DETAILED ACTION
In application filed on 02/27/2023, Claims 1-18 are pending. The claim set submitted on 10/31/2025 is considered because this is the most recent claim set with some preliminary amendments. Claims 1-12 are considered in the current office 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 without traverse of Group I in the reply filed on 10/31/2025 is acknowledged. Claims 13-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/31/2025.
Group I, Claims 1-12 are considered on the merits below.
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 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 1-3 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Dennis et al. (US20170074857A1).
Regarding Claim 1, Dennis teaches a method for determining medication adherence (See Para 0045…method for medication adherence monitoring), comprising the step of administering to a patient in need thereof a medication (See Para 0045…The API, the AEM, or both when taken or administered to a subject…a) A SMART® (Self Monitoring And Reporting Therapeutic) medication’) having a stable non-radioactive taggant (See Para 0045…AEM; See Para 0313…enable use of AEMs comprising non-ordinary (but preferably stable, i.e. non-radioactive); See Para 0313… AEMs comprising non-ordinary (but preferably stable, i.e. non-radioactive) isotopes in the AEM. Such AEMs are referred to herein as i-AEMs… stable (non-radioactive), atomic isotopes, referred to as i-EBMs, (Exhaled Breath Markers containing at least one non-ordinary, but stable (non-radioactive) isotope)) added to the medication (See Para 0045…The API, the AEM, or both when taken or administered to a subject…a) A SMART® (Self Monitoring And Reporting Therapeutic) medication is provided to a subject which enables monitoring of the subject's adherence in taking or administration of at least one Active Pharmaceutical Ingredient (API) included in the medication);
obtaining a sample from the patient (See Para 0007…obtaining a sample of the patient's gaseous exhaled breath; See Para 0031… the gas sample is provided by the subject to the apparatus);
assaying (‘measurement’) the sample (‘exhaled breath’) for a concentration of the non-radioactive taggant (‘AEMs’) in the sample (‘exhaled breath’) (See Para 0306…device measurement in the exhaled breath of AEMs (which may appear in the exhaled breath); See Para 0064… AEM concentrations of said subject or population of subjects).
Regarding Claim 2, Dennis teaches that the stable non-radioactive taggant (See Para 0045…AEM; See Para 0313…enable use of AEMs comprising non-ordinary (but preferably stable, i.e. non-radioactive); See Para 0313… AEMs comprising non-ordinary (but preferably stable, i.e. non-radioactive) isotopes in the AEM. Such AEMs are referred to herein as i-AEMs… stable (non-radioactive), atomic isotopes, referred to as i-EBMs, (Exhaled Breath Markers containing at least one non-ordinary, but stable (non-radioactive) isotope)) is added to the medication (See Para 0045…The API, the AEM, or both when taken or administered to a subject…a) A SMART® (Self Monitoring And Reporting Therapeutic) medication’) as an excipient (See Para 0045…AEM; See Para 0049… a medication comprising an API and an AEM…; See Para 0174…Where the AEMs are FDA designated Generally Recognized as Safe (GRAS) compounds, they are co-packaged or co-formulated with an active drug; Examiner submits that that an excipient is a substance formulated alongside the active ingredient of a medication).
Further, Examiner submits that Dennis et al. (US20070224128A1) teaches that numerous such compounds are available that could be used as markers (‘stable non-radioactive taggant’) and could be added as excipients during the manufacture of drugs (Para 0043) and this is evidence that it is well known to one of ordinary skill in the art that the stable non-radioactive taggant is added to the medication as an excipient.
Regarding Claim 3, Dennis teaches that the stable non-radioactive taggant (See Para 0045…AEM; See Para 0313…enable use of AEMs comprising non-ordinary (but preferably stable, i.e. non-radioactive); See Para 0313… AEMs comprising non-ordinary (but preferably stable, i.e. non-radioactive) isotopes in the AEM. Such AEMs are referred to herein as i-AEMs… stable (non-radioactive), atomic isotopes, referred to as i-EBMs, (Exhaled Breath Markers containing at least one non-ordinary, but stable (non-radioactive) isotope)) is added to the medication (See Para 0045…The API, the AEM, or both when taken or administered to a subject…a) A SMART® (Self Monitoring And Reporting Therapeutic) medication’) as a spray (See Para 1148… formulation strategy of simply spraying a few mg of cold isotopologue-based AEM(s) on the surface of a solid oral dosage form (SODF) ).
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.
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 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Dennis et al. (US20170074857A1) as applied to claim 1 above, and further in view of Kell et al. (US006136801A).
Regarding Claim 4, Dennis teaches that the method of Claim 1, wherein the stable non-radioactive taggant (See Para 0045…AEM; See Para 0313…enable use of AEMs comprising non-ordinary (but preferably stable, i.e. non-radioactive); See Para 0313… AEMs comprising non-ordinary (but preferably stable, i.e. non-radioactive) isotopes in the AEM. Such AEMs are referred to herein as i-AEMs… stable (non-radioactive), atomic isotopes, referred to as i-EBMs, (Exhaled Breath Markers containing at least one non-ordinary, but stable (non-radioactive) isotope)) is added to the medication (See Para 0045…The API, the AEM, or both when taken or administered to a subject…a) A SMART® (Self-Monitoring And Reporting Therapeutic) medication’).
While Dennis teaches AEM at a dosage level (See Para 0091… oral ingestion of 2-butanol (40 mg) in subjects; See Para 1175…after the oral administration of the AEM 2-butanol (40 and 60 mg) to humans),
Dennis does not explicitly teach that the stable non-radioactive taggant is added to the medication at a dosage level between about 0.1 mg to about 50 mg.
In the analogous art of Quantitative compliance markers and associated methods for monitoring patient compliance with medication prescriptions associated with compliance markers, Kell teaches that the stable non-radioactive taggant (referred to as compliance marker 2mg diazepam [Col. 14, lines 38-40]) is added to the medication (referred to as 15 mg methadone HCL [Col. 14, lines 38-40]) at a dosage level between about 0.1 mg to about 50 mg (See 2mg diazepam [Col. 14, lines 38-40]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Dennis to incorporate that the stable non-radioactive taggant is added to the medication at a dosage level between about 0.1 mg to about 50 mg, as taught by Kell for the benefit of using diazepam as a compliance marker for methadone drug (Kell, [Col. 14, lines 38-40]), allowing for the provision of a predictable method of monitoring patients who have been placed on potentially abusable and dangerous maintenance medications or new experimental drugs for compliance therewith (Kell, Col. 4, lines 9-12).
Regarding Claim 5, Dennis teaches that the method of Claim 4, wherein the stable non-radioactive taggant (See Para 0045…AEM; See Para 0313…enable use of AEMs comprising non-ordinary (but preferably stable, i.e. non-radioactive); See Para 0313… AEMs comprising non-ordinary (but preferably stable, i.e. non-radioactive) isotopes in the AEM. Such AEMs are referred to herein as i-AEMs… stable (non-radioactive), atomic isotopes, referred to as i-EBMs, (Exhaled Breath Markers containing at least one non-ordinary, but stable (non-radioactive) isotope)) further comprises at least one of a stable isotope of carbon, nitrogen or oxygen (See Para 0324…-EBMs—Exhaled Breath Markers (including EDIMs and EDEMs) containing at least one non-ordinary, but stable (non-radioactive) isotope of hydrogen (i.e. deuterium), carbon (e.g., C13), or the like.).
Claims 6 and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Dennis et al. (US20170074857A1) as applied to claim 1 above, and further in view of Jimenez et al. (US20100196308A1).
Regarding Claim 6, Dennis teaches that the method of Claim 1, wherein the stable non-radioactive taggant (See Para 0045…AEM; See Para 0313…enable use of AEMs comprising non-ordinary (but preferably stable, i.e. non-radioactive); See Para 0313… AEMs comprising non-ordinary (but preferably stable, i.e. non-radioactive) isotopes in the AEM. Such AEMs are referred to herein as i-AEMs… stable (non-radioactive), atomic isotopes, referred to as i-EBMs, (Exhaled Breath Markers containing at least one non-ordinary, but stable (non-radioactive) isotope)).
Dennis does not teach that the stable non-radioactive taggant is added to an endogenous molecule.
In the analogous art of the use of vitamin D compounds, such as vitamin D3, or analogs and/or metabolites thereof, to modulate bone marrow progenitors and stromal cells prior to the administration of antineoplastic agents, Jimenez teaches that the stable non-radioactive taggant (See Para 0107… Examples of isotopes suitable for inclusion in the compounds of the invention comprises isotopes of hydrogen, such as 2H and 3H, carbon, such as 13C and 14C, chlorine, such as 36Cl, fluorine, such as 18F, iodine, such as 123I and 125I, nitrogen, such as 13N and 15N, oxygen, such as 15O, 17O and 18O, phosphorus, such as 32P, and sulphur, such as 35S) is added to an endogenous molecule (See Para 0002… vitamin D compounds, such as vitamin D3 and analogs ;See Para 0107… isotopically-labeled vitamin D compounds, thereby teaching “endogenous molecule”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Dennis to incorporate that the stable non-radioactive taggant is added to an endogenous molecule, as taught by Jimenez for the benefit of preventing or reducing chemotherapy-induced myelosuppression in a subject being treated with a chemotherapeutic agent which induces myelosuppression by administering to the subject an effective amount of a vitamin D compound or …(Jimenez, Para 0009), allowing for the use of vitamin D compounds, such as vitamin D3 and analogs thereof, having calcemic and non-calcemic activity, administered in a pharmaceutically acceptable manner prior to the administration of anti-neoplastic drugs to treat solid tumors and/or leukemia (Jimenez, Para 0002).
Regarding Claim 10, the method of Claim 6 is obvious over Dennis in view of Jimenez.
Dennis does not teach that the stable non-radioactive taggant is added to a vitamin
In the analogous art of the use of vitamin D compounds, such as vitamin D3, or analogs and/or metabolites thereof, to modulate bone marrow progenitors and stromal cells prior to the administration of antineoplastic agents, Jimenez teaches that the stable non-radioactive taggant (See Para 0107… Examples of isotopes suitable for inclusion in the compounds of the invention comprises isotopes of hydrogen, such as 2H and 3H, carbon, such as 13C and 14C, chlorine, such as 36Cl, fluorine, such as 18F, iodine, such as 123I and 125I, nitrogen, such as 13N and 15N, oxygen, such as 15O, 17O and 18O, phosphorus, such as 32P, and sulphur, such as 35S) is added to a vitamin (See Para 0107… isotopically-labeled vitamin D compounds).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Dennis to incorporate that the stable non-radioactive taggant is added to an vitamin, as taught by Jimenez for the benefit of preventing or reducing chemotherapy-induced myelosuppression in a subject being treated with a chemotherapeutic agent which induces myelosuppression by administering to the subject an effective amount of a vitamin D compound or …(Jimenez, Para 0009), allowing for the use of vitamin D compounds, such as vitamin D3 and analogs thereof, having calcemic and non-calcemic activity, administered in a pharmaceutically acceptable manner prior to the administration of anti-neoplastic drugs to treat solid tumors and/or leukemia (Jimenez, Para 0002).
Regarding Claim 11, the method of Claim 6 is obvious over Dennis in view of Jimenez.
Dennis does not teach that the endogenous molecule is selected from the group consisting of adenine, vitamin D, thyroxine, hypoxanthine, uracil, creatine, and pyridoxine.
In the analogous art of the use of vitamin D compounds, such as vitamin D3, or analogs and/or metabolites thereof, to modulate bone marrow progenitors and stromal cells prior to the administration of antineoplastic agents, Jimenez teaches that the endogenous molecule (See Para 0002… vitamin D compounds, such as vitamin D3 and analogs ;See Para 0107… isotopically-labeled vitamin D compounds, thereby teaching “endogenous molecule”) is selected from the group consisting of adenine, vitamin D, thyroxine, hypoxanthine, uracil, creatine, and pyridoxine (See Para 0002… vitamin D compounds, such as vitamin D3 and analogs ;See Para 0107… isotopically-labeled vitamin D compounds).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Dennis to incorporate that the endogenous molecule is selected from the group consisting of adenine, vitamin D, thyroxine, hypoxanthine, uracil, creatine, and pyridoxine, as taught by Jimenez for the benefit of preventing or reducing chemotherapy-induced myelosuppression in a subject being treated with a chemotherapeutic agent which induces myelosuppression by administering to the subject an effective amount of a vitamin D compound or …(Jimenez, Para 0009), allowing for the use of vitamin D compounds, such as vitamin D3 and analogs thereof, having calcemic and non-calcemic activity, administered in a pharmaceutically acceptable manner prior to the administration of anti-neoplastic drugs to treat solid tumors and/or leukemia (Jimenez, Para 0002).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Dennis et al. (US20170074857A1) in view of Jimenez et al. (US20100196308A1) as applied to claim 6 above, and further in view of Karger et al. (EP1637163A1).
Regarding Claim 7, the method of Claim 6 is obvious over Dennis in view of Jimenez.
The combination of Dennis and Jimenez does not teach that the stable non-radioactive taggant is added to an amino acid.
In the analogous art of a composition comprising an agent for the prevention, alleviation, treatment or diagnosis of a disease and a pharmaceutically acceptable excipient, Karger teaches that the stable non-radioactive taggant (‘at least one type of stable rare isotopes’) is added to an amino acid (See Para 0016; Claim 16… wherein at least one amino acid or salt thereof is enriched with at least one type of stable rare isotopes).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the combination of Dennis and Jimenez to incorporate that the stable non-radioactive taggant is added to an amino acid, as taught by Karger for the benefit of enriching the amino acid(s) or salt(s) with at least one type of stable rare isotopes (Karger, Para 0016) as an indicator for compliance with an administration plan for the composition (Karger, Claim 1), allowing for the provision of a composition comprising an agent for the prevention, alleviation, treatment or diagnosis of a disease and a pharmaceutically acceptable excipient, wherein said excipient is enriched with at least one type of a stable rare isotopes as a indicator of compliance with an administration plan for the composition (Karger, Para 0008).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Dennis et al. (US20170074857A1) in view of Jimenez et al. (US20100196308A1) as applied to claim 6 above, and further in view of Sturm et al. ("Absolute quantification of prion protein (90–231) using stable isotope-labeled chymotryptic peptide standards in a LC-MRM AQUA workflow." Journal of the American Society for Mass Spectrometry 23.9 (2012): 1522-1533.).
Regarding Claim 8, the method of Claim 6 is obvious over Dennis in view of Jimenez.
The combination of Dennis and Jimenez does not teach that the stable non-radioactive taggant is added to a protein.
In the analogous art of the absolute quantification of prion protein (90–231) using stable isotope-labeled chymotryptic peptide standards in a LC-MRM AQUA workflow, Sturm teaches that the stable non-radioactive taggant (referred to as Stable Isotope-Labeled Chymotryptic Peptide Standards [Figs 2-3]) is added to a protein (referred to as prion protein [See Title, Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the combination of Dennis and Jimenez to incorporate that the stable non-radioactive taggant is added to a protein, as taught by Sturm for the benefit of quantifying Prion Protein in biosamples using mass spectrometry because it offers high-throughput, direct measurement of a protein’s signature peptide with subfemtomole sensitivities (Sturm, See Title, Conclusion), allowing for the provision of an inexpensive, high-throughput, and accurate LC-MRM AQUA method for quantification of prion protein in a variety of economically and research important species (Sturm, Conclusion).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Dennis et al. (US20170074857A1) in view of Jimenez et al. (US20100196308A1) as applied to claim 6 above, and further in view of Dennis et al. (US20070224128A1, hereinafter Dennis’128).
Regarding Claim 9, the method of Claim 6 is obvious over Dennis in view of Jimenez.
The combination of Dennis and Jimenez does not teach that the stable non-radioactive taggant is added to an enzyme.
In the analogous art of novel methods for monitoring subject adherence in taking prescribed drugs by detecting markers in exhaled breath after a subject takes the prescribed drug, Dennis’128 teaches that the stable non-radioactive taggant (referred to as Molecular beacons [Para 0112]) is added to an enzyme (See Para 0112… are attached to natural or synthetic ligands (such as aptamers, enzymes, antibodies, etc.)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the combination of Dennis and Jimenez to incorporate that the stable non-radioactive taggant is added to an enzyme, as taught by Dennis’128 for the benefit of providing fluorescence signal increases in the presence of particular target sequences (Dennis’128, Para 0112), allowing for the provision of systems and methods for non-invasive monitoring of subject adherence in taking drug(s) by analyzing a subject's exhaled breath for the presence of a marker indicative of drug absorption, distribution, metabolism, and/or excretion in the subject's body (Dennis’128, Para 0039).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Dennis et al. (US20170074857A1) as applied to claim 1 above, and further in view of Rohan et al. (US20200253885A1).
Regarding Claim 12, Dennis does not teach that the medication further comprises an HIV pre- exposure prophylaxis medication.
In the analogous art of o pharmaceutical vehicles for use in delivering therapeutic compositions to patients, more particularly, the present invention relates to films for the delivery of antiviral compositions to patients, Rohan teaches that the medication further comprises an HIV pre- exposure prophylaxis medication. (See Para 0004… Microbicides may be candidates applied vaginally or rectally for protection from sexually transmitted infections, including human immunodeficiency virus (HIV) infection. Preexposure prophylaxis (PrEP) with oral Truvada® (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg)/emtricitabine reduces HIV acquisition in women who demonstrate high adherence to the daily medication.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Dennis to incorporate that the medication further comprises an HIV pre- exposure prophylaxis medication, as taught by Rohan for the benefit of demonstrating the reduction of HIV acquisition in women who demonstrate high adherence to the daily medication (Rohan, Para 0004), further disclosing the effectiveness of microbicides which may be candidates applied vaginally or rectally for protection from sexually transmitted infections, including human immunodeficiency virus (HIV) infection (Rohan, Para 0004).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Melker et al. (US20140364384A1) teaches the detection of markers in exhaled breath, wherein the detection of the presence or absence of the marker(s) in exhaled breath is used to assess various clinical data, including patient adherence in taking the medication and patient enzymatic (metabolic) competence in metabolizing the medication.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OYELEYE ALEXANDER ALABI whose telephone number is (571)272-1678. The examiner can normally be reached on M-F 7:30am-5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached on (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/OYELEYE ALEXANDER ALABI/ Examiner, Art Unit 1797