DETAILED ACTION
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 .
Applicant's amendments to the claims filed on 10-27-2025 have been received and entered. Claim 12 have been added. Claims 1-12 are pending in the instant application.
Election/Restrictions
Applicant's election with traverse of Group III, Claims 6-12, in the reply filed on 10-27-2025 is acknowledged. The traversal is on the ground(s) that a search of all the claims would not impose a serious burden on the Office and the Office has not established that the proposed alternative is a materially different process, nor an example of a process practiced with a materially different product. This is not found persuasive because Group I, claims 1-4, is drawn to a method of producing a conditioned medium; Group II, claim 5, is drawn to a conditioned medium; and Group III, claims 6-11, is drawn to a method of culturing a patient-derived cancer cell. They differ in objectives, method steps, reagents and dosages used, schedules used, response variants and criteria of success. They are different in methodology and application. They have different classifications and require separate search and the search would not be coextensive. Thus, inventions I - III are not obvious variants and are patentably distinct from each other. There would be a serious search and/or examination burden if restriction were not required because: a. the inventions have acquired a separate status in the art in view of their different classification; b. the inventions have acquired a separate status in the art due to their recognized divergent subject matter; c. the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries).
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-5 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10-27-2025.
Claims 6-12 are under consideration.
Priority
This application is a CON of PCT/JP2021/030361 filed on 08/19/2021 which claim priority from foreign applications JAPAN 2020-140076 filed on 08/21/2020. 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 filing date of the foreign application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02-21-2023 are in compliance with the provisions of 37 CPR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
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.
Claims 6, 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Taniguchi et al (US 2017/0285002 A1, Pub . Date: Oct. 5 , 2017) in view of Naughton et al (Pub. No.: US 2017/0055561 A1, Pub. Date: Mar. 2, 2017).
Claim interpretation:
The specification of the claimed invention teaches that “The term "polymer electrolyte" as used in the present specification refers to a polymer having a dissociable functional group in the polymer chain. As the polymer electrolyte used in the present embodiment, any polymer electrolyte can be used as long as it does not adversely affect the growth of cells and the formation of cell aggregates. Examples of the polymer electrolyte include, but are not limited to, glycosaminoglycans such as heparin, chondroitin sulfate (e.g., chondroitin 4-sulfate and chondroitin 6-sulfate), heparan sulfate, dermatan sulfate, 20 keratan sulfate, hyaluronic acid, and the like; dextran sulfate, rhamnan sulfate, fucoidan, carrageenan, polystyrene sulfonic acid, polyacrylamide-2-methylpropanesulfonic acid, polyacrylic acid, and derivatives thereof. Any one of these polymer electrolytes may be used singly or in combination of two or more kinds” (Page 6, lines 14-23). Thus, glycosaminoglycans such as heparin, chondroitin sulfate (e.g., chondroitin 4-sulfate and chondroitin 6-sulfate), heparan sulfate, dermatan sulfate, 20 keratan sulfate, hyaluronic acid, and the like; dextran sulfate, rhamnan sulfate, fucoidan, carrageenan, polystyrene sulfonic acid, polyacrylamide-2-methylpropanesulfonic acid, polyacrylic acid, and derivatives thereof are interpreted as polymer electrolytes.
The specification of the claimed invention teaches that “Examples of the extracellular matrix component include, but are not limited to, collagen, laminin, fibronectin, vitronectin, elastin, tenascin, entactin, fibrillin, proteoglycan, and modifications or variants thereof. The extracellular matrix component may be used singly or in combination of two or more kinds”. Thus, collagen, laminin, fibronectin, vitronectin, elastin, tenascin, entactin, fibrillin, proteoglycan, and modifications or variants thereof are interpreted as the extracellular matrix components.
Regarding to claim 6, Taniguchi et al teach “…The present invention also provides a method for preparing a cancer organoid from cancer tissue …” (Abstract); “… a method for reconstituting cancer tissue using primary cultured cancer cells derived from a cancer patient have so far been developed as approaches for artificially reconstituting human cancer tissue” ([0003], page 1); and “FIG. 10 The upper panel shows two culture methods of primary culture cells isolated from cancer patients” ([0026], page 3).
Taniguchi et al teach the medium for use in the culture may be any medium as long as the cancer organoid can be formed ([0062], page 7). Taniguchi et al teach reconstitution of pancreatic cancer organoid from primary pancreatic cancer cell with conditioned medium (a second medium) : Pancreatic cancer cyst was dispersed by the same approach as in the passage and then three-dimensionally cocultured with HUVECs and hMSCs using Matrigel ([0102] - [0103], page 11, see below [0103] for Composition of Culture Solution).
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Taniguchi et al do not teach preparing a conditioned medium (in a first medium). Naughton et al cure the deficiency.
Naughton et al teach “Novel products comprising conditioned cell culture medium compositions and methods of use are described” (Abstract). Naughton et al teach three-dimensional cell cultures: “The stromal cells used in the three-dimensional cultures comprise fibroblasts, mesenchymal stem cells, liver reserve cells, neural stem cells, pancreatic stem cells, and/or embryonic stem cells with or without additional cells and/or elements described more fully herein” ([0078], page 6); “Fibroblasts will support the growth of many different cells and tissues in the three-dimensional culture system, and, therefore, can be inoculated onto the matrix to form a “generic' stromal Support matrix for culturing any of a variety of cells and tissues” ([0079], page 6). Naughton et al teach establishment of three-dimensional stromal tissue: “The three-dimensional support or framework may be of any material and/or shape that (a) allows cells to attach to it (or can be modified to allow cells to attach to it); and (b) allows cells to grow in more than one layer. …. collagen, collagen sponges ….” ([0091], page 7). The growth of cells in the three-dimensional stromal cell culture may be further enhanced by adding to the framework, or coating the support with proteins (e.g., collagens, elastic fibers, reticular fibers) glycoproteins, glycosaminoglycans (e.g., heparin Sulfate, chondroitin-4-Sulfate, chondroitin-6-sulfate, dermatan Sulfate, keratin Sulfate, etc.), a cellular matrix, and/or other materials ([0094], page 7). (For the claimed: a three-dimensional cell tissue including an extracellular matrix component, a polymer electrolyte, and a cell cluster including a fibroblast)
Naughton et al teach recovery of the conditioned media: “In a preferred embodiment, the medium conditioned by the three-dimensional cell culture is collected after exposure of the medium to the cells at days 10 through day 14 of culturing” ([0124], page 12) (For the claimed: “culturing, in a first medium for 24 hours or longer” and “collecting the first medium in which the three-dimensional cell tissue has been cultured as the conditioned medium”).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Taniguchi et al by using conditioned media as taught by Naughton et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Naughton et al teach “the compositions of the invention may be used to culture cells. The conditioned cell media of the invention contains factors useful in promoting cell attachment and growth. Further, the cell medium may be conditioned by cells which are genetically engineered and which may, for example, contain increased fibronectin or collagen concentrations beneficial in promoting cell attachment to a scaffold or culture surface.” ([0024], page 3), and Naughton et al stated that “Increasing fibronectin or collagen concentrations may be beneficial for promoting cell attachment to a scaffold or culture surface. Rather than add these factors to the medium, conditioned medium may be used for culturing cells and preparing three-dimensional tissue constructs, such as Dermagraft. Applicants have demonstrated that the conditioned medium increases cell proliferation of fibroblasts and keratinocytes, see FIG. 3” ([0171], page 17). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Naughton et al were successful in establishment of three-dimensional stromal tissue (fibroblast culture) and recovery of the conditioned media with working examples and data.
Regarding to claim 8, Naughton et al teach stromal cells of liver may include fibroblasts, Kupffer cells, and vascular and bile duct endothelial cells ([0094], page 7).
Regarding to claim 9, Naughton et al teach “Human dermal fibroblasts were seeded onto the substrate of the apparatus …. The substrate is within the casing designed to facilitate three-dimensional tissue growth on its surface and the cells were cultured in a closed system in cultured in high glucose DMEM” ([0185], Page 19).
Regarding to claim 10, Taniguchi et al teach Wnt3 conditioned medium (50% v/v ) ([0103], page 11).
Regarding to claim 11, Taniguchi et al “Any medium for cancer cell culture may be used, and examples thereof include DMEM medium. It has been confirmed that a medium of EGM:DMEM = 1 : 1 is suitable for the preparation of a pancreatic cancer organoid” ([0062], page 7).
Claims 7 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Taniguchi et al (US 2017/0285002 A1, Pub . Date: Oct. 5 , 2017) in view of Naughton et al (Pub. No.: US 2017/0055561 A1, Pub. Date: Mar. 2, 2017) as applied to claims 6, 8-11 above, and further in view of Matsusaki et al (Pub .No.: US 2018 /0355308 A1, Pub. Date: Dec. 13, 2018) (Applicant’s own work).
The teachings of Taniguchi et al and Naughton et al above are incorporated herein in their entirety.
Although Taniguchi et al teach prepared paraffin block containing tissue was sliced into a thickness of 4 to 6 using a microtome ([0096], page 10) and Naughton et al teach establishment of three-dimensional fibroblast culture with heparin and collagen ([0091] and [0094], page 7), the above references differ from the instant claims in that they don’t specify concentration of heparin and collagen, and three-dimensional cell tissue has a thickness of 5 µm or more. Matsusaki et al cure the deficiency.
Regarding to claim 7, Matsusaki et al teach “a method of producing a three-dimensional cell tissue” (Abstract), and “a thickness of the constructed three-dimensional cell tissue is from about 5 to about 300 µm, about 5 to about 400 µm, or about 5 to about 500 µm” ([0091], page 5).
Regarding to claim 12, Matsusaki et al teach Example 2: Construction of Three -Dimensional Cell Tissue Using Heparin and Collagen: normal human thermal fibroblast (NHDF ) cells of 3.5x106 cells were suspended in a mixture solution of 250 µL of a solution of 0.1 mg/mL of heparin/50 mM tris-hydrochloric acid buffer solution (pH 7.4 ) and 250 µL of 0.1 mg/mL of collagen /acetic acid solution (pH 3.7 ) (that is, each of the final concentrations of collagen and heparin was 0.05 mg/mL) ([0101], page 7), and Matsusaki et al teach “culture was performed in a CO2 incubator (37°C., 5 % CO2) for 24 hours” ([0103], page 7).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Taniguchi et al and Naughton et al above by using concentrations of 0.05 mg/mL collagen and 0.05 mg/mL heparin with a thickness of the constructed three-dimensional cell tissue is from about 5 to about 300 µm as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Matsusaki et al stated that “According to each of the aspects of the present invention, it is possible to produce a three-dimensional cell tissue in a faster and convenient manner compared to the related art. In addition , it is possible to produce a thicker three-dimensional cell tissue compared to the related art by using a method of each of the aspects of the present invention. Accordingly, it is possible to produce a three-dimensional cell tissue with a thickness that could have not been constructed until now” ([0051], page 2). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Matsusaki et al were successful in generation of a three-dimensional cell tissue in a faster and convenient manner with a thicker three-dimensional cell tissue, with detailed instructions and working examples.
Conclusion
No claim is allowed.
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/KHOA NHAT TRAN/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632