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.
Election/Restrictions
Applicants elected group I and SEQ ID 15 without traverse in the reply filed on 29 July, 2025.
Claims Status
Claims 2-5, 11, 14, and 15 are pending.
Claims 2-5, 11, and 14 have been amended.
Withdrawn Objections
The objection to the disclosure due to the lack of a sequence listing is hereby withdrawn due to amendment.
New Objections
Claim Objections
first objection
Claim 14 is objected to because of the following informalities: applicants have amended the claim, but deletions are just deleted, without showing what was deleted with strikethroughs. Appropriate correction is required.
second objection
Applicant is advised that should claim 3 be found allowable, claim 4 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Withdrawn Rejections
The rejection of claims 1-6, 9, 11, 14, and 15 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is hereby withdrawn due to amendment.
The rejection of claims 1-6, 9, 11, 14, and 15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to uncertainty as to what constitutes a glycine/serine rich linker is hereby withdrawn due to amendment.
The rejection of claims 1-6, 9, 11, 14, and 15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to length limitations paired with arbitrary cutoffs is hereby withdrawn due to amendment.
The rejection of claims 1-6, 9, 11, 14, and 15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to uncertainty as to what a helical promoting motif means is hereby withdrawn due to amendment.
The rejection of claim(s) 2, 3, 5, 9, and 14 under 35 U.S.C. 102(a)(1) or 102(a)(2) as being anticipated by Merriman et al (US 20170044605) is hereby withdrawn due to amendment.
The rejection of claim(s) 2-6, 9, and 14 under 35 U.S.C. 103 as being unpatentable over Merriman et al (US 20170044605, cited by applicants) in view of Guo et al (Mol. Biosyst. (2017)13 p598-606), Chiu et al (Nanoscale (2010) 2 p927-930), and Rohl et al (PNAS (1999) 96 p3682-3687) is hereby withdrawn as duplicative to a rejection that was maintained.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
first rejection
Claims 3-5, 11, 14, and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 14, and claims dependent on it, requires a polymerase enzyme conjugated to the conjugation site. There is no antecedent support for the conjugation site.
response to applicant’s arguments
Applicants state that their amendments have overcome this rejection.
Applicant's arguments filed 14 Nov, 2025 have been fully considered but they are not persuasive.
Applicants have not corrected this issue.
second rejection
Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 mentions a conjugation site, while claim 14, from which it depends, discusses a polymerase enzyme attached to the conjugation site. It is not clear if this is the same conjugation site or if claim 2 has an additional material conjugated to the construct.
response to applicant’s arguments
Applicants state that their amendments have overcome this rejection.
Applicant's arguments filed 14 Nov, 2025 have been fully considered but they are not persuasive.
Applicants have not corrected this issue.
third rejection
Claim 14 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 14 lists multiple percent identities. This makes it unclear which one is the cutoff between embodiments that read on the claim and those that do not.
response to applicant’s arguments
Applicants state that their amendments have overcome this rejection.
Applicant's arguments filed 14 Nov, 2025 have been fully considered but they are not persuasive.
Applicants have corrected this issue for the previously rejected claims, but reintroduced it into claim 14. As it is the same issue, the same rejection is used.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2-5 and 11 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. All of these claims are dependent on claim 14, but this statute requires that a claim be dependent on another claim previously set forth.
response to applicant’s arguments
Applicants state that their amendments have overcome this rejection.
Applicant's arguments filed 14 Nov, 2025 have been fully considered but they are not persuasive.
Applicants have not corrected this issue.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
first rejection
Claim(s) 14 is rejected under 35 U.S.C. 103 as being unpatentable over Merriman et al (US 20170044605, cited by applicants) in view of Guo et al (Mol. Biosyst. (2017)13 p598-606) and Chiu et al (Nanoscale (2010) 2 p927-930).
Merriman et al discuss electronic sensors comprising two electrodes separated by a sensor gap, coupled by a biopolymer bridge and a probe that can interact with a target molecule (abstract). The bridge molecule can self assemble on the electrodes (paragraph 11). These electrodes can be operatively connected to a circuit to detect a change of an electrical property (paragraph 42). The bridge is sized to span the sensor gap using precise molecular subunits (paragraph 52), such as helix turns (paragraph 57). The bridge molecule can be made of amino acid motifs known to form a helix, such as SEQ ID 9 (EAAAK), identical with SEQ ID 1 of the examined claims, which can be modified to have a conjugation site, such as lysine, to bind to the probe molecule (paragraph 61). These can have a metal binding sequence that binds strongly to the metal contacts, such as gold, palladium, or platinum, with sequences such as SEQ IDs 3-5, with C-terminal Ser residues (Gly/Ser rich linker). The probe can be a polymerase (paragraph 65).
The difference between this reference and the rejected claims is that this reference does not discuss a peptide with at least 90% identity to SEQ ID 15.
Guo et al discuss linker lengths (title). In fusion proteins, such as the sequence of Merriman et al, linkers between the various segments can improve folding and stability, enhance expression, and elevate biological activity (p598, 1st column, 1st paragraph). Length has a direct impact on the activity of the fusion protein (p598, 1st column, 1st page), making it obvious to vary the length of the linker to determine the optimum length (MPEP 2144.05(II)). Among the most common linkers used are (Gly-Ser-Gly)n (p598, 2nd column, 1st paragraph). This reference discusses applicant’s elected linker, stating it is one of the most common linkers used.
Chiu et al discusses peptides involved in palladium nanoparticle synthesis (title). Phage display finds a sequence QQSWIPS, which binds specifically to the metal surface (p927, 2nd column, 2nd paragraph). Combined with a teaching of Merriman et al of palladium electrodes and using sequences that bind to those electrodes, this renders obvious using the sequence of Chiu et al.
Therefore, it would be obvious to use the linkers of Guo et al between the segments of Merriman et al, to improve folding, stability, activity, and enhance expression. As this is one of the most commonly used linkers, an artisan in this field would attempt this modification with a reasonable expectation of success.
Furthermore, it would be obvious to use the metal binding peptide of Chiu et al to specifically bind to the palladium electrodes of Merriman et al. As Merriman et al functionally discuss peptides that bind to these electrodes, an artisan in this field would attempt this modification with a reasonable expectation of success.
Chiu et al discusses a peptide of SEQ ID 16, and describes it in a way that makes it obvious to use in the construct of Merriman et al. Thus, the combination of references renders obvious claim 4. Note that duplication or repeating a sequence is not considered a patentable distinction, absent secondary considerations (MPEP 2144.04 (VI)(B)), relevant to applicant’s elected species. This generates a polypeptide that varies by the alanine helix promoting motifs, the conjugation site, and the protease site, which is less than 10% of the peptide. Thus, the combination of references renders obvious claim 14.
response to applicant’s arguments
Applicants state that their amendments have overcome this rejection.
Applicant's arguments filed 14 Nov, 2025 have been fully considered but they are not persuasive.
Applicants have not corrected this issue.
second rejection
Claim(s) 2-5, 11, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Merriman et al (US 20170044605, cited by applicants) in view of Guo et al (Mol. Biosyst. (2017)13 p598-606), Chiu et al (Nanoscale (2010) 2 p927-930), Rohl et al (PNAS (1999) 96 p3682-3687), Stein et al (US 20170315114), To et al (PNAS (2015) 112(11) p3338-3343), Cesaratto et al (J. Biotech. (2015) 212 p159-166), and Strop et al (Chem. Biol. (2013) 20 p161-167).
Merriman et al discuss electronic sensors comprising two electrodes separated by a sensor gap, coupled by a biopolymer bridge and a probe that can interact with a target molecule (abstract). The bridge molecule can self assemble on the electrodes (paragraph 11). These electrodes can be operatively connected to a circuit to detect a change of an electrical property (paragraph 42). The bridge is sized to span the sensor gap using precise molecular subunits (paragraph 52), such as helix turns (paragraph 57). The bridge molecule can be made of amino acid motifs known to form a helix, such as SEQ ID 9 (EAAAK), identical with SEQ ID 1 of the examined claims, which can be modified to have a conjugation site, such as lysine, to bind to the probe molecule (paragraph 61). These can have a metal binding sequence that binds strongly to the metal contacts, such as gold, palladium, or platinum, with sequences such as SEQ IDs 3-5, with C-terminal Ser residues (Gly/Ser rich linker). The probe can be a polymerase (paragraph 65). The bridge molecule itself can be a probe molecule as well (paragraph 67).
Guo et al discuss linker lengths (title). In fusion proteins, such as the sequence of Merriman et al, linkers between the various segments can improve folding and stability, enhance expression, and elevate biological activity (p598, 1st column, 1st paragraph). Length has a direct impact on the activity of the fusion protein (p598, 1st column, 1st page). Among the most common linkers used are (Gly-Ser-Gly)n (p598, 2nd column, 1st paragraph). This reference discusses applicant’s elected linker, stating it is one of the most common linkers used.
Chiu et al discusses peptides involved in palladium nanoparticle synthesis (title). Phage display finds a sequence QQSWIPS, which binds specifically to the metal surface (p927, 2nd column, 2nd paragraph). Combined with a teaching of Merriman et al of palladium electrodes and using sequences that bind to those electrodes, this renders obvious using the sequence of Chiu et al.
As noted above, these references render obvious claim 14.
The difference between the compound of these references and the remaining claims is that the references do not discuss a helix propensity residue or a cleavage site, and does not describe the protease attachment site.
Rohl et al discuss alanine in the context of helices (title). Alanine has a propensity to form helices (p3682, 2nd column, 2nd paragraph). While more alanines will more strongly promote helical structure, even a single one will promote that tertiary structure (fig 2, p3684, 2nd column, top of page). This reference discusses the propensity of alanines to promote a helix.
Stein et al discusses biosensors (title). A protease activity can be detected by the protease digesting a conducting substrate, changing conductivity of the construct (paragraph 162). This reference teaches using a protease sensitive substrate for electrochemical detection of a protease.
To et al discusses a protease sensor (title). As proof of concept, the TEV cleavage sequence was used in their protease scaffold (p3339, 1st column, 2nd paragraph). Cesaratto et al teaches that the substrate for this protease is ENLYFQ-G/S (p159, 1st column, 2nd paragraph).
Strop et al discuss how the location of conjugation affects stability of constructs (title). In the context of antibody-drug conjugates, the location of conjugation significantly affects stability (abstract). Conjugation usually is via Cys or Lys residues (p161, 1st column, 1st paragraph). Engineered cysteines allow a practitioner in this field to conjugate at a specific location (p161, 2nd column, 1st paragraph). Note that the reference discusses embodiments that use Cys residues for conjugation as conventional (p163, 2nd column, 2nd paragraph). This reference discusses using Cys residues for conjugation.
Therefore, it would be obvious to add one or more alanines to either side of the helix of Merriman et al, to promote folding into a helical conformation, as described by Rohl et al. As this reference shows that Ala is a helix forming residue, an artisan in this field would attempt this modification with a reasonable expectation of success.
Furthermore, it would be obvious to add one or more protease sequences to the polypeptide of Merriman et al, to allow for detection of a protease. As Merriman state that the bridge molecule can also be a probe, an artisan in this field would attempt this modification with a reasonable expectation of success.
In addition, it would be obvious to use the TEV protease sequence of To et al as a proof of principle. As this is a very robust protease, an artisan in this field would attempt this sequence with a reasonable expectation of success.
Plus, it would be obvious to use a Cys residue for conjugation of the probe molecule of Merriman et al), rather than the Lys reside of that reference, as a simple substitution of one known element (the Lys conjugation of Merriman et al) for another (the Cys conjugation of Strop et al) yielding expected results (conjugation of the probe molecule). As Strop et al discusses conjugation via Cys as conventional, an artisan in this field would attempt this modification with a reasonable expectation of success.
Finally, as Strop et al teaches that the location of the conjugation affects stability, it would be obvious to try the various locations in the molecule to maximize stability. As this would attempt numerous positions in the molecule, an artisan in this field would attempt this process with a reasonable expectation of success.
Applicant’s elected species, SEQ ID 15, is three copies of SEQ ID 16 (obvious by Chiu et al), separated by GSG linkers (obvious by Guo et al) on either side of the sequence, with the body of the sequence a helix made of repeating motifs of SEQ ID 1 (obvious by Merriman et al), with an alanine on either side of that sequence (obvious by Rohl et al), a protease sequence between two of the binding sequences (obvious by To et al and Stein et al), with a Cys residue in the center to conjugate the polymerase to (obvious by Strop et al). In other words, this is merely a combination of known elements yielding expected results, rendering obvious claims 2-5 and 11.
response to applicant’s arguments
Applicants point out the differences between the primary reference and their claims, that there are a large number of references required to render the claims obvious, there is no articulated motivation to combine, the length of the combination renders it invalid, that the references are from disparate technical domains, the references fail to teach the position of the conjugation site, that folding and conductivity is unpredictable, leaving to a lack of a reasonable expectation of success, that the rejection is based on hindsight reasoning, claim the unexpected result of improved conductivity, failure of others, long felt need, and commercial and research recognition.
Applicant's arguments filed 14 Nov, 2025 have been fully considered but they are not persuasive.
Applicants point out that the primary reference does not anticipate the claims. While true, it is not clear how this overcomes the rejection. There is no requirement that all limitations be found in a single reference for a rejection to be valid under this statute.
Applicants argue that the rejection relies upon a large number of references. That has not been considered sufficient to overcome an obviousness rejection by the courts (MPEP 2145((V)).
Applicants argue that there is no clear motivation to combine. That is not correct. Most of the differences between the primary reference and applicant’s claims use a teaching-suggestion-motivation rationale. The ones that do not use rationales that the courts have determined to be appropriate in other rejections. (MPEP 2145(X)(C)).
Applicants argue that the length of the combination renders it invalid. This is a repetition, using different words, that the rejection uses too many references, which the courts have not found a persuasive argument.
Applicants argue that the references are from disparate technical domains. This is an argument of non-analogous art. The test the courts require is that a reference is analogous if 1) the reference is from the same field of endeavor as the claimed invention, even if it addresses a different problem, or 2) the reference is reasonable pertinent to the problem faced by the inventor (MPEP 2141.01(a)(I)). Applicant’s field of endeavor is detection of chemical moieties – that is the utility of their invention. Merriman et al, Stein et al, and To et al all are drawn to detection of chemical moieties; they clearly pass the first test. Merriman et al discusses using a helical sequence as part of a fusion protein in a detection system, so Guo et al (discussing linkers in fusion proteins) and Rohl et al (alanine in promoting helicity) are clearly relevant. Merriman et al also discusses binding to metal electrodes and conjugation of a detector molecule (the protease), clearly rendering Chiu et al (alternative metal binding sequences) and Strop et al (stability of conjugates) relevant to applicant’s problem.
Applicants argue that the references fail to teach the position of the conjugation site. Strop et al suggests that the position of the conjugation site influences stability, rendering obvious optimizing the location of the conjugation site.
Applicants argue that folding and conjugation is unpredictable, leading to a lack of a reasonable expectation of success. Applicants have not explained how any of the modifications in the rejection would be expected to cause the conjugate to misfold; note that two modifications, the linker of Guo et al and the alanines of Rohl et al, are explicitly included to increase the ability of the material to fold properly. A mere statement of unpredictability is not sufficient to overcome the rejection (MPEP 2145(I)).
Applicants argue that the rejection is based on hindsight reasoning. The courts have ruled that if the rejection takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a rejection is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Applicants have not pointed to any feature in the rejection that is not obtained from the cited references, rather than applicant’s disclosure.
Applicants argue the alleged unexpected result of increased conductivity. There are a number of issues with this argument. First, it is not clear that there is a statistically significant difference. Fig 20 shows the conductivity of two separate peptides over multiple trials, with a large degree of overlap. It is the responsibility of applicants to demonstrate the results are statistically different (MPEP 716.02(b)). Second, unexpected results are compared to the closest prior art (MPEP 716.02(e)), which uses the same helix repeating sequence (EAAAR) as SEQ ID 15. Third, unexpected results must be commensurate in scope with the claimed invention (MPEP 716.02(d). It is not clear if the variability allowed by claim 15 impacts this parameter.
Applicants argue failure of others. This has not been demonstrated.
Applicants argue long felt need. Applicants have not established a long felt need (MPEP 716.04(I)), nor have they explained how Merriman et al fails to meet the long felt need.
Applicants argue commercial and research recognition. No evidence beyond applicant’s word has been given to support this argument (MPEP 716.01(c)(II)).
third rejection
Claim(s) 2-5, 11, 14, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Merriman et al (US 20170044605, cited by applicants) in view of Guo et al (Mol. Biosyst. (2017)13 p598-606), Chiu et al (Nanoscale (2010) 2 p927-930), Rohl et al (PNAS (1999) 96 p3682-3687), Stein et al (US 20170315114), To et al (PNAS (2015) 112(11) p3338-3343), Cesaratto et al (J. Biotech. (2015) 212 p159-166), Strop et al (Chem. Biol. (2013) 20 p161-167), and Pease (Electronic design library, 2001).
Merriman et al discuss electronic sensors comprising two electrodes separated by a sensor gap, coupled by a biopolymer bridge and a probe that can interact with a target molecule (abstract). The bridge molecule can self assemble on the electrodes (paragraph 11). These electrodes can be operatively connected to a circuit to detect a change of an electrical property (paragraph 42). The bridge is sized to span the sensor gap using precise molecular subunits (paragraph 52), such as helix turns (paragraph 57). The bridge molecule can be made of amino acid motifs known to form a helix, such as SEQ ID 9 (EAAAK), identical with SEQ ID 1 of the examined claims, which can be modified to have a conjugation site, such as lysine, to bind to the probe molecule (paragraph 61). These can have a metal binding sequence that binds strongly to the metal contacts, such as gold, palladium, or platinum, with sequences such as SEQ IDs 3-5, with C-terminal Ser residues (Gly/Ser rich linker). The probe can be a polymerase (paragraph 65). The bridge molecule itself can be a probe molecule as well (paragraph 67).
Guo et al discuss linker lengths (title). In fusion proteins, such as the sequence of Merriman et al, linkers between the various segments can improve folding and stability, enhance expression, and elevate biological activity (p598, 1st column, 1st paragraph). Length has a direct impact on the activity of the fusion protein (p598, 1st column, 1st page). Among the most common linkers used are (Gly-Ser-Gly)n (p598, 2nd column, 1st paragraph). This reference discusses applicant’s elected linker, stating it is one of the most common linkers used.
Chiu et al discusses peptides involved in palladium nanoparticle synthesis (title). Phage display finds a sequence QQSWIPS, which binds specifically to the metal surface (p927, 2nd column, 2nd paragraph). Combined with a teaching of Merriman et al of palladium electrodes and using sequences that bind to those electrodes, this renders obvious using the sequence of Chiu et al.
Rohl et al discuss alanine in the context of helices (title). Alanine has a propensity to form helices (p3682, 2nd column, 2nd paragraph). While more alanines will more strongly promote helical structure, even a single one will promote that tertiary structure (fig 2, p3684, 2nd column, top of page). This reference discusses the propensity of alanines to promote a helix.
Stein et al discusses biosensors (title). A protease activity can be detected by the protease digesting a conducting substrate, changing conductivity of the construct (paragraph 162). This reference teaches using a protease sensitive substrate for electrochemical detection of a protease.
To et al discusses a protease sensor (title). As proof of concept, the TEV cleavage sequence was used in their protease scaffold (p3339, 1st column, 2nd paragraph). Cesaratto et al teaches that the substrate for this protease is ENLYFQ-G/S (p159, 1st column, 2nd paragraph).
Strop et al discuss how the location of conjugation affects stability of constructs (title). In the context of antibody-drug conjugates, the location of conjugation significantly affects stability (abstract). Conjugation usually is via Cys or Lys residues (p161, 1st column, 1st paragraph). Engineered cysteines allow a practitioner in this field to conjugate at a specific location (p161, 2nd column, 1st paragraph). Note that the reference discusses embodiments that use Cys residues for conjugation as conventional (p163, 2nd column, 2nd paragraph). This reference discusses using Cys residues for conjugation.
As noted above, these rejections render obvious claims 2-5, 11, and 14.
The difference between these references and the remaining claim is that this reference does not specify a transimpedance amplifier.
Pease discusses transimpedance amplifiers (title). These are quite useful to amplify a signal from a sensor (3d page, 1st paragraph). This reference discusses using transimpedance amplifiers to amplify a signal from a sensor.
Therefore, it would be obvious to use the transimpedance amplifier of Pease to amplify the signal of the sensor of Merriman et al. As Merriman et al discusses additional circuitry in their system for similar purposes, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants have not argued this rejection.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 2-5, 11, and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-5 of copending Application No. 18/843,280 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the competing claims anticipate the examined claims.
Competing claim 1 describes a sensor comprising a bridge molecule between an electrode with a probe molecule connected to the bridge molecule, while claim 3 specifies a conjugation site for the probe. Competing claim 4 specifies that the probe is a polymerase, while competing claim 5 specifies a Markush group including SEQ ID 18, which comprises SEQ ID 15 of the examined claims. While the competing claims only mention one electrode, duplication of parts is not a patentable distinction (MPEP 2144.03(VI)(B)).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
response to applicant’s arguments
Applicants argue that the competing claims have the same priority date as the examined claims, and that they will file a terminal disclaimer once the claims in both applications are found allowable.
Applicant's arguments filed 14 Nov, 2025 have been fully considered but they are not persuasive.
It is not clear how the common priority date renders the rejection invalid. Applicants have pointed to no law, regulation, or court case showing that the fact pattern leads to the rejection being invalid.
Applicants have stated that they will file a TD to overcome the rejection. However, until the TD is filed (or the rejection overcome in some other way), it will remain valid.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
Examiner interviews are available via telephone 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, Melissa Fisher can be reached at 571-270-7430. 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.
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658