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 .
This is a complete Office action. Any rejection not reiterated or specifically addressed in this Office action was overcome by amendment.
Election/Restrictions
Upon further consideration all elections of species required in the paper mailed are WITHDRAWN. Group I is examined herein.
Claims 25-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2/18/2025.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4 and 6-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more.
The claim(s) recite(s)
(a) determining the binding yield of the probe to the patched nucleic acid, or in some claims, the probes and patched nucleic acids. The specification teaches that determining the binding yield of the probe oligonucleotide to the patched nucleic acid is accomplished by “integrating the pixels within the spot” of a microarray. Thus, the broadest reasonable interpretation of “determining the first binding yield” is that the step is a mathematical calculation or mathematical concept abstract idea.
(b) comparing the binding yields which is a mental process judicial exception
(c) the two “whereby” clauses in the independent claim set forth correlations which are additional mental processes
(d) “identify coupling between patch binding sites and probe binding sites” and “analyzed to generate secondary structure of the nucleic acid” are a mental process judicial exception.
This judicial exception is not integrated into a practical application because the claims do not apply or use the judicial exceptions in any way. The steps in the claims in addition to the judicial exceptions are data gathering steps necessary to practice the judicial exceptions.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps in addition to the judicial exceptions are pre-solution data gathering steps required at a high level of generality, employing well established, conventional techniques, see Kapliniski et al. (cited and discussed herein), US 2003/0165833, para 34 and throughout, and DE10021947. Regarding the newly added limitation, this limitation is taught at least by Kapliniski et al.
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.
Claim(s) 1-4, 6-18 and 22-24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kaplinski et al. BMC Biotechnology 2010, 10:34, 10 pages.
The reference teaches a method of analyzing secondary structure of a nucleic acid that comprises combining the nucleic acid (i.e. a labeled tmRNA) with a patch oligonucleotide (referred to therein as a chaperone or helper oligonucleotide) to form a patched nucleic acid; combining the patched nucleic acid with a probe oligonucleotide and forming a patch-probed nucleic acid; determining a first binding yield of the probe oligonucleotide to the patched nucleic acid. The reference also teaches determining a second binding yield of the probe oligonucleotide to a naked nucleic acid. See "Methods" and Figure 4 and throughout.
The reference teaches "The chaperone binds to region 248-261 and the signals in the immediately preceding region (230-245) are strongly amplified in its presence. Thus, one can infer that without treatment, these regions are probably hybridized, forming a hairpin" (p. 4. Col. 2).
The region comprising 230-245 (the probe binding site) and the 248-261 (patch/chaperone binding site) comprise complementary base pairings, see Figure 4.
Note, the claim does not require complement complementarity. The claim merely requires that the patch binding site and the probe binding site “comprise” (have within them” complementary base pairings. The breadth of the claim allows for the sites to also have non-complementary positions.
Nucleotides 238-239 are 5’TA3’ and nucleotides 249-50 are 3’AT5’ which are complementary base pairs.
Nucleotides 240-242 are 5’GAC3’ and nucleotides 254-256 are 3’GTC5’ which are complementary base pairs.
Thus, the probe binding site and the patch/chaperone binding site comprise complementary base pairings.
With regard to claims 2 and 3, the nucleic acid is tmRNA, which is transfer messenger RNA.
With regard to claim 4, the reference teaches "The chaperone binds to region 248-261 and the signals in the immediately preceding region (230-245) are strongly amplified in its presence. Thus, one can infer that without treatment, these regions are probably hybridized, forming a hairpin" (p. 4. Col. 2).
With regard to claim 6, the nucleic acid has greater than 200 nucleotides, see Figure 4.
With regard to claim 7, the patch oligonucleotides are all between 2 and 200 nucleotides in length (see Figure 4, chaperones).
With regard to claim 8, the nucleic acid ant the patch oligonucleotide are combined in a reaction volume under hybridization conditions (see Microarray experiment, p. 7).
With regard to claim 9, the probe oligonucleotides are attached to a microarray and the patched nucleic acid is contacted to the microarray and the microarray is under hybridization conditions (see Microarray experiment, p. 7).
With regard to claim 10, a plurality of probe oligonucleotides are attached to the microarray (see Streptococcus pneumoniae-specific microarray, p. 7).
With regard to claims 11-12, a plurality of patched oligonucleotides are combined to form a plurality-patched nucleic acid (p. Microarray experiment "a mixture of all six chaperones."
With regard to claim 13, a binding yield for each probe oligonucleotide is determined (see figures 2 and 3).
With regard to claim 14, the binding yields are compared to a binding yield for each probe to the nucleic acid without the patch oligonucleotides (Figures 2 and 3, y axis "signal intensity change").
With regard to claim 15, the reference teaches "The chaperone binds to region 248-261 and the signals in the immediately preceding region (230-245) are strongly amplified in its presence. Thus, one can infer that without treatment, these regions are probably hybridized, forming a hairpin" (p. 4. Col. 2).
With regard to claim 16, the reference teaches the intramolecular base pairings are analyzed to generate secondary structure of the nucleic acid. See p. 4, Col. 2, "Thus, one can infer that without treatment, these regions are probably hybridized, forming a hairpin."
With regard to claim 17, the nucleic acid is RNA.
With regard to claim 18, the reference teaches a method further comprising using a DNA/RNA folding package to determine the tmRNA secondary structure (p. 8, Col. 2).
With regard to claims 22 and 23 the patch and probe oligonucleotides are DNA.
With regard to claim 24, a plurality of patch and probe oligonucleotides are used to determine binding yields for a set of combinations of patch oligonucleotides and probe oligonucleotides (Figures 2 and 3).
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) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kaplinski et al.
The teachings of the reference as they pertain to claim 1, from which claim 19 depends are given previously in this Office action.
Kaplinski et al. does not a method the does not include using an RNA folding algorithm.
However, the reference teaches that the use of DNA helper oligonucleotides (i.e. chaperones or patches) increased signal strength. The reference teaches that due to the complexity of RNA secondary and tertiary structures, the effect of any individual chaperone is not currently predictable (abstract) and that there was no correlation between predicted folding patterns and regions of greatly amplified signal strength (p. 3, 2nd column).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art before the effective filing date that the method of identifying chaperone probes for amplifying hybridization signals could be accomplished without the use of an RNA folding algorithm, and to have practiced the method taught by the reference without consulting the algorithm. One would have been motivated to do so because the reference teaches that the effectiveness of the chaperone probes is unpredictable, and therefore it is evident that they must be determined empirically.
Claim(s) 20 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kaplinski et al. in view of Wang et al. (Analytica Chimica Acta 687 (2011) 12–27).
The teachings of the Kaplinski as they pertain to claim 1, from which claim 19 depends are given previously in this Office action.
Kaplinski does not teach combining oligonucleotides in a microfluidic system.
Wang teaches that by combining the fields of microfluidics and DNA microarrays the advantages of both fields can be exploited simultaneously. Since microfluidics deals with the transfer and control of small amount of fluids in microscale flow configurations, one obvious advantage of using microfluidic system is the dramatic reduction in the sample volume (p. 13, 1st column).
It would have been prima facie obvious to have modified the method taught by Kaplinski et al. so as to have used a microfluidic system to combine sample with probes in order to test the effects of the patch molecules. One would have been motivated to use a microfluidic system to take advantage of the dramatic reduction of sample volume and reagent use.
Response to Remarks
Regarding the rejection under 101, applicant argues that the claimed steps are not mental processes or an abstract idea, at least because the combining steps require human intervention. Applicant further argues transforms the target nucleic acid into a non-natural structure. Applicant argues that the newly amended language is novel and unobvious so amounts to significantly more than the judicial exception. The rejection addresses the aspects of the claim that are not judicial exceptions; those steps (the “combining” steps) do not use or apply the judicial exceptions in any way. Furthermore, they are recited at an extremely high level of generality and employ conventional laboratory techniques.
Applicant argues that the steps recite “a practical application” in which one determines whether the patch binding site and the probe binding site are coupled or independent. There is no active step that makes this determination; even if there were, “determining” a relationship is itself an abstract idea. The “whereby” clauses that end the claims do not require active steps but simply set forth relationships that flow from the combining and determining steps.
Regarding the prior art rejections applicant argues that Kaplinski Figure 4 fails to show that the region comprising 230-245 and the region comprising 248-261 comprise complementary base pairings. This has been addressed in the modified prior art rejections.
The rejection is updated to address the amendment and maintained.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Sohail et al. each a method for analyzing the folding of large RNAs by hybridization to arrays of complementary oligonucleotides.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliet Switzer whose telephone number is (571)272-0753. The examiner can normally be reached Monday to Thursday, 8:00 AM-3:30 PM.
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/Primary Examiner, Art Unit 1682