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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Drawings
The drawings are objected to because the drawings use the designation “FIGURE” instead of “FIG.” (37 CFR 1.84(u)) and, in some instances, the view numbers (e.g. FIGURE 1) are not oriented in the same direction as the view (37 CFR 1.84(p)(1)). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 3 is objected to because of the following informalities: it is presumed the claim should end with “1 to 50 nucleotides”, not “1 to 50 nucleic acids”. Appropriate correction is required.
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 1-12 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.
The term “closely adjacent” in claims 1 and 2 is a relative term which renders the claim indefinite. The term “closely adjacent” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification states at page 4, para [16]: “wherein closely adjacent shall comprise sequence stretches with not more than 1 o 2 separating nucleic acid positions”. It is not understood if this is supposed to be “1 or 2”. Appropriate correction is required.
Regarding claim 1, the phrase "such as" (line 4) renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
As claims 3-12 depend from or otherwise refer to claim 1, they are rejected for the same reasons.
Regarding claim 9, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 12, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 8-12, claim 8 recites “the at least one indicator sequencing read”. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 8 directly depends, does not say anything about sequencing reads. Claim 12 also refers to “the dataset of nucleic acid sequencing reads” and similarly lacks antecedent basis. As claims 9-12 depend from claim 8, they are rejected for the same reason.
Regarding claim 4, claims are to be complete in themselves. References to figures or tables "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.” (MPEP 2173.05(s)).
Regarding claim 6, it is unclear how “providing a biological sample” as recited in claim 1 could constitute a solely in silico method, an alternative encompassed by claim 6.
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 2 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) “Detecting within the dataset of nucleic acid sequencing reads the presence or absence of at least one indicator sequencing read which is characterized by having a nucleic acid sequence comprising…”, and then goes on to describe the indicator sequence. This would encompass merely looking at a list of sequences and observing, entirely within the mind, the presence or absence of such a sequence. This is purely mental activity (MPEP 2106.04(a)(2)(III)). This judicial exception is not integrated into a practical application because the only other elements of the claim are “providing” the dataset (which is considered extra-solution activity; MPEP 2106.05(g)), and a wherein clause that merely indicates that the presence of the indicator sequence indicates the presence of a telomere fusion (which does not represent any actual physical step of the method, but rather expresses the natural correlation between the indicator sequence and a telomere fusion, which is itself a judicial exception discussed in a separate rejection). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because providing sequencing data is considered extra-solution activity (MPEP 2106.05(g)), and because providing sequencing data is well-known, routine and conventional in molecular diagnostics as shown by the disclosure of Otte (US 11,514,289); see column 6, line 19: “For example, nucleic acids in a biological sample may be sequenced to provide sequencing data.”
Claims 1-12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural phenomenon without significantly more. The claims recite (claims 1 and 2) “Detecting…the presence or absence of at least one indicator nucleic acid…wherein the presence of the at least one indicator nucleic acid sequence indicates the presence of the at least one telomere fusion event.” This constitutes a natural correlation between the sequence and a telomere fusion event. This judicial exception is not integrated into a practical application because the only other elements of the claim are “providing” a sample (claim 1) or dataset (claim 2). Each of these is considered extra-solution activity; MPEP 2106.05(g). The claims also recite a wherein clause that merely indicates that the presence of the indicator sequence indicates the presence of a telomere fusion (which does not represent any actual physical step of the method but simply expresses the natural correlation between the indicator sequence and a telomere fusion). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because providing samples or sequencing data are considered extra-solution activity (MPEP 2106.05(g)), and because providing samples or sequencing data are well-known, routine and conventional in molecular diagnostics. See Otte (US 11,514,289) column 6, line 19: “For example, nucleic acids in a biological sample may be sequenced to provide sequencing data.”
The claims also describe the characteristics of the “indicator nucleic acid”. However, these limitations are directed to the natural correlation since they merely describe the naturally occurring nucleic acid sequence of the telomere fusion; this sequence was not invented by the Applicant.
Claim 5 merely recites a “name” for the telomere fusion.
Claim 6 recites that the method is an in silico and/or in vitro method. Regarding in silico (and the computer readable medium of claim 7), merely practicing the claimed method on a generic computer does not confer patentability on an otherwise patent-ineligible process; MPEP 2106.05(f). The term in vitro is construed as using the actual physical sample, rather than simply sequencing data. As noted above, obtaining a sample is regarded as extra-solution activity, and so does not integrate the judicial exception into a practical application of the exception, and is well-known, routine and conventional, and so does not represent significantly more than the judicial exception itself.
Claims 8-12 recite diagnosing cancer based on the detection of the indicator nucleic acid. However, this represents a judicial exception itself, which is the subject of a separate rejection.
Claims 8-12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite “wherein the presence of the at least one indicator sequencing read indicates the presence of a cancer disease characterized by the presence of a telomere fusion event in the subject”. This constitutes a natural correlation between the sequence, a telomere fusion event, and cancer. This judicial exception is not integrated into a practical application because the other elements of the claims include “providing” a sample (via claim 1). This is considered extra-solution activity; MPEP 2106.05(g). The claims also recite (via claim 1) a wherein clause that merely indicates that the presence of the indicator sequence indicates the presence of a telomere fusion (which does not represent any actual physical step of the method but simply expresses the natural correlation between the indicator sequence and a telomere fusion). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because providing samples or sequencing data are considered extra-solution activity (MPEP 2106.05(g)), and because providing samples was well-known, routine and conventional in molecular diagnostics. See Otte (US 11,514,289) column 6, line 19: “For example, nucleic acids in a biological sample may be sequenced to provide sequencing data.”
The claims also describe the characteristics of the “indicator nucleic acid”. However, these limitations are directed to the natural correlation since they merely describe the naturally occurring nucleic acid sequence of the telomere fusion; this sequence was not invented by the Applicant.
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.
Claim(s) 1-6 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Letsolo (Nucleic Acids Research 38(6):1841-1852 (2010), IDS ref).
Regarding claim 1, Letsolo provided biological samples containing nucleic acids; page 1844, last paragraph, HEK293 and MRC5 cells. Letsolo performed sequence analysis on single fusion events isolated from these cells (id. and see Fig. 2). Letsolo detected the presence of a nucleic acid sequence comprising first and second sequence stretches as recited in claim 1; see Fig. 2:
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Regarding claim 2, the sequences shown in Letsolo’s Fig. 2 constitute a data set of nucleic acid sequencing reads. As discussed for claim 1, this set of sequencing reads contains at least one indicator sequence meeting the structural limitations of the claim.
Regarding claim 3, as shown above, the first and second sequences are separated from one another by approximately 20 nucleotides. Note however that different segments of this disclosed sequence could be designated as the claimed “first sequence-stretch” and “second sequence-stretch” such that different spacing would apply.
Regarding claim 4, as shown above, the first sequence is 5’ of the second sequence, and thus represents an “inward telomere fusion” (according to instant Figure 1).
Regarding claim 5, the term “ALT-TF” does not structurally distinguish over the telomere fusion detected by Letsolo.
Regarding claim 6, Letsolo performed actual sequencing of actual DNA obtained from actual samples, which qualifies as an in vitro method.
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.
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) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Letsolo (Nucleic Acids Research 38(6):1841-1852 (2010), IDS ref) in view of Martens (US 2013/0288255).
The teachings of Letsolo have been discussed.
Martens disclosed the computer-implementation of telomere analysis and computer-readable media for such; paragraph [0099].
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the application to computerize the analysis of telomeres in the method of Letsolo, and create computer-readable media for such purpose. Computerized analysis would have offered the advantage of speed and accuracy, as well as reducing human labor.
Claim(s) 8-10 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Letsolo (Nucleic Acids Research 38(6):1841-1852 (2010), IDS ref) in view of Goggins (US 2020/0255903).
The teachings of Letsolo have been discussed.
Goggins disclosed the use of detecting telomere fusions, including those produced by the ALT pathway (paragraph [0005]), for detecting and characterizing cancer (abstract; paragraph [0009]; claim 1). Goggins disclosed (paragraph [0009]): “The biological sample could be pancreatic tissue, cells, or fluid such as pancreatic cyst fluid…”. Goggins further characterized the length of the breakpoint sequence for each TF (paragraph [0037]: “The length of telomeric DNA within fusion junctions.”).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the application to use the sequence analysis method disclosed by Letsolo to detect telomere fusions for the purpose of detecting and characterizing cancer, as Goggins taught this to be an application of the detection of telomere fusions.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, GARY BENZION can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681
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