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 .
Remarks
This Office Action fully acknowledges Applicant’s remarks filed on August 7th, 2025. Claims 28-33, and 35-39 are pending. Claims 1-27 and 34 are canceled.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 28, 30, 33, 35, 37, and 38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dolley et al. (US 2005/0170498), hereafter Dolley (and evidenced through “Loctite” and “Corning” attached technical data sheets) in view of Liu (US 2008/0153135).
With regard to claim 28, Dolley discloses an apparatus for bio/chemical assays including cell cultures, including a sample holder plate 200 comprising a plurality of bottomless test wells 160 (the wells are bottomless in that an adhesive layer 280 and transparent bottom glass plate 260 close and form the wells to be “closed” likewise to that of Applicant’s disclosed “bottomless” test wells), a bottom plate 260 (comprising glass as in cl. 30) attached to the sample holder plate 200 via a material that is an adhesive thereby forming a well bottom wall of said plurality of bottomless test wells (pars.[0006,0028-0032], figs. 1-3, for example). With regard to claim 33, the material is UV curvable (Dolley discloses development of cationically photocurable adhesives in cell-based applications but also discloses known UV curable adhesives utilized in likewise multiwell plate arrangements; pars.[0007-0010]; see also par.[0067] and Loctite 3340 which is both UV curable and cationically curable optical adhesives* evidentiary technical data sheet attached herein*) and/or resistant to buffer solutions in as much as recited and required herein (pars.[0035] preventing degradation and pars.[0068-0076]). With regard to claim 35, Dolley discloses that the sample holder is a microtiter plate (par.[0028] ; multiwell plate/microplate 100 being analogous terms in the art). With regards to claims 37 and 38, the recitations are drawn to intended usage recitations not afforded patentable weight wherein “microscopy” (neither the technique nor the physical structure) are a positive element of the device and is intended drawn to an intended workpiece and process recitations (with respect to “microscopy” in terms of its application) that are not afforded patentable weight in a device claim; and wherein the commensurately structured and arranged device of Dolley is full capable of being used with such microscopy/TIRF microscopy in as much as required and recited herein.
With regard to claim 28, Dolley does not specifically disclose that the adhesive material has an RI that is lower than the RI of the glass bottom plate.
Liu discloses methods and apparatuses for conducting amplification reactions on patterned microplates (abstract). Liu discloses providing a sealing liquid as in a photocurable adhesive to become a solid/semi-solid applied to a surface of the microplate, wherein the sealing liquid can be transparent and have a refractive index that is similar to or less than glass and having low to no fluorescence, and said microplate comprising a plurality of reaction spots 10, wherein the sealing material provides to contain the materials present in the plurality of reaction spots and substantially prevents movement of material from one of the plurality of reaction spots to another of the plurality of reaction spots (par.[0069], for example).
It would have been obvious to one of ordinary skill in the art to utilize an adhesive material having a refractive index that is smaller than the glass bottom plate such as suggested by Liu in the analogous art of microplates with individual wells/reaction areas that suitably affords useful optical properties for biochemical studies as likewise desired in Dolley and would have a reasonable expectation of success therein.
Further, to this end, it is noted that Dolley provides a glass bottom plate preferably of boroaluminosilicate (Corning 1737), which has an RI of about 1.52, along with optical adhesives such as Loctite 3337 that has an RI of about 1.52 (see attached technical data sheets). This speaks analogously to that of Liu in the adhesive being similar to or less than that of the glass and providing a reasonable expectation of success in usage of an adhesive that is less than that of the glass/boroaluminosilicate glass; wherein it is further noted that the present claims broadly require “lower than” that can naturally be said to fall within general manufacturing tolerances appreciated by those of ordinary skill in the art. Herein, and speaking back to the breadth of the claim, Applicant has not quantified the “lower than” qualification.
Claim(s) 29, 31, 36 and 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dolley in view of Liu as applied to claims 28, 30, 33, 35, 37, and 38 above, and further in view of Modlin (US 2003/0205681).
With regard to claims 29 and 31, Dolley/Liu does not specifically disclose that the well bottom is functionalized with a second ligand as claimed (Examiner notes that a “first” ligand has not been claimed prior to this and “second” is treated as-claimed, which is to a nominal designation), and wherein the second ligand is a pharmaceutical drug.
With regard to claims 36 and 39, Dolley discloses that the bottom plate is made of a transparent glass that allow for light emissions to be measured through the bottom walls (par.[0031-0032], for example), however, Dolley/Liu does not specifically disclose the sample holder assembly is combined with a light source configured to provide a light beam into the well bottom as claimed.
Modlin discloses evanescent field illumination devices (abstract). Modlin disclose that the microplate wells of the system may be tagged on their surface with various ligands for application in various assays, including high-throughput screening of candidate drug compounds (pars.[0009,0075-0078], for example). Modlin discloses a microplate 41 combined with a light source 50 (and given as a TIRF source as it is providing total internal reflection to generate an evanescent wave) configured to provide a light beam into the well bottom such that the light beam propagates through the entire well bottom wall thereby creating an evanescent field in the plurality of test wells (pars.[0034,0039,0075,0077,0142], figs. 1-4,10 for example), and wherein the composition or sample in the wells can include cell cultures, cells, tissues, etc. (par.[0120]).
It would have been obvious to one of ordinary skill in the art to modify Dolley/Liu to provide the well bottom functionalized with a second light that faces the interior of a bottomless test well as claimed so as to provide application with various binding assays that allow for optical assaying of the wells for various targets of interest, and such as in a pharmaceutical drug in order to allow for high-throughput screening thereof as a part of its development and various interaction-testing.
It would have been obvious to one of ordinary skill in the art to modify Dolley/Liu to combine the microplate with a light source as in a TIRF light source configured as claimed such as taught by Modlin in order to provide an integrated light source to the microplate for carrying out optical assays of the cell cultures in the wells as likewise desired in Dolley in which such evanescent field provides a response that is majorly related to the targets within the wells and avoids unwanted background signals.
Claim(s) 29, 31, and 32 /are rejected under 35 U.S.C. 103 as being unpatentable over Dolley in view of Liu and Modlin as applied to claims 29, 31, 36, and 39 in further view of Alstermark et al. (US 2008/0221063), hereafter Alstermark.
With regard to claims 29, 31, and 32 Dolley/Liu does not specifically disclose that the well bottom is functionalized with a second ligand as claimed (Examiner notes that a “first” ligand has not been claimed prior to this and “second” is treated as-claimed, which is to a nominal designation), and wherein the second ligand is a pharmaceutical drug as in melagatran.
Modlin has been discussed above.
Alstermark discloses measuring FXa inhibitor potency with a chromogenic substrate method with a 96-well microtiter plate in which melagatran was provided as a control to the wells (par.[0077], for example).
It would have been obvious to one of ordinary skill in the art to modify Dolley/Liu/Modlin to provide well bottom functionalized with a second ligand as in a pharmaceutical drug as melagatran such as suggested by Alstermark in order to provide screening application with respect to thrombin inhibitor in which a likewise microtiter plate arrangement affords a variety of measurements in serial dilutions and controls are afforded to be analyzed in a short time frame in order provide substantive information to the drug’s effect as a FXa inhibitor and Dolley/Liu/Modlin are likewise concerned with bio/chemical assays and screening.
Response to Arguments
Applicant's arguments filed August 7th, 2025 have been fully considered but they are not persuasive.
With regards to claims 28, 30, 33, 34, 35, 37, and 38 rejected under 35 USC 103 as being unpatentable over Dolley, evidenced through “Loctite” and “Corning,” and in view of Liu, Applicant traverses the rejection.
Applicant asserts that the holder assembly is useful for the detection of biological binding events using microscopy, such as in TIRF microscopy, and wherein it is critical that the adhesive to have a refractive index that is lower than the refractive index of the bottom plate.
Examiner asserts that such argument is not persuasive as it is not commensurate in scope with the claims. The claims are drawn to a device and do not require any such active process of TIRF microscopy that includes creating an evanescent field.
The added arguments with respect to the binding assay therewith such TIRF microscopy are not commensurate in scope with the claims as the claims are drawn to a device and do not require any such active steps to the particularly-discussed TIRF microscopy with specific binding applications.
With regard to claim 36, as discussed above, Examiner asserts that a structurally-commensurate sample holder (which includes the provision of a material being an adhesive and having a refractive index lower than a refractive index of the bottom plate) is given by the applied art of Dolly in view of Liu and in further view of Modlin, wherein such sample holder is fully capable of (herein “configured to…”) providing a light beam creating an evanescent field in the plurality of bottomless test wells in as much as claimed.
With regard to the evidentiary references of “Dolley” and “Corning,” Applicant asserts that the value of boroaluminosilicate is 1.516 and the refractive index of uncured Loctite 3337 is 1.527, and the evidence does not state “about 1.52.”
Examiner initially notes that this is not an anticipation rejection under 35 USC 102a1 wherein it has been previously provided that the primary reference of Dolley does not specifically disclose that the adhesive material has an RI that is lower than the RI of the glass bottom plate.
However, the applied secondary reference of Liu in the analogous field of microplates, teaches an adhesive and provides that it is suitable to utilize an adhesive having a refractive index similar to or less than glass.
As seen from the “Dolley” and “Corning” material data sheets (and their enumerated RI’s as cited by Applicant), the respective RI’s speak analogously to that disclosed in Liu, and wherein it would be seen to one of ordinary skill in the art that a reasonable expectation of success would be had in utilizing an adhesive material with a refractive index lower than the refractive index of the bottom glass layer.
Examiner further assert that, as previously discussed, that the present claims broadly require a “lower than” qualification that can naturally be said to fall within general manufacturing tolerances of the adhesive material and bottom plate appreciated by those of ordinary skill in the art.
Herein, and speaking back to the breadth of the claim, Applicant has not quantified the “lower than” qualification.
The claimed “lower than” qualification affords differences in the RI such as in 0.0001, wherein such a difference qualifies as “lower than” while subsequently providing no effective difference to the refractive index.
Applicant is invited to quantity the refractive indices and/or materials of construction utilized for such adhesive material and bottom plate.
Examiner notes that Applicant’s remarks do not address this additional assertion of obviousness made in the office action mailed on May 16th, 2025.
Further, with regard to the argument with respect to uncured Loctite RI as opposed to cured Loctite RI that has RI of 1.618, Examiner asserts that Applicant’s argument is not persuasive as the claims do not necessitate the state of the adhesive material to be that of a solid. The present claims do not preclude a liquid or semi-solid adhesive material from reading on the claimed adhesive material.
This is further clearly seen in dependent claim 33 in which it is discussed that the adhesive material is UV curable.
Applicant further asserts that it is critical that the adhesive have both good adhesion properties between the plastic upper plate and glass lower plate and low cytotoxicity, and there is nothing in Liu that discloses or suggests an adhesive with either good adhesion properties between a plastic upper plate and a glass lower plate, or an adhesive having low cytotoxicity.
Examiner asserts that Applicant’s argument is not persuasive as the secondary prior art of Liu has not been relied upon for such teaching.
As discussed above, Dolley is only deficient in providing that the refractive index of the adhesive material is lower than a refractive index of the bottom plate, and Liu, which is analogously in the field of microplates with an adhesive layer and utilized in sensitive biological applications (herein, PCR), provides that it is suitable to utilize an adhesive that is similar or less than the glass bottom plate.
Examiner further asserts that there is also no such rigid requirement given by Dolley that does not afford a coincident utilization of the adhesive material having a lower refractive index than that of a refractive index of the bottom plate.
Examiner further asserts that while Applicant asserts that the sealing liquid in Liu contains materials present in the plurality of reaction spots, Liu explicitly discloses that the sealing material may be a curable adhesive (par.[0069]). Liu has not been relied upon for disclosure to all of the particularly claimed elements of the sample holder, and is provided as analogous art to a microplate utilizing an intervening adhesive.
Further, the base reference of Dolley is not deficient in providing an adhesive material in a stacked sample holder. Dolley provides the claimed sample holder absent particularly disclosing the adhesive material having a refractive index lower than that of the glass bottom.
Liu provides analogous art in microplates utilizing curable adhesives wherein it is shown that such material may have a refractive index that is similar to or less than glass (the bottom plate in Dolley and in the claim), which provides to one of ordinary skill in the art that there is a reasonable expectation of success to modify the adhesive material to have an RI lower than that of an RI of the bottom plate.
It is further noted that, while not relied upon herein with Liu, PCR is a sensitive biological assay that would be readily understood to be negatively impacted by contaminants as in cytotoxic material that would damage or inhibit the reaction.
Nowhere is it seen that this modification to the adhesive material to have an RI lower than that of an RI of the bottom plate imparts cytotoxicity and lack of adhesive properties as purported by Applicant.
Further, as discussed above, the present claims broadly require a “lower than” qualification that can naturally be said to fall within general manufacturing tolerances of the adhesive material and bottom plate appreciated by those of ordinary skill in the art.
As there are no such deficiencies in the rejection of independent claim 28 by way of Dolley in view of Liu, the remaining dependent claims are maintained at least for the reasons discussed above in the body of the action.
Conclusion
THIS ACTION IS MADE FINAL. 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 NEIL N TURK whose telephone number is (571)272-8914. The examiner can normally be reached M-F 930-630.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jill Warden can be reached at 571 272-1267. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NEIL N TURK/Primary Examiner, Art Unit 1798