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 .
Claim Status
Applicant’s election without traverse of claims 1 – 18 in the reply filed on 08/24/2026 is acknowledged.
Claims 19 – 20 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 08/24/2026.
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, 4 – 7, 10 – 14, 16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Neal et al. (U.S. Patent Application Publication No. 2018/0119107 A1; hereinafter Neal) and Penderecka et al. (Implementation of a dynamic culture condition to the heterotypic 3D breast cancer model. J Biomed Mater Res. 2020; 108: 1186–1197; hereinafter Penderecka).
Regarding claims 1, 4 – 7, 13 – 14, 16 and 18, Neal discloses methods to preserve tumor-stromal interactions in culture and therapeutic predictive applications, in which they establish Patient-Derived Organoids using a single 3-dimensional air-liquid interface methodology (para. [0025] and [0091]). The surface tension arising from molecular interactions between the liquid and the gas phase acts on the cells forming an organoid. Neal further discloses plating mechanically dissociated tumor fragments in a Type I collagen matrix (para. [0092]). Neal also discloses obtaining a tumor tissue sample comprising stromal and immune cells (claim 3; T cells, MDSCs). Although, Neal (para. [0013] and [0094]) does disclose FACS analysis of dissociated PDOs. Neal does not explicitly teach dissociating a tissue into individual cells and then mixing the individual cells to form the organoid.
However, Penderecka discloses/provides the motivation with a study related to the implementation of a dynamic culture condition to the heterotypic 3D breast cancer model, in which NIH3T3/635 fibroblast and EMT6 breast cancer cells are seeded on scaffolds as a monoculture of fibroblasts, monoculture of breast cancer cells, and coculture of fibroblasts and cancer cells at a ratio of 9:1, respectively (p. 1188, Section 2.3.2, 3D cell cultures). Penderecka further discloses that the presence of regulatory factors secreted by cancer cells, fibroblasts, immune cells, and endothelial cells fulfill the crucial role in tumor biology. Thus, a search for a new cancer model that would better imitate the in vivo conditions is needed (p. 1187, 1st para.).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the reconstituted 3D cluster of Neal with the 3D cell culture method of Penderecka. Doing so would generate a Patient-Derived reconstituted 3D cluster with optimizable cell types/numbers in order to further mimic and study the molecular and cellular dynamics of the tumor microenvironment in order to produce therapies.
Regarding claims 10 and 12, Neal discloses contacting the (para. [0035]) tissue explants with candidate cells or candidate agents prior to forming the PDO. Neal suggests contacting the PDO culture with (para. [0011]) checkpoint inhibitors, etc., and CAR-T cells (para. [0033]), respectively.
Regarding claim 11, Neal discloses that candidate agents are screened for activity that is anti-tumorigenic or anti-tumoral (para. [0088]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the anti-tumor treatment options of Neal in the reconstituted 3D cellular cluster of Neal and Penderecka. Doing so would provide a 3D cell cluster model to study the effects of individual and combination cancer therapy.
Claims 2 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Neal and Penderecka as applied to claims 1, 4 – 7, 13, 14, 16 and 18 above, and further in view of Guo et al. (W.O. Patent Application Publication No. 2020/198455; cited on IDS, hereinafter Guo).
Regarding claims 2 and 15, Neal and Penderecka teach all of the elements of the current invention as stated above except applying an acoustic force to the mixture of dissociated tumor cells. However, Guo discloses an acoustofluidic device that produces standing surface acoustic waves to force the clustering of individual cells into multicellular clusters (para. [0002]). Guo discloses the motivation for using an acoustic force by stating that the acoustofluidic device provides a simple and efficient way to produce large numbers of uniformly-shaped multicellular clusters (para. [0057]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the 3D cell cluster aggregation method of Neal and Penderecka with the acoustic force of Guo. Doing so would provide an efficient method to produce uniformly shaped multicellular clusters formed by acoustic waves.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Neal and Penderecka as applied to claims 1, 4 – 7, 13, 14, 16 and 18 above, and further in view of Kang et al. (Engineered Microsystems for Spheroid and Organoid Studies, p. 1 – 36, Advanced Healthcare Materials. Vol. 10, No. 2, (2021); cited on IDS, hereinafter Kang).
Regarding claim 3, Neal and Penderecka teach all of the elements of the current invention as stated above except applying a centrifugal force to the mixture of dissociated tumor cells. However, Kang discloses centrifugation-based culture (p. 5, 2.2 Centrifugation-Based Culture). Kang discloses/provides the motivation for applying an inertial force to a 3D cell cluster by stating that it provides the efficient generation (p. 7, 2nd para.) of multicellular spheroids and organoids.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the 3D cell cluster aggregation method of Neal and Penderecka with the centrifuge-based system of Kang. Doing so would utilize a technique that has been used for a long time due to the ease of operation and the advantage of rapid formation of 3D cellular structures.
Claims 8 – 9 are rejected under 35 U.S.C. 103 as being unpatentable over Neal and Penderecka as applied to claims 1, 4 – 7, 13, 14, 16 and 18 above, and further in view of Jensen et al. (Is it time to start transitioning from 2D to 3D cell culture?”, pages 1 – 15, Frontiers in Molecular Biosciences. Vol. 7, No. 33, 06 March (2020); cited on IDS, hereinafter Jensen).
Regarding claims 8 – 9, Neal and Penderecka teach all of the elements of the current invention as stated above except stabilizing the reconstituted 3D cell clusters by inducing the liquid medium to form the matrix after cells are aggregated into the reconstituted 3D cell clusters. However, Jensen discloses stabilizing 3D cell clusters by inducing a liquid medium to form a matrix after cells are aggregated into reconstituted 3D cell clusters through freeze-drying (p. 9, Freeze-Drying section).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the reconstituted 3D cell clusters of Neal and Penderecka with the matrix stabilizing liquid of Jensen. Doing so would provide a method of creating hydrogel scaffolds that are effective in 3D cell culture wherein the cell environment can be manipulated to mimic that of a cell in vivo.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Neal and Penderecka as applied to claims 1, 4 – 7, 13, 14, 16 and 18 above, and further in view of Gallego-Perez et al. (High throughput assembly of spatially controlled 3D cell clusters on a micro/nanoplatform, Lab Chip, 10 (6): 775 – 782, (2010); hereinafter Gallego-Perez).
Regarding claim 17, Neal and Penderecka teach all of the elements of the current invention as stated above except the size of the organoid being about 150 µm to 250 µm. However, Gallego-Perez discloses that the maximum spheroid diameter that avoids impaired oxygen transport is about 100 µM (p. 778, 2nd col. 1st para). Further Gallego-Perez discloses a study that compares 3D organoids at a size of 150 µM to 300 µM (Fig. 3) and reveals that smaller wells tend to favor longer term cell activity, as it is well established that 3D cell clustering, if uncontrolled, could affect cell viability and functionality.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the reconstituted 3D cell clusters of Neal and Penderecka with the size of Gallego-Perez. Doing so would allow for long term cell activity and optimal oxygen transport in the organoid, according to Gallego-Perez.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER JACKSON III whose telephone number is (571)272-0247. The examiner can normally be reached M-F 9:00A - 5:00P.
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, Tracy Vivlemore can be reached at 571-272-2914. 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.
/WALTER JACKSON III/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
Prosecution Insights