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 .
DETAILED ACTION
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 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.
Election/Restrictions
Applicant’s election without traverse of Invention I, claims 1-18, in the reply filed on Jun. 17, 2026 is acknowledged.
Claims 1-20 remain pending in the current application, claims 19 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
The requirement for the restriction of Inventions I and II is still deemed proper and is therefore made FINAL.
Claims 1-18 have been considered on the merits.
Status of the Claims
Claims 1-20 are currently pending.
Claims 19 and 20 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 1-18 have been considered on the merits.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in WIPO on August 31, 2022. It is noted, however, that applicant has not filed a certified copy of the International Application No. PCT/JP2022/032772 application as required by 37 CFR 1.55.
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.
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, 3-7, 9, 10 and 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Herlyn et al. (US 2006/0073469 A1) (ref. of record) in view of Friedl et al. (Cellular and Molecular Life Sciences, 2000).
With respect to claim 1, Herlyn teaches a method for evaluating the migration ability of migratory cells (abstract, 0003 and 0010). With respect to the first recited step of claim 1 and claims 2, 3 and 5, Herlyn teaches culturing a cell structure containing multiple layers including a first solid layer containing fibroblasts (stromal cells and a migratory cell-free layer), a second layer that is a cellular layer containing a first cell type that can be tumor cells (a migratory cell-free cell layer), a third solid layer containing fibroblasts (a migratory cell-free layer) and fourth layer that is another cell layer containing a second cell type that is cytotoxic T lymphocytes (0011 and 0013). With respect to the second recited step of claim 1, Herlyn teaches the method of evaluating the migration ability of the migratory cells in the structure where the first positions of the migratory cells are detected at a first time, then second positions are detected at a second time and the difference in the first and second positions indicates the active migration of the cells (0013). This corresponds to the limitations of “evaluating migration ability of the migratory cells in the cell structure based on mobility of the migratory cells in the cell structure such that the mobility of the migratory cells is a ratio of a height Hm of the migratory cells in the cell structure to a height Hs of the cell structure, wherein the height Hm of the migratory cells in the cell structure is a distance between a point Pb and the migratory cells such that the point Pb is an intersection where a perpendicular line down from the migratory cells to a bottom of the cell structure intersects the bottom of the cell structure, and the height Hs of the cell structure is a distance between the point Pb and a point Pt such that the point Pt is an intersection where a straight line obtained by extending the perpendicular line to a top surface of the cell structure intersects the top surface of the cell structure.”
Herlyn is silent with respect to the orientation of the cell layers, and does not teach the cell structure where the bottom cell layer contains stromal cells and migratory cells and a second cell layer on top containing no migratory cells as recited in claim 1.
However, Friedl teaches “depending on the cellular composition and tissue context of migration, diverse cellular and molecular migration strategies can be developed by different cell types” (abstract). Friedl teaches that cell motility is essential in many different processes including embryological morphogenesis, wound healing, immune surveillance, and inflammation and tumor cell dissemination and metastasis (pg. 41 para. 1). Friedl further teaches that the biomechanical architecture of the tissue has a major impact on cell function (pg. 42 Col. 1 para. 1).
Accordingly, at the effective time of filing of the claimed invention one of ordinary skill in the art would have been motivated to change the configuration of the different layers of the cell structure of Herlyn depending on the desired tissue to be mimic or situation as taught by Friedl. It would have been obvious to one of ordinary skill in the art to adapt the different cell layers of the cell structure taught by Herlyn depending on the desired tissue context, since Herlyn teaches mimicking a tumor environment (0007 and 0010) and Friedl teaches that different cell structures can be devised depending on the cells and tissues being studied. Therefore, it would have been obvious to one of ordinary skill to arrive at a cell structure with a bottom cell layer containing stromal cells and migratory cells and a top second cell layer containing no migratory cells. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in modifying the cell structure taught by Herlyn so that the bottom cell layer contains stromal cells and migratory cells and a second cell layer on top containing no migratory cells, since Friedl teaches adapting the cell structure according to the desired situation and migratory cells being studied.
With respect to claims 4, 5, 13 and 14, Herlyn teaches the method where the migratory cells are cytotoxic T lymphocytes (0013).
With respect to claims 6 and 15, Herlyn teaches the method where the migratory cell-free layer contains tumor cells (migration target cells) which determine the direction of migration of the migratory cells (0015).
With respect to claims 7 and 16, Herlyn teaches the method where there is a migratory cell-free layer that contains only fibroblasts and no tumor cells or migration target cells (0013).
With respect to claim 9, Herlyn teaches the method where the cytotoxicity of the migratory cell against the migration target cells is evaluated and teaches detecting tumor cell lysis caused by the cytotoxic T lymphocytes (0015).
With respect to claim 10, Herlyn teaches the migration target cells are cancer cells (0013 and 0015).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 3 and 12 are rejected under 35 U.S.C. 103(a) as being unpatentable over Herlyn in view of Friedl (as applied to claims 1, 3-7, 9, 10 and 13-16 above), and further in view of Lee et al. (Lab on a Chip, Apr. 14, 2021).
The teachings of Herlyn and Friedl can be found in the previous rejection above.
Herlyn does not teach the method where the stromal cell layer includes vascular endothelial cells as recited in claims 3 and 12.
However, Lee teaches T cells infiltrate into solid tumor tissues by a multi-step process where T cells in the blood circulation exit the blood vessels, pass through the vessel and migrate through the tumor stroma (pg. 2142-2143 bridging para. and Fig. 1). Lee further teaches in vitro tumors mimicking the tumor microenvironment containing cancer-associated fibroblasts to study T cell migration (pg. 2143 para. 2). Lee teaches that the extravasation step, where the T cells cross the blood vessel is a critical step in the analysis of therapeutic immune cells and is a bottleneck of immune cell-based therapy (pg. 2143 para. 2). In addition, Lee teaches that they “developed multilayered blood vessel/tumor tissue chips and demonstrated that MBTCs recapitulate various aspects of T cell dynamics in TMEs” (multilayered blood vessel/tumor tissue chip (MBTC) and transendothelial migration (TME)) (pg. 2148-2149 bridging para.).
Accordingly, at the effective time of filing of the claimed invention one of ordinary skill in the art would have been motivated to modify the cell structure of Herlyn to include vascular endothelial cells in the stromal layers to model the tumor environment as taught by Lee. It would have been obvious to one of ordinary skill in the art to include additional known cell types in tumor or tissue environments in the cell structure taught by Herlyn for the purpose of measuring the motility of cells in the particular tissue type, since Herlyn teaches mimicking a tumor environment (0007 and 0010) and Lee teaches vascular endothelial cells are an important component for T cell motility in a tumor environment. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in modifying the cell structure taught by Herlyn so that the stromal cell layer includes vascular endothelial cells, since Lee teaches tumor models including vascular endothelial cells for studying T cell motility.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 8 and 17 are rejected under 35 U.S.C. 103(a) as being unpatentable over Herlyn in view of Friedl (as applied to claims 1, 3-7, 9, 10 and 13-16 above), and further in view of Bryant et al. (Arthritis & Rheumatism, 2012).
The teachings of Herlyn and Friedl can be found in the previous rejection above.
Herlyn does not teach the method according to claims 8 and 17, where the culturing the cell structure includes culturing a first cell structure and a second cell structure such that the first cell structure includes the migratory cell-free cell layer comprising migration target cells and that the second cell structure includes the migratory cell-free cell layer containing no migration target cell, the evaluating the migration ability of the migratory cells includes evaluating the migration ability of the migratory cells based on the mobility of the migratory cells in the first cell structure and the mobility of the migratory cells in the second cell structure, and the migration target cells are cells that determine the migration direction of the migratory cells.
However, Bryant teaches a method of evaluating the migration ability of Tck (cytokine-activated T) cells (migratory cells) when a target cell is present. Specifically, Bryant compared the migration of the Tck cells in chemotaxis plates containing target cells RA FLS (rheumatoid arthritis fibroblast-like synoviocytes) cells (target cells) in the lower layer to Tck cells in chemotaxis plates containing no cells and just medium in the lower layer (Fig. 5A, pg. 2139 Col. 1 last para., and pg. 2143 last para.).
Accordingly, at the effective time of filing of the claimed invention one of ordinary skill in the art would have been motivated to modify the method of Herlyn to include a second cell structure that does not include the target cells for the benefit of determining the affect the presence of target cells has on motility of the migratory cells as taught by Bryant. It would have been obvious to one of ordinary skill in the art to include a control which does not include target cells in the method of Herlyn for the purpose of measuring the motility of cells in response to the presence of the target cells, since Bryant teaches a similar method of evaluating the motility of migratory cells where a comparison is made between cell structures including target cells and cell structures excluding target cells. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in modifying the method taught by Herlyn to include a control without target cells, since Bryant teaches a similar method of evaluating cells with such a control.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 11 and 18 are rejected under 35 U.S.C. 103(a) as being unpatentable over Herlyn in view of Friedl (as applied to claims 1, 3-7, 9, 10 and 13-16 above), and further in view of McGhee et al. (Cancer Research, 2019).
The teachings of Herlyn and Friedl can be found in the previous rejection above.
Herlyn is silent with respect the height of the different layers and does not teach the method wherein the height Hs of the cell structure is 50 μm or more as recited in claims 11 and 18.
However, McGhee teaches a tumor model for evaluating T cell migration where T cells diffused a distance in the range of 250 µm (pg. 2) which mean that the structure is at least 250 µm long or tall.
Accordingly, at the effective time of filing, one of ordinary skill in the art would have been motivated to modify the method of Herlyn so that the cell structure has a height of at least 50 μm or more for the benefit of having a structure tall enough for the T cell or migratory cell to travel through as taught by McGhee. Additionally, it would have been obvious to one of ordinary skill in the art to adjust the height of the cell structure in the method of Herlyn so that it is appropriate for the migratory cells being studied and for the tissue being studied. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification, since similar cell structures used to evaluated the migration ability of migratory cells were known to have heights or at least lengths greater than 50 μm as taught by McGhee.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632
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