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 .
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.
Withdrawn Objection
In light of the amendments, the objection is hereby withdrawn.
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, 5, 7-11, 18 and 20 are 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 MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.” MPEP 2163.
MPEP § 2163 further states that, for a claimed genus, the written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
The nature of claims relates to a four part biological probe configured to competitively assay small molecules comprising: the four part biological probe including: 1) a signaling molecule bound to a DNA segment at a first end, 2) a cDNA segment
The claims are broad and generic to having the biological probe comprising ssDNA with one signaling molecule. Implicit in the claims is that such signaling molecule attached to the ssDNA as a whole must possess certain functional characteristics; namely the claimed signal molecule attached to the ssDNA would produce a distinguishable and measurable signal when attached on any ssDNA.
Simeonov et al. (“Interference with Fluorescence and Absorbance”, Assay Guidance Manual: Eli Lilly & Company and the National Center for Advancing Translational Sciences, pgs. 1-12, published 2015, of record) teach there are many fluorophores available that span of a wide energy spectrum, and it is important to select the appropriate fluorophore and assay conditions for a given assay to minimize assay interference and similarly, for absorbance assays, colored compounds can interfere with the detection (see abstract). Simeonov further teaches Alexa dyes have higher charge, which can limit the formation of these dimers and dimer formation results in a decreased assay performance due to self-quenching of the fluorescence, spurious changes in fluorescence polarization as a function of probe concentration, and solubility issues (see page 3, para. 2).
Kurata et al. (“Fluorescent quenching-based quantitative detection of specific DNA/RNA using a BODIPY-FL-labeled probe or primer”, Nucleic Acids Research, vol. 29, no 6 e34, published 2001, pgs. 1-5, of record) teach BODIPY FL fluorescence was quenched by its interaction with a uniquely positioned guanine (G) of DNA or RNA (see abstract; and Table 1). Kurata further teaches in the abstract that when such a probe was hybridized with a target DNA, its fluorescence was quenched by the guanine (G) in the target, complementary to the modified cytosine, and the quench rate was proportional to the amount of target DNA (also see pg. 1, left col., para. 2).
Tomita et al. (“A Multi-Fluorescent DNA/Graphene Oxide Conjugate Sensor for Signature-Based Protein Discrimination”, Sensors, vol. 17, 2194, pgs. 1-12, published 09/23/2017, of record) teach ssDNAs labeled with carboxyfluorescein (FAM) at the 3’ terminus (P1-FAM), with carboxytetramethylrhodamine (TAMRA) at the 3’ terminus (P2-TAMRA), or with indodicarbocyanine (Cy5) at the 5’ terminus (P3-Cy5) were synthesized (see pg. 3, section 2.1 Materials). Tomita further teaches P1-FAM, P2-TAMRA, and P3-Cy5 have different wavelengths but similar absorbance or fluorescence (see Fig. 2). Tomita further teaches that P1-FAM and P3-CY5 showed a similar pronounced decreased in fluorescence emission, the corresponding quenching efficacies were lower than that of P2-TAMRA and this may be attribute to the shielding of nucleobases in P1-FAM and P3-Cy5, caused by the DNA folding (see pg. 4, last para.).
Peeters et al. (“Impact of spacers on the hybridization efficiency of mixed self-assembled DNA/alkanethiol films”, Biosensors and Bioelectronics, vol. 24, pgs. 72-77, published 2008) teach immobilization of DNA strands is an essential step in the development of any DNA biosensor and evaluating spacers to assess their impact on sensitivity and reproducibility (see abstract). Peeters further teaches that there is a considerable and clear impact of spacers on the biosensor performance (see abstract and conclusion). Peeters teaches dynamic range was negatively affected and the maximum hybridization signal dropped from spacers (see pg. 76, last para. right col., section 3.3).
Meanwhile, the instant specification has only provided two examples having specific fluorophores conjugated to a defined range of lengths of oligonucleotides (see pages 17-19, as filed). The disclosed fluorophores are attached to 14-22 nucleotide sequences in length at the phosphate group (see Fig. 5, as filed). Additionally, the instant specification has only provided a single example having a specific spacer and linker to conjugate the claimed fluorophores and competitive ligand to the claimed DNA lengths (see Fig. 4, as filed) for the claimed sensitivities. The specification lacks guidance to a wide range of DNA lengths coupled to the claimed signal molecule to provide a competitive biological probe. Also, the disclosed fluorophores conjugated with a specific hydrocarbon and PEG spacers/linkers (see Fig. 4, as filed) while attached to 14-22 nucleotide sequences at a phosphate group of a particular nucleotide base to produce the claimed functions. Thus, the specification lacks guidance to a wide range of DNA structures coupled to the claimed fluorophores to provide specific sensitivities as a probe in competitive assay. The courts have stated that “tossing out the mere germ of an idea does not constitute enabling disclosure.” Genentech, 108 F.3d at 1366 (quoting Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in context of the utility requirement, that “a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion”)). “[R]easonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id.
In this instant case, such reasonable detail is lacking in these claims. For example, chemical sensitivities would encompass a wide range of chemical structures which has not been described in the instant specification. There is nothing in the application, as filed, to suggest that, for example, the DNA sequences above 22 nucleotides or below 14 nucleotides would be able to produce a similar competitive outcome.
Meanwhile, Peeters teaches that there is a considerable and clear impact of spacers on the biosensor performance (see abstract and conclusion). Peeters teaches dynamic range was negatively affected and the maximum hybridization signal dropped from spacers (see pg. 76, last para. right col., section 3.3). Tomita teaches that fluorescence emission may be shielded by nucleobases which is caused by the DNA folding. In addition, Simeonov teaches that interferences occur in assays. Likewise, Kurata teaches specific DNA or RNA molecules quenched fluorophores by simply the position of guanine and these are short DNA sequence (see abstract; and Table 1). Therefore, based from the prior art and the instant disclosure, there would be undue experimentations to determine which DNA length and position attachment of the claimed signaling molecule would produce the competitive outcome.
As stated above, the state of the art teaches the unpredictability associated with fluorophore signaling when attached to DNA sequences. Due to the state of the prior art and the lack of the instant specification in not disclosing a representative number of oligonucleotide lengths conjugated to the claimed fluorophores. Additionally, the DNA sequence also contains a competitive ligand. Thus, the fluorescent signaling as claimed would be unpredictable, as spacers clearly impact hybridization and sensitivity of DNA. In summary, due to the state of the prior art and the lack of the instant specification in not disclosing a representative number of attaching DNA probes with fluorophores and competitive ligands, as well as the lack of direction/guidance or working examples, the specification fails to teach the skilled artisan how to make the claimed invention without undue experimentations. Therefore, the claims fail to comply with the written description requirement of a representative number species.
Response to Arguments
Applicant's arguments filed 08/07/2025 have been fully considered but they are not persuasive.
Applicant argues on pages 6-7 that the amended claims are in accordance with the Office Action and the claims are in condition for allowance and this rejection be withdrawn. In particular, Applicant argues that the claimed sequences have specific nucleotides long within 14-22 nucleotides in length.
The arguments are not found persuasive because although, for example, claim 1 recites a sequence that has 18 residues, the claim is reciting the DNA segment comprises which is an open-ended limitation. In other words, the DNA segment as claimed may be longer in length.
As stated above, the instant specification has only provided two examples having specific fluorophores conjugated to a defined range of lengths of oligonucleotides (see pages 17-19, as filed). The disclosed fluorophores are attached to 14-22 nucleotide sequences in length at the phosphate group (see Fig. 5, as filed). Additionally, the instant specification has only provided a single example having a specific spacer and linker to conjugate the claimed fluorophores and competitive ligand to the claimed DNA lengths (see Fig. 4, as filed) for the claimed sensitivities. The specification lacks guidance to a wide range of DNA lengths coupled to the claimed signal molecule to provide a competitive biological probe. Also, the disclosed fluorophores conjugated with a specific hydrocarbon and PEG spacers/linkers (see Fig. 4, as filed) while attached to 14-22 nucleotide sequences at a phosphate group of a particular nucleotide base to produce the claimed functions. Thus, the specification lacks guidance to a wide range of DNA structures coupled to the claimed fluorophores to provide specific sensitivities as a probe in competitive assay.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678