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 .
Claims 117-136 are pending and are being examined on the merits.
Preliminary Amendment
The Preliminary Amendment filed February 2, 2024 is acknowledged.
Information Disclosure Statement
The Information Disclosure Statements submitted February 2, 2024 and July 16, 2024 have been considered.
Claim Objections
Claim 125 is objected to because of the following informalities:
In claim 125, the limitation “wherein the partner probe and the interrogatory probe
each comprises a splint …” should be “wherein the partner probe and the interrogatory probe each comprise a splint …”.
Appropriate correction is required.
Claim Interpretation
Claim 117 recites, in part, the limitations “a first target nucleic acid” and a partner probe comprising, in part, “a constant hybridization region complementary to a constant target sequence in the first nucleic acid”. Claim 117 additionally recites that the first target nucleic acid additionally comprises a “variable target sequence”, and claim 120 recites an SNP as an embodiment of such a variable target sequence. Thus, in claim 117, the limitation “a first target nucleic acid” is being interpreted not as a single molecule, but as two molecules with a high degree of homology, or perhaps as referring to a particular locus in a genome.
In the SNP embodiment, the “first target nucleic acid” is construed as two molecules that are identical except for the SNP position, and where one of the two “first target nucleic acid” molecules comprises the first allele at the SNP position and the second of the two “first target nucleic acid” molecules comprises the second allele at the SNP position. Further, the “constant target sequence in the first nucleic acid” is the sequence that both of the two first target nucleic acid molecules share, and “variable target sequence[s]” are the nucleotides at the positions that are not shared between the two first target nucleic acid molecules. Both of the two first target nucleic acid molecules do not have to be present in the claim 117 method, but they do have to exist, and the constant hybridization region of the partner probe and the interrogatory hybridization region of the interrogatory probe have to be designed to be complementary to them, otherwise the terms “constant hybridization region” and “variable target sequence” have no patentable weight. Stated differently, “constant” and “variant” sequences have to be “constant” and “variant”, respectively, relative to another sequence.
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 126 and 134 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.
Claims 126 recites the limitation “the first target nucleic acid or a sequence thereof”,
the meaning of which is unclear. Specifically, it is not clear what the distinction is between “the first target nucleic acid” and “a sequence [of] [the first target nucleic acid]”. Further, it is not clear if Applicant intended that the limitation “a barcode region” in claim 126 is construed as meaning that the “barcode region corresponding to the variant”, previously recited in claim 117 and which is comprised within the interrogatory probe, is the same “barcode region” that is recited in claim 126. Stated differently, is claim 126 just requiring that the claim 117 interrogatory probe barcode is located in the splint hybridization region, or is claim 126 referring to a second barcode that is in addition to the claim 117 (first) barcode? Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
Claim 134 recites the limitations “a plurality of nucleic acid probes, wherein each nucleic acid probe: (i) comprises a hybridization region complementary to a sequence in one of the RCPs …”, the meaning of which is unclear. Specifically, it is not clear if it is intended that every probe in the plurality of probes is identical (because each one comprises a region that is complementary to one RCP), or if it is intended that there are different sets of probes comprised within the plurality, wherein, within each set the probes are identical (perhaps, to detect a specific target), but that the probes differ from one set to another (perhaps, to detect multiple, different specific targets). Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 118 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 118 recites the limitation “wherein the interrogatory hybridization region
comprises one or more internal interrogatory nucleotides, and each internal interrogatory nucleotide is complementary to a corresponding nucleotide of interest in the variant”. Neither claim 118 nor the specification describes the phrase “a nucleotide of interest” in a way that requires that the “nucleotide of interest” be any particular nucleotide in the portion of the variant that hybridizes to the interrogatory hybridization region of the probe1. Thus, the “nucleotide of interest” can be any nucleotide in that region. To the extent that the limitation “nucleotide of interest” is construed to mean any nucleotide in the relevant region of the first target nucleic acid, then claim 118 does not clearly limit claim 117, from which it depends and is in improper dependent form.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Prior Art and Allowable Subject Matter
Independent claim 117, and its dependent claims, are free of the art.
The closest prior art is Bava2 (US Patent App. Pub. No. 2021/0238662 A1), which is
directed to analyzing target nucleic acids using rolling circle amplification. Bava teaches a method for analyzing a biological sample in situ comprising contacting the sample with a two-part probe, where each part of the probe comprises regions that hybridize to complementary sequences in a target nucleic acid. Each part of the probe can additionally comprise barcodes. After hybridization to the target nucleic acid the probe parts are ligated together, optionally through the use of a splint and the probe is then used as a template for rolling circle amplification. Finally, the RCA product is detected. Bava also teaches that multiplex detection of different targets can be accomplished by using multiple probes (Figs. 2, 4, 6; paras. 7, 13, 37, 39, 44, 326, 337; Example 4; claims).
However, Bava does not teach, at least, a multiplex embodiment where the two-part probe is multiplexed with a “circularizable probe for a second target nucleic acid” with the structure recited in claim 117. While such circularizable probes exist in the art, there does not appear to be any reason to modify the Bava multiplex embodiment to change one probe to the “circularizable probe” structure, nor is it clear that the Bava method would work as intended if such a modification was made to the “circularizable probe”.
Claims 117, 119-124, 127-133 and 135-136 are allowed. Claims 118, 126 and 134 are free of the art, but stand rejected under 35 USC § 112. Claim 125 is objected to, but is otherwise directed to allowable subject matter.
Conclusion
Claims 117-136 are being examined. Claims 118, 126 and 134 are rejected. Claim 125 is objected to. Claims 117, 119-124, 127-133 and 135-136 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
1 In contrast, claim 120 recites that the nucleotide of interest is a SNV, SNP, a point mutation, etc.
2 Bava was cited in the Information Disclosure Statement submitted February 2, 2024.
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