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 .
DETAILED ACTION
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, 365(c), or 386(c) is acknowledged. Claims 58-79, and 82-87 have an effective filing date of 02NOV2018.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 3/12/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restriction
In the response filed on 5/1/2024 Applicant elected, with traverse:
Group II, claims 58-80
Species
A distinct subject – a human
A distinct treatment – a biologic
A distinct form of immunotherapy – a cancer vaccine
A distinct combination of treatment types used – small molecule and biologic
Status of Claims
Claims 58-79, and 82-87 are currently pending and presented for examination on the merits.
Claims 59, 61-62, 64-68, 71, and 73-78 are withdrawn from further examination by Examiner under 37 CFR 1.142(b) as being drawn to a non-elected invention.
Claims 1-57, and 80-81 are canceled.
Rejection Maintained
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.
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 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.
Claims 58, 60, 63, 69-70, 82-85, and 87 are rejected under 35 U.S.C. 103 as being unpatentable over O'Toole et al (WO 2018109219 A1, IDS 4/16/2021), and further in view of Huang et al (Analysis of microbial sequences in plasma cell-free DNA for early -onset breast cancer patients and healthy females, BMC Medical Genomics FEB 2018, 11(Suppl 1):16).
With respect to claim 58, O’Toole et al teaches a method of determining cancer status in an individual by abundance profiling of the individual’s microbiome [Abstract]. O’Toole et al further teaches using an oral sample to diagnose colorectal cancer (CRC) [1st Paragraph, pg. 2]. O’Toole et al further teaches individuals that exhibit modulated abundance with CRC [4th Paragraph, pg. 2]. O’Toole et al further teaches the ability to determine staging of the CRC in an individual [1st Paragraph, pg. 31]. O’Toole et al further teaches method of determining CRC status comprises assaying an oral sample from an individual and determining an abundance profile of the oral microbiome (individual oral microbiome abundance profile), comparing the individual oral microbiome abundance profile with a reference oral microbiome abundance profile, and correlating the difference between the individual oral microbiome abundance profile and the reference oral microbiome abundance profile with CRC status [5th Paragraph, pg. 31]. O’Toole et al further teaches the isolation of DNA and RNA using standard protocols, which would be expected to remove contaminants (decontaminate) patient samples [Example 2]. O’Toole et al further teaches treatments for CRC [4th Paragraph, pg. 39]. O’Toole et al further teaches administering a therapeutically effective amount of the CRC therapy [2nd Paragraph, pg. 31]. O’Toole et al further teaches correlating abundance of OTUs sample using a mathematical model [3rd Paragraph, pg. 33].
O’Toole et al does not specifically teach detecting a microbial presence in a blood-derived sample. However, this deficiency is made up in the teachings of Huang et al.
Huang et al teaches the identification of microbial cfDNA in the blood plasma of early-onset breast cancer (EOBC) patients and healthy females [Abstract]. Huang et al further teaches to improve diagnosis and treatment incorporate microbial cfDNA sequencing [Right Column, 2nd Paragraph, pg. 34]. Huang et al further teaches this method id personalized treatment of disease [Right Column, 2nd Paragraph, pg. 38]. Huang et al further teaches the samples are all plasma cfDNA samples were isolated from blood using Quick-cfDNA Serum and Plasma Kit (Zymo Research, D4076) [Right Column, 4th Paragraph, pg. 38]. Huang et al further teaches removing contaminants [Left column, 3rd Paragraph, pg. 39].
One of ordinary skill, before the effective filing date, would have been motivated to combine O’Toole’s method of treating a human cancer comprising taking a sample from a cancer patient to diagnose the cancer, comparing the microbial presence to a reference sample, and administering immunotherapy to treat the cancer, with Huang’s method of detecting microbial cfDNA in blood samples in EOBC patients. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to use O’Toole and Huang’s methods for a method for treating a mammalian cancer based on a blood-derived sample and detecting the non-mammalian, microbial presence or abundance and using a statistical model trained on cancers and administering a treatment, because the resultant method would be useful in diagnosing and treating cancer.
With respect to claim 60, O’Toole et al teaches the subject is human [2nd Paragraph, pg. 37].
With respect to claim 63, O’Toole et al teaches the treatment is a biopharmaceutical agent [4th Paragraph, pg. 39].
With respect to claim 69, Henn et al teaches administering an adjuvant with the treatment [0409].
With respect to claim 70, O’Toole et al teaches treating the cancer with immunotherapy [5th paragraph, pg. 31].
With respect to claims 82-83, and 87, Huang et al teaches cfDNA samples were isolated from blood using Quick-cfDNA Serum and Plasma Kit [Right Column, 4th Paragraph, pg. 38].
With respect to claim 84, Huang et al teaches microbial profiling of EOBC patients [Abstract]. Furthermore, O’Toole et al teaches detecting microbial presence in colorectal patients [1st Paragraph, pg. 2].
With respect to claim 85, Huang et al teaches detecting microbial presence in cfDNA [Right Column, 4th Paragraph, pg. 38].
Claims 58, 60, 63, 69-70, 72, 79, 82-85, and 87 are rejected under 35 U.S.C. 103 as being unpatentable over O'Toole et al (WO 2018109219 A1, IDS 4/16/2021) and Huang et al (Analysis of microbial sequences in plasma cell-free DNA for early -onset breast cancer patients and healthy females, BMC Medical Genomics FEB 2018, 11(Suppl 1):16) as applied to claims 58, 60, 63, 69-70, 82-85, and 87 above, and further in view of Goodman et al (WO 2018136598 A1, IDS 4/16/2021).
The teachings of O’Toole et al and Huang et al are discussed above.
O’Toole et al does not specifically teach that the cancer vaccine exploits the microbial antigens associated with the cancer. However, this deficiency is made up in the teachings of Goodman et al.
With respect to claims 72 and 79, Goodman et al teaches a method of treating cancer in a subject [0003]. Goodman et al further teaches administering immunotherapy comprising a cancer vaccine, which generally comprise microbial antigens [0008]. Goodman et al further teaches a method of treating comprising depleting the tumor of a bacterium of a genus overrepresented in tumors [0004]. Goodman et al further teaches treatments that include immunotherapy, small molecules, cancer vaccine [ 0121 ,0136].
One of ordinary skill, before the effective filing date, would have been motivated to use O’Toole and Huang’s method for a method for treating a mammalian cancer based on a blood-derived sample and detecting the non-mammalian, microbial presence or abundance and using a statistical model trained on cancers and administering a treatment, with Goodman’s method of treating cancer comprising two or more treatments that exploit microbial presence. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to use O’Toole, Huang, and Goodman’s methods for a method for treating a mammalian cancer based on a blood-derived sample and detecting the non-mammalian, microbial presence or abundance and using a statistical model trained on cancers and administering a treatment that exploits cancer microbial presence, because the resultant method could be used to diagnose and treat cancer.
Claims 58, 60, 63, 69-70, and 82-87 are rejected under 35 U.S.C. 103 as being unpatentable over O'Toole et al (WO 2018109219 A1, IDS 4/16/2021), Huang et al (Analysis of microbial sequences in plasma cell-free DNA for early -onset breast cancer patients and healthy females, BMC Medical Genomics FEB 2018, 11(Suppl 1):16) as applied to claims 58, 60, 63, 69-70, 82-85, and 87 above, and further in view of Henn et al (US 20160030494 A1).
O’Toole does not specifically teach microbial variable domain regions. However, this deficiency is made up in the teachings of Henn et al.
With respect to claim 86, Henn et al teaches first through ninth hypervariable regions of the 16S rRNA gene that are used for genetic typing of bacterial samples [0176]. Henn et al further teaches at least one of the V, V2, V3, V4, V5, V6, V7, VS, and V9 regions are used to characterize an OTU [0176].
One of ordinary skill, before the effective filing date, would have been motivated to use O’Toole and Huang’s method for a method for treating a mammalian cancer based on a blood-derived sample and detecting the non-mammalian, microbial presence or abundance and using a statistical model trained on cancers and administering a treatment, with Henn’s method characterizing microbial variable regions of 16s rRNA. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to use O’Toole, Huang, and Henn’s methods for a method for treating a mammalian cancer based on a blood-derived sample and detecting the non-mammalian, microbial presence or abundance variable domain region of 16S rRNA and using a statistical model trained on cancers and administering a treatment.
Applicant’s Arguments:
Huang does not disclose or suggest identifying microbial features as contaminants based on their biological origin, nor does it teach selectively removing such features while retaining true microbial signal.
..there is no articulated rationale as to why a person of ordinary skill in the art would have combined O'Toole and Huang to arrive at the claimed invention. O'Toole does not recognize contamination as a technical problem requiring solution, and Huang does not address contamination in the relevant sense.
Huang does not teach decontamination in the sense required by the claims but instead describes routine sequencing quality control and computational filtering for taxonomic classification. Huang does not address biological contamination, nor does it disclose identifying or removing contaminant microbial features based on their origin or behavior across samples.
Examiner’s Response:
Claim 58, “..decontaminating the microbial presence and abundance data by identifying and selectively removing certain non-mammalian, microbial features as contaminants from the microbial presence, while selectively retaining other non-mammalian, microbial features as non-contaminants, thereby separating noise contaminants from microbial signal for cancer treatment;…”
With respect to Applicant’s assertion that O’Toole and Huang do not teach the claimed decontamination process, based upon the teachings of the cited references, one of ordinary skill in the art would have had ample motivation to remove unwanted microbial agents.
Table 3 of Huang et al. indicates different types of microbial cfDNA sample, including those from bacteria, fungi, and viruses/phages. Given that O’Toole et al. teach assessing bacterial profiles in cancer diagnosis, it would have been obvious to decontaminate or remove contaminating cfDNA from, for example, fungi or viruses/phages.
Applicant states, O'Toole does not disclose "identifying and selectively removing certain non-mammalian, microbial features as contaminants from the microbial presence, while selectively retaining other non-mammalian, microbial features as non-contaminants, thereby separating noise contaminants from microbial signal,".
Huang et al further teaches the samples are all plasma cfDNA samples were isolated from blood using Quick-cfDNA Serum and Plasma Kit (Zymo Research, D4076) [Right Column, 4th Paragraph, pg. 38]. Huang et al further teaches removing contaminants [Left column, 3rd Paragraph, pg. 39].
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
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/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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