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 .
Information Disclosure Statement
The IDS received on September 13, 2024 is proper and is being considered by the Examiner. The NPL#14 has been lined-through as the citation did not contain at least a publication year.
Drawings
The drawings received on September 6, 2024 are acceptable.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 3, line 29). Applicant is required to peruse the specification and delete all such embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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 4, 8, 9, 11, 16, 19, and 20 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 4 is indefinite for reciting the phrase, “protein having a known nucleic acid sequence” because a protein is made up of an amino acid sequence, not nucleic acid sequence. For the purpose of prosecution, the phrase has been construed to mean, “protein having amino acid sequence encoded by a known nucleic acid sequence”.
Claim 8 is indefinite for reciting the phrase, “identifier element is not specific to any individual probe of the population of binding probes” for the following reasons. Claim 8 depends from claim 1. Claim 1 recites the phrase, “no individual member of the population of binding probes is identifiable by the identifier element,” which already means that identifier element is not associated with any specific individual binding probes. Therefore, it is unclear what additional limitation is imposed by claim 8.
Claims 9, 11, and 16 are also indefinite for the same reasoning.
Claims 8, 9, 11, and 16 have not been searched for the purpose of prior art as no meaningful interpretation could be made for these claims.
Claims 19 and 20 are indefinite for reciting the limitation, “the decoder probes” as the limitation does not have a proper antecedent basis, per se. This is because parent claim 15 recites the limitation, “decoder element population”. While this “population” is recited as having a “probe” the claim does not provide an antecedent basis for the term, “decoder probes” per se. In addition, the phrase is indefinite because parent claim 15 recites a first and a second decoder element population and therefore, it becomes unclear which of the two, “the” decoder probes is referring to (this applies to the term, “signal element probes”. For the purpose of prosecution, the phrase has been construed to refer to both.
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.
Claims 15-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Geipel et al. (WO 2020/254519 A1, published December 2020).
With regard to claim 15, Geipel et al. teach a method of detecting nucleic acid analytes in a sample as depicted below (from FIG 5):
PNG
media_image1.png
618
704
media_image1.png
Greyscale
As seen, the method comprises the steps of:
contacting a sample to a population of binding probes, wherein members of the populations of probes comprise i) non-overlapping analyte binding regions (see series of T1, T2, and T3 probes that anneal to their respective target nucleic acids in a non-overlapping way) and ii) a copy of common identifier element, such that no individual member of the population of binding probes is identifiable by the identifier element, to form an identifier element bound analyte complex (see “t1” region “t2” region and “t3” region on the probes that are identical and therefore no single oligonucleotide probe is identifiable by the common identifier sequence);
contacting the identifier element bound analyte complex to a first decoder element population, the first decoder element population comprising probes having a region complementary to the identifier element and a region having a first signal element binding domain (see the t1/c1, t2/c2, and t3/c2 oligonucleotides, wherein c1 and c2 are signal element binding domain);
PNG
media_image2.png
607
633
media_image2.png
Greyscale
contacting the identifier element bound analyte complex to a first signal element probe comprising a first fluorophore (see below FIG. 5, step 5, also “[h]ybridization of signal oligonucleotides … each type of translator element, a signal oligonucleotide with a certain signal (2), differentiable from signals of other signal oligonucleotides is applied”, section [0094]);
detecting a first fluorophore emission spectrum and removing the first decoder element population (see Fig. 5, step 6, also “decoding (and signal) oligonucleotides of all nucleic acid sequences to be detected are selectively denatured and eliminated”, section [0096]);
contacting the identifier element bound analyte complex to a second decoder element population, the second decoder element population comprising probes having a region complementary to the identifier element and a regio having a second signal element binding domain (see FIG. 5, step 7, also “decoding oligonucleotide of nucleic acid sequence (A) used in the first round comprised of sequence elements (t1) and (c1) while the new decoding oligonucleotide comprises the sequence elements (t1) and (c2)”, section [0097]); and
associating a pattern of first fluorophore emission spectra and second fluorophore emission spectra consistent with an order of addition of first decoder element population and second decoder element populations (see section [0098], “the new combination of decoding oligonucleotides is used leading to new signal combinations …” also step 8, wherein target A, B, and C result in different emission spectra 1-2-2; 1-1-1; and 2-1-2).
With regard to claims 16 and 17, the identifier element is not specific to any individual probe or does not identify any individual probe (see above),1 wherein at least two probes share a common identifier element (see t1, for example).
With regard to claim 18, the first and second fluorophore emission spectra is independent of the sequence of the identifier element, and decoder probes bind the identifier elements successively at a single binding site, and the decoder and signal element probes do not comprise analyte-specific sequence2.
Therefore, Geipel et al. anticipate the invention as claimed.
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.
Claims ??? are rejected under 35 U.S.C. 103 as being unpatentable over Geipel et al. (WO 2020/254519 A1, published December 2020).
With regard to claim 1, Geipel et al. teach a method of detecting nucleic acid analytes in a sample as depicted below (from FIG 5):
PNG
media_image1.png
618
704
media_image1.png
Greyscale
As seen, the method comprises the steps of:
contacting a sample to a population of binding probes, wherein members of the populations of probes comprise i) non-overlapping analyte binding regions (see series of T1, T2, and T3 probes that anneal to their respective target nucleic acids in a non-overlapping way) and ii) a copy of common identifier element, such that no individual member of the population of binding probes is identifiable by the identifier element, to form an identifier element bound analyte complex (see “t1” region “t2” region and “t3” region on the probes that are identical and therefore no single oligonucleotide probe is identifiable by the common identifier sequence);
contacting the identifier element bound analyte complex to a first decoder element population, the first decoder element population comprising probes having a region complementary to the identifier element and a region having a first signal element binding domain (see the t1/c1, t2/c2, and t3/c2 oligonucleotides, wherein c1 and c2 are signal element binding domain);
PNG
media_image2.png
607
633
media_image2.png
Greyscale
contacting the identifier element bound analyte complex to a first signal element probe comprising a first fluorophore (see below FIG. 5, step 5, also “[h]ybridization of signal oligonucleotides … each type of translator element, a signal oligonucleotide with a certain signal (2), differentiable from signals of other signal oligonucleotides is applied”, section [0094]);
detecting a first fluorophore emission spectrum and removing the first decoder element population (see Fig. 5, step 6, also “decoding (and signal) oligonucleotides of all nucleic acid sequences to be detected are selectively denatured and eliminated”, section [0096]);
contacting the identifier element bound analyte complex to a second decoder element population, the second decoder element population comprising probes having a region complementary to the identifier element and a regio having a second signal element binding domain (see FIG. 5, step 7, also “decoding oligonucleotide of nucleic acid sequence (A) used in the first round comprised of sequence elements (t1) and (c1) while the new decoding oligonucleotide comprises the sequence elements (t1) and (c2)”, section [0097]); and
associating a pattern of first fluorophore emission spectra and second fluorophore emission spectra consistent with an order of addition of first decoder element population and second decoder element populations (see section [0098], “the new combination of decoding oligonucleotides is used leading to new signal combinations …” also step 8, wherein target A, B, and C result in different emission spectra 1-2-2; 1-1-1; and 2-1-2).
With regard to claims 4 and 6, the target is protein, such as antibodies (see Fig. 2, also “analyte or target is a protein and the probe set comprises one or more proteins, e.g., antibodies”, section [0070]).
With regard to claim 7, the probe comprises aptamers (see section [0026], also “‘analyte-specific probe’ consists of at least two elements, namely the so-called binding element (S) … binding element (S) may be a nucleic acid such as hybridization sequence or an aptamer”).
With regard to claim 10, the identifier element is common to at least two probes of the population of binding probes (see t1, for example).
With regard to claim 13, the order of addition of first and second decoder elements is not specified by common identifier (the decoder elements order need not be ordered according to the identifiers).
With regard to claim 14, the order of observation of the first and second fluorophore is not specified by the common identifier (the signal oligonucleotide order is independent of the sequence of the common identifier).
While Geipel et al. teach that different target nucleic acids can be identified by their system, the artisans do not explicitly teach all types of nucleic acids which can be detected by their method. Consequently, the artisans do not explicitly teach that the method is for detecting a variant analyte, wherein the signal pattern is distinguishable from non-variant analyte (claim 1, in-part), wherein the variant analyte is an allelic variant (claim 2), or spliced variant (claim 3), or protein variant comprise a post-translation modification (claim 5), wherein the failure of at least some members of the different members of the population of binding probes to bind the variant analyte does not preclude formation of the identifier element bound analyte complex (claim12).
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to take the teachings of Geipel et al. and apply them for detecting the presence of other types of target analytes known to be assayed, such as nucleic acid sequence variants, such as deletion/insertion mutants that arise from alternative splicing events, as well as protein variants which arise from post-translational modification for the following reasons.
Geipel et al. teach that the disclosed method allows for the “specific quantitative and/or spatial detection or counting of different single analyte molecules in a sample in parallel via specific hybridization” (section [0019]). Given that alternative splice variants or mutation variants are comprised of different sequences, utilizing the probe set of Geipel et al. to hybridize to a sequence harboring a variant sequence or a variant protein and detecting the presence of such target molecules based on their fluorescent spectra by comparing the fluorescent spectra to that which contains a wild-type counterpart (i.e., control) would have been within the purview of the ordinarily skilled artisan, yielding a predictable outcome.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YOUNG J KIM/Primary Examiner
Art Unit 1637 August 10, 2026
/YJK/
1 The identifier element is common to the target nucleic acid, but not to the specific probe itself as discussed above.
2 the decoder and signal element bind to sequences other than that analyte sequence.
Prosecution Insights