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 .
Claim Status
Claims 1-21 are pending and under examination. Claims 1, 3, 6, 9-10, 15-17, and 20-21 have been amended. Claims 1 and 21 are independent claims.
Response to Arguments
Objections Withdrawn
The objection to claims 3, 6, 12, 15, 16 because of the minor informalities is withdrawn.
Rejections Maintained
The rejection of claim 21 under 35 U.S.C. 103 as being unpatentable over Lin et al. (US 2012/0316086 A1, published Dec. 13, 2012, on IDS 10/14/2022) in view of Gao et al. (Nucleic Acids Research, published 2006) and Bowen et al. (US 2013/0116153 A1, published May 9, 2013, on IDS 10/14/2022) is maintained as Applicant did not argue the rejection in their remarks nor make meaningful amendments to the claim.
The rejection of claims 1-20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn following Applicant’s amendments.
The rejection of claims 1-20 under 35 U.S.C. 103 as being unpatentable over Lin et al. (US 2012/0316086 A1, published Dec. 13, 2012, on IDS 10/14/2022) in view of Gao et al. (Nucleic Acids Research, published 2006) and Bowen et al. (US 2013/0116153 A1, published May 9, 2013, on IDS 10/14/2022) is withdrawn following Applicant’s amendments and remarks, specifically regarding the motivation to combine Gao with Bowen and Lin.
New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 15-17 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 15, for which claims 16 and 17 depend, depends upon claim 1213, which does not exist, and therefore does not supply any limitations for claims 15 to further limit. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Interpretation
Claim 15 is examined as if the claim depended on claim 12, which the claim depended upon in the prior claim set. This dependency is further continued for examination of claims 16 and 17 which depend from claim 15.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Applicant’s arguments, filed 06/05/2026, with respect to the rejection(s) of claims 1 -20 under 35 U.S.C. 103 have been fully considered and are persuasive. Specifically, Applicant argues that Gao does not provide a sufficient articulated reason why a person of ordinary skill in the art would have selected the claimed salt concentration ranges for the template attachment and primer attachment steps of claims 1 and 12, respectively, and that Gao’s disclosure is directed to the effect of ionic strength on DNA hybridization kinetics rathe than on surface loading density or occupancy at a discrete capture site. The Examiner agrees.
Therefore, the rejection of claims 1-20 under 35 U.S.C. 103 as being unpatentable over Lin et al. (US 2012/0316086 A1, published Dec. 13, 2012, on IDS 10/14/2022) in view of Gao et al. (Nucleic Acids Research, published 2006) and Bowen et al. (US 2013/0116153 A1, published May 9, 2013, on IDS 10/14/2022) is withdrawn following Applicant’s amendments and remarks.
However, upon further consideration, a new ground(s) of rejection is made.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over under Bowen et al. (US 2013/0116153 A1, published May 9, 2013, on IDS 10/14/2022) in view of Lin et al. (US 2012/0316086 A1, published Dec. 13, 2012, on IDS 10/14/2022) and Herne et al. (“Characterization of DNA Probes Immobilized on Gold Surfaces”, J. Am. Chem. Soc., 1997, 119,8916-8920).
Regarding claim 1, Bowen teaches a method of preparing a substrate for sequencing, comprising forming an array of base pads at predetermined sites on a substrate, wherein individual base pads are configured to capture a nucleic acid molecule and placing a nucleic acid molecule capture substance over each of the base pads (see Bowen [0006] - [0008]). Bowen further teaches that a porous attachment layer is placed over the base pads, configured to attach primer oligonucleotides used to prime amplification of capture template, distinct from the capture substance used to bind the template directly to the base pad (see Bown [0080] - [0084]). Thus, Bowen teaches a surface comprising a first plurality of bonding sites for capturing template polynucleotides and a second plurality of bonding sites for capturing primer oligonucleotides, as recited in claim 1.
Bowen further teaches contacting a solution comprising template polynucleotides with the base pad bearing surface and attaching the template polynucleotides to the surface via covalent or non-covalent bonding, including via biotin-streptavidin/avidin capture or click chemistry linkages (see Bowen [0079], [0083], [0101]). Thus, Bowen taches “a method of preparing a substrate for sequencing, comprising contacting a first buffer solution comprising template polynucleotides with a surface of the substrate wherein the surface of the substrate comprises a first plurality of bonding sites for capturing template polynucleotides and a second plurality of bonding sites for capturing primer oligonucleotides and attaching the template polynucleotides to the surface of the substrate by forming covalent bonding or non-covalent bonding between the template polynucleotides and the first plurality of the bonding sites of the surface” as recites in claim 1.
Lin similarly teaches methods for preparing sequencing substrates comprising contacting a solution comprising template polynucleotides with a surface of a substrate having bonding sites for capturing nucleic acids and attaching the template polynucleotides to the surface via covalent or non-covalent interactions (see Lin [0040] - [0044], [0060] - [0068]). Lin further teaches that such substrates comprise functionalize surfaces having immobilized oligonucleotides that serve as primers for sequencing reactions thereby providing multiple bonding sites for nucleic acid interactions, including two or more populations of bonding sites (see Lin [0060] - [0068], [0073]). Thus, Lin teaches “a method of preparing a substrate for sequencing, comprising: contacting a first buffer solution comprising template polynucleotides with a surface of the substrate, wherein the surface wherein the surface of the substrate comprises a first plurality of bonding sites … and a second plurality of bonding sites; and attaching the template polynucleotides to the surface of the substrate by forming covalent bonding or non-covalent bonding between the template polynucleotides and first plurality of bonding sites of the surface. ”
Thus, Lin and Bowen teach “a method of preparing a substrate for sequencing, comprising: contacting a first buffer solution comprising template polynucleotides with a surface of the substrate.” Furthermore, Lin teaches using two populations of bonding sites (see Lin [0073]) reading “wherein the surface of the substrate comprises a first plurality of bonding sites … and a second plurality of bonding sites; and attaching the template polynucleotides to the surface of the substrate.”
However, neither Lin nor Bowen explicitly disclose that the template polynucleotides are contacted with the substrate using buffer solution comprising a total salt concentration of about 100 mM or less.
Herne teaches that the concentration of buffer salt (KH2PO4) used during immobilization of single-stranded DNA onto a surface has a direct and quantifiable effect on the resulting surface density of bound DNA. Specifically, Herne reports that X-ray photoelectron spectroscopy N 1s peak area, a direct measure of the quantity of DNA adsorbed to the surface, grows 5-fold as buffer concentration is increased from 2.7 x 10-4 M to 1.0 M KH2PO4 with essentially no adsorption accruing in the absence of buffer salt (see Herne pg. 8918 3rd para., Fig. 2 and 3). Herne further discloses the underlying mechanism for this relationship “we postulate that intermolecular electrostatic repulsion between neighboring strands of DNA is minimized under the high ionic strength conditions, as the charged strands are better
electrostatically shielded, thus allowing higher surface coverages” (see Herne pg. 8918 3rd para.). Herne additionally demonstrates that surface density directly governs the accessibility and behavior of individual capture sites. A surface prepared with maximal DNA coverage was found to be functionally inhibited, exhibiting no detectable hybridization activity, which Herne attributes to “steric and electrostatic factors” arising from overly dense packing of bound strands (see Herne pg. 8919 4th para.). This confirms that ionic strength during surface immobilization is a result-effective variable directly controlling the density and accessibility of nucleic acid molecules bound at a given surface location, and that reduced ionic strength predictably yields reduced, more sparsely distributed surface occupancy.
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to employ a first buffer solution having a total salt concentration of 100 mM or less, a concentration falling within the low-ionic strength regime shown by Herne to correspond to substantially reduced DNA surface coverage relative to the higher-concentration conditions tested, for the template-polynucleotide contacting step of Bowen’s capture method. Bowen itself recognizes the importance of limiting each capture site to a single captured template molecule, teaching that “certain embodiments of the present disclosure relate to capture of a single molecule of interest per site on a microarray” (see Bowen [0069]), and that site design and capture moiety valency are deliberately engineered towards this end “if the number of binding moieties on the DNA is equal or greater than the number of capture moieties on the pad, one, and only one, DNA molecule can bind to a pad… Steric hindrance may prevent multiple DNA molecules from binding to the same gold pad” (see Bowen [0111]). Bowen further discloses multiple strategies specifically directed at maximizing the likelihood of single-template occupancy per site, including multidentate capture ligands and dual-end template capture schemes (see Bowen [0112]-[0116]). A person of ordinary skill in the art, already motivated by Bowen’s own disclosure of limiting templates captured at each discrete site to a single molecule, would have recognized in Heren’s teaching a further, complementary tool for achieving that same goal. Because Herne demonstrates that lower buffer ionic strength predictably and controllably reduces DNA surface density through well-understood electrostatic screening mechanism, a general physiochemical property of the negatively charged phosphate backbone common to all single-stranded DNA regardless of the specific surface chemistry employed. A skilled artisan would have been motivated to employ a low ionic strength buffer during Bowen’s template contacting step as an additional or alternative means of suppressing multiple templates from binding at a given capture site, complementing Bowen’s own strategies. Because electrostatic screening is a general property of the negatively charged nucleic acid backbone common to single-stranded DNA regardless of capture chemistry, a skilled artisan would have had a reasonable expectation of success in applying Herne’s ionic strength teaching to Bowen’s capture architecture. Selection of the specific claimed range of 100 mM or less, being within and at the low end of the ionic strength range over which Herne demonstrates a clear, monotonic, and quantified relationship between salt concentration and surface coverage, would have been a matter of routine optimization of a recognized result-effective variable. See In re Aller, 220 F.2d 454, 105 USPQ 233 (CCPA 1955), MPEP 2144.05(II).
Accordingly, claim 1 would have been obvious over the combined teachings of Bowen Herne, and Lin.
Regarding claim 12, Bowen further teaches that primer oligonucleotides are attached to the porous attachment layer disposed over the base pads, separately from the template-capture step, in order to prime subsequent bridge amplification of the captured template (see Bowen [0083]-[0084]). Bowen additionally discloses that such primers may include distinct P5 and P7 adapter sequences forming a primer lawn on the attachment layer (see Bowen [0115]). Thus, Bowen teaches contacting a second buffer solution comprising primer oligonucleotides with the surface of the substrate and attaching the primer oligonucleotides via covalent or non-covalent bonding to the second plurality of bonding sites, as recited in claim 12. Lin similarly teaches contacting oligonucleotides with the substrate surface and immobilizing them to the gel layer to serve as amplification primers (see Lin [0073], [0077]), reinforcing this teaching.
Neither Bown nor Lin explicitly discloses that the primer oligonucleotides are contacted with the substrate using a second buffer solution comprising a total salt concentration of 250 mM or greater.
As discussed above in respect to claim 1, Herne teaches that increasing buffer ionic strength during nucleic acid immobilization increases the resulting surface density of bound oligonucleotide, with the data in Herne’s Figure 3 indicating that maximal surface coverage is achieved at buffer concentrations exceeding approximately 0.4 M, a concentration within, and above the floor of the range recited in claim 12.
It would have been obvious to one of ordinary skill in the art to employ a second buffer solution having a total salt concentration of about 250 mM or greater for the primer-grafting step of Bowen’s metho. A person of ordinary skill in the art would have been motivated to select a comparatively high ionic strength for this step because, in contrast to the template-capture step (for which limited, controlled surface density is desirable, as discussed above), a dense and robust primer lawn is understood to be beneficial for efficient priming of bridge amplification and formation of a clonal nucleic acid cluster at each capture site, precisely the outcome Herne’s data associates with higher buffer ionic strength. A skilled artisan applying Herne’s discloses electrostatic screening mechanism would have had a reasonable expectation that increasing the salt concentration of the primer-contacting buffer towards or above the range shown by Herne to yield maximal surface coverage would predictably increase primer density and thereby improve amplification efficiency. Selection of the specific claimed threshold of 250 mM or great, falling within the higher-ionic strength regime associated with maximal coverage in Herne, would have been a matter of routine optimalization of a recognized result effective variable. See In re Aller, 220 F.2d 454, 105 USPQ 233 (CCPA 1955), MPEP 2144.05(II).
In regards to claim 2, Lin teaches using single-stranded primers as the template polynucleotide (see Lin [0052]-[0055]). Lin teaches that nucleic acid templates introduced into sequencing flow cells are typically single-stranded nucleic acids that hybridize to complementary oligonucleotides immobilized on the surface of the sequencing substrate (see Lin [0045]-[0048], [0052]-[0055]). Sequencing-by-synthesis reactions performed on flow-cell substrates require single-stranded templates so that complementary primers can hybridize and polymerase extension can occur from the primer-binding site (see Lin [0060]-[0063]). While Bowen teaches the use of either single- or double-stranded DNA (see Bowen [0074])
In regards to claims 3-5, Lin teaches that the bonding sites of the surface comprise non-covalent bonding sites, including affinity binding and the use of streptavidin and biotin binding pairs (see Lin [0050]). Likewise, Bowen teaches using either covalent or non-covalent linkages (see Bowen [0079], [0086], [0089]-[0098]), and teaches the use of streptavidin and biotin binding pairs (see Bowen [0078]-[0079], [0107], [0111]).
In regards to claims 6-8 and 15-17, Lin teaches sequencing substrates in which nucleic acids are immobilized on functionalized surfaces through chemical attachment reactions between reactive functional groups on the surface and complementary reactive groups on the nucleic acid or linker molecules used for immobilization, including binding surface comprise covalent bonding sites (see Lin [0072]), wherein the covalent bonding sites comprise amino bonding sites (see Lin [0101]), azido bonding sites or NHS ester moieties (see Lin [0102]-[0103]). While Bowen teaches a wide variety of functional groups including aminos, azides, and click-chemistry groups, and thiol bonding (see Bowen [0077]-[0081]). It was well known in the art that biomolecules such as nucleic acids may be immobilized on solid substrates using a wide variety or reactive functional groups including amino, carboxyl, thiol, aldehyde, azide, alkyne, and related click-chemistry groups, as well as enzyme-mediated ligation systems such as sortase-based coupling and protein tag systems (e.g., SNAP-tag or CLIP-tag). These functional groups represent well-known alternative coupling chemistries used to covalently attach biomolecules to functionalized surfaces, many of which are taught by Bowen (see 0079], [0086], [0089]-[0098], and throughout). It therefore would have been obvious to one of ordinary skill in the art at the time of filing to employ any of the recited functional groups as bonding sites on the sequencing substrate in order to covalently attach nucleic acid molecules to the surface as a matter of routine selection among known chemical coupling strategies for biomolecule immobilization.
In regards to claim 9, Bowen teaches that the concentration of template nucleic acids in the solution contacted with the capture surface is a variable that affects the rate and extent of template capture at the sites. Specifically, Bowen discloses the use of molecular crowding agents to increase the effective local concentration of template molecules at the substrate surface, teaching that “adding suitable concentration of PEG solutions of an appropriate molecular weight may concentrate template molecules within the flowcell leading to an enhanced rate of capture at the sites” (see Bowen [0107]), and reporting comparative capture density data demonstrating that increasing effective template concentration at the surface increased site occupancy from approximately 200K/mm2 to greater than 900K/mm2 (see Bowen [0107]).This confirms that the concentration of template polynucleotides available for capture at the substrate surface is a recognized result-effective variable directly affecting the degree of template loading achieved.
Bowen further teaches, as discussed above with respect to claim 1, that capture of a single template molecule per site is a desirable design objective and that the number of template molecules made available for capture relative to the number of valency of capture sites govern whether single or multiple molecule occupancy is achieved (see Bowen [0069], [0111]).
While, neither Bowen, Herne, or Lin explicitly discloses a first buffer solution wherein the concentration of template polynucleotides is 10 pM to 2000 pM, it would have been obvious to one of ordinary skill in the art to select a template polynucleotide concentration within the claimed range. A skilled artisan, aware from Bowen that the concentration of template molecules available for capture governs the resulting site occupancy density, and further aware from Bowen’s own disclosed objective of achieving single-template occupancy per capture site, would have recognized template concentration as a parameter to be optimized, alongside buffer ionic strength, towards that same objective. Selecting a dilute picomolar template concentration, such as the claimed 10 pM to 2000 pM, would have been a predictable and routine means of limiting the number of template molecules statistically available to compete for occupancy at any individual capture site, consistent with Bowen’s stated goal of single molecule capture. Absent showing of criticality or unexpected results associated with the specific claimed boundary values, the selection of an operative concentration range for template capture, from among the finite and predictable range of dilute solution concentration suitable for a limited occupancy capture scheme, would have been a matter of routine optimization of a recognized result-effective variable within the level of ordinary skill in the art. See In re Aller, 220 F.2d 454, 105 USPQ 233 (CCPA 1955), MPEP 2144.05(II).
In regards to claim 10, Herne discloses that ssDNA immobilization surfaces were prepared at a pH of 3.8, demonstrating that acidic buffer conditions at approximately pH 3.8 are suitable and effective for immobilizing ssDNA onto a capture surface (see Herne pg. 8917 3rd para.).
Neither Bowen, Herne, nor Lin explicitly discloses a first buffer solution having a pH of 3.5 or less, though it would have been obvious to one of ordinary skill in the art at the time of filing to employ a first buffer solution having a pH of 3.5 or less. Herne’s disclosed working pH of 3.8 is closely proximate to, and immediately adjacent to, the claimed boundary of 3.5 or less. Where the prior art discloses a value or range so close to the claimed range that one of ordinary skill in the art would have expected them to have the same properties, a prima facie case of obviousness exists. See In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). MPEP 2144.05(I). A person of ordinary skill in the art, aware from Heren of immobilization of ssDNA at pH 3.8, would have had a reasonable expectation that immobilization would likewise be effective at pH values marginally below this demonstrated point, including pH values of 3.5 or less, and would be motivated to explore this adjacent, immediately neighboring range as part of routine optimization of buffer pH, a parameter well understood in the art to influence nucleic acid stability and surface binding. Absent a showing that the claimed boundary of 3.5 produces a result that is unexpected or different in kind, rather than degree, from the results obtained at the pH disclosed by Herne, the selection of a pH of 3.5 or less would have been a matter of routine optimization of a recognized result effective variable. See In re Aller, 220 F.2d 454, 105 USPQ 233 (CCPA 1955), MPEP 2144.05(II).
In regards to claim 11, depends on claim 1 and further recites that “the first buffer solution further comprises one or more crowding agents.” Macromolecular crowding agents such as polyethylene glycol (PEG) are well known in the art for user in nucleic acid hybridization and enzymatic reactions involving nucleic acids because such agents increase the effective concentration of macromolecules in solution and promote intermolecular interactions influencing nucleic acid hybridization. Bowen teaches using PEG to encourage molecular crowding and concentrate template molecules leading to enhanced rates of capture (see Fig. 34, [0051], [0107]). A person of ordinary skill in the art would have recognized that adding a crowding agent such as PEG to the buffer solution used during template hybridization in the sequencing method of Lin would increase the efficiency of nucleic acid interactions and surface capture of template molecules. Because crowing agents such as PEG were well known additives in nucleic acid reaction buffers used to enhance hybridization and related reactions, selecting a buffer that further comprises one or more crowding agents would have been an obvious modification of the buffer conditions used in the method of Lin as a matter of routine optimization of reaction conditions.
In regards to claims 13 and 14, Bowen teaches sequencing substrates comprising immobilized oligonucleotides that serve as primers for amplification and sequencing reactions in a flow-cell environment, including methods using multiple types of primer oligonucleotides with distinct primer sequences immobilized of the surfaces to enable amplification and sequencing of nucleic acid templates, including forward and revers primer sequences that correspond to adaptor sequences on the template molecules such as the combination of P5 and P7 paired end primers (see Bowen [0112], [0115]). It was well known in the art at the time of the invention that sequencing by synthesis systems, including those used in flow-cell platforms utilize paired adaptor-specific primer sequences (e.g., P5 and P7 sequences) to facilitate cluster amplification and sequencing of template nucleic acids. Accordingly, selecting primer oligonucleotides comprising P5 and P7 primer sequences represents the use of known, standard sequencing primers in the sequencing system taught by Lin and would have been an obvious design choice for one of ordinary skill in the art.
In regards to claim 18, Lin expressly teaches that the nucleic acid templates immobilized on a sequencing substrate are amplified on the surface to generate clusters of clonal copies of the template polynucleotides for sequencing (see [0052], [0073]).
In regards to claim 19, the claim depends on claim 1 and further recites that “the surface of the substrate comprises a plurality of patterned nanowells.” While Lin teaches sequencing substrates comprising functionalized surfaces for attachment of nucleic acids and subsequent amplification, including patterned surfaces (see Title, Abstract, throughout) and that the surfaces may be in wells of a multiwell plate (see [0032], [0042], [0046]-[0047]), Lin does not expressly teach using a nanowell format.
Bowen however, teaches an alternative substrate architecture for sequencing systems of the type taught by Lin, comprising arrays of discrete, patterned reaction sites including wells having sub-micron dimensions (e.g., less than 1 µm, such as approximately 30-500 nm, or openings of about 100 nm2) configured to localize nucleic acids molecules at defined positions on the substrate surface (see [0082], [0095], [0103]). Such structures constitutes patterned nanowells that confine nucleic acid molecules within discrete locations and enable controlled loading and sequencing of nucleic acid templates. It would have been obvious to one of ordinary skill in the art to modify the sequencing substrate of Lin to include patterned nanowell structures taught by Bowen in order to improve spatial organization of template molecules, reduce cluster overlap, and enhance sequencing accuracy and signal resolution. Furthermore, one would expect a high likelihood of success as both references are directed to sequencing substrate technologies employing related surface chemistries and architecture.
In regards to claim 20, Bowen teaches that the patterned sites are configured to enable capture of single nucleic acid molecules per site, thereby promoting formation of a single template or dominant clonal population at each site, which corresponds to the claimed single-cluster occupancy of nanowells (see Title, [0067], [0069], [0111]). Achieving such occupancy levels represents an expected result of controlling template loading and confinement within discreate wells and would have been an obvious outcome of implementing the patterned nanowell structures taught by Bowen.
Conclusion
No claim is allowed.
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/MATTHEW HAROLD RAYMONDA/Examiner, Art Unit 1684 /AARON A PRIEST/Primary Examiner, Art Unit 1681