DETAILED ACTION
Response to Amendment
Applicant’s response to the office action filed on March 30, 2026 have been entered. The claims pending in this application are claims 1, 2, 4, 6-8, 10-15, 17, 19, 20, 22, 24-27, 30, 31, 33-37, 39-42, 45, 46, 48, and 49 wherein claims 22, 24-27, 30, 31, 33-37, 39-42, 45, 46, 48, and 49 have been withdrawn due to the restriction requirement mailed on July 29, 2025. The objections not reiterated from the previous office action are hereby withdrawn in view of applicant’s amendment filed on March 30, 2026. Claims 1, 2, 4, 6-8, 10-15, 17, 19, 20 will be examined.
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.
Scope of Enablement
Claims 1, 2, 4, 6-8, 10-15, 17, 19, and 20 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 an apparatus comprising a plurality of magnetic sensors, a plurality of binding areas disposed above the plurality of magnetic sensors wherein each binding area of the plurality of binding areas is used for holding fluid, and at least one line includes a first line disposed above a top surface of a first magnetic sensor of the plurality of magnetic sensors and a first binding area of the plurality of binding areas is located within a trench in the first line and the trench is above the top surface of the first magnetic sensor, does not reasonably provide enablement for using the apparatus recited in claims 1, 2, 4, 6-8, 10-15, 17, 19, and 20 as an apparatus for nucleic acid sequencing. 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 an apparatus for nucleic acid sequencing. 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 1, 2, 4, 6-8, 10-15, 17, 19, and 20 encompass an apparatus for nucleic acid sequencing, the apparatus comprising: a plurality of magnetic sensors; a plurality of binding areas disposed above the plurality of magnetic sensors, each binding area of the plurality of binding areas for holding fluid; and at least one line for detecting any kind of characteristic of at least a first magnetic sensor of the plurality of magnetic sensors, the characteristic indicating presence or absence of one or more magnetic nanoparticles coupled to a first binding area associated with the first magnetic sensor, wherein the at least one line includes a first line disposed above a top surface of the first magnetic sensor, and wherein the first binding area is located within a trench in the first line, the trench being above the top surface of the first magnetic sensor.
Working Examples
The specification provides no working example for using the apparatus recited in claims 1, 2, 4, 6-8, 10-15, 17, 19, and 20 as an apparatus for nucleic acid sequencing.
The Amount of Direction or Guidance Provided and The State of The Prior Art
The specification provides no working example for using the apparatus recited in claims 1, 2, 4, 6-8, 10-15, 17, 19, and 20 as an apparatus for nucleic acid sequencing. 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 office found a prior art (US 2010/0289483 A1, published on November 18, 2010) which teaches the apparatus recited in claim 1 (see below 102 (a) (1) rejection).
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 apparatus recited in claims 1, 2, 4, 6-8, 10-15, 17, 19, and 20 can be used as an apparatus for nucleic acid sequencing.
Since the specification shows that “[A]s shown in FIG. 4A, the apparatus 100 comprises a magnetic sensor array 110 that includes a plurality of magnetic sensors 105, with sixteen magnetic sensors 105 shown in the array 110. To avoid obscuring the drawing, only seven of the magnetic sensors 105 are labeled in FIG. 4A, namely the magnetic sensors 105A, 105B, 105C,
105D, 105E, 105F, and 105G. (For simplicity, this document refers generally to the magnetic sensors by the reference number 105. Individual magnetic sensors are given the reference number 105 followed by a letter.) The apparatus 100 also includes at least one line 120, and, for at least some of the magnetic sensors 105, a binding area 115 for each of those magnetic sensors 105, both discussed in further detail below”, “[T]he magnetic sensors 105 and portions of the lines 120 within the magnetic sensor array 110 are illustrated using dashed lines to indicate that they might not be visible in the top view of the apparatus 100. As explained in further detail below, the magnetic sensors 105 are embedded in the apparatus 100 and are protected from the contents of the binding areas 115 (e.g., by an insulator). Accordingly, it is to be understood that the various illustrated components (e.g., lines 120, magnetic sensors 105, etc.) might not be visible in a physical instantiation of the apparatus 100 (e.g., they may be embedded in or covered by protective material, such as an insulator)”, “[I]n some embodiments, each of the magnetic sensors 105 of the magnetic sensor array 110 is a thin film device that uses the magnetoresistance (MR) effect to detect magnetic labels in an associated binding area 115, described in further detail below. As described in more detail below, each magnetic sensor
105 may operate as a potentiometer with a resistance that varies as the strength and/or direction of the sensed magnetic field changes”, “[I]n some embodiments, nucleic acid is sequenced using immobilized nucleic acid strands (potentially in clonal clusters) that are tethered to the apparatus 100 in the proximity of the magnetic sensors 105 of the magnetic sensor array 110. Four types of reversible terminator bases (RT-bases) may then be added, either together or one at a time, and non-incorporated nucleotides are washed away. Then the magnetic labels, along with the terminal 3’ blocker, may be chemically removed from the nucleic acid strands before the next sequencing cycle begins”, “[T]he nucleic acid strands can be prepared in any suitable manner. For example, the nucleic acid strands can be prepared by random fragmentation of a nucleic acid sample, followed by 5’ and 3’ adapter ligation. These strands of the nucleic acid may then be captured on oligos bound or attached to the surfaces 116 of at least some of the binding areas
115. Linear or exponential amplification including bridge amplification may be used to amplify the strands prior to sequencing”, “[B]ridge amplification and other amplification techniques are well known in the art and can be used with the apparatus 100 in accordance with some embodiments. To begin bridge amplification, the nucleic acid to be sequenced can be attached to a substrate using, for example, adapter strands that are, for example, immobilized in a hydrogel. Then polymerase, primers, and nucleotide precursors may be introduced into the binding area 115 to create double-stranded nucleic acids from the single target strands. Next, the double strands are denatured, which separates the double-sided nucleic acid strands into two single strands that are complements of each other. Bridge formation involves chemistry to cause the single strands to fold over and attach to the complementary adapter strands immobilized on the substrate as shown. Once again, polymerase, primers, and nucleotide precursors are introduced into the binding area 115 to convert individual single strand ‘bridges’ into double-sided strands. Following this step, the double strands are denatured to produce complementary single strands, one being the original ‘forward’ strand and the other a copied ‘reverse’ strand. After repeating these steps many times, clonal clusters are formed with both forward and reverse copies. One of the two clusters (e.g., the reverse strands) can then be cleaved from the binding area 115 before sequencing the remaining cluster (e.g., the forward strands)”, “[T]he use of an amplification procedure in connection with the apparatus 100 for nucleic acid sequencing can improve the SNR of the sequencing process and thereby improve accuracy of the sequencing. The SNR improvement results because the presence of many copies of the same nucleic acid strand to be sequenced within a binding area 115 allows a larger number of magnetically-labeled nucleotide precursors to be incorporated within the binding area 115. The incorporation of a larger number of magnetically-labeled nucleotide precursors, in turn, increases the likelihood that the magnetic sensor 105 associated with that binding area 115 will detect the presence of the magnetic labels within the binding area 115. Thus, having a larger number of copies of the strand to be sequenced reduces the likelihood that the magnetic sensor 105 will miss the incorporation of a magnetically-labeled nucleotide precursor and thereby make a sequencing error”, “[T]o sequence the nucleic acid strands, magnetically-labeled nucleotide precursors may be introduced one at a time or all at once”, and “[I]n some embodiments, the nucleic acid strands are extended one nucleotide at a time, and the magnetic sensor array 110 is used to identify the bound magnetically-labeled nucleotide precursors” (see paragraphs [0063] to [0065], [0097] to [0101], and [0103] and Figure 4A of US 2023/0340589 A1, which is US publication of this instant application), the specification clearly indicates that nucleic acid strands are attached to the surfaces 116 of at least some of the binding areas 115 before sequencing the nucleic acid strands and sequencing the nucleic acid strands within the binding areas 115 allows a larger number of magnetically-labeled nucleotide precursors to be incorporated within the binding area 115, and the magnetic sensor array 110 is used to identify the bound magnetically-labeled nucleotide precursor. Although claim 1 requires an apparatus for nucleic acid sequencing, the apparatus comprising: a plurality of magnetic sensors; a plurality of binding areas disposed above the plurality of magnetic sensors, each binding area of the plurality of binding areas for holding fluid; and at least one line for detecting a characteristic of at least a first magnetic sensor of the plurality of magnetic sensors, the characteristic indicating presence or absence of one or more magnetic nanoparticles coupled to a first binding area associated with the first magnetic sensor, wherein the at least one line includes a first line disposed above a top surface of the first magnetic sensor, and wherein the first binding area is located within a trench in the first line, the trench being above the top surface of the first magnetic sensor, since claim 1 does not require nucleic acid strands are attached to the surfaces of the first binding area of the first line before sequencing the nucleic acid strands, the first magnetic sensor is used to identify labeled nucleotide precursors on one or more magnetic nanoparticle, and the one or more magnetic nanoparticle are contacted with the first magnetic sensor, without attaching the nucleic acid strands to the surfaces of the first binding area of the first line before sequencing the nucleic acid strands, without identifying labeled nucleotide precursors on one or more magnetic nanoparticle using the first magnetic sensor, and without contacting the one or more magnetic nanoparticle with the first magnetic sensor, it is unpredictable how detecting a characteristic of at least the first magnetic sensor of the plurality of magnetic sensors can indicate presence or absence of one or more magnetic nanoparticles coupled to the first binding area associated with the first magnetic sensor and how the apparatus recited in claims 1, 2, 4, 6-8, 10-15, 17, 19, and 20 can be used for nucleic acid sequencing. Furthermore, since claim 1 does not indicate how detecting a characteristic of at least a first magnetic sensor of the plurality of magnetic sensors such as a magnetic field or any kind of resistance, a change in the magnetic field or a change in the electric resistance in claim 8 or a noise level in claim 11 is correlated to sequencing nucleic acids, it is unpredictable how the apparatus recited in claims 1, 2, 4, 6-8, 10-15, 17, 19, and 20 can be used as an apparatus for nucleic acid sequencing.
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 apparatus recited in claims 1, 2, 4, 6-8, 10-15, 17, 19, and 20 can be used as an apparatus for nucleic acid sequencing.
Conclusion
In the instant case, as discussed above, the level of unpredictability in the art is high, the specification provides one with no guidance that leads one to claimed methods. One of skill in the art cannot readily anticipate the effect of a change within the subject matter to which the claimed invention pertains. Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of any working example related to claimed invention and the no teaching in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Response to Arguments
In page 10, fourth paragraph bridging to page 15, fourth paragraph of applicant’s remarks, applicant argues that: (1) “[A]pplicants respectfully disagree and submit that the Office's rejection is legally and factually erroneous. The specification provides extensive structural disclosure of the apparatus, detailed description of magnetically labeled nucleotide precursors, explicit sequencing workflows, and multiple detection approaches for identifying nucleotide incorporation. A person having ordinary skill in the art-which the Office has acknowledged is a high level of skill-would be fully enabled to make and use the claimed apparatus for nucleic acid sequencing without undue experimentation”; (2) “[T]he Specification Explicitly Teaches Use of the Apparatus for Sequencing The Office's rejection incorrectly asserts that the specification provides ‘no working example’ and suggests that there is insufficient guidance for using the apparatus for nucleic acid sequencing. Office Action, p. 8. This characterization is incorrect and overlooks substantial disclosure. First, the specification describes sequencing by synthesis (SBS) using magnetically labeled nucleotide precursors. See, e.g., PCT/US21/21274, p. 5, 1. 25 - p. 7, 1. 2; id. at p. 17, 1. 31 - p. 25, 1. 30. The application explains how magnetic nanoparticles can be attached to nucleotide precursors and subsequently cleaved after detection. See, e.g., id. at p. 7, 1. 16 - p. 8, 1. 31. It also discloses immobilization of nucleic acid strands within binding areas disposed above magnetic sensors. See, e.g., id. at p. 17, 1. 32 - p. 18, 1. 31. It provides detailed sequencing workflows (see, e.g., FIGS. 7 and 8 and the descriptions thereof), including binding, amplification, nucleotide incorporation, detection, label removal, and repetition of sequencing cycles. Furthermore, the application describes specific detection mechanisms (e.g., resistance changes, frequency shifts in spin torque oscillators, noise detection) that correlate the presence of magnetic nanoparticles to nucleotide incorporation. See, e.g., id. at p. 8, 1. 32 - p. 10, 1. 16. These disclosures go well beyond a mere conceptual statement of intended use. They provide operational detail sufficient for implementation by a skilled artisan”; (3) “[T]he Office Improperly Conflates Claim Scope With Enablement The Office asserts that enablement is lacking, in part, because ‘claim 1 does not require nucleic acid strands are attached to the surfaces of the first binding area of the first line before sequencing the nucleic acid strands, the first magnetic sensor is used to identify labeled nucleotide precursors on one or more magnetic nanoparticle, and the one or more magnetic nanoparticle are contacted with the first magnetic sensor.’ Office Action, pp. 12-13. Applicants disagree. Claim 1 is directed to an apparatus, and, as such, it properly recites structural components (e.g., a plurality of magnetic sensors, a plurality of binding areas, and at least one line). An apparatus claim defines what the device is, not the specific steps by which it is made or used. See, e.g., MPEP § 2114 (‘Apparatus claims cover what a device is, not what a device does.’). Furthermore, an apparatus claim is not required to recite operational steps (e.g., attaching nucleic acid strands, using the first magnetic sensor) in order to be enabled. The proper inquiry under 35 U.S.C. § 112(a) is whether the application as a whole teaches a person having ordinary skill in the art how to make and use the recited structure for its intended purpose without undue experimentation. Here, the specification and drawings provide detailed disclosure of the structure of the apparatus, and the application explains in detail how to make the disclosed apparatus and how it can be used in nucleic acid sequencing. See, e.g., PCT/US21/21274, p. 10, 1. 17 - p. 15, 1. 19; id. at p. 17, 1. 31 - p. 25, 1. 30, FIGS. 6-8”; and (4) “[T]he Office invokes In re Wands but misapplies its factors” because “[T]he application provides detailed structural, functional, and operational disclosures sufficient to enable a person having ordinary skill in the art to make and use the claimed apparatus for nucleic acid sequencing without undue experimentation. The Office's rejection improperly conflates apparatus claiming with the recitation of method steps, misapplies the Wands factors, demands experimental proof rather than enabling disclosure, and ignores the extensive sequencing techniques that are disclosed in the specification”.
The above argument has been fully considered but it is not persuasive toward the withdrawal of the rejection.
First, although applicant argues that “[T]he specification provides extensive structural disclosure of the apparatus, detailed description of magnetically labeled nucleotide precursors, explicit sequencing workflows, and multiple detection approaches for identifying nucleotide incorporation. A person having ordinary skill in the art-which the Office has acknowledged is a high level of skill-would be fully enabled to make and use the claimed apparatus for nucleic acid sequencing without undue experimentation”, “the specification describes sequencing by synthesis (SBS) using magnetically labeled nucleotide precursors. See, e.g., PCT/US21/21274, p. 5, 1. 25 - p. 7, 1. 2; id. at p. 17, 1. 31 - p. 25, 1. 30. The application explains how magnetic nanoparticles can be attached to nucleotide precursors and subsequently cleaved after detection. See, e.g., id. at p. 7, 1. 16 - p. 8, 1. 31. It also discloses immobilization of nucleic acid strands within binding areas disposed above magnetic sensors. See, e.g., id. at p. 17, 1. 32 - p. 18, 1. 31. It provides detailed sequencing workflows (see, e.g., FIGS. 7 and 8 and the descriptions thereof), including binding, amplification, nucleotide incorporation, detection, label removal, and repetition of sequencing cycles. Furthermore, the application describes specific detection mechanisms (e.g., resistance changes, frequency shifts in spin torque oscillators, noise detection) that correlate the presence of magnetic nanoparticles to nucleotide incorporation. See, e.g., id. at p. 8, 1. 32 - p. 10, 1. 16”, “[C]laim 1 is directed to an apparatus, and, as such, it properly recites structural components (e.g., a plurality of magnetic sensors, a plurality of binding areas, and at least one line). An apparatus claim defines what the device is, not the specific steps by which it is made or used. See, e.g., MPEP § 2114 (‘Apparatus claims cover what a device is, not what a device does.’)”, and “the specification and drawings provide detailed disclosure of the structure of the apparatus, and the application explains in detail how to make the disclosed apparatus and how it can be used in nucleic acid sequencing. See, e.g., PCT/US21/21274, p. 10, 1. 17 - p. 15, 1. 19; id. at p. 17, 1. 31 - p. 25, 1. 30, FIGS. 6-8”, the specification only indicates that nucleic acid strands are attached to the surfaces 116 of at least some of the binding areas 115 before sequencing the nucleic acid strands and sequencing the nucleic acid strands within the binding areas 115 allows a larger number of magnetically-labeled nucleotide precursors to be incorporated within the binding area 115, and the magnetic sensor array 110 is used to identify the bound magnetically-labeled nucleotide precursor (see paragraphs [0063] to [0065], [0097] to [0101], and [0103] and Figure 4A of US 2023/0340589 A1, which is US publication of this instant application). Since claim 1 does not require that nucleic acid strands are attached to the surfaces of the first binding area of the first line before sequencing the nucleic acid strands, the first magnetic sensor is used to identify labeled nucleotide precursors on one or more magnetic nanoparticle, and the one or more magnetic nanoparticle are contacted with the first magnetic sensor, without attaching the nucleic acid strands to the surfaces of the first binding area of the first line before sequencing the nucleic acid strands, without identifying labeled nucleotide precursors on one or more magnetic nanoparticle using the first magnetic sensor, and without contacting the one or more magnetic nanoparticle with the first magnetic sensor, it is unpredictable how detecting a characteristic of at least the first magnetic sensor of the plurality of magnetic sensors can be indicate presence or absence of one or more magnetic nanoparticles coupled to the first binding area associated with the first magnetic sensor and how the apparatus recited in claims 1, 2, 4, 6-8, 10-15, 17, 19, and 20 can be used for nucleic acid sequencing.
Second, although the examiner agrees with applicant that “an apparatus claim is not required to recite operational steps (e.g., attaching nucleic acid strands, using the first magnetic sensor) in order to be enabled”, when nucleic acid strands is not attached to the surfaces of the first binding area of the first line of the apparatus recited in claim 1 before sequencing the nucleic acid strands, it is unpredictable how the apparatus recited in claims 1, 2, 4, 6-8, 10-15, 17, 19, and 20 can be used for nucleic acid sequencing.
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.
Claim 8 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 8 is rejected as vague and indefinite. Since there are at least two kinds of resistances, electric resistance and magnetoresistance, and the specification teaches that “[F]IGS. 2A and 2B illustrate the resistance of magnetoresistive (MR) sensors in accordance with some embodiments” (see paragraph [0010] of US 2023/0340589 A1, which is US publication of this instant application), does the resistance in the claim mean a magnetoresistance or an electric resistance? Please clarify.
Response to Arguments
In page 15, fifth paragraph bridging to page 16, second paragraph of applicant’s remarks, applicant argues that “[A]pplicants respectfully submit that no clarification or amendment is required. As described in the application, the disclosed magnetic sensors may include magnetoresistive (MR) sensors that detect magnetic fields through changes in the electrical resistance of the sensor. PCT/US21/21274, p. 8, 1. 32 - p. 10, 1. 16. Magnetoresistance refers to the change in electrical resistance resulting from magnetic field interactions. For example, the specification explains that ‘the resistance of MR sensors is proportional to 1-cos(Θ), where Θ is the angle between the moments of the two ferromagnetic layers,’ and ‘[m]agnetic fields parallel to FM1 then rotate FM2 about this 90 degree configuration,’ which causes a change in resistance that results in a voltage signal that can be calibrated to measure the field acting upon the magnetic sensor. Id. at p. 9, 11. 14-15, 26-28. The quantity measured by the sensing circuitry is therefore the electrical resistance of the sensor, and the presence of magnetic nanoparticles produces a magnetic field that causes a change in that electrical resistance via magnetoresistive effects. Thus, the claim language referring to ‘resistance’ or ‘a change in the resistance’ properly describes the electrical resistance of the magnetic sensor and is consistent with the operation of MR sensors disclosed in the specification. Accordingly, Applicants respectfully submit that the claim language is clear to a person having ordinary skill in the art and is fully supported by the specification”.
These arguments have been fully considered but they not persuasive toward the withdrawal of the rejection. Although applicant argues that “the claim language referring to ‘resistance’ or ‘a change in the resistance’ properly describes the electrical resistance of the magnetic sensor and is consistent with the operation of MR sensors disclosed in the specification”, in view of claim 8, a person having ordinary skill in the art cannot understand that the resistance recited in claim 8 is a magnetoresistance or an electric resistance.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 20 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Immink et al., (US 2010/0289483 A1, published on November 18, 2010).
Regarding claims 1 and 20, Immink et al., teach an apparatus for nucleic acid sequencing, the apparatus (ie., a sensor cartridge) comprising: a plurality of magnetic sensors (ie., sensor elements such as GMR elements 8a and 8b in Figure 2); a plurality of binding areas (ie., the first region 2 and second region 3 in Figure 2) disposed above the plurality of magnetic sensors, each binding area of the plurality of binding areas for holding fluid; and at least one line (ie., a line having the first region 2 and the second region 3 in Figure 2) for detecting a characteristic (ie., a sensor signal) of at least a first magnetic sensor of the plurality of magnetic sensors, the characteristic indicating presence or absence of one or more magnetic nanoparticles coupled to a first binding area associated with the first magnetic sensor, wherein the at least one line includes a first line (ie., a line having the first region 2 and the second region 3 in Figure 2) disposed above a top surface of the first magnetic sensor (ie., GMR elements 8a), and wherein the first binding area is located within a trench in the first line, the trench being above the top surface of the first magnetic sensor as recited in claim 1 wherein the first binding area comprises a structure configured to anchor a nucleic acid (ie., having an ability to anchor a nucleic acid) to the first binding area and the structure comprises a cavity (ie., trench which is a specific kind of cavity with defined dimensions) or a ridge as recited in claim 20 (see paragraphs [0061], [0080], [0092], [0097] to [0099], [0102], and [0105], Figures 1-3, claims 1-17).
Therefore, Immink et al., teach all limitations recited in claims 1 and 20.
Response to Arguments
In page 16, third paragraph bridging to page 22, last paragraph of applicant’s remarks, applicant argues that: (1) “[I]mmink is directed to a sensor cartridge for determining the presence of target moieties in a sample fluid, such as in molecular diagnostics or drug testing. Immink, Abstract. Immink's consistently describes detection of target moieties using magnetic particles labeled with probes. See, e.g., id. at Abstract, ¶¶[0019], [0038], [0045], [0070], [0071], [0075], [0079], [0080]. Immink does not disclose an apparatus for nucleic acid sequencing (e.g., determining base order by sequential detection of nucleotide incorporation events). There is no disclosure in Immink of sequencing-by-synthesis chemistry, extendable primers, polymerase reactions, or base-by-base detection. At most, Immink describes that magnetic particles may be labeled with probes that include oligonucleotides. But this description is of generic binding chemistry for detecting target moieties. It is not nucleic acid sequencing, and Applicants submit that a device for detecting the presence of target molecules is not inherently an apparatus ‘for nucleic acid sequencing.’ Therefore, Immink does not disclose the preamble of claim 1, and the rejection should be withdrawn for at least this reason”; (2) “[T]he Office has not identified anything in Immink as allegedly disclosing the "at least one line" of claim 1. See Office Action, pp. 15-16 (‘and at least one line for detecting a characteristic (ie., frequency or pulse) of at least a first magnetic sensor of the plurality of magnetic sensors, the characteristic indicating presence or absence of one or more magnetic nanoparticles coupled to a first binding area associated with the first magnetic sensor’). Therefore, the Office has failed to meet its burden to show that each and every element of claim 1 is disclosed by Immink, and the rejection should be withdrawn for at least this reason. Moreover, as Applicants explained in the response to the Office’s restriction requirement, Immink does not disclose the ‘at least one line’ of claim 1. Specifically, Immink does not disclose any line for detecting any characteristic of any magnetic sensor. The only wires disclosed in Immink are current wires used to generate magnetic fields to manipulate magnetic particles. See, e.g., Immink, 1 [0092]”; (3) “the wires 16a-d are used to magnetize particles, and, like the current wires 6a, 6b, they are not ‘at least one line for detecting a characteristic of at least a first magnetic sensor of the plurality of magnetic sensors, the characteristic indicating presence or absence of one or more magnetic nanoparticles coupled to a first binding area associated with the first magnetic sensor.’ Immink does not describe read circuitry at all, other than to say, in the context of FIG. 4, copied below, that ‘[t]he small squares 15 at the right hand side of FIG. 4 indicate electrical contacts to connect the sensor substrate 8 to a (portable) reader device.’ Immink, ¶ [0102]. These portions of Immink also do not disclose or render obvious ‘at least one line for detecting a characteristic of at least a first magnetic sensor of the plurality of magnetic sensors.’”; (4) “[B]ut even if Immink's wires were detection lines-which they are not-Immink does not disclose any trenches in the wires. As shown in FIG. 2 of Immink, copied below, the first and second regions (2, 3), which the Office contends are trenches, are in the walls of the reaction chamber, not in the wires 6a, 6b: See also Immink, ¶ [0082]. Likewise, the sensor substrate surface 5 of Immink is not within a trench in any line, much less in a line for detecting a characteristic of at least a first magnetic sensor of the plurality of magnetic sensors, the characteristic indicating presence or absence of one or more magnetic nanoparticles coupled to a first binding area associated with the first magnetic sensor. See, e.g., id. at ¶¶ [0080], [0092]-[0099], [0105]. The Office attempts to equate Immink's ‘regions’ with a ‘trench,’ apparently asserting that a trench is merely a type of cavity. The Office's mapping is incorrect for several reasons. First, Immink's regions (2, 3) are functional reagent regions in a reaction chamber. See, e.g., Immink, ¶ [0092]. These regions are not trenches formed within a detection line. Second, Immink contains no disclosure of creating a trench in any conductive line. Third, Immink does
not disclose any line having a surface with a recessed cavity or any other feature that could be considered a trench. Applicants respectfully submit that the Office's interpretation of Immink is contrary to the limitations of claim 1 and to the specification and drawings of Applicant’s application. Immink does not disclose a first line disposed above a top surface of the first magnetic sensor, wherein the first binding area is located within a trench in the first line, the trench being above the top surface of the first magnetic sensor as required by claim 1”; and (5) “[C]laim 20 depends from claim 1 and is therefore patentable over Immink for at least the same reasons that claim 1 is patentable over Immink. Furthermore, claim 1 recites that the first binding area is located within a trench in the first line, and claim 20 recites that the first binding area comprises a structure, ‘wherein the structure comprises a cavity or a ridge.’ The Office appears to assert that Immink’s regions, which the Office asserts are the trench of claim 1, are also the structure recited in claim 20. This mapping of Immink onto claim 20 is inconsistent with the plain language of the claims, which is clear that the cavity or ridge of claim 20 is a separate element from the trench of claim 1”.
These arguments have been fully considered but they not persuasive toward the withdrawal of the rejection.
First, although applicant argues that “[I]mmink does not disclose the preamble of claim 1” which is “an apparatus for nucleic acid sequencing”, applicant’s arguments rely on language solely recited in preamble recitations in claim 1. When reading the preamble in the context of the entire claim, the recitation “for nucleic acid sequencing” in claim 1 is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of claim 1 is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02.
Second, since Immink et al., teach that “[T]he first and second type of magnetic particles 4a, 4b, however, will stay at the first region 2, respectively the second region 3 due to the control of the control means, e.g. the magnetic field generated by the current wires 6a, 6b. The first and second type of target moieties present in the biological fluid can then specifically react with respectively the first and second type of magnetic particles 4a, 4b at respectively the first and second region 2, 3 in the reaction chamber 1. After some time, the flow of biological fluid stops and the control means may be steered so as to release the first and second type of magnetic particles 4a, 4b from respectively the first and second region 4a, 4b, e.g. magnetic fields generated by the current wires 6a, 6b may be switched off. This may be done synchronously for the first and second regions 2, 3 or sequentially (see further). When the control means is steered to release the first and second types of magnetic particles 4a, 4b, e.g. flowing of current through the current wires 6a, 6b is switched off, a further magnetic field may be generated for attracting the first and second type of magnetic particles 4a, 4b with attached thereto respectively the first and second target moiety towards the sensor substrate surface 5 where they can bind to respectively a first and second type of target homologues. The magnetic field for attracting the magnetic particles 4a, 4b towards the sensor substrate surface 5 may be generated by an external magnetic field generation means, for example by actuation coil 7a as indicated in FIG. 1. A further magnetic coil 7b may be present to achieve a bound-free separation after incubation of the magnetic particles 4a, 4b on the sensor substrate surface 5 in a magnetic washing step, or in other words to remove non-specifically bound magnetic particles 4a, 4b from the sensor substrate surface 5. The magnetic field generated by actuation coils 7a, 7b may also magnetize the magnetic particles 4a, 4b. The magnetic particles 4a, 4b thereby develop a magnetic moment”, “first the first type of magnetic particles 4a may be released from the first region 2 by appropriately steering the control means, e.g. by switching off the magnetic field generated by current wire 6a. The first magnetic particles 4a with attached thereto the first target moiety may then be attracted toward the sensor substrate surface 5 to bind to respective target homologues at the sensor substrate surface 5 and may be actuated by means of a magnetic field generated by the actuation coils 7a, 7b, or alternatively by on-chip current wires. At the sensor substrate surface 5, the first magnetic particles 4a with attached thereto the first type of target moieties may bind to a first type of target homologues which are specific for the first type of target moiety. A first sensor signal which is representative for the amount of first type of magnetic particles 4a bound to the sensor substrate surface 5 may be provided by the GMR element 8a. The first type of magnetic particles 4a may then be removed from the sensor substrate surface 5 by switching off the magnetic field generated by the actuation coil 7a, and/or by performing a washing step by switching on actuation coil 7b”, “[I]n a next step, the control means is appropriately steered, e.g. flowing of current through current wire 6b is switched off, for selectively releasing the second type of magnetic particles 4b with attached thereto the second type of target moieties. The actuation coil 7a is turned on for generating a magnetic field for attracting the second type of magnetic particles 4b towards the sensor substrate surface 5, hereby allowing them to bind to the second type of target homologues present at the sensor substrate surface 5. A second signal of the GMR element 8a may then be representative for the amount of second type magnetic particles 4b bound to the sensor substrate surface 5”, and “the control means may be appropriately steered, e.g. flowing of current through the second current wire 6b may be switched off, and the second type of magnetic particles 4b may be attracted to the sensor substrate surface 5 to bind to the second type of target homologues while the first type of magnetic particles 4a are still bound to the sensor substrate surface 5. Because target homologues are generally provided in excess with respect to an expected concentration of target moieties, there will always be enough target homologues left for binding the second target moiety even if some of the first type of magnetic particles 4a have erroneously bound to the second type of target homologues. Binding of the second type of magnetic particles 4b to the sensor substrate surface 5 will then change the sensor signal. It has to be noted that during binding of the second type of magnetic particles 4b to the sensor substrate surface 5 cross-reactivity may also occur with the first target homologue present at the sensor substrate surface 5 in case not all first target homologues would have been taken by the first type of magnetic particles 4a. The value of the change of the sensor signal is then a measure for the amount of second type of magnetic particles 4b bound to the sensor substrate surface 5” (see paragraphs [0092] and [0097] to [0099], and Figures 1 and 2), the specification clearly indicates that a line having the first region 2 and the second region 3 in Figure 2 taught by Immink et al., is used for attaching magnetic particles 4a having a first target moiety and magnetic particles 4b having a second target moiety to the plurality of binding areas and releasing the magnetic particles 4a having a first target moiety and magnetic particles 4b having a second target moiety to sensor substrate surface 5 having GMR elements 8a and 8b for binding a first type of target homologues and a second type of target homologues and generating senor signals. Thus, Immink et al., disclose at least one line (ie., a line having the first region 2 and the second region 3 in Figure 2) for detecting a characteristic (ie., sensor signal) of at least a first magnetic sensor of the plurality of magnetic sensors and the characteristic indicating presence or absence of one or more magnetic nanoparticles coupled to a first binding area associated with the first magnetic sensor as recited in claim 1.
Third, although applicant argues that “[I]mmink's regions (2, 3) are functional reagent regions in a reaction chamber. See, e.g., Immink, ¶ [0092]. These regions are not trenches formed within a detection line” and “[I]mmink contains no disclosure of creating a trench in any conductive line”, claim 1 does not require that at least one line for detecting a characteristic of at least a first magnetic sensor of the plurality of magnetic sensors is a detection line or a conductive line as argued by applicant. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In fact, since a line having the first region 2 and the second region 3 in Figure 2 taught by Immink et al., has two trenches (see Figures 1 and 2), Immink et al., disclose that the first binding area is located within a trench in the first line wherein the trench is above the top surface of the first magnetic sensor as recited in claim 1.
Fourth, although applicant argues that “claim 1 recites that the first binding area is located within a trench in the first line, and claim 20 recites that the first binding area comprises a structure, ‘wherein the structure comprises a cavity or a ridge.’ The Office appears to assert that Immink’s regions, which the Office asserts are the trench of claim 1, are also the structure recited in claim 20. This mapping of Immink onto claim 20 is inconsistent with the plain language of the claims, which is clear that the cavity or ridge of claim 20 is a separate element from the trench of claim 1”, claim 20 does not require that the structure comprising a cavity or ridge is different from the trench as argued by applicant. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
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.
No claim is allowed.
Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center. The faxing of such papers must conform with the notices published in the Official Gazette, 1096 OG 30 (November 15, 1988), 1156 OG 61 (November 16, 1993), and 1157 OG 94 (December 28, 1993)(See 37 CAR § 1.6(d)). The CM Fax Center number is (571)273-8300.
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 on Monday-Friday from 9 A.M. to 5 P.M.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Dr. Anne Gussow, Ph.D., can be reached on (571)272-6047.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/FRANK W LU/Primary Examiner, Art Unit 1683
June 23, 2026
Prosecution Insights