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 .
The Response of 28 May 2026 has been entered.
Claims 1-3 and 5-23 are currently pending.
Election/Restrictions
Applicant’s election without traverse of the species of: an enclosing gel structure; a chemically degradable linkage and cell morphology as the optical indicator in the reply filed on 28 May 2026 is acknowledged.
Claims 1-3 and 5-23 are considered here with respect to the elected species.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 18974436, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. In particular, the '436 App does not describe the features of instant claims 20 and 21. The effective filing date for such claims is thus that of the instant application, 26 Jan. 2026.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: "spatial energy modulating element" in claim 6.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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 1-3, 5-19, 22 and 23 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative (in the case of claims 7, 10, 11, 13, 18, 19), under 35 U.S.C. 103 as obvious over Oldenhof et al., Scientific Reports 10.1 (2020): 6595, as evidenced by (in the case of claim 9) van Dijk-Wolthuis et al., Macromolecules 30.16 (1997): 4639-4645.
Regarding claim 1, Oldenhof teaches a method for sorting and isolating cells, comprising (a) inputting a plurality of cells into a fluidic device (a glass slide, See Pg. 3, "Results section, 2nd full paragraph; also, petri dishes, See Pg. 4, 2ⁿᵈ full paragraph) along with one or more polymer precursors (See pg. 3, 2ⁿᵈ full paragraph for discussion of the deposition of solution of Dex-MA containing LAP and Dex-FITC; Pgs. 4-5 discusses seeding cells in several glass-bottom petri dishes, and then replacing the culture medium with a 5% solution of Dex-MA containing 5 mg/mL LAP in PBS); (b) immobilizing a cell from the plurality of cells using light; and (c) flowing a liquid through the device such that the immobilized cells are retained in the device while other non-immobilized cells from the plurality of cells are removed (Under Results, including p. 2, 1st ¶ and p. 6, steps a)-f); Figs. 1 and 7)).
Regarding claims 2 and 3, the immobilizing comprises enclosing one or more cells of the plurality of cells by forming a gel structure around the cell(s) via photo-induced cross-linking of the hydrogel precursor polymers (p. 2, 1st ¶; p. 5, last ¶ to p. 6, last full ¶; p. 9, under CLSM hydrogel fabrication procedure). The term "enclose" is not expressly defined in the specification and is given its broadest reasonable interpretation consistent with the specification (see MPEP 2111). The term is construed herein to have its ordinary meaning of: to surround at least partially.
Regarding claims 5, 12, 13, 22 and 23, Oldenhof teaches that the method is carried out using adherent cells bound to a surface of the fluidic device, and that the bound cells are optically imaged to locate and select cells around which hydrogel structures are formed (p. 2, 1st ¶; p. 5, last ¶ to p. 6, last full ¶; Fig. 7). Regarding claim 13, teaches labeling of different cell types and selectively enclosing/isolating one of the cell types via the method " thus demonstrating the applicability of our technique for cell isolation based on their phenotypic properties, such as size and shape" (i.e. cell morphology) (p. 5, last ¶).
Regarding claim 6, Oldenhof teaches that the hydrogel is formed by projecting 405 nm laser light into the device using a spatial energy modulating element (confocal laser-scanning microscope (CLSM), which allows for spatial control of the photo-induced gel formation (p. 1, 3rd ¶ to p. 3, 3rd full ¶).
Regarding claim 7, Oldenhof teaches that the Dex-MA precursors are inputted to the fluidic device in which the cells reside (i.e. with the cells) (p. 2, 1st ¶; p. 6, step a)). Claim 7 is construed to require only that the precursor and cells are combined in the device. To the extent Applicant intends claim 7 to require adding a mixture of cells and precursor to the device, claim 7 should be amended to indicate that the inputting in step a) comprises adding such a mixture. Alternatively, Oldenhof teaches the combining of cells and precursor in the device and it would have been obvious to add such ingredients in a single step (see MPEP 2144.04, IV. - changes to the sequence of adding ingredients is prima facie obvious in the absence of new or unexpected results).
Regarding claim 8, Oldenhof teaches formation of a gel structure that encapsulates mammalian (spherical) cells and as such the formed gel structure would include a circular/spherical (i.e. annular) shape that at least partially defines an open interior space in which the cell is enclosed.
Regarding claim 9, Oldenhof teaches formation of Dex-MA hydrogels which are degradable with dextranase (p. 2, last ¶ to p. 3, 1st ¶), and van Dijk-Wolthuis evidences that such Dex-MA hydrogels can be chemically degraded (via acid) (van Dijk-Wolthuis, p. 4641, last full ¶). It is noted that claim 9 requires only that the gel structure has a "chemically degradable linkage", not that the method comprises a chemical degradation step.
Regarding claim 10, Oldenhof teaches that the formed hydrogel allows for "bio-orthogonal hydrogel degradation" (p. 2, last ¶). Oldenhof further teaches that "sequential application of the approach presented here using different cross-linkable polymers and, potentially, different patterns presents the means to fabricate multi-layer composite hydrogel objects" (p. 3, 4th full ¶). It would have thus been obvious to prepare a composite hydrogel structure comprising two or more different hydrogels, e.g. to provide for different degradation characteristics in hydrogels enclosing selected cells.
Regarding claim 11, Oldenhof teaches carrying out the method with a mixture of different adherent cell types (i.e. with a first and a second plurality of cells inputted to the device and immobilized thereon), and selectively removing one of the cell types by forming hydrogels around the other cell type (thus enclosing and immobilizing such cells) and flowing a trypsin solution through the device to remove non-enclosed cells (p. 5, last ¶ to p. 6, last full ¶; Fig. 7). Oldenhof further teaches that "sequential application of the approach presented here using different cross-linkable polymers and, potentially, different patterns presents the means to fabricate multi-layer composite hydrogel objects" (p. 3, 4th full ¶). It would have been obvious in view of the above to carry out the method of Oldenhof such that more than one type of hydrogel structure is formed around selected cell types (e.g., wherein the mixture of cells includes three different cell types, and a first hydrogel is formed around a first cell type and a second hydrogel is formed around a second cell type), and the method comprises successive steps of selectively eluting cells (e.g., a first step using trypsin solution which elutes non-enclosed cells, followed by a second step using dextranase to elute Dex-MA enclosed cells). One of ordinary skill would have had a reasonable expectation of success in doing so because Oldenhof suggests forming different hydrogels with different cross-linkable polymers and such a method involves only repeating the steps taught by Oldenhof.
Regarding claim 13, teaches labeling of different cell types (3T3 and A549 cells) and selectively enclosing/isolating one of the cell types based on imaging of the cells (p. 5, last ¶), which would involve identifying the cell type of the cells. Moreover, Oldenhof teaches a general cell isolation method and it would have been obvious to subject the isolated cells to any type of analysis known in the art, including identification, classification, etc. (see Oldenhof, under Discussion).
Regarding claims 15 and 16, Oldenhof teaches that the surface of the device was pre-functionalized with methacrylate groups to which the cells attached prior to forming of the hydrogel (p. 4, last ¶; p. 9, under Glass surface modification).
Regarding claim 17, Oldenhof teaches that the non-enclosed cells (i.e. additional cell) are removed via a trypsin solution (i.e. such that the additional cell is not coupled to the substrate) (p. 5, last ¶ to p. 6, last full ¶).
Regarding claim 18, Oldenhof teaches that the " versatility and accessibility of the method presented here make it a useful tool in the field of cell culturing/isolation with a potential application for single cell genomics and proteomics, investigation of cellular heterogeneity and isolation of best performing mutant-cells for development of new cell lines" (p. 8, 1st ¶). It would have thus been obvious to analyze cells isolated by the method of Oldenhof using assays relating to genomics. proteomics and cellular heterogeneity.
Regarding claim 19, Oldenhof teaches that cells are optically imaged to locate and select cells around which hydrogel structures are formed, e.g. based on fluorescent labeling (see above; see also, p. 6, 2nd full ¶ - "we envision that the selection process could be further optimized and even potentially automated in the future if the desired cells could be tagged with a specific fluorescent marker"). Since cells are selected based on the position of the cell in the device, it would have been obvious to associate the result of any subsequent assay with such position (e.g., where a specific cell type is located and selected/immobilized based on its position in the device, and a subsequent assay result is associated with the selected cell type). It is noted that claim 19 does not require any specific type of assay, association or use of positional information.
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.
Claims 18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Oldenhof, as applied to claims 1-3, 5-19, 22 and 23, in view of Negishi et al., Analytical chemistry 90.16 (2018): 9734-9741.
Claims 18 and 20 differ from Oldenhof, as applied to claims 1-3, 5-19, 22 and 23, in that: the method further comprises performing an assay on the immobilized cell (claim 18); and the plurality of cells are from a human subject, and the method further comprises identifying a health status of the human subject based at least in part on a result of the assay (claim 20).
Negishi teaches a method of isolating circulating tumor cells (CTCs) using a method similar to that of Oldenhof, wherein selected CTCs are captured via spatially selective photo-induced hydrogel formation around the cells (under EXPERIMENTAL SECTION). The encapsulated cells were subjected to genotyping (i.e. an assay) (p. 9738, right col.). Negishi teaches that CTCs isolated from peripheral blood can be used to predict cancer prognosis of human patients (i.e. to identify a health status) via genome/transcriptome analysis (p. 9734, 1st ¶). Negishi further teaches that CTCs are genetically heterogeneous and that analyses should thus take place at the single cell level, and that CTCs are extremely rare cells within peripheral blood samples (p. 9734, 1st-2nd ¶).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the method of Oldenhof to selectively isolate cells from a heterogeneous mixture of cells wherein the cells are CTCs used to provide cancer prognostic information as taught by Negishi because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to use the method of Oldenhof to isolate CTCs because Negishi teaches that CTCs are valuable for cancer prognosis and are rare cells that are difficult to isolate from peripheral blood samples. Using the method of Oldenhof to isolate CTCs would have led to predictable results with a reasonable expectation of success because Negishi teaches that CTCs can be encapsulated by a similar photo-induced spatial hydrogel forming process as in Oldenhof, and that the cells can then be subject to genotyping analyses of the type used for cancer prognosis.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Oldenhof in view of Negishi, as applied to claims 18 and 20, further in view of Iyer et al., Journal of clinical medicine 9.4 (2020): 1206.
Claim 21 differs from Oldenhof in view of Negishi, as applied to claims 18 and 20, in that: the identifying of the health status comprises inputting the result of the assay into a trained machine learning model.
Iyer teaches a method of cancer prognosis by subjecting CTCs to genetic analysis and inputting the results into a trained machine learning model (entire doc, including 4. Discussion). Iyer teaches that the machine learning approach reliably distinguishes CTCs from other relatively way more abundant immune cell types and provides a probabilistic score indicating the cancer origin of individual cells (under 4. Discussion).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the method of Oldenhof in view of Negishi to selectively isolate CTCs for cancer prognosis wherein the method involves using a machine learning method as taught by Iyer because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to use the method of Iyer in the cancer prognosis because Iyer teaches that the machine learning approach reliably distinguishes CTCs from other relatively way more abundant immune cell types and provides a probabilistic score indicating the cancer origin of individual cells. Using the machine learning method of Iyer to analyze data obtained via the method of Oldenhof in view of Negishi would have led to predictable results with a reasonable expectation of success because Oldenhof in view of Negishi teach a generally applicable method for isolating and assaying CTCs, and one of ordinary skill would recognize that such CTCs and the genetic information therefrom could be used in any beneficial manner known in the art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3 and 5-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 12553819 in view of Oldenhof, Negishi and/or Iyer. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the '818 patent render the instant claims obvious in view of Oldenhof, Negishi and/or Iyer. The '819 claims recite a method comprising the same steps a)-c) of instant claim 1 for the same purpose of cell isolation ('819, claim 1), and the remaining features of the dependent claims are taught by Oldenhof, Negishi and/or Iyer (see above), which teach a substantially identical method for the same purpose.
Claims 1-3 and 5-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-22 of copending Application No. 19429978 in view of Oldenhof, Negishi and/or Iyer, as applied above. The '978 claims recite a method comprising the same steps a)-c) of instant claim 1 for the same purpose of cell isolation ('978, claims 1, 7-12), and the remaining features of the dependent claims are taught by Oldenhof, Negishi and/or Iyer (see above), which teach a substantially identical method for the same purpose.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT J YAMASAKI whose telephone number is (571)270-5467. The examiner can normally be reached M-F 930-6 PST.
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/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657
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