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 .
Election/Restrictions
Applicant's election with traverse of Group II, claims 6-28, in the reply filed on 12/15/2025 is acknowledged. The arguments are deemed persuasive, and therefore the restriction requirement as set forth in the Office action mailed on 10/23/2025 is hereby withdrawn.
In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 1-28 remain pending in the application.
Claim Objections
Claim 2 is objected to because of the following informalities: in lines 3-4, “substantially equal first maximum absorption wavelength” should read “substantially equal to the first maximum absorption wavelength”. Appropriate correction is required.
Claim 7 is objected to because of the following informalities: in lines 3-4, “substantially equal first maximum emission wavelength” should read “substantially equal to the first maximum emission wavelength”. Appropriate correction is required.
Claim 16 is objected to because of the following informalities: in line 5, “he third dye” should read “the third dye”. Appropriate correction is required.
Claim 16 is objected to because of the following informalities: in lines 3-4, “substantially equal first maximum absorption wavelength” should read “substantially equal to the first maximum absorption wavelength”. Appropriate correction is required.
Claim 16 is objected to because of the following informalities: in lines 6-7, “substantially equal second maximum absorption wavelength” should read “substantially equal to the second maximum absorption wavelength”. Appropriate correction is required.
Applicant is advised that should claim 7 be found allowable, claim 10 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Applicant is advised that should claim 9 be found allowable, claim 12 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Interpretation
Note that an “off-axis dye” is defined as a dye having a first maximum
absorption or excitation wavelength that is an absolute maximum over an entire spectrum of the dye and having a second maximum absorption or excitation wavelengths that is a local
maximum and is separated from the first maximum absorption or excitation wavelength by at
least 60 nanometers (specification, paragraph [0072]). And note that an “on-axis dye” is defined as any dye that is not an off-axis dye (specification, paragraph [0072]).
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:
“chromatically dispersive optical element” in claim 24;
“dispersive optical element” in claim 26.
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.
In this case, “chromatically dispersive optical element” of claim 24 is being interpreted as a prism, diffractive optical element, spectrometer, or spectrophotometer (specification, paragraph [0056]) or equivalents thereof; and
“dispersive optical element” of claim 26 is being interpreted as a prism, diffractive grating or holographic grating (specification, paragraph [0059]) or equivalents thereof.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11, 13, 17, 23, and 25-27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 11, claim 11 recites the limitations "the first maximum emission wavelength or second maximum emission wavelength" and “the respective absorption spectrum”. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 13, claim 13 recites four paragraphs that each different define the first average excitation wavelength, the second average excitation wavelength, the first average emission wavelength, and the second emission spectral element, however, the four paragraphs are not separated by an “or” statement (similar to claim 5). Therefore, it is unclear if all four paragraphs and the specific wavelengths are required or if applicant intends for one of the four paragraphs to be required. It does not appear that all four paragraphs can be required at the same time; for example the first average emission wavelengths of each paragraph are 587, 623, 682, and 711 nm respectively. It is unclear how the first average emission wavelength can be each wavelength. For examination purposes, claim 13 is interpreted as requiring one of the four paragraphs.
Regarding claim 13, claim 13 recites the limitations "the second emission spectral element” in lines 7-8. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 17, claim 17 recites the limitations " the first maximum absorption wavelength, the second maximum absorption wavelength, second maximum emission wavelength, or third maximum emission wavelength…the respective spectrum”. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 23, claim 23 recites the limitation "the filters" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 25, claim 25 recites the limitation "the radiant generator" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 26, claim 26 recites the limitation "the radiant generator" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 27, claim 27 recites “the emission spectral element” in line 2. It is unclear if which emission spectral element is being referred to since claim 14 establishes a first emission spectral element and a second emission spectral element.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 4, 19, and 28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Claim 4 recites “determine an amount…based on the measured emissions”; claim 19 recites “determine an amount…based on the measured emissions”; and claim 28 recites “determine an amount…based on the measured emission(s)”.
In accordance with MPEP 2106, the claims are found to recite statutory subject matter (Step 1: YES) and are analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A: Prong 1).
In the instant application, the limitations of “determine an amount…based on the measured emissions” (claim 4), “determine an amount…based on the measured emissions” (claim 19), and “determine an amount…based on the measured emission(s)” (claim 28) covers performance of a limitation in the mind, i.e. mental process or mathematical calculation. Other than a processor and memory, if the claim limitations, under its broadest reasonable interpretation, covers performance of the limitations in the mind but for the recitation of generic computer components (e.g. processor and memory), then the claim limitations fall within the “Mental Processes” grouping of abstract ideas (MPEP 2106.05(f)). Accordingly, the claims recite abstract ideas (Step 2A: Prong 1: Yes).
This judicial exception is not integrated into a practical application because the claims do not recite any additional elements that reflects an improvement to technology or applies or uses the judicial exception in some other meaningful way (Step 2A, Prong 2: No). In claim 1, once the processor and memory “determine an amount…based on the measured emissions” (claim 4), “determine an amount…based on the measured emissions” (claim 19), and “determine an amount…based on the measured emission(s)” (claim 28), no further action is performed. Therefore, the claimed limitations do not integrate the abstract idea into a practical application because it does not impose any meaningful limits on practicing the abstract idea. The processor and memory limitations are recited at a high-level of generality (i.e., as generic computer) such that it amounts no more than mere instructions to apply the exception using a generic computer component; wherein a general purpose computer is not a particular machine (MPEP 2106.05(b)). Additionally, the preceding steps and limitations are used for data gathering in the abstract idea; wherein, data gathering to be used in the abstract idea is insignificant extra-solution activity, and not a particular practical application. See MPEP 2106.05(g). Therefore, the claimed limitations do not integrate the abstract idea into a practical application because it does not impose any meaningful limits on practicing the abstract idea. Thus, the claims are directed to an abstract idea that is not integrated into a practical application (Step 2A, Prong 2: No).
The claims 4, 19, and 28 do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Regarding the abstract idea, the claims merely recites a processor and memory, wherein the claimed limitations of the computing device amount to no more than mere instructions to apply the exception using a generic computer component; wherein a general purpose computer is not a particular machine (MPEP 2106.05(b)). Claim 4, 19, and 28 further recite limitations, however these limitations generally link the judicial exception to a particular field of use (MPEP 2106.05(h)) and are used for data gathering, wherein data gathering to be used in the abstract idea is an insignificant extra-solution activity, and not a practical application (see MPEP 2106.05(g)), which alone or in combination do not amount to significantly more. Additionally, the limitations of claims 4, 19, and 28 are well-understood, routine and conventional activities as evidenced by the prior art of Unger (US 20060006067 A1), Mao et al. (US 20090305410 A1). See MPEP 2106.05(d). The additional elements of the claims 4, 19, and 28 do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). The claims are not patent eligible.
Claim Rejections - 35 USC § 102/103
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 6, 14, 20-23, and 25-28 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Unger (US 20060006067 A1).
Regarding claim 1, Unger teaches a system (abstract; Fig. 1A), comprising:
a radiant source (Fig. 1A, light source 242 and excitation filter wheel 244) characterized by an average excitation wavelength (paragraphs [0104]-[0107]);
a sample (Figs. 1A and 1C teaches microfluidic device 205 including sample array 206, therefore the microfluidic device includes a sample; paragraph [0015], “samples in the at least one chamber of the at least one microfluidic device”; paragraph [0132] teaches fluorescent emissions from first, second, and third dyes, therefore the microfluidic devices at least comprises a sample including dyes) disposed to receive radiation from the radiant source (Fig. 1A), the sample comprising:
a first dye (paragraph [0132], “first fluorescent dye”);
a second dye (paragraph [0132], “second fluorescent dye”); and
a detector (Fig. 1A, CCD 260) configured to measure emissions from the sample (Fig. 1A; paragraph [0135]);
a first emission spectral element characterized by a first average emission wavelength (paragraph [0132], “a first section of the emission filter wheel is adapted to pass fluorescent emissions produced by a first fluorescent dye”);
a second emission spectral element characterized by a second average emission wavelength that is different than the first average emission wavelength (paragraph [0132], a “second section of the emission filter wheel is adapted to pass fluorescent emissions produced by a second fluorescent dye”, wherein the fluorescent emissions by the second fluorescent dye is interpreted as a second average emission wavelength different than the first average emission wavelength of the first fluorescent dye; paragraph [0173] teaches different filters that pass different wavelength regions);
at least one processor comprising at least one memory (Fig. 1A teaches a computer with a database 270 which is coupled to the light source 242, filter wheels 244,213, and CCD 260; paragraph [0023] teaches a computer adapted to illuminate a microfluidic array device; paragraphs [0104],[0133] teaches a computer controls the filters; paragraph [0139] teaches a CCD in communication with processors to detect a signal) including instructions to:
illuminate the sample with the radiant source and, in response, (1) measure emissions from the sample using the detector and the first emission spectral element and (2) measure emissions from the sample using the detector and the second emission spectral element (Fig. 1A teaches a computer with a database 270 which is coupled to the light source 242, filter wheels 244,213, and CCD 260; paragraph [0023] teaches a computer adapted to illuminate a microfluidic array device; paragraphs [0104],[0133] teaches a computer controls the filters; paragraph [0139] teaches a CCD in communication with processors to detect a signal; therefore, it is implied that the computer 270 includes a processor and memory including instructions to perform the steps as claimed in order to properly control the optical elements to illuminate and measure emissions of the sample in the microfluidic device 205 using the respective filters of the filter wheels).
In the alternative, if Unger fails to teach: at least one processor comprising at least one memory including instructions to: illuminate the sample with the radiant source and, in response, (1) measure emissions from the sample using the detector and the first emission spectral element and (2) measure emissions from the sample using the detector and the second emission spectral element, Unger teaches: a computer with a database 270 which is coupled to the light source 242, filter wheels 244,213, and CCD 260 (Fig. 1A); a computer adapted to illuminate a microfluidic array device (paragraph [0023]); multiple differently labeled probes each designed to hybridize to a particular target and detecting each target based on different fluorescent signals (paragraph [0070]); a computer controlling the filters wheels (paragraphs [0104],[0133]); and a CCD in communication with processors to detect a signal (paragraph [0139]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the system of Unger to incorporate Unger’s teachings of a computer adapted to illuminate the microfluidic array device, control the filter wheels, and detect signals from a CCD (Fig. 1A, paragraphs [0023],[0104],[0133],[0139]) and detecting targets based on different fluorescent signals from different labeled probes (paragraph [0070]) to provide: at least one processor comprising at least one memory including instructions to: illuminate the sample with the radiant source and, in response, (1) measure emissions from the sample using the detector and the first emission spectral element and (2) measure emissions from the sample using the detector and the second emission spectral element. Doing so would have a reasonable expectation of successfully improving control and automation of performing sample analysis using appropriate excitation and emission filters.
Regarding claim 6, Unger a system (abstract; Fig. 1A), comprising:
a first radiant source (Fig. 1A and paragraphs [0104],[0105] light source 242 and a first filter of an excitation filter wheel 244) characterized by a first average excitation wavelength (paragraph [0105]);
a second radiant source (Fig. 1A and paragraphs [0104],[0106],[0107] light source 242 and a second or third filter of an excitation filter wheel 244) characterized by a second average excitation wavelength that is different than the first average excitation wavelength (paragraph [0106] or [0107]);
a nucleic acid sample (Figs. 1A and 1C teaches microfluidic device 205 including sample array 206, therefore the microfluidic device includes a sample; paragraph [0015], “samples in the at least one chamber of the at least one microfluidic device”; paragraph [0076] teaches samples containing target DNA, i.e. nucleic acid sample; paragraph [0132] teaches fluorescent emissions from first, second, and third dyes, therefore the microfluidic devices at least comprises the sample including dyes) disposed to receive radiation from the radiant sources (Fig. 1A), the sample comprising:
a first dye (paragraph [0132], “first fluorescent dye”) configured to bind to a first target molecule (paragraph [0070] teaches multiple differently labeled probes each of which is designed to hybridize only to a particular target; therefore, the sample would include at least a first dye to bind to a first target molecule);
a second dye (paragraph [0132], “second fluorescent dye”) configured to bind to a second target molecule (paragraph [0070] teaches multiple differently labeled probes each of which is designed to hybridize only to a particular target; therefore, the sample would include at least a second dye to bind to a second target molecule); and
a detector (Fig. 1A, CCD 260) configured to measure emissions from the sample (Fig. 1A; paragraph [0135]);
an emission spectral element (Fig. 1A and paragraph [0132], emission filter wheel 213) characterized by an average emission wavelength (paragraph [0132] teaches the emission filter wheel includes sections to pass specific fluorescent emissions, therefore is characterized by at least an average emission wavelength);
at least one processor comprising at least one memory (Fig. 1A teaches a computer with a database 270 which is coupled to the light source 242, filter wheels 244,213, and CCD 260; paragraph [0023] teaches a computer adapted to illuminate a microfluidic array device; paragraphs [0104],[0133] teaches a computer controls the filters; paragraph [0139] teaches a CCD in communication with processors to detect a signal) including instructions to:
illuminate the sample with the first radiant source and, in response, measure emissions from the sample using the detector and the emission spectral element; illuminate the sample with the second radiant source and, in response, measure emissions from the sample using the detector and the emission spectral element (Fig. 1A teaches a computer with a database 270 which is coupled to the light source 242, filter wheels 244,213, and CCD 260; paragraph [0023] teaches a computer adapted to illuminate a microfluidic array device; paragraphs [0104],[0133] teaches a computer controls the filters; paragraph [0139] teaches a CCD in communication with processors to detect a signal; therefore, it is implied that the computer 270 includes a processor and memory including instructions to perform the steps as claimed in order to properly control the optical elements to illuminate and measure emissions of the sample in the microfluidic device 205 using the respective filters of the filter wheels).
In the alternative, if Unger fails to teach: the first dye configured to bind to a first target; the second dye configured to bind to a second target molecule; and at least one processor comprising at least one memory including instructions to: illuminate the sample with the first radiant source and, in response, measure emissions from the sample using the detector and the emission spectral element; illuminate the sample with the second radiant source and, in response, measure emissions from the sample using the detector and the emission spectral element, Unger teaches: a computer with a database 270 which is coupled to the light source 242, filter wheels 244,213, and CCD 260 (Fig. 1A); a computer adapted to illuminate a microfluidic array device (paragraph [0023]); multiple differently labeled probes each designed to hybridize to a particular target and detecting each target based on different fluorescent signals (paragraph [0070]); three different fluorophores (paragraph [0116]); a computer controlling the filters wheels (paragraphs [0104],[0133]); and a CCD in communication with processors to detect a signal (paragraph [0139]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the system of Unger to incorporate Unger’s teachings of a computer adapted to illuminate the microfluidic array device, control the filter wheels, and detect signals from a CCD (Fig. 1A, paragraphs [0023],[0104],[0133],[0139]) and detecting targets based on different fluorescent signals from different labeled probes such as three fluorophores (paragraphs [0070],[0116]) to provide: the first dye configured to bind to a first target; the second dye configured to bind to a second target molecule; and at least one processor comprising at least one memory including instructions to: illuminate the sample with the first radiant source and, in response, measure emissions from the sample using the detector and the emission spectral element; illuminate the sample with the second radiant source and, in response, measure emissions from the sample using the detector and the emission spectral element. Doing so would have a reasonable expectation of successfully improving control and automation of performing sample analysis using appropriate excitation and emission filters and improving analysis of multiple target analytes.
Regarding claim 14, Unger a system (abstract; Fig. 1A), comprising:
a first radiant source (Fig. 1A and paragraphs [0104],[0105] light source 242 and a first filter of an excitation filter wheel 244) characterized by a first average excitation wavelength (paragraph [0105]);
a second radiant source (Fig. 1A and paragraphs [0104],[0106] light source 242 and a second filter of an excitation filter wheel 244) characterized by a second average excitation wavelength that is different than the first average excitation wavelength (paragraph [0106]);
a nucleic acid sample (Figs. 1A and 1C teaches microfluidic device 205 including sample array 206, therefore the microfluidic device includes a sample; paragraph [0015], “samples in the at least one chamber of the at least one microfluidic device”; paragraph [0076] teaches samples containing target DNA, i.e. nucleic acid sample; paragraph [0132] teaches fluorescent emissions from first, second, and third dyes, therefore the microfluidic devices at least comprises the sample including dyes) disposed to receive radiation from the radiant sources (Fig. 1A), the sample comprising:
a first dye (paragraph [0132], “first fluorescent dye”) configured to bind to a first target molecule (paragraph [0070] teaches multiple differently labeled probes each of which is designed to hybridize only to a particular target; therefore, the sample would include at least a first dye to bind to a first target molecule);
a second dye (paragraph [0132], “second fluorescent dye”) configured to bind to a second target molecule (paragraph [0070] teaches multiple differently labeled probes each of which is designed to hybridize only to a particular target; therefore, the sample would include at least a second dye to bind to a second target molecule); and
a third dye (paragraph [0132], “third fluorescent dye”) configure to bind to a third target molecule (paragraph [0070] teaches multiple differently labeled probes each of which is designed to hybridize only to a particular target; therefore, the sample would include at least a third dye to bind to a third target molecule);
a detector (Fig. 1A, CCD 260) configured to measure emissions from the sample (Fig. 1A; paragraph [0135]);
a first emission spectral element characterized by a first average emission wavelength (paragraph [0132], “a first section of the emission filter wheel is adapted to pass fluorescent emissions produced by a first fluorescent dye”);
a second emission spectral element characterized by a second average emission wavelength that is different than the first average emission wavelength (paragraph [0132], a “second section of the emission filter wheel is adapted to pass fluorescent emissions produced by a second fluorescent dye”, wherein the fluorescent emissions by the second fluorescent dye is interpreted as a second average emission wavelength different than the first average emission wavelength of the first fluorescent dye; paragraph [0173] teaches different filters that pass different wavelength regions);
at least one processor comprising at least one memory (Fig. 1A teaches a computer with a database 270 which is coupled to the light source 242, filter wheels 244,213, and CCD 260; paragraph [0023] teaches a computer adapted to illuminate a microfluidic array device; paragraphs [0104],[0133] teaches a computer controls the filters; paragraph [0139] teaches a CCD in communication with processors to detect a signal) including instructions to:
illuminate the sample with the first radiant source and, in response, (1) measure emissions from the sample using the detector and the first emission spectral element and (2) measure emissions from the sample using the detector and the second emission spectral element; illuminate the sample with the second radiant source and, in response, measure emissions from the sample using the detector and the second emission spectral element (Fig. 1A teaches a computer with a database 270 which is coupled to the light source 242, filter wheels 244,213, and CCD 260; paragraph [0023] teaches a computer adapted to illuminate a microfluidic array device; paragraphs [0104],[0133] teaches a computer controls the filters; paragraph [0139] teaches a CCD in communication with processors to detect a signal; therefore, it is implied that the computer 270 includes a processor and memory including instructions to perform the steps as claimed in order to properly control the optical elements to illuminate and measure emissions of the sample in the microfluidic device 205 using the respective filters of the filter wheels).
In the alternative, if Unger fails to teach: the first dye configured to bind to a first target; the second dye configured to bind to a second target molecule; the third configure to bind to a third target molecule; and at least one processor comprising at least one memory including instructions to: illuminate the sample with the first radiant source and, in response, (1) measure emissions from the sample using the detector and the first emission spectral element and (2) measure emissions from the sample using the detector and the second emission spectral element; illuminate the sample with the second radiant source and, in response, measure emissions from the sample using the detector and the second emission spectral element, Unger teaches: a computer with a database 270 which is coupled to the light source 242, filter wheels 244,213, and CCD 260 (Fig. 1A); a computer adapted to illuminate a microfluidic array device (paragraph [0023]); multiple differently labeled probes each designed to hybridize to a particular target and detecting each target based on different fluorescent signals (paragraph [0070]); three different fluorophores (paragraph [0116]); a computer controlling the filters wheels (paragraphs [0104],[0133]); and a CCD in communication with processors to detect a signal (paragraph [0139]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the system of Unger to incorporate Unger’s teachings of a computer adapted to illuminate the microfluidic array device, control the filter wheels, and detect signals from a CCD (Fig. 1A, paragraphs [0023],[0104],[0133],[0139]) and detecting targets based on different fluorescent signals from different labeled probes such as three fluorophores (paragraphs [0070],[0116]) to provide: the first dye configured to bind to a first target; the second dye configured to bind to a second target molecule; the third configure to bind to a third target molecule; and at least one processor comprising at least one memory including instructions to: illuminate the sample with the first radiant source and, in response, (1) measure emissions from the sample using the detector and the first emission spectral element and (2) measure emissions from the sample using the detector and the second emission spectral element; illuminate the sample with the second radiant source and, in response, measure emissions from the sample using the detector and the second emission spectral element. Doing so would have a reasonable expectation of successfully improving control and automation of performing sample analysis using appropriate excitation and emission filters and improving analysis of multiple target analytes.
Regarding claim 20, Unger further teaches wherein each of the radiant sources is characterized by radiation having a maximum wavelength and/or average wavelength in the visible light spectrum or the infrared wavelength band and/or ultraviolet wavelength band (paragraphs [0104]-[0106] teaches the center wavelengths of 485 and 530, which are in the visible light spectrum).
Regarding claim 21, Unger further teaches wherein at least one of the radiant sources comprises a light emitting diode (LED) or a laser (paragraph [0103]).
Regarding claim 22, Unger further teaches wherein:
the first radiant source comprises a radiant generator (Fig. 1A, light source 242) and a first filter (Fig. 1A and paragraphs [0104],[0105] a first filter of an excitation filter wheel 244) are configured to filter radiation from the radiant generator (paragraphs [0104],[0105]); and
the second radiant source comprises the radiant generator (Fig. 1A, light source 242) and a second filter (Fig. 1A and paragraphs [0104],[0106] a second filter of an excitation filter wheel 244) are configured to filter radiation from the radiant generator (paragraphs [0104],[0106]).
Regarding claim 23, Unger further teaches the system of claim 14, further comprising a filter wheel comprising the filters (Fig. 1A and paragraphs [0104], filter wheel 244 or 213).
Regarding claim 25, Unger further teaches wherein the radiant generator comprises a light source (Fig. 1A, light source 242).
Regarding claim 26, Unger further teaches system of claim 14, wherein:
- the radiant generator (Fig. 1, light source 242) comprises a white light source characterized by over at least a portion of the visible band of radiation (paragraph [0103] teaches a white light source producing optical radiation over a spectral range from about 400 nm to about 700 nm),
- the radiant generator comprises a light emitting diode or a halogen lamp (paragraph [0103]),
- the detector comprises an array sensor comprising an array of sensors or pixels (Fig. 1A and paragraph [0135], CCD camera array),
- the array sensor comprises a charge coupled device (CCD) or a complementary metal-oxide- semiconductor (CMOS) (Fig. 1A and paragraph [0135], CCD camera array), or
- the emission spectral elements comprise a dispersive optical element configure to disperse emissions from the sample along a first optical path and second optical path, wherein the detector comprises a first detector configured to receive emissions along the first optical path and a second detector configured to receive emissions along the second optical path, optionally wherein the first detector comprises a first location on a CCD detector or CMOS detector and the second comprises a second location on a CCD detector or CMOS detector that is spatially separated from the first location, optionally wherein the first location comprises a pixel or a group of pixels, and the second location comprises a different pixel or group of pixels (interpreted as not required due to the “or” statement).
Regarding claim 27, Unger further teaches the system of claim 14, further comprising a filter wheel comprising the emission spectral elements (paragraph [0132] and Fig. 1A teaches emission filter wheel 213), the filter wheel being configured to sequentially place the emission spectral element along an optical path between the sample and the detector in order to measure emissions from the sample (Fig. 1A and paragraphs [0132]-[0133], [0166],[0168]-[0169]).
Regarding claim 28, Unger further teaches the system of claim 14, further comprising:
providing a third radiant source (interpreted as an intended use, see MPEP 2114; Fig. 1A and paragraphs [0104],[0107] light source 242 and a third filter of an excitation filter wheel 244) characterized by a third average excitation wavelength that is different than the first average excitation wavelength of the first radiant source or the second average excitation wavelength of the second radiant source (paragraphs [0107]);
illuminating the sample with radiation from a third radiant source and, in response, measuring an emission from the sample using one or more of the first emission spectral element or the second emission spectral element (interpreted as an intended use, see MPEP 2114; paragraph [0104] teaches the excitation filter wheel including the third filter filters light emitted by the optical source for exciting a sample; Fig. 1A teaches a computer with a database 270 which is coupled to the light source 242, filter wheels 244,213, and CCD 260; paragraph [0023] teaches a computer adapted to illuminate a microfluidic array device; paragraphs [0104],[0133] teaches a computer controls the filters; paragraph [0139] teaches a CCD in communication with processors to detect a signal; therefore, the system is capable of illuminating the sample with the third filter of the excitation filter wheel 244 and measuring an emission from the emission filter wheel 213 using CCD 260);
determining an amount of one or more of target molecules is based on the measured emission(s) from the sample in response to illuminating the sample with radiation from the third radiant source (interpreted as an intended use, see MPEP 2114; paragraph [0034] teaches single cell macro molecule quantification; paragraph [0066] teaches determining the quantity of a target nucleic acid; paragraph [0070] teaches detecting several targets based on fluorescence signals; therefore, the system is capable of being used for determining an amount or quantifying a target molecule based on emission by illumination using the third filter of the excitation filter wheel 244).
Claims 2, 4, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Unger as applied to claims 1 and 14 above, and further in view of Mao et al. (US 20090305410 A1).
Regarding claim 2, Unger fails to teach: wherein the first dye comprises a first absorption spectrum comprising a first maximum absorption wavelength and the second dye comprises a second absorption spectrum comprising a second maximum absorption wavelength that is equal to or substantially equal first maximum absorption wavelength, optionally wherein one or more of the first maximum absorption wavelength or second maximum absorption wavelength is an absolute maximum over an entirety of the respective spectrum.
Mao teaches fluorescent dyes and kits for labeling biomolecules for research and development, forensic identification, environmental studies, diagnosis, prognosis, and/or treatment of disease conditions (abstract). Mao teaches probes labeled with fluorescent groups for use as a PCR probe are well known to one skilled in the art (paragraph [0310]). Mao teaches the use of tandem dyes are useful for multi-color detections where only a limited number of excitation light sources may be available (paragraph [0304]) and in order to detect multiple targets, each target may be stained with a different fluorescent group having a different emission and the different fluorescent groups all need to be efficiently excited by a common excitation source (paragraph [0304]), wherein different tandem dyes having the same excitation maxima but different emission maxima can be readily prepared (paragraph [0304]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first dye and the second dye to incorporate the teachings of different fluorescent dyes having the same excitation maxima but different emission maxima of Mao (paragraph [0304]) to provide: wherein the first dye comprises a first absorption spectrum comprising a first maximum absorption wavelength and the second dye comprises a second absorption spectrum comprising a second maximum absorption wavelength that is equal to or substantially equal first maximum absorption wavelength, optionally wherein one or more of the first maximum absorption wavelength or second maximum absorption wavelength is an absolute maximum over an entirety of the respective spectrum. Doing so would have a reasonable expectation of successfully improving detection of multiple targets efficiently using a common light source as taught by Mao.
Regarding claim 4, while Unger teaches single cell macro molecule detection and quantification (paragraph [0034]), determining the quantity of a target nucleic acid present in a sample by measuring the amount of amplification product formed during or after the amplification process itself (paragraph [0066]), and detecting several targets based on fluorescence signals (paragraph [0070]), Unger fails to teach: wherein the at least one memory includes instructions to determine an amount of any target molecules present in the sample based on the measured emissions.
Mao teaches fluorescent dyes and kits for labeling biomolecules for research and development, forensic identification, environmental studies, diagnosis, prognosis, and/or treatment of disease conditions (abstract). Mao teaches probes labeled with fluorescent groups for use as a PCR probe are well known to one skilled in the art (paragraph [0310]). Mao teaches contacting a labeled polynucleotide with a target nucleic acid and detecting or quantifying the nucleic acid target by measuring a change in fluorescence of the probe (paragraph [0311]). Mao teaches quantitative fluorescence analysis performed with software (paragraph [0380]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the at least one memory of Unger to incorporate Unger’s teachings of quantifying a target nucleic acid (paragraphs [0034],[0066],[0070]) and Mao’s teachings of quantifying a nucleic acid target based on measured fluorescence and software for quantitative analysis (paragraphs [0310]-[0311],[0380]) to provide: wherein the at least one memory includes instructions to determine an amount of any target molecules present in the sample based on the measured emissions. Doing so would have a reasonable expectation of successfully improving automation of calculation of target molecules.
Regarding claim 19, while Unger teaches single cell macro molecule detection and quantification (paragraph [0034]), determining the quantity of a target nucleic acid present in a sample by measuring the amount of amplification product formed during or after the amplification process itself (paragraph [0066]), and detecting several targets based on fluorescence signals (paragraph [0070]), Unger fails to teach wherein the at least one memory further comprises instructions to determine an amount of any target molecules present in the sample based on the measured emissions.
Mao teaches fluorescent dyes and kits for labeling biomolecules for research and development, forensic identification, environmental studies, diagnosis, prognosis, and/or treatment of disease conditions (abstract). Mao teaches probes labeled with fluorescent groups for use as a PCR probe are well known to one skilled in the art (paragraph [0310]). Mao teaches contacting a labeled polynucleotide with a target nucleic acid and detecting or quantifying the nucleic acid target by measuring a change in fluorescence of the probe (paragraph [0311]). Mao teaches quantitative fluorescence analysis performed with software (paragraph [0380]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the at least one memory of Unger to incorporate Unger’s teachings of quantifying a target nucleic acid (paragraphs [0034],[0066],[0070]) and Mao’s teachings of quantifying a nucleic acid target based on measured fluorescence and software for quantitative analysis (paragraphs [0310]-[0311],[0380]) to provide: wherein the at least one memory further comprises instructions to determine an amount of any target molecules present in the sample based on the measured emissions. Doing so would have a reasonable expectation of successfully improving automation of calculation of target molecules.
Claims 3, 5, 9, 12, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Unger as applied to claims 1, 6, and 14 above, and further in view of Natt et al. (US 20110097716 A1).
Regarding claim 3, Unger further teaches the first dye is an on-axis dye (paragraph [0132] teaches the first fluorescent dye is Cy3 Fluor; wherein, Cy3 Fluor dye is interpreted as an on-axis dye since it is a dye without a first and second maximum absorption or excitation wavelength that is separated by at least 60 nm).
Unger fails to teach: wherein the second dye is an off-axis dye.
Unger teaches detection including oligonucleotides and FRET-based assays using donor/acceptor fluorophore pair (paragraphs [0064]-[0065]). Unger teaches dual-labeled fluorogenic oligonucleotide probes are used for real time quantitative PCR (paragraph [0066]). Unger teaches fluorophores such as Rox, Vic, and Fam (paragraph [0116]).
Natt teaches methods and compositions for detecting and quantifying nucleic acid oligonucleotides in a biological sample (abstract). Natt teaches a need exists to develop more rapid, sensitive methods for detecting small RNA molecules (paragraph [0005]). Natt teaches signal emitting probes that bind with oligonucleotide molecules include FAM, VIC, JOE, NED, CY5 dye, CY3-dye, TAMRA labeled probe; and a preferred embodiment of a FAM/TAMRA detection group (paragraph [0014]). Natt teaches real-time quantitation comprises reporter probes including FAM/TAMRA (paragraph [0040]). Natt teaches reporter probes can be singly labeled or doubly labeled, where dual probe systems comprise FRET between adjacently hybridized probes (paragraph [0045]). Natt teaches multi-element interacting reporter groups include fluorophore-quencher pairs, such as a FAM-TAMRA pair (paragraph [0057]). Natt teaches the invention improves sensitivity for quantifying oligonucleotide molecules (paragraph [0015]). Note that FAM-TAMRA is interpreted as an off-axis dye since the instant specification, paragraph [0115] includes FAM-TAMRA as an off-axis dye.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the second dye of Unger to incorporate Unger’s teachings of FRET-based assays using donor/acceptor fluorophore pair and dual-labeled fluorogenic oligonucleotide probes (paragraphs [0064]-[0065]) and Natt’s teachings of signal emitting probes, i.e. dyes, including FAM-TAMRA, i.e. off-axis dye, for quantifying nucleic acid oligonucleotides (paragraphs [0014],[0045],[0057]) to provide: wherein the second dye is an off-axis dye. Doing so would have a reasonable expectation of successfully utilizing known dyes for improving sensitivity for quantifying oligonucleotide molecules (Natt, paragraph [0015]).
Regarding claim 5, Unger further teaches: wherein:
the average excitation wavelength of the first radiant source is 480 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to ± 12 nanometers about the average excitation wavelength (Fig. 1A and paragraphs [0104],[0105] light source 242 and a first filter of an excitation filter wheel 244, wherein the center wavelength of 485 nm with a spectral bandwidth of 20 nm).
Unger fails to teach: the first average emission wavelength of the first emission spectral element is 520 +-5 nanometers and/or the first emission spectral element is characterized by a wavelength band that is less than or equal to +- 20 nanometers about the first average emission wavelength, and the second average emission wavelength of the second emission spectral element is 587 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the second average emission wavelength;
the first average emission wavelength of the first emission spectral element is 520 +-5 nanometers and/or the first emission spectral element is characterized by a wavelength band that is less than or equal to +- 18 nanometers about the first average emission wavelength; and the second average emission wavelength of the second emission spectral element is 623 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +- 18 nanometers about the second average emission wavelength;
or
the average excitation wavelength of the first radiant source is 550 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +- 14 nanometers about the average excitation wavelength, the first average emission wavelength of the first emission spectral element is 587 +-5 nanometers and/or the first emission spectral element is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the first average emission wavelength, and the second average emission wavelength of the second emission spectral element is 682 +-5 or 711 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +-16 nanometers about the second average emission wavelength.
Unger teaches a section of the emission filter is adapted to pass fluorescence emission from Alexa Fluor 488 (paragraph [0132]). Unger teaches a spectral filter of the emission filter having an average emission wavelength of the first emission spectral element is 520 +-5 nanometers and/or the spectral filter is characterized by a wavelength band that is less than or equal to +- 18 nanometers about the average emission wavelength (paragraph [0168] teaches a spectral filter centered at 518 nm with a bandwidth of 25 nm). Unger teaches detection including oligonucleotides and FRET-based assays using donor/acceptor fluorophore pair (paragraphs [0064]-[0065]). Unger teaches dual-labeled fluorogenic oligonucleotide probes are used for real time quantitative PCR (paragraph [0066]). Unger teaches fluorophores such as Rox, Vic, and Fam (paragraph [0116]).
Natt teaches a need exists to develop more rapid, sensitive methods for detecting small RNA molecules (paragraph [0005]). Natt teaches signal emitting probes that bind with oligonucleotide molecules include FAM, VIC, JOE, NED, CY5 dye, CY3-dye, TAMRA labeled probe; and a preferred embodiment of a FAM/TAMRA detection group (paragraph [0014]). Natt teaches real-time quantitation comprises reporter probes including FAM/TAMRA (paragraph [0040]). Natt teaches reporter probes can be singly labeled or doubly labeled, where dual probe systems comprise FRET between adjacently hybridized probes (paragraph [0045]). Natt teaches multi-element interacting reporter groups include fluorophore-quencher pairs, such as a FAM-TAMRA pair, which emits fluorescence at 580 nm (paragraph [0057]). Natt teaches the invention improves sensitivity for quantifying oligonucleotide molecules (paragraph [0015]). Natt teaches alternative reporter groups with an emission wavelength of 584 nm (paragraph [0058]). Note that FAM-TAMRA is interpreted as a suitable dye with an emission band of 587 +-10 nm since the instant specification, paragraph [0111], table 1, includes FAM-TAMRA as having an emission band of 587 +-10 nm.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first emission spectral element and the second emission spectral element of Unger to incorporate Unger’s teachings of FRET-based assays using donor/acceptor fluorophore pair and dual-labeled fluorogenic oligonucleotide probes (paragraphs [0064]-[0065]), emission filter to pass emission from Alexa Fluor 488 (paragraph [0132]), and an emission filter of 518 nm +-25nm (paragraph [0168]) and Natt’s teachings of signal emitting probes, i.e. dyes, including FAM-TAMRA, i.e. off-axis dye, for quantifying nucleic acid oligonucleotides (paragraphs [0014],[0045],[0057]) to provide: the first average emission wavelength of the first emission spectral element is 520 +-5 nanometers and/or the first emission spectral element is characterized by a wavelength band that is less than or equal to +- 20 nanometers about the first average emission wavelength, and the second average emission wavelength of the second emission spectral element is 587 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the second average emission wavelength. Doing so would have a reasonable expectation of successfully optimizing the spectral elements to properly filter desired emission wavelengths of desired dyes, therefore improving sensitivity for quantifying oligonucleotide molecules (Natt, paragraph [0015]).
Note that the limitations of “the average excitation wavelength of the first radiant source is 480 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the average excitation wavelength, the first average emission wavelength of the first emission spectral element is 520 +-5 nanometers and/or the first emission spectral element is characterized by a wavelength band that is less than or equal to +- 18 nanometers about the first average emission wavelength; and the second average emission wavelength of the second emission spectral element is 623 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +- 18 nanometers about the second average emission wavelength; or the average excitation wavelength of the first radiant source is 550 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +- 14 nanometers about the average excitation wavelength, the first average emission wavelength of the first emission spectral element is 587 +-5 nanometers and/or the first emission spectral element is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the first average emission wavelength, and the second average emission wavelength of the second emission spectral element is 682 +-5 or 711 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +16 nanometers about the second average emission wavelength” are interpreted as not required.
Regarding claim 9, Unger fails to teach: wherein the second dye is an off-axis dye.
Unger teaches detection including oligonucleotides and FRET-based assays using donor/acceptor fluorophore pair (paragraphs [0064]-[0065]). Unger teaches dual-labeled fluorogenic oligonucleotide probes are used for real time quantitative PCR (paragraph [0066]). Unger teaches fluorophores such as Rox, Vic, and Fam (paragraph [0116]).
Natt teaches methods and compositions for detecting and quantifying nucleic acid oligonucleotides in a biological sample (abstract). Natt teaches a need exists to develop more rapid, sensitive methods for detecting small RNA molecules (paragraph [0005]). Natt teaches signal emitting probes that bind with oligonucleotide molecules include FAM, VIC, JOE, NED, CY5 dye, CY3-dye, TAMRA labeled probe; and a preferred embodiment of a FAM/TAMRA detection group (paragraph [0014]). Natt teaches real-time quantitation comprises reporter probes including FAM/TAMRA (paragraph [0040]). Natt teaches reporter probes can be singly labeled or doubly labeled, where dual probe systems comprise FRET between adjacently hybridized probes (paragraph [0045]). Natt teaches multi-element interacting reporter groups include fluorophore-quencher pairs, such as a FAM-TAMRA pair (paragraph [0057]). Natt teaches the invention improves sensitivity for quantifying oligonucleotide molecules (paragraph [0015]). Note that FAM-TAMRA is interpreted as an off-axis dye since the instant specification, paragraph [0115] includes FAM-TAMRA as an off-axis dye.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the second dye of Unger to incorporate Unger’s teachings of FRET-based assays using donor/acceptor fluorophore pair and dual-labeled fluorogenic oligonucleotide probes (paragraphs [0064]-[0065]) and Natt’s teachings of signal emitting probes, i.e. dyes, including FAM-TAMRA, i.e. off-axis dye, for quantifying nucleic acid oligonucleotides (paragraphs [0014],[0045],[0057]) to provide: wherein the second dye is an off-axis dye. Doing so would have a reasonable expectation of successfully utilizing known dyes for improving sensitivity for quantifying oligonucleotide molecules (Natt, paragraph [0015]).
Regarding claim 12, Unger fails to teach: wherein the second dye is an off-axis dye.
Unger teaches detection including oligonucleotides and FRET-based assays using donor/acceptor fluorophore pair (paragraphs [0064]-[0065]). Unger teaches dual-labeled fluorogenic oligonucleotide probes are used for real time quantitative PCR (paragraph [0066]). Unger teaches fluorophores such as Rox, Vic, and Fam (paragraph [0116]).
Natt teaches methods and compositions for detecting and quantifying nucleic acid oligonucleotides in a biological sample (abstract). Natt teaches a need exists to develop more rapid, sensitive methods for detecting small RNA molecules (paragraph [0005]). Natt teaches signal emitting probes that bind with oligonucleotide molecules include FAM, VIC, JOE, NED, CY5 dye, CY3-dye, TAMRA labeled probe; and a preferred embodiment of a FAM/TAMRA detection group (paragraph [0014]). Natt teaches real-time quantitation comprises reporter probes including FAM/TAMRA (paragraph [0040]). Natt teaches reporter probes can be singly labeled or doubly labeled, where dual probe systems comprise FRET between adjacently hybridized probes (paragraph [0045]). Natt teaches multi-element interacting reporter groups include fluorophore-quencher pairs, such as a FAM-TAMRA pair (paragraph [0057]). Natt teaches the invention improves sensitivity for quantifying oligonucleotide molecules (paragraph [0015]). Note that FAM-TAMRA is interpreted as an off-axis dye since the instant specification, paragraph [0115] includes FAM-TAMRA as an off-axis dye.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the second dye of Unger to incorporate Unger’s teachings of FRET-based assays using donor/acceptor fluorophore pair and dual-labeled fluorogenic oligonucleotide probes (paragraphs [0064]-[0065]) and Natt’s teachings of signal emitting probes, i.e. dyes, including FAM-TAMRA, i.e. off-axis dye, for quantifying nucleic acid oligonucleotides (paragraphs [0014],[0045],[0057]) to provide: wherein the second dye is an off-axis dye. Doing so would have a reasonable expectation of successfully utilizing known dyes for improving sensitivity for quantifying oligonucleotide molecules (Natt, paragraph [0015]).
Regarding claim 18, Unger fails to teach wherein the second dye is an off-axis dye.
Unger teaches detection including oligonucleotides and FRET-based assays using donor/acceptor fluorophore pair (paragraphs [0064]-[0065]). Unger teaches dual-labeled fluorogenic oligonucleotide probes are used for real time quantitative PCR (paragraph [0066]). Unger teaches fluorophores such as Rox, Vic, and Fam (paragraph [0116]).
Natt teaches methods and compositions for detecting and quantifying nucleic acid oligonucleotides in a biological sample (abstract). Natt teaches a need exists to develop more rapid, sensitive methods for detecting small RNA molecules (paragraph [0005]). Natt teaches signal emitting probes that bind with oligonucleotide molecules include FAM, VIC, JOE, NED, CY5 dye, CY3-dye, TAMRA labeled probe; and a preferred embodiment of a FAM/TAMRA detection group (paragraph [0014]). Natt teaches real-time quantitation comprises reporter probes including FAM/TAMRA (paragraph [0040]). Natt teaches reporter probes can be singly labeled or doubly labeled, where dual probe systems comprise FRET between adjacently hybridized probes (paragraph [0045]). Natt teaches multi-element interacting reporter groups include fluorophore-quencher pairs, such as a FAM-TAMRA pair (paragraph [0057]). Natt teaches the invention improves sensitivity for quantifying oligonucleotide molecules (paragraph [0015]). Note that FAM-TAMRA is interpreted as an off-axis dye since the instant specification, paragraph [0115] includes FAM-TAMRA as an off-axis dye.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the second dye of Unger to incorporate Unger’s teachings of FRET-based assays using donor/acceptor fluorophore pair and dual-labeled fluorogenic oligonucleotide probes (paragraphs [0064]-[0065]) and Natt’s teachings of signal emitting probes, i.e. dyes, including FAM-TAMRA, i.e. off-axis dye, for quantifying nucleic acid oligonucleotides (paragraphs [0014],[0045],[0057]) to provide: wherein the second dye is an off-axis dye. Doing so would have a reasonable expectation of successfully utilizing known dyes for improving sensitivity for quantifying oligonucleotide molecules (Natt, paragraph [0015]).
Claims 7-8, 10-11, 13, 17, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Unger as applied to claims 6 and 14 above, and further in view of Oldham et al. (US 20060252079 A1).
Regarding claim 7, Unger fails to teach: wherein the first dye comprises a first emission spectrum comprising a first maximum emission wavelength and the second dye comprises a second emission spectrum comprising a second maximum emission wavelength that is equal to or substantially equal first maximum emission wavelength.
Oldham teaches a system including at least two excitation sources to provide different wavelengths, at least one detector, and a plurality of spectrally resolvable dyes (abstract). Oldham teaches the detection system can include a set of dyes and one of more of a PCR detection system (paragraph [0005]). Oldham teaches a set of dyes for the system includes at least two dyes of the set having different absorption wavelengths but the same emission wavelength ranges (paragraphs [0006],[0012]). Oldham teaches a set of energy transfer dyes including acceptor dye moieties of the same emission wavelength as acceptor dye moieties of other dyes of the set (paragraph [0006]). Oldham teaches embodiments using set of dyes, where each dye emits the same peak emission, can be beneficial; wherein the detector can be tuned for optimum detection of the shared emission wavelengths of the dyes (paragraph [0024]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first and second dye of Unger to incorporate the teachings of dyes having different absorption wavelengths but the same emission wavelengths of Oldham (paragraphs [0006],[0012],[0024]) to provide: wherein the first dye comprises a first emission spectrum comprising a first maximum emission wavelength and the second dye comprises a second emission spectrum comprising a second maximum emission wavelength that is equal to or substantially equal first maximum emission wavelength. Doing so would have a reasonable expectation of successfully optimizing detection of emission wavelengths dyes as taught by Oldham (paragraph [0024]).
Regarding claim 8, modified Unger fails to teach: wherein one or more of the first maximum emission wavelength or second maximum emission wavelength is an absolute maximum over an entirety of the respective spectrum.
Oldham teaches a system including at least two excitation sources to provide different wavelengths, at least one detector, and a plurality of spectrally resolvable dyes (abstract). Oldham teaches the detection system can include a set of dyes and one of more of a PCR detection system (paragraph [0005]). Oldham teaches a set of dyes for the system includes at least two dyes of the set having different absorption wavelengths but the same emission wavelength ranges (paragraphs [0006],[0012]). Oldham teaches a set of energy transfer dyes including acceptor dye moieties of the same emission wavelength as acceptor dye moieties of other dyes of the set (paragraph [0006]). Oldham teaches embodiments using set of dyes, where each dye emits the same peak emission, can be beneficial; wherein the detector can be tuned for optimum detection of the shared emission wavelengths of the dyes (paragraph [0024]). Oldham teaches peak wavelength refers to peak wavelength that provides maximum energy released as radiation from a dye (paragraph [0022]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first and second dye of Unger to incorporate the teachings of dyes having different absorption wavelengths but the same emission wavelengths of Oldham (paragraphs [0006],[0012],[0024]) and the teachings of maximum or peak emission of Oldham (paragraphs [0022],[0024]) to provide: wherein one or more of the first maximum emission wavelength or second maximum emission wavelength is an absolute maximum over an entirety of the respective spectrum. Doing so would have a reasonable expectation of successfully optimizing detection of emission wavelengths dyes as taught by Oldham (paragraph [0024]).
Regarding claim 10, Unger fails to teach: wherein the first dye comprises a first emission spectrum comprising a first maximum emission wavelength and the second dye comprises a second emission spectrum comprising a second maximum emission wavelength that is equal to or substantially equal the first maximum emission wavelength.
Oldham teaches a system including at least two excitation sources to provide different wavelengths, at least one detector, and a plurality of spectrally resolvable dyes (abstract). Oldham teaches the detection system can include a set of dyes and one of more of a PCR detection system (paragraph [0005]). Oldham teaches a set of dyes for the system includes at least two dyes of the set having different absorption wavelengths but the same emission wavelength ranges (paragraphs [0006],[0012]). Oldham teaches a set of energy transfer dyes including acceptor dye moieties of the same emission wavelength as acceptor dye moieties of other dyes of the set (paragraph [0006]). Oldham teaches embodiments using set of dyes, where each dye emits the same peak emission, can be beneficial; wherein the detector can be tuned for optimum detection of the shared emission wavelengths of the dyes (paragraph [0024]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first and second dye of Unger to incorporate the teachings of dyes having different absorption wavelengths but the same emission wavelengths of Oldham (paragraphs [0006],[0012],[0024]) to provide: wherein the first dye comprises a first emission spectrum comprising a first maximum emission wavelength and the second dye comprises a second emission spectrum comprising a second maximum emission wavelength that is equal to or substantially equal the first maximum emission wavelength. Doing so would have a reasonable expectation of successfully optimizing detection of emission wavelengths dyes as taught by Oldham (paragraph [0024]).
Regarding claim 11, Unger fails to teach: wherein one or more of the first maximum emission wavelength or second maximum emission wavelength is an absolute maximum over an entirety of the respective absorption spectrum.
Oldham teaches a system including at least two excitation sources to provide different wavelengths, at least one detector, and a plurality of spectrally resolvable dyes (abstract). Oldham teaches the detection system can include a set of dyes and one of more of a PCR detection system (paragraph [0005]). Oldham teaches a set of dyes for the system includes at least two dyes of the set having different absorption wavelengths but the same emission wavelength ranges (paragraphs [0006],[0012]). Oldham teaches a set of energy transfer dyes including acceptor dye moieties of the same emission wavelength as acceptor dye moieties of other dyes of the set (paragraph [0006]). Oldham teaches embodiments using set of dyes, where each dye emits the same peak emission, can be beneficial; wherein the detector can be tuned for optimum detection of the shared emission wavelengths of the dyes (paragraph [0024]). Oldham teaches peak wavelength refers to peak wavelength that provides maximum energy released as radiation from a dye (paragraph [0022]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first and second dye of Unger to incorporate the teachings of dyes having different absorption wavelengths but the same emission wavelengths of Oldham (paragraphs [0006],[0012],[0024]) and the teachings of maximum or peak emission of Oldham (paragraphs [0022],[0024]) to provide: wherein one or more of the first maximum emission wavelength or second maximum emission wavelength is an absolute maximum over an entirety of the respective absorption spectrum. Doing so would have a reasonable expectation of successfully optimizing detection of emission wavelengths dyes as taught by Oldham (paragraph [0024]).
Regarding claim 13, Unger further teaches wherein:
the average excitation wavelength of the first radiant source is 480 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to ± 12 nanometers about the average excitation wavelength (Fig. 1A and paragraphs [0104],[0105] teach light source 242 and a first filter of an excitation filter wheel 244, wherein the center wavelength of 485 nm with a spectral bandwidth of 20 nm), the second average excitation wavelength of the second radiant source is 580 +-5 nanometers and/or the second radiant source is characterized by a wavelength band that is less than or equal to + 12 nanometers about the second average excitation wavelength (Fig. 1A and paragraphs [0104],[0107] teach light source 242 and a third filter of an excitation filter wheel 244, wherein the center wavelength of 580 nm with a spectral bandwidth of 20 nm).
Unger fails to teach: wherein:
the second average excitation wavelength of the second radiant source is 550 +-5 nanometers and/or the second radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the second average excitation wavelength, the first average emission wavelength of the first emission spectral element is 587 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +-12 nanometers about the average emission wavelength;
the average emission wavelength of the first emission spectral element is 623 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +-18 nanometers about the average emission wavelength;
the first average excitation wavelength of the first radiant source is 550 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +- 14 nanometers about the first average excitation wavelength, the second average excitation wavelength of the second radiant source is 640 +-5 nanometers and/or the second radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the second average excitation wavelength, the average emission wavelength of the first emission spectral element is 682 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +- 16 nanometers about the average emission wavelength;
the first average excitation wavelength of the first radiant source is 550 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +- 14 nanometers about the first average excitation wavelength, the second average excitation wavelength of the second radiant source is 662 +-5 nanometers and/or the second radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the second average excitation wavelength; and the average emission wavelength of the first emission spectral element is 711 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +-16 nanometers about the average emission wavelength.
Unger teaches wavelengths produced including 621 nm (paragraph [0185]).
Oldham teaches a system including at least two excitation sources to provide different wavelengths, at least one detector, and a plurality of spectrally resolvable dyes (abstract). Oldham teaches the detection system can include a set of dyes and one of more of a PCR detection system (paragraph [0005]). Oldham teaches a set of dyes for the system includes at least two dyes of the set having different absorption wavelengths but the same emission wavelength ranges (paragraphs [0006],[0012]). Oldham teaches a set of energy transfer dyes including acceptor dye moieties of the same emission wavelength as acceptor dye moieties of other dyes of the set (paragraph [0006]). Oldham teaches embodiments using set of dyes, where each dye emits the same peak emission, can be beneficial; wherein the detector can be tuned for optimum detection of the shared emission wavelengths of the dyes, such as 620 nm (paragraph [0024]). Oldham teaches examples of suitable dyes, including Alexa Fluor 594, which has an emission of 617 (paragraph [0032], table 1). Note that Alexa Fluor 594 is interpreted as a suitable dye with an emission band of 623 +-14 nm since the instant specification, paragraph [0111], table 1, includes Alexa Fluor 594 as having an emission band of 623 +-14 nm.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first emission spectral element of Unger to incorporate Unger’s teachings of wavelengths produced including 621 nm (paragraph [0185]), and Oldham’s teachings of dyes having different absorption wavelengths but the same emission wavelengths (paragraphs [0006],[0012],[0024]) optimizing detection of emission wavelength of 620 nm (paragraph [0024]), and suitable dyes including Alexa Fluor 594 (paragraph 0032], table 1) to provide: the average emission wavelength of the first emission spectral element is 623 +-5 nanometers. Doing so would have a reasonable expectation of successfully optimizing detection of emission wavelengths of known dyes, e.g. Alexa Fluor 594, as taught by Oldham (paragraph [0024]).
Note that the limitations of “the second average excitation wavelength of the second radiant source is 550 +-5 nanometers and/or the second radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the second average excitation wavelength, the first average emission wavelength of the first emission spectral element is 587 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +-12 nanometers about the average emission wavelength; and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +-18 nanometers about the average emission wavelength; the first average excitation wavelength of the first radiant source is 550 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +- 14 nanometers about the first average excitation wavelength, the second average excitation wavelength of the second radiant source is 640 +-5 nanometers and/or the second radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the second average excitation wavelength, the average emission wavelength of the first emission spectral element is 682 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +- 16 nanometers about the average emission wavelength; the first average excitation wavelength of the first radiant source is 550 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +- 14 nanometers about the first average excitation wavelength, the second average excitation wavelength of the second radiant source is 662 +-5 nanometers and/or the second radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the second average excitation wavelength; and the average emission wavelength of the first emission spectral element is 711 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +-16 nanometers about the average emission wavelength” are interpreted as not required (see above rejection of claim 13 under 35 U.S.C. 112(b); claim 13 is interpreted as requiring one of the four paragraphs).
Regarding claim 17, Unger fails to teach wherein one or more of the first maximum absorption wavelength, the second maximum absorption wavelength, second maximum emission wavelength, or third maximum emission wavelength, is an absolute maximum over an entirety of the respective spectrum.
Oldham teaches a system including at least two excitation sources to provide different wavelengths, at least one detector, and a plurality of spectrally resolvable dyes (abstract). Oldham teaches the detection system can include a set of dyes and one of more of a PCR detection system (paragraph [0005]). Oldham teaches a set of dyes for the system includes at least two dyes of the set having different absorption wavelengths but the same emission wavelength ranges (paragraphs [0006],[0012]). Oldham teaches a set of energy transfer dyes including acceptor dye moieties of the same emission wavelength as acceptor dye moieties of other dyes of the set (paragraph [0006]). Oldham teaches embodiments using set of dyes, where each dye emits the same peak emission, can be beneficial; wherein the detector can be tuned for optimum detection of the shared emission wavelengths of the dyes (paragraph [0024]). Oldham teaches peak wavelength refers to peak wavelength that provides maximum energy released as radiation from a dye (paragraph [0022]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Unger to incorporate the teachings of dyes having different absorption wavelengths but the same emission wavelengths of Oldham (paragraphs [0006],[0012],[0024]) and the teachings of maximum or peak emission of Oldham (paragraphs [0022],[0024]) to provide: wherein one or more of the first maximum absorption wavelength, the second maximum absorption wavelength, second maximum emission wavelength, or third maximum emission wavelength, is an absolute maximum over an entirety of the respective spectrum. Doing so would have a reasonable expectation of successfully optimizing excitation and detection of dyes as taught by Oldham (paragraph [0024]).
Regarding claim 24, Unger further teaches wherein the radiant sources each comprise a radiant generator (Fig. 1A and paragraph [0104] teaches each of filter of excitation filter wheel 244 includes a light source 242).
Unger fails to teach the radiant sources each comprise a chromatically dispersive optical element configured to transmit or reflect radiation from the radiant generator, each radiant source including a different portion of a spectrum from the chromatically dispersive optical element.
Oldham teaches a system including at least two excitation sources to provide different wavelengths, at least one detector, and a plurality of spectrally resolvable dyes (abstract). Oldham teaches the detection system can include a set of dyes and one of more of a PCR detection system (paragraph [0005]). Oldham teaches a set of dyes for the system includes at least two dyes of the set having different absorption wavelengths but the same emission wavelength ranges (paragraphs [0006],[0012]). Oldham teaches a set of energy transfer dyes including acceptor dye moieties of the same emission wavelength as acceptor dye moieties of other dyes of the set (paragraph [0006]). Oldham teaches embodiments using set of dyes, where each dye emits the same peak emission, can be beneficial; wherein the detector can be tuned for optimum detection of the shared emission wavelengths of the dyes (paragraph [0024]). Oldham teaches embodiments, where if a single source is used, one or more filters, prisms, diffraction gratings, other spectra-separating devices, or a combination thereof, can be used to independently provide radiation of a first peak wavelength range and radiation of a different, second peak wavelength range (paragraph [0049]; wherein “prisms, diffraction gratings” are interpreted as chromatically dispersive optical elements).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the radiant sources of Unger to provide: the radiant sources each comprise a chromatically dispersive optical element configured to transmit or reflect radiation from the radiant generator, each radiant source including a different portion of a spectrum from the chromatically dispersive optical element. Doing so would utilize known optical elements which would have a reasonable expectation of successfully improving separation and transmission of desired wavelengths from the radiant generators.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Unger as applied to claim 14 above, and further in view of McMillan et al. (US 20020034746 A1; cited in the IDS filed 04/21/2023).
Regarding claim 15, Unger fails to explicitly teach: wherein the first dye is covalently attached to a first probe, and the second dye is covalently attached to conjugate second probe, and the third dye is covalently attached to a third probe, wherein the first, second, and third probes are configured to bind to a first, a second, and a third target molecule, respectively.
Unger teaches multiplex amplification systems and multiple differently labeled probes each of which is designed to hybridize only to a particular target (paragraph [0070]).
McMillan teaches a method for determining a quantity of nucleic acid sequence in a test sample (abstract). McMillan teaches labeling of nucleic acid sequences may be achieved by a number of means, including by chemical modification of a nucleic acid primer or probe; where the use of covalently-binding fluorescent agents is preferred (paragraph [0140]). McMillan teaches indicators of nucleic acid concentration may be provided by labels that produce signals detectable by fluorescence; wherein suitable labels include fluorophores having specific binding partners for detecting a target nucleic acid (paragraph [0139]). McMillan teaches detecting three different targets (paragraph [0238]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first, second, and third dyes of Unger to incorporate the teachings of multiplex amplification systems using multiple different labeled probes designed to hybridize to particular targets of Unger (paragraph [0070]) and the teachings of nucleic acid probes with covalently-binding fluorescent agents and detecting three different targets of McMillan (paragraphs [0139],[0140],[0238]) to provide: wherein the first dye is covalently attached to a first probe, and the second dye is covalently attached to conjugate second probe, and the third dye is covalently attached to a third probe, wherein the first, second, and third probes are configured to bind to a first, a second, and a third target molecule, respectively. Doing so would have a reasonable expectation of successfully improving multiplexing of the system by allowing for labeling of multiple probes with the dyes for detecting three different targets.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Unger as applied to claim 14 above, and further in view of Mao et al. (US 20090305410 A1) and Oldham et al. (US 20060252079 A1).
Regarding claim 16, Unger fails to teach: wherein (1) wherein the first dye comprises a first absorption spectrum comprising a first maximum absorption wavelength and the second dye comprises a second absorption spectrum comprising a second maximum absorption wavelength that is equal to or substantially equal first maximum absorption wavelength and (2) the second dye comprises a second emission spectrum comprising a second maximum emission wavelength and the third dye comprises a third emission spectrum comprising a third maximum emission wavelength that is equal to or substantially equal second maximum emission wavelength.
Mao teaches fluorescent dyes and kits for labeling biomolecules for research and development, forensic identification, environmental studies, diagnosis, prognosis, and/or treatment of disease conditions (abstract). Mao teaches probes labeled with fluorescent groups for use as a PCR probe are well known to one skilled in the art (paragraph [0310]). Mao teaches the use of tandem dyes are useful for multi-color detections where only a limited number of excitation light sources may be available (paragraph [0304]) and in order to detect multiple targets, each target may be stained with a different fluorescent group having a different emission and the different fluorescent groups all need to be efficiently excited by a common excitation source (paragraph [0304]), wherein different tandem dyes having the same excitation maxima but different emission maxima can be readily prepared (paragraph [0304]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first dye and the second dye to incorporate the teachings of different fluorescent dyes having the same excitation maxima but different emission maxima of Mao (paragraph [0304]) to provide: wherein (1) wherein the first dye comprises a first absorption spectrum comprising a first maximum absorption wavelength and the second dye comprises a second absorption spectrum comprising a second maximum absorption wavelength that is equal to or substantially equal first maximum absorption wavelength. Doing so would have a reasonable expectation of successfully improving detection of multiple targets efficiently using a common light source as taught by Mao.
Modified Unger fails to teach: (2) the second dye comprises a second emission spectrum comprising a second maximum emission wavelength and the third dye comprises a third emission spectrum comprising a third maximum emission wavelength that is equal to or substantially equal second maximum emission wavelength.
Oldham teaches a system including at least two excitation sources to provide different wavelengths, at least one detector, and a plurality of spectrally resolvable dyes (abstract). Oldham teaches the detection system can include a set of dyes and one of more of a PCR detection system (paragraph [0005]). Oldham teaches a set of dyes for the system includes at least two dyes of the set having different absorption wavelengths but the same emission wavelength ranges (paragraphs [0006],[0012]). Oldham teaches a set of energy transfer dyes including acceptor dye moieties of the same emission wavelength as acceptor dye moieties of other dyes of the set (paragraph [0006]). Oldham teaches embodiments using set of dyes, where each dye emits the same peak emission, can be beneficial; wherein the detector can be tuned for optimum detection of the shared emission wavelengths of the dyes (paragraph [0024]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the second and third dye of modified Unger to incorporate the teachings of dyes having different absorption wavelengths but the same emission wavelengths of Oldham (paragraphs [0006],[0012],[0024]) to provide: (2) the second dye comprises a second emission spectrum comprising a second maximum emission wavelength and the third dye comprises a third emission spectrum comprising a third maximum emission wavelength that is equal to or substantially equal second maximum emission wavelength. Doing so would have a reasonable expectation of successfully optimizing detection of emission wavelengths dyes as taught by Oldham (paragraph [0024]).
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 1-2 and 5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of copending Application No. 18/006,559 (reference application) (herein, “App ‘559”). Although the claims at issue are not identical, they are not patentably distinct from each other because the entire scope of the reference claim falls within the scope of the examined claim.
Regarding claim 1, App ‘559 recites a system (claim 1), comprising:
a radiant source characterized by an average excitation wavelength (claim 1);
a sample disposed to receive radiation from the radiant source (claim 1), the sample comprising:
a first dye (claim 1);
a second dye (claim 1); and
a detector configured to measure emissions from the sample (claim 1);
a first emission spectral element characterized by a first average emission wavelength (claim 1);
a second emission spectral element characterized by a second average emission wavelength that is different than the first average emission wavelength (claim 1);
at least one processor comprising at least one memory including instructions to (claim 1):
illuminate the sample with the radiant source and, in response, (1) measure emissions from the sample using the detector and the first emission spectral element (claim 1)and (2) measure emissions from the sample using the detector and the second emission spectral element (claim 1).
Regarding claim 2, App ‘559 recites wherein the first dye comprises a first absorption spectrum comprising a first maximum absorption wavelength (claim 1) and the second dye comprises a second absorption spectrum comprising a second maximum absorption wavelength that is equal to or substantially equal first maximum absorption wavelength (claim 1), optionally wherein one or more of the first maximum absorption wavelength or second maximum absorption wavelength is an absolute maximum over an entirety of the respective spectrum (interpreted as not required).
Regarding claim 5, App ‘559 recites wherein:
the average excitation wavelength of the first radiant source is 480 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to ± 12 nanometers about the average excitation wavelength, the first average emission wavelength of the first emission spectral element is 520 +-5 nanometers and/or the first emission spectral element is characterized by a wavelength band that is less than or equal to +-20 nanometers about the first average emission wavelength, and the second average emission wavelength of the second emission spectral element is 587 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +-12 nanometers about the second average emission wavelength (claim 4);
the average excitation wavelength of the first radiant source is 480 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +-12 nanometers about the average excitation wavelength, the first average emission wavelength of the first emission spectral element is 520 +-5 nanometers and/or the first emission spectral element is characterized by a wavelength band that is less than or equal to +- 18 nanometers about the first average emission wavelength; and the second average emission wavelength of the second emission spectral element is 623 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +- 18 nanometers about the second average emission wavelength (claim 4);
or
the average excitation wavelength of the first radiant source is 550 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +- 14 nanometers about the average excitation wavelength, the first average emission wavelength of the first emission spectral element is 587 +-5 nanometers and/or the first emission spectral element is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the first average emission wavelength, and the second average emission wavelength of the second emission spectral element is 682 +-5 or 711 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +-16 nanometers about the second average emission wavelength (interpreted as not required).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 6-7, 9-10, 12-16, 18, 22-23, and 25-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6, and 8 of copending Application No. 18/006,559 in view of Unger (US 20060006067 A1).
Regarding claim 6, App ‘559 recites a system (claim 1), comprising:
a first radiant source characterized by a first average excitation wavelength (claim 1);
a second radiant source characterized by a second average excitation wavelength that is different than the first average excitation wavelength (claim 1);
a sample disposed to receive radiation from the radiant sources (claim 1), the sample comprising:
a first dye (claim 1);
a second dye (claim 1); and
a detector configured to measure emissions from the sample (claim 1);
an emission spectral element characterized by an average emission wavelength (claim 1);
at least one processor comprising at least one memory including instructions to (claim 1):
illuminate the sample with the first radiant source and, in response, measure emissions from the sample using the detector and the emission spectral element (claim 1);
illuminate the sample with the second radiant source and, in response, measure emissions from the sample using the detector and the emission spectral element (claim 1).
App ‘559 fails to recite the sample is a nucleic acid sample; the first dye configured to bind to a first target molecule; the second dye configured to bind to a second target molecule.
Unger a system (abstract; Fig. 1A), comprising: a first radiant source (Fig. 1A and paragraphs [0104],[0105] light source 242 and a first filter of an excitation filter wheel 244) characterized by a first average excitation wavelength (paragraph [0105]); a second radiant source (Fig. 1A and paragraphs [0104],[0106] light source 242 and a second filter of an excitation filter wheel 244) characterized by a second average excitation wavelength that is different than the first average excitation wavelength (paragraph [0106]); a nucleic acid sample (Figs. 1A and 1C teaches microfluidic device 205 including sample array 206, therefore the microfluidic device includes a sample; paragraph [0015], “samples in the at least one chamber of the at least one microfluidic device”; paragraph [0076] teaches samples containing target DNA, i.e. nucleic acid sample; paragraph [0132] teaches fluorescent emissions from first, second, and third dyes, therefore the microfluidic devices at least comprises the sample including dyes). Unger teaches: a computer with a database 270 which is coupled to the light source 242, filter wheels 244,213, and CCD 260 (Fig. 1A); a computer adapted to illuminate a microfluidic array device (paragraph [0023]); multiple differently labeled probes each designed to hybridize to a particular target and detecting each target based on different fluorescent signals (paragraph [0070]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified App ‘559 to incorporate Unger’s teachings of nucleic acid samples and labeled probes designed to hybridize to each target to provide: the sample is a nucleic acid sample; the first dye configured to bind to a first target molecule; the second dye configured to bind to a second target molecule. Doing so would have a reasonable expectation of successfully improving analysis of nucleic acids and improving specificity of binding the dye with the desired target.
Regarding claim 7, App ‘559 recites wherein the first dye comprises a first emission spectrum comprising a first maximum emission wavelength and the second dye comprises a second emission spectrum comprising a second maximum emission wavelength that is equal to or substantially equal first maximum emission wavelength (claim 2).
Regarding claim 9, App ‘559 recites wherein the second dye is an off-axis dye (claim 6).
Regarding claim 10, App ‘559 recites wherein the first dye comprises a first emission spectrum comprising a first maximum emission wavelength and the second dye comprises a second emission spectrum comprising a second maximum emission wavelength that is equal to or substantially equal the first maximum emission wavelength (claim 2).
Regarding claim 12, App ‘559 recites wherein the second dye is an off-axis dye (claim 6).
Regarding claim 13, App ‘559 recites wherein:
the first average excitation wavelength of the first radiant source is 480 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the first average excitation wavelength, the second average excitation wavelength of the second radiant source is 550 +-5 nanometers and/or the second radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the second average excitation wavelength, the first average emission wavelength of the first emission spectral element is 587 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +-12 nanometers about the average emission wavelength (interpreted as not required);
the first average excitation wavelength of the first radiant source is 480 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the first average excitation wavelength, the second average excitation wavelength of the second radiant source is 580 +-5 nanometers and/or the second radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the second average excitation wavelength, the average emission wavelength of the first emission spectral element is 623 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +-18 nanometers about the average emission wavelength (interpreted as not required);
the first average excitation wavelength of the first radiant source is 550 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +- 14 nanometers about the first average excitation wavelength, the second average excitation wavelength of the second radiant source is 640 +-5 nanometers and/or the second radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the second average excitation wavelength, the average emission wavelength of the first emission spectral element is 682 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +- 16 nanometers about the average emission wavelength (claim 4);
the first average excitation wavelength of the first radiant source is 550 +-5 nanometers and/or the first radiant source is characterized by a wavelength band that is less than or equal to +- 14 nanometers about the first average excitation wavelength, the second average excitation wavelength of the second radiant source is 662 +-5 nanometers and/or the second radiant source is characterized by a wavelength band that is less than or equal to +- 12 nanometers about the second average excitation wavelength; and the average emission wavelength of the first emission spectral element is 711 +-5 nanometers and/or the second emission spectral element is characterized by a wavelength band that is less than or equal to +-16 nanometers about the average emission wavelength (claim 4).
Regarding claim 14, App ‘559 recites a system (claim 1), comprising:
a first radiant source characterized by a first average excitation wavelength (claim 1);
a second radiant source characterized by a second average excitation wavelength that is different than the first average excitation wavelength (claim 1);
a sample disposed to receive radiation from the radiant sources (claim 1), the sample comprising:
a first dye (claim 1);
a second dye (claim 1); and
a third dye (claim 1);
a detector configured to measure emissions from the sample (claim 1);
a first emission spectral element characterized by a first average emission wavelength (claim 1);
a second emission spectral element characterized by a second average emission wavelength that is different than the first average emission wavelength (claim 1);
at least one processor comprising at least one memory including instructions to (claim 1):
illuminate the sample with the first radiant source and, in response, (1) measure emissions from the sample using the detector and the first emission spectral element and (2) measure emissions from the sample using the detector and the second emission spectral element (claim 1);
illuminate the sample with the second radiant source and, in response, measure emissions from the sample using the detector and the second emission spectral element (claim 1).
App ‘559 fails to recite the sample is a nucleic acid sample; the first dye configured to bind to a first target molecule; the second dye configured to bind to a second target molecule; the third dye configure to bind to a third target molecule.
Unger a system (abstract; Fig. 1A), comprising: a first radiant source (Fig. 1A and paragraphs [0104],[0105] light source 242 and a first filter of an excitation filter wheel 244) characterized by a first average excitation wavelength (paragraph [0105]); a second radiant source (Fig. 1A and paragraphs [0104],[0106] light source 242 and a second filter of an excitation filter wheel 244) characterized by a second average excitation wavelength that is different than the first average excitation wavelength (paragraph [0106]); a nucleic acid sample (Figs. 1A and 1C teaches microfluidic device 205 including sample array 206, therefore the microfluidic device includes a sample; paragraph [0015], “samples in the at least one chamber of the at least one microfluidic device”; paragraph [0076] teaches samples containing target DNA, i.e. nucleic acid sample; paragraph [0132] teaches fluorescent emissions from first, second, and third dyes, therefore the microfluidic devices at least comprises the sample including dyes). Unger teaches: a computer with a database 270 which is coupled to the light source 242, filter wheels 244,213, and CCD 260 (Fig. 1A); a computer adapted to illuminate a microfluidic array device (paragraph [0023]); multiple differently labeled probes each designed to hybridize to a particular target and detecting each target based on different fluorescent signals (paragraph [0070]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified App ‘559 to incorporate Unger’s teachings of nucleic acid samples and labeled probes designed to hybridize to each target to provide: the sample is a nucleic acid sample; the first dye configured to bind to a first target molecule; the second dye configured to bind to a second target molecule; the third dye configure to bind to a third target molecule. Doing so would have a reasonable expectation of successfully improving analysis of nucleic acids and improving specificity of binding the dye with the desired target.
Regarding claim 16, App ‘559 recites wherein (1) wherein the first dye comprises a first absorption spectrum comprising a first maximum absorption wavelength and the second dye comprises a second absorption spectrum comprising a second maximum absorption wavelength that is equal to or substantially equal first maximum absorption wavelength (claim 1) and (2) the second dye comprises a second emission spectrum comprising a second maximum emission wavelength and the third dye comprises a third emission spectrum comprising a third maximum emission wavelength that is equal to or substantially equal second maximum emission wavelength (claim 1).
Regarding claim 18, App ‘559 recites wherein the second dye is an off-axis dye (claim 6).
Regarding claim 22, App ‘559 fails to recite wherein: the first radiant source comprises a radiant generator and a first filter are configured to filter radiation from the radiant generator; and the second radiant source comprises the radiant generator and a second filter are configured to filter radiation from the radiant generator.
Unger further teaches wherein: the first radiant source comprises a radiant generator (Fig. 1A, light source 242) and a first filter (Fig. 1A and paragraphs [0104],[0105] a first filter of an excitation filter wheel 244) are configured to filter radiation from the radiant generator (paragraphs [0104],[0105]); and the second radiant source comprises the radiant generator (Fig. 1A, light source 242) and a second filter (Fig. 1A and paragraphs [0104],[0106] a second filter of an excitation filter wheel 244) are configured to filter radiation from the radiant generator (paragraphs [0104],[0106]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the radiant sources of App ‘559 to incorporate the teachings of optical element configurations of Unger to provide: the first radiant source comprises a radiant generator and a first filter are configured to filter radiation from the radiant generator; and the second radiant source comprises the radiant generator and a second filter are configured to filter radiation from the radiant generator. Doing so would have a reasonable expectation of successfully providing and allowing for desired wavelengths of light to be generated and directed towards a sample.
Regarding claim 23, App ‘559 fails to recite the system of claim 14, further comprising a filter wheel comprising the filters.
Unger further teaches the system of claim 14, further comprising a filter wheel comprising the filters (Fig. 1A and paragraphs [0104], filter wheel 244 or 213).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified App ‘559 to incorporate the teachings of filter wheels of Unger to provide: the system of claim 14, further comprising a filter wheel comprising the filters. Doing so would have a reasonable expectation of successfully improving control and ease of changing filters for desired excitation and emission wavelengths.
Regarding claim 25, App ‘559 fails to recite wherein the radiant generator comprises a light source.
Unger further teaches wherein the radiant generator comprises a light source (Fig. 1A, light source 242).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified App ‘559 to incorporate the teachings of optical element configurations of Unger to provide: wherein the radiant generator comprises a light source.. Doing so would have a reasonable expectation of successfully providing and allowing for desired wavelengths of light to be generated and directed towards a sample.
Regarding claim 26, App ‘559 recites system of claim 14, wherein:
- the radiant generator comprises a white light source characterized by over at least a portion of the visible band of radiation (interpreted as not required),
- the radiant generator comprises a light emitting diode or a halogen lamp (interpreted as not required),
- the detector comprises an array sensor comprising an array of sensors or pixels (claim 8, “CCD detector or CMOS detector”),
- the array sensor comprises a charge coupled device (CCD) or a complementary metal-oxide- semiconductor (CMOS) (claim 8), or
- the emission spectral elements comprise a dispersive optical element configure to disperse emissions from the sample along a first optical path and second optical path (claim 8), wherein the detector comprises a first detector configured to receive emissions along the first optical path and a second detector configured to receive emissions along the second optical path (claim 8), optionally wherein the first detector comprises a first location on a CCD detector or CMOS detector and the second comprises a second location on a CCD detector or CMOS detector that is spatially separated from the first location, optionally wherein the first location comprises a pixel or a group of pixels, and the second location comprises a different pixel or group of pixels (claim 8).
Regarding claim 27, App ‘559 fails to recite the system of claim 14, further comprising a filter wheel comprising the emission spectral elements, the filter wheel being configured to sequentially place the emission spectral element along an optical path between the sample and the detector in order to measure emissions from the sample.
Unger further teaches the system of claim 14, further comprising a filter wheel comprising the emission spectral elements (paragraph [0132] and Fig. 1A teaches emission filter wheel 213), the filter wheel being configured to sequentially place the emission spectral element along an optical path between the sample and the detector in order to measure emissions from the sample (Fig. 1A and paragraphs [0132]-[0133], [0166],[0168]-[0169]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified App ‘559 to incorporate the teachings of filter wheels of Unger to provide: the system of claim 14, further comprising a filter wheel comprising the emission spectral elements, the filter wheel being configured to sequentially place the emission spectral element along an optical path between the sample and the detector in order to measure emissions from the sample. Doing so would have a reasonable expectation of successfully improving control and ease of changing filters for desired excitation and emission wavelengths.
Regarding claim 28, App ‘559 recites the system of claim 14, further comprising:
providing a third radiant source characterized by a third average excitation wavelength that is different than the first average excitation wavelength of the first radiant source or the second average excitation wavelength of the second radiant source (claim 5);
illuminating the sample with radiation from a third radiant source and, in response, measuring an emission from the sample using one or more of the first emission spectral element or the second emission spectral element (claim 5).
App ‘559 fails to recite: determining an amount of one or more of target molecules is based on the measured emission(s) from the sample in response to illuminating the sample with radiation from the third radiant source.
Unger teaches single cell macro molecule quantification (paragraph [0034]); determining the quantity of a target nucleic acid (paragraph [0066]); detecting several targets based on fluorescence signals (paragraph [0070]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified App ‘559 to incorporate the teachings of quantitative analysis of target nucleic acids of Unger to provide: determining an amount of one or more of target molecules is based on the measured emission(s) from the sample in response to illuminating the sample with radiation from the third radiant source. Doing so would have a reasonable expectation of successfully improving quantification of target molecules based on the three light sources.
This is a provisional nonstatutory double patenting rejection.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Puskas et al. (US 20060078998 A1) teaches analyzers and methods for multiplexing (abstract), wherein the methods allow for use with PCR for detection of presence, absence, and concentration of target molecules and allowing for rapid and sensitive screening of a sample (paragraph [0269]). Puskas teaches the analyzer provides for improved detection of multiple particles in a single sample (paragraph [0093]). Puskas teaches labeling a particle that binds specifically to a target nucleic acid sequence is known (paragraph [0195]). Puskas teaches labels includes dyes (paragraph [0196]). Puskas teaches the dyes have the same or overlapping excitation spectra, but possess distinguishable emission spectra, wherein filters and diffraction gratings allow for respective emission spectra to be independently detected (paragraph [0203]).
Straus et al. (US 20030082516 A1) teaches a system including an excitation filter wheel and emission filter wheel (Fig. 3).
Wilson et al. (US 20110042580 A1) teaches alternatives of: the emission spectra for the target and reference fluorophores can be similar, but the absorption spectra can be different (paragraph [0036]); and in another alternative, the absorption spectra for the target and reference fluorophores can be similar, but the emission spectra can be different (paragraph [0037]).
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/HENRY H NGUYEN/ Primary Examiner, Art Unit 1758