply in a short period of time without needing a stain such as a fluorescent dye or the like.” ).
As per claims 3 and 13, Watanabe in view of Zhang teaches, the system of claim 1, wherein the organoid analysis method includes preprocessing the image of the organoid (Watanabe, ¶[0079] “This thereby enables observations to be made of the changes over time in the cross-sectional area of the same organoids. Obviously statistical processing may be performed for plural organoids.” This represents the processing).
As per claims 4 and 14, Watanabe in view of Zhang teaches, the system of claim 3, wherein preprocessing the image for the organoid comprises adjusting the brightness or contrast of the image (Watanabe, ¶[0020] “Moreover, taking the optical density of the pixel intensity values of maximum brightness to be 0 and the optical density of the pixel intensity values of minimum brightness to be 400, then an object for which the average optical density of the pixels configuring the object is 30 or less may be determined to be a living object.” adjusting the brightness and ¶[0086] “using phase contrast images of intestinal organoids at 10 days after the passage.” Using contrast as it reads on the claimed language).
As per claims 5 and 15, Watanabe in view of Zhang teaches, the system of claim 3, wherein preprocessing the image for the organoid comprises removing noise from the image (Watanabe, ¶[0013] “ greater is taken as a confirmed-edge pixel; and a region surrounded by confirmed-edge pixels alone” confirming edge alone would represent removing noise).
As per claims 6 and 16, Watanabe in view of Zhang teaches, the system of claim 1, wherein the organoid analysis method includes analyzing the image for the organoid (Watanabe, ¶ [0014] “For example, when pixel intensity values are expressed as on an 8 bit display as is employed for ordinary image analysis” this represents analyzing the image).
As per claims 7 and 17, Watanabe in view of Zhang teaches, the system of claim 6, wherein analyzing the image for the organoid comprises calculating the area of the organoid in the image (Watanabe, ¶ [0016] Furthermore, a third aspect of the present invention is the first or second aspect, wherein in the selection process: for a compactness C.sub.P defined by C.sub.P=P.sup.2/(4π.Math.A), in which A (μm.sup.2) is an area of the object and P (μm) is a perimeter length of the object, an object having a compactness C.sub.P of 2.0 or less is selected as being derived from the organoid.” This represents calculating the area).
As per claims 8 and 18, Watanabe in view of Zhang teaches, the system of claim 6, wherein analyzing the image of the organoid comprises determining the intensity of an organoid-by-organoid area (Watanabe, ¶[006] “edges configured by pixels having at least a prescribed difference in pixel intensity value with respect to that of a background, the background being an average pixel intensity value of a prescribed region having a size capable of containing an organoid subject to measurement.” determining the intensity of an organoid-by-organoid area since it is at a pixel level).
As per claims 9 and 19, Watanabe in view of Zhang teaches, the system of claim 1, wherein the organoid analysis method includes performing a fractal analysis of the image (Watanabe, ¶[0055] “The organoids 700 in the culture gel 610 are recognized as objects by the difference in their refractive indices to that of the culture gel 610.” This represents performing a fractal analysis of the image ).
As per claims 10 and 20, Watanabe in view of Zhang teaches, the system of claim 9, wherein analyzing the image for the organoid comprises determining a feature importance value for each of a plurality of the differentiation factors (Zhang, ¶[0107] “Furthermore, to form the hydrogel and liquid interface with the design herein, micro-structures (any features that is less than 300 microns, for example) are not needed.” This represents determining a feature importance value and ¶[0109] “Moreover, because of the innovation in the design of the plate and the use of hydrogel, users do not need to pipette or cast any gel solution that is less than 15 microliters” ).
Conclusion
THIS ACTION IS MADE FINAL. 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 SANTIAGO GARCIA whose telephone number is (571)270-5182. The examiner can normally be reached Monday-Friday 9:30am-5:30pm.
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, Chineyere Wills-Burns can be reached at (571) 272-9752. 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.
/SANTIAGO GARCIA/Primary Examiner, Art Unit 2673
/SG/
Prosecution Insights