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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 26 November 2025 has been entered.
Restriction
Claims 4-9 and 11-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 02/17/2025.
Claim Status
Claim 1 has been amended, claims 4-9 and 11-13 are withdrawn, and claims 1-3 and 10 have been considered on their merits.
Rejection Status
The rejections under 35 U.S.C. § 103 have been withdrawn due to Applicants amendments. New grounds of rejection are set forth below.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation “substantially regularly arranged”, substantially is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is therefore unclear what the phrase “substantially regularly arranged” means. Applicant must recite plainly what the intended meaning of the claim is.
Claim 1 recites the limitation “a polymerized layer filling in gaps between the one or more kinds of particles and a substrate to fix the particles layer on the substrate”. It is unclear if the first and second mention of “substrate” are the same substrate or different. It is unclear if the first mention of “substrate” is referring to the polymerized layer itself and is fixing the particles to a separate substrate (i.e., a culture dish), if the polymerized layer acts as a substrate to fix the particle layer to itself, or if there is a separate substrate from the particle layer and this separate substate is fixing particles to itself. The claim limitation is being interpreted as the polymerized layer fixes the particle layer to any substrate.
Claim 1 recites the limitation regarding the particle layer, “partially exposed and not covered by the polymerized layer”. It is unclear if “not covered” means the particle is not covered at all or is partially exposed, as in, not completely covered by the polymerized layer. The claim limitation is being interpreted as the particles of the particle layer are partially exposed and not completely covered by the polymerized layer.
The language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds". See, e.g., the following decisions: In re Hammack, 427 F 2d. 1378, 1382, 166 USPQ 204, 208 (CCPA 1970); In re Venezia 530 F 2d. 956, 958, 189 USPQ 149, 151 (CCPA 1976); In re Goffe, 526 F 2d. 1393, 1397, 188 USPQ 131, 135 (CCPA 1975); In re Watson, 517 F 2d. 465, 477, 186 USPQ 11, 20 (CCPA 1975); In re Knowlton 481 F 2d. 1357, 1366, 178 USPQ 486, 492 (CCPA 1973).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Schlenoff et al. (US 2005/028711, published 29 Dec 2005, of record) in view of Yang et al. (US 2010/0317112 A1, published 16 December 2010) and Kaminaga et al. (Micromachines 2015).
This is a new rejection, necessitated by the amendments to the claims. A response to applicant’s traversal follows the rejection.
Yang et al. was used in previous office actions, the US PGpub was utilized in place of the previously used, related foreign patent document.
Regarding claim 1, the statement in the preamble of claim 1, “configured to expand circulating tumor cells ex vivo” and at the last two lines of claim 1 “configured to attach the circulating tumor cells”, recite intended purpose/use clauses. Intended purpose/use limitations do not result in a structural difference of the composition and thus, they do not add any additional structural limitation to the claimed composite material film. Therefore, if the film as defined by the claims is formed, the properties of said film would be inherently present.
Thus, in light of the 112b rejection and intended purpose/use clauses, claim 1 is interpreted as a composite material film comprising one or more kinds of particles substantially regularly arranged, wherein the particles are selected from the group consisting of metal particles, metal oxide particles, silicon oxide particles, and combinations thereof; and a polymerized layer filling in gaps between one or more kinds of particles and fixes the particle layer on any substrate, wherein the polymerized layer is selected from the group consisting of polystyrene and its derivatives, polyester, silicon dioxide, silica gel, silicone, silicone rubber and combinations thereof, wherein surfaces of some of the particles are partially exposed and not completely covered by the polymerized layer.
Regarding claims 1-3, Schlenoff et al. teach an article for controlling the attachment and growth of cells on a surface of the article comprising a substratum (substrate) having a surface and a film on the surface (Abstract). Schlenoff et al. teach both dip coating and spraying permit a wide variety of additives to be incorporated into a film as it is formed and additives may be incorporated into polyelectrolyte multilayers include inorganic materials such as metallic oxide particles (e.g., silicon dioxide, or titanium dioxide (claim 2)) which typically range in size from about 1 nanometer (nm) to about 10 micrometers (µm) (claim 3) (para. [0106]). The additives to be incorporated into the film would necessarily fill in the gaps between the particles as they are incorporated into the layers of the film, thus, leaving no gaps. Schlenoff et al. teach a method for building multilayers of polymer via ion pairing forces to the oppositely-charged surface and reverses the surface charge thereby priming the film for the addition of the next layer (para. [0006]). The ion pairing method of Schlenoff et al. reads as the layers are fixed to each other, thereby fixing the film which comprises particles (particle layer) to the previous layer, which reads as a substrate.
Schlenoff et al. teach thin films of polyelectrolyte complexes have been prepared using polyelectrolytes which are made using a dipping method which builds up layers, noting films prepared in this manner then to be uniform (para. [0006]), which suggests the particles within the polymerized layer would necessarily be substantially regularly arranged.
Additionally, even if the particles of Schlenoff et al. were not substantially regularly arranged, Kaminaga et al. teach one of the most important factors in cellular research is the density of the cells in the culture medium (p. 410, Introduction). Kaminaga et al. teach cellular density affects many properties of cells, such as morphology, viability, metabolism, reaction toward cytokines, expression pattern of intracellular proteins, and differentiation (p. 410, Introduction). Kaminaga et al. teach the conditions around cells, such as concentrations of growth factors, nutrients, and waste from cells are also affected by cellular density (p. 410, Introduction). Kaminaga et al. suggest considering these problems, uniformly aligned cells is necessary (p. 410, Introduction). Kaminaga et al. was cited to inform the importance of uniformly aligned cells, not the methods or techniques taught by Kaminaga et al.
Therefore, it would have been obvious to one of ordinary skill in the art to substantially regularly arrange the particles with a reasonable expectation of success because Kaminaga et al. teach the importance of uniformly aligned cells and the particle layer of Schlenoff et al. is for controlling the attachment and growth of cells. One would be motivated to substantially regularly arrange the particles because this would allow the ability to monitor and manipulate individual cellular microenvironments.
It is noted, the open language of claim 1, “comprising” , not limit the number of layers of the claimed composite material film. Schlenoff et al. teach the film comprises a polyelectrolyte which may be derived directly from monomer units or they may be introduced by chemical reactions on a precursor polymer, such as Poly(styrenesulfonic acid) is often made by the sulfonation of neutral polystyrene or Poly(styrenesulfonic acid) can also be made by polymerizing the negatively charged styrene sulfonate monomer (polystyrene and its derivatives) (para. [0044]).
Yang et al. teach a cell culture support having increased specific gravity including mixing an inorganic compound with a biocompatible polymer, then cleaning and drying the mixture to produce the support (para. [0019-0020]). The inorganic compound is ceramic, including titanium dioxide and silicon dioxide among others, and metal, including titanium (para. [0024-0025]). The inorganic compound reads as a particle layer consisting of metal (titanium) and metal oxide (titanium dioxide) particles. Yang et al. teach the inorganic compounds (metal oxide particles) in the polymer can be used to adjust cell adhesion (para. [0026]).
Schlenoff et al. is silent to the orientation of the particles, i.e., being partially exposed.
However, Schlenoff et al. teach nanoparticles of zirconium oxide added to a polyelectrolyte solution or complex solution tend to improve the abrasion resistance of the deposited film (para. [0106]). Therefore, it would have been obvious to one of ordinary skill in the art to expect the nanoparticles to be present above the surface of the solution with a reasonable expectation of success because Schlenoff et al. teach the zirconium oxide nanoparticles protect improve abrasion resistance which indicates the nanoparticles are, at least partially, above the surface in order to protect said surface. Additionally, Schlenoff et al. teach the film layers are typically between 10 nm and 10,000 nm (10 µm) thick (para. [0006]) and the particle sizes range from 1 nm to about 10 µm (para. [0106]). Therefore, it would be reasonable to expect a larger particle combined with a thinner layer of film would result in the particles to be partially exposed and not covered by the polymerized layer. One would have been motivated to arrange the particles of said particle layer to be partially exposed because Yang et al. teach the inorganic compounds (metal oxide particles) in the polymer can be used to adjust cell adhesion (para. [0026]), which suggests the metal oxide particles would be present above the surface of the polymer.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Schlenoff et al. (US 2005/028711, published 29 Dec 2005, of record) in view of Yang et al. (US 2010/0317112 A1, published 16 December 2010) and Kaminaga et al. (Micromachines 2015), as applied to claims 1-3 above, and further in view of Wang et al. (US 2019/0300832 A1, of record).
Regarding claim 10, Schlenoff et al. in view of Yang et al. and Kaminaga et al. are silent to a kit for expanding circulating tumor cells ex vivo comprising a culture vessel, comprising: a substrate; and composite material film attached to the substrate; and a culture medium comprising a stem cell culture medium.
However, Wang et al. teach a cell culture tool (kit) comprises a substrate, consisting of a two-dimensional planar surface, and a multi-particle colloidal crystal layer (para. [0065]). Wang et al. teach the multi-particle colloidal crystal layer is located on the substrate, which may be a culture dish, a culture plate, a glass slide, a plastic slide, etc. (para. [0065]). Wang et al. teach a cell solution is prepared comprising circulating tumor cells and a culture medium wherein the isolated circulating tumor cells are mixed with the culture medium to form the cell solution (para. [0066]). The circulating tumor cells read as expanding circulating tumor cells ex vivo. Wang et al. teach the cell solution is contacted with the multi-particle colloidal crystal layer on the cell culture tool to attach the circulating tumor cells in the cell solution to the
multi-particle colloidal crystal layer and expand to a given condition (para. [0067]) and Figs. 4 and 5). Wang et al. teach the basal medium in the culture medium is DMEM/F12 medium (para. [0072]), which is commonly used as a basal medium for the culture of stem cells. Wang et al. teach multiple examples where the surfaces of some of the particles are partially exposed and not covered by the medium layer, as evidenced by SEM images of the surface of the multi-particle colloidal crystal layer (Figs. 9-36). The crystal structure of the multi-particle colloidal crystal layer would inherently have particles substantially regularly arranged, as can be seen in Fig. 10A, below, which show a multi-particle colloidal crystal layer formed by silicon particles having a particle size of 2000 nm (first particle, 121) and polystyrene particles having a particle size of 100 nm (second particles 122) (para. [0078]). The first particle is indicative of the particle layer and the second particle is indicative of the medium layer.
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Therefore, it would have been obvious to one of ordinary skill in the art to utilize the polymerized layer of Schlenoff et al. with the kit of Wang et al. with a reasonable expectation of success because while Wang et al. is silent to the specific polymerized layer comprising a particle layer, Wang et al. demonstrates the adhesive properties of metal particles as it relates to cell adhesion along with the ability to expand circulating tumor cells using a similar substrate. One would be motivated to utilize the polymerized layer of Schlenoff et al. with the kit of Wang et al. because both references utilize a composite material film with particles for the purpose of expanding cells. Additionally, Wang et al. teach the multi-particle colloidal crystal layer may further comprise additional particles, wherein, the particles may be from silicon, polystyrene, carboxylated polystyrene, polystyrene sulfonic acid, and other alternative polymer materials (para. [0070-0071]), suggesting the cell culture tool of Wang et al. could incorporate a polymerized layer.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Traversal
Applicant's arguments filed 26 November 2025 have been fully considered but they are not persuasive.
The above rejections have been updated to highlight where the references teach substantially arranged particles, a polymerized layer filling in gaps between the particles, fixing the particles on a substrate, and the particles being partially exposed.
In response to applicant's argument that Schlenoff does not disclose the particle layer are configured to attach the circulating tumor cells, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Applicant's arguments filed 04 July 2025 regarding Wang were previously not considered because the arguments were considered moot as the action following these arguments did not rely on Wang, however, the arguments have now been fully considered. Wang was utilized as a reference in a different context in the present Official action. Wang does not specifically teach a polymerized layer but the teachings of Wang suggest the polymers could be utilized with composite layer (para. [0070-0071]) for use in expanding circulating tumor cells.
Relevant prior art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Lerman et al. (Tissue Engineering, 2018)
Lerman et al. teach polystyrene has been the fundamental substrate for cell culture for more than 50 years. Lerman et al. teach many functional moieties exist and the next steps should look at mechanisms to target specific cell types and means to sequester and expand these cells.
Conclusion
No claims are allowed.
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/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631