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 remarks and amendments to the claims, filed 28 July 2026, have been received and entered into the case. The amendments to the claims do not appear to contain new matter.
Restriction
Applicant’s election with traverse of Group 2, claims 1-3 and 10, in the reply filed on 17 February 2025 was previously acknowledged.
Claims 4-9 and 11-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 17 February 2025.
Claim Status
Claim 1 has been amended, claims 4-9 and 11-13 were previously withdrawn, and claims 1-3 and 10 have been considered on their merits.
Rejection Status
The rejections under 35 U.S.C. § 112(b) have been withdrawn due to Applicants amendments. Specifically, the amendment regarding the distance between the particles.
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, of record) and Kaminaga et al. (Micromachines 2015, of record).
This rejection is substantial similar to the rejection of record, however, this is considered a new rejection, necessitated by the amendments to claim 1. A response to Applicant’s traversal follows the rejection.
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.
Regarding claims 1-3, Schlenoff teaches an article for controlling the attachment and growth of cells on a surface of the article comprising a substratum having a surface and a film on the surface (Abstract). Schlenoff teaches preferred substrates are cell and tissue culturing substrates, such as Petri dishes (para. [0038]). The Petri dishes of Schlenoff read as a first substrate is glass or plastic. Schlenoff teaches 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 teaches 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 reads as the layers are fixed to each other, thereby fixing the film which comprises particles (particle layer) to the previous layer.
Schlenoff teaches 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 regularly arranged.
Additionally, even if the particles of Schlenoff et al. were not regularly arranged, Kaminaga teaches one of the most important factors in cellular research is the density of the cells in the culture medium (p. 410, Introduction). Kaminaga teaches 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 teaches 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 suggests considering these problems, uniformly aligned cells is necessary (p. 410, Introduction). Kaminaga was cited to inform the importance of uniformly aligned cells, not the methods or techniques taught by Kaminaga.
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 teaches the importance of uniformly aligned cells and the particle layer of Schlenoff is for controlling the attachment and growth of cells. One would be motivated to substantially regularly arrange the particles because this would allow one to monitor and manipulate individual cellular microenvironments.
Regarding the limitation directed to a distance between the particles is in a range of between zero and three times a diameter of the particles, the distance between particles would be determined based on the intension of the composite material as a matter of routine optimization, for example to equally space a specific size cell, if the cells are too close it would be challenging to monitor and manipulate individual cellular microenvironments, as discussed above in Kaminaga. MPEP 2144.05.II.A. states "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller,220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, it would have been obvious to one of ordinary skill in the art to have recognized that the spacing between particles was a result effective variable because Kaminaga teaches cellular density affects many properties of cells, such as morphology, viability, metabolism, reaction toward cytokines, expression pattern of intracellular proteins, and differentiation. Kaminaga teaches the conditions around cells, such as concentrations of growth factors, nutrients, and waste from cells are also affected by cellular density. Kaminaga suggests considering these problems, uniformly aligned cells is necessary. As the intended use is clearly stated in the claims, to expand circulating tumor cells, the spacing of the particles to which the cells attach would be based on the size of these cells along with the desired cellular spacing. Since the distance between particles is recognized as a result effective variable, one of ordinary skill would be motivated to optimize by routine experimentation to determine the optimal distance. Absent evidence of criticality, the claimed range from between zero and three times a diameter of the particles would be obvious.
It is noted, the open language of claim 1, “comprising” , not limit the number of layers of the claimed composite material film. Schlenoff teaches 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 teaches 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 teaches the inorganic compounds (metal oxide particles) in the polymer can be used to adjust cell adhesion (para. [0026]).
Schlenoff is silent to the orientation of the particles, i.e., portions of surfaces of particles are exposed.
However, Schlenoff teaches 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 teaches 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 teaches 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 teaches 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.
Response to Traversal
Applicant's arguments filed 28 July 2026 have been fully considered but they are not persuasive.
Applicant has supplied a comparison table on page 3 of the remarks, comparing the limitations of the claims and the prior art references utilized in the rejections of record. This table is highlighting individual references, however, the rejections are based on obviousness rationales. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Due to the nature of this table, it is interpreted as targeting individual references and is stating the specific references are deficient in the manner indicated in the corresponding rows and columns. Therefore, regarding the arguments directed to the individual references not correcting the deficiencies of the preceding references, this is not persuasive because, as indicated above, the references utilized are shown to not be deficient. As such, the references have been found to be obvious over the claimed composition.
In response to Applicant's perceived assertion that the references do not teach the exposed particle surfaces are configured to attach circulating tumor cells, which is considered an intended use/result of the claimed composition. 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.
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, of record) and Kaminaga et al. (Micromachines 2015, of record), as applied to claims 1-3 above, and further in view of Wang et al. (US 2019/0300832 A1, of record).
This rejection is substantial similar to the rejection of record, however, this is considered a new rejection, necessitated by the amendments to claim 1. A response to Applicant’s traversal follows the rejection.
Regarding claim 10, Schlenoff in view of Yang and Kaminaga 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 teaches 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 teaches 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 teaches 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 teaches 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 teaches 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 teaches 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 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 with the kit of Wang with a reasonable expectation of success because while Wang is silent to the specific polymerized layer comprising a particle layer, Wang 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 with the kit of Wang because both references utilize a composite material film with particles for the purpose of expanding cells. Additionally, Wang teaches 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 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 28 July 2026 have been fully considered but they are not persuasive.
Applicant has supplied a comparison table on page 3 of the remarks, comparing the limitations of the claims and the prior art references utilized in the rejections of record. This table is highlighting individual references, however, the rejections are based on obviousness rationales. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Due to the nature of this table, it is interpreted as targeting individual references and is stating the specific references are deficient in the manner indicated in the corresponding rows and columns. Therefore, regarding the arguments directed to the individual references not correcting the deficiencies of the preceding references, this is not persuasive because, as indicated above, the references utilized are shown to not be deficient. As such, the references have been found to be obvious over the claimed composition.
In response to Applicant's perceived assertion that the references do not teach the exposed particle surfaces are configured to attach circulating tumor cells, which is considered an intended use/result of the claimed composition. 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.
Conclusion
No claims are allowed.
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 NICHOLAS A. HUMPHRIES whose telephone number is (703)756-5556. The examiner can normally be reached Monday - Friday, 7:30am - 4:30 pm.
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/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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