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 of claims (48-64) in the reply filed on 09/05/2025 is acknowledged. The traversal is on the ground that there is unity of invention between Group I and Group II because the detection of specific protein biomarkers from exhaled breath condensate (EBC) is a special technical feature over the cited reference.
The Applicant alleged that Ferns does not collect breath condensate and instead only collects a gaseous sample of human breath.
This argument is not found persuasive because according to the broadest reasonable interpretation and in lights of the specification, the claim is inclusive of both exhaled breath and exhaled breath condensate. Claim 48 recites a method of “comprising” collecting a sample of exhaled breath condensate from said human being. The specification further notes an exhaled breath sample as one of the samples to use in the invention (Page 2, lines 25-27, “One embodiment relates to a method for determining pulmonary embolism and/or increased risk thereof in a human being comprising assaying a sample of exhalation air from said human being.”). Last, the sample is collected in the gaseous form and then condensed post collection by cooling as noted by the specification (Page 7, lines 30-31, “In one embodiment, the exhaled air sample can be cooled and the resulting exhaled air sample can be collected in collection tube”).
The Applicant alleged that Fens does not detect or teach specific biomarkers but rather measures nonspecific volatile organic compounds (VOCs) in exhaled breath via sensors that have different binding properties towards different VOCs.
This argument is not found persuasive because the independent claims are very broad and only requires a biomarker as recited in claims 48 and 65.
The Applicant alleged that one of ordinary skill in the art recognizes that it is not possible to detect protein or polypeptide biomarkers through exhaled breath alone because the protein biomarkers are only present in the condensate of the breath, i.e. the aqueous fraction of exhaled air.
This argument is not found persuasive because protein or polypeptide biomarkers can be part of exhaled particles (PEx) as noted by Beck et al. (Page 87, left column, second paragraph, “a major locally produced protein involved in both surfactant and host-defense functions, was established for PEx”, right column, second paragraph, “The observed proteins were compared to those previously reported
in BAL and were shown to have a good agreement between them, with >80% of the identified PEx proteins being previously reported in BAL”). Beck noted that the part of EBC that contains the nonvolatile components is the aerosol particles or exhaled particles (PEx) (Page 85, left column, third and fourth paragraph). Beck also noted the presence of sampling techniques for PEx that are different from EBC (Page 85, left column, third paragraph). Beck noted measuring protein biomarkers from exhaled particles (Page 87, left column, second paragraph, “As an alternative to immunoassay, MS-based proteomics may facilitate discovery of new biomarkers in PEx.”).
The Applicant also provisionally elected one species from Group A (claim 57) and one species from Group B (claim 51) per the interview of 10/09/2025 with Attorney, Weston Gould, PhD.
Thus, the restriction/ election requirement is still deemed proper and is therefore made FINAL.
Claims 52-53, 55-56 and 58-66 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09/05/2025.
Therefore, claims 48-51, 54 and 57 are pending and are under examination.
Priority
This application is a U.S. National Stage (371) application of PCT/EP2020/065352 filed on 06/03/2020 which claims priority to Foreign Application No. EP19177903.2 filed on 06/03/2019.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 03/01/2022 have been received. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner and all references are considered except where they were lined through.
Specification
The disclosure is objected to because of the following informalities:
The following species were recited as abbreviations in the specification without any description: SERPINC1, PLG, A2M, FGA, FGB, FGG, KLKB, ORM1 and ORM2.
Page 13 is left blank without any print.
Appropriate correction is required.
Claim Objections
Claim 57 is objected to because of the following informalities:
The claim lists multiple species without providing a description for each abbreviation.
The claim lists duplicate species: “HP, TF … HP, TF”
The claim recites abbreviations for multiple biomarkers that do not have a description for in the claim nor in the specification (“SERPINC1, PLG, A2M, FGA, FGB, FGG, KLKB, ORM1 and ORM2”). The Specification only recites “SERPINC1, PLG, A2M, FGA, FGB, FGG, KLKB … ORM1 and/or ORM2” without any description (Page 20, lines 5-6; page 21, lines 5-6).
To move the prosecution, the Examiner is interpreting the abbreviated species as: Serpin C1 (SERPINC1), plasminogen (PLG), alpha 2 macroglobulin (A2M), fibrinogen alpha (FGA), fibrinogen beta (FGB), fibrinogen gamma (FGG), Plasma Kallikrein B (KLKB), orosomucoid 1 (ORM1) and orosomucoid 2 (ORM2).
Appropriate correction is required.
Claim Interpretation
Regarding claim 48, the claim according to the broadest reasonable interpretation and in lights of the specification, is inclusive of both exhaled breath and exhaled breath condensate. Claim 48 recites a method of “comprising” collecting a sample of exhaled breath condensate from said human being. The specification further notes an exhaled breath sample as one of the samples to use in the invention (Page 2, lines 25-27, “One embodiment relates to a method for determining pulmonary embolism and/or increased risk thereof in a human being comprising assaying a sample of exhalation air from said human being.”).
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 48-51, 54 and 57 are rejected under 35 U.S.C. 101 because the claimed invention is for a process or a method that is directed to at least one judicial exception without significantly more. The claims recite a mere collection of information in the form of data from which the applicant or doctor may draw an inference in light of the correlations. Such an inference is not sufficient to transform natural correlations into a patentable application.
The judicial exceptions are not integrated into a practical application because the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions. The claims recite several judicial exceptions, i.e., a mental process (determining the presence or absence in exhaled breath condensate of one or more biomarkers associated with pulmonary embolism or increased risk of pulmonary embolism) and a law of nature (the correlation of selected biomarkers with pulmonary embolism or increased risk of having pulmonary embolism). These judicial exceptions are not integrated into a practical application because the additional limitations of the claims amount to insignificant extra-solution activity. The claims do not include additional elements that are sufficient to significantly amount to any added inventive concept to the judicial exceptions as recognized by the court decisions listed in MPEP § 2106.05(d).
Step 1: Is the claim to a process, machine, manufacture or composition of matter?)
This part of the eligibility analysis evaluates whether the claim falls within any statutory category per MPEP 2106.03.
Claim 48 of the instant application is directed to a statutory class of a method as it recites “A method for determining pulmonary embolism and/or increased risk thereof in a human being…” (Step 1: YES).
(Step 2A, Prong 1: Does the claim recite an abstract idea, law of nature or natural phenomenon?)
Regarding claim 48 of the instant application and per Step 2A, prong 1, the claim recites the judicial exceptions of an abstract idea of a mental process (determining the presence or absence in exhaled breath condensate of one or more biomarkers associated with pulmonary embolism or increased risk of pulmonary embolism) as it recites “determining the presence or absence in said exhaled breath condensate of one or more biomarkers” and a law of nature (the correlation of selected biomarkers with pulmonary embolism or increased risk of having pulmonary embolism) as it recites determining the presence or absence in said exhaled breath condensate of one or more biomarkers associated with pulmonary embolism or increased risk thereof.”.
(Step 2A, Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application?)
Regarding claim 48 of the instant application and per Step 2A, prong 2, the claim as a whole does not integrate the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application.
Claim 48 of the instant application has steps of detecting the presence or absence of one or more biomarkers in an exhaled breath condensate and assessing the patient’s risk of having pulmonary embolism or being diagnosed with pulmonary embolism. These steps do not integrate the judicial exceptions into a practical application because they do not amount to more than the judicial exceptions themselves, analogous to Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 80, 84, 101 USPQ2d 1961, 1968-69, 1970 (2012). Furthermore, the claims do not act on or use the judicial exceptions in any further steps as required by MPEP 2106.04(d). Therefore, claim 48 does not integrate the judicial exceptions into a practical application.
(Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?)
Regarding claim 48 of the instant application and per Step 2B, this part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to Step 2A Prong Two, the claim simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, such as determining the presence or absence in exhaled breath condensate of one or more biomarkers by mass spectrometry (Specification, page 8, lines 23-26). Furthermore, the claim itself is recited at a high level of generality in which any assay can be used as the detection method for claim 48.
Thus, claim 48 is rejected under 35 USC 101.
Regarding claims 49-50 and 54, the claims further recite determining protein biomarkers which does not integrate the judicial exceptions into a practical application because they do not amount to more than the judicial exceptions themselves, nor do they amount to significantly more.
Regarding claim 51, the claim teaches the method to use to detect proteins which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more.
Regarding claim 57, the claim provides a list of biomarker that can be measured which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more.
Claim Rejections - 35 USC § 102
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 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.
Claims 48-49 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fens et al. (J Thromb Haemost 2010; 8: 2831–3).
Regarding claim 48, Fens teaches a method for exhaled breath molecular fingerprinting by eNose diagnostic tool that could differentiate between pulmonary embolism (PE) and absence of PE in patients with suspected acute PE (Page 2831, right column, third paragraph).
Fens teaches that by means of electronic noses (eNoses), the sampling of exhaled breath and its volatile organic compounds (VOCs) has become readily available, owing to their ability to discriminate biomarker profiles or breathprints with composite nanosensor arrays (breathomics) (Page 2831, left column, last paragraph).
Fens teaches collecting an exhaled breath sample by using eNoses (Page 2831, left column, second paragraph; page 2831, right column, third paragraph).
Fens teaches that exhaled breath molecular profiling with a portable eNose can adequately identify or exclude PE in patients without relevant comorbidity in a non-invasive way (Page 2832, right column, third paragraph).
Regarding claim 49, Ferns teaches discriminating biomarker profiles or breathprints with composite nanosensor arrays (breathomics) (Page 2831, left column, last paragraph).
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 (PHOSITA) to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 50-51 and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Fens et al. (J Thromb Haemost 2010; 8: 2831–3) as applied to claims 48-49 above, and further in view of Beck et al. (Clinical Chemistry 62:1, 84-91 (2016)).
Regarding claims 50-51 and 54, Ferns teaches all of the limitations of the claims but fails to teach the following limitations.
Regarding claim 50, Ferns does not teach that the level of one or more biomarkers is determined by methods of protein detection.
Regarding claim 51, Ferns does not teach that the method of protein detection is mass spectrometry.
Regarding claim 54, Ferns does not teach that the one or more biomarkers are proteins.
Regarding claim 50, Beck teaches that one or more biomarkers is determined by method of protein detection (Page 87, left column, last paragraph, “Recently, detection of 167 proteins has been reported in pooled EBC samples collected from healthy nonsmoking individuals”; page 89, first paragraph, “Targeted MS offers reproducible protein quantification, an alternative to antibody-based
assays, with detection limits similar to those for the existing immunoassays”).
Regarding claim 51, Beck teaches that the method of protein detection is mass spectrometry (Page 84, right column, third paragraph; page 89, first paragraph).
Regarding claim 54, Beck teaches that one or more biomarkers are proteins such as isoprostane-8 (Page 87, right column, third paragraph, “Isoprostane-8 has repeatedly been subject to study in EBC as a marker of oxidative stress. Recent applications of isoprostane-8 as a biomarker of oxidative stress comprise demonstration of its response to air pollution”).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine the protein detection method of Beck with the diagnostic tool of Fens to develop a method that can cover volatile and nonvolatile biomarkers for diagnosing pulmonary embolism because Beck showed that nonvolatile compounds can be sampled easily and selectively (Page 84, summary) and noted the ability to use nonvolatile compounds from exhaled breath as biomarkers for diagnosing a disease (Page 84, summary). Fens further noted the ability to discriminate biomarker profiles or “ breathprints” by sampling exhaled breath with volatile organic compounds to aid in diagnosing a disease such as pulmonary embolism (Page 2831, left column, second paragraph; page 2831, right column, third paragraph). A skilled artisan would have had a reasonable expectation of success in combining the methods of Beck and Fens because the methods are based on detecting different biomarkers from the exhaled breath.
A skilled artisan would have been motivated to detect protein biomarkers from exhaled breath with mass spectrometry as taught by Beck and to combine with the method of Fens to produce a specific and sensitive method that can be used for diagnosing a patient of having or being at risk of developing pulmonary embolism.
Claim 57 is rejected under 35 U.S.C. 103 as being unpatentable over Fens et al. (J Thromb Haemost 2010; 8: 2831–3) as applied to claim 48 above, and further in view of Kline et al. (WO 2005/085870 A1).
Regarding claim 57, Fens teaches all of the limitations of claim 57 but fails to teach the following limitations.
Regarding claim 57, Ferns does not teach that the one or more biomarkers are one or more proteins selected from the group consisting of: Serum albumin (ALB), Hemoglobin subunit beta (HBB), Hemoglobin subunit alpha 1 (HBA1), Hemoglobin subunit alpha 2 (HBA2), Heme oxygenase (HMOX), Hemopexin (HPX), Haptoglobin (HP), Serotransferrin (TF), Alpha-1-antitrypsin (SERPINA1), Complement C3 (C3), Fibronectin (FN1), lactotransferrin (LTF), Serpin C1 (SERPINC1), plasminogen (PLG), alpha 2 macroglobulin (A2M), fibrinogen alpha (FGA), fibrinogen beta (FGB), fibrinogen gamma (FGG), Plasma Kallikrein B (KLKB), serpins superfamily, Immunoglobulin superfamily, orosomucoid 1 (ORM1) and orosomucoid 2 (ORM2).
Regarding claim 57, Kline teaches using haptoglobin or free hemoglobin as a biomarker for pulmonary hypertension from exhaled breath condensate and show that the experimental model that they proposed is related to pulmonary embolism (Abstract; page 7, [0030]; page 9, [0036]).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine the biomarkers of pulmonary hypertension of Kline with the diagnostic tool of Fens to develop a method that can cover biomarkers that are involved in pulmonary embolism because Kline noted that their experimental model has clinical relevance for humans because it is seen as in humans with large pulmonary embolism (Page 7, [0030]) and further noted that as the severity of pulmonary embolism increases, the occurrence and severity of pulmonary hypertension also increases along with the release of vasoconstrictive agents (Page 8, [0031]). A skilled artisan would have had a reasonable expectation of success in combining the methods of Kline and Fens because the methods are based on detecting different biomarkers from the exhaled breath.
A skilled artisan would have been motivated to detect protein biomarkers from exhaled breath as taught by Kline and to combine with the method of Fens to produce a specific and sensitive method that can be used for diagnosing a patient of having or being at risk of developing pulmonary embolism.
Conclusion
No claims are allowed.
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/OMAR RAMADAN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678