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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 08/14/2025 has been entered.
Accordingly, claims 2-5 and 7-16 are under examination.
Response to Arguments
Applicant's arguments filed 08/14/2025 have been fully considered but they are not persuasive since they are directed to previous versions of claims. Arguments pertaining to any remaining rejections are addressed in this Office Action.
Priority
Claims 2-5 and 7-16 have an effective filing date of 9/26/2013, which is the filing date of PCT/US2013/062062.
It is noted that Applicant states that the statements made in the NFOA regarding priority be held in abeyance.
Amendments
Receipt is acknowledged of an amendment, filed 08/14/2025, in which claims 2 and 12 were amended and no claims were cancelled or added. All of the amendments have been thoroughly reviewed and entered.
Applicant has:
1. amended claim 2 to overcome the 102 and 103 rejections; the 102 rejection is withdrawn; the 103 rejection of claim 2 is maintained.
The amendments have been addressed by new references applied in the 103 rejection made in this Office Action.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(u)(1) because:
i) the view numbers for the partial views for Figures 17 - 18 that appear on several sheets are followed by "Continued" instead of the same number followed by a capital letter such as FIG. 17A, FIG. 17B, etc.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The specification is objected to as failing to provide proper antecedent basis for the amended claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: Claim 2 recites: …is adapted to capture a single live cell,... However, the specification does not define the adaptation.
Claim Objections
Claim 2 is objected to because of the following informalities:
Claim 2 recites: each cell-philic site: comprises a cell capture moiety, is adapted to capture a single live cell,…
Interpretation 1: each cell-philic site is adapted to capture a single live cell. It would be clearer if Applicant wrote the limitations following each cell-philic site: in bulleted form; i.e., each cell-philic site:
comprises a cell capture moiety
is adapted to capture a single live cell
and is surrounded by at least one cell-phobic…
Interpretation 2: Perhaps Applicant meant to say that the cell capture moiety is adapted to capture a single live cell….. If this was Applicant’s intention, then it would be clearer to recite: cell capture moiety, which is adapted to capture a single live cell….Further, if this is Applicant’s intention, then the objection to specification, as discussed above, stands.
In the second to last line of claim 2, the word “to” appears twice.
Appropriate correction is required.
Claim Interpretation
Claim interpretation for amended phrase cell-phobic area is, as per specification last para on pg. 30; i.e., a surface or region, which is prohibitive to cell binding. The specification further states that examples of materials that make such a surface include any materials that are known to be prohibitive of cell binding and sell adhesion. One example listed is PEG.
The recitation the contacting allows the inducible-release stimulus to be transferred, and to create the three-dimensional cell microenvironment in claims 2 and 13 respectively, simply express the intended result of a process step positively recited. Therefore, these phrases are not given weight to be examined for patentability. See MPEP 2111.04.
Interpretation of Claim 2 under 112(f)
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
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.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but nonetheless invoke 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: “adapted to capture” in Claim 2.
However, these claim limitation(s)are NOT being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because there is no corresponding limiting structure described in the specification as performing the claimed function, or equivalents thereof.
If applicant does 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 present a sufficient showing that the specification recites sufficient structure to perform the claimed function so as to be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
See further discussion of these claims under §112(b) and §112(a) 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 2-5 and 7-16 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.
Regarding claim 2, it is noted that the claim recites a moiety … adapted to capture a single live cell.
Thus, the claim recites a function, adapted to capture …, but there is nothing in the specification that describes how that function will be carried out; i.e., there is no structure associated with that function. Therefore, there is a question or doubt as to how the artisan may carry out or design the moiety to carry out the intended function.
Claim 13 recites the limitation "the" in the portion of . There is insufficient antecedent basis for this limitation in the claim. Neither claim 13 nor Claim 2 on which claim 13 depends recite the phrase “a portion of the cells”.
Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
Therefore, the claims are rejected for being indefinite.
Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 2-5 and 7-16 are rejected under 35 U.S.C. § 112(a), as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention.
The crux of the statutory requirement governing written description is whether one skilled in the art, familiar with the practice of the art at the time of the filing date, could reasonably have found the later claimed invention in the specification as filed. Moreover, the courts have stated that the evaluation of written description is highly fact-specific, and that broadly articulated rules are inappropriate. It is also important to remember that the true issue in question is not whether the specification enables one of ordinary skill in the art to make the later claimed invention, but whether or not the disclosure is sufficiently clear that those skilled in the art will conclude that the applicant made the invention having the specific claim limitations.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor has possession of the claimed invention. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 U.S.P.Q.2d at 1116. An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 U.S.P.Q.2d 1961, 1966 (Fed. Cir. 1997). The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule described only by a functional characteristic, without any known or disclosed correlation between that function and a possible structure, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process. Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 U.S.P.Q.2d 1895, 1905 (Fed. Cir. 1996).
Scope of the Invention
In the instant case, the genera are:
cell capture moiety adapted to capture a single live cell.
The broadest reasonable interpretation of the scope of this genera are any moiety that is confined to a small space such that it can bind only to a single cell.
Disclosure of a Complete or Partial structure
Regarding cell capture moieties, the specification lists cell capture moieties as a peptide, a protein, a small molecule, a ligand, an antibody, a receptor, a nucleic acid, a glycoprotein, an oligosaccharide, and combinations thereof (middle of pg. 3), but describes no example of any such capture moiety or how these generic listings may be adapted to capture a single live cell.
Structure/Function Correlation
Regarding the cells that the cell capture moiety must bind to as discussed above, Applicant’s claims encompasses any cell, i.e, prokaryotic and eukaryotic cells, adherent and suspension, that are listed in the instant specification [0016], [0048], [0052]. The breadth of the claimed cells is enormously broad with an unfathomable number of structurally divergent and diverse cells that must be captured, and subsequently immobilized, as single cells. Therefore, Applicants claim is broad because Applicant’s claim requires that the cell capture moiety bind to any or all of these various cell types such that only a single cell is captured, and subsequently immobilized, in each of the cell-philic areas.
As such, the breadth of the claimed cell is enormously broad with an unfathomable number of structurally divergent and diverse cells, most of which will need their specific capture moieties that will bind to them and later immobilize them singly, as the claim requires.
For e.g., if the cell capture moiety is an antibody, the structure of the cell (tumor) antigen must be known first, in order to describe an antibody that will bind to it. Then, the antibody must be placed such that a single cell is captured. While it is well-known that an antigen will bind to an antibody, it is not known, from instant disclosure, how this interaction can be limited to a single antigen (cell) – antibody interaction. Kim et al., further discussed in the 103 rejection, describe single cells are captured by placing antibodies in wells which are confined to a space only sufficiently large for single cells to enter. In contrast, instant application claims require the antibody, as an example of a cell capture moiety, to be adapted to capture a single cell without any description of what this adaptation entails.
Dependent claims 4 – 5 limit the cells to a clinical sample and tumor biopsy, thus narrowing the scope of claim to a particular genus of cells but still shed no light on the adaption of the cell capture moiety to capture a single live cell specifically, the § 112(f) and (b) discussed the intended function of these claims.
Accordingly, when all the aforementioned factors are considered together, the skilled artisan would reasonably conclude that Applicants were not in possession of the claimed invention to support the full breadth of the patent protection desired.
Examiner Suggestion: Amend the claim 2 to recite “captures a single live cell”..
Claim Rejections - 35 USC § 102
The following rejection is based on Interpretation 1: each cell-philic site is adapted to capture a single live cell.
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 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.
Claim(s) 2 - 5 and 7 – 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Khademhosseini (WO 2011035177, IDS).
Khademhosseini teaches a method wherein cytotoxicity profiles of test and lead compounds can be obtained as a function of drug concentration and IC50 values (drug concentration at which 50% of the cell growth is inhibited) (e.g., paragraphs [00146] and Figure 3) that utilizes a solid substrate comprising live cells, and a second solid substrate comprising test compound (agent).
Regarding claim 2, Khademhosseini teaches a high throughput screening device, the device comprising: i) a microwell plate comprising an array of microwells and ii) a cover plate comprising a microarray of test compounds, wherein (i) and (ii) are aligned to fit each other (para 0007). The cover plate comprises an array of posts on its surface on which a test compound(s) is deposited (para 00103). Both the microwell plate and the cover plate are made of suitable materials, an exemplary material is PEG, which is a hydrogel (para 00104). The microwell plate can be fabricated from a cell-repelling substrate that repels cells, such as: polyacrylamides, polysaccharides, phospholipids, poly(ethylene glycol) (PEG), and natural polymers including but not limited to hyaluronic acid and alginate (beginning of para 00112). In addition part of the microwell is modified with a substrate comprising a cell-adhering surface that adheres cells such as ECM molecules such as fibronectin or collagen (middle of para 00112). The cover plate provides a microarray of test compounds (para 0008). The microwell plate comprises at least one cell (para 0039; Figure 1). Cells can be encapsulated in a hydrogel and the hydrogel integrated into the microwells. Encapsulating the cells in hydrogel can allow culturing of cells in 3D (para 0050). Khademhosseini further teaches a method for screening a test compound, the method comprising seeding the microwell plate with cells, depositing the cover plate with the test compound, and contacting the microarray with the cover plate for sufficient amount of time to challenge the cell with the test compound present on the cover plate, resulting in controlled release of test compound to stimulate the cell (Figure 10; a single cell-seeded microwell prior to pressing with the chemical-laden arrayed posts, paras 0011, 00992 – 00101; release compound, para 00154; stimulate cells 0085).
Khademhosseini’s teachings of microwell plate, cover plate, cell-repelling surface, cell-adhering surface, single cell-seeded microwell, and contacting resulting in controlled release and stimulating a response, read on instant application’s cell capture array, agent transfer device comprising second solid substrate, cell-philic, cell-phobic, adapted to capture a single live cell, and inducible-release stimulus, respectively. Regarding, adapted to capture a single live cell, the specification does not limit the cell-philic site to a particular structure that would exclude capturing of more than a single cell. Therefore, the device of Khademhosseini is interpreted to capture a single cell as described in para 0011; i.e., a single cell-seeded microwell. This meets the requirement of adapted to capture a single live cell of instant invention. See relevant citations from Khademhosseini below:
[0011]:
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Regarding claim 3, Khademhosseini teaches that the microwell plate and cover plate are incubated together for a time to allow transfer of the test compounds (agent) into the cell-containing microwells (assumes that all of the deposited compound is released into the microwell, para 0076). This reads on transferring at least 50% of the original concentration of the agent on the agent transfer device to the plurality of three dimensional cell microenvironments.
Where the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of the claimed product. See In re Ludtke 441 F.2d 660, 169 USPQ 563 (CCPA 1971). Whether the rejection is based on "inherency" under 35 U.S.C. 102, or "prima facie obviousness" under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. In re Best, Bolton, and Shaw, 195 USPQ 430, 433 (CCPA 1977) citing In re Brown, 59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972). The prior art products taught by Khademhosseini are capable of the transferring as recited in instant claim 3.
Regarding claims 4 - 5, Khademhosseini teaches the method where the cells comprise a biological sample [0086], tumor cells (MCF-7) [0011], and cells from malignant tumors [0052]. These disclosures read on clinical sample and tumor biopsy respectively.
Regarding claims 7 - 9, Khademhosseini teaches the method where the hydrogel comprises a cross-linked hydrogel (e.g., the term "hydrogel" refers to polymeric materials …prepared through the cross linking, paragraphs [0080], low molecular weight PEG diacrylate (PEGDA) is used for fabricating the microwells and high molecular weight PEGDA is used for encapsulating the test compounds on the printed microarray, same para; Khademhosseini claims 5 – 7; [00115]).
Regarding claim 10, Khademhosseini teaches the method where the test compound comprise polynucleotide (nucleic acids, paragraphs [0070]; Khademhosseini claim 9).
Regarding claim 11, Khademhosseini teaches the method where the test compound comprise small molecules (e.g., paragraphs [0070] and [00137]; Khademhosseini claim 9).
Regarding claim 12, Khademhosseini teaches the method where the microwell has an aperture and depth of from about 5 μm to about 1000 μm. (e.g., paragraphs [0028]; microwell size can be adjusted depending on the cell type [0029]; Khademhosseini claims 3 - 4). This range encompasses the range of instant claim limitation.
Regarding claim 13, Khademhosseini teaches the method where the hydrogel is cross-linked by applying ultraviolet light [00115].
Regarding claim 14, Khademhosseini teaches the method where the bottom surface of microwells is modified with a cell adhering surface (para 00112); i.e., the cell-philic sites, while the rest of the microwell is fabricated from a material that repels cells (same paragraph). This reads on instant limitation, cells separated from each other by hydrophobic regions.
Regarding claims 15 and 16, Khademhosseini teaches the method where the test compounds are encapsulated in a hydrogel, which comprises a cross-linked hydrogel (Khademhosseini claims 7 – 8; para [00115]).
Claim Rejections - 35 USC § 103
The following rejection is based on Interpretation 2: cell capture moiety is adapted to capture a single live cell.
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:
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 2 - 5 and 7 – 16 are rejected under 35 U.S.C. 103 as being unpatentable over Khademhosseini (WO 2011035177, IDS) in view of Kim (Kim et al., Advanced Functional Materials, May 200616(10):1313 – 1323).
The teachings of Khademhosseini have been discussed above and apply.
Regarding claim 2, Khademhosseini teaches a high throughput screening device, the device comprising: i) a microwell plate comprising an array of microwells and ii) a cover plate comprising a microarray of test compounds, wherein (i) and (ii) are aligned to fit each other (para 0007). The cover plate comprises an array of posts on its surface on which a test compound(s) is deposited (para 00103). Both the microwell plate and the cover plate are made of suitable materials, an exemplary material is PEG, which is a hydrogel (para 00104). The microwell plate can be fabricated from a cell-repelling substrate that repels cells, such as: polyacrylamides, polysaccharides, phospholipids, poly(ethylene glycol) (PEG), and natural polymers including but not limited to hyaluronic acid and alginate (beginning of para 00112). In addition part of the microwell is modified with a substrate comprising a cell-adhering surface that adheres cells such as ECM molecules such as fibronectin or collagen (middle of para 00112). The cover plate provides a microarray of test compounds (para 0008). The microwell plate comprises at least one cell (para 0039; Figure 1). Cells can be encapsulated in a hydrogel and the hydrogel integrated into the microwells. Encapsulating the cells in hydrogel can allow culturing of cells in 3D (para 0050). Khademhosseini further teaches a method for screening a test compound, the method comprising seeding the microwell plate with cells, depositing the cover plate with the test compound, and contacting the microarray with the cover plate for sufficient amount of time to challenge the cell with the test compound present on the cover plate, resulting in controlled release of test compound to stimulate the cell (Figure 10; a single cell-seeded microwell prior to pressing with the chemical-laden arrayed posts, paras 0011, 00992 – 00101; release compound, para 00154; stimulate cells 0085).
Khademhosseini’s teachings of microwell plate, cover plate, cell-repelling surface, cell-adhering surface, and contacting resulting in controlled release and stimulating a response, read on instant application’s cell capture array, agent transfer device comprising second solid substrate, cell-philic, cell-phobic, and inducible-release stimulus, respectively. See relevant citations from Khademhosseini below:
[0022]:
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Regarding claim 3, Khademhosseini teaches that the microwell plate and cover plate are incubated together for a time to allow transfer of the test compounds (agent) into the cell-containing microwells (assumes that all of the deposited compound is released into the microwell, para 0076). This reads on transferring at least 50% of the original concentration of the agent on the agent transfer device to the plurality of three dimensional cell microenvironments.
Where the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of the claimed product. See In re Ludtke 441 F.2d 660, 169 USPQ 563 (CCPA 1971). Whether the rejection is based on "inherency" under 35 U.S.C. 102, or "prima facie obviousness" under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. In re Best, Bolton, and Shaw, 195 USPQ 430, 433 (CCPA 1977) citing In re Brown, 59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972). The prior art products taught by Khademhosseini are capable of the transferring as recited in instant claim 3.
Regarding claims 4 - 5, Khademhosseini teaches the method where the cells comprise a biological sample [0086], tumor cells (MCF-7) [0011], and cells from malignant tumors [0052]. These disclosures read on clinical sample and tumor biopsy respectively.
Regarding claims 7 - 9, Khademhosseini teaches the method where the hydrogel comprises a cross-linked hydrogel (e.g., the term "hydrogel" refers to polymeric materials …prepared through the cross linking, paragraphs [0080], low molecular weight PEG diacrylate (PEGDA) is used for fabricating the microwells and high molecular weight PEGDA is used for encapsulating the test compounds on the printed microarray, same para; Khademhosseini claims 5 – 7; [00115]).
Regarding claim 10, Khademhosseini teaches the method where the test compound comprise polynucleotide (nucleic acids, paragraphs [0070]; Khademhosseini claim 9).
Regarding claim 11, Khademhosseini teaches the method where the test compound comprise small molecules (e.g., paragraphs [0070] and [00137]; Khademhosseini claim 9).
Regarding claim 12, Khademhosseini teaches the method where the microwell has an aperture and depth of from about 5 μm to about 1000 μm. (e.g., paragraphs [0028]; microwell size can be adjusted depending on the cell type [0029]; Khademhosseini claims 3 - 4). This range encompasses the range of instant claim limitation.
Regarding claim 13, Khademhosseini teaches the method where the hydrogel is cross-linked by applying ultraviolet light [00115].
Regarding claim 14, Khademhosseini teaches the method where the bottom surface of microwells is modified with a cell adhering surface (para 00112); i.e., the cell-philic sites, while the rest of the microwell is fabricated from a material that repels cells (same paragraph). This reads on instant limitation, cells separated from each other by hydrophobic regions.
Regarding claims 15 and 16, Khademhosseini teaches the method where the test compounds are encapsulated in a hydrogel, which comprises a cross-linked hydrogel (Khademhosseini claims 7 – 8; para [00115]).
Khademhosseini does not teach each cell-philic site:
comprises a cell capture moiety, (which) is adapted to capture a single live cell, as recited in claim 2, rather a single cell microenvironment is created in each microwell coated with cell-adhering material with cells encapsulated in hydrogel, by limiting the seeding density and microwell diameter.
However, before the effective filing date of instant invention, Kim taught a single-cell microarray for analyzing a cellular response, where the microarray is fabricated with a patterned hydrogel microwell functionalized at their bases with antibodies to promote specific immobilization of lymphocytes and used to array single T cells in a regular pattern on a substrate. (e.g., Title; Abstract; Lymphocytes suspended in medium were injected into the …and were then immobilized on contact with the anti-CD44-coated well-bottoms, paragraph on top of right column of pages 1316; Anti-CD44 antibody was conjugated to the floor of the microwell via streptavidin—biotin interactions, middle paragraph on right column of page 1321; Figure 2). Kim also taught that the diameter of the microwells was selected to allow entry of a single cell (live single T-cell arrays were readily prepared, as shown in Figure 5D, where 12 µm microwells were utilized, paragraph on bottom of left column of pages 1316). Thus, antibody-functionalized patterned microwells provided a platform for simple, robust, and reproducible high-fidelity arraying of single B or T lymphocytes (paragraph on middle of right column of pages 1316). Kim also taught hydrogel comprises PEGDMA, further UV-crosslinked (middle paragraph right column of page 1321).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of high throughput screening of test compounds using cells encapsulated in a hydrogel of Khademhosseini to include a cell-capture moiety as taught by Kim, because Khademhosseini taught it is within the ordinary skill in the art to use a hydrogel to encapsulate a cell, and Kim specifically taught encapsulation of cells captured by a cell-binding moiety (antibody) in a hydrogel comprising PEGDMA produced from poly(ethylene glycol) by applying ultraviolet light. Because Kim taught the encapsulation of single cells in the PEGDMA hydrogel one would have had a reasonable expectation of success in using the hydrogel of Kim in the method of Khademhosseini. See MPEP 2143 I A.
One would have been motivated to make such a modification in order to receive the expected benefit of interrogating a single live cell as taught by Kim.
Response to Arguments
Applicant’s arguments, see Pgs. 5 - 10, filed 14th Aug 2025, with respect to rejections under 35 USC § 103 have been fully considered and are not persuasive for the reasons discussed below.
Applicants essentially assert that:
1) the primary reference of Lee fails to disclose multiple claimed points relating to a single live cell (as amended); and
2) the secondary reference of
i) Hume does not teach the limitation encapsulation of live cells;
ii) Wheeldon (referenced in this OA as Khademhosseini) does not teach the (amended) limitations: a cell-philic site located on a cell capture surface of a solid substrate that is adapted to capture a single live cell, immobilizing a single live cell in a hydrogel composition at each cell-philic site to create a cell microenvironment at each cell-philic site, an agent transfer array element that contacts one cell microenvironment, or transfer of an inducible-release stimulus from each transfer array element to one cell microenvironment. encapsulation of live cells;
iii) Yamamura may not be combined with Lee;
iv) Kwon does not teach the limitation a single cell.
The arguments are not persuasive because:
Regarding 1), i) this is a new limitation not considered in the previous office action and ii) Lee contemplates using their invention to determine the fate of single cells live cells but does not include a step that will only capture a single live cell to a specific location within the cell array.
Regarding 2), i) Hume does not teach the limitation encapsulation of live cells. The reference of Hume has been replaced with the reference of Kim that teaches the limitation being discussed.
ii) These newly recited limitations, except for cell capture moiety, as shown by the citations are taught by Khademhosseini. The deficiency of Khademhosseini are cured by the newly applied reference of Kim thus rendering the amended limitations obvious for reasons set forth above.
iii) Since Lee is no longer being relied upon for the present 103 rejection, the argument, Yamamura may not be combined with Lee, is moot.
iv) Kwon does not teach the limitation single cell. The reference of Kwon has been replaced with the reference of Kim that teaches the limitation being discussed.
Relevant Prior Art not used in Rejection
Kapur (US Patent Application Publication No. US 2007/0166771 A1) teaches a method comprising (a)(i) preparing a Cassette comprising a matrix of openings or depressions comprising a substrate with a pre-coating of independent hydrophilic spots surrounded by hydrophobic material, to become independent cell-binding locations (abstract, [0049], [0051 - 0053], [0129], [0316 – 0318], Fig. 1); (ii) dispensing cells (which may be any cell type [0073], [0437], Fig. 14A) to the substrate comprising the independent spots to (b) localize and immobilize live cells on the spots to assay individual live cells and unbound cells are then rinsed off of the cell binding locations ([0143], [0326], [0244]); (c) preparing a multi-level chamber that mates with the substrate [0033], wherein the multi-level chamber comprises, at least one source receptacle in fluid connection with the one or more input manifolds/ channels ([0038],[0153], Figs. 7, 15); and (d) contacting the substrate which comprises the live cells with the test substance, flowing through the chamber which mates with the substrate to induce a response (e.g., paragraphs [0030], [0040], [0153], [0191], [0242], [0375], [0428]; Figs. 7, 35, 44 - 45). Kapur’s teachings of substrate, chamber with input manifolds/channels, and mating to induce a response read on instant application’s cell capture array, agent transfer device comprising second solid substrate, and inducible-release stimulus, respectively.
Kapur differs from instant invention by not including a means to capture a single live cell.
Conclusion
No claim is allowed.
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/SHABANA S MEYERING/Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635