DETAILED ACTION
Response to Amendment
Applicant’s response to the office action filed on January 2, 2026 has been entered. The claims pending in this application are claims 41-44 and 46-54. The objections and rejections not reiterated from the previous office action are hereby withdrawn in view of applicant’s amendment filed on January 2, 2026. Claims 41-44 and 46-54 will be examined.
Claim Objections
Claim 41 is objected to because of the following informality: “a processive enzyme” in line 6 should be “the processive enzyme”.
Claim 52 is objected to because of the following informality: “(CMOS”)” should be “(CMOS)”.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
New Matter
Claims 41-44 and 46-54 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
A limitation “the distinguishable signaling features defined by a chemical anomaly to encode information in the synthetic DNA molecule” is added to independent claim 41 and a limitation “wherein the first electrode and the second electrode spaced apart from the first electrode by the electrode gap define a pixel formed in a Complementary Metal-Oxide-Semiconductor (CMOS”)” is added to dependent claim 52. However, nowhere in the specification describes such limitations recited in claims 41 and 52 since the specification does not describe a chemical anomaly and does not describe that the first electrode and the second electrode define a pixel formed in a CMOS sensor array chip and the abbreviation “CMOS” means Complementary Metal-Oxide-Semiconductor. Furthermore, in applicant’s remarks filed on January 2, 2026, applicant does not indicate which parts in the specification support above claim limitations recited in claims 41 and 52. In addition, newly added claim 54 contains a limitation “the encoding information in the synthetic DNA molecule further includes translocating a synthetic DNA molecule through a processive enzyme while the processive enzyme is electrically connected to the sensor to generate at least one signal to correspond to a chemical anomaly included as encoded information”. Although the specification describes that “[T]he method comprises: translocating a synthetic DNA molecule through a processive enzyme, where the processive enzyme is electrically connected in a molecular sensor circuit; and generating signals in a measurable electrical parameter of the circuit, wherein the signals correspond to the encoded information” (see paragraph [0018] of US 2022/0390407 A1, which is US publication of this instant case), paragraph 22 of the specification suggested by applicant does not describe such limitation recited in claim 54 because the specification does not describe that the processive enzyme is electrically connected to the sensor to generate at least one signal to correspond to a chemical anomaly included as encoded information.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application.” MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure” (emphasis added).
Scope of Enablement
Claims 41-44 and 46-54 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for making a DNA information system comprising a synthetic DNA molecule comprising a DNA template strand and distinguishable signaling features bonded thereon, a buffer, and a sensor comprising a first electrode, a second electrode spaced apart from the first electrode by an electrode gap, a processive enzyme conjugated to both the first and second electrodes, and a trans-impedance amplifier electrically connected to at least one of the first and second electrodes, does not reasonably provide enablement for reading the information encoded in the synthetic DNA molecule in the DNA information system recited in claims 41-44 and 46-53 using a sensor comprising a first electrode, a second electrode spaced apart from the first electrode by an electrode gap, any kind of processive enzyme conjugated to both the first and second electrodes, and a trans-impedance amplifier electrically connected to at least one of the first and second electrodes wherein the trans-impedance amplifier is configured to provide an output comprising a measurable electrical parameter when in contact with a buffer solution. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The Nature of The Invention
The claims are drawn to a DNA information system. The invention is a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The Breadth of The Claims
Claims 41-44 and 46-54 encompass a DNA information system comprising: a synthetic DNA molecule comprising a DNA template strand and distinguishable signaling features bonded thereon, the distinguishable signaling features defined by a chemical anomaly to encode information in the synthetic DNA molecule; a buffer solution in contact with the synthetic DNA molecule, the first and second electrodes, and a processive enzyme; and a sensor capable of reading the information encoded in the synthetic DNA molecule, the sensor further comprising: a first electrode; a second electrode spaced apart from the first electrode by an electrode gap; a processive enzyme conjugated to both the first and second electrodes; and a trans-impedance amplifier electrically connected to at least one of the first and second electrodes, the trans-impedance amplifier configured to provide an output comprising a measurable electrical parameter when in contact with the buffer solution; wherein the measurable electrical parameter comprises distinguishable signals corresponding to the encoded information.
Working Examples
The specification provides no working example for reading the information encoded in the synthetic DNA molecule in the DNA information system recited in claims 41-44 and 46-54 using a sensor comprising a first electrode, a second electrode spaced apart from the first electrode by an electrode gap, any kind of processive enzyme conjugated to both the first and second electrodes, and a trans-impedance amplifier electrically connected to at least one of the first and second electrodes wherein the trans-impedance amplifier is configured to provide an output comprising a measurable electrical parameter when in contact with a buffer solution.
The Amount of Direction or Guidance Provided and The State of The Prior Art
The specification provides no working example for reading the information encoded in the synthetic DNA molecule in the DNA information system recited in claims 41-44 and 46-54 using a sensor comprising a first electrode, a second electrode spaced apart from the first electrode by an electrode gap, any kind of processive enzyme conjugated to both the first and second electrodes, and a trans-impedance amplifier electrically connected to at least one of the first and second electrodes wherein the trans-impedance amplifier is configured to provide an output comprising a measurable electrical parameter when in contact with a buffer solution.
Furthermore, there is no experimental condition and/or experimental data in the specification to support the claimed invention. During the process of the prior art search, the examiner has not found any prior art which is related to read the information encoded in the synthetic DNA molecule in the DNA information system recited in claims 41-44 and 46-54 using a sensor comprising a first electrode, a second electrode spaced apart from the first electrode by an electrode gap, any kind of processive enzyme conjugated to both the first and second electrodes, and a trans-impedance amplifier electrically connected to at least one of the first and second electrodes wherein the trans-impedance amplifier is configured to provide an output comprising a measurable electrical parameter when in contact with a buffer solution.
Level of Skill in The Art, The Unpredictability of The Art, and The Quantity of Experimentation Necessary
While the relative skill in the art is very high (the Ph.D. degree with laboratory experience), there is no predictability whether the information encoded in the synthetic DNA molecule in the DNA information system recited in claims 41-44 and 46-54 can be read using a sensor comprising a first electrode, a second electrode spaced apart from the first electrode by an electrode gap, any kind of processive enzyme conjugated to both the first and second electrodes, and a trans-impedance amplifier electrically connected to at least one of the first and second electrodes wherein the trans-impedance amplifier is configured to provide an output comprising a measurable electrical parameter when in contact with a buffer solution.
Since the specification teaches that “signaling feature” refers to “a characteristic of a data-encoding DNA molecule that, when encountered and processed by the processive enzyme of a processive enzyme molecular sensor, produces a signal in a monitored electrical parameter of the sensor circuit, such as current (i). Arrangements of signaling features on a DNA molecule are used to encode information in a synthetic DNA molecule. The broader group of signaling
features herein further comprise both ‘bound groups’ capable of displacement by a processive enzyme of a sensor and ‘perturbing groups’ that are not displaced from the DNA molecule by the processive enzyme. Both types of signaling features on a DNA molecule provide distinct signals in a monitored electrical parameter of the sensor circuit when encountered by the processive enzyme of the sensor. Signaling features comprise, for example, hybridization-bound oligonucleotides, chemical groups conjugated to the DNA, or combinations of such to achieve arrangements of features that produce distinguishable signals when processed by the sensor processive enzyme”, “[F]IG. 5 shows embodiments of a processive enzyme molecular sensor 50 wherein the processive enzyme comprises a polymerase 54 having strand displacing activity. As shown, sensor 50 comprises processive enzyme 54 conjugated at one or more attachment points 55 to a bridge molecule 53 bonded between electrode pairs and spanning the electrode gap 59. The bridge molecule 53 comprises first and second ends functionalized to bond to the electrode pair at conjugation points 51 and 52. In this case, the processive translocation occurs as the polymerase 54 extends the 3′ end of the primed strand 58, and synthesizes the complementary strand 58’ of the underlying template strata. This takes place in a suitable buffer that also supplies dNTPs 56 for the synthesis of the complementary strand, as indicated. In the embodiment shown in FIG. 5, the signaling features 57 are DNA oligonucleotides hybridized to the template strand 58. The strand displacing polymerase 54 will displace and remove these oligonucleotides (as exemplified by the displacement of oligonucleotide 57’) as it translocates in the course of synthesis. Each strand displacement event may generate a signal in the measured current of the circuit, as indicated by perturbations 501, 502 and 503 in the (i) versus (t) plot. The hybridizing oligonucleotides 57 may be DNA or DNA analogs, and may have further groups attached to enhance signaling, such as described further below in the context of FIG. 14”, “[F]IG. 8 shows embodiments of a processive enzyme molecular sensor wherein the processive enzyme 84 comprises an exonuclease also having strand displacing activity. As shown, sensors 80 comprises processive enzyme 84 conjugated at one or more attachment points 85 to a bridge molecule 83 bonded between electrode pairs and spanning the electrode gap 89. The bridge molecule 83 comprises first and second ends functionalized to bond to the electrode pair at conjugation points 81 and 82. In this case, the signaling features comprise DNA oligonucleotides 87 hybridized to the template strand 88. The strand displacing exonuclease
84 will displace and remove these oligonucleotides (such as illustrated by the displacement of 87’) as it translocates and digests the primary strand 88. Each strand displacement event may generate a signal in the measured current of the circuit, as indicated by the perturbations 801,
802, and 803 in the (i) versus (t) plot. The hybridizing oligonucleotides 87 may comprise DNA or DNA analogs, and may further comprise groups attached to enhance signaling, such as described further below in the context of FIG. 14. In various embodiments, some exonucleases may displace oligonucleotides 87 from the primary strand 88 by digesting entirely through the double stranded region of the paired segment, or by digesting only partially through it, at which point the remainder of the oligonucleotide dissociates from the primary strand”, and “[F]IG. 11
shows embodiments of processive enzyme molecular sensors 110 wherein the processive enzyme 114 comprises an exonuclease. As shown, sensor 110 comprises processive enzyme 114 conjugated at one or more attachment points 115 to a bridge molecule 113 bonded between electrode pairs and spanning the electrode gap 119. The bridge molecule 113 comprises first and second ends functionalized to bond to the electrode pair at conjugation points 111 and
112. In this case, the signaling features 117 are perturbing groups on the DNA strand 118. As each perturbing group 117 passes near the exonuclease, it generates a signal in a monitored electrical parameter of the circuit, such as indicated by the perturbations 108, 108’, and 108’’ in the (i) versus (t) plot. The action of the exonuclease 114 on the functionalized DNA 118
produces digestion products 116 as the DNA is digested by the enzyme. The digestion products comprise a mixture of bases and functionalized bases that retain a perturbation group, as shown. The illustration of this particular sequence of perturbing groups 117 is not intended to be limiting, and any number of different perturbing groups arranged in any pattern may be used in order to encode information. The DNA molecule 118 may be single stranded, with the perturbing groups 117 positioned on the single strand, for an exonuclease that digests a single strand, or the DNA may be double stranded, for an exonuclease that processes double stranded DNA, and the perturbing groups may be on either strand, and in the case where only one strand of a double stranded DNA is digested, the perturbing groups 117 may reside on the digested or on the non-digested strand, or both. Such groups are described further below in the context of FIG. 14” (see paragraphs [0092], [0119], [0122], and [0125], and Figures 5, 8 and 11 of US 2022/0390407 A1, which is US publication of this instant case), the specification clearly indicates that the information encoded in the synthetic DNA molecule in the DNA information system recited in claims 41-44 and 46-54 can be read using a sensor comprising a first electrode, a second electrode spaced apart from the first electrode by an electrode gap, a processive enzyme conjugated to both the first and second electrodes, and a trans-impedance amplifier electrically connected to at least one of the first and second electrodes when the distinguishable signal features are bound groups capable of displacement by the processive enzyme of the sensor and perturbing groups that are not displaced from the synthetic DNA molecule by the processive enzyme wherein the processive enzyme is either a polymerase having strand displacing activity or an exonuclease which is used to displace and/or remove the bound groups or the perturbing groups from the synthetic DNA molecule, the bound groups are different DNA oligonucleotides hybridized to a DNA template strand of the synthetic DNA molecule, and the perturbing groups are retained in digested products of the synthetic DNA molecule cleaved by the exonuclease, and the scope of the claims is much broader than the scope of the specification. Since the claims do not limit that the processive enzyme is a specific enzyme such as a polymerase having strand displacing activity or an exonuclease having strand displacing activity which is used to displace and/or remove the bound groups or the perturbing groups from the synthetic DNA molecule, the bound groups are different DNA oligonucleotides hybridized to a DNA template strand of the synthetic DNA molecule, and the perturbing groups are retained in digested products of the synthetic DNA molecule cleaved by the exonuclease, and the specification and available arts do not show that any kind of distinguishable signal features defined by any kind of chemical anomaly of the synthetic DNA molecule, based on encountering and processing by any kind of processive enzyme of a processive enzyme molecular sensor, can produce a signal in a monitored electrical parameter of the sensor such as current, without limiting the processive enzyme to an enzyme having a specific function and limiting the distinguishable signal features to specific characters of the synthetic DNA molecule, it is unpredictable how a measurable electrical parameter such as a current produced by the trans-impedance amplifier can correspond to the information in the synthetic DNA molecule such that the information encoded in the synthetic DNA molecule in the DNA information system recited in claims 41-44 and 46-54 cannot be read using a sensor comprising a first electrode, a second electrode spaced apart from the first electrode by an electrode gap, any kind of processive enzyme conjugated to both the first and second electrodes, and a trans-impedance amplifier electrically connected to at least one of the first and second electrodes wherein the trans-impedance amplifier is configured to provide an output comprising a measurable electrical parameter when in contact with a buffer solution.
Case law has established that “(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that “[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art”. The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Furthermore, the Court in Genentech Inc. v Novo Nordisk 42 USPQ2d 1001 held that “[I]t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement”.
In view of above discussions, the skilled artisan will have no way to predict the experimental results. Accordingly, it is concluded that undue experimentation is required to make the invention as it is claimed. These undue experimentation at least includes to test whether the information encoded in the synthetic DNA molecule in the DNA information system recited in claims 41-44 and 46-54 can be read using a sensor comprising a first electrode, a second electrode spaced apart from the first electrode by an electrode gap, any kind of processive enzyme conjugated to both the first and second electrodes, and a trans-impedance amplifier electrically connected to at least one of the first and second electrodes wherein the trans-impedance amplifier is configured to provide an output comprising a measurable electrical parameter when in contact with a buffer solution.
Response to Arguments
In page 7, first paragraph of applicant’s remarks, applicant argues that “[N]onetheless,
and to expedite examination, claim 41 has been amended to recite ‘a synthetic DNA molecule
comprising a DNA template strand and distinguishable signaling features bonded thereon, the
distinguishable signaling features defined by a chemical anomaly to encode information in the
synthetic DNA molecule’. Support for the amendment is found throughout the specification, for
example, at paragraph [0018] of the published application. Applicant respectfully submits that the amendment coupled with the knowledge available to one of ordinary skill in the art and the
abundant description in the specification (as noted by the Examiner) render the claim enabled”.
The above arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection. Since the claims do not limit that the processive enzyme is a specific enzyme such as a polymerase having strand displacing activity or an exonuclease having strand displacing activity which is used to displace and/or remove the bound groups or the perturbing groups from the synthetic DNA molecule, the bound groups are different DNA oligonucleotides hybridized to a DNA template strand of the synthetic DNA molecule, and the perturbing groups are retained in digested products of the synthetic DNA molecule cleaved by the exonuclease, and the specification and available arts do not show that any kind of distinguishable signal features defined by any kind of chemical anomaly of the synthetic DNA molecule, based on encountering and processing by any kind of processive enzyme of a processive enzyme molecular sensor, can produce a signal in a monitored electrical parameter of the sensor such as current, without limiting the processive enzyme to an enzyme having a specific function and limiting the distinguishable signal features to specific characters of the synthetic DNA molecule, it is unpredictable how a measurable electrical parameter such as a current produced by the trans-impedance amplifier can correspond to the information in the synthetic DNA molecule such that the information encoded in the synthetic DNA molecule in the DNA information system recited in claims 41-44 and 46-54 cannot be read using a sensor comprising a first electrode, a second electrode spaced apart from the first electrode by an electrode gap, any kind of processive enzyme conjugated to both the first and second electrodes, and a trans-impedance amplifier electrically connected to at least one of the first and second electrodes wherein the trans-impedance amplifier is configured to provide an output comprising a measurable electrical parameter when in contact with a buffer solution.
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.
Claims 41-44 and 46-54 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 41 is rejected as vague and indefinite. Although it is known that a geochemical anomaly represents a localized deviation in the concentration of one or more chemical elements in rock, soil, sediment, or water, significantly differing from the normal background levels for that area (see the definition of “Geochemical Anomaly”) and “anomaly” means “something different, abnormal, peculiar, or not easily classified” (see the definition of “Anomaly”), “chemical anomaly”, since there is no phrase “chemical anomaly” in the specification, it is unclear what means “chemical anomaly”. If, according to the plain meaning of “chemical anomaly”, “chemical anomaly” means something different, abnormal, peculiar, or not easily classified in chemistry, it is unclear why something different, abnormal, peculiar, or not easily classified in chemistry can be used for defining any kind of distinguishable signaling features bonded to a DNA template. Please clarify.
Claim 54 recites the limitation “the encoding information” in line 1 of the claim. There is insufficient antecedent basis for this limitation in the claim because there is no phrase “encoding information” in claim 41. Please clarify.
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.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Frank Lu, Ph. D., whose telephone number is (571)272-0746. The examiner can normally be reached Monday to Friday, 9 AM to 5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow, Ph.D., can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/FRANK W LU/
Primary Examiner, Art Unit 1683
March 19, 2026