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 .
Status of Claims
Claims 27-50 are pending. Claim 27, 31, 36 and 39 have been amended. Claims 27-50 are examined.
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.
Claim 27 and 39 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 claims 27 and 39, the presence of phrases within parenthesis renders the claims indefinite because it is unclear whether the limitation(s) within the parenthesis are part of the claimed invention or just an example of dimensions that can be limited by the claim. See MPEP § 2173.05(d).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 39 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 27 has already limited the at least one fluidic connection to include cross-section dimensions H and/or W between 1-20 micrometers. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim(s) 27-36 and 38-50 are rejected under 35 U.S.C. 103 as being unpatentable over Niggemann et al. (US 2018/0127698, hereinafter “Niggemann”) in view of Yung et al. (US 2019/0247847, hereinafter “Yung”).
Regarding claim 27, Niggemann teaches throughout the publication a multi-well plate comprising at least 96 directly accessible open wells having a optically transparent bottom (paragraph 0057) and whose surface properties enables culturing of cells (paragraph 0056), wherein said cells are directly accessible for chemical and physical manipulations (paragraph 0065), and wherein at least two wells in said plate are in direct fluidic connection through at least one closed microchannel having a floor, a roof and two walls, and a fixed wall height throughout its length and where said at least one microchannel is located essentially in the plane of the bottom of the well, wherein a fluidic connection is formed between at least two non-adjacent wells and where the fluidic connection is traversing through the bottom of a well adjacent to at least one of the fluidically connected wells (paragraphs 0061-0065 and see, for example, Figure 12 illustrating channel 17 at the bottom of the wells, with channels 11 and 11’ in direct fluidic connection and channel 17 also fluidically connecting two non-adjacent cells 11’ and 11’’).
While Niggemann does not specifically teach the adherence of neuronal cells or that the microchannel is of a sufficiently small size to prevent cell migration and minimize mass transport via flow or molecular diffusion between the wells, such limitations are drawn to intended use of the well-plate. As the claims are directed to the plate itself, such method steps would not correspond to any structural differences in the claimed product. For these reasons, the recitations do not clearly invoke any additional structural limitations of the system itself, particularly when the claims are given their broadest reasonable interpretation. 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. In this case, Niggemann teach that the plate can be used for cell culture (paragraph 0056) and that the microchannel is sized for fluid control and further teaches that the plate comprises the limitations as recited in the instant claims, as discussed supra. Therefore, these features would appear to necessarily have the capability of performing the intended use limitations as claimed. See also MPEP 2112.
Niggemann does not specifically teach that the at least one fluidic connection comprises cross-sectional dimensions between 1-20µm and wherein the plate further comprises optical detection markers to facilitate microscope autofocusing in at least one well that is fluidically connected to another well.
Yung teaches throughout the publication, an apparatus to measure properties on cultured cells (abstract). More specifically, Yung teaches the presence of optical detection markers such as fluorescence or chromogenic molecules which can be detecting using the optics of the system that can also be analyzed with microscopy (paragraphs 0065-0067).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to incorporate within the well plate of Niggemann, an optical detection marker as taught by Yung because it would have been desirable to facilitate analysis of the desired components within the wells. Although Yung does not specifically teach that the detection markers facilitate autofocusing, such limitation is drawn to intended use of the optical markers and therefore the prior art only needs to be capable of performing the recited intended use. Yung teaches the presence of optical markers compatible with microscopy and therefore would be considered capable of performing the recited intended use of the claim.
While Niggemann in view of Yung do not explicitly teach that the at least one fluidic connection comprises cross-sectional dimensions between 1-20µm, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 27 are for any particular purpose or solve any stated problem, and the prior art teaches that dimensions within the plate may be varied based on the standard format multiwell plate dimensions used in molecular biology laboratories (Niggemann, paragraph 0096) and that dimensions of the microchannel can be chosen to control the flow rate of fluid (Niggemann, paragraph 0064). Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the micro-well plate art.
Regarding claim 28, Niggemann teaches the plate wherein a fluidic connection is formed between at least two adjacent wells (paragraphs 0061-0064 and see channel 17 of Figure 12).
Regarding claim 29, Niggemann teaches the plate wherein the multi-well plate complies with American National Standards Institute of the Society for Laboratory Automation and Screening (ANSI/SLAS) microplate standards (paragraph 0057).
Regarding claims 30-31, Niggemann teaches the plate wherein the multi-well plate comprises a substrate produced from a thermoplastic material such as polystyrene (paragraphs 0120).
Regarding claim 32, Niggemann teaches the plate wherein the multi-well plate comprises a substrate produced from polystyrene (paragraph 0120).
Regarding claim 33, Niggemann teaches the plate wherein the multi-well plate comprises a substrate produced from silicon (paragraph 0068).
Regarding claim 34, Niggemann teaches the plate wherein the plate comprises a substrate comprising more than one layer (paragraph 0059). As the claim also states an optional limitation, this limitation is not required to be present.
Regarding claim 35, Niggemann teaches the plate wherein the plate comprises a substrate coated with a polymer (paragraph 0059).
Regarding claim 36, Niggemann in view of Yung teach the plate wherein the plate comprises a substrate coated with lysine, collagen or laminin, Matrigel (Yung, paragraph 0034). One skilled in the art would have been motivated to include a coating such as lysine, collagen or laminin as taught by Yung, on the well-plate of Niggemann because Yung teaches that these coating can promote cell adherence.
Regarding claim 38, Niggemann teaches the plate wherein the plate comprises at least two, at least four, at least 8, at least 16, or at least 32 groups of three fluidically connected wells (paragraph 0061). As the claim does not provide any structural components that group the fluidically connected wells, the wells of the rows of Niggemann are found to read on this limitation as a plate of 96 wells can be split into 32 groups of 3 wells.
Regarding claims 39-40 and 42-43, while Niggemann in view of Yung do not specifically teach the plate wherein the at least one fluidic connection comprises cross-sectional dimensions (H and/or W) between 1-20 µm, or comprising cross-sectional dimensions (H and/or W) of 1 µm, 2 µm, 3 µm, 4 µm, 5 µm, 6 µm, 7 µm, 8 µm, 9 µm, 10 µm, 11 µm, 12 µm, 13 µm, 14 µm, 15 µm, 16 µm, 17 µm, 18 µm, 19 µm, or 20 µm, and optionally also having an aspect ratio (H x W) ranging from 1:5 - 2:1; wherein the fluidic connection comprises cross- sectional dimensions of equal to or less than 5 x 5 µm, or of 3 x 3 µm to 5 x 5 µm; wherein the length of the at least one fluidic connection is at least 0.25 mm and at the most 5.0 mm; and wherein the aspect ratio of the dimensions of the at least one fluidic connection ranges from 20:1 (W:H) to 1:5 (W:H), it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 39-40 and 42-43 are for any particular purpose or solve any stated problem, and the prior art teaches that dimensions of the microchannel can be chosen to control the flow rate of fluid (Niggemann, paragraph 0064). Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the micro-well art.
Regarding claim 41, Niggemann teaches the plate wherein the dimensions, shape and number of fluidic connections are varied across the length of the at least one fluidic connection (paragraphs 0064-0065). Although the reference does not specifically teach that the dimensions are varied to improve neurite penetration and producibility, such limitation is drawn to intended use of the microtiter plate and therefore the prior art only needs to be capable of performing the recited intended use.
Regarding claim 44, Niggemann teaches the plate wherein the multi-well plate comprises a 96 or 384 well format (paragraph 0057).
Regarding claims 45-47, Niggemann teaches the plate wherein the multi-well plate comprises at least 2 groups of three neighboring and fluidically interconnected wells; wherein the multi-well plate comprises at least 3 groups of two neighboring and fluidically interconnected wells; and wherein the multi-well plate comprises at least 1 group of four neighboring and fluidically interconnected wells (paragraph 0061). As the claim does not provide any structural components that group the fluidically connected wells, the wells of the rows of Niggemann are found to read on this limitation as a plate of 96 wells can be split into various groups having 2-4 wells.
Regarding claim 48, Niggemann teaches a method for high throughput screening of a material of interest, comprising screening the material of interest using the multi-well plate of claim 27 (paragraph 0056).
Regarding claim 49, Niggemann teaches a method wherein the material of interest is a 2D cell culture (paragraphs 0054-0055).
Regarding claim 50, Niggemann teaches a method wherein the material of interest is a 3D cell culture (paragraphs 0054-0055).
Claim 37 is rejected under 35 U.S.C. 103 as being unpatentable over Niggemann et al. (US 2018/0127698, hereinafter “Niggemann”) in view of Yung et al. (US 2019/0247847, hereinafter “Yung”), as applied to claim 27 above (hereinafter “Modified Niggemann”), and further in view of Qian et al. ("Enhancement of the propagation of human embryonic stem cells by modifications in the gel architecture of PMEDSAH polymer coatings", Biomaterials, 35, pages 9581-9590, published online 2 September 2014, hereinafter “Qian”).
Regarding claim 37, Modified Niggemann teaches that the well can be provided with an attachment surface by covalent binding molecules or including polymers (Niggemann, paragraph 0059). However, the references fail to teach the plate comprises a substrate comprising a surface chemically modified with one or more of poly[carboxybetaine methacrylate] (PCBMA), poly[ [2--methacryloyloxy)ethyl]trimethylammonium chloride](PMETAC), poly[poly(ethylene glycol) methyl ether methacrylate] (PPEGMA), poly[2- hydroxyethyl methacrylate] (PHEMA), poly[3-sulfopropyl methacrylate] (PSPMA), and poly[2- (methacryloyloxy)ethyl dimethyl-(3-sulfopropyl)ammonium hydroxide] (PMEDSAH).
Qian teaches the use of polymer coatings to enhance propagation of cells (abstract). More specifically, Qian teaches the use of PMEDSAH coatings on tissue culture polystyrene (page 9582, first full paragraph in left column).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to incorporate within the plate of Modified Niggemann, a PMEDSAH polymer coating as taught by Qian because it would have been desirable to utilize a polymer coating that can support cell expansion for use in regenerative medicine (Qian, page 9589, Conclusion section).
Response to Arguments
Applicant’s arguments filed 10/09/2025 have been considered.
Firstly, Applicant argues that Niggemann explicitly and unambiguously teaches away from the essential feature of the claim that the microchannel be located essentially in the plane of the bottom of the well since Niggemann teaches at paragraph 0145 that “In a preferred embodiment, the one or more channels connecting neighboring wells is/are not disposed at the lower end of the well, but at a distance in height from the bottom of the wells”. This argument is not persuasive because as seen in Figure 12, the channel 17 is located in a plane of the bottom of the well. The claim does not provide any relative placement to specify what constitutes the “bottom” or “essentially” in the bottom and thus the channel 17 of Figure 12 is interpreted as being in the bottom of the well since it is not present at the top of the well. Additionally, while the citation argued by Applicant as teaching away states one preferred embodiment, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure of non-preferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). Furthermore, "[t]he prior art's mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed ...." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). (see MPEP § 2123). Moreover, as the claim states “essentially” in the plane of the bottom of the well, Niggemann teaching the channel can be at a distance in height from the bottom of the wells would still read on the claimed limitation since even a small distance in height would read on “essentially” at the bottom.
Lastly, Applicant argues that Yung’s markers are fundamentally different from the claimed optical detection markers since the markers of Yung cannot provide a fixed, stable reference point required to facilitate microscope autofocusing. However, it is noted that the features upon which Applicant relies (i.e., provide a fixed, stable reference point, contrast enhancing prints or contrast enhancing microstructures) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Additionally, although Yung does not specifically teach that the detection markers facilitate autofocusing, such limitation in the claim is drawn to intended use of the optical markers and therefore the prior art only needs to be capable of performing the recited intended use. Yung teaches the presence of optical markers compatible with microscopy and therefore would be considered capable of performing the recited intended use of the claim. As the claim does not provide any structural configurations of the optical detection markers (placement within the well, marker structure, etc.), Yung is interpreted as reading upon the claimed optical detection marker since its presence can assist the microscope with focusing on a desired object.
To further differentiate the claims from the teachings of Niggemann in view of Yung, Examiner recommends providing additional structure to the fluid connection and the optical detection markers (placement within the well, marker structure, etc.), as described above.
Conclusion
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 REBECCA M GIERE whose telephone number is (571)272-5084. The examiner can normally be reached M-F 8:30-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy L Nguyen can be reached at 571-272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/REBECCA M GIERE/Primary Examiner, Art Unit 1677