DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application was filed 09/05/2024 and is a national stage entry of PCT/US2023/014971 with an international filing date: 03/10/2023 and claims priority from provisional application 63319021 , filed 03/11/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/5/2024 and 3/5/2026 are being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 1-2, 6-12, 16-22, 29-31, 50 objected to because of the following informalities:
Claims 1 recites, “a.”, “b.”,”c.” , “i.”, “ii.” .”MPEP 608.01(m) states: Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v.Manbeck, 36 USPQ2d 1211 (D.D.C. 1995).
Claims 2 recites, “a.”, “b.”,”c.” , “i.”, “ii.” .”MPEP 608.01(m) states: Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v.Manbeck, 36 USPQ2d 1211 (D.D.C. 1995).
Claims 31 recites, “i.”, “ii.” “iii.” .”MPEP 608.01(m) states: Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v.Manbeck, 36 USPQ2d 1211 (D.D.C. 1995).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 6-12, 16-22, 29-31, 50 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The independent claim 1 is drawn to a method for detecting a target molecule in a sample, the method comprising: a. binding a first nucleic acid strand to a target molecule, wherein the first nucleic acid strand comprises a first hybridization domain and is linked to a target binding agent capable of binding with the target molecule;b. contacting a probe set with the target molecule from step (a), wherein the probe set comprises: i. a second nucleic acid strand comprising a second hybridization domain linked to a third hybridization domain, wherein the second hybridization domain comprises a nucleotide sequence substantially complementary to a nucleotide sequence of the first hybridization domain, and wherein the second nucleic acid strand comprises a reporter molecule capable of producing a detectable signal; andii. a third nucleic acid strand comprising a fourth hybridization domain, wherein the fourth hybridization domain comprises a nucleotide sequence substantially complementary to a nucleotide sequence of the third hybridization domain, wherein the third nucleic acid strand comprises a quencher molecule, and wherein the quencher molecule quenches the detectable signal from the reporter molecule when the nucleic acid probe is not hybridized to the amplicon, and wherein a melting temperature of the third strand hybridizing with the second strand is lower than a melting temperature of the second strand hybridizing with the first strand, and wherein a wherein a melting temperature of the third strand hybridizing with the second strand is lower than a melting temperature of the first strand binding with the target molecule; and c. analyzing the binding of the probe-set to the target by assessing a detectable signal produced as a function of temperature.
The independent claim 2 is drawn to a method for multiplex detecting of target molecules in a sample, the method comprising: a. binding a first nucleic acid strand to a plurality of target molecules, wherein each first nucleic acid strand comprises a first hybridization domain and is linked to a target binding agent capable of binding with the target molecule, and wherein the first hybridization domain of the first nucleic acid strands linked to different target binding agents are different; b. contacting a plurality of detection probe sets with the target molecules from step (a), wherein each detection probe set comprises :i. a second nucleic acid strand comprising a second hybridization domain linked to a third hybridization domain, wherein the second hybridization domain comprises a nucleotide sequence substantially complementary to a nucleotide sequence of the first hybridization domain, and wherein the second nucleic acid strand comprises a reporter molecule capable of producing a detectable signal; and ii. a third nucleic acid strand comprising a fourth hybridization domain, wherein the fourth hybridization domain comprises a nucleotide sequence substantially complementary to a nucleotide sequence of the third hybridization domain, wherein the third nucleic acid strand comprises a quencher molecule, and wherein the quencher molecule quenches the detectable signal from the reporter molecule when the nucleic acid probe is not hybridized to the amplicon, and Page 4 of 9 wherein in each probe set a melting temperature of the third strand hybridizing with the second strand is lower than a melting temperature of the second strand hybridizing with the first strand, and wherein in each probe set a melting temperature of the third strand hybridizing with the second strand is lower than a melting temperature of the first strand binding with the target molecule, and wherein the melting temperature of the third strand hybridizing with the second strand in at least one probe set is different from the melting temperature of the third strand hybridizing with the second strand in at least one other probe set, and a melting temperature of the second strand in the probe set having the third strand with the lower melting temperature is about same or lower than a melting temperature of the second strand in the probe set having the third strand with the higher melting temperature; and c. analyzing the binding of the probe-sets to the targets by assessing a detectable signal produced as a function of temperature.”
Independent claim 31 is drawn to probe set for detecting a target molecule, the probe set comprising i. a first nucleic acid strand comprising a first hybridization domain and linked to a target binding agent capable of binding with the target molecule; ii. a second nucleic acid strand comprising a second hybridization domain linked to a third hybridization domain, wherein the second hybridization domain comprises a nucleotide sequence substantially complementary to a nucleotide sequence of the first hybridization domain, and wherein the second nucleic acid strand comprises a reporter molecule capable of producing a detectable signal; and iii. a third nucleic acid strand comprising a fourth hybridization domain, wherein the fourth hybridization domain comprises a nucleotide sequence substantially complementary to a nucleotide sequence of the third hybridization domain, wherein the third nucleic acid strand comprises a quencher molecule, and wherein the quencher molecule quenches the detectable signal from the reporter molecule when the nucleic acid probe is not hybridized to the amplicon.”
Thus the claims encompass any target molecule, any target binding agent, any reporter molecule capable by any standard of producing a signal detectable by any standard or method.
Further the claims require first nucleic acid strand, second nucleic acid strand and third nucleic acid strand which are “substantially complementary” by any standard and can be of any length. Further the claims encompass hybridization under any conditions.
Dependent claims draw the invention to “the target binding agent is selected from the group consisting of nucleic acids, proteins, peptides, peptidomimetics, amino acids, disaccharides, trisaccharides, oligosaccharides, polysaccharides, lipopolysaccharides, lectins, nucleosides, nucleotides, vitamins, steroids, hormones, cofactors, receptors and receptor ligands.” This is an enormous genus and requires the attachment of this target binding agents to nucleic acid strands.
Further dependent claim draws the invention to wherein the reporter molecule and the quencher molecule are a FRET pair. Thus the independent claim encompasses where the reporter molecule and quenching molecule are not a FRET pair, which appears to contradict the requirement of a quencher molecule which quenches the detectable signal.
Further the dependent claims require the target molecule is selected from the group consisting of nucleic acids, proteins, saccharides, lipids, small molecules, and antigens.” This is an enormous genus.
The teachings of the specification are limited detection of RNA or DNA in the examples as exemplified by figure 1A
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However, the claims encompass the structure of the claims it is not limited to the claims.
Thus the claims lack adequate written description for the genus claimed.
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 1-2, 6-12, 16-22, 29-31, 50 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites, “target binding agent capable of binding with the target molecule.” The recitation of capable of binding suggests there is incapable of binding with the target molecule.” Thus capable is relative term. The specification and claims provide no standard to differentiate capable of binding with the target molecule from incapable of binding with the target molecule. Thus the metes and bounds are unclear.
Claim 1 recites, “a nucleotide sequence substantially complementary to a nucleotide sequence.” The recitation of “substantially complementary to a nucleotide sequence” suggests there is “not substantially complementary to a nucleotide sequence.” Thus substantially is a relative term. The specification and claims provide no standard to differentiate substantially complementary to a nucleotide sequence from not substantially complementary to a nucleotide sequence.
Claim 1 recites, “capable of producing a detectable signal.” Both capable and detectable are relative terms. The specification and claims provide no standard on how to differentiate capable of producing a detectable signal from incapable of producing a detectable signal or detectable from non-detectable.
Claim 2 recites, “target binding agent capable of binding with the target molecule.” The recitation of capable of binding suggests there is incapable of binding with the target molecule.” Thus capable is relative term. The specification and claims provide no standard to differentiate capable of binding with the target molecule from incapable of binding with the target molecule. Thus the metes and bounds are unclear.
Claim 2 recites, “a nucleotide sequence substantially complementary to a nucleotide sequence.” The recitation of “substantially complementary to a nucleotide sequence” suggests there is “not substantially complementary to a nucleotide sequence.” Thus substantially is a relative term. The specification and claims provide no standard to differentiate substantially complementary to a nucleotide sequence from not substantially complementary to a nucleotide sequence.
Claim 2 recites, “capable of producing a detectable signal.” Both capable and detectable are relative terms. The specification and claims provide no standard on how to differentiate capable of producing a detectable signal from incapable of producing a detectable signal or detectable from non-detectable.
Claim 11 recites, “wherein the melting temperature of the third strand hybridizing with the second strand is at least 5°C lower than the melting temperature of the first strand binding with the target molecule.” The target molecule can be, “the target molecule is selected from the group consisting of nucleic acids, proteins, saccharides, lipids, small molecules, and antigens.” (claim 22). Thus the metes and bounds are unclear how to determine the melting strand binding to proteins, saccharides, lipids, small molecules, and antigens.
Claim 12 recites, “wherein the melting temperature of the second strand hybridizing with the first strand is at least 5°C lower than the melting temperature of the first strand binding with the target molecule.” The target molecule can be, “the target molecule is selected from the group consisting of nucleic acids, proteins, saccharides, lipids, small molecules, and antigens.” (claim 22). Thus the metes and bounds are unclear how to determine the melting strand binding to proteins, saccharides, lipids, small molecules, and antigens.
Claim 20 recites, ““a nucleotide sequence substantially complementary to a nucleotide sequence.” The recitation of “substantially complementary to a nucleotide sequence” suggests there is “not substantially complementary to a nucleotide sequence.” Thus substantially is a relative term. The specification and claims provide no standard to differentiate substantially complementary to a nucleotide sequence from not substantially complementary to a nucleotide sequence.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claim(s) 31, 50is/are rejected under 35 U.S.C. 102(a)(1) as being anticiapted by Duose (BIOCONJUGATE CHEMISTRY, vol. 21, no. 12, 15 December 2010 (2010-12-15), pages 2327-2331.)
With regards to claim 31, 50 Douse teaches DNA circuits (i.e. probe sets) adapted as erasable molecular imaging probes that allow fluorescent reporting complexes to be assembled and disassembled on a biological specimen. The DNA circuit (see scheme 1) involves a molecular marker (i.e. target molecule) bound by a targeting agent (i.e. target binding agent) comprising a catalyst nucleic acid strand (i.e. first hybridization domain). A substrate complex (i.e. second and third nucleic acid strand) is added. The substrate complex comprises a strand (purple strand in scheme 1; i.e. second strand) comprising a fluorescent dye (Cy3 or Cy5) (i.e. reporter molecule) and a domain/toehold hybridizing to the catalyst (i.e. second hybridization domain) as well as a domain (i.e. third hybridization domain) hybridizing to a domain (i.e. fourth hybridization domain) of another nucleic acid strand (blue strand/O1 in scheme 1; i.e. third strand). This other strand comprises a quencher (Iowa Black). The quencher quenches the fluorescent dye when the substrate (i.e. nucleic acid probe) is not hybridized to the catalyst (i.e. not hybridized to an amplicon). Experiments are shown on fixed and permeabilized Hela cells (see fig. 2).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-2, 6-8, 10-12, 16-22, 29 are is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen (WO2015010020) and Urdea (US Patent 5,681,697 issued Oct 28, 1997)
With regards to claim 1-2, Chen teaches barcoding method with melting temperature using Temperature Barcoded Hydrolysis Probe (TBHP). The TBHP comprises a Probe Strand and a Free Quencher Strand. The Probe strand comprises a first domain having a fluorophore (i.e. reporter molecule; i.e. second nucleic acid strand), and a second domain having a sequence complementary or partially complementary to a target strand (i.e. target binding agent; i.e. first nucleic acid strand). The Free Quencher Strand (i.e. third nucleic acid strand) comprises a domain complementary or partially complementary to the first domain of the Probe Strand and comprises a quencher (see p. 37, I. 6-20; fig. 14). Multiplex can be performed using a plurality of TBHPs with the Probe Strands and the corresponding Free Quencher Strands having different melting profiles (i.e. analyzing the binding of the probe-set to the target molecule by assessing a detectable signal produced as a function of temperature) (see p. 37, I. 18-20; p. 38, I. 10-20). It is specified that in some embodiments the Probe Strand is formed by multiple molecules that interact with non-covalent interactions.”
Chen does not specifically teach based on melting temperature.
However, Urdea teaches a method of detecting nucleic acids with diminished background (abstract). Urdea teaches, “This invention relates generally to nucleic acid chemistry and hybridization assays. More particularly, the invention relates to methods for generating a more target-dependent signal in solution phase sandwich hybridization assays by minimizing background noise deriving primarily from nonspecific hybridization and/or nonspecific binding. The invention additionally relates to methods for compensating for lost signal while reducing background noise.” (Column 1, technical field). Urdea teaches a method of binding two or more label extenders to an analyte to allow detection (column 2, last paragraph). Urdea teaches, “In this aspect, the assay is carried out at conditions which favor formation of hybrid complexes in which analyte molecule is bound to the amplification multimers or label probes. This technique is premised on the enhanced stability of the multi-component complex relative to the much less stable two-component complexes. A preferred method of favoring analyte-amplification multimer hybrid complexes includes running one or more steps of the assay at a temperature between T.sub.ml and T.sub.m2.’’Urdea teaches binding two or more capture sequences (LE 1 and LE2) to a target nucleic acid (t section); amplifier or preamplifier (C section) a label probe (L section) in figure 11. The section of LEI and LE2 hybridizing the target sequences are the T sections and the sections hybridizing to target nucleic acid, the c section attach the T sections to the L section (or labels).
Urdea’s teaches, “The present invention, which does not rely on the detection of the presence of double-stranded regions, is also designed to increase the accuracy of detection and quantitation of polynucleotide analytes in hybridization assays. The invention increases both the sensitivity and specificity of such assays, by reducing the incidence of signal generation that occurs in the absence of target, and does not involve a substantial increase in either time or cost relative to current assay configurations. In certain embodiments, the invention is also effective in compensating for the loss in signal that can result when background noise is reduced.. “ (column 2, line 40-51)
Urdea teaches, “This method is premised on the design and construction of hybrid complexes such that the melt temperature Tm1 at which the analyte dissociates from the capture probe in the capture probe-capture extender-analyte hybrid is at least about 5.degree. C. greater than, preferably at least about 10.degree. C. greater than the melt temperature Tm2 at which a capture extender dissociates from a capture probe in the capture probe-capture extender hybrid.” Urdea continues to suggest carrying out the assay at a temperature higher than Tm2, which is the melting temperature of the capture probe and label probe, amplifier or preamplifier of the instant claims.
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to design the strands( probes) of Chen with decreasing melting temperatures for the third strand to the second strand which is lower than the melting temperature of the second strand to the first strand. The artisan would be motivated to allow for formation of a stable probe complex to allow for detection of nucleic acids. The artisan would have a reasonable expectation of success as Urdea teaches designing probe based on melting temperatures were known.
With regards to claim 6-8, Chen teaches target is nucleic acids (figure 1)
With regards to claims 10-12,, Urdea teaches, “hybridization assay is provided which is configured such that the temperature T ml at which the target molecule "melts" from the support-bound capture probes ( defined as the temperature at which 50% of the individual capture probes participating in target molecule/capture extender/capture probe complexes are no longer bound to the target molecule) is significantly higher than the temperature T m2 at which an individual capture extender molecule "melts" from a single capture probe. This procedure may be used in virtually any type of hybridization assay wherein capture probes and capture extender molecules are used, including a wide range of solution phase hybridization assays, amplification assays, filter hybridization methods, assays involving the polymerase chain reaction ("PCR"), and the like. One example of a hybridization assay with which the present technique is useful is that described in U.S. Pat. No. 4,868,105 to Urdea et al., or, preferably, that described above in conjunction with the configuration illustrated in FIG. 1 and described above. This method is premised on the design and construction of hybrid complexes such that the melt temperature Tm1 at which the analyte dissociates from the capture probe in the capture probe-capture extender-analyte hybrid is at least about 5° C. greater than, preferably at least about 10° C. greater than the melt temperature T m2 at which a capture extender dissociates from a capture probe in the capture probe-capture extender hybrid..” (column 12, lines 41-68)
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to design the third strand hybridizing second strand in 5oC lower than hybridizing of the second strand to first strand or the first strand to the target molecule. The artisan would be motivated to allow for formation of a stable probe complex to allow for detection of nucleic acids. The artisan would have a reasonable expectation of success as Urdea teaches designing probe based on melting temperatures were known.
With regards to claim 16, Chen teaches signal generating moiety which includes fluorophores (page 39, lines 21-34) and signal modulating moiety with encompass quenchers (page 40, lines 1-7). Thus a fluorophore and quencher which modulates signal is a FRET pair.
With regards to claim 17, Chen teaches signal generating moiety which includes fluorophores (page 39, lines 21-34).
With regards to claim 18, Chen teaches, “dark quenchers (e.g., dyes with no native fluorescence such as dabsyl, dark hole quenchers, Qxl quenchers, Iowa black FQ, Iowa Black RQ, IRDye QC-1)” (page 40, lines 4-7).
With regards to claim 19, Chen teaches a target nucleic acid binding domain (figure1).
MPEP 2144.04 VI. B states:
B.Duplication of Parts
In reHarza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960) (Claims at issue were directed to a water-tight masonry structure wherein a water seal of flexible material fills the joints which form between adjacent pours of concrete. The claimed water seal has a “web” which lies in the joint, and a plurality of “ribs” projecting outwardly from each side of the web into one of the adjacent concrete slabs. The prior art disclosed a flexible water stop for preventing passage of water between masses of concrete in the shape of a plus sign (+). Although the reference did not disclose a plurality of ribs, the court held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced.).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to provide fourth and fifth strands, wherein the fourth strand has a reporter molecule. Thea artisan would be motivated to provide additional labels to increase fluorescence. The artisan would have a reasonable expectation of success as the artisan is merely duplicating parts.
With regards to claim 21, Chen teaches, “by spontaneous dissociation (e.g., if the temperature of the reaction is held at or raised to a temperature similar to or above the melting temperature of the duplex formed by binding of the specificity domain to a strand of the rare target allele),” (page 3, lines 2729).
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claim to determine fluorescence at two temperature. The artisan would be motivated as Chen suggests assaying at two different temperatures. The artisan would have a reasonable expectation of success as the artisan is merely using known method and assaying as suggested by the art of record.
With regards to claim 22, Chen teaches nucleic acids as a target. (figure 1).
With regards to claim 29, Chen teaches the nucleic acids can be extracted from cells (page 44, line 21)
Claim(s) 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen (WO2015010020) and Urdea (US Patent 5,681,697 issued Oct 28, 1997) as applied to claims 1-2, 6-8, 10-12, 16-22, 29 above, and further in view of Lou (US20080038725).
The teachings of Chen and Urdea are set forth above.
Chen and Urdea do not specifically teach fixed cells.
However, Lou teaches in situ hybridization for detection of nucleic acids (0008). Lou teaches detection by nucleic acid complexes. (figures).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims. The artisan would be motivated to assaying fixed samples would allow for analysis of archived fixed samples. The artisan would have a reasonable expectation of success as the artisan is merely using known methods on known samples.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen (WO2015010020) and Urdea (US Patent 5,681,697 issued Oct 28, 1997) as applied to claims 1-2, 6-8, 10-12, 16-22, 29 above, and further in view of Kozlov (US 20200048682).
The teachings of Chen and Urdea are set forth above.
Chen and Urdea do not specifically teach use of antibodies for targets.
However, Kozlov teaches, “[0048] The terms “target” or “target nucleic acid” as used herein are intended to mean any molecule whose presence is to be detected or measured or whose function, interactions or properties are to be studied. Therefore, a target includes essentially any molecule for which a detectable probe (e.g., oligonucleotide probe) or assay exists, or can be produced by one skilled in the art. For example, a target may be a biomolecule, such as a nucleic acid molecule, a polypeptide, a lipid, or a carbohydrate, which is capable of binding with or otherwise coming in contact with a detectable probe (e.g., an antibody), wherein the detectable probe also comprises nucleic acids capable of being detected by methods of the invention. As used herein, “detectable probe” refers to any molecule or agent capable of hybridizing or annealing to a target biomolecule of interest and allows for the specific detection of the target biomolecule as described herein. In one aspect of the invention, the target is a nucleic acid, and the detectable probe is an oligonucleotide. “
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to substitute an antibody for the target of Chen and Urdea. The artisan would be motivated to substitute the nucleic acid for the antibody to detect proteins instead of nucleic acids. The artisan would have a reasonable expectation of success as the artisan is merely substituting one target binding molecule for another target binding molecule.
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, 6-12, 16-22, 29-31, 50 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,359,229 and Urdea (US patent 5681697) . Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
The independent claims are drawn to method for detecting a target molecule in a sample, the method comprising: a. binding a first nucleic acid strand to a target molecule, wherein the first nucleic acid strand comprises a first hybridization domain and is linked to a target binding agent capable of binding with the target molecule; b. contacting a probe set with the target molecule from step (a), wherein the probe set comprises: i. a second nucleic acid strand comprising a second hybridization domain linked to a third hybridization domain, wherein the second hybridization domain comprises a nucleotide sequence substantially complementary to a nucleotide sequence of the first hybridization domain, and wherein the second nucleic acid strand comprises a reporter molecule capable of producing a detectable signal; andii. a third nucleic acid strand comprising a fourth hybridization domain, wherein the fourth hybridization domain comprises a nucleotide sequence substantially complementary to a nucleotide sequence of the third hybridization domain, wherein the third nucleic acid strand comprises a quencher molecule, and wherein the quencher molecule quenches the detectable signal from the reporter molecule when the nucleic acid probe is not hybridized to the amplicon, and wherein a melting temperature of the third strand hybridizing with the second strand is lower than a melting temperature of the second strand hybridizing with the first strand, wherein a wherein a melting temperature of the third strand hybridizing with the second strand is lower than a melting temperature of the first strand binding with the target molecule; and c. analyzing the binding of the probe-set to the target by assessing a detectable signal produced as a function of temperature.
The claims of 229 are drawn to product authentication method, comprising: (a) combining (i) a surface associated with a product with (ii) a solution comprising a first nucleic acid strand comprising a 5′ domain, a 3′ domain, and a 5′ fluorescent molecule or a 5′ quencher molecule, wherein the surface comprises a second nucleic acid strand comprising a 5′ domain complementary to the 3′ domain of the first strand, a 3′ domain complementary to the 5′ domain of the first strand, and a 3′ quencher molecule or a 3′ fluorescent molecule, wherein binding of the first strand to the second strand quenches fluorescent signal emitted by the 5′ fluorescent molecule or the 3′ fluorescent molecule and wherein the first strand and/or the second strand comprise(s) L-DNA or a molecule that terminates polymerization; and (b) assaying for fluorescence on the surface or in the solution.
However, Urdea teaches a method of detecting nucleic acids with diminished background (abstract). Urdea teaches, “This invention relates generally to nucleic acid chemistry and hybridization assays. More particularly, the invention relates to methods for generating a more target-dependent signal in solution phase sandwich hybridization assays by minimizing background noise deriving primarily from nonspecific hybridization and/or nonspecific binding. The invention additionally relates to methods for compensating for lost signal while reducing background noise.” (Column 1, technical field). Urdea teaches a method of binding two or more label extenders to an analyte to allow detection (column 2, last paragraph). Urdea teaches, “In this aspect, the assay is carried out at conditions which favor formation of hybrid complexes in which analyte molecule is bound to the amplification multimers or label probes. This technique is premised on the enhanced stability of the multi-component complex relative to the much less stable two-component complexes. A preferred method of favoring analyte-amplification multimer hybrid complexes includes running one or more steps of the assay at a temperature between T.sub.ml and T.sub.m2.’’Urdea teaches binding two or more capture sequences (LE 1 and LE2) to a target nucleic acid (t section); amplifier or preamplifier (C section) a label probe (L section) in figure 11. The section of LEI and LE2 hybridizing the target sequences are the T sections and the sections hybridizing to target nucleic acid, the c section attach the T sections to the L section (or labels).
Urdea’s teaches, “The present invention, which does not rely on the detection of the presence of double-stranded regions, is also designed to increase the accuracy of detection and quantitation of polynucleotide analytes in hybridization assays. The invention increases both the sensitivity and specificity of such assays, by reducing the incidence of signal generation that occurs in the absence of target, and does not involve a substantial increase in either time or cost relative to current assay configurations. In certain embodiments, the invention is also effective in compensating for the loss in signal that can result when background noise is reduced.. “ (column 2, line 40-51)
Urdea teaches, “This method is premised on the design and construction of hybrid complexes such that the melt temperature Tm1 at which the analyte dissociates from the capture probe in the capture probe-capture extender-analyte hybrid is at least about 5.degree. C. greater than, preferably at least about 10.degree. C. greater than the melt temperature Tm2 at which a capture extender dissociates from a capture probe in the capture probe-capture extender hybrid.” Urdea continues to suggest carrying out the assay at a temperature higher than Tm2, which is the melting temperature of the capture probe and label probe, amplifier or preamplifier of the instant claims.
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to design the strands( probes) of the claims with decreasing melting temperatures for the third strand to the second strand which is lower than the melting temperature of the second strand to the first strand. The artisan would be motivated to allow for formation of a stable probe complex to allow for detection of nucleic acids. The artisan would have a reasonable expectation of success as Urdea teaches designing probe based on melting temperatures were known.
Dependent claims are obvious as they are commensurate in scope.
Summary
No claims are allowed.
Conclusion
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/Steven Pohnert/ Primary Examiner, Art Unit 1683
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