859DETAILED 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 .
Claim Status and Formal Matters
This action is in response to papers filed 4/21/2025.
Claims 1-34 are pending.
Claims 31-34 have been added by amendment.
Applicant’s election without traverse of Group I, claims 1-26 in the reply filed 8/4/2023 is acknowledged.
The response traverses the election of
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The response provides traverses the rejection asserting there is no search burden. This argument is not persuasive as each compound has a different chemical structure and thus requires a separate search as searching one will not inherently provide art on the other. .
The response correctly notes there is only one species in claim 8..
The response asserts, “The Restriction Requirement stated that Applicant must elect a species from wherein the first fluorescent label is also detectable by the second detector or wherein the second fluorescent label is also detectable by the first detector. Applicant elects the species of Claim 12, wherein the first fluorescent label is also detectable by the second detector, with traverse. Applicant submits that the species restriction is from Claim 12 is improper because it is not a significant burden to search the elected species and the one alternative species mentioned in Claim 12” This argument has been thoroughly reviewed but is not considered persuasive as searching the first fluorescent label is also detectable by the second detector will not inherently
provide art on wherein the second fluorescent label is also detectable by the first
detector.
The response continues by asserting, “Applicant elects the species of Claim 18, wherein the detectors comprise charge-coupled device image sensors, with traverse. Independent Claim 1 recites a system for identifying nucleotides in a nucleic acid sequence, including a first detector, a second detector, a light source and a processor configured to generate light at an optical frequency to stimulate an emission from the nucleic acid sequence and identify a nucleotide based on whether the emission is received by the first detector, the second detector, both the first and second detectors, or neither the first nor second detector. The claimed system of Claim 1 does not depend on the type of detector that is used and Claim 18 merely list options for sensors that could work within the recited system. Applicant respectfully submits that the subject matter of the identified species is sufficiently related so as to be searchable together. “ This argument has been thoroughly reviewed but is not considered persuasive as searching CCD will not inherently provide art on metal-oxide semiconductor image sensors, photomultiplier tubs, photodiodes, or any combination thereof. Thus searching more than one would be a serious search burden, unless the representative wants to concede they are all obvious variants.
The response continues by asserting, “Applicant elects one or more optical filter materials, with traverse. These alternatives are not required by the base claim and thus this requirement for an election of species is improper.” The response appears to be alleging all the limitations of dependent claims are obvious or nor required of the independent claim. However searching additional elements is a search burden.
The response continues by asserting, “Applicant elects the species of Claim 21, wherein the substrate comprises a plurality of cavities, with traverse. Applicant respectfully submits that the subject matter of the identified species is sufficiently related so as to be searchable together. Thus, it would not present a burden on the Examiner to search the alternatives provided in Claim 21 all together.” This argument has been thoroughly reviewed but is not considered persuasive as searching a plurality of cavities will not inherently provide art on chemically functionalized regions, a plurality of optical resonators, a plurality of optical waveguides, or any combination thereof.
The response continues by asserting, “Applicant elects the species of Claim 23, wherein the nucleotides are an analog of dTTP, with traverse. Applicant elects with traverse on the basis that searching the additional species would not present a burden on the Examiner. If the members of a Markush group are sufficiently few in number or so closely related that a search and examination of the entire claim can be made without serious burden, the examiner must examine all of the members of the Markush group in the claim on the merits, even though they may be directed to independent and distinct inventions. See M.P.E.P. § 803.02.” This argument has been thoroughly reviewed but is not considered persuasive as MPEP 803.02 states, “When examining a Markush claim, the examiner may generally choose to require a provisional election of species from among patentably indistinct species or patentably indistinct groups of species. See subsection III, below. The applicant’s election serves as a starting point for the search and examination of the claim.” Further each dNTP has a different structure, if applicant wishes to concede that all dNTPs are obvious variants of other the examiner will withdraw the species election.
The response continues by asserting, “. Applicant elects wherein first nucleotide is a first reversibly blocked nucleotide triphosphate (rbNTP), the second nucleotide is a second rbNTP, the third nucleotide is a third rbNTP, and the fourth nucleotide is a fourth rbNTP with traverse and argues that the election of one species from Claim 24 is improper because Claim 24 only contains a single species of the four nucleotides.” This argument has been thoroughly reviewed but is not considered persuasive as the representative would not allow the examiner to merely asserts that a teaching of a single rbNTP would anticipate a second and third rbNTP.
The response continues by asserting, “Applicant elects with traverse on the basis that searching the additional species of a nucleotide of rbUTP would not present a burden on the Examiner. If the members of a Markush group are sufficiently few in number or so closely related that a search and examination of the entire claim can be made without serious burden, the examiner must examine all of the members of the Markush group in the claim on the merits, even though they may be directed to independent and distinct inventions. See M.P.E.P. § 803.02.” This argument has been thoroughly reviewed but is not considered persuasive as MPEP 803.02 states, “When examining a Markush claim, the examiner may generally choose to require a provisional election of species from among patentably indistinct species or patentably indistinct groups of species. See subsection III, below. The applicant’s election serves as a starting point for the search and examination of the claim.” Further each dNTP has a different structure, if applicant wishes to concede that all dNTPs are obvious variants of other the examiner will withdraw the species election.
Newly submitted claim 31 directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Claim 31 provides the requirement of three different primers with different labels. Thus it has materially different design, is of different scope, and is not an obvious variant of claim1.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 31-34 withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 27-30 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/4/2023
Claims 1-26 are being examined.
The objection to the specification has been withdrawn in view of the arguments.
Priority
The instant application was filed on 06/03/2021.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or presented in an IDS, they have not been considered.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: configured to in claims 1-2, 17, 20,.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-6, 10-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Langlois (USPGPUB20200080142) and Sun (Dyes and Pigments 164 (2019) 287–295).
With regards to claim 1, Langlois claims , “ A system for determining the nucleotide sequence of polynucleotides, comprising: a single light source configured to stimulate emission of fluorescent light; at least one detector configured to detect fluorescent emissions off a fluorophore attached to a nucleotide, the at least one detector being configured to detect the fluorescent emissions at a first wavelength and a second wavelength; a processor configured to execute instructions that perform a method comprising: generating light from the light source onto a nucleotide; identifying the nucleotide as a first type when no fluorescent emission is detected by the at least one detector; identifying the nucleotide as a second type when a fluorescent emission at the first wavelength of light is detected by the at least one detector; identifying the nucleotide as a third type when a fluorescent emission at the second wavelength of light is detected by the at least one detector; and identifying the nucleotide as a fourth type when fluorescent emissions from the nucleotide at the first wavelength and the second wavelength of light are detected by the at least one detector..“
Langlios does not expressly teach a single fluorescent label with an emission at a first and second wavelength.
However, it would have been prima facie obvious to one of skill in the art prior to the effective filing date of the claims to provide a single label that emits fluorescence in more than one wavelength. The artisan would have been motivated to use a single label to eliminate the need of a two labels. The artisan would have a reasonable expectation of success as the artisan is merely using known labels in a known system.
Langlois while teaching the use of a fluorescent labels for nucleotides does not explicitly teach the label of claim 4.
However, Sun teaches coumarin-benzoxazole derivatives (title). Sun in figure 1 teaches
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Sun teaches, “Coumarin derivatives are an important class of heterocyclic compounds due to their physical and biological properties. Coumarin derivatives are reported to have many important electro-optical properties [23] and biological activities [24]. They have been widely used in the field of biology, medicine, perfumes and cosmetics [25,26]. Recently, more and more researches are devoting themselves to the photophysical properties of coumarin derivatives, such as the high fluorescence quantum yield, large stokes shift, and excellent light stability, as well as the low toxicity [27]”
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use the coumarin derivatives of Sun in the system to Langlois. The artisan would be motivated as Sun teaches, “of coumarin derivatives, such as the high fluorescence quantum yield, large stokes shift, and excellent light stability, as well as the low toxicity.” The artisan would have a reasonable expectation of success as the artisan is merely using known coumarin derivatives in a known system.
With regards to claim 2, 5, Langlois claims , “identifying the nucleotide as a first type when no fluorescent emission is detected by the at least one detector; identifying the nucleotide as a second type when a fluorescent emission at the first wavelength of light is detected by the at least one detector; identifying the nucleotide as a third type when a fluorescent emission at the second wavelength of light is detected by the at least one detector; and identifying the nucleotide as a fourth type when fluorescent emissions from the nucleotide at the first wavelength and the second wavelength of light are detected by the at least one detector.
With regards to claim 3, Langlois teaches Cy3, cy5 0017).
With regards to claim 10, Langlois teaches, “[0033] The fluorescent labels can have different stokes shift, for example, ranging from 10 nm to 200 nm. In some embodiments, the stoke shift can be, or be about, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 nm, or a number or a range between any two of these values. In some embodiments, the stoke shift can be at least, or at most, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or 200 nm.”
With regards to claim 11-12 Langlois teaches, “[0034] The systems and methods disclosed herein can utilize two fluorescent labels, for example a first fluorescent label and a second fluorescent label, can have overlapping emission spectra and can be subject to cross-talk. In some embodiments, the peak emission wavelengths of the two fluorescent labels can vary, for example, ranging from 10 nm to 200 nm. In some embodiments, the peak emission wavelengths of the two fluorescent labels can be, or be about, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 nm, or a number or a range between any two of these values. In some embodiments, the peak emission wavelengths of the two fluorescent labels can be at least, or at most, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or 200 nm. The detector 126, with one of the filters in the filter assembly 128, can detect fluorescent emissions of the first fluorescent label. The detector 126, with another filter in the filter assembly 128, can detect fluorescent emissions of the second fluorescent label..”
With regards to claim 13, Langlois teaches, “In some embodiments, the two fluorescent dyes can be Cy3 (with emission peak at around 575 nm) and a fluorescence resonance energy transfer (FRET) pair dye Cy3-Cy5 (with emission peak at 670 nm).” (0035)
Claims 14 and 16 recite, ”corresponding.” ”Corresponding” is not defined by the specification and is not an art accepted term. Thus these claims are broad.
With regards to claim 14, Langlois teaches, “The normal stokes shift dye can be excited with a laser or a LED light source with a wavelength of 488 nm and can have an emission peak at 520 nm” (0035)
With regards to claim 15, Langlois claims generating light 450 nm (claim 15-16)
With regards to claim 17, Langlois teaches the use of lasers or light emitting diodes (claims 15-16). These are capable of performing the claimed process.
With regards to claim 18,Langlois teaches CMOS (0023).
With regards to claim 19, Langlois teaches, “0024] A filter assembly 128 of the optics system 102 can be configured to filter the fluorescent emissions of the fluorescent labels in the flowcell 114. The filter assembly 128 can include a first filter and a second filter. Each filter can be a longpass filter, a shortpass filter, or a bandpass filter, depending on the types of fluorescent molecules being used in the system. The first filter can be configured to detect the fluorescent emissions of the first fluorescent labels by the detector 126. The second filter can be configured to detect the fluorescent emissions of the second fluorescent labels by the detector 126. With two filters in the filter assembly 128, the detector 126 can detect two different wavelengths of light. The two wavelengths of light can be from the same fluorescent label or different fluorescent labels. The two wavelengths of light can be, for example, at least 20 nm apart.”
With regards to claim 20, Langlois teaches extending a primer by use of a polymerase.
With regards to claim 21, Langlois teaches the use of multiple flow cells or cavities (0025).
With regards to claims 22-26, Langlois teaches, “0045] During each sequencing cycle, four types of nucleotide analogs can be added and incorporated onto the growing primer-polynucleotides. The four types of nucleotide analogs can have different modifications. For example, the first type of nucleotide can be an analog of deoxyguanosine triphosphate (dGTP) not conjugated with any fluorescent label. The second type of nucleotide can be an analog of deoxythymidine triphosphate (dTTP) conjugated with the first type of fluorescent label via a linker. The third type of nucleotide can be an analog of deoxycytidine triphosphate (dCTP) conjugated with the second type fluorescent label via a linker. The fourth type of nucleotide can be an analog of deoxyadenosine triphosphate (dATP) conjugated with both the first type of fluorescent label and the second type of fluorescent label via one or more linkers. The linkers may include one or more cleavage groups. Prior to the subsequent sequencing cycle, the fluorescent labels can be removed from the nucleotide analogs. For example, a linker attaching a fluorescent label to a nucleotide analog can include an azide and/or an alkoxy group, for example on the same carbon, such that the linker may be cleaved after each incorporation cycle by a phosphine reagent, thereby releasing the fluorescent label from subsequent sequencing cycles.”
Response to Arguments
The response traverse the rejection asserting, “Langlois further teaches that extracted intensities from emissions by each fluorescent label can be color corrected to reduce or eliminate cross-talk between the first and second fluorescent labels.
See id. at ¶¶ [0040], [0075] and [0076]. Thus, Langlois would be understood by a person of skill in the art as teaching a one-excitation, two-dye system for base calling, wherein cross-talk between the two dyes should be minimized for base calling. “ This argument has been thoroughly reviewed but is not considered persuasive as the response to the 112(a) and 112(b) rejection of the instant response make it argue that different wavelengths of a nucleotide having a single label encompasses any tow points or ranges on the emission curve as exemplified by figure 4.
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Lanlios teaches, “FIG. 7C shows a schematic illustration of a radius-weighted histogram when the two fluorescent labels have overlapping emission spectra and are subject to cross-talk.” However as in instant figure 4, the skilled artisan could easily choose a first range of wavelengths from the trough of the curve between C to the left of peak of A for one wavelength range and from the right of peak A to the trough between A and T as the second wavelength range.
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The response continues by providing arguments about significant overlap between the fluorescent labels being an issue. This argument has been thoroughly reviewed as figure 4 of the instant application exemplifies greater overlap than figure 7C of Langlios.
The response continues by arguing the label of Sun does not overcome the deficiencies of the prior art. This argument is confusing in view of the breadth of the claim as argued int eh 112(a) and 112(b) rejections of the instant response Langlios renders obvious the limitations of the claims and Sun teaches the structure of the dye or label required of claim 4.
Further Illumina (Do you have two colors or four colors in Illumina (Last
updated on February 27, 2017), Illumina Two-channel SBS seuqencings Technology ( Current as of 30 January 2014), Andrews (Illumina 2 colour chemistry can overcall high confidence G bases, May 4, 2016)), Drmanac US9222132B2, and Drmanac US10662473B2 demonstrate the claims are not novel.
Thus the rejection is maintained.
Claim(s) 1-3, 5-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Langlois (USPGPUB20200080142) and Gorka (Org. Biomol. Chem., 2015, 13, 7584.)
.Langlois claims, “ A system for determining the nucleotide sequence of polynucleotides, comprising: a single light source configured to stimulate emission of fluorescent light; at least one detector configured to detect fluorescent emissions off a fluorophore attached to a nucleotide, the at least one detector being configured to detect the fluorescent emissions at a first wavelength and a second wavelength; a processor configured to execute instructions that perform a method comprising: generating light from the light source onto a nucleotide; identifying the nucleotide as a first type when no fluorescent emission is detected by the at least one detector; identifying the nucleotide as a second type when a fluorescent emission at the first wavelength of light is detected by the at least one detector; identifying the nucleotide as a third type when a fluorescent emission at the second wavelength of light is detected by the at least one detector; and identifying the nucleotide as a fourth type when fluorescent emissions from the nucleotide at the first wavelength and the second wavelength of light are detected by the at least one detector.Langlios does not expressly teach a single fluorescent label with an emission at a first and second wavelength.
However, it would have been prima facie obvious to one of skill in the art prior to the effective filing date of the claims to provide a single label that emits fluorescence in more than one wavelength. The artisan would have been motivated to use a single label to eliminate the need of a two labels. The artisan would have a reasonable expectation of success as the artisan is merely using known labels in a known system.
Langlois while teaching the use of a fluorescent labels for nucleotides including cyanine dye does not explicitly teach the photo switchable cyanine label of claim 6-9.
However, Gorka teaches commercially available cyanine dyes including
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Gorka teaches, “Super resolution methods that exceed the diffraction limit are revolutionizing fluorescence microscopy. Among several general approaches, one set of methods relies on imaging single molecules undergoing controlled switching between dark and emissive states. By collecting photons from a few single-molecule emitters, which represent only a fraction of all the labels in the sample, sub-diffraction limit resolution can be achieved by calculating the center of the single-molecule emission pattern (generally assumed to be a simple Gaussian distribution) prior to its return to a dark state. Repeated activation, localization, and deactivation forms a high-resolution pattern (Fig. 6A). The two most common methods of this type are referred to as photoactivated localization microscopy (PALM), which generally involves photoactivateable fluorescent proteins, and stochastic optical reconstruction microscopy (STORM), which usually employs cyanine fluorophores (particularly Alexa 647). While key aspects of these methods span numerous scientific disciplines, with many details residing beyond the scope of this review, a critical component is the chemistry controlling the pivotal on/off events.102,103 The chemistry of cyanine photoswitching, which featured prominently in the early methodological developments and is still a pillar of these approaches, has been elucidated to a detailed molecular level and is reviewed below.” (pages 7591-7592)
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use the cyanine derivatives of Gorka in the system to Langlois. The artisan would be motivated as to take advantage of photoswitching. The artisan would have a reasonable expectation of success as the artisan is merely using known cyanine derivatives in a known system.
With regards to claim 2, 5, Langlois teaches, “[0052] The nucleotide analogs can include a first type of nucleotide, a second type of nucleotide, a third type of nucleotide, and a fourth type of nucleotide. The first type of nucleotide, for example an analog of deoxyguanosine triphosphate (dGTP), is not conjugated to the first fluorescent label or the second fluorescent label. The second type of nucleotide, for example an analog of deoxythymidine triphosphate (dTTP), can be conjugated with the first type of fluorescent label, and not the second type of fluorescent label. The third type of nucleotide, for example an analog of deoxycytidine triphosphate (dCTP), can be conjugated with the second type fluorescent label, and not the first type of fluorescent label. The fourth type of nucleotide, for example an analog of deoxyadenosine triphosphate (dATP), can be conjugated with both the first type of fluorescent label and the second type of fluorescent label.
With regards to claim 3, Langlois teaches Cy3, cy5 0017).
With regards to claim 10, Langlois teaches, “[0033] The fluorescent labels can have different stokes shift, for example, ranging from 10 nm to 200 nm. In some embodiments, the stoke shift can be, or be about, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 nm, or a number or a range between any two of these values. In some embodiments, the stoke shift can be at least, or at most, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or 200 nm.”
With regards to claim 11-12 Langlois teaches, “[0034] The systems and methods disclosed herein can utilize two fluorescent labels, for example a first fluorescent label and a second fluorescent label, can have overlapping emission spectra and can be subject to cross-talk. In some embodiments, the peak emission wavelengths of the two fluorescent labels can vary, for example, ranging from 10 nm to 200 nm. In some embodiments, the peak emission wavelengths of the two fluorescent labels can be, or be about, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 nm, or a number or a range between any two of these values. In some embodiments, the peak emission wavelengths of the two fluorescent labels can be at least, or at most, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or 200 nm. The detector 126, with one of the filters in the filter assembly 128, can detect fluorescent emissions of the first fluorescent label. The detector 126, with another filter in the filter assembly 128, can detect fluorescent emissions of the second fluorescent label..”
With regards to claim 13, Langlois teaches, “In some embodiments, the two fluorescent dyes can be Cy3 (with emission peak at around 575 nm) and a fluorescence resonance energy transfer (FRET) pair dye Cy3-Cy5 (with emission peak at 670 nm).” (0035)
Claims 14 and 16 recite, ”corresponding.” ”Corresponding” is not defined by the specification and is not an art accepted term. Thus these claims are broad.
With regards to claim 14, Langlois teaches, “The normal stokes shift dye can be excited with a laser or a LED light source with a wavelength of 488 nm and can have an emission peak at 520 nm” (0035)
With regards to claim 15, Langlois claims generating light 450 nm (claim 15-16)
With regards to claim 17, Langlois teaches the use of lasers or light emitting diodes (claims 15-16). These are capable of performing the claimed process.
With regards to claim 18,Langlois teaches CMOS (0023).
With regards to claim 19, Langlois teaches, “0024] A filter assembly 128 of the optics system 102 can be configured to filter the fluorescent emissions of the fluorescent labels in the flowcell 114. The filter assembly 128 can include a first filter and a second filter. Each filter can be a longpass filter, a shortpass filter, or a bandpass filter, depending on the types of fluorescent molecules being used in the system. The first filter can be configured to detect the fluorescent emissions of the first fluorescent labels by the detector 126. The second filter can be configured to detect the fluorescent emissions of the second fluorescent labels by the detector 126. With two filters in the filter assembly 128, the detector 126 can detect two different wavelengths of light. The two wavelengths of light can be from the same fluorescent label or different fluorescent labels. The two wavelengths of light can be, for example, at least 20 nm apart.”
With regards to claim 20, Langlois teaches extending a primer by use of a polymerase.
With regards to claim 21, Langlois teaches the use of multiple flow cells or cavities (0025).
With regards to claims 22-26, Langlois teaches, “0045] During each sequencing cycle, four types of nucleotide analogs can be added and incorporated onto the growing primer-polynucleotides. The four types of nucleotide analogs can have different modifications. For example, the first type of nucleotide can be an analog of deoxyguanosine triphosphate (dGTP) not conjugated with any fluorescent label. The second type of nucleotide can be an analog of deoxythymidine triphosphate (dTTP) conjugated with the first type of fluorescent label via a linker. The third type of nucleotide can be an analog of deoxycytidine triphosphate (dCTP) conjugated with the second type fluorescent label via a linker. The fourth type of nucleotide can be an analog of deoxyadenosine triphosphate (dATP) conjugated with both the first type of fluorescent label and the second type of fluorescent label via one or more linkers. The linkers may include one or more cleavage groups. Prior to the subsequent sequencing cycle, the fluorescent labels can be removed from the nucleotide analogs. For example, a linker attaching a fluorescent label to a nucleotide analog can include an azide and/or an alkoxy group, for example on the same carbon, such that the linker may be cleaved after each incorporation cycle by a phosphine reagent, thereby releasing the fluorescent label from subsequent sequencing cycles.”
Response to Arguments
The response traverses the rejection for the arguments with respect to the independent claim. These arguments are not persuasive for the reasons of record.
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 1-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-25 of copending Application No. 17823036. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are drawn to aA system, comprising:a substrate; a nucleic acid sequence bound to the substrate and comprising a plurality of nucleotides; a first detector configured to detect a first range of wavelengths of light; a second detector configured to detect a second range of wavelengths of light; a primer hybridized to the nucleic acid sequence and comprising a nucleotide analog having a single fluorescent label that emits light in the first range of wavelengths and the second range of wavelengths so that the single fluorescent label is detectable by both the first and second detectors;a light source comprising a laser or a light-emitting diode which outputs light at an excitation wavelength; and a processor configured to execute instructions that perform a method to: generate light from the light source at the excitation wavelength to stimulate an emission from the[[a]] single fluorescent label on the[[a]] nucleotide analog on the primer hybridized to the nucleic acid sequence on the substrate; and identify at least one nucleotide from the plurality of nucleotides in the nucleic acid sequence ifthe emission from the single fluorescent labelis received by
The claims of 036 are drawn to a system for identifying a nucleotide in a nucleic acid sequence bound to a substrate, comprising: a first detector configured to detect a first range of wavelengths of light; a second detector configured to detect a second range of wavelengths of light; a light source comprising a laser or a light-emitting diode which outputs light at an optical frequency; and a processor configured to: generate light at the optical frequency to stimulate an emission from the nucleic acid sequence on the substrate; and identify a nucleotide in the nucleic acid sequence based on whether the emission is received by the first detector, the second detector, both the first and second detectors, or neither the first nor second detector. Dependent claims draw the invention to wherein the processor is further configured to: determine a signal-to-noise ratio of emissions from a plurality of polynucleotides bound to the substrate; and in response to the determined signal-to-noise ratio, actuate the second detector, the second light source, or both, and switch from a first mode of identifying a nucleobase based on the intensity of the emission received by the first detector to a second mode of identifying a nucleobase based on the intensity of the emission received by the first detector and by the second detector.
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims the claims of 036 render the instant claims obvious. The artisan would be motivated as both sets of claims encompass systems for detection nucleotides using a light source, detectors and processor. The artisan would have a reasonable expectation of success as the system is merely art known detectors and reagents.
Dependent claim are obvious for as they are co-extensive in scope and/or reasons set for in 103 rejections.
Response to Arguments
The response request the instant rejection be withdrawn as it is the earlier filed application. This argument has been thoroughly reviewed but is not considered persuasive as the instant claims are not allowable.
Summary
No claims are allowed.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Illumina Two-channel SBS sequencings Technology ( C2015).
(high data accuracy with faster data)
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.
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/Steven Pohnert/Primary Examiner, Art Unit 1683
Prosecution Insights