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 .
Status of the Claims
Claim 1 has been amended. Claim 2 has been cancelled. Claims 1, and 3-9 are pending and examined herein.
Priority
This application, filed 06/28/2022, is a DIV of 15/501,338, filed 02/02/2017, which is a 371 of PCT/US/048343, filed on 09/03/2015, which claims benefit to PRO 62/046,466, filed 09/05/2014. The benefit is acknowledged and the claims examined herein are treated as having an effective filing date of 09/05/2014.
Withdrawn Objections/Rejections
The rejection of claim 2 under 35 U.S.C. 112(b) is withdrawn in response to Applicant’s cancellation of claim 2.
The rejection of claim 2 under 35 U.S.C. 112(d) is withdrawn in response to Applicant’s cancellation of claim 2.
Claim Rejections - 35 USC § 112
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 6-9 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.
Written Description
Claims 6 and 8 recite that signals detected from biological samples are correlated to a disease state; in particular, cancer. These claims amount to the detection of volatile organic compounds detected from any biological sample can be correlated to a disease state, further specifying that any cancer can be correlated to volatile organic compounds from any biological sample. Claim 9 further specifies that the disease states could be ovarian, breast, lung, and prostate cancer.
The scope of the claims therefore covers correlation of signals from biological samples correlated to the entire genus of cancer.
The specification notes that “there is at present no sufficiently accurate screening test for early detection of cancer” (para. 0004, lines 1-2) but “cells release odorants” (para. 0065, line 1) and “As cells turn malignant, analysis of these odorants provides insight into cancer diagnosis” (para. 0065, lines 2-3).
The specification describes a method for correlating volatile organic compound signals from biological samples to ovarian cancer. The biological samples used for these examples were an ovarian cell cancer line (“OVCAR3” para. 0093) and pooled patient serum samples (para. 00110). The pooled ovarian cancer patient serum sample consisted of 10 patient samples and was compared to pooled samples from patients with benign ovarian growths, and age-matched healthy controls. The specification discloses that “measurements of pooled plasma samples from the three populations provided strong evidence that their odorant profiles can be differentiated” (para. 00110, lines 6-8).
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (See MPEP 2163(3)(ii)). In this case, the description of a correlation of volatile organic compounds detected to ovarian cancer is not sufficient to be representative of the entire genus of cancer.
The specification does not go beyond describing a correlation to ovarian cancer; however, the number of cancers is many and the potential volatile organic compound signatures are vast and unpredictable. The level of skill in the art is high, insofar as methods of detecting volatile organic compounds. At the same time, however, as described in the specification (para. 0004, lines 1-2), it was not within the skill of the art to reliably predict whether detected volatile organic compound signatures could be correlated to cancers.
It was well-known that volatile organic compound detection resulted in complex signatures and that correlation to biological states was not predictable. For example, Buszewski et al. (“Identification of volatile organic compounds secreted from cancer tissues and bacterial cultures” Journal of Chromatography B, published 06/01/2008) teaches that a volatile organic compound detection result “is very complicated because the cels release a lot of VOCs and some of them are difficult to identify” (p. 90, col. 1, para. 3, lines 10-12). Further, exemplifying the challenge of formulating correlations based on these results, they state that the chromatogram of detected volatile organic compounds “gives insufficient information about the state of patient health and it is not possible to analyse all of identified substances” (p. 90, col. 1, para. 3, lines 14-16).
Moreover, at the time of the invention, it was recognized that cancer diagnosis by volatile organic compound detection was not well-established. As described in Badjagbo (“Exhaled breath analysis for early cancer detection: principle and progress in direct mass spectrometry techniques” Clinical Chemistry and Laboratory Medicine, published 05/30/2012), cancer diagnosis by VOC detection was a challenge because of the lack of VOC profiles, the wide variation in results, and no validated diagnostic procedure (p. 1893, col. 2, para. 2, lines 14-19).
Beyond the detection of volatile organic compounds, further experimentation would be necessary to correlate any detected compounds to a disease state, especially for the genus of cancer.
Therefore, the specification does not provide a disclosure of sufficient variety in sufficient detail to demonstrate to one of ordinary skill in the art that the inventor possessed the invention, including detecting volatile organic compounds from any biological sample and correlating the detected signals to cancer as recited in the claims. Furthermore, as claims 2-5 and 7 depend from claims 1 and/or 6, these claims are also rejected.
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 5 and 6 rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas and to laws of nature/natural phenomena without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to§ 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is "directed to," we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a
fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical
application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an "'inventive concept' sufficient to 'transform"' the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not "well-understood,
routine, conventional" in the field (see MPEP § 2106.0S(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception. See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
Claim 5 recites “comparing the signal…to a standard” and claim 6 recites “correlating the signal…to a disease state).
Each of the above indicated limitations of “comparing the signal” and “correlating the signal” are characterized as abstract ideas. In particular, “comparing” is considered to be a mental process, the act of comparing the result of two experiments could for example include comparing performed solely in the human mind (such as thinking about the difference between two results). “Correlating” is considered a mathematical concept, and further, is drawn to a law of nature/natural phenomena between levels of volatile organic compounds and the disease state of a sample.
Step 2A, Prong 2
The above-discussed steps of “comparing” and “correlating” are insufficient themselves to integrate into a practical application because, as discussed above, these steps themselves are directed to abstract ideas; such steps represent judicial exceptions and not a practical application thereof.
Regarding independent claim 1, the claim recites the steps “effecting release of…volatile organic compounds from a biological sample”, “contacting the [sample] and a detection moiety”, and “detecting a signal”. However, these steps fail to further amount to a practical application of the indicated judicial exceptions. Specifically, these steps are steps considered to be insignificant extra-solution activity, as they are mere data gathering steps (necessary in order to gather the data, namely the assay to generate data to be compared and correlated).
Regarding claims 7-9, these claims limit the disease states that the signal will be correlated to, which merely limits the breadth of the law of nature/natural phenomena that the judicial exception is drawn to. Therefore, these steps fail to integrate the judicial exceptions into a practical application.
ELIGIBILITY OF STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN “INVENTIVE CONCEPT”
Further, the additional elements of the claims (the active method steps/limitations recited in addition to the judicial exceptions themselves) do not add significantly more to the judicial exception(s); the additional recited claim elements are recited at a high level of generality, and are not, for example, limited to any particular testing technique or platform as claimed.
US 2011/0259080 “GAS SENSOR” (published 10/27/2011, herein referred to as Ratcliffe) supports that detecting volatile organic compounds in a sample (para. 0045, lines 1-5), comparing these results to a sample from a healthy patient (para. 0045, lines 6-8), and correlating this data for use to help diagnose other patients (para. 0045, lines 8-10) was routine and conventional activity previously performed by those of skill in the art.
It does not appear to be the case that the active steps recited, which are performed in order to gather the data or perform the assay, are steps recited or performed in an unconventional or non-routine way, such to provide an inventive concept under step 2B.
The claimed limitations as currently presented fail to recite limitations that add a feature that is more than well-understood, conventional or routine in the field of medical diagnostics.
For all of these reasons, the claims fail to include additional elements that are sufficient to either integrate the judicial exception(s) into practical application(s) thereof, or amount to significantly more than the judicial exception(s).
Claim Rejections - 35 USC § 103
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 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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-6, 8, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Ratcliffe in view of “DNA-decorated carbon nanotube-based FETs as ultrasensitive chemical sensors: Discrimination of homologues, structural isomers, and optical isomers” AIP Advances (published 04/17/2012, referred to herein as Khamis).
Regarding claim 1, Ratcliffe teaches a method of detecting one or more volatile compounds in an atmosphere (para. 0005, lines 1-3) where volatile compounds are organic (para. 0006, lines 1-2). Ratcliffe teaches a method to contact a detection moiety (i.e. metal oxides) on a semiconductor with the atmosphere (para. 0005, line 5), and detect a signal by monitoring a change in electrical conductivity of the semiconductor (para. 0005, lines 6-8). Ratcliffe teaches that the samples can be biological (para. 0012, lines 11-18).
Regarding claim 3, Ratcliffe teaches the effectuating the release of volatile compounds from biological samples are desorbed (para. 0044, lines 13-15). As evidenced by Sethi et al., “Clinical Application of Volatile Organic Compound Analysis for Detection Infectious Diseases” (published July 2013), biological samples processed to release volatile compounds undergo thermal desorption (p. 463, col. 1, para. 5, lines 21-22), i.e. heat is used to effectuate the release of volatile organic compounds from biological samples.
Regarding claim 4, Ratcliffe teaches that the measured signal is resistance change with time of the semiconductor (para. 0014, lines 1-4) which is the result of gaseous compounds interacting with semiconducting metal oxides (para. 0014, lines 1-4).
Regarding claim 5, Ratcliffe teaches comparing the signal from the sample with a sample from a patient without the given disease state, i.e. a standard (para. 0045, lines 6-8).
Regarding claim 6, Ratcliffe teaches correlating the signal with the disease state to “identify one or more volatile compounds or patterns thereof that are indicative of a disease state” (para. 0045, lines 2-3), then “the so identified volatile compounds or patterns thereof can subsequently be used to determine the presence or absence of disease” (para. 0045, lines 8-10). This analysis amounts to correlating the signal to a disease state.
Regarding claim 8 and 9, Ratcliffe teaches measuring samples from patients with lung cancer (para. 0045, lines 1-6).
However, Ratcliffe does not teach a method using a detection moiety comprising a polynucleotide, a polypeptide, a nucleic acid-polypeptide complex, a carbohydrate, an aptamer, a ribozyme, a homolog, an analog, a conjugate, or a derivative of a polynucleotide, a polypeptide, a nucleic acid-polypeptide complex, a carbohydrate, an aptamer, a ribozyme, or a protein.
Khamis teaches a method comprising contacting vapor containing analytes (p. 3, para. 2, lines 1-2) with a detection moiety comprising polynucleotides (p. 2, para. 2, lines 1-3, Figure 1). Khamis teaches that this device can be used to rapidly and selectively respond to a variety of vapors (p. 8, para. 3, lines 1-4). Khamis teaches that this device allows for fingerprint-like matching of a mixture of analytes (p. 8, para. 3, lines 9-10). Khamis teaches that this device can be used to detect compounds associated with infectious disease and cancer (p. 9, paras. 4 and 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Ratcliffe by using the detection device taught by Khamis. An artisan would be motivated to make this modification and have a reasonable expectation of success because, as taught by Khamis, this device is intended for use in detection of volatile organic compounds in gas, including compounds associated with a disease state, as in the method taught by Ratcliffe. Further, Khamis teaches that this device is versatile, due to the variability of nucleic acid sequences, and can be tuned to specific purposes (p. 1, para. 1, lines 7-8).
Claims 7 is rejected under 35 U.S.C. 103 as being unpatentable over Ratcliffe in view of Khamis and further in view of Sethi et al., “Clinical Application of Volatile Organic Compound Analysis for Detection Infectious Diseases” (published July 2013, referred to herein as Sethi).
The combination of Ratcliffe and Khamis, as described above regarding claims 1, 5, and 6, teaches a method of correlating a volatile organic compound signal to a disease state.
The combined teachings of Ratcliffe and Khamis fail to teach a gastrointestinal disorder or an infection as a disease state.
However, Sethi teaches that “[volatile organic compound] ‘fingerprinting’ or ‘smell printing’ has been used for in vitro identification, classification, and discrimination of micro-organisms” (p. 446, col. 1, para. 3, lines 4-6) and gas sensor devices have “provided necessary tools to identify disease-specific [volatile organic compound] biomarkers in clinical matrices” (p. 466, col. 1, para. 3, lines 8-10). Sethi teaches that analytical approaches have been used to “identify [volatile organic compound] biomarkers associated with infectious disease states” (p. 466, col. 1, para. 4, lines 2-3).
It would have been obvious to one skilled in the art at the time of the effective filing date of the application to use the method taught by Ratcliffe to characterize the volatile organic compound signatures of infectious disease states as taught by Sethi. Doing so would increase the clinical applicability of the method to a larger patient population. One skilled in the art would have a reasonable expectation of success in doing so because both methods are drawn to the use of analytical measurements of volatile organic compounds in the field of medical diagnostics.
Response to Arguments
Applicant's arguments filed 10/06/2025 have been fully considered but they are not persuasive for the following reasons:
Regarding the remarks on page 4 of Applicant’s Remarks regarding the 35 U.S.C. 112(a) Written Description rejection, the rejected claims have been corrected to state that claims 6-9 are rejected.
Regarding the remarks on page 4, paragraphs 4 and 5, Applicant argues that the claims comply with the written description requirement because the specification states that “[t]he methods may further include correlating the signal, the change in signal, or both, to a disease state of the patient.” (Specification, para. 0057) and that "[a] disease state may be cancer[.]" (Specification para. 0058). Applicant further argues that the features of claims 6 and 8 are recited in the disclosure.
This argument is not persuasive. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (See MPEP 2163(3)(ii)). In this case, merely stating that the invention correlates the measured signal to a disease state or cancer is not sufficient to satisfy the requirements to comply with the written description requirement.
Regarding the remarks on page 5, paragraph 2, Applicant argues that, regarding the predictability of the claimed method, that the claimed method does not recite a “predicting” step; therefore, the analysis is misplaced.
This argument is not persuasive. When determining whether a claimed genus satisfies the written description requirement, the recognized predictability of the claimed invention by an ordinary artisan is a necessary consideration. "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) (See MPEP 2163(II)(A)(3)(a)(ii)). In this case, the description of a single species, i.e. the correlation of signals to ovarian cancer, in not sufficient to satisfy the written description requirement of the claimed genus, i.e. the correlation of signals to cancer, due to the unpredictability of correlating signals to cancer.
Regarding the remarks on page 5 regarding the rejection of claim 2 under 35 U.S.C. 112(b), this is considered moot due to the cancellation of claim 2 by Applicant.
Regarding the remarks on page 5 regarding the rejection of claim 2 under 35 U.S.C. 112(d), this is considered moot due to the cancellation of claim 2 by Applicant.
Regarding the remarks on page 6 paragraph 1 regarding the rejection of claims 5 and 6 under 35 U.S.C. 101, Applicant argues that claims 5 and 6, by virtue of being dependent on claim 1, include features outside of abstract ideas and laws of nature/natural phenomena.
This argument is not persuasive. As described above in the rejection under 35 U.S.C. 101, although the steps recited in claim 1 are not directed to abstract ideas of laws of nature/natural phenomena, these steps fail to integrate the judicial exception into a practical application. Specifically, these steps are steps considered to be insignificant extra-solution activity, as they are mere data gathering steps (necessary in order to gather the data, namely the assay to generate data to be compared and correlated).
Further regarding the remarks on page 6 paragraph 1, Applicant argues that the features of claims 5 and 6 provide an inventive concept because of the lack of a cited reference that teaches or suggests the features of newly amended claim 1. This argument is considered moot in view of the new rejection of claim 1 in response to Applicant’s amendments.
Regarding the remarks on page 6 regarding the rejection under 35 U.S.C. 102(a)(1) and (a)(2), this argument is considered moot in view of the new rejection under 35 U.S.C. 103 in response to Applicant’s amendments.
Regarding the remarks on page 7 regarding the rejection under 35 U.S.C. 103, Applicant argues that the cited art of record does not teach or motivate an artisan to arrive at newly amended claim 1. This argument is considered moot in view of the new rejection under 35 U.S.C. 103 in response to Applicant’s amendments.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 November 5, 2025