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 .
Information Disclosure Statement
The IDS filed 1/12/2024 has been considered by the Examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Priority of US application PCT/US2021/041643 filed 7/14/2021 is acknowledged.
Status of Claims
Claims 1, 23, 25, 26, 32, 34-48, 50, 51, 53, 56-59, and 83 are under examination.
Claims 2-22, 24, 27-31, 33, 49, 52, 54-55, 60-82 and 84-111 are cancelled.
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 1, 23, 25, 26, 32, 34-48, 50, 51, 53, 56-59, and 83 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Step 1: Process, Machine, Manufacture or Composition
Claims 1, 23, 25, 26, 32, 34-48, 50, 51, 53, 56-59 are drawn to a method, so a process.
Claim 83 is drawn to a system comprising a processor, so a machine.
Step 2A Prong One: Identification of an Abstract Idea
The claim(s) recite(s):
1. identifying, by one or more processors, a set of microsatellite loci from the plurality of microsatellite loci based on a coverage requirement.
This step is drawn to information analysis that can be performed by the human mind and is therefore an abstract idea.
2. applying, by the one or more processors, a set of sequence-based exclusion criteria to the set of microsatellite loci to identify a subset of the set of microsatellite loci.
This step is drawn to a process of comparing information which is the exclusion criteria to microsatellite loci information which can be performed by the human mind or with math. The step is therefore an abstract idea.
3. determining, by the one or more processors, a microsatellite instability (MSI) score for the sample based on a number of microsatellite loci in the set and a number of microsatellite loci in the subset.
This step reads on a process of evaluating numbers which can be performed by the human mind or with math. The step is therefore an abstract idea.
4. comparing, by the one or more processors, the MSI score to a threshold.
This step of comparing a score to a threshold can be performed by the human mind and is therefore an abstract idea.
5. determining an MSI status of high microsatellite instability for the sample if the MSI score is greater than or equal to the threshold, wherein the MSI status of high microsatellite instability is indicative of a deficient DNA mismatch repair mechanism in the sample.
This step of evaluating a score compared to a threshold can be performed by the human mind and is therefore an abstract idea. The recited correlation between microsatellite instability and mismatch repair mechanism deficiency is also a natural correlation which is a judicial exception.
Dependent claims 23, 25, 26, 32, 34-48, 50, 51, 53, and 56-59 further characterize the abstract idea steps and are therefore also judicial exceptions.
Step 2A Prong Two: Consideration of Practical Application
The claims result in evaluating an MSI score against a threshold and determining that a microsatellite instability is indicative of a deficient DNA mismatch repair mechanism in the sample. The claims result in an abstract idea and do not recite any additional elements that integrate the abstract idea into a practical application.
This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than
a drafting effort designed to monopolize the exception.
Step 2B: Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea. The recited additional elements are drawn to:
1. providing a plurality of nucleic acid molecules obtained from the sample.
2. ligating one or more adapters onto one or more nucleic acid molecules from the plurality of nucleic acid molecules.
3. amplifying nucleic acid molecules from the plurality of nucleic acid molecules.
4. capturing nucleic acid molecules from the amplified nucleic acid molecules.
5. sequencing, by a sequencer, the captured nucleic acid molecules to obtain a plurality of sequence reads corresponding to a plurality of microsatellite loci.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because litigating adapters to nucleic acids extracted from a sample followed by amplification is a core process in Next Generation Sequencing library preparation. The additional elements of claim 1 are well known, routine and conventional processes that lead to sequencing nucleic acids from a sample.
Other elements of the method include a processor (claims 1 and 83) and memory (claim 83) which is a recitation of generic computer structure that serves to perform generic computer functions that are well-understood, routine, and conventional activities previously known to the pertinent industry. Viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1, 23, 25, 32-35, 38, 44-48, 50, 51, 53, 56-59 and 83 are rejected under 35 U.S.C. 103(a) as being unpatentable over Artsiomenka et al. (US 2021/0363586).
Artsiomenka et al. teach (par. 0006) determining the microsatellite and/or other repetitive DNA instability status of cell-free DNA (cfDNA) samples from patients (i.e. providing a plurality of nucleic acid molecules obtained from a sample), as in claim 1.
Artsiomenka et al. teach (par. 0024) attaching adapters comprising molecular barcodes to the nucleic acids prior to amplification; and Next Generation Sequencing with sequencing by ligation (par. 0083)(i.e. ligating one or more adapters onto nucleic acid molecules from the plurality of nucleic acid molecules), as in claims 1 and 83.
Artsiomenka et al. teach (par. 0024) amplification after attaching adapters (i.e. amplifying nucleic acid molecules from the plurality of nucleic acid molecules), as in claims 1 and 83.
Artsiomenka et al. teach (par. 0128) enriching for targeted segments of the nucleic acids using various target capturing strategies, after amplification (i.e. capturing nucleic acid molecules from the amplified nucleic acid molecules), as in claims 1 and 83.
Artsiomenka et al. teach (par. 0004, 0024 and 0026) sequencing target regions after amplification (i.e. sequencing the captured nucleic acid molecules to obtained a plurality of sequence reads corresponding to microsatellite loci), as in claims 1 and 83.
Artsiomenka et al. teach (par. 0047) determining coverage for loci to determine microsatellites and identifying 99 microsatellite loci consisting of short tandem repeats (par. 0219)(i.e. identifying a set of microsatellite loci from the plurality of microsatellite loci based on a coverage requirement), as in claims 1 and 83.
Artsiomenka et al. teach “specificity” (par. 0100) that detects target analyte to the exclusion of other components of a given sample and excluding (par. 0219) uninformative sites from the final MSI detection algorithm by assessing coverage and noise profiles (i.e. applying a set of sequence-based exclusion criteria to the microsatellite loci to identify a subset of the set of microsatellite loci), as in claims 1 and 83.
Artsiomenka et al. teach (Abstract) quantifying a number of different repeat lengths present at each of a plurality of microsatellite loci from sequence information to generate a site score for each of the plurality of the microsatellite loci (i.e. determining a microsatellite instability score for the sample based on a number of microsatellite loci in the set and a number of microsatellite loci in the subset), as in claims 1 and 83.
Artsiomenka et al. teach (Abstract) comparing the site score of a given microsatellite locus to a site specific trained threshold for the given microsatellite locus for each of the plurality of the microsatellite loci (i.e. comparing the MSI score to a threshold), as in claims 1 and 83.
Artsiomenka et al. teach (Abstract) calling the given microsatellite locus as being unstable when the site score of the given microsatellite locus exceeds the site specific trained threshold for the given microsatellite locus; MSI-High is determined based on being above a threshold (par. 0052 and 0075) (i.e. determining an MSI status of high microsatellite instability for the sample if the MSI score is greater than or equal to the threshold), as in claims 1 and 83.
Artsiomenka et al. teach (par. 0110 and 0212) that cancer is linked to an impaired DNA mismatch repair mechanism (MMR) and that MSI is the archetypical manifestation of defecting DNA mismatch repair which leads to increased mutation rates and cancers (par. 0212). Artsiomenka et al. teach also teach that cancer patients can have high microsatellite instability (MSI-H or MSI-High)(par. 0110).
Artsiomenka et al. do not specifically teach that an MSI status of high microsatellite instability is indicative of deficient DNA mismatch repair mechanism in a sample, as in claims 1 and 83. However, it would be obvious to one or ordinary skill to combine the teaching of Artsiomenka et al. for associating MSI-High status with cancer with the teaching of Artsiomenka et al. for associating MMR with cancer. It would be predictable to one of ordinary skill to conclude that an MSI-High status is indicative of cancer and therefore a mismatch repair mechanism (MMR), in a subject sample. Such is a combination of known elements that would yield a predictable result.
Artsiomenka et al. teach (par. 0023) a tissue sample from a subject including blood, plasma, urine and sputum, as in claims 23 and 25.
Artsiomenka et al. teach (par. 0241) mononucleotide repeats and a single trinucleotide repeat with a repeat lengths of 7 or above and microsatellite of less than 10 base pairs (par. 0078) or minisatellite of 10 to 60 base pairs (par. 0079), as in claim 32.
Artsiomenka et al. teach a known coverage (par. 0068-0069) and a coverage of up to 100% of the genome (par. 0153) and a coverage above 05x medial sample coverage which suggests at least 75x for various loci (par. 0241), as in claims 34-35.
Artsiomenka et al. teach error modes based on allele frequencies and probability criterion (par. 0015) and determining allele frequencies and read-level errors (par. 0016), as in claim 38.
Artsiomenka et al. teach (par. 0219) excluding uninformative sites from the final MSI detection algorithm based on coverage noise profiles (i.e. exclusion criteria is locus-dependent), as in claim 44.
Artsiomenka et al. teach (par. 0114) a microsatellite instability score is generated, which includes the number of microsatellite loci called as being unstable from the plurality of the microsatellite loci (e.g., is an overall or aggregate MSI score for the sample), as in claim 45.
Artsiomenka et al. teach MSI score used to identify unstable cfDNA or predict a sample as being MSI-Hight (par. 0114)(i.e. confirm diagnosis of disease in the subject) and determining MSI scores as associated with a tumor (par. 0207), as in claims 46-47.
Artsiomenka et al. teach their method as applied to various cancers (par. 0021) as listed in claim 48.
Artsiomenka et al. teach selecting therapies (par. 0022) and therapies based on MSI (par. 0036), as in claim 50.
Artsiomenka et al. teach determining and administering customized therapies (par. 0013-0014), as in claim 51.
Artsiomenka et al. teach (par. 0168) chemotherapy, immunotherapy, surgery, or therapies to target MMR( par. 0110), as in claim 53.
Artsiomenka et al. teach (par. 0010) a site specific trained threshold and a population trained threshold (i.e. second threshold) wherein an MSI score exceeds the population threshold indicates an MSI status being unstable; the nucleic acid instability score is below or at the population trained then the sample is stable (par. 0037)(i.e. MSI is stable is MSI score is less than or equal to the second threshold) and that the site specific trained threshold and population trained threshold are the not the same (par. 0019), as in claim 56.
Artsiomenka et al. teach (par. 0125) using about 50 repetitive nucleic acid loci to determine instability status of a given sample and that the and that the site specific threshold is a separately determined maximum value of a site score for a given repetitive nucleic acid locus (par. 0098) which suggests that the value is averaged, as in claim 57.
Artsiomenka et al. teach site specific thresholds can be modified based on DNA sample size (par. 0115), wherein it would be obvious to one of ordinary skill to set a threshold value according to sample data as needed, as in claims 58-59.
E-mail communication Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anna Skibinsky whose telephone number is (571) 272-4373. The examiner can normally be reached on 12 pm - 8:30 pm.
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/Anna Skibinsky/
Primary Examiner, AU 1635
