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 .
Election/Restrictions
Applicant’s election without traverse of Group II (claims 8-11) and the species of the combination of all of the CpG islands listed in Table 1 in the reply filed on 7/15/2026 is acknowledged.
It is noted that the species election required election of a particular combination of CpG sites, not CpG islands. However, in the interest of compact prosecution and customer service, the claims are being examined as requiring at least one CpG site from every CpG island listed in claim 8.
Claims 1-12 are pending.
Claims 1-7 and 12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 7/15/2026.
Claims 8-11 are being examined on the merits.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement (e.g., see pages 1-2, 16-17). 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Abstract
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because the abstract is 159 words long. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 1, ln 19). Applicant is required to delete the 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.
The use of the term “Infinium” (pages 22 and 24, ln 22), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 8 and 10 are objected to because of the following informalities:
Claims 8 and 10 read “comprising at least on CpG site within each CpG islands listed in Table 1” and should read “comprising at least on CpG site within each CpG [[islands]]island listed in Table 1”.
Appropriate correction is required.
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 8-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim(s) is/are directed to a judicial exception encompassing a product of nature. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception as set forth below. The judicial exception is not integrated into a practical application of the judicial exception.
The following inquiries are used to determine whether a claim is drawn to patent- eligible subject matter:
Step 1. Is the claim to a process, machine, manufacture, or composition of matter? Yes - the claims are directed to a composition of matter (a kit).
Step 2A, prong 1. Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)? Yes — Where the claims are directed to a “set of probes” that can hybridize with a nucleic acid sequence that comprises a CpG site within each CpG island listed in Table 1, the claims are directed to a product of nature. Given that the probes have been given no structural definition between the ability to hybridize to DNA within the listed island regions and containing a CpG, these probes are not significantly different than naturally occurring sequences in the human genome. For example, depicted below is a sequence within CpG island 311 from table 1. The sequence comprises CpG sites, is within a CpG island as defined by Table 1, and the complement of said naturally occurring sequence (the second strand in naturally occurring double-stranded DNA) would be able to hybridize with said nucleic acid sequence.
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Step 2A, prong 2. Does the claim recite additional elements that integrate the judicial exception into a practical application? No - The judicial exception(s) to which the claims are directed are not integrated into a practical application. The claims are directed to the product, not a method of use, and therefore the judicial exception is not integrated into a practical application.
Step 2B. Does the claim recite additional elements that amount to significantly more than the judicial exception? No – The claims only recite what the product may be used for and the inclusion of the product within a kit, which does not impart further structural limitation to the product of nature. In the broadest reasonable interpretation of the claims, the kits of the claims encompass nucleic acids that lack markedly different characteristics from a naturally occurring counterpart such as portions of naturally occurring genomes (MPEP 2106.04(b)(II)).
For these reasons the claims are rejected under 35 USC 101 as directed to subject matter that is not significantly more than a judicial exception.
Claim Rejections - 35 USC § 112b - Indefiniteness
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 8-11 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 8-11 are rejected over the recitation of Tables from the specification as elements of the claims. For example, “comprising at least one CpG site within each CpG islands listed in Table 1” are recited in claims 8 and 10 and “from the group consisting of CpG sites listed in Table 1” in claims 9 and 11.
As stated in the MPEP (2173.05(s)):
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Claims 8 and 10 recite the limitation “comprises/comprising a set of probes which each hybridizes with a nucleic acid sequence comprising at least one CpG site within each CpG islands listed in Table 1”. It is unclear if this means that ANY CpG site within the genomic coordinates of each CpG island can be targeted by the set of probes, OR if it is only CpG sites that are listed within Table 1 as well, within each CpG island, that is being considered. Clarification is required.
Claims 9 and 11 depend from claim 8, inherit this deficiency, and are rejected on the same basis.
Claim 8 recites the limitation that the kit comprises a set of probes which each hybridizes with a nucleic acid sequence comprising at least on CpG site within each CpG islands listed in Table 1. However, no other structural limitations are supplied for these probes. Does the probe hybridize to a single CpG site or multiple CpG sites? Does the probe fully cover the CpG (as in the C and G are included) or does the probe only cover the C?
Claim 10 is directed to the kit of claim 8 “further comprising a set of probes which each hybridizes with a nucleic acid sequence comprising at least on CpG site within each CpG islands listed in Table 1, wherein cytosines are replaced by uracils”. It is unclear by this sentence structure whether the cytosines within the CpG sites are replaced by uracils or if it is the probe set that has their cytosines replaced by uracils. In the context of the specification, given the usage of the Infinium HumanMethylation 450K Bead Chip (pg 22, ln 22-23), it is being interpreted that the set of probes hybridize to bisulfite converted CpG sites in which the DNA has been treated to convert unmethylated cytosine bases to uracil. Addtionally, it is unclear if every CpG site within the nucleic acid sequence which the probe hybridizes to is converted, just a subset, or just one. Further clarification is required.
Claim 11 depends from claim 10, inherits this deficiency, and is rejected on the same basis.
Claim Rejections - 35 USC § 112d – Failure to Further Limit
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.
Claims 9 and 11 are 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. In the instant case, claim 9 recites that CpG sites are selected from the Group of CpG sites listed in Table 1. However, claim 8, from which claim 9 depends, already recites the limitation “comprising at least one CpG site within each CpG islands listed in Table 1”. As noted in the 112b of claim 8 above, it is unclear whether the CpG sites recited in claim 8 are only those listed within Table 1, or any CpG site within the CpG island. If the intention is that the CpG sites defined in claim 8 are only those present in Table 1, then 9 fails to further limit 8. Additionally, claim 11 recites that CpG sites are selected from the Group of CpG sites listed in Table 1. However, claim 10, from which claim 11 depends, already recites the limitation “comprising at least one CpG site within each CpG islands listed in Table 1”. As noted in the 112b of claim 10 above, it is unclear whether the CpG sites recited in claim 10 are only those listed within Table 1, or any CpG site within the CpG island. If the intention is that the CpG sites defined in claim 10 are only those present in Table 1, then 11 fails to further limit 10. 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 Interpretation
Claim 8 is directed to a kit “for predicting hepatocellular carcinoma disease in a subject”. This is an intended use of the kit and as such does not impart any further structural limitations to the kit.
Claim Rejections - 35 USC § 102
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.
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 8-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the Infinium Human Methylation 450K BeadChip (Infinium HumanMethylation450K v1.2 Manifest File with relevant CpG site probes is provided, 2013; full product Manifest can be found at support.illumina.com/downloads/infinium_humanmethylation450_product_files.html), as evidenced by Weisenberger (Weisenberger et al., Application Note: Epigenetic Analysis, Illumina, 2010).
The Infinium HumanMethylation 450K BeadChip teaches a kit that comprises a set of probes which each hybridize to a nucleic acid sequence comprising at least one CpG site from all of the CpG islands listed in Table 1 (relevant to claims 8 and 9 and consonant with the election of the combination of all CpG islands from Table 1; see relevant probes in Manifest document provided). The CpG sites from the Infinium HumanMethylation 450K BeadChip listed in the included relevant probes Manifest includes a first and second probe for each CpG site that hybridizes to a nucleic acid sequence of at least one CpG site within all of the CpG islands listed in Table 1, wherein the nucleic acid sequence has been bisulfite treated to convert unmethylated cytosines to uracils (relevant to claims 10 and 11; Weisenberger, Description of the Infinium Methylation Assay).
Claims 8-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the Random Hexamer kit of Boehringer (1997).
The Boehringer catalog teaches a kit that includes a hexanucleotide mix that is a mixture of hexamer nucleotides of all possible sequences that can be used as primers or probes. Regarding the functional limitations of claim 8, because of the comprehensive nature of the hexamer mixture (i.e. the mix contains every 6-mer sequence), such a mixture contains a set of probes that can hybridize to nucleic acids sequences that comprise CpG sites within each CpG island listed in Table 1. Furthermore, the hexamer mix contains hexamers that can hybridize to a nucleic acid sequence comprising at least one CpG site within each CpG island in Table 1 wherein the cytosines of the sites are replaced by uracils.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILEY E CASH whose telephone number is (571)272-0971. The examiner can normally be reached Monday-Friday 8:30am-6pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571)272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KAILEY ELIZABETH CASH/Examiner, Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
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