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 with traverse of Group I, claims 1-18 in the reply filed on 6/5/2026 is acknowledged. The traversal is on the ground(s) that there would be no search burden. However, the instant case is a 371 and lack of unity standards apply. Applicant has not traversed the finding of lack of unity.
The requirement is still deemed proper and is therefore made FINAL.
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 4-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and an abstract idea without significantly more.
The claim(s) each recite(s) one or more of:
-the association between increased levels of gene expression and active or progressing to active tuberculosis. This is a law of nature judicial exception because these correlations exist naturally.
-“generating a report” which is a mental process and mathematical process abstract idea where the “report” can be given orally, the “generating” involves reviewing data, making a comparison and determining if gene levels are “increased” and associating that increase with recited phenotypes
-“calculating a tuberculosis score” which is a mathematical process abstract idea
-“diagnosing” which is a mental process abstract idea
-“identifying” which is a mental process abstract idea
-“monitoring” which is a mental process abstract idea
This judicial exception is not integrated into a practical application because with regard to claims 4, 5, and 6, the claims do not apply or use the judicial exception in any way. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because with regard to claims the only steps in addition to the exceptions are data gathering steps recited at an extremely high level of generality. Furthermore, methods for measuring gene expression were well established at the time of the invention, for example a commercial microarray (Affymetrix U133 2.0) was available to measure the expression of all of the recited genes.
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, 2, 3, 11, and 12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cliff et al. (The Journal of Infectious Diseases 2013;207:18–29), as evidenced by the Probeset listing for the Human Genome U133 Plus 2.0, 7/1/2025; cited on 892 4/7/2026.
Cliff teaches a method that includes obtaining a sample of RNA from the a subject and measuring the amount of RNA transcripts encoded by each of the nine genes recited in instant claim 1.
The reference teaches that messenger RNA was isolated from venous blood taken at diagnosis and intervals during treatment (p. 19, 2nd column). The samples were hybridized to the human genome U133 plus 2.0 array GeneChips by Affymetrix, washed and stained. The arrays were scanned to produce expression data (p. 10, 2nd column).
Cliff does not specifically mention the 9 genes recited in claim 1. However, each of these genes is a target of the Affymetrix assay employed by the reference, as evidenced at least by the Probeset list of record 4/7/2026, where each gene is named. The currently claimed PLAAT4 is identified by synonym RARRES3. See pages 160, 102, 368, 286, 95, 108, 136, 233, and 203.
Thus, the method taught by Cliff inherently teaches a method as claimed.
With regard to claim 2, the subjects tested had symptoms of active tuberculosis.
With regard to claim 3, the sample comprises RNA isolated from whole blood.
With regard to claims 11 and 12, the measuring step is done by labeling cDNA made from RNA and hybridizing to a support, herein the Affymetrix microarray, see p. 19, 2nd column. Hybridizing to the array and detecting the result is considered “sequencing” since it determines that the target sequence is present, or at least something with enough identity to hybridize to the array under test conditions. Sequence information of the target is obtained enough to identify the expressed transcript.
Conclusion
Claims 13-18 are allowed.
Claims 8-10 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
At the time the invention was made, transcriptional signatures for identifying tuberculosis or progression to tuberculosis were known, see review by Gupta et al., especially figure 1. None of these taught a method which considered all 9 of the recited genes when indicating that tuberculosis was present or progressing, as is currently claimed.
IL210121A teaches that FRRS2, CYB561, LAX1, RARRES3 (synonym for PLAAT4), CA5B, CD83 and GBP5 are genes that were differentially expressed across active TB and latent TB and healthy controls (See p. 24, line 25 and Table beginning on p. 81). The reference does not teach, however, the complete set of nine recited genes. No reference teaches the claimed method.
With regard to claims 9 and 10, no reason was identified to amplify all nine of these genes using RT-PCR or an isothermal amplification method. While a the high-throughput microarray method taught by Cliff inherently detected the level of these transcripts and sequenced portions of them, there is nothing in the reference to suggest amplifying these nine transcripts as currently claimed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliet Switzer whose telephone number is (571)272-0753. The examiner can normally be reached Monday to Thursday, 8:00 AM-3:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Winston Shen can be reached at (571)-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/Primary Examiner, Art Unit 1682
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