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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/15/2026 has been entered.
Effective Filing Date
The present application was filed on November 9, 2021 and is a 371 of PCT/KR2020/004093, filed March 26, 2020 and claims foreign priority to KOREA 10-2019-0037358, filed March 29, 2019. A certified copy of KOREA 10-2019-0037358 was submitted on 11/09/2021 and a certified English language translation was submitted on 03/13/2026.
Election/Restrictions
Applicant’s election without traverse of the invention of Group II, claims 8-11 in the response filed March 6, 2025 is acknowledged.
Claim Status/Action Summary
This office action is in response to the papers filed on April 15, 2026.
Claims 1-8 and 11 are pending. Claims 1-7 are withdrawn as directed to a non-elected invention. Claims 9 and 10 were canceled by applicant.
Claims 8 and 11 are under examination.
Any objections and rejections not reiterated below are hereby withdrawn.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 8 reads: “A composition comprising a primer pair capable of amplifying a fragment comprising one or more thyroid cancer biomarker CpG site selected from the group consisting of…”
Claim 8, broadly interpreted, encompasses any composition comprising any primer pair having the recited functionality “capable of amplifying…” any fragment (i.e. any nucleic acid) comprising at least one of the recited CpG sites. As such, the claim encompasses all possible pairs of polynucleotides that can be used as primers to amplify the recited CpG dinucleotide(s), including: naturally occurring fragments of the human genome having a “reference” or “wild-type” sequence (of unspecified length), some unspecified subset of these fragments of the human genome having an unspecified number of nucleotide differences (i.e. mutations) relative to the “reference” or “wild-type” sequence that retain the required functionality under unspecified conditions and to an unspecified degree, mixtures of random polynucleotide primers which necessarily comprise polynucleotides having the claimed sequences, “universal” primer sequences (e.g. adapter primers) that are capable of amplifying fragments containing the recited CpG dinucleotide(s) that comprise corresponding primer binding sites at the 5’ and 3’ termini (e.g. “adapter-ligated”, “tagmented”, or otherwise “cloned” (such as in a plasmid) fragments).
Claim 11, further requiring that the composition comprises a “sequencing primer for sequencing…” is of similar breadth to claim 8, from which it depends.
Specification
The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
The attempt to incorporate subject matter into this application by reference to "Illumina ID in HumanEPIC BeadChip" or "Infinium MethylationEPIC BeadChip (Illumina)" or "Infinium Methylation EPIC BeadChip technique" is ineffective because: i) the nucleotide sequences identified by the sequence designators “cg########” are essential material recited by the claims which is necessary to provide a written description of the claimed invention as required by 35 U.S.C. 112(a); ii) the specification does not provide the nucleotide sequences of these particular genomic loci; iii) the reference document is not clearly identified as required by 37 CFR 1.57(c)(2); and iv) the essential material attempted to be incorporated into this application by reference does not incorporate by “reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference” (see MPEP R-1.57(d)).
The incorporation by reference will not be effective until correction is made to comply with 37 CFR 1.57(c), (d), or (e). If the incorporated material is relied upon to meet any outstanding objection, rejection, or other requirement imposed by the Office, the correction must be made within any time period set by the Office for responding to the objection, rejection, or other requirement for the incorporation to be effective. Compliance will not be held in abeyance with respect to responding to the objection, rejection, or other requirement for the incorporation to be effective. In no case may the correction be made later than the close of prosecution as defined in 37 CFR 1.114(b), or abandonment of the application, whichever occurs earlier.
Any correction inserting material by amendment that was previously incorporated by reference must be accompanied by a statement that the material being inserted is the material incorporated by reference and the amendment contains no new matter. 37 CFR 1.57(g).
Claim Rejections - 35 USC § 112(a) – Written Description
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.
Claims 8 and 11 are rejected under 35 U.S.C. 112(a) 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, at the time the application was filed, had possession of the claimed invention.
Relevant to the lack of particular structural limitations in the rejected claims drawn to “a composition comprising a primer pair capable of amplifying…”,
MPEP 2163 states:
“The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.”
Additionally, at 2163IIA3(a), the MPEP states:
“…describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene “because it is only an indication of what the gene does, rather than what it is.”); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or a plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916,927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene produce, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
The present claims are broadly drawn to a composition comprising any primer pair capable of amplifying any “fragment” comprising one or more of a set of CpG dinucleotides identified by reference to the sequence designators having the form “cg########” in "Illumina ID in HumanEPIC BeadChip" or "Infinium MethylationEPIC BeadChip (Illumina)" or "Infinium Methylation EPIC BeadChip technique".
In the case of the instant claims, the functionality of “capable of amplifying…” is a critical feature of the claimed products.
The specification teaches a set of CpG dinucleotides referenced by the commercial identifiers “cg########” “represented by” probes on a commercial array that are differentially methylated in thyroid cancer samples relative to controls (paragraph 0067) and further employs “a pyrosequencing technique… to validate the selected DNA methylation markers… [where] forward, reverse, and sequencing primers were designed using PSQ Assay Design v2.0.1.15” (paragraph 0076). The specification teaches one exemplary primer pair and one exemplary sequencing primer for each of cg10705422, cg17707274 (which is not among the claimed set), and cg26849382 (i.e. a total of 1 forward, 1 reverse, and 1 sequencing primer for each of these three CpG biomarkers).
However, the specification does not teach any exemplary primers for cg15441605, cg00567113, cg06034194, or cg05763918. Nor does the specification teach any additional primers having the recited functionality “capable of amplifying a fragment comprising… [one of the recited CpG sites]”.
Furthermore, the specification does not include the actual nucleotide sequences or unambiguous genomic coordinates of the essential CpG dinucleotides.
While the skilled artisan may be capable of: identifying the essential recited CpG dinucleotides by looking up the recited sequence identifiers of form “cg########” on the referenced commercial array and making primer pairs with the claimed functionality “capable of amplifying a fragment comprising” the recited CpG dinucleotides, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
The claims encompass an extremely large genus of structurally undefined polynucleotides which have the recited functionality. This genus encompasses: a) a very large number of naturally occurring polynucleotides in a reference human genome which may be used to perform the recited function, b) a very large number of polynucleotides comprising an undefined amount of sequence variation relative to the “reference” sequence that maintain the recited functionality, c) mixtures of random polynucleotides available from commercial suppliers which are frequently used for random priming amplification which comprise all possible polynucleotide sequences of a given length (i.e. necessarily comprising a number of primers “capable of amplifying” the recited sites), and d) any “adapter” or “vector” or “plasmid” sequence(s) which may have been appended to the 5’ and 3’ ends of the “fragment” to generate a “fragment” having known primer-binding sites, for example, i) any polynucleotide cloning sequences, ii) any “adapter” sequences which are commonly ligated onto such fragments for high throughput sequencing, iii) any “tagmentation adapter” sequences which are added to the fragment at the same time the fragment is produced from a longer polynucleotide.
For claims drawn to a genus, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. Further, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“ [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
An adequate written description of a DNA, such as the cDNA of the recombinant plasmids and microorganisms of the ‘525 patent, “requires a precise definition, such as by structure, formula, chemical name, or physical properties,” not a mere wish or plan for obtaining the claimed chemical invention. Fiers v. Revel, 984 F.2d 1164, 1171, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). Accordingly, “an adequate written description of a DNA requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of the DNA itself.” Id. At 1170, 25 USPQ2d at 1606.
Thus, considering the breadth of the claimed compositions, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
Claim Rejections - 35 USC § 112(b) and (d)
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.
Claims 8 and 11 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 8 recites “a composition comprising a primer pair capable of amplifying a fragment comprising one or more thyroid cancer biomarker CpG site selected from the group…”
It is unclear whether the claim is intended to cover compositions comprising a primer pair (singular, i.e. one pair of primers) capable of amplifying a fragment (singular, i.e. one contiguous polynucleotide) that comprises one or more CpG site(s) selected from the recited group or whether the claim is intended to cover compositions comprising multiple primer pairs having the recited functionality “amplifying a fragment that comprises one or more CpG site(s) selected from…”.
It is noted that the recited CpG sites (according to a manifest of the commercial array) are not all located on one chromosome, but rather “cg10705422” is located on chromosome 11, “cg15441605” and “cg06034194” are located on chromosome 9, “cg00567113” is located on chromosome 3, “cg05763918” is located on chromosome 4, and “cg26849382” is located on chromosome 5. Therefore, it is unclear what “fragment(s)” comprise(s) one or more CpG site selected from the recited group commensurate in scope with the claims as presently written.
Claim 11 recites “The composition of claim 8, further comprising a sequencing primer for sequencing an amplification product amplified by the primer pair.”
It is unclear whether this limitation is intended to encompass a sequencing primer that is identical to one of the primers in the primer pair of claim 8, as such a sequencing primer is functional “for sequencing an amplification product…”, or whether the claim is intended to require that the sequencing primer is selected from some unspecified sequence that is internal to (i.e. not identical to or complementary to either of the primers of claim 8) the amplification product.
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.
Claim 11 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends.
Under the interpretation/embodiments identified in the 112(b) indefiniteness rejection above, it is unclear whether claim 11 requires anything more than one of the primers of the primer pair already required by claim 8.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 8 and 11 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, the rejected claims do not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
Claims 8 and 11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. MPEP 2106.
Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also MPEP 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Step 1
The claimed invention is directed to “a composition comprising a primer pair” (i.e. products) encompassing/comprising natural phenomena/products of nature.
Step 2A prong I
The claims are taken to be directed to natural phenomena.
Claim 8 is directed to “a composition comprising a primer pair” capable of amplifying a fragment comprising one or more thyroid cancer biomarker CpG site selected from the group consisting of: [a list of CpG dinucleotides identified by sequence designators from a commercial product of form “cg########”].
Claim 11 further requires that the composition “further compris[es] a sequencing primer for sequencing an amplification product amplified by the primer pair”.
The CpG dinucleotides recited by the claims are naturally occurring CpG dinucleotides in the human genome. Therefore, “a primer pair” and “a sequencing primer” with the recited functionality “capable of amplifying” and “for sequencing…” encompasses any number and any combination of naturally occurring DNA sequences found in the human genome at an unspecified “distance” in basepairs relative to the recited CpG site(s).
Therefore, the claims are directed to naturally occurring polynucleotide sequences (i.e. the judicial exception of natural phenomena/products of nature).
Having established that the claims include a naturally occurring product that is a judicial exception, it must now be determined whether or not the claims recite an element or combination of elements that amount to significantly more than that exception, and whether those additional elements also amount to significantly more for any other claimed exception(s), which ensures that the claim does not have a preemptive effect with respect to any of the recited exceptions. To determine whether a claim that includes a nature-based product limitation recites a “product of nature” exception, an analysis is performed in which it is first determined if a claim includes a nature-based product that has markedly different characteristics from the corresponding naturally occurring product, and if it does not, then it is determined whether or not other elements of the claim are sufficient to ensure that the claim as a whole amounts to significantly more that the exception itself. In order to be markedly different, the claimed product must possess at least one characteristic that is different from that of the counterpart.
In the instant case, the claims do not include any additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
The courts have identified the following concepts and products as examples of laws of nature or natural phenomena (see MPEP 2106.04(b)(I):
isolated DNA, Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589-91, 106 USPQ2d 1972, 1978-79 (2013);
single-stranded DNA fragments known as "primers", University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 761, 113 USPQ2d 1241, 1244 (Fed. Cir. 2014).
The claims encompass products that are not markedly different from products of nature for the following reasons:
Regarding claims 8 and 11, the claimed compositions comprising primer pairs or comprising primer pairs and a sequencing primer only require that the primers are capable of amplifying a fragment comprising one or more of a set of CpG dinucleotide sequences identified as “thyroid cancer biomarker” CpG sites which are naturally occurring in the human genome. Because the natural counterpart of each of the claimed “primers” which comprise the claimed compositions is a segment of a chromosome, the combination of the claimed but unspecified polynucleotide primers is not markedly different from the naturally occurring DNA sequences found in the human genome.
Step 2A prong II and step 2B
In the instant case, none of the claims provide any additional elements in addition to the judicial exceptions already claimed that would prevent the claims from having a pre-emptive effect on the use of the judicial exception. The fact that these natural products are organized into a “composition comprising… the natural products” and no other required constituents adds nothing to the judicial exceptions that would distinguish them from the naturally occurring material.
Therefore, the claims are properly rejected under 35 U.S.C. 101 as being drawn to patent-ineligible subject matter.
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 8 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NEB catalog (1996/1997), p.111.
The claims are broadly directed to a composition comprising a primer pair for any polynucleotide fragment comprising one or more recited CpG dinucleotides (claim 8), further comprising a sequencing primer (claim 11). The claim contains additional language regarding the intended use of the composition. A recitation of intended use of the claimed products must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.
The NEB catalog offered for sale a random primer mixture (i.e. a composition comprising primer pairs) of 12mer and 24mer nucleotide primers. As the calculation below shows, about 3.2 x 108 molecules of every 12mer and about 9 molecules of every single 24mer are present in each tube of the respective 12mer and 24mer mixtures.
Molecular weight of 12mer:
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48
312
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Greyscale
Total number of possible 12mers:
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28
176
media_image2.png
Greyscale
Number of molecules of 12mer in a vial sold by NEB:
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media_image3.png
24
228
media_image3.png
Greyscale
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media_image4.png
45
263
media_image4.png
Greyscale
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media_image5.png
49
438
media_image5.png
Greyscale
Number of molecules of each 12mer in a vial sold by NEB:
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media_image6.png
53
463
media_image6.png
Greyscale
Molecular weight of 24mer:
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media_image7.png
44
344
media_image7.png
Greyscale
Total number of possible 24mers:
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media_image8.png
35
191
media_image8.png
Greyscale
Number of molecules of 24mer in a vial sold by NEB:
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media_image3.png
24
228
media_image3.png
Greyscale
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media_image9.png
45
259
media_image9.png
Greyscale
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media_image10.png
55
464
media_image10.png
Greyscale
Number of molecules of each 24mer in a vial sold by NEB:
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media_image11.png
46
417
media_image11.png
Greyscale
The claims encompass a large genus of possible nucleic acid primers with no particular base composition or length. The NEB catalog kits will inherently and necessarily contain 12 and 24 nucleotide-long primers encompassed by the claims as presently recited.
Claims 8 and 11 are/remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yim et al., “Identification of Tissue-Specific DNA Methylation Signatures for Thyroid Nodule Diagnostics” Clin Cancer Res; 25(2) January 15, 2019 as evidenced by Hahn et al., “Single Base Resolution Analysis of 5-Methylcytosine and 5-Hydroxymethylcytosine by RRBS and TAB-RRBS” In: Verma, M. (eds) Cancer Epigenetics. Methods in Molecular Biology, vol 1238. Humana Press, New York, NY (2015).
This rejection is directed to the interpretation of the claims as encompassing “linker” or “adapter” primers, which are capable of amplifying a fragment (i.e. a library fragment) comprising the recited CpG dinucleotides.
Regarding claim 8, Yim teaches a composition comprising substances for whole-genome reduced representation bisulfite sequencing (Yim, page 545, column 2, paragraph 2). Yim teaches analyzing methylation levels of CpG sites genome-wide in 109 thyroid specimens including 28 benign nodules, 39 PTCs, and 42 adjacent normal thyroid tissues. (Yim, page 546, column 1, paragraph 2-column 2) (i.e. the composition is capable of analyzing a methylation level of a thyroid cancer biomarker CpG site, including those “represented by Illumina ID in HumanEPIC BeadChip”). Yim et al. teach that “the reduced representation bisulfite sequencing (RRBS) procedure was previously described by Hahn and colleagues” with particular citation to Hahn et al.
Hahn et al. evince RRBS comprises steps of “linker ligation” (i.e. attaching known primer binding sequences to the 5’ and 3’ ends of genomic DNA fragments) and “Library amplification” (i.e. amplifying DNA fragments comprising genome-wide CpG sites using a composition comprising primers capable of amplifying fragments containing all CpG sites genome-wide) (Hahn et al., page 275, Figure 1 A (reproduced below for clarity).
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567
461
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Greyscale
Therefore, Yim et al. necessarily teach the claimed composition because the primers for the “library amplification” step necessarily amplify DNA fragments comprising the recited CpG dinucleotides.
Regarding claim 11, Yim further teaches sequencing the RRBS libraries products (i.e. the composition further comprises a primer for sequencing an amplification product comprising the CpG site) (Yim, page 545, column 2, paragraph 2).
Response to arguments
The response asserts that the present claims are not anticipated by Yim et al. because as amended, the claims are directed to “a composition comprising a primer pair capable of amplifying a fragment comprising at least one of six specifically recited CpG loci” and “Yim discloses genome-wide methylation analysis” and “Yim does not directly and unambiguously disclose a primer pair composition directed to the presently recited loci”.
These arguments have been thoroughly reviewed and are not persuasive because, as described above, the broadest reasonable interpretation of “a primer pair capable of amplifying… one or more” of the recited CpG sites encompasses primers that amplify genome-wide RRBS library fragments, such as those taught by Yim et al. (see above) which necessarily comprise the recited CpG sites.
Therefore, the present claims, given their broadest reasonable interpretation, are properly rejected under 35 USC 102 as being anticipated by Yim et al., as evidenced by Hahn et al.).
Claims 8 and 11 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Widschwendter (US 20190330703 A1, filed December 15, 2017 and published October 31, 2019).
This rejection is directed to the interpretation of the claims as encompassing “linker” or “adapter” primers, which are capable of amplifying a fragment (i.e. a library fragment) comprising the recited CpG dinucleotides.
Regarding claim 8, Widschwendter teaches compositions for cancer-specific differentially methylated region discovery comprising reduced representation bisulfite sequencing (RRBS) (Widschwendter, paragraph 0305). Widschwendter teaches RRBS comprises adapter ligation (i.e. attaching known primer binding sequences to the 5’ and 3’ ends of genomic DNA fragments) after which the libraries were PCR amplified (i.e. amplifying DNA fragments comprising genome-wide CpG sites)
Therefore, Widschwendter necessarily teach the claimed composition because the primers for the “library amplification” step necessarily amplify DNA fragments comprising the recited CpG dinucleotides.
Regarding claim 11, Widschwendter further teaches sequencing the RRBS libraries products (i.e. the composition further comprises a primer for sequencing an amplification product comprising the CpG site) (Widschwendter, paragraph 0305).
Response to arguments
The response argues that the presently amended claims are not anticipated by Widschwendter because “the issue is whether Widschwendter discloses the claimed composition, namely a composition comprising a primer pair capable of amplifying a fragment containing at least one of the recited six loci. Widschwendter does not disclose such a specific targeted primer-pair composition”.
This argument has been thoroughly reviewed and is not persuasive. First, the assertion that the claims require “a specific targeted primer-pair composition” is not commensurate in scope with the present claims, which merely require a composition comprising a primer pair capable of amplifying at least one of the recited loci. As described above, the broadest reasonable interpretation of “a primer pair capable of amplifying… one or more” of the recited CpG sites encompasses primers that amplify genome-wide RRBS library fragments, such as those taught by Widschwendter. (see above) which necessarily comprise the recited CpG sites.
Therefore, the present claims, given their broadest reasonable interpretation, are properly rejected under 35 USC 102 as being anticipated by Widschwendter.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY MARK TURPIN whose telephone number is (703)756-5917. The examiner can normally be reached Monday-Friday 8:00 am - 5:00 pm.
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/Z.M.T./Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
