DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Response to Amendment
The amendment filed February 13th, 2026 is acknowledged. Regarding the Office Action mailed November 14th, 2025:
Modified and new rejections are set forth below, as necessitated by the amendments. Responses to arguments, if necessary, follow their respective rejection sections.
Claim Summary
Claims 2, 6, 12, and 16 have been amended. Claims 1, 9, and 19 have been canceled. Claims 22 and 23 have been added. Claims 2-8, 10-18, and 20-23 are pending. Claims 2-8, 10-18, and 20-23 are under examination and discussed in this Office action.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Modified - Necessitated by Amendment
Claims 2-8, 10-18, and 20-21 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Labaer (US20020192673A1; previously cited), in view of Binkhert et al. (A Microwell Array Platform for Picoliter Membrane Protein Assays, Small, April 2009, 9, 1070-1077; previously cited).
Regarding instant claim 2, Labaer teaches a method of detecting protein-protein interactions using a high-density nucleic acid programmable array (HD-NAPPA), the method comprising: (a) expressing a plurality of nucleic acids attached to surfaces of a plurality of nanowells in an HD-NAPPA, wherein the surfaces of the plurality of nanowells are functionalized with a plurality of capture reagents (Page 12, paragraph [0125]; Page 30, paragraphs [0337] and [0338]), and wherein the plurality of nucleic acids each encode a peptide (Page 12, paragraphs [0125] and [0126]; Page 36, paragraphs [0434]-[0436]); (b) adding a sample to the plurality of nanowells, wherein the sample comprises co-expressing at least one query nucleic acid encoding the at least one query polypeptide in the plurality of nanowells (Page 12, paragraphs [0125] and [0126]); and (c) detecting the query polypeptide using a detection label (Page 12, paragraph [0128]); wherein each nanowell of the plurality of nanowells in the HD-NAPPA comprises a diameter that is from about 10% to about 95% of the center-to-center spacing between each nanowell of the plurality of nanowells in the HD-NAPPA (Page 30, paragraph [0331]: presented diameters can be from about 10% to about 95% of the center-to-center spacing based on the also provided center-to-center distances).
Labaer does not teach wherein each of the plurality of nanowells comprises a depth from about 10 µm to about 150 µm.
Binkhert, in a reasonably pertinent field, teaches wherein a well depth can be 25 µm (Page 1072, column 2, paragraph 2).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the array of Labaer with the well depth of Binkhert. Since Binkhert teaches microwell arrays for protein assays, which is reasonably pertinent to the array as described in Labaer, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it was known in the art to use a well size that allows for high special density on an array (Binkhert, Page 1075, column 2, paragraph 3).
Regarding instant claim 3, Labaer, in view of Binkhert, teaches the method of claim 2. Labaer further teaches wherein each nucleic acid of the plurality of nucleic acids is attached to a different nanowell of the plurality of nanowells (Page 13, paragraph [0133]).
Regarding instant claim 4, Labaer, in view of Binkhert, teaches the method of claim 2. Labaer further teaches wherein the plurality of capture reagents bind an epitope tag expressed by the plurality of nucleic acids (Page 31, paragraphs [0361]-[0363]).
Regarding instant claim 5, Labaer, in view of Binkhert, teaches the method of claim 4. Labaer further teaches wherein the plurality of capture reagents comprise an antibody or an epitope tag-binding fragment thereof (Page 31, paragraphs [0361]-[0363]).
Regarding instant claim 6, Labaer, in view of Binkhert, teaches the method of claim 2. Labaer further teaches wherein detecting the query polypeptide comprises binding of the at least one query polypeptide to the peptide encoded by and expressed from at least one of the plurality of nucleic acids (Page 12, paragraphs [0125] and [0126]; Page 36, paragraphs [0434]-[0436]).
Regarding instant claim 7, Labaer, in view of Binkhert, teaches the method of claim 2. Labaer further teaches wherein detecting the query polypeptide comprises the detection label binding to at least a portion of the query peptide (Page 12, paragraph [0128]).
Regarding instant claim 8, Labaer, in view of Binkhert, teaches the method of claim 2. Labaer further teaches wherein the plurality of nanowells are arranged in the HD-NAPPA to minimize protein diffusion (Page 30, paragraphs [0337] and [0338]).
Regarding instant claim 10, Labaer, in view of Binkhert, teaches the method of claim 8. Labaer further teaches wherein each nanowell of the plurality of nanowells in the HD-NAPPA comprises a center-to-center spacing from about 20 nm to about 400 µm (Page 30, paragraph [0331]).
Regarding instant claim 11, Labaer, in view of Binkhert, teaches the method of claim 2. Labaer further teaches wherein each of the plurality of nanowells comprises a diameter from about 15 nm to about 0.75 mm (Page 30, paragraph [0331]).
Regarding instant claim 12, Labaer teaches a method of detecting protein-protein interactions using a high-density nucleic acid programmable array (HD-NAPPA), the method comprising: (a) expressing a plurality of nucleic acids attached to surfaces of a plurality of nanowells in an HD-NAPPA (Page 12, paragraph [0125]; Page 30, paragraphs [0337] and [0338]), wherein the plurality of nucleic acids each encode a peptide (Page 12, paragraphs [0125] and [0126]; Page 36, paragraphs [0434]-[0436]); (b) exposing the plurality of nanowells to a substrate functionalized with a plurality of capture reagents (Page 14, paragraph [0145]); (c) adding a sample to the plurality of nanowells, wherein the sample comprises co-expressing at least one query nucleic acid encoding the at least one query polypeptide in the plurality of nanowells (Page 12, paragraphs [0125] and [0126])); and (d) detecting the query polypeptide using a detection label (Page 12, paragraph [0128]); wherein each nanowell of the plurality of nanowells in the HD-NAPPA comprises a diameter that is from about 10% to about 95% of the center-to-center spacing between each nanowell of the plurality of nanowells in the HD-NAPPA (Page 30, paragraph [0331]: presented diameters can be from about 10% to about 95% of the center-to-center spacing based on the also provided center-to-center distances).
Labaer does not teach wherein the plurality of nanowells comprise a depth from about 10 µm to about 150 µm.
Binkhert, in a reasonably pertinent field, teaches wherein a well depth can be 25 µm (Page 1072, column 2, paragraph 2).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the array of Labaer with the well depth of Binkhert. Since Binkhert teaches microwell arrays for protein assays, which is reasonably pertinent to the array as described in Labaer, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it was known in the art to use a well size that allows for high special density on an array (Binkhert, Page 1075, column 2, paragraph 3).
Regarding instant claim 13, Labaer, in view of Binkhert, teaches the method of claim 12. Labaer further teaches wherein each nucleic acid of the plurality of nucleic acids is attached to a different nanowell of the plurality of nanowells (Page 13, paragraph [0133]).
Regarding instant claim 14, Labaer, in view of Binkhert, teaches the method of claim 12. Labaer further teaches wherein the plurality of capture reagents bind an epitope tag expressed by the plurality of nucleic acids (Page 31, paragraphs [0361]-[0363]).
Regarding instant claim 15, Labaer, in view of Binkhert, teaches the method of claim 14. Labaer further teaches wherein the plurality of capture reagents comprise an antibody or an epitope tag-binding fragment thereof (Page 31, paragraphs [0361]-[0363]).
Regarding instant claim 16, Labaer, in view of Binkhert, teaches the method of claim 12. Labaer further teaches wherein detecting the query polypeptide comprises binding of the at least one query polypeptide to the peptide encoded and expressed from at least one of the plurality of nucleic acids (Page 12, paragraphs [0125] and [0126]; Page 36, paragraphs [0434]-[0436]).
Regarding instant claim 17, Labaer, in view of Binkhert, teaches the method of claim 12. Labaer further teaches wherein detecting the query polypeptide comprises the detection label binding to at least a portion of the query peptide (Page 12, paragraph [0128]).
Regarding instant claim 18, Labaer, in view of Binkhert, teaches the method of claim 12. Labaer further teaches wherein the plurality of nanowells are arranged in the HD-NAPPA to minimize protein diffusion (Page 30, paragraphs [0337] and [0338]).
Regarding instant claim 20, Labaer, in view of Binkhert, teaches the method of claim 12. Labaer further teaches wherein each nanowell of the plurality of nanowells in the HD-NAPPA comprises a center-to-center spacing from about 20 nm to about 400 µm (Page 30, paragraph [0331]), and wherein each of the plurality of nanowells comprise a diameter from about 15 nm to about 0.75 mm (Page 30, paragraph [0331]).
Regarding instant claim 21, Labaer, in view of Binkhert, teaches the method of claim 12. Labaer further teaches wherein each of the plurality of nanowells comprises a diameter from about 15 nm to about 0.75 mm (Page 30, paragraph [0331]).
Response to Arguments
Applicant's arguments filed February 13th, 2026 have been fully considered but they are not persuasive.
The Applicant first summarizes the Examiner’s previous rejection, with particular focus on the combination of Labaer and Binkert (Page 6 of the Remarks filed February 13th, 2026). The Applicant then provides a summary regarding the aspect of prior art wherein it must be considered in its entirety (Pages 6-7 of the Remarks filed February 13th, 2026). The Applicant argues that the Examiner has not considered Binkert in its entirety (Page 7 of the Remarks filed February 13th, 2026). The Applicant states that Binkert is directed to solving the problem of solvent evaporation, and that their solution was to add 50% glycerol to each well (Page 7 of the Remarks filed February 13th, 2026). The Applicant then provides a short summary of the invention as claimed, concluding that one of ordinary skill in the art would appreciate that expression of a nucleic acid encoding a protein includes in vitro transcription and translation (Page 7 of the Remarks filed February 13th, 2026). The Applicant further states that one of ordinary skill in the art would recognize that a high concentration of glycerol would disrupt the function of the enzymes used in in vitro expression of a protein (Page 7 of the Remarks filed February 13th, 2026). The Applicant then provides citations from the art supporting the idea that high concentrations of glycerol will interfere with both protein structure, protein-protein interactions, transcription and translation, and enzyme-catalyzed reactions, arguing that it was known that glycerol inhibits biochemical reactions (Pages 8-9 of the Remarks filed February 13th, 2026). The Applicant argues that Binkert teaches the 25um well depth only in combination with the use of 50% glycerol, and given the cited art, this concentration of glycerol would inhibit expression of nucleic acids as claimed (Page 9 of the Remarks filed February 13th, 2026). The Applicant argues that the combination of Labaer and Binkert would make the assays/methods of Labaer inoperable for their intended purpose (Page 9 of the Remarks filed February 13th, 2026). The Applicant argues that, for all these reasons, it would not have been obvious to combine Labaer and Binkert and arrive at the methods as claimed with any reasonable expectation of success (Page 9 of the Remarks filed February 13th, 2026).
In response to these arguments, it is noted that the Examiner has considered Binkert in its entirety, including aspects taught beyond that of using 50% glycerol in 25um deep wells. Binkert notes that glycerol content can vary between 10-60% depending on the application (Binkert, Page 1072, column 2, paragraph 3). One of ordinary skill in the art could reasonably adjust the glycerol content to a lower concentration given that glycerol concentration can vary depending on application. The Applicant’s own cited art of Demidenko (Effects of Viscogens on RNA Transcription inside Reovirus Particles, August 2011, 286, 29521-29530) teaches that glycerol concentration at 10% increases transcription (Figure 1). Demidenko further teaches that glycerol concentration at 20% does appear to slow down transcription, but not fully inhibit it (Figure 1). Pocker and Janjic (Enzyme kinetics in solvents of increased viscosity. Dynamics aspects of carbonic anhydrase catalysis, May 1987, 26, 2597-2606) teaches that lower concentrations of glycerol have less of an effect on enzyme function (Figure 2). Binkert teaches that no evaporation could be observed using 20% glycerol, and that 50% glycerol was used simply to be cautious (Binkert, Page 1072, column 2, paragraph 3). Therefore, Binkert’s well depth does not specifically require 50% glycerol concentration and can in fact be used with as low a concentration as 20%, which does not fully inhibit the transcription that is required by the claims. Binkert also makes clear that a lower concentration can be used. Furthermore, while glycerol is used with the particular combination of sample volume in Binkert, the well depth still does not become inoperable because there is no glycerol in the well. A sample may still be deposited into the well, which is all that is required given what is currently claimed.
It should also be noted that glycerol is used to prevent evaporation in Binkert given that Binkert is definitively teaching away from using a cover or humidity because of their electronics and visualization set up (Binkert, Page 1072, column 2, paragraph 2). However, Labaer does not teach on this same set up because they do not use an electronic spotter and visualization in the same way. Nucleic acids of Labaer are spotted and may dry before undergoing transcription (Labaer, Page 31, paragraph [0346]), which does not require prevention of evaporation. Labaer further offers options for their array substrate wherein a cover or humidity may be used to prevent evaporation of transcription/translation mixes after samples have been spotted (Labaer, Page 31, paragraph [0346]). Therefore, Labaer has options other than glycerol to prevent evaporation and is then only missing the well depth as taught by Binkert.
It is also noted that, while the arguments of the Applicant directed towards glycerol and evaporation have been fully considered and responded to, there is still no claim related to prevention of evaporation or inclusion of glycerol in the invention. Labaer teaches all aspects of the claimed invention besides well depth. Binkert is relied upon to teach well depths, with a motivation for the use of the well depth taught. Furthermore, Binkert teaches on performing protein assays in their wells, indicating that this well depth is adequate for protein assay applications.
Finally, with regard to the arguments related to what one of ordinary skill in the art would know outside of what is covered by the teachings of the provided references (see Page 7 and Page 9 of the Remarks filed February 13th, 2026), the Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record. It is noted that the Response above should not be construed as an invitation to file an after final declaration. See MPEP 715.09.
Given all of these considerations, the arguments are not found persuasive.
New - Necessitated by Amendment
Claims 22 and 23 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Labaer (US20020192673A1; previously cited), in view of Binkhert et al. (A Microwell Array Platform for Picoliter Membrane Protein Assays, Small, April 2009, 9, 1070-1077; previously cited).
Regarding instant claims 22 and 23, Labaer, in view of Binkert, teaches the methods of claims 1 and 12. Labaer does not directly teach that expression a plurality of nucleic acids comprises in vitro transcription and translation. However, Labaer does teach that the nucleic acids of the array are contacted with a translation effector to translate them into amino acid sequences (Page 12, paragraph [0125]; Page 30, paragraph [0337]). Labaer also teaches the use of an expression vector for expression of a coding region of interest, and the use of commercially available in vitro transcription/translation kits to generate the proteins of interest (Page 33, paragraph [0391]). Therefore, it would be obvious that expression of the plurality of nucleic acids may be performed by in vitro transcription and translation.
Conclusion
All claims are rejected.
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 Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
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/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
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