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 .
The amended claim set filed 9/3/2021 is under consideration.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-11, in the reply filed on 9/15/2025 is acknowledged. The traversal is on the ground(s) that it would not be unduly burdensome to perform a search on all the claims together in the present application. This is not found persuasive because the instant application is a 371 national stage entry of a filed PCT application. The restriction requirement is based on a lack of unity of invention. The requirements for a lack of unity finding do not require a consideration of burden under 37 CFR 1.475.
The requirement is still deemed proper and is therefore made FINAL.
Applicant’s election of a predetermined length of 80 nucleotides in the reply filed on 9/15/2025 is acknowledged. In view of the examination of the elected species, the election of species requirement has been reconsidered and is withdrawn.
Priority
The present application is a 371 national stage entry of PCT/KR2021/002149 (filed 2/19/2021), which claims benefit of REPUBLIC OF KOREA 10-2020-0020974 (filed 2/20/2020). It is noted that no English translation of the certified foreign priority document has been received.
Information Disclosure Statement
The listing of references in the specification or citation of references throughout the specification is not a proper information disclosure statement. 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 or cited on a submitted IDS, they have not been considered.
Drawings
High resolution copies of the drawings may be accessed via PAIR/Patent Center Retrieval using the Supplemental Content tab.
Claim Objections
Claim 1 is objected to because of the following informalities: the claim recites “cfDNA (cell free DNA)” rather than simply “cfDNA”, which may be interpreted in view of the specification. Appropriate correction is required.
Claim 1 is objected to because of the following informalities: the claim lacks the word “and” between elements (d) and (e). Appropriate correction is required.
Claim 7 is objected to because of the following informalities: “calculating the frequency…and determining cancer”. The phrase “determining cancer” is grammatically improper. Appropriate correction is required.
Claim Interpretation
Claims 1-10 require processing cfDNA and “analyzing the sequence of each fragment”. The amount of data to be collected and processed from analyzing bulk sequences of cfDNA as claimed is outside of the capabilities of the human mind, even with the aid of pen and paper.
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.
Claim 11 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
The claim(s) recite(s) “analyzing sequence information of a predetermined length at the 5’ end of a methylation-sensitive restriction enzyme fragment of cfDNA isolated from a subject to provide information necessary for cancer diagnosis”. The language broadly encompasses considering sequence information in either raw form or compiled data. The amount of data is not limited to a particular amount of data and broadly encompasses data for a single fragment of cfDNA. This amount of data may be considered purely by the human mind or with the aid of pen and paper.
The judicial exceptions are not integrated into a practical application because the claims do not involve:
improvements to the functioning of a computer or to any other technology or technical field;
applying or using the judicial exceptions to effect a particular treatment or prophylaxis for a disease or medical condition;
applying the judicial exception with, or by use of, a particular machine; or
effecting a transformation or reduction of a particular article to a different state or thing.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional active steps or additional elements are recited in the claim.
Claim 11 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claim is drawn to a method but does not recite any active method steps. The claim is essentially written as a preamble with an intended purpose.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 broadly encompasses “screening cancer-specific sequence information as a cancer-specific demethylation marker in cfDNA”. The instant specification describes screening for cancer-specific demethylation markers by comparing cancer samples and non-cancerous samples. See p. 20, 1. Isolation of cfDNA from blood, p. 22, Example 1, p. 22, Example 2. The instant specification does not describe how to “screen” for cancer-specific demethylation markers without comparing cfDNA fragment sequences between cancer and healthy samples.
The claim also broadly encompasses “screening” for previously identified cancer-specific demethylation markers. However, the claim and the instant specification does not describe how the counting of frequencies of sequence information is related to cancer-specific demethylation markers. The method as claimed broadly analyzes all fragments, including sequences that are not cancer-specific. There is no description of using bulk sequencing data and counting sequences to screen only “cancer-specific demethylation markers”.
Claims 2-6 depend from claim 1 and are rejected for the same reasons as claim 1.
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 1-11 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.
Regarding claim 1, the claims is generally narrative and indefinite, failing to conform with current U.S. practice. It appears to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors.
For example, the recitation to “each fragment” lacks proper antecedent basis. It is unclear if the fragments are referring to the cfDNA (which the instant specification describes as “polynucleotides”, p. 9, having particular lengths, p. 10) or fragments derived from the cleavage of the cfDNA by the methylation sensitive restriction enzymes.
Regarding claim 1, the claim recites “a predetermined length from the 5’ end of the fragment”. It is unclear if the sequence information obtained for the fragment is to start at a certain length from the 5’ terminus of the fragment, e.g. sequence information for positions 25 to 75, positions 26 to 101, etc.
Claims 2-6 depend from claim 1 and are rejected for the same reasons as claim 1 above.
Regarding claim 5, the claim recites “the nucleotide sequence”, which lacks proper antecedent basis.
Regarding claim 7, the claims is generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors.
For example, the recitation to “each fragment” lacks proper antecedent basis. It is unclear if the fragments are referring to the cfDNA (which the instant specification describes as “polynucleotides”, p. 9, having particular lengths, p. 10) or fragments derived from the cleavage of the cfDNA by the methylation sensitive restriction enzymes.
The claim concludes with “determining cancer”, which is incomplete because what is “determined” about cancer is not set forth.
There is a disconnect between “calculating the frequency of cancer-specific demethylation markers” and the data gathered in steps (a) to (d).
Claims 8-10 depend from claim 7 and are rejected for the same reasons as claim 7.
Regarding claim 11, the preamble of the claim states it is a method of “analyzing sequence information of a predetermined length at the N-terminus of a methylation-sensitive restriction enzyme fragment of cfDNA isolated from a subject to provide information necessary for cancer diagnosis”. There is no body of the claim that sets forth the active method steps required by the claim. The claim is incomplete and it is in unclear what is required by the claim.
Claim Rejections - 35 USC § 103
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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) 1-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhou (WO 2019/006269 A1; cited on the 9/3/2021 IDS).
Regarding claims 1, 2 and 4, Zhou teaches treating cfDNA from a subject with HpaII as a methylation sensitive restriction enzymes (p. 5, lines 9-27).
Zhou teaches analyzing the sequence of fragments by sequencing the fragments (p. 6, lines 6-15; p. 10, lines 11-20; p. 11, lines 14-22).
Zhou teaches obtaining sequence information of fragments by aligning sequences to reference genomes representing genetic loci (p. 40, lines 15-29).
Zhou teaches counting genetic loci by quantitating sequence reads for the genetic loci (p. 40, line 30 to p. 41, line 6).
Zhou teaches screening cancer-specific sequence information as a cancer-specific demethylation marker in cfDNA by of given genetic locus (p. 41, lines 1-6).
While Zhou does not specifically teach the sequence information is of a predetermined length from the 5’ end of the fragment, Zhou does teach size selection of fragments that are 30 nucleic acid bases (p. 6 line 25 to p. 7, line 8; and p. 64). Zhou further teaches identifying fragment sequences having adapters on both the 5’ and 3’ end and removing those sequences (p. 4, lines 20-25).
The identification of size selected fragments having adaptor sequences at both ends renders obvious the “obtaining sequence information of predetermined length from the 5’ end” because one would recognize that sequencing these size selected fragments and comparing them to a reference genome identifies sequences at and around the 5’ end of the fragment.
Regarding claim 3, Zhou teaches next-generation sequencing in the form of multiplexed sequencing (p. 36, lines 17-26) and high-throughput sequencing (p. 39, lines 15-27).
Regarding claim 5, Zhou teaches digesting cfDNA with HpaII as noted above, which results in the fragments and markers having a cohesive end sequence of the recognition sequence of HpaII. Zhou teaches size selection of fragments as noted above, which results in the nucleotide sequence consisting of the same length as the predetermined size selected fragment.
Regarding claim 6, Zhou teaches the cancer is lung cancer (p. 8, lines 5-12).
Regarding claim 7, Zhou teaches treating cfDNA from a subject with HpaII as a methylation sensitive restriction enzymes (p. 5, lines 9-27).
Zhou teaches analyzing the sequence of fragments by sequencing the fragments (p. 6, lines 6-15; p. 10, lines 11-20; p. 11, lines 14-22).
Zhou teaches obtaining sequence information of fragments by aligning sequences to reference genomes representing genetic loci (p. 40, lines 15-29).
Zhou teaches counting genetic loci by quantitating sequence reads for the genetic loci (p. 40, line 30 to p. 41, line 6), which results in calculating the frequency of cancer-specific demethylation marker in cfDNA by of given genetic locus (p. 41, lines 1-6). Zhou further teaches determining cancer.
While Zhou does not specifically teach the sequence information is of a predetermined length from the 5’ end of the fragment, Zhou does teach size selection of fragments that are 30 nucleic acid bases (p. 6 line 25 to p. 7, line 8; and p. 64). Zhou further teaches identifying fragment sequences having adapters on both the 5’ and 3’ end and removing those sequences (p. 4, lines 20-25).
The identification of size selected fragments having adaptor sequences at both ends renders obvious the “obtaining sequence information of predetermined length from the 5’ end” because one would recognize that sequencing these size selected fragments and comparing them to a reference genome identifies sequences at and around the 5’ end of the fragment.
Regarding claim 8, Zhou teaches the subject needs a second opinion about cancer (p. 18, line 26-32).
Regarding claim 9, Zhou teaches size selection of fragments as noted above, which results in the nucleotide sequence consisting of the same length as the predetermined size selected fragment.
Regarding claim 10, Zhou teaches the genetic loci is 20 distinct genetic loci (p. 42, lines 23-32).
Regarding claim 11, the above teachings of Zhou are encompassed by the broad scope of claim 11.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682