DETAILED ACTION
CONTINUED EXAMINATION UNDER 37 CFR 1.114 AFTER FINAL REJECTION
This office action is used to replace the non-final action mailed on February 25, 2026 due to errors in the previous office action. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission of RCE and amendment filed on September 29, 2025 have been entered. The claims pending in this application are claims 1, 5-8, 10-19, 21, and 22 wherein claims 15 and 19 have been withdrawn due to the restriction requirement mailed on August 24, 2024. The rejections not reiterated from the previous office action are hereby withdrawn in view of applicant’s amendment filed on September 29, 2025. Claims 1, 5-8, 10-14, 16-18, 21, and 22 will be examined.
Specification
The disclosure is objected to because of the following informality: the clean copy of the amended specification filed on May 7, 2025 has not been entered since the marked copy of the amended specification was labeled as paragraph [0001] while the clean copy of the amended specification was labeled as paragraph [0002]. Note that applicant has not addressed this issue in the response filed on September 29, 2025.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informality: “one or more detection reagents” should be “one or more first detection agents”.
Claim 5 is objected to because of the following informality: “or a 2,4-dinitrophenyl moiety” should be “and a 2,4-dinitrophenyl moiety”.
Claim 10 or 11 or 12 is objected to because of the following informality: “from between” should be “from”.
Claim 14 is objected to because of the following informality: “one or more second detection reagents” should be “one or more second detection agents”.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 5-8, 10, and 18 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Haralambidis et al., (US Patent No. 5,525,465, published on June 11, 1996) in view of Kawa et al., (US 2005/0158768 A1, published on July 21, 2005), Drmanac (US 2007/ 0037152 A1, published on February 15, 2007), and 1988 Stratagene catalog (page 39).
Regarding claims 1, 5, 8, 10, and 18, Haralambidis et al., teaches a kit comprising a first oligonucleotide probe (ie., KBIB-SL-[Aha2Lys(Biotin)]10Ala (stage III)) comprises at least one first hapten (ie., 10 biotin molecules) and the at least one first hapten is the same for the first oligonucleotide probe and one or more first detection agents (ie., agents in BlueGene kit) wherein the one or more agents are specific for the detection of hybridization of at least one of the first oligonucleotide probes to at least one of the subsequences of the genomic target of interest in a chromogenic reaction (ie., a streptavidin alkaline phosphatase conjugate in BlueGene kit that binds to biotin and a subsequent development reaction in which the enzyme acts on substrates nitro blue tetrazolium (NBT) and 5-bromo-4-chloro-3-indoyl phosphate (BCIP) in BlueGene kit generates an insoluble dye precipitate) or a metallographic reaction as recited in claim 1, the at least one first hapten are selected from the group consisting of biotin, digoxigenin, and a 2,4-dinitrophenyl moiety as recited in claim 5, each of the at least one labels are attached to a moiety selected from the group consisting of a base, a sugar, and a phosphate as recited in claim 8, each of the first oligonucleotide probes of the first probe set comprises at least five haptens (ie., 10 biotin molecules), and wherein a length of each of the first oligonucleotide probes ranges from about 20 nucleotides to about 200 nucleotides (ie., KBIB is 30 nucleotides) as recited in claim 10 (see columns 13, 16, and 17 and claims 1-19). Although Haralambidis et al., do not disclose that the first oligonucleotide probe comprises a different nucleotide sequence complementary to a different subsequence of the first genomic target sequence of interest as recited in claim 1 and the first genomic target sequence of interest is a region which is spread over different regions of one chromosome as recited in claim 18, since the first genomic target sequence of interest is not a structure limitation of claim 1 and the first genomic target sequence of interest can be a nucleic acid sequence artificially synthesized based on the nucleic acid sequences of the one chromosome, a different nucleotide sequence of the first oligonucleotide probes has an ability to be complementary to a different subsequence of the first genomic target sequence of interest wherein the first genomic target sequence of interest is a region which is spread over different regions of the one chromosome. Note that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In a claim drawn to a process of making, the intended use must result in a manipulative difference as compared to the prior art. In re Casey , 152 USPQ 235 (CCPA 1967); In re Otto , 136 USPQ 458, 459 (CCPA 1963).
Haralambidis et al., do not disclose a kit comprising the set comprising at least 100 different first oligonucleotide probes wherein the at least one first label in each of the first oligonucleotide probes in the first probe set is positioned at a substantially identical position and the at least one first hapten is directly attached to a nucleotide in each of the first oligonucleotide probes as recited in claim 1, the first probe set comprises at least 200 different oligonucleotide probes as recited in claim 6, and the first probe set comprises at least 500 different oligonucleotide probes as recited in claim 7. However, Haralambidis et al., teach that at least one first hapten (ie., 10 biotin molecules) is located on 3’ end of the first oligonucleotide probe (see KBIB-SL-[Aha2Lys(Biotin)]10Ala (stage III)) in columns 13 and 16).
Kawa et al., teach that one or more biotin molecules are covalently bound either
directly to a primer or indirectly through intervening linker molecules (see paragraph [0179]).
Regarding claims 1, 6, and 7, Drmanac teaches the set comprising at least 100 different first oligonucleotide probes (ie., 100 to 10,000 probe molecules having informative regions that are distinct from each other) as recited in claim 1 wherein the first probe set comprises at least 200 different oligonucleotide probes as recited in claim 6, and the first probe set comprises at least 500 different oligonucleotide probes as recited in claim 7 (see paragraphs [0029] to [0046], [0089] and [0090]). Drmanac also teaches a kit comprising a first set of probes associated with a FRET acceptor molecule, a second set of probes associated with a FRET donor molecule, and a ligating reagent (see claim 20).
1988 Stratagene catalog teaches a motivation to combine reagents into kit format (page 39).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kits recited in claims 1, 6, and 7 wherein the set comprises at least 500 different oligonucleotide probes, the at least one first hapten in each of the first oligonucleotide probes in the first probe set is positioned at a substantially identical position (ie., at 3’ end of each of the first oligonucleotide probes), and the at least one first hapten (ie., 10 biotin molecules) is directly attached to a nucleotide in each of the first oligonucleotide probes in view of the prior arts of Haralambidis et al., Kawa et al., Drmanac, and 1988 Stratagene catalog. One having ordinary skill in the art would have been motivated to do so because Haralambidis et al., have shown that at least one first label (ie., 10 biotin molecules) is located on 3’ end of the first oligonucleotide probe (see KBIB-SL-[Aha2Lys(Biotin)]10Ala (stage III)) in columns 13 and 16) and an oligonucleotide probe containing ten biotin residues gives a signal that is approximately ten times stronger than that of an oligonucleotide probe containing singly labelled biotin residue and sensitivity of the singly labelled probes is 0.5 ng (220 µmol) and the multi-labelled probes 0.05 ng (22 µmol) by a dot blot method (see column 17), Kawa et al., teach that one or more biotin molecules are covalently bound either directly to a primer or indirectly through intervening linker molecules (see paragraph [0179]), Drmanac has shown the set comprising at least 100 different first oligonucleotide probes (ie., 100 to 10,000 probe molecules having informative regions that are distinct from each other) wherein the first probe set comprises at least 200 different oligonucleotide probes, the first probe set comprises at least 500 different oligonucleotide probes, and a kit comprises a first set of probes associated with a FRET acceptor molecule, a second set of probes associated with a FRET donor molecule, and a ligating reagent (see paragraphs [0029] to [0046], [0089] and [0090], and claim 20), and 1988 Stratagene catalog teaches a motivation for combining reagents of use in an assay into a kit, “[E]ach kit provides two services: 1) a variety of different reagents have been assembled and pre-mixed specifically for a defined set of experiments. 2) The other service provided in a kit is quality control” (page 39, column 1), the simple substitution of one kind of biotin labeling method (ie., labeling an oligonucleotide by a linkage taught by Haralambidis et al.,) from another kind of biotin labeling method (ie., directly labeling a primer taught by Kawa et al.,), during the process of making the first probe set recited in claim 1, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made since the biotin labeling method taught by Haralambidis et al., and biotin labeling method taught by Kawa et al., are used for the same purpose (ie., labeling biotin residues to oligonucleotides). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the kits comprising the first probe set recited in claims 1, 6, 7, and 21 by making at least 500 different oligonucleotides having the same numbers of biotin residues (eg., ten biotin residues) located on their 3’ ends by directly attaching biotin residues to a nucleotide in each of at least 500 different oligonucleotides in view of the prior arts of Haralambidis et al., Kawa et al., Drmanac, and 1988 Stratagene catalog in order to make the at least one first hapten in each of the first oligonucleotide probes in the first probe set which is positioned at a substantially identical position (ie., at 3’ end of each of the first oligonucleotide probes), increase the detection sensitivity of hybridization assays, and take advantages of a kit format as discussed by 1988 Stratagene catalog.
Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09.
Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955).
Claims 11 and 12 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Haralambidis et al., in view of Kawa et al., Drmanac and 1988 Stratagene catalog as applied to claims 1, 5-8, 10, and 18 above, and further in view of Sussman et al., (US 2010/0056382 A1, priority date: May 30, 2008).
The teachings of Haralambidis et al., Kawa et al., Drmanac and 1988 Stratagene catalog have been summarized previously, supra.
Haralambidis et al., Kawa et al., Drmanac and 1988 Stratagene catalog do not disclose that the length ranges from about 60 to about 150 nucleotides as recited in claim 11, and the length ranges from about 80 to about 120 nucleotides as recited in claim 12.
Sussman et al., teach that oligonucleotide probes are about 30 to about 100 nucleotides in length (see paragraphs [0012] and [0016]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kits recited in claims 11 and 12 wherein the length of each of the first oligonucleotide probes ranges from about 80 to about 120 nucleotides in view of the prior arts of Haralambidis et al., Kawa et al., Drmanac, 1988 Stratagene catalog and Sussman et al.. One having ordinary skill in the art would have been motivated to do so because Sussman et al., teach that oligonucleotide probes are about 30 to about 100 nucleotides in length (see paragraphs [0012] and [0016]) and optimization of the size of each of the first oligonucleotide probes during the process for constructing the kits of claim 10, in the absence of convincing evidence to the contrary, would have been obvious to one having ordinary skill in the art at the time the invention was made. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to construct the kits recited in claims 11 and 12 using oligonucleotide probes ranging from about 80 to about 120 nucleotides in length in view of the prior arts of Haralambidis et al., Kawa et al., Drmanac, 1988 Stratagene catalog and Sussman et al.. More particularly, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Where the general conditions of a claim are disclosed in the prior art, it is not inventive, in the absence of an unexpected result, to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 13, 14, and 17 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Haralambidis et al., in view of Kawa et al., Drmanac and 1988 Stratagene catalog as applied to claims 1, 3-8, 10, and 18 above, and further in view of Haralambidis (US Patent No. 5,552,540, published on September 3, 1996).
The teachings of Haralambidis et al., Kawa et al., Drmanac and 1988 Stratagene catalog have been summarized previously, supra.
Haralambidis et al., Kawa et al., Drmanac and 1988 Stratagene catalog do not disclose a second probe set comprising at least 100 different second oligonucleotide probes, wherein each of the second oligonucleotide probes of the second probe set comprises a different nucleotide sequence complementary to a different subsequence of a second genomic target sequence of interest, wherein each of the second oligonucleotide probes of the second probe set comprise at least one second labels, and wherein the at least one second labels are the same for each of the second oligonucleotide probes of the second probe set, and wherein the at least one second labels are different than the at least one first hapten as recited in claim 13, one or more second detection agents as recited in claim 14, and the second genomic target sequence of interest is other than a HER2 gene locus as recited in claim 17.
Haralambidis teaches a second probe set (ie., an oligonucleotide probe KPIB having 4.1 FITC and an oligonucleotide probe HCAL having 7.2 FITC), each of the second oligonucleotide probes of the second probe set comprises a different nucleotide sequence, each of the second oligonucleotide probes of the second probe set comprise at least one second labels (ie., FITC), and the at least one second labels are the same for each of the second oligonucleotide probes of the second probe set, and wherein the at least one second labels are different than the at least one first hapten as recited in claim 13 and one or more second detection agents (eg., an agent for ammonia treatment to remove those groups on a fluorophore precursor which suppress fluorescence thus converting the fluorophore precursor to a fluorescent form) as recited in claim 14 (see column 8 and Examples 4, 7, and 8 in columns 16, 18 and 19). Although Haralambidis does not disclose that each of the second oligonucleotide probes of the second probe set comprises a different nucleotide sequence complementary to a different subsequence of a second genomic target sequence of interest as recited in claim 13 and the second genomic target sequence of interest is other than a HER2 gene locus as recited in claim 17, since the second genomic target sequence of interest is not a structure limitation of claim 13 and the second genomic target sequence of interest can be a nucleic acid sequence artificially synthesized based on the nucleic acid sequences of one chromosome, a different nucleotide sequence of each of the second oligonucleotide probes has an ability to be complementary to a different subsequence of the second genomic target sequence of interest. Note that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In a claim drawn to a process of making, the intended use must result in a manipulative difference as compared to the prior art. In re Casey , 152 USPQ 235 (CCPA 1967); In re Otto , 136 USPQ 458, 459 (CCPA 1963).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kits recited in claims 13, 14, and 17 wherein the second set comprises at least 100 different oligonucleotide probes and one or more second detection agents, each of the second oligonucleotide probes of the second probe set comprise at least one second labels, the at least one second labels are the same for each of the second oligonucleotide probes of the second probe set, and the at least one second labels are different than the at least one first hapten in view of the prior arts of Haralambidis et al., Kawa et al., Drmanac, 1988 Stratagene catalog, and Haralambidis. One having ordinary skill in the art would have been motivated to do so because Haralambidis have shown a second probe set (ie., an oligonucleotide probe KPIB having 4.1 FITC and an oligonucleotide probe HCAL having 7.2 FITC) wherein each of the second oligonucleotide probes of the second probe set comprises a different nucleotide sequence, each of the second oligonucleotide probes of the second probe set comprise at least one second labels (ie., FITC), the at least one second labels are the same for each of the second oligonucleotide probes of the second probe set, the at least one second labels are different than the at least one first hapten and one or more second detection agents (eg., an agent for ammonia treatment to remove those groups on a fluorophore precursor which suppress fluorescence thus converting the fluorophore precursor to a fluorescent form) (see column 8 and Examples 4, 7, and 8 in columns 16, 18 and 19), Drmanac has shown the set comprising at least 100 different first oligonucleotide probes (ie., 100 to 10,000 probe molecules having informative regions that are distinct from each other) wherein the first probe set comprises at least 200 different oligonucleotide probes, the first probe set comprises at least 500 different oligonucleotide probes, and a kit comprises first set of probes associated with a FRET acceptor molecule, a second set of probes associated with a FRET donor molecule, and a ligating reagent (see paragraphs [0029] to [0046], [0089] and [0090], and claim 20), and the Stratagene catalog teaches a motivation for combining reagents of use in an assay into a kit, “[E]ach kit provides two services: 1) a variety of different reagents have been assembled and pre-mixed specifically for a defined set of experiments. 2) The other service provided in a kit is quality control” (page 39, column 1). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the kits comprising the second set of oligonucleotide and one or more second detection agents as recited in claims 13, 14, and 17 by making at least 100 different oligonucleotides having the same numbers of FITC (eg., 4.1 or/and 7.2 FITC) in each of the oligonucleotides such that each of the second oligonucleotide probes of the second probe set comprise at least one second labels, the at least one second labels are the same for each of the second oligonucleotide probes of the second probe set, and the at least one second labels are different than the at least one first hapten in view of the prior arts of Haralambidis et al., Kawa et al., Drmanac, and Stratagene catalog in order to enhance the read-out signal (see column 8 from Haralambidis) and take advantages of a kit format as discussed by Stratagene catalog.
Claim 16 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Haralambidis et al., in view of Kawa et al., Drmanac, and 1988 Stratagene catalog as applied to claims 1, 3-8, 10, and 18 above, and further in view of Somiari et al., (US 2004/0048258 A1, published on March 11, 2004).
The teachings of Haralambidis et al., Kawa et al., Drmanac, and 1988 Stratagene catalog have been summarized previously, supra.
Haralambidis et al., Kawa et al., Drmanac, and 1988 Stratagene catalog do not disclose that the first genomic target sequence of interest comprises a HER2 gene locus as recited in claim 16.
Somiari et al., teach to make 6 different HER2 gene primers based on known HER2 gene (see paragraph [0045]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kit recited in claim 16 wherein the first genomic target sequence of interest comprises a HER2 gene locus in view of the prior arts of Haralambidis et al., Kawa et al., Drmanac, 1988 Stratagene catalog, and Somiari et al.,. One having ordinary skill in the art would have been motivated to do so because Somiari et al., teach to make 6 different HER2 gene primers based on known HER2 gene (see paragraph [0045]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the kit recited in claim 16 by producing a first probe set comprising at least 100 different first oligonucleotide probes for HER2 gene locus based on known HER2 gene in view of the prior arts of Haralambidis et al., Kawa et al., Drmanac, 1988 Stratagene catalog, and Somiari et al., such that each of the first oligonucleotide probes of the first probe set comprises a different nucleotide sequence complementary to a different subsequence of HER2 gene locus, each of the first oligonucleotide probes of the first probe set comprises at least one first hapten, the at least one first hapten is the same for each of the first oligonucleotide probes of the first probe set, and the at least one first hapten in each of the first oligonucleotide probes in the first probe set is positioned at a substantially identical position in order to make a HER2 gene array.
Claims 21 and 22 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Heller in view of Drmanac, Stender et al., (US 2007/0111960 A1, published on May 17, 2007), Egholm et al., (US 6,297,016 B1, published on October 2, 2001), Van Der Wijk et al., (US 2009/0117670 A1, priority date: April 27, 2007), and 1988 Stratagene catalog (page 39).
Regarding claims 21 and 22, Heller teaches a first probe set comprising different first oligonucleotide probes (eg., two multiple donor oligomers in Figure 2B), wherein each of the first oligonucleotide probes of the first probe set comprises a different nucleotide sequence, wherein each of the first oligonucleotide probes of the first probe set comprises at least one first labels, wherein the at least one first label (ie., fluorescein, see column 19, fourth paragraph) is the same for each of the first oligonucleotide probes of the first probe set, and wherein the at least one first label is a hapten (ie., fluorescein) as recited in claim 21 and each of the first oligonucleotide probes of the first probe set comprises at least three first labels (ie., three fluorescein molecules), wherein each of the at least three first labels in each of the first oligonucleotide probes are about equally spaced (ie., having 6 base pair spacing between two adjacent fluorescein molecules) as recited in claim 22 (see abstract, columns 3-5, 10-12, 18, 19, 21, and 22, claims 1-21 and Figures 2A and 2B). Although Heller does not disclose that each of the first oligonucleotide probes of the first probe set comprises a different nucleotide sequence complementary to a different subsequence of the first genomic target sequence of interest as recited in claim 21, since the first genomic target sequence of interest is not a structure limitation of claim 21 and the first genomic target sequence of interest can be an artificially synthesized nucleic acid sequence, a different nucleotide sequence of each of the first oligonucleotide probes of the first probe set has an ability to be complementary to a different subsequence of the first genomic target sequence of interest. Note that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In a claim drawn to a process of making, the intended use must result in a manipulative difference as compared to the prior art. In re Casey , 152 USPQ 235 (CCPA 1967); In re Otto , 136 USPQ 458, 459 (CCPA 1963).
Heller does not disclose a kit comprising the set comprising at least 100 different first oligonucleotide probes and a first anti-hapten antibody specific to the 2,4-dinitrophenyl hapten wherein the at least one first label is a 2,4-dinitrophenyl hapten as recited in claim 21. However, Heller teaches that a synthetic DNA is easily modified with fluorophores, chromophores, affinity labels, metal chelates, and enzymes (see column 5, seventh paragraph).
Regarding claim 21, Drmanac teaches the set comprising at least 100 different first oligonucleotide probes (ie., 100 to 10,000 probe molecules having informative regions that are distinct from each other) (see paragraphs [0029] to [0046], [0089] and [0090]). Drmanac also teaches a kit comprising a first set of probes associated with a FRET acceptor molecule, a second set of probes associated with a FRET donor molecule, and a ligating reagent (see claim 20).
Stender et al., teach that “the probe or probes may be labeled with multiple detectable moieties. The multiple detectable moieties may be identical or different labels on a single probe, or they may be identical or different labels on multiple probes. In a preferred embodiment, multiple similarly labeled probes are used in combination” (see paragraph [0023]).
Egholm et al., teach that an affinity ligand is a label selected from the group consisting of biotin, 2,4-dinitrophenyl, digoxigenin, cholesterol, polyethyleneoxy, peptides, and fluorescein (see claims 16 and 21).
Van Der Wijk et al., teach an antibodies against 2,4-dinitrophenyl (DNP) (see paragraph [0058]).
1988 Stratagene catalog teaches a motivation to combine reagents into kit format (page 39).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kits recited in claims 21 and 22 comprising a first probe set comprising at least 100 different oligonucleotide probes and a first anti-hapten antibody specific to the 2,4-dinitrophenyl hapten wherein the at least one first label is a 2,4-dinitrophenyl hapten in view of the prior arts of Heller, Drmanac, Stender et al., Egholm et al., Van Der Wijk et al., and 1988 Stratagene catalog. One having ordinary skill in the art would have been motivated to do so because Heller suggests that a synthetic DNA is easily modified with fluorophores, chromophores, affinity labels, metal chelates, and enzymes (see column 5, seventh paragraph), Drmanac has shown the set comprising at least 100 different first oligonucleotide probes (ie., 100 to 10,000 probe molecules having informative regions that are distinct from each other) wherein the first probe set comprises at least 200 different oligonucleotide probes, the first probe set comprises at least 500 different oligonucleotide probes, and a kit comprises a first set of probes associated with a FRET acceptor molecule, a second set of probes associated with a FRET donor molecule, and a ligating reagent (see paragraphs [0029] to [0046], [0089] and [0090], and claim 20), Stender et al., teach that “the probe or probes may be labeled with multiple detectable moieties. The multiple detectable moieties may be identical or different labels on a single probe, or they may be identical or different labels on multiple probes. In a preferred embodiment, multiple similarly labeled probes are used in combination” (see paragraph [0023]), Egholm et al., teach that an affinity ligand is a label selected from the group consisting of biotin, 2,4-dinitrophenyl, digoxigenin, cholesterol, polyethyleneoxy, peptides, and fluorescein (see claims 16 and 21), Van Der Wijk et al., teach an antibodies against 2,4-dinitrophenyl (DNP) (see paragraph [0058]), and 1988 Stratagene catalog teaches a motivation for combining reagents of use in an assay into a kit, “[E]ach kit provides two services: 1) a variety of different reagents have been assembled and pre-mixed specifically for a defined set of experiments. 2) The other service provided in a kit is quality control” (page 39, column 1). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the kits as recited in claims 21 and 22 by making at least 100 different oligonucleotides having the same numbers of 2,4-dinitrophenyl and putting the at least 100 different oligonucleotides and an antibodies against 2,4-dinitrophenyl
(DNP) taught by Van Der Wijk et al., into a kit format in view of the prior arts of Heller, Drmanac, Stender et al., Egholm et al., Van Der Wijk et al., and the Stratagene catalog in order to detect 2,4-dinitrophenyl hapten in the first probe set and take advantages of a kit as discussed by 1988 Stratagene catalog.
Conclusion
No claim is allowed.
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/FRANK W LU/
Primary Examiner, Art Unit 1683
March 5, 2026