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 .
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.
Withdrawn Objections/Rejections
The rejections of claim 73 under 112a and 112b are withdrawn in response to the amendments.
The rejection of claims 9-10 and 71-75 under 102 is withdrawn in response to the amendments. However, new grounds of rejection are set forth below under 103.
Priority
The present application claims benefit under 35 U.S.C. 119(e) to provisional application 63/179,731 filed on 04/26/2021.
Status of the Claims
Claims 1-4, 9-11, 23-24, 28, 38-40, 42, 47, 51, 55 and 72-76 are pending; claims 1, 9 and 73 are amended; claims 5-8, 12-22, 25-27, 29-37, 41, 43-46, 48-50, 52-54 and 56-71 are canceled; claim 76 is newly recited. Claims 1-4, 9-11, 23-24, 28, 38-40, 42, 47, 51, 55 and 71-76 are examined below.
Maintained Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 4, , 28, 42, 47, 51 and 55 stand rejected under 35 U.S.C. 103 as being unpatentable over Terbrueggen (WO 02/43864 A2) (Cited on PTO-892 3/18/2025).
Regarding claim 1, Terbrueggen teaches “devices that allow for simultaneous multiple biochip analysis. In particular, the devices are configured to hold multiple cartridges comprising biochips comprising arrays such as nucleic acid arrays, and allow for high throughput analysis of samples” (Abstract). Terbrueggen teaches that “the biochip cartridge comprises a detection chamber with an array of electrodes” (page 2 paragraph 4) “preferably gold electrodes” (page 31 paragraph 2). Terbrueggen teaches that the gold electrodes contain carbon, i.e., a carbon-containing assay surface from the added organic brighteners (grain refining additives) (“[d]etection electrodes on circuit board material (or other substrates) are generally prepared in a wide variety of ways. In general, high purity gold is used, and it may be deposited on a surface via vacuum deposition processes (sputtering and evaporation) or solution deposition (electroplating or electroless processes)… When electroplated metal (either the adhesion metal or the electrode metal) is used, grain refining additives, frequently referred to in the trade as brighteners, can optionally be added to alter surface deposition properties. Preferred brighteners are mixtures of organic and inorganic species” page 31 last paragraph and page 32 paragraph 1). Note that carbon is inherently present in “organic species”. Terbrueggen teaches a method of preparing a bifunctional assay surface, the method comprising: a. dispensing a coating solution comprising a proteinaceous primary reagent and a thiol-containing secondary reagent onto a carbon-containing assay surface to form a coated assay surface (“[e]ach electrode preferably comprises a self-assembled monolayer” page 31 paragraph 2, “[i]n general, the SAMs [self-assembled monolayers] of the invention can be generated in a number of ways and comprise a number of different components” page 38 paragraph 3, “[f]ollowing cleaning, the gold substrate is exposed to the SAM species… A preferred embodiment utilizes a deposition solution comprising a mixture of various SAM species in solution, generally thiol-containing species” page 54 paragraph 4, “[a] binding ligand deposition solution in organic solvent is prepared in which the total thiol concentration is between…from about 1 μM to 10 mM…the deposition solution contains thiol modified DNA (i.e. nucleic acid attached to an attachment linker) and thiol diluent molecules (either conductive oligomers or insulators” page 54 last paragraph, “the conductive oligomer has the structure depicted in Structure 1” page 40 last paragraph, “as depicted in Structure 1, the left "Y" is connected to the electrode… In this embodiment, Y is an aromatic group…the Y aromatic groups of the conductive oligomer may be different” page 41 paras. 1-2 and 4, “The aromatic group may be substituted with a substitution group, generally depicted herein as R… Suitable R groups include… sulfur containing moieties” page 42 paras. 2 and 4, “By "sulfur containing moieties" herein is meant compounds containing sulfur atoms, including but not limited to, thia-, thio- and sulfo- compounds, thiols (-SH and -SR)” page 43 para. 4, “Linkers are well known in the art; for example homo-or hetero-bifunctional linkers… In this way, capture binding ligands comprising proteins… nucleic acids…etc. can be added” page 58 paras. 2-3).. Terbrueggen teaches a step of incubating the coated assay surface under conditions in which the proteinaceous primary reagent and thiol-containing secondary reagent are immobilized on the assay surface (“[t]he gold substrate is allowed to incubate at ambient temperature or slightly above ambient temperature for a period of time ranging from seconds to hours, with 5-30 minutes being preferred…The gold substrate is allowed to incubate at room temperature or above room temperature for a period of time (seconds to days, with from about 10 minutes to about 24 hours being preferred)” page 55 paragraph 1 ). Terbrueggen further suggests wherein the thiol-containing secondary reagent is immobilized on the assay surface through a thiol group of the thiol-containing secondary reagent (“the discussion herein is mainly directed to gold electrodes and thiol-containing monolayer forming species” page 39 paragraph 1, page 41 para. 1, page 42 para. 4). Terbrueggen further teaches that “the composition of the binding ligand will depend on the
composition of the target analyte… When the analyte is a protein, the binding ligands include
proteins” (page 57 para. 2). Terbrueggen further teaches that “is known in the art, any
number of techniques may be used to attach a proteinaceous capture binding ligand to an attachment linker. A wide variety of techniques are known to add moieties to proteins” (page 58 para. 4).
Terbrueggen fails to teach the proteinaceous primary reagent in a manner consistent with anticipation, i.e., there is some picking and choosing involved to arrive at the proteinaceous primary reagent, i.e. the proteinaceous primary reagent is taught in a separate embodiment. Terbrueggen teaches the method of preparing a bifunctional assay surface of claim 1 in page 54 last paragraph and page 55 paragraph 1 using “thiol modified DNA”, and in page 58 paragraphs 2-3, Terbrueggen teaches that “capture binding ligands comprising proteins…can be added”.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have picked a proteinaceous primary reagent as the capture binding ligand because Terbrueggen suggests that this enables high throughput analysis of multiple proteins in a sample. A person having ordinary skill in the art would have had a reasonable expectation of success given that Terbrueggen teaches that there are a wide variety of techniques known to add moieties to proteins.
Regarding claim 4, Terbrueggen teaches the method of claim 1 as discussed above.
Terbrueggen further suggests wherein the coating solution comprises from about 1000 nM to about 10000000 nM thiol-containing secondary reagent (page 54 last paragraph). Terbrueggen further teaches that “the discussion herein is mainly directed to gold electrodes and thiol-containing monolayer forming species” (page 39 paragraph 1). Terbrueggen further teaches that “[t]here are a number of assays and sensors for the detection of the presence and/or concentration of specific substances in fluids and gases” (page 1 paragraph 3). Terbrueggen further teaches that “[h]owever, to date none of these methods have been used in highly parallel systems to allow biochip multiplexing. Accordingly, it is an object of the present invention to provide devices and methods for multiplex analysis of biochips, particularly nucleic acid biochips” (page 2 paragraph 2).
Applicant is reminded that generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” MPEP 2144.05.
With regards to the claimed range of thiol-containing secondary reagent, the prior art teaches a range of 1000-10000000 nM. In such a case, since there is a substantial overlap of the claimed range and the prior art range, a prima facie case of obviousness exists because it would have been obvious to a person having ordinary skill in the art to arrive at the claimed range by selecting values disclosed within the prior art range. See MPEP 2144.05.
In the present case, it would have been obvious to arrive at the claimed invention by optimizing within prior art conditions. Absent evidence of criticality, it would have been obvious to employ a concentration of about 1000 nM to about 1500 nM thiol-containing secondary reagent as the teachings of Terbrueggen indicate that the concentration will depend on saturation of the reagent. Therefore, it is understood that a range that falls squarely within the claimed range of concentration of thiol-containing secondary reagent is suggested by Terbrueggen, i.e., 1000 nM to 1500 nM. Furthermore, given that there is a market pressure to develop multiplex assays, a person having ordinary skill in the art would have found it obvious to try choosing from the finite list of possible predictable concentrations of thiol-containing secondary reagent taught by Terbrueggen, thereby arriving at a range that is within the claimed range. A person having ordinary skill in the art would have a reasonable expectation of success given that the teachings of Terbrueggen are mainly directed to gold electrodes and thiol-containing monolayer forming species.
Regarding claims 28 and 42, Terbrueggen suggests the method of claim 1 as discussed above.
Terbrueggen further suggests wherein thiol-containing secondary reagent comprises a thiolated oligonucleotide, wherein thiol-containing secondary reagent comprises a thiolated member of a binding pair (“As will be understood by those in the art, all of the structures depicted herein may have additional atoms or structures; e.g. the conductive oligomer of Structure 1 may be attached to …nucleic acids” page 41 para. 1). Note that Terbrueggen suggests that “[b]y "nucleic acid" or "oligonucleotide" or grammatical equivalents herein means at least two nucleotides covalently linked together” (page 13 paragraph 4).
Regarding claim 47, Terbrueggen teaches the method of claim 1 as discussed above.
Terbrueggen further teaches wherein the proteinaceous primary reagent comprises a proteinaceous capture reagent that specifically binds to a target analyte (page 58 paras. 2-3, “As will be appreciated by those in the art, the composition of the binding ligand will depend on the composition of the target analyte… When the analyte is a protein, the binding ligands include proteins (particularly including antibodies or fragments thereof (FAbs, etc.)), small molecules, or aptamers, described above. Preferred binding ligand proteins include peptides… Suitable analyte/binding ligand pairs include, but are not limited to, antibodies/antigens, receptors/ligand, … enzymes/substrates and/or inhibitors, carbohydrates (including glycoproteins and glycolipids)/lectins, carbohydrates and other binding partners, proteins/proteins; and protein/small molecules” page 57 para. 2, “A preferred embodiment utilizes proteinaceous capture binding ligands” page 58 paragraph 4, “a "capture" or "anchor'' binding ligand ([is] also referred to herein as a "capture probe" page 56 paragraph 2).
Regarding claim 51, Terbrueggen teaches the method of claim 47 as discussed above.
Terbrueggen further teaches wherein the proteinaceous primary reagent comprises a first member of a binding pair and the target analyte comprises a second member of the binding pair (“For example, when the analyte is an enzyme, suitable binding ligands include substrates, inhibitors, and other proteins that bind the enzyme, i.e. components of a multi-enzyme (or protein) complex. As will be appreciated by those in the art, any two molecules that will associate, preferably specifically, may be used, either as the analyte or the binding ligand. Suitable analyte/binding ligand pairs include, but are not limited to, antibodies/antigens, receptors/ligand, proteins/nucleic acids… enzymes/substrates and/or inhibitors…proteins/proteins” page 57 para. 2).
Regarding claim 55, Terbrueggen teaches the method of claim 1 as discussed above.
Terbrueggen further suggests wherein the carbon-containing assay surface comprises a multi-well plate and one or more wells of the multi-well plate comprise one or more electrodes (“In a preferred embodiment, platforms for multi-well plates…are accommodated on an upgradable modular platform for additional capacity” page 90 paragraph 3).
Claims 2, 23-24 and 38-40 stand rejected and claim 76 is newly rejected under 35 U.S.C. 103 as being unpatentable over Terbrueggen (WO 02/43864 A2) as applied to claim 1 above, and further in view of Kenten et al. (WO 2020227016 A1)-Cite No. 2 of IDS dated 10/19/2022 ("Kenten").
Regarding claim 2, Terbrueggen teaches the method of claim 1 as discussed above.
Terbrueggen further teaches comprising dispensing 30 nl of the coating solution (“a circuit board is used as the substrate for the gold electrodes. Formation of the SAMs on the gold surface is generally done by first cleaning the boards… The boards are then dried… Spotting of the deposition solution onto the boards is done using any number of known spotting systems… The size of the spotting drop will vary with the size of the electrodes on the boards and the equipment used for delivery of the solution; for example, for 250 μM size electrodes, a 30 nanoliter drop is used. The volume should be sufficient to cover the electrode surface completely” (page 55 last paragraph and page 56 paragraph 1).
Terbrueggen fails to teach wherein the coating solution covers the assay surface at a ratio of about 50 nl per binding domain of the assay surface.
Kenten teaches “Oligonucleotides, methods and kits are provided for detecting, identifying or quantifying one or more target analytes in a sample as well as methods for immobilizing oligonucleotides onto a support surface” (Abstract). Kenten further teaches wherein the coating solution covers the assay surface at a ratio of about 50 nl per binding domain of the assay surface (“Capture oligonucleotide arrays of SEQ IDS 1 to 10 were printed on these plates by depositing 50 nL droplets containing thiol-modified capture oligonucleotides (using the n mercaptopropanol modification linked to the 3' end of the oligonucleotide through a 6-mer
Polyethylene glycol (PEG6) spacer as shown in the structure below) on individual spots on the
electrodes. The printing solutions included thiol oligonucleotide in a buffered solution
25 containing sodium phosphate, NaCl, EDTA, Trehalose, and Triton X-100, with an excess of
oligonucleotide relative to amount needed to saturate the carbon ink surface, and sufficient
Triton X-100 so that the droplets spread to the edge of the spot as defined by the printed
dielectric ink layer” page 205 lines 20-28). Kenten further suggests that the method wherein the coating solution covers the assay surface at a ratio of about 50 nl per binding domain of the assay surface produces a uniform coating onto the surface with high specificity (“A lot of plates prepared as described in Example 2 were tested for uniformity of coating and for cross-reactivity between array elements” page 207 lines 20-21, “The average intraplate CV [coefficient of variation] across the six plates were less than 5% for all of the capture oligonucleotides and ranged from 3.6% to 4.6%. The CV of the intraplate signal averages were less than 6% for all capture oligonucleotides and ranged from 3.5% to 5.5%... For the 90 possible non-specific probe/capture interactions, 81 (90%) had a cross-reactivity of 0.01 % or less and maximum cross-reactivity was 0.03%” page 208 lines 5-8 and 17-19).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Terbrueggen to rely on the ratio of 50 nl of coating solution per binding domain of the assay surface taught by Kenten because it would be a simple matter of applying a known technique to a known method. In this case, both Terbrueggen and Kenten teach dispensing a coating solution onto a carbon-containing assay surface. Terbrueggen teaches wherein the coating solution covers the assay surface at a ratio of about 30 nl per binding domain, and Kenten teaches wherein the coating solution covers the assay surface at a ratio of about 50 nl per binding domain. Therefore, a person having ordinary skill in the art would have found it obvious to apply the art-recognized technique of Kenten to the base method taught by both references. One would be motivated to make such a modification because Kenten teaches that the coating had high uniformity and specificity (low cross-reactivity). A person having ordinary skill in the art would have had a reasonable expectation of success because both Terbrueggen and Kenten teach dispensing a coating solution onto an assay surface.
Regarding claim 23, Terbrueggen teaches the method of claim 1 as discussed above.
Terbrueggen fails to teach wherein the proteinaceous primary reagent is immobilized on the carbon-containing assay surface via a binding pair.
Kenten suggests wherein the proteinaceous primary reagent is immobilized on the carbon-containing assay surface via a binding pair (“the capture oligonucleotide is attached ( directly or through a linker) to a first binding partner from a binding partner pair and immobilization is achieved by binding of this first binding partner to a second binding partner from the binding partner pair that is immobilized on the support surface. Binding partner pairs that are suitable for use in immobilizing capture oligonucleotides include binding partner pairs know in the art such as biotin-streptavidin, biotin-avidin, antibody-hapten, antibody-epitope tag (for example, antibody-FLAG), nickel-NTA and receptor-ligand pairs” page 52 lines 9-15, “In one aspect, one or more aptamers are immobilized onto a support surface by binding to one or more single stranded capture molecules that are immobilized to the support surface as described herein)… In another aspect, the aptamer is a peptide” page 68 lines 5-7 and 11). Kenten further teaches that “the support surface is a carbon-based support surface” (page 54 lines 14-15). Kenten further teaches that “one or more capture oligonucleotides are covalently or non-covalently immobilized on one or more binding domains on one or more electrodes on the support surface. In one aspect, multiple distinct binding domains are present on one or more electrodes for multiplexed measurement of target analytes in a sample” (page 56 lines 14-17).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Terbrueggen to rely on the immobilization of the proteinaceous primary reagent on the carbon-containing surface via a binding pair taught by Kenten because it would be a simple matter of applying a known technique to a known method. In this case, both Terbrueggen and Kenten teach binding of a proteinaceous primary reagent on a carbon-containing surface. Kenten simply uses the technique of a binding pair for the immobilization. Therefore, a person having ordinary skill in the art would have found it obvious to apply the art-recognized technique of Kenten to the base method taught by both references. One would be motivated to make such a modification because Kenten suggests this is a suitable way for immobilizing proteinaceous primary reagents on carbon-containing assay surfaces. A person having ordinary skill in the art would have had a reasonable expectation of success because Kenten also provides a list of binding pair options and both references are drawn to immobilization of reagents onto carbon-containing surfaces for bifunctional assays.
Regarding claim 24, Terbrueggen in view of Kenten teach the method of claim 23 as discussed above.
Terbrueggen fails to teach wherein the proteinaceous primary reagent comprises a first member of a binding pair and the carbon-containing assay surface comprises a second member of the binding pair.
Kenten suggests wherein the proteinaceous primary reagent comprises a first member of a binding pair and the carbon-containing assay surface comprises a second member of the binding pair (page 52 lines 9-15, page 68 lines 5-7 and 11). Kenten further teaches that “the support surface is a carbon-based support surface” (page 54 lines 14-15).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Terbrueggen to rely on wherein the proteinaceous primary reagent comprises a first member of a binding pair and the carbon-containing assay surface comprises a second member of the binding pair taught by Kenten because for the same reason as discussed above, i.e., it would be a simple matter of applying a known technique to a known method. In this case, both Terbrueggen and Kenten teach binding of a proteinaceous primary reagent on a carbon-containing surface. Kenten simply uses the technique of a binding pair for the immobilization wherein the proteinaceous primary reagent comprises a first member of a binding pair and the carbon-containing assay surface comprises a second member of the binding pair. Therefore, a person having ordinary skill in the art would have found it obvious to apply the art-recognized technique of Kenten to the base method taught by both references. One would be motivated to make such a modification because Kenten suggests this is a suitable way for immobilizing proteinaceous primary reagents on carbon-containing assay surfaces. A person having ordinary skill in the art would have had a reasonable expectation of success because Kenten also provides a list of binding pair options and both references are drawn to immobilization of reagents onto carbon-containing surfaces for bifunctional assays.
Regarding claim 38, Terbrueggen teaches the method of claim 28 as discussed above.
Terbrueggen fails to teach, i.e., is silent regarding wherein the thiolated oligonucleotide comprises an oligonucleotide sequence having a 5'- and a 3'- end and a thiol group incorporated at the 5' end (a 5'-terminal thiolated oligonucleotide), at the 3' end (a 3'-terminal thiolated oligonucleotide), at an internal position of the oligonucleotide, or a combination thereof.
Kenten suggests wherein the thiolated oligonucleotide comprises an oligonucleotide sequence having a 5'- and a 3'- end and a thiol group incorporated at the 5' end (a 5'-terminal thiolated oligonucleotide), at the 3' end (a 3'-terminal thiolated oligonucleotide), at an internal position of the oligonucleotide, or a combination thereof (“the capture oligonucleotide is covalently bound to a protein and immobilization on the support surface is achieved through adsorption of the protein to the support surface… the capture oligonucleotide is covalently bound to the protein or the first binding partner through a thiol (SH) or amine (-NH2) group… In one aspect, the thiol or amine group is at the 5' - or 3 ' - end of the capture oligonucleotide. In one aspect, the capture oligonucleotide is a 5' -terminal thiolated oligonucleotide. In one aspect, the capture oligonucleotide is a 3 '-terminal thiolated oligonucleotide. In one aspect, the thiol group is incorporated at an internal position of the capture oligonucleotide. In one aspect, the capture oligonucleotide has a nucleotide sequence that includes a sequence shown in any of SEQ ID 25 NOs: 1489-1498 (Table 25) ” page 52 lines 5-7, 15-17 and 19-25).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Terbrueggen to rely on the thiolated oligonucleotide comprising an oligonucleotide sequence having a 5'- and a 3'- end and a thiol group incorporated at the 5' end (a 5'-terminal thiolated oligonucleotide), at the 3' end (a 3'-terminal thiolated oligonucleotide), at an internal position of the oligonucleotide, or a combination thereof as taught by Kenten because it would have been a simple matter of applying a known technique to a known method. In this case, both Terbrueggen and Kenten teach a thiolated oligonucleotide. Kenten simply applies the art-recognized technique of wherein the thiolated oligonucleotide comprises an oligonucleotide sequence having a 5'- and a 3'- end and a thiol group incorporated at the 5' end (a 5'-terminal thiolated oligonucleotide), at the 3' end (a 3'-terminal thiolated oligonucleotide), at an internal position of the oligonucleotide, or a combination thereof. Therefore, a person having ordinary skill in the art would have found it obvious to apply the technique taught by Kenten to the base method taught by both references. One would be motivated to make such a modification because Kenten suggests this enables the immobilization of the capture oligonucleotide to the support surface in different possible ways, i.e., with different geometries through the use of the thiol group at different parts of the oligonucleotide. A person having ordinary skill in the art would have had a reasonable expectation of success because both references are drawn to immobilization of reagents onto carbon-containing surfaces for bifunctional assays and Kenten teaches sequences of possible thiolated oligonucleotides.
Regarding claims 39-40, Terbrueggen in view of Kenten teach the method of claim 38 as discussed above.
Terbrueggen fails to teach, i.e., is silent regarding wherein the thiolated oligonucleotide comprises DNA, RNA, LNA, PNA, or a combination thereof or one or more non-natural nucleotide bases.
Kenten suggests wherein the thiolated oligonucleotide comprises DNA, RNA, and one or more non-natural nucleotide bases (“capture oligonucleotides include single stranded nucleic acid sequences, including for example, nucleic acid sequences including deoxyribonucleic acids (DNA), ribonucleic acids (RNA), or structural analogs that include nonnaturally occurring chemical structures that can also participate in hybridization reactions” page 70 lines 18-21).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Terbrueggen to rely on the thiolated oligonucleotide comprising DNA or RNA or one or more non-natural nucleotide bases taught by Kenten because it would be a simple matter of applying a known technique to a known method. In this case, both Terbrueggen and Kenten teach thiolated oligonucleotides. Kenten simply applies the art-recognized technique of wherein the thiolated oligonucleotide comprises one or more non-natural nucleotide base. Therefore, a person having ordinary skill in the art would have found it obvious to apply the art-recognized technique of Kenten to the base method taught by both references. One would be motivated to make such a modification because Kenten suggests that this enables the detection of a target analyte through a hybridization reaction. A person having ordinary skill in the art would have had a reasonable expectation of success because both references are drawn to immobilization of reagents onto carbon-containing surfaces for bifunctional assays.
Regarding claim 76, Terbrueggen teaches the method of claim 1 as discussed above.
Terbrueggen further suggests wherein the thiol-containing secondary reagent comprises a thiolated polyethylene glycol (Thiol-PEG) (“Suitable R groups include… sulfur containing moieties,… and ethylene glycols…It should be noted that some positions may allow two substitution groups, R and R', in which case the R and R' groups may be either the same or different” page 42 para. 4).
Terbrueggen teaches wherein the thiol-containing secondary reagent comprises a thiolated polyethylene glycol (Thiol-PEG) by combining a sulfur moiety and a PEG moiety from a list of other possible moieties in page 42 paragraph 4. However, there is not enough guidance in Terbrueggen to try choosing thiol-PEG from said finite list.
Kenten suggests wherein the thiol-containing secondary reagent comprises a thiolated polyethylene glycol (Thiol-PEG) (“Capture oligonucleotide arrays of SEQ IDS 1 to 10 were printed on these plates by depositing 50 nL droplets containing thiol-modified capture oligonucleotides (using the n mercaptopropanol modification linked to the 3' end of the oligonucleotide through a 6-mer Polyethylene glycol (PEG6) spacer as shown in the structure below) on individual spots on the electrodes” page 205 lines 20-24, see the structure in page 206 showing the thiol-PEG). Kenten further suggests that the PEG linker length increases the signal produced in the assay (“Fig. 3 shows the measured ECL signal as a function of the number of probe molecules in a well for the different linkers and demonstrates that the ECL signal from the binding of the QC probes to the capture oligonucleotides increased with linker length for both the 12-mer and 24-mer capture oligonucleotides” page 209 lines 5-8).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have tried picking thiol-PEG from the finite list of possible moieties taught by Terbrueggen because Kenten suggests that the thiol-PEG increases the signal produced in the assay. A person having ordinary skill in the art would have had a reasonable expectation of success because both Terbrueggen and Kenten are drawn to immobilization of reagents onto carbon-containing surfaces for bifunctional assays.
Claim 3 stands rejected under 35 U.S.C. 103 as being unpatentable over Terbrueggen (WO 02/43864 A2) as applied to claim 1 above, and further in view of Cornelia Kuschel, Heiko Steuer, Andreas N. Maurer, Britta Kanzok, Reinout Stoop & Brigitte Angres (2006) Cell Adhesion Profiling Using Extracellular Matrix Protein Microarrays, BioTechniques, 40:4, 523-531, DOI: 10.2144/000112134 (Cited on PTO-892 3/18/2025) ("Kuschel").
Regarding claim 3, Terbrueggen teaches the method of claim 1 as discussed above.
Terbrueggen fails to teach wherein the coating solution comprises from about 100 µg/ml to 750 µg/ml proteinaceous primary reagent.
Kuschel teaches “a microarray-based system for cell adhesion profiling of large panels of cell-adhesive proteins to increase the throughput of in vitro cell adhesion assays, which are currently primarily performed in multiwell plates” (Abstract). Kuschel further teaches “Preparation of Microarrays” (page 524 column 1 paragraph 2). Kuschel teaches that “economic considerations were taken into account when expensive proteins were used as well as technical feasibility of printing these protein solutions with the ink-jet arrayer. Unless otherwise indicated, proteins were spotted at the following concentrations: 200 μg/mL poly-L-lysine, type III collagen, type V collagen, type VI collagen, fibronectin (human cellular), laminin (human placenta), and laminin (EHS); 400 μg/mL BSA…; 100 μg/mL type IV collagen (human placenta), type IV collagen (EHS), fibronectin (human plasma), thrombospondin, and HSPG; 250 μg/mL vitronectin” (page 524 column 1 paragraph 2, and column 2 paragraph 1). Kuschel further teaches that “After microspotting, the slides were stored dry (without dessicant) at 4°C in a microslide storage box” (page 524 column 2 paragraph 2). Kuschel further suggests that an optimal concentration of proteinaceous primary reagent is between 100 µg/ml to 200 µg/ml (“We used such arrays to determine different binding properties between a chondrocyte cell line (27) and primary chondrocytes on type III collagen. For both cell lines, up to a protein coating concentration of 100 μg/mL, the number of cells increased with increasing coating concentrations (Figure 5). At a coating concentration of 100 μg/mL and above, both cell lines reached a plateau in cell numbers binding to the microspots. A reason for this could be that the nitrocellulose surface was saturated with protein at these high coating concentrations or cells could not increase their avidity to the protein when the protein was present above a certain density. The number of attached cells did not significantly differ between the two cell types at a coating concentration of 100 μg/mL and above. This indicates that a difference in adhesion cannot be detected at a concentration of 200 μg/mL, which is the coating concentration used for most proteins in our ECM microarray. At lower concentrations, however, the primary cells reached half-maximal binding at approximately six times lower coating concentrations than the cell line” (page 527 column 3 paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Terbrueggen to rely on the coating solution comprising from about 100 µg/ml to about 400 µg/ml proteinaceous primary reagent taught by Kuschel because Kuschel suggests 100 µg/ml to 200 µg/ml is an optimal concentration for proteinaceous primary reagent for multiplex binding assays. And as such, a person having ordinary skill in the art would be motivated to make such a modification because it would be a simple matter of applying a known technique to a known method. In this case, both Terbrueggen and Kuschel teach a method of preparing a bifunctional assay surface comprising dispensing a coating solution comprising a proteinaceous primary reagent and incubating the coated assay surface under conditions in which the proteinaceous primary reagent is immobilized on the assay surface. Kuschel simply applies the art-recognized technique of using from about 100 µg/ml to about 400 µg/ml proteinaceous primary reagent. Therefore, a person having ordinary skill in the art would have found it obvious to apply the technique taught by Kuschel to the base method taught by both references. A person having ordinary skill in the art would have had a reasonable expectation of success because Kuschel reports data showing that a coating solution of proteinaceous primary reagent is optimal between 100 µg/ml to 200 µg/ml and both Kuschel and Terbrueggen teach a method of preparing a bifunctional assay surface comprising dispensing a coating solution comprising a proteinaceous primary reagent and incubating the coated assay surface under conditions in which the proteinaceous primary reagent is immobilized on the assay surface.
New Rejections
Claims 9-10 and 72-75 are rejected under 35 U.S.C. 103 as being unpatentable over Kenten et al. (WO 2020227016 A1)-Cite No. 2 of IDS dated 10/19/2022 ("Kenten") as evidenced by Laxman et al. Cell 154, 416–429, July 18, 2013 http://dx.doi.org/10.1016/j.cell.2013.06.043 (“Laxman”).
Regarding claim 9, Kenten teaches a method of preparing a bifunctional assay surface, the method comprising:(a) dispensing an overcoating solution comprising a thiol-containing secondary reagent (“the washing or blocking step comprises adding the wash or blocking solution to the surface ( e.g., 50 uL of solution per well for a 96-well assay plate)” page 63 lines 21-22, “the wash solution includes a thiol-containing compound” page 63 line 27) onto a carbon-containing assay surface on which one or more proteinaceous primary reagents are immobilized to form a coated assay surface, (“In one aspect, the capture oligonucleotide is covalently bound to a protein and immobilization on the support surface is achieved through adsorption of the protein to the support surface. Examples of proteins that may be used include an albumin, … an immunoglobulin or another protein selected for its ability to adsorb to the support surface” page 52 lines 1-9, “the carbon-based support surface is pretreated with a protein” page 63 lines 8-9). Kenten further teaches (b) incubating the coated assay surface under conditions in which the thiol- containing secondary reagent is immobilized on the carbon-containing assay surface through a thiol group (“and incubating for 30 to 60 minutes. The incubation temperature may be any convenient temperature, e.g., room temperature or 37°C. The incubation may take place while shaking the surface” page 63 lines 22-24, “the wash solution includes a water-soluble thiol containing compound, for example, cysteine, at great molar excess over the capture oligonucleotides (at least 10,000x), which allows the thiol-group of the thiol containing compound to bind and outcompete the loose capture oligonucleotides for binding to available sites on the surface.” page 135 lines 26-29). Kenten further suggests wherein the thiol-containing secondary reagent comprises a thiolated oligonucleotide (“In one aspect, the wash or blocking solution includes… yeast tRNA” page 64 lines 25 and 30). Note that although Kenten fails to use the language “thiolated oligonucleotide” the teaching of using yeast tRNA inherently provides a thiolated oligonucleotide as evidenced by Laxman. Laxman teaches that yeast tRNA naturally undergo tRNA thiolation (“Sulfur Amino Acids Regulate Translational Capacity and Metabolic Homeostasis through Modulation of tRNA Thiolation” Title, “tRNA thiolation is important for growth” Abstract, “studies in yeast link these tRNA modifications to nutrient-dependent responses” page 417 col. 1 para. 2, “Of 274 yeast tRNA genes, 30 (10.5%) encode just the three tRNAs with thiolated uridines (UUU, UUC, and UUG anticodons), out of 61 anticodon tRNAs” page 426 col. 1 para. 2). Kenten further suggests the thiolated oligonucleotide reduces cross-contamination, which is a problem in the field (“it is believed that non-specific hybridization can be the result of the probes hybridizing to the target nucleotide sequence and remaining hybridized without ligation, which results in a signal that is not due to a ligation reaction product, but a non-specific signal referred to as bridging background” page 86 lines 27-31 and page 87 lines 1-2, “Other blocking agents that were useful for reducing cross-contamination (data not shown)… include…yeast tRNA” page 209 line 26 and page 210 line 1). Kenten further teaches that the thiolated oligonucleotide can be used during manufacturing of arrays, prior to packaging of the arrays, or just prior to use of the arrays (“It should be noted that the blocking and washing step can be carried out during manufacturing of arrays and prior to packaging of the arrays. The best performance, however, is achieved if this step is carried out just prior to use of the arrays” page 210 lines 6-8).
Kenten fails to teach wherein the thiol-containing secondary reagent comprises a thiolated oligonucleotide in a manner consistent with anticipation, i.e. there is some picking and choosing involved in order to arrive at the thiolated oligonucleotide. Kenten teaches the thiolated oligonucleotide, i.e. “yeast tRNA” (page 64 line 30) from a list of other possible reagents to be used in the overcoating solution.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have tried picking the thiolated oligonucleotide (“yeast tRNA” page 64 line 30) reagent from the finite list of possible overcoating solution reagents taught by Kenten because Kenten teaches that these help reduce cross-contamination in assays which is a problem in the field. A person having ordinary skill in the art would have had a reasonable expectation of success because Kenten teaches that the thiolated oligonucleotide can be used during manufacturing of arrays, prior to packaging of the arrays, or just prior to use of the arrays.
Regarding claim 10, Kenten addresses the method of claim 9 as discussed above.
Kenten further suggests comprising dispensing from about 10 µL to about 100 µL of the overcoating solution comprising the thiol-containing secondary reagent onto the carbon-containing assay surface (“the washing or blocking step comprises adding the wash or blocking solution to the surface ( e.g., 50 uL of solution per well for a 96-well assay plate)” page 63 lines 21-22).
Regarding claims 72-75, Kenten addresses the method of claim 9 as discussed above.
Kenten further suggests wherein the proteinaceous primary reagent comprises a proteinaceous capture reagent that specifically binds to a target analyte, wherein the proteinaceous capture reagent is a peptide, an antigen, an antigen-binding substance, an antibody, an antigen-binding fragment or a combination thereof, wherein the proteinaceous primary reagent, the thiol- containing secondary reagent, or both comprises a member of a binding pair, wherein the binding pair is complementary oligonucleotides or antibody and antigen (page 52 lines 1-9, page 64 lines 25-26 and 28-30).
New Rejection
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Kenten as applied to claim 9 above, and further in view of Terbrueggen.
Regarding claim 11, Kenten addresses the method of claim 9 as discussed above.
Kenten fails to teach wherein the overcoating solution comprises from about 0.01 µM and up to about 20 µM thiol-containing secondary reagent.
Terbrueggen teaches “devices that allow for simultaneous multiple biochip analysis. In particular, the devices are configured to hold multiple cartridges comprising biochips comprising arrays such as nucleic acid arrays, and allow for high throughput analysis of samples” (Abstract). Terbrueggen teaches that “the biochip cartridge comprises a detection chamber with an array of electrodes” (page 2 paragraph 4) “preferably gold electrodes” (page 31 paragraph 2). Terbrueggen teaches that the gold electrodes contain carbon, i.e., a carbon-containing assay surface from the added organic brighteners (grain refining additives) (page 31 last paragraph and page 32 paragraph 1). Terbrueggen teaches a method of preparing a bifunctional assay surface, the method comprising: a. dispensing a coating solution comprising a proteinaceous primary reagent and a thiol-containing secondary reagent onto a carbon-containing assay surface to form a coated assay surface (page 31 paragraph 2, page 38 paragraph 3, page 54 paragraph 4, page 54 last paragraph, page 40 last paragraph, page 41 paras. 1-2 and 4, page 42 paras. 2 and 4, page 43 para. 4, page 58 paras. 2-3). Terbrueggen further teaches dispensing an overcoating solution comprising a thiol-containing secondary reagent onto the carbon-containing assay surface on which one or more proteinaceous primary reagents are immobilized to form a coated assay surface (page 55 para. 1). Terbrueggen teaches a step of incubating the coated assay surface under conditions in which the proteinaceous primary reagent and the thiol-containing secondary reagent is immobilized on the assay surface (page 55 paragraph 1 ). Terbrueggen further suggests wherein the thiol-containing secondary reagent is immobilized on the assay surface through a thiol group of the thiol-containing secondary reagent (page 39 paragraph 1, page 41 para. 1, page 42 para. 4). Terbrueggen further teaches that “the composition of the binding ligand will depend on the composition of the target analyte… When the analyte is a protein, the binding ligands include proteins” (page 57 para. 2). Terbrueggen further teaches that “is known in the art, any number of techniques may be used to attach a proteinaceous capture binding ligand to an attachment linker. A wide variety of techniques are known to add moieties to proteins” (page 58 para. 4). Terbrueggen further suggests wherein the overcoating solution comprises from about 0.01 µM and up to about 20 µM thiol-containing secondary reagent (“the deposition solution is removed and a solution of diluent molecule only (from about 1 μM to 10 mM, … in organic solvent is added” page 55 paragraph 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Kenten to rely on the overcoating solution comprising from about 0.01 µM and up to about 20 µM thiol-containing secondary reagent taught by Terbrueggen because it would have been a simple matter of applying a known technique to a known method. In this case, Kenten and Terbrueggen both teach the base method of preparing a bifunctional assay surface comprising steps (a)-(b). Terbrueggen simply applies the art-recognized technique of the overcoating solution comprising from about 0.01 µM and up to about 20 µM thiol-containing secondary reagent. Therefore, a person having ordinary skill in the art would have found it obvious to apply the art-recognized technique of Terbrueggen to the base method taught by both Kenten and Terbrueggen. One would have been motivated to make such a modification because Terbrueggen suggests this facilitates high throughput analysis of samples. A person having ordinary skill in the art would have had a reasonable expectation of success because both Kenten and Terbrueggen are drawn to methods of preparing a bifunctional assay surfaces.
Response to Arguments
Applicant's arguments filed 5/15/2026 have been fully considered but they are not persuasive.
Regarding the previous 102 rejections from the previous Office Action (11/18/2025),
Applicant argues that “Kenten discloses a thiolated capture oligonucleotide and a washing/blocking buffer which can comprise a thiol-containing compound (e.g., cysteine), and in separate embodiments, comprises an oligonucleotide (e.g., salmon sperm DNA)…Since each and every element as set forth in claim 9 is not disclosed, either expressly or inherently described, in Kenten, claim 9 is not anticipated by Kenten” (page 7 last paragraph and page 8 paras. 1-2).
This is found persuasive and the 102 rejection is withdrawn. However, new grounds of rejection are set forth above under 103 (see rejection above). In short, Kenten also teaches “yeast tRNA” which is reasonably interpreted as a thiolated oligonucleotide as evidenced by Laxman. Therefore, it would have been obvious to try picking yeast tRNA as the thiolated oligonucleotide from the finite list of possible reagents taught by Kenten, thereby addressing the claim (see rejection above for the complete analysis).
Regarding the 103 rejections,
Applicant argues that “As acknowledged by the Office, Terbrueggen does not disclose a deposition solution comprising both a proteinaceous primary reagent and a thiol-containing secondary reagent. OA, p. 2. The Office has not adequately presented evidence why this combination would have been prima facie obvious in view of the technical challenges associated with dispensing and assaying two different reagents on the same surface, such as sensitivity of the assay and its robustness” (page 9 para. 1).
However, Office Action (11/18/2025) page 2 states that Terbrueggen does not disclose the solution comprising both a proteinaceous primary reagent and a thiol-containing secondary reagent “given that the appropriate citations and analysis were not made of record in the previous Office Action… new grounds of rejection under 103 are set forth below”. The Office Action (11/18/2025) states that Terbrueggen teaches both a proteinaceous primary reagent and a thiol-containing secondary reagent, and the Office Action (11/18/2025) does provide a full obviousness analysis, including that “[a] person having ordinary skill in the art would have had a reasonable expectation of success given that Terbrueggen teaches that there are a wide variety of techniques known to add moieties to proteins” (page 11 of Office Action (11/18/2025)). The rejection is maintained, see the 103 rejections over Terbrueggen above.
Applicant further argues that “The assay surfaces prepared by the claimed methods were shown to have equivalent or better performance and sensitivity as compared to bifunctional surfaces in the absence of the secondary reagent or surfaces in which the secondary reagent was immobilized via a non-thiol group in the presence of a proteinaceous primary reagent…Assay sensitivity was improved about 5-fold for all conditions with an anchor oligonucleotide compared to no anchor control…No sensitivity loss was observed and variability was not increased as compared to the standard assay format” (page 9 paras. 2-4 and page 10 para. 1).
However, as stated above, given that Terbrueggen discloses every limitation of claim 1, including both a proteinaceous primary reagent and a thiol-containing secondary reagent, the arguments regarding the “equivalent or better performance” are not persuasive. Furthermore, as stated above, there is a reasonable expectation of success in including both a proteinaceous primary reagent and a thiol-containing secondary reagent from the teachings of Terbrueggen (see 103 rejection above).
Applicant further argues that “Terbrueggen does not disclose the method of method claim 1 nor does it acknowledge or suggest the advantages of the claimed method. Claim 1 therefore would not have been obvious in view of Terbrueggen” (page 10 para. 2).
However, Terbrueggen does suggest the method of claim 1 (see rejection above). Furthermore, Terbrueggen suggests the method allows “high throughput analysis of samples” (Abstract).
Applicant further argues that “Terbrueggen also does not disclose the features of claim 9” (page 10 para. 3).
However, Terbrueggen is no longer used in the rejection of claim 9. The amendments to claim 9 changed the scope of the claim such that Terbrueggen is no longer considered to address claim 9.
Applicant further argues that “At best, Terbrueggen discloses overcoating an organic solution comprising oligomers or insulators onto an assay surface on which one or more thiol modified DNA were immobilized on the surface. In alternative embodiments, Terbrueggen utilizes proteinaceous capture binding ligands, however, even in this embodiment a thiol-containing secondary reagent comprising an oligonucleotide is not overcoated onto a surface comprising one or more proteinaceous primary reagents” (page 10 para. 5).
However, as stated above, the amendments to claim 9 changed the scope of the claim such that Terbrueggen is no longer considered to address claim 9. Therefore, the arguments drawn to Terbrueggen not teaching “a thiol-containing secondary reagent comprising an oligonucleotide” are not persuasive.
Applicant further argues that “Claims 4, 11, 28, 42, 47, 51, 55, and 72-75 depend directly or indirectly from claim 1 or 9 and therefore would not have been obvious in view of Terbrueggen for at least the same reasons as claim 1 and 9” (page 11 para. 2).
However, contrary to Applicant’s remark, claim 1 is obvious in view of Terbrueggen and claim 9 is obvious in view of Kenten (see new103 rejections above).
Applicant further argues that “As presented above, Terbrueggen is silent on a method of preparing a bifunctional assay surface comprising dispensing a coating solution comprising a proteinaceous primary reagent and a thiol-containing secondary reagent wherein the proteinaceous primary reagent and the thiol-containing secondary reagent are immobilized on the same carbon-containing assay surface, wherein the proteinaceous primary reagent and the thiol-containing secondary reagent are immobilized on the assay surface through different surface chemistries” (page 11 para. 5).
However, contrary to Applicant’s remark Terbrueggen teaches all the limitations of claim 1 as discussed above (see rejection above). In short, Terbrueggen teaches coating a gold electrode (which comprises carbon, see Terbrueggen page 31 last paragraph and page 32 paragraph 1) with a “deposition solution” which contains “thiol modified DNA (i.e. nucleic acid attached to an attachment linker) and thiol diluent molecules (either conductive oligomers or insulators” (page 54 last paragraph) and incubating the coated assay surface (page 55 para. 1). Terbrueggen teaches in page 58 paragraphs 2-3, that “capture binding ligands comprising proteins…can be added” to the thiol modified DNA; thereby providing the claimed “proteinaceous primary reagent” (see obviousness analysis above). The “conductive oligomers or insulators” taught by Terbrueggen provide the thiol-containing secondary reagent claimed given that the oligomers comprise "sulfur containing moieties" (page 42 paras. 2 and 4) and Terbrueggen teaches that “the discussion herein is mainly directed to gold electrodes and thiol-containing monolayer forming species” (page 39 paragraph 1).
Applicant further argues that “A POSA would not have had a reason to modify Terbrueggen with Kuschel to arrive at the claimed invention when all of the recited features of claim 1, from which claim 3 depends, are neither disclosed nor suggested in Terbrueggen and/or Kuschel” (page 11 last paragraph and page 12 para. 1).
However, contrary to Applicant’s remark and as stated in the rejection above, a person having ordinary skill in the art would have had a reason and motivation to modify Terbrueggen with Kuschel, thereby arriving to the claimed invention, with a reasonable expectation of success (see 103 rejection above).
Applicant further argues that “Claim 2, 23, 24, and 38-40 depend directly or indirectly from claim 1 and therefore include each and every feature of claim 1. As presented above, Terbrueggen is silent on a method of preparing a bifunctional assay surface comprising dispensing a coating solution comprising a proteinaceous primary reagent and a thiol-containing secondary reagent wherein the proteinaceous primary reagent and the thiol-containing secondary reagent are immobilized on the same carbon-containing assay surface, wherein the proteinaceous primary reagent and the thiol-containing secondary reagent are immobilized on the assay surface through different surface chemistries. Kenten does not remedy the deficiencies in Terbrueggen and is also silent on the method of claim 1” (page 13 para. 3).
However, contrary to Applicant’s remark Terbrueggen teaches all the limitations of claim 1 as discussed above (see rejection above). Also, contrary to Applicant’s remark and as stated in the rejection above, a person having ordinary skill in the art would have had a reason and motivation to modify Terbrueggen with Kenten, thereby arriving at the claimed invention, with a reasonable expectation of success (see 103 rejection 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 FERNANDO IVICH whose telephone number is (703)756-5386. The examiner can normally be reached M-F 9:30-6:00 (E.T.).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory S. Emch can be reached at (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Fernando Ivich/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
Prosecution Insights