DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 24 August 2026 has been entered.
3. This action is in response to the papers filed on 24 August 2024. All objections and rejections not reiterated herein are hereby withdrawn.
In particular, the objection over claims 5 and 6 has been obviated by the amendment to claim 5.
The declaration under 37 CFR 1.132 filed 24 August 2026 is effective to obviate the previous rejections of the claims under 35 U.S.C. 103 as being unpatentable over Kim (U.S. 20200354795), in view of in view of Skog et al (20100196426) and Schorey et al (U.S. 20170253916) and over Kim (WO 2018124618, English translation included), in view of Skog et al (20100196426) and Schorey et al (U.S. 20170253916), alone or in combination with Kalluri et al (U.S. 20170059572). Note that the declaration clarified the description in the specification of Figures 1A and 1B by stating:
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The declaration states that Figure 1B shows that “some exosomal DNA samples from healthy serum did not include detectable bacterial DNA. Specifically, the second lane of the "Exosomal DNA (healthy serum)" group in Figure 1B lacks a PCR amplicon corresponding to bacterial DNA, demonstrating that all exosome isolation methods do not necessarily result in an isolated exosomes fraction having a mixture of mammalian and bacterial exosomes.” The results shown in Figure 1B support Applicant’s argument that “the method of Kim does not necessarily result in a fraction having bacterial and mammalian exosomes.” Further, Kim et al does not specifically disclose the concept of performing a method of detecting a microbiome in a patient, wherein the method comprises (in part) isolating an exosomes fraction of the body fluid sample from a patient, wherein the isolated exosomes fraction comprises a mixture of mammalian and bacterial exosomes.
Claim Status
4. Claims 1-3, 5-8, 12, 14, 16, 18, 19 and 23-25 are pending.
Claims 7 and 8 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Note that Applicant elected, without traverse, the species of the microbial macromolecule of DNA in the reply filed on 11 November 2024.
Claims 1-3, 5-6, 12, 14, 16, 18, 19, and 23-25 on the elected invention and have been examined herein.
New Claim Rejections - 35 USC § 112(a) – New Matter
5. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 5-6, 12, 14, 16, 18, 19, and 23-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The disclosure as originally filed does not provide basis for the recitation in the claims of “(b) isolating an exosomes fraction of the body fluid sample, wherein the isolated exosomes fraction comprises a mixture of mammalian and bacterial exosomes; (c) treating the mixed exosomes fraction with DNAse” (see the amendment to claim 1 in the papers filed on 19 May 2025).
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In the papers filed on 19 May 2025, Applicant pointed to the originally filed claims and paragraphs [0018-0019] and [0038] of the specification as providing support for the amendment.
However, the originally filed claims and the cited portions of the specification do not teach isolating, from a body fluid sample of a patient, a mixture of exosomes that contain both mammalian exosomes and bacterial exosomes. Rather, the teachings in the specification and Figures 1A and 1B teach isolating, from a body fluid sample of a patient, a sample of exosomes that contains bacterial and mammalian DNA.
Specifically, Figures 1A and 1B and paragraphs [0037-0038] disclose the presence of E. coli 16S rDNA and eucaryotic 18S rDNA in serum-derived exosome samples that were “treated with DNAse prior to DNA extraction to remove any freely circulating nucleic acids” (para [0018]). These teachings do not specifically teach that the serum-derived exosome sample contained both mammalian exosomes and bacterial exosomes.
Para [0019] of the specification teaches:
“Exosomes in the blood of healthy individuals contain bacterial microbiome. These exosomes can be generated by microbes in the body or by cells infected with bacteria. As such, a patient's microbiome can be assessed by isolation circulating exosomes and detecting the microbial components, such as microbial nucleic acids, present therein.”
Thus, the specification teaches that exosomes in blood can be generated by bacteria present in the blood or can be generated from a patient’s cell that is infected with bacteria. These teachings do not provide support for the concept of a method that isolates a fraction of exosomes that contains both mammalian exosomes and bacterial exosomes. There is no showing in the example provided in the specification that the isolated exosome fraction contained both mammalian exosomes and bacterial (or other microbial) exosomes, as opposed to only containing mammalian exosomes that contained microbial DNA. Rather, the example provided in the specification shows that, following DNase treatment, the exosome sample contained mammalian DNA and E. coli DNA.
In the Declaration of 24 August 2026, it is stated that Figure 1B “demonstrates that a mixture of bacterial exosomes and mammalian exosomes cannot necessarily be obtained with any exosome isolation method.”
Herein, it has not been shown that the exosome isolation method isolated a mixture of bacterial exosomes and mammalian exosomes. Nor is there a clear disclosure in the present application to provide basis for the concept required by the claims of isolating an exosome fraction from a body fluid sample of an individual wherein the exosome fraction comprises a mixture of both mammalian and bacterial exosomes.
Note also that the specification (para [0008]) states “In some aspects, the disease is cancer and the methods further comprise isolating glypican 1-containing exosomes from the exosomes fraction.” Also, claim 16 recites that the method “further comprises isolating glypican 1-containng exosomes from the exosomes fraction.” However, the specification does not teach that the (mammalian) protein glypican 1, which is frequently expressed on the surface of cancer-cell-derived exosomes, is also expressed on the surface of microbial exosomes. Nor does the specification identify any markers used to isolate / identify microbial exosomes present in the serum-derived exosome fraction in which the 18S rDNA was detected.
If Applicant maintains that the originally filed disclosure provides basis for the amended claims, Applicant should explain how the cited teachings in the present application to establish basis for the limitation that the exosome fraction contains both mammalian exosomes and microbial exosomes.
See MPEP 2163 II at “(b) New Claims, Amended Claims, or Claims Asserting Entitlement to the Benefit of an Earlier Priority Date or Filing Date under 35 U.S.C. 119, 120, 365, or 386” which states:
“To comply with the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, or to be entitled to an earlier priority date or filing date under 35 U.S.C. 119, 120, 365, or 386, each claim limitation must be expressly, implicitly, or inherently supported in the originally filed disclosure.”
6. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Gho et al (WO2016140540; English translation included; citations are with respect to the English translation) teaches a method for detecting bacterial RNA and eucaryotic RNA present in extracellular vesicles isolated from a blood sample of a subject. Gho (p. 3, fifth para) teaches:
“In order to achieve the object of the present invention as described above, the present invention comprises the steps of (a) separating the extracellular vesicles from the sample; (b) treating the extracellular vesicles with nucleases; (c) analyzing the nucleic acid using a bacterial species specific primer for the product treated with the nuclease; And (d) provides a method of identifying bacteria using the nuclease-treated bacteria-derived extracellular vesicles comprising the step of determining the presence of bacteria in accordance with the presence or absence of detection of the assay product.”
In Example 5 (p. 8-9), Gho exemplifies a method wherein Pseudomonas aeruginosa 16S rRNA and mouse 18S rRNA are detected in RNA isolated from extracellular vesicles obtained from a blood sample from the mouse, following treatment of the extracellular vesicles with ribonuclease. It is stated: (p. 9, 2nd para):
“As a result, as shown in Figure 6a, Pseudomonas species-specific 16S rRNA in mouse blood begins to be identified from 0.5 hours and then shows a tendency to decrease to 24 hours, mouse specific 18S rRNA only in 0.5 hours was identified.”
Gho does not specifically teach that the isolated extracellular vesicles (EVs) contain a mixture of mouse exosomes and Pseudomonas aeruginosa-derived exosomes.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached on 571-272-0731. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682
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