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 examiner reviewing this application in the USPTO has changed. All new correspondence should be directed to examiner Bailey Buchanan, Art Unit 1682.
Election/Restrictions
Applicant’s election without traverse of Group in the reply filed on 08/26/2025 is acknowledged. Group I, claims 1-3, Group II, claim 4, Group III, claims 5 & 6, and Group IV, claim 7, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
A first office action on the merits of claims 8-11 is set forth herein and claims 1-7 are withdrawn from consideration.
Information Disclosure Statement
The listing of references in the specification, on pages 72-82 of the instant 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, they have not been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pages 62, 65, & 69 of the instant specification. 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.
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 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.
Regarding claim 8, the recitation of “an analysis of single-molecule sequencing data” in line 3 of the claim is unclear what steps are involved. In addition, the recitation of “the analysis comprises deducing knowledge of a DNA sequence and the boundaries of genetic elements encoded therein” in lines 4-5 of the claim is unclear what deducing knowledge of a sequence and the boundaries of genetic elements entails. In addition, the recitation of “deducing knowledge of the base modification status of the bases” in line 6 of the claim is unclear what deducing knowledge of a base modification status entails. In addition, the claim recites the limitation of “the deduced DNA sequence” in lines 6-7 of the claim and there is insufficient antecedent basis for this limitation in the claim and it is unclear the deduced DNA sequence that is being referred to is from “deducing knowledge of a DNA sequence” or from “deducing knowledge of the base modification status of the bases”.
Regarding claim 9, the recitations of “provides evidence of druggability” and “such that their coincidence is inferred and coincidence between base modification and identified genetic elements of the sequence that evidence druggability” in lines 2 & 5-7 of the claim is unclear what providing evidence of druggability would entail? Determining a drug would be effective? Determining the presence of a disease? Further, what determines a coincidence between a base modification and a identified genetic element? Further, what determines a coincidence that evidences druggability from one that does not? In addition, the recitation of “a series of single-molecule sequencing data processing steps that incorporate signals of DNA sequence and DNA sequence modification” in lines 3-5 of the claim is unclear. What steps are required in a series of single-molecule data processing steps? How are signals of DNA sequence and DNA sequence modification incorporated?
Regarding claim 10, the recitation of “the genetic elements encoding a plurality of base modifying enzymes are deduced” in lines 1-2 of the claim is unclear what specific properties are deduced. In addition, the recitation of “prior knowledge of the identity of a plurality of genetic elements encoding base modifying enzymes are collated and correlated to sequencing kinetics of sequence contexts that are known/deduced to methylate” in lines 3-5 of the claim is unclear. How are identity of a plurality of genetic elements encoding base modifying enzymes determined to be correlated to sequencing kinetics? In addition, the claim recites the limitation “the analyzed sample” in line 7 of the claim and there is insufficient antecedent basis for this limitation in the claim.
Regarding claim 11, the recitation of “the single-molecule sequencing data in processed through a series of analyses and return estimates of the likelihood of prognostic outcomes” in lines 1-3 of the claim is unclear. What does a “return estimates” entail? Estimation with specific values indicating likelihood of prognostic outcome? Estimation of good or poor prognosis? In addition, the recitation of “based on the presence, absence, or contingencies dictating the presence/absence of the phenomenon of intercellular mosaic methylation” in lines 3-5 of the claim is unclear. It is unclear what contingencies are being measured and how they relate to intercellular mosaic methylation. Finally, the claim recites the limitation “the embodiment” in lines 5-6 of the claim and there is insufficient antecedent basis for this limitation in the claim.
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 natural correlation/law of nature without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
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. M.P.E.P. § 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 M.P.E.P. § 2106. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to methods and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites a method for identifying targets for treating, ameliorating, diagnosing, or prognosing infection by a microbial agent through analysis of single-molecule sequencing data. This recitation is a natural correlation between diagnosing or prognosing infection by a microbial agent and analyzing and deducing DNA sequence and modification of bases from single-molecule sequencing reads. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. It is therefore determined that the claims are directed to judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps of deducing knowledge of a DNA sequence and the boundaries of genetic elements and deducing knowledge of the base modification status, however this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method.
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the steps of detecting a DNA sequence, the boundaries of genetic elements, and base modification status of bases in the DNA sequenced through single-molecule sequencing are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible 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.
Claim(s) 8-11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gomez-Gonzalez (Gomez-Gonzalez et al.; Scientific Reports, Vol. 9, pages 1-11, March 2019), as cited on the IDS dated 06/17/2022.
Regarding claim 8, it is noted as discussed above the recitation of “an analysis of single-molecule sequencing data” in line 3 of the claim is unclear what steps are involved. In addition, the recitation of “the analysis comprises deducing knowledge of a DNA sequence and the boundaries of genetic elements encoded therein” in lines 4-5 of the claim is unclear what deducing knowledge of a sequence and the boundaries of genetic elements entails. In addition, the recitation of “deducing knowledge of the base modification status of the bases” in line 6 of the claim is unclear what deducing knowledge of a base modification status entails. In addition, the claim recites the limitation of “the deduced DNA sequence” in lines 6-7 of the claim and it is unclear the deduced DNA sequence that is being referred to is from “deducing knowledge of a DNA sequence” or from “deducing knowledge of the base modification status of the bases”. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to encompass detection of epigenetic mechanisms such as DNA methylation and gene expression through single-molecule sequencing.
Gomez-Gonzalez teaches a method for integrated analysis across 22 Mycobacterium tuberculosis clinical isolate samples through analysis of epigenetic mechanisms such as DNA methylation and its effect on gene expression through single-molecule real time (SMRT) sequencing (method comprising an analysis of single-molecule sequencing data) in order to reveal new insights that may help improve diagnostics, treatments, vaccines, and other control measures (method for identifying targets for treating, ameliorating, diagnosing, or prognosing infection by a microbial agent) (abstract lines 6-16; pg. 1 1st full paragraph lines 1-3; pg. 2 2nd full paragraph lines 1-4; pg. 9 4th full paragraph lines 1-13; pg. 9 5th full paragraph lines 1-10). In addition, Gomez-Gonzalez teaches analyzing motif and methylation through SMRT-sequencing and through analysis of the kinetic variation through the inter-pulse duration ratio (IPD) at each nucleotide in the genome to identify a large number of modifications (deducing knowledge of a DNA sequence and the boundaries of genetic elements encoded therein and deducing knowledge of the base modification status of bases) (pg. 6-7 paragraph bridging pg. 6 & pg. 7 lines 1-5).
Regarding claim 9, it is noted that as discussed above the recitations of “provides evidence of druggability” and “such that their coincidence is inferred and coincidence between base modification and identified genetic elements of the sequence that evidence druggability” in lines 2 & 5-7 of the claim is unclear what providing evidence of druggability would entail and what determines a coincidence between a base modification and a identified genetic element. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to encompass determining druggability through analysis of base modifications and identified genetic elements in a sequence.
Gomez-Gonzalez teaches that this method of studying the lineage-specific transcriptomic profiles and the mechanisms that regulate gene expression through SMRT-sequencing can give insights into mechanisms underlying these biological differences and that such insights will be useful to identify potential targets for the development of new anti-tuberculosis drugs or vaccines (provides evidence of druggability and/or utility to a user for helping clear microbial infection) (pg. 2 2nd full paragraph lines 1-4; pg. 9 3rd full paragraph lines 1-4). In addition, Gomez-Gonzalez teaches analyzing motif and methylation through SMRT-sequencing and through analysis of the kinetic variation through the inter-pulse duration ratio (IPD) at each nucleotide in the genome (series of single-molecule sequencing data processing steps) to identify a large number of modifications to analyze epigenetic mechanisms such as DNA methylation and its effect on gene expression (incorporates signals of DNA sequence order and DNA sequence modification such that coincidence is inferred and coincidences between modification and identified genetic elements of the sequence that evidence druggability) (pg. 2 2nd full paragraph lines 1-4; pg. 6-7 paragraph bridging pg. 6 & pg. 7 lines 1-5).
Regarding claim 10, it is noted that as discussed above the recitation of “prior knowledge of the identity of a plurality of genetic elements encoding base modifying enzymes are collated and correlated to sequencing kinetics of sequence contexts that are known/deduced to methylate” in lines 3-5 of the claim is unclear how are identity of a plurality of genetic elements encoding base modifying enzymes determined to be correlated to sequencing kinetics. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to encompass determining base modifications and kinetic variation in sequences to analyze differential intragenic methylation sites and differential expression.
Gomez-Gonzalez teaches analyzing motif and methylation through SMRT-sequencing and through analysis of the kinetic variation through the inter-pulse duration ratio (IPD) at each nucleotide in the genome to identify a large number of modifications in which lack of methylation was observed in some isolates that were correlated to the loss of function of the MTases enzymes (plurality of base modifying enzymes are deduced and/or prior knowledge of the identity of a plurality of genetic elements encoding base modifying enzymes are collated and correlated to sequencing kinetics of sequence contexts that are known to methylate) (pg. 6-7 paragraph bridging pg. 6 & pg. 7 lines 1-5; pg. 7 1st full paragraph lines 1-8). Gomez-Gonzalez also teaches that 5,326 different intragenic methylated sites were analyzed to obtain correlation between methylation status and gene expression level (presence or absence of intercellular mosaic methylation in the analyzed sample) (pg. 7 2nd full paragraph lines 1-19).
Regarding claim 11, it is noted as discussed above the recitation of “return estimates of the likelihood of prognostic outcomes” in line 3 of the claim and the recitation of “based on the presence, absence, or contingencies dictating the presence/absence of the phenomenon of intercellular mosaic methylation” in lines 3-5 of the claim is unclear. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to encompass determining the prognostic outcome through the presence or absence of intercellular mosaic methylation.
Gomez-Gonzalez teaches analysis of epigenetic mechanisms such as DNA methylation and its effect on gene expression through single-molecule real time (SMRT) sequencing (single-molecule sequencing data) in order to reveal new insights that may help improve diagnostics, treatments, vaccines, and other control measures through analyzing motif and methylation with the SMRT-sequencing and through analysis of the kinetic variation through the inter-pulse duration ratio (IPD) at each nucleotide in the genome to identify a large number of modifications in which 5,326 different intragenic methylated sites were analyzed to obtain correlation between methylation status and gene expression level (series of analyses and return estimates of the likelihood of prognostic outcome through the presence or absence of intercellular mosaic methylation) (abstract lines 6-16; pg. 1 1st full paragraph lines 1-3; pg. 2 2nd full paragraph lines 1-4; pg. 6-7 paragraph bridging pg. 6 & pg. 7 lines 1-5; pg. 7 2nd full paragraph lines 1-19).
Conclusion
Claims 8-11 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682