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 .
Election/Restrictions
Applicant's election with traverse of the species (LI) in the reply filed on 01/05/2026 is acknowledged. The traversal is on the ground(s) that they species share common technical feature because all the identified species are directed to fluorescent energy-transfer dye conjugates. This is not found persuasive because the different species have in common only the acceptor and/or donor label but the linkers have different structures that comprise different substituents which can provide a very high number of different combinations for the fluorescent energy transfer dye conjugate.
The requirement is still deemed proper and is therefore made FINAL.
No prior art was found for a conjugate comprising (LI) linker, wherein A is an oligonucleotide. The examination has been extended to both (LII) and (LIII) linkers.
Claim Objections
Claim 9 is objected to because of the following informalities: R2 recites the moiety “-C(O)N(R3)-*” twice. See the first and fifth moieties for R2. Appropriate correction is required.
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 7, 9-13 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.
Claims 7 and 9 are vague and indefinite because it is unclear of what are the metes and bounds of the limitations provided in the parentheses (e.g., Na+, K+, NH4+) as the parentheses make it unclear to what part of the claim said limitations apply. Additionally, the claims are vague and indefinite because the term "e.g." means "for example" each time it is used, and therefore it is unclear of what are the metes and bounds of said term. The addition of "e.g." to an otherwise definite expression extends the scope of the expression and therefore renders it indefinite.
Claim 10 is vague and indefinite because it recites the limitation “wherein each R2, m, and * is as defined above”. Claim 10 depends from claim 1 and claim 1 does not recite said limitation.
Claim 11 is vague and indefinite because it is unclear what are the metes and bounds for the term “a fragment of the formula”. It is unclear what exactly is a fragment. Is the fragment “*-N(R5)-“ or –(CH)n-, or another part of the formula? Additionally , the groups –(CH)n- in the formula is either missing an atom or should be –(CH2)n-. Clarification is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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) 1-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al.
Lee et al. (figure 5; page 2818, column 1; page 2819, column 2 - page 2820) describes the preparation of bifluor dye comprising a fluorescein and a rhodamine moiety linked together by a linker. The dual dyes are disclosed to be attached to
oligonucleotides in order to label them and sequencing experiments were
performed using primers labelled with such dyes (inherently including the limitation of claim 2). The linker disclosed in Lee et al. corresponds to the formula (LII) wherein L2 is an arylene with both a methylamine and an amide substituent. Figure 5 shows that the linker can comprise moieties like -(C=O)-NH- and -CH2-NH- linked to the arylene, this is viewed to be inclusive of claims 9-10, wherein R1 is -C1-C10 alkyl-N(R3)-, and R2 is -C(O)N(R3)-, with R3 being H, and n+m=2.
Claims 7-8, 11-15 are also rejected because the limitations in said claims do not further limit that the linker for the fluorescent energy transfer conjugate of claim 6 is (LI) for claims 7-8, or the linker for the fluorescent energy transfer of claim 6 is (LIII) for claims 11-15.
Claim(s) 1-9, 11-18 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Evans et al. (WO2020/132487).
Evans et al. describes oligonucleotides labelled with a fluorescent energy transfer dye conjugate comprising a donor dye and an acceptor dye linked together via a linker. Evans et al. (compound 13, [0277]; example 2, pages 77-82; figure 10; claims; [0248]) describes an oligonucleotide bearing a dual tagged moiety having a rhodamine
and a fluorescein attached via phosphate bound to the oligonucleotide (inherently including the limitation of claim 2), the two fluorophores being linked together via a phosphate chain comprising polyethylene glycol units (this is viewed to be inclusive of claims 12-15). The linker disclosed in Evans et al. corresponds to the linker of formula (LIII) of the present claims.
Claims 7-8, 9 are also rejected because the limitations in said claims do not further limit that the linker for the fluorescent energy transfer conjugate of claim 6 is (LI) for claims 7-8; or the linker for the fluorescent energy transfer of claim 6 is (LII) for claim 9.
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 1-9, 11-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Evans et al. (WO2020/132487) in view of Campbell et al. “Locked vs. unlocked nucleic acids (LNA vs. UNA): contrasting structures work towards common therapeutic goals”, Chem. Soc. Rev., 2011,40,5680–5689.
Evans et al. describes oligonucleotides labelled with a fluorescent energy transfer dye conjugate comprising a donor dye and an acceptor dye linked together via a linker. Evans et al. (compound 13, [0277]; example 2, pages 77-82; figure 10; claims; [0248]) describes an oligonucleotide bearing a dual tagged moiety having a rhodamine
and a fluorescein attached via phosphate bound to the oligonucleotide (inherently including the limitation of claim 2), the two fluorophores being linked together via a phosphate chain comprising polyethylene glycol units (this is viewed to be inclusive of claims 12-15). The linker disclosed in Evans et al. corresponds to the linker of formula (LIII) of the present claims.
Claims 7-9 are also rejected because the limitations in said claims do not further limit that the linker for the fluorescent energy transfer conjugate of claim 6 is (LI) for claims 7-8; or the linker for the fluorescent energy transfer of claim 6 is (LII) for claim 9.
Evans et al. does not specifically teach the conjugate of present claim 19 in that the oligonucleotide further comprises a quencher attached to it, or the modification of the oligonucleotide of claims 20-22. However, Evans et al. teaches the reagents may include solid support and additional groups or moieties, such as additional label moieties, quenching moieties, synthesis handles and/or groups useful for, among other thing stabilizing oligonucleotide duplexes, such as, for example, agents that intercalate between base pairs (intercalating agents) and agent that bind the duplex minor groove (minor groove binding, or MGB, agents). The solid support, label moiety, synthesis handle and any optional additional moieties may be linked to one another in any fashion or orientation that permits them to perform their respective functions [0195]; In a further aspect, methods of performing singleplex or multiplex PCR, such as qPCR or end-point PCR, using the described probe are provided [0217] (this is viewed to be inclusive of the hydrolysis probe); Also provided are compositions, such as a reaction mixture or master mix, comprising the described probe. In one embodiment, the composition for PCR, such as for real-time or quantitative PCR or end-point PCR, comprises at least one of the described probes. In one embodiment, the composition or reaction mixture or master mix for PCR (e.g., qPCR or end-point PCR) comprises probes for allowing for detection of 4 target nucleic acids and the described probe(s) allowing for detection of at least one of a 5th and/or a 6th target nucleic…[0248].
Therefore, the use of further quencher is common in the art and the limitations of instant claims 20-26, are either suggested in Evans et al. or are common modifications in the art made to probes (See for example Campbell et al. teaching LNA offers increase binding affinity and their application in biotechnology, drug research, and antisense where it can stabilize interactions with target RNA (abstract)). Therefore, one of ordinary skill in the art seeking to solve the stated problem, according to the circumstances, would have been motivated to modify the primary reference in the manner of the claims, without exercising inventive skill, to achieve the expected benefits, optimizations and/or expanded applications as this is well known practice in the art.
MPEP states wherein the “[W]here 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.” In re Alter, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Routine optimization is not considered inventive and no evidence has been presented that the selection of the modifications was other than routine, that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEZIA RILEY whose telephone number is (571)272-0786. The examiner can normally be reached 7:30-6:00pm.
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/JEZIA RILEY/Primary Examiner, Art Unit 1681 4 February 2026