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 without traverse of Group I and species of 3-ethyl-hexane in the reply filed on July 6, 2026 is acknowledged.
Because of the enablement issue of the elected species, the search and examination was expanded to another species, 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne. 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne reads on claims 1, 2, 9, and 26.
Drawings
The drawings are objected to because Figure 1 contains the individual ROC curves for Cycles 1 through 5 which overlap significantly. Because the lines share similar thin stroke weights and solid/semi-solid line styles, it is impossible to differentiate Cycles 1 through 5 from one another. The lines used to depict individual curves are faint and blurry, making them difficult to discern. Additionally, Tables contain dark background shading (gray scale/fill). The shading reduces contrast, obscures text/numbers, and degrades photo reproduction quality.
Appropriate correction is required.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: The specification does not include section headings such as BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S).
The following guidelines illustrate the preferred layout for the specification of a utility application. These guidelines are suggested for the applicant’s use.
Arrangement of the Specification
As provided in 37 CFR 1.77(b), the specification of a utility application should include the following sections in order. Each of the lettered items should appear in upper case, without underlining or bold type, as a section heading. If no text follows the section heading, the phrase “Not Applicable” should follow the section heading:
(a) TITLE OF THE INVENTION.
(b) CROSS-REFERENCE TO RELATED APPLICATIONS.
(c) STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT.
(d) THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT.
(e) INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A READ-ONLY OPTICAL DISC, AS A TEXT FILE OR AN XML FILE VIA THE PATENT ELECTRONIC SYSTEM.
(f) STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINT INVENTOR.
(g) BACKGROUND OF THE INVENTION.
(1) Field of the Invention.
(2) Description of Related Art including information disclosed under 37 CFR 1.97 and 1.98.
(h) BRIEF SUMMARY OF THE INVENTION.
(i) BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S).
(j) DETAILED DESCRIPTION OF THE INVENTION.
(k) CLAIM OR CLAIMS (commencing on a separate sheet).
(l) ABSTRACT OF THE DISCLOSURE (commencing on a separate sheet).
(m) SEQUENCE LISTING. (See MPEP § 2422.03 and 37 CFR 1.821 - 1.825).
Appropriate correction is required.
Claim Rejections - 35 USC § 112 Written Description
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, 9, and 26 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.
Claim 1 recites “a therapeutic agent capable of treating colorectal cancer, or a pre- disposition thereto.” The specification does not sufficiently describe the genus of “a therapeutic agent” that is claimed. The claim functionally define “a therapeutic agent” as “capable of treating colorectal cancer, or a pre- disposition thereto.” A therapeutic agent can encompass a large number of structurally unrelated compound. Similarly, the term “pre-disposition” can encompass a vast and undefined range of factors, including genetic mutations, family history, and lifestyle factors. The specification does not sufficiently describe the genus of “a pre- disposition thereto” that is claimed. A generic claim must be supported by a disclosure that shows possession of the entire claimed genus. Written description support for a chemical genus requires a representative number of species falling within the scope of the genus. Satisfactory disclosure of a representative number depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. See MPEP § 2163. Because the present disclosure fails to disclose a representative number of species or common features across the broad genus of therapeutic agents and pre-disposition, written description requirement is not satisfied to demonstrate possession of the full scope of the claimed genus. Accordingly, the claim 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, at the time the application was filed, had possession of the claimed invention.
The dependent claims fall therewith.
Amendment is required.
Claim 2 is 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.
Claim 2 recites “a therapeutic agent or a specialized diet capable of treating colorectal cancer.” The specification does not sufficiently describe the genus of “a therapeutic agent or a specialized diet” that is claimed. The claim functionally define “a therapeutic agent or a specialized diet” as “capable of treating colorectal cancer.” A therapeutic agent or a specialized diet can encompass a large number of structurally unrelated compound or any eating plan that alters a standard food choices, respectively. A generic claim must be supported by a disclosure that shows possession of the entire claimed genus. Written description support for a chemical genus requires a representative number of species falling within the scope of the genus. Satisfactory disclosure of a representative number depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. See MPEP § 2163. Because the present disclosure fails to disclose a representative number of species or common features across the broad class of a therapeutic agents or a specialized diet, written description requirement is not satisfied to demonstrate possession of the full scope of the claimed genus. Accordingly, the claim 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, at the time the application was filed, had possession of the claimed invention.
Clarification and/or amendment is required.
Claim Rejections - 35 USC § 112 Scope of Enablement
Claims 1, 9, and 26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a breath sample, certain signature compounds in a breath sample, and for treating a colorectal cancer (CRC), does not reasonably provide enablement for other bodily samples, certain signature compounds in a breath sample, and for treating a pre-disposition thereto. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue. Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
See MPEP § 2164.01(a).
The breadth of the claims
Claim 1 broadly recites analyzing “a signature compound” in “a bodily sample” for treating a subject suffering from CRC or a pre-disposition thereto. The term “bodily sample” is broad and includes breath, blood, urine, feces, saliva, and other biological fluids as disclosed in the specification (PGPub of instant application, ¶ 107). However, the claim is not limited to the specific matrix (breath) tested in the specification.
The claim also recites broad chemical genera, such as C3-20 cycloalkane and alcohol of formula (I) in group (i), C1-20 alkane and alcohol of formula (III) in group (ii), and further extend each class by adding “an analogue or derivative thereof.” The claims are not limited to the specific signature compounds tested in the specification.
The claim encompass treating “a subject suffering from colorectal cancer or a pre-disposition thereto.” The term “pre-disposition” encompasses a vast and undefined range of factors, including genetic mutations, family history, and lifestyle factors. Neither claims nor specification defines what quantitative biomarker threshold, specific risk factor, or concrete clinical intervention constitutes identifying or treating a pre-disposition, rendering the scope of the claim functionally unlimited regarding pre-symptomatic subjects.
The nature of the invention
The invention relates to diagnosis and treatment methods based on metabolic biomarker concentrations in bodily samples from a subject suffering form CRC or pre-disposition thereto.
The state of the prior art
Kim et al, (Journal of chromatographic science, 2019; cited on PTO-892) teaches that 3-ethyl-hexane concentration increases in the blood of CRC patients (page 389, column 2, ¶ 1). This directly contradicts the limitation of claim 1, which requires a decrease in the concentration of 3-ethyl-hexane to indicated CRC when applied to blood samples (another bodily sample). In light of conflicting prior art teachings regarding biomarker behavior across different biological matrices, the specification fails to provide sufficient disclosure to resolve these contradictions or enable the full scope of bodily samples. Kim teaches that there have been few overlaps in candidate CRC specific VOCs confirmed in multiple studies and the reproducibility of specific compounds or combinations has been poor between studies (page 393, column 1, ¶ 3). Kim teaches that various bodily fluids have been used to identify cancer specific VOCs, including breath, blood, feces, and urine (page 393, column 1, ¶ 3). Kim teaches that there is a matrix effect on the stability of VOCs, for example, breath is more liable to the degradation, while liquid masses are less liable (page 394, column 1, ¶ 1). Therefore, it would be expected that the concentration of signature compound can increase or decrease in CRC patients depending on the bodily samples analyzed.
Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892) teaches 2,2-dimethyldecane concentration increases in the breath of CRC patients (abstract). This directly contradicts the limitation of claim 1, which requires a decrease in the concentration of C1-20 alkane to indicated CRC. The prior art provides no predictable structure-activity relationship or chemical framework to determine which functional analogues of derivatives would retain the diagnostic utility of the primary signature compounds. A POSITA would recognize that chemical modifications converting a target compounds into an analogue or derivative fundamentally alter its physical and chemical properties such as volatility, solubility, metabolic stability, and matrix interaction. Because the specification fails to provide structural boundary rules or selection criteria, it fails to enable the full scope of signature compounds.
The prior art contains no established biological framework establishing that signature compounds in bodily samples shift predictably during a healthy, pre-lesion stage to signal a pre-disposition. Without prior art knowledge or mechanisms connecting biomarker shifts to non-symptomatic risk states, a POSITA cannot reply on external knowledge to bridge the gaps in the specification.
The level of one of ordinary skill
The level of one of ordinary skill in the art is high. A POSITA is capable of measuring signature compound levels in bodily samples. However, even an expert possesses no inherent predictive tools or theoretical model to determine a priori whether an untested biomarker will increase or decrease in an untested bodily sample without empirical clinical testing. The level of skill in the art cannot substitute for the specification’s insufficient disclosure in predicting biomarker behavior across non-disclosed matrices and chemical classes.
The level of skill in the art is insufficient to deduce which biomarkers correlate with a pre-disposition to CRC. A POSITA cannot infer how early-stage cellular changes translate into detectable signature compounds alterations prior to tumor formation across unstudied biological fluids.
The level of predictability in the art
Biomarker diagnostics and metabolic profiles across different biological matrices fall under an unpredictable art. One cannot reasonably predict or extrapolate that a biomarker showing a decrease in breath will exhibit the same directional change in blood, urine, or other bodily samples, nor can a biomarker be predictably assumed to function as an analogue of another biomarker. Kim teaches that the concentration of a biomarker (3-ethyl-hexane) can change in different directions than those required by the claims. Analysis in one sample type is not a reliable predictor for the entire genus. Because the art is highly unpredictable, the specification’s insufficient disclosure prevent a POSITA from practicing the claimed invention across the full breadth of the claims without extensive empirical validation.
Predicting metabolic variations prior to actual disease manifestation is unpredictable because the human body changes constantly. Small shifts in diet, stress, sleep, and activity mask early warning signs. Standard tests only show a single moment in time, making it hard to see a slow drift toward illness. Cancer develops from a complex mix of pre-disposition inherited genetic traits, spontaneous cell changes, and outside environmental exposures that do not share a single metabolic pathway (Perera, Science 1997; cited on PTO-892; abstract; page 1069, Fig. 1; page 1072, Table 1). It is highly unpredictable whether a single biomarker or compound class can reliably identify such heterogeneous pre-cancerous states.
The amount of direction provided by the inventor
The specification only provides technical guidance for measuring a limited number of signature compounds in breath samples, and contains no teaching, guidance, or predictive framework regarding how signature compounds behave in other bodily samples such as blood.
The specification discloses that examples of suitable analogues or derivatives of chemical groups which may be assayed include alcohols, ketones, aromatics, organic acids and gases (such as CO, CO2, NO, NO2, H2S, SO2, and CH4) (PGPub of instant application, ¶ 62). There are conflicting and overlapping species which are supposed to show increase or decrease concentration in a CRC patient. For example, cyclic alkanes in group (i), which are supposed to show increased concentration in a CRC patient, are analogue of alkanes in group (ii), which are supposed to show decreased concentration in a CRC patient. If a cycloalkane is interpreted as an analogue of an alkane under group (ii), it creates a direct conflict with group (i). The specification fails to provide any guidance or structural rules explaining how a POSITA can distinguish which cycloalkane structures act as alkane analogues versus independent cycloalkanes. Similarly, an alcohol of formula (I) in group (i) is a structural sub-genus of an alcohol of formula (III) in group (ii). However, the specification only provides technical guidance for measuring a limited number of signature compounds in breath samples, and contains no teaching or guidance regarding how to select functional analogues or derivatives or how to resolve contradictory biomarker behavior across different matrices. The specification provides no structural boundary rules such as the difference between a cycloalkane and an alcohol of formula (I) in group (i) and an alkane derivative and an alcohol of formula (III) in group (ii).
The specification provide no technical direction or guidance for identifying or treating a pre-disposition. It fails to state what baseline parameters or percentage changes in signature compound concentration signify a pre-disposition versus active disease. Asserting therapeutic intervention for a pre-disposition based solely on biomarker correlation in active cancer patients is purely speculative and fails to provide a POSITA with sufficient guidance to practice the invention over this claimed aspect
Accordingly, the specification fails to provide adequate direction, guidance, or selection criteria necessary to enable a POSITA to practice the invention beyond breath samples, disclosed signature compounds or active cancer states.
The existence of working examples
Working examples in the specification are limited to breath samples in patients with active disease. There are no working examples for blood or any other non-breath bodily fluid. The single working matrix is insufficient to support the generic genus of “a bodily sample,” especially in light of counter-evidence in blood (Kim).
The specification provides a limited set of signature compounds as listed in Tables 4 and 6. Applicant’s limited working examples do not enable one skilled in the art to analyze various samples encompassed by the entire genus. The specification is deficient in working examples, as a single working matrix and a limited set of signature compounds are insufficient to support the generic broad claims.
The specification contains no working examples, clinical data, or biological mechanisms demonstrating that analyzing the recited signature compounds can successfully identify a pre-disposition prior to lesion/tumor formation. Furthermore, there are no working examples demonstrating that administering a generic therapeutic agent to a non-cancerous subject with a pre-disposition effectively prevents or altered disease progression.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
To practice the full scope of the claim across all bodily samples, all signature compounds, and different subject states, a POSITA would need to conduct extensive, screening-style empirical testing on every bodily sample matrix against every claimed compound class including analogues and derivatives to categorize which combinations conform to the claimed diagnostic logic and which sample types fail. To enable the pre-disposition scope, a POSITA would be required to design and conduct massive, multi-layer prospective clinical trials across large populations with diverse genetic and environmental risk factors to identify which specific biomarker patterns correlate with a pre-disposition state. This constitutes undue experimentation. Because the specification fails to enable one skilled in the art to optimize the conditions without undue experimentation, the amount of experimentation required to bridge the gap between the provided example and the entire genus of the claims is vast and undue.
Because of all the factors discussed above, claim 1 is not enable under 35 USC § 112(a). The specification fails to provide an enabling disclosure that would allow a POSITA to use the full scope of the claimed invention without undue experimentation.
The dependent claims fall therewith.
Amendment is required.
Claim 2 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a breath sample and certain signature compounds in a breath sample, does not reasonably provide enablement for other bodily samples, and certain signature compounds in a breath sample. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue. Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
See MPEP § 2164.01(a).
The breadth of the claims
Claim 2 broadly recites analyzing “a signature compound” in “a bodily sample” for determining the efficacy of treating a subject suffering from CRC with a therapeutic agent or a specialized diet. The term “bodily sample” is broad and includes breath, blood, urine, feces, saliva, and other biological fluids as disclosed in the specification (PGPub of instant application, ¶ 107). However, the claim is not limited to the specific matrix (breath) tested in the specification.
The claim also recites broad chemical genera, such as C3-20 cycloalkane and alcohol of formula (I) in group (i), C1-20 alkane and alcohol of formula (III) in group (ii), and further extend each class by adding “an analogue or derivative thereof.” The claims are not limited to the specific signature compounds tested in the specification.
The nature of the invention
The invention relates to therapeutic monitoring methods based on metabolic biomarker concentrations in bodily samples from a subject suffering from CRC.
The state of the prior art
Kim et al (Journal of chromatographic science, 2019; cited on PTO-892) teaches that 3-ethyl-hexane concentration increases in the blood of CRC patients (page 389, column 2, ¶ 1). This directly contradicts the limitation of claim 2, which requires a decrease in the concentration of 3-ethyl-hexane to indicated that the treatment is ineffective. In light of conflicting prior art teachings regarding biomarker behavior across different biological matrices, the specification fails to provide sufficient disclosure to resolve these contradictions or enable the full scope of bodily samples. Kim teaches that there have been few overlaps in candidate CRC specific VOCs confirmed in multiple studies and the reproducibility of specific compounds or combinations has been poor between studies (page 393, column 1, ¶ 3). Kim teaches that various bodily fluids have been used to identify cancer specific VOCs, including breath, blood, feces, and urine (page 393, column 1, ¶ 3). Kim teaches that there is a matrix effect on the stability of VOCs, for example, breath is more liable to the degradation, while liquid masses are less liable (page 394, column 1, ¶ 1). Therefore, it would be expected that the concentration of signature compound can increase or decrease in CRC patients depending on the bodily samples analyzed.
Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892) teaches 2,2-dimethyldecane concentration increases in the breath of CRC patients (abstract). This directly contradicts the limitation of claim 2, which requires a decrease in the concentration of C1-20 alkane to indicated that the treatment is ineffective. The prior art provides no predictable structure-activity relationship or chemical framework to determine which functional analogues of derivatives would retain the diagnostic utility of the primary signature compounds. A POSITA would recognize that chemical modifications converting a target compounds into an analogue or derivative fundamentally alter its physical and chemical properties such as volatility, solubility, metabolic stability, and matrix interaction. Because the specification fails to provide structural boundary rules or selection criteria, it fails to enable the full scope of signature compounds.
The level of one of ordinary skill
The level of one of ordinary skill in the art is high. A POSITA is capable of measuring signature compound levels in bodily samples. However, even an expert possesses no inherent predictive tools or theoretical model to determine a priori whether an untested biomarker will increase or decrease in an untested bodily sample without empirical clinical testing. The level of skill in the art cannot substitute for the specification’s insufficient disclosure in predicting biomarker behavior across non-disclosed matrices and chemical classes.
The level of predictability in the art
Biomarker diagnostics and metabolic profiles across different biological matrices fall under an unpredictable art. One cannot reasonably predict or extrapolate that a biomarker showing a decrease in breath will exhibit the same directional change in blood, urine, or other bodily samples, nor can a biomarker be predictably assumed to function as an analogue of another biomarker. Analysis in one sample type is not a reliable predictor for the entire genus. The specification does not provide sufficient detail to overcome this inherent unpredictability. Because the art is highly unpredictable, the specification’s insufficient disclosure prevent a POSITA from practicing the claimed invention across the full breadth of the claims without extensive empirical validation.
The amount of direction provided by the inventor
The specification only provides technical guidance for measuring a limited number of signature compounds in breath samples, and contains no teaching, guidance, or predictive framework regarding how signature compounds behave in other bodily samples such as blood.
The specification discloses that examples of suitable analogues or derivatives of chemical groups which may be assayed include alcohols, ketones, aromatics, organic acids and gases (such as CO, CO2, NO, NO2, H2S, SO2, and CH4) (PGPub of instant application, ¶ 62). There are conflicting and overlapping species which are supposed to show increase or decrease concentration in a CRC patient. For example, cyclic alkanes in group (i), which are supposed to show increased concentration in a CRC patient, are analogue of alkanes in group (ii), which are supposed to show decreased concentration in a CRC patient. If a cycloalkane is interpreted as an analogue of an alkane under group (ii), it creates a direct conflict with group (i). The specification fails to provide any guidance or structural rules explaining how a POSITA can distinguish which cycloalkane structures act as alkane analogues versus independent cycloalkanes. Similarly, an alcohol of formula (I) in group (i) is a structural sub-genus of an alcohol of formula (III) in group (ii). However, the specification only provides technical guidance for measuring a limited number of signature compounds in breath samples, and contains no teaching or guidance regarding how to select functional analogues or derivatives or how to resolve contradictory biomarker behavior across different matrices. The specification provides no structural boundary rules such as the difference between a cycloalkane and an alcohol of formula (I) in group (i) and an alkane derivative and an alcohol of formula (III) in group (ii).
Accordingly, the specification fails to provide adequate direction, guidance, or selection criteria necessary to enable a POSITA to practice the invention beyond breath samples or disclosed signature compounds.
The existence of working examples
Working examples in the specification are limited to breath samples in patients with active disease. There are no working examples for blood or any other non-breath bodily fluid. The single working matrix is insufficient to support the generic genus of “a bodily sample,” especially in light of counter-evidence in blood (Kim).
The specification provides a limited set of signature compounds. Applicant’s limited working examples do not enable one skilled in the art to analyze various samples encompassed by the entire genus. The specification is deficient in working examples, as a single working matrix and a limited set of signature compounds are insufficient to support the generic broad claims.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
To practice the full scope of the claim across all bodily samples and all signature compounds, a POSITA would need to conduct extensive, screening-style empirical testing on every bodily sample matrix against every claimed compound class and analogues or derivatives to monitor and determine the efficacy of a therapeutic agent or a specialized diet. This constitutes undue experimentation. Because the specification fails to enable one skilled in the art to optimize the conditions without undue experimentation, the amount of experimentation required to bridge the gap between the provided example and the entire genus of the claims is vast and undue.
Because of all the factors discussed above, claim 2 is not fully enable under 35 USC § 112(a). The specification fails to provide an enabling disclosure that would allow a POSIAT to use the full scope of the claimed invention without undue experimentation.
Claim Rejections - 35 USC § 112 Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 2, 9, and 26 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 2 define a diagnostic threshold based on either (i) an increase in the concentration of an alcohol of formula (I), or (ii) a decrease in the concentration of an alcohol of formula (III). However, formula (I) represents a structural sub-genus of formula (III) when L2 is absent. For instance, ethanol falls under both formulas (I) and (III). Consequently, the same biomarker such as ethanol yields contradictory diagnostic outcomes under the claim language. Due to this structural overlap between formulas (I) and (III), one skilled in the art cannot determine the true scope or metes and bounds of the diagnostic criteria.
Furthermore, claims 1 and 2 broaden each chemical class by reciting “an analogue or derivative thereof.” The specification discloses that examples of suitable analogues or derivatives of chemical groups which may be assayed include alcohols, ketones, aromatics, organic acids and gases (such as CO, CO2, NO, NO2, H2S, SO2, and CH4) (PGPub of instant application, ¶ 62). This open-ended definition blurs the boundary between categories (i) and (ii). For instance, cyclic alkanes are structural analogues of alkanes, thus a cyclic alkane could be interpreted as belonging to both category (i) and (ii) simultaneously. Due to these conflicting and overlapping definitions, claims 1 and 2 fail to render the claimed subject matter sufficiently clear.
The dependent claims fall therewith.
Clarification and/or amendment is required.
Claims 1 and 2 recites the limitation “the concentration of a signature compound.” The claim lacks an antecedent basis for this limitation. It is suggested that claims 1 and 2 be amended to “a concentration of a signature compound” to obviate this rejection.
Clarification and/or amendment is required.
Claims 9 and 26 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 9 and 26 recite "preferably" and this renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention.
Clarification and/or amendment is required.
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 1, 9, and 26 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and an abstract idea without significantly more. Claim 1 recites treating a subject by comparing the biological correlation between the altered concentration of signature compounds in a bodily sample and the presence of colorectal/pre-disposition cancer, which constitutes a naturally occurring principle (a law of nature), as well as comparing concentration values to reach a diagnostic conclusion, which constitutes a mental process (an abstract idea). This judicial exception is not integrated into a practical application because the additional administration step are set forth at a high level of generality and merely instruct the practitioner to apply the exception without imposing any meaningful limitation on the claim scope. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claimed invention constitutes simple combining conventional diagnostic monitoring steps with generic treatment instructions, which relies solely on well-understood, routine, and conventional techniques in the art.
Claim interpretation: Under the broadest reasonable interpretation in light of the specification, claims 1 recites the analyzing and comparing steps (a)-(c) that are broadly interpreted to encompass both mental calculations or evaluations and conventional laboratory assay techniques for measuring biomarker concentrations in a biological sample. Furthermore, step (d), which recites “administering a therapeutic agent capable of treating CRC or a pre-disposition thereto,” is broadly interpreted to cover administering any generic, unspecified pharmaceutical drug, biologic, or standard-of-care medical compound known in the art for CRC treatment, without limitation to any specific active ingredient, dosage regimen, or therapeutic protocol.
Step 1: Claims 1 recites a series of acts/steps. Thus, the claims are to a process, which is one of the statutory categories of invention.
Step 2A Prong 1: Claim 1 recites the biological correlation between the altered concentration (increase or decrease) of specific signature compounds in a bodily sample and the presence of colorectal cancer/pre-disposition to cancer. These correlations exist in nature independently of human invention and represent underlying scientific truths regarding human metabolism and pathology. Comparing the measured concentration values against a reference standard to reach a diagnostic conclusion can be performed entirely within the human mind. Accordingly, the claims are directed to a judicial exception (a law of nature and an abstract idea).
Step 2A, Prong 2: Claim 1 as a whole fails to integrate the recited judicial exception into a practical application because the additional treatment-related elements are set forth at a high level of generality and merely instruct the practitioner to apply the exception. See MPEP § 2106.05(f). Step (c) recites “administering a therapeutic agent.” This limitation fails to specify any particular therapeutic agent, dosage, or specific clinical regimen. It broadly encompasses any generic treatment for CRC. Merely adding a generic instruction to administer a non-specific treatment to a patient identified via a natural law does not meaningfully limit the claim or transform the exception into a practical application.
Step 2B: Claim 1 fails to recite any additional elements that amount to significantly more than judicial exception. Sample collection and biomarker analysis (steps (a) and (b)) rely on well-understood, routine, and conventional techniques in the art. The generic administration of treatment (step (c)) is a conventional medical practices that add nothing significantly more to the claims. Simply combining conventional diagnostic monitoring steps with generic treatment instructions does not add significantly more than the judicial exception.
Regarding claims 9 and 26, these dependent claims recite further limitations of the signature compounds, rather than specifying administration methods or adding practical applications.
Therefore, the claims 1, 9, and 26 are not patent-eligible under 35 U.S.C. 101 because they are directed to a judicial exception and do not recite additional elements sufficient to amount to significantly more than the exception.
Claim 2 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and an abstract idea without significantly more. Claim 2 recites determining the efficacy of treatment by comparing the biological correlation between the altered concentration of signature compounds in a bodily sample and the effectiveness of the treatment, which constitutes a naturally occurring principle (a law of nature), as well as comparing concentration values, which constitutes a mental process (an abstract idea). This judicial exception is not integrated into a practical application because the additional administration and continued treatment steps are set forth at a high level of generality and merely instruct the practitioner to apply the exception without imposing any meaningful limitation on the claim scope. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claimed invention constitutes simple combining conventional diagnostic monitoring steps with generic treatment instructions, which relies solely on well-understood, routine, and conventional techniques in the art.
Claim interpretation: Under the broadest reasonable interpretation in light of the specification, step (a) reciting administering a treatment comprising a therapeutic agent or a specialized diet is broadly interpreted to encompass any routine medical treatment, generic pharmaceutical compound, or standard dietary modification aimed at treating CRC. The analyzing and comparing steps (b)-(c) are interpreted to cover temporal biomarker comparisons conducted via basic mental comparison or routine analytical methods. Finally, step (d), which recites “continuing with the treatment,” is broadly construed as merely maintaining an unchanged, pre-existing treatment or dietary regimen without requiring any affirmative therapeutic intervention, dosage adjustment, or specific treatment modification tied to the measured concentration levels.
Step 1: Claim 2 recites a series of acts/steps. Thus, the claims are to a process, which is one of the statutory categories of invention.
Step 2A Prong 1: Claim 2 recites the biological correlation between temporal changes in the concentration of these signature compounds and the clinical efficacy of a therapeutic agent or specialized diet. These correlations exist in nature independently of human invention and represent underlying scientific truths regarding human metabolism and pathology. Comparing the measured concentration values against a reference standard to reach a diagnostic conclusion can be performed entirely within the human mind. Accordingly, the claims are directed to a judicial exception (a law of nature and an abstract idea).
Step 2A, Prong 2: Claim 2 as a whole fails to integrate the recited judicial exception into a practical application because the additional treatment-related elements are set forth at a high level of generality and merely instruct the practitioner to apply the exception. See MPEP 2106.05(f). Step (a) reciting generic administration and step (d) reciting “continuing with treatment” fail to integrate the exception because these represents a generic, routine clinical instruction that fails to impose any meaningful limit on the abstract diagnosis and underlying natural law. Accordingly, claim 2 do not recite additional elements that integrate the judicial exception into a practical application.
Step 2B: Claim 2 fails to recite any additional elements that amount to significantly more than judicial exception. Sample collection and biomarker analysis (steps (b) and (c)) rely on well-understood, routine, and conventional techniques in the art. The generic administration of treatment (step (a)) and the instruction to continue effective treatment (step (d)) are conventional medical practices that add nothing significantly more to the claims. Simply combining conventional diagnostic monitoring steps with generic treatment instructions does not add significantly more than the judicial exception.
Therefore, the claim 2 is not patent-eligible under 35 USC § 101 because they are directed to a judicial exception and do not recite additional elements sufficient to amount to significantly more than the exception.
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.
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, 9, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892) in view of Chee et al. (Gastroenterology Clinics of North America, 2010; cited on PTO-892).
Wang discloses a method for noninvasive detection of CRC by analysis of exhaled breath (title). Wang discloses that the method can comprise collecting a breath sample from CRC patients and healthy controls; analyzing the exhaled volatile organic compounds (VOC)s using solid-phase microextraction–gas chromatography/mass spectrometry (SPME-GC/MS); and comparing the concentration of the VOCs using statistical methods of principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) (abstract). Wang discloses that the VOCs in the exhalations show significantly different profiles between CRC patients and healthy controls, and that the concentration of 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne decreases in the exhalations from CRC patients, compared to the control (abstract). Wang discloses analyses of breath VOCs can represent an effective and convenient screening method for CRC as breath biomarkers of CRC (abstract).
Wang does not disclose the step of administering a therapeutic agent.
Chee discloses therapeutic agents for CRC (title). Chee discloses that cetuximab or panitumumab can be administered to patients with a diagnosis of metastatic CRC (page 5, ¶ 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Wang by adding a step of administering a therapeutic agent such as cetuximab after diagnosing CRC. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Chee teaches a therapeutic agent such as cetuximab can be used for treating CRC after diagnosis. The primary target and practical objective of diagnosing a medical condition such as CRC is to guide subsequent therapeutic intervention. Once a patient is identified as having CRC using the diagnostic method taught by Wang, a person of ordinary skill in the art would have been naturally motivated to administer an effective therapeutic agent to treat the diagnosed disease. Providing medical treatment upon a positive diagnosis represents a predictable application of known medical procedures with expected results. Especially, claim 1 recites the administration step at a high level of generality. Therefore, combining Wang’s diagnostic detection with the routine administration of a known CRC therapeutic agent would have been a matter of conventional medical practice and obvious to a person of ordinary skill in the art.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Wang and Chee as applied to claims 1, 9, and 26 above, and further in view of de Boer et al. (Clinical Gastroenterology and Hepatology, 2014; cited on PTO-892).
Wang and Chee are discussed above.
Neither Wang nor Chee discloses a method for determining the efficacy of treating a subject.
De Boer discloses the potential of VOCs as fully noninvasive markers for the detection of neoplastic lesions of the colon (abstract). De Boer discloses that VOCs can be used to monitor therapeutic response in the treatment of CRC (abstract; page 1087, column 2, ¶ 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Wang and Chee by replacing an individual who does not suffer from cancer with the subject at an earlier time point as a reference in order to monitor the response to therapy. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because de Boer teaches signature compounds (VOCs) analysis as a noninvasive method to monitor response to therapy for CRC. Further, a person of ordinary skill in the art would have been motivated to compare the concentration of signature compound such as 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne before and after treatment, rather than between a CRC patient and a non-CRC patient in order to monitor individual-specific response to the treatment efficiency and determine the continuation of the effective treatment depending on the changes in concentrations of the signature compound. It is well settled in the art that tracking drug-responsive biomarkers pre- and post-treatment provides immediate empirical feedback on therapeutic efficacy. It would be expected that the concentration of the signature compound can increase or decrease depending on the compound in response to the treatment. It would have been obvious to a person of ordinary skill in the art to continue the treatment as the change in the concentration of the signature compound suggests the efficacy of the treatment.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 9, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,618,844 in view of Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892).
Claim 1 of the ‘844 recites a method of treating an individual suffering from oesophagogastric cancer, the method comprising detecting the level of a signature compound in a bodily sample from a test subject; treating the test subject with a therapeutic agent and/or radiotherapy, if there is an increase or decrease in the level of the signature compound in the bodily sample from the test subject, compared to a reference, wherein the reference level is the level of the signature compound in an individual, or the average level for a group of individuals, wherein the individual or group of individuals do not suffer from oesophagogastric cancer, wherein the treatment reduces or delays progression of cancer and/or treats cancer. Claim 1 of the ‘844 recites that the level of the signature compound can increase and decrease depending on the signature compound and that for example the concentration of 1-tetradecanol can increase. Claim 1 of the ‘844 recites that the bodily sample can be a breath sample.
Claims of the ‘844 do not recite CRC and a different concentration of a signature compound in a CRC patient compared to a reference.
As discussed above, Wang discloses a method of noninvasive detection of CRC by analysis of exhaled breath (title). Wang discloses that the VOCs in the exhalations shows significantly different profiles between CRC patients and healthy controls, and that the concentration of 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne decreases in the exhalations from CRC patients, compared to the control (abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘844 for treating a subject suffering from CRC utilizing a signature compound such as 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne, as taught by Wang. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Wang teaches such method can be used for treating CRC. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘844 for treating other cancers in order to expand the applications of the method.
Claim 2 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,618,844 in view of Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892) and de Boer et al. (Clinical Gastroenterology and Hepatology, 2014; cited on PTO-892).
Claims of the ‘844 are discussed above.
Wang is discussed above.
Claims of the ‘844 do not recite a method for determining the efficacy of treating a subject suffering from CRC.
As discussed above, de Boer discloses the potential of VOCs as fully noninvasive markers for the detection of neoplastic lesions of the colon (abstract). De Boer discloses that VOCs can be used to monitor therapeutic response in the treatment of CRC (abstract; page 1087, column 2, ¶ 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘844 for determining the efficacy of treating a subject suffering from CRC with a therapeutic agent as taught by Wang and de Boer. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Wang and de Boer teach such method can be used for determining the efficacy of treating a subject suffering from CRC. It is well established in clinical practice that tracking pre- and post-treatment biomarker levels provides direct feedback on therapeutic efficacy to guide ongoing treatment decisions. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘844 for determining the efficacy of treating a subject suffering from CRC in order to expand the applications of the method.
Claims 1, 9, and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of copending Application No. 16/646,339 in view of Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892).
Claim 1 of the ‘339 recites a method for treating a subject suffering from localised pancreatic cancer, the method comprising analyzing the concentration of at least one signature compound in the breath sample from the test subject; comparing the concentration of the signature compounds with a reference for the concentration of the signature compounds in an individual who does not suffer from pancreatic cancer, wherein a decrease in the concentration of the signature compound selected from a C1-C20 alkane; and (d) administering a therapeutic agent capable of treating pancreatic cancer to the test subject whose concentration of the signature compounds in the breath sample indicates that the subject is suffering from pancreatic cancer.
Claims of the ‘339 do not recite CRC and different concentration of a signature compound in CRC patient compared to reference.
As discussed above, Wang discloses a method of noninvasive detection of CRC by analysis of exhaled breath (title). Wang discloses that the VOCs in the exhalations shows significantly differences between CRC patients and healthy controls, and that the concentration of 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne decreases in the exhalations from CRC patients, compared to the control (abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘339 for treating a subject suffering from CRC utilizing a signature compound such as 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne, as taught by Wang. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Wang teaches such method can be used for treating CRC. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘339 for treating other cancers in order to expand the applications of the method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of copending Application No. 16/646,339 in view of Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892).
Claim 2 of the ‘339 recites a method for determining the efficacy of treating a subject suffering from localised pancreatic cancer with a therapeutic agent, the method comprising administering a treatment to a test subject suffering from localised pancreatic cancer, the treatment comprising a therapeutic agent capable of treating pancreatic cancer; analyzing the concentration of signature compound in the breath sample from the test subject; comparing the concentration of the signature compound with a reference for the concentration of the signature compounds in an individual who does not suffer from pancreatic cancer, wherein an increase in the concentration of the signature compound selected from a C1-C20 alkane; continuing with the treatment to the test subject whose concentration of the signature compounds indicates the treatment with the therapeutic agent is effective.
Claims of the ‘339 do not recite CRC and different concentration of a signature compound in CRC patient compared to reference.
Wang is discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘339 for treating a subject suffering from CRC utilizing a signature compound such as 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne, as taught by Wang. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Wang teaches such method can be used for treating CRC. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘339 for treating other cancers in order to expand the applications of the method. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘339 for treating other cancers in order to expand the applications of the method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 9, and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 28 of copending Application No. 16/766,956 in view of Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892).
Claim 1 of the ‘956 recites a method for treating a subject who has oesophago-gastric cancer, the method comprising detecting, in a bodily sample from the subject, the concentration of the signature compound; comparing the concentration of the signature compound in the bodily sample from the subject with a reference for the concentration of the signature compound in an individual who does not have the cancer, wherein an increase in the concentration of the signature compound in the bodily sample from the subject compared to the reference indicates that the subject has the cancer, wherein the signature compound can be phenol; and administering a therapeutic agent capable of treating the oesophago-gastric cancer to the subject whose concentration of the signature compound in the bodily sample indicates that the subject has the cancer, thereby treating the cancer in the subject. It would be expected that the concentration of the signature compound can increase or decrease depending on the compound. Claim 28 of the ‘956 recites that the bodily sample can be a breath sample.
Claims of the ‘956 do not recite CRC and different concentration of a signature compound in CRC patient compared to reference.
As discussed above, Wang discloses a method of noninvasive detection of CRC by analysis of exhaled breath (title). Wang discloses that the VOCs in the exhalations shows significantly differences between CRC patients and healthy controls, and that the concentration of 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne decreases in the exhalations from CRC patients, compared to the control (abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘956 for treating a subject suffering from CRC utilizing a signature compound such as 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne, as taught by Wang. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Wang teaches such method can be used for treating CRC. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘956 for treating other cancers in order to expand the applications of the method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 28 of copending Application No. 16/766,956 in view of Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892) and de Boer et al. (Clinical Gastroenterology and Hepatology, 2014; cited on PTO-892).
Claims of the 956 are discussed above.
Wang is discussed above.
Claims of the ‘956 do not recite a method for determining the efficacy of treating a subject suffering from CRC.
As discussed above, de Boer discloses the potential of VOCs as fully noninvasive markers for the detection of neoplastic lesions of the colon (abstract). De Boer discloses that VOCs can be used to monitor therapeutic response in the treatment of CRC (abstract; page 1087, column 2, ¶ 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘956 for determining the efficacy of treating a subject suffering from CRC with a therapeutic agent as taught by Wang and de Boer. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Wang and de Boer teach such method can be used for determining the efficacy of treating a subject suffering from CRC. It is well established in clinical practice that tracking pre- and post-treatment biomarker levels provides direct feedback on therapeutic efficacy to guide ongoing treatment decisions. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘956 for determining the efficacy of treating a subject suffering from CRC in order to expand the applications of the method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 9, and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 11 of copending Application No. 17/430,639 in view of Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892).
Claim 1 of the ‘639 recites a method for treating a subject suffering from oesophagogastric cancer, the method comprising obtaining an endoluminal sample of a test subject comprising compounds; determining the concentration of the compounds; and administering a therapeutic agent to the test subject if there is an increase in the concentration of the compounds detected in the endoluminal sample from the test subject relative to a reference for the concentration of the compounds. Clam 11 of the ‘639 recites that the compound can be VOC.
Claims of the ‘639 do not recite CRC and different concentration of a signature compound in CRC patient compared to reference.
As discussed above, Wang discloses a method of noninvasive detection of CRC by analysis of exhaled breath (title). Wang discloses that the VOCs in the exhalations shows significantly differences between CRC patients and healthy controls, and that the concentration of 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne decreases in the exhalations from CRC patients, compared to the control (abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘639 for treating a subject suffering from CRC utilizing a signature compound such as 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne, as taught by Wang. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Wang teaches such method can be used for treating CRC. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘639 for treating other cancers in order to expand the applications of the method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 11 of copending Application No. 17/430,639 in view of Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892) and de Boer et al. (Clinical Gastroenterology and Hepatology, 2014; cited on PTO-892).
Claims of the ‘638 are discussed above.
Wang is discussed above.
Claims of the ‘639 do not recite a method for determining the efficacy of treating a subject suffering from CRC with a therapeutic agent or a specialized diet.
As discussed above, de Boer discloses the potential of VOCs as fully noninvasive markers for the detection of neoplastic lesions of the colon (abstract). De Boer discloses that VOCs can be used to monitor therapeutic response in the treatment of CRC (abstract; page 1087, column 2, ¶ 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘639 for determining the efficacy of treating a subject suffering from CRC with a therapeutic agent as taught by Wang and de Boer. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Wang and de Boer teach such method can be used for determining the efficacy of treating a subject suffering from CRC. It is well established in clinical practice that tracking pre- and post-treatment biomarker levels provides direct feedback on therapeutic efficacy to guide ongoing treatment decisions. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘639 for determining the efficacy of treating a subject suffering from CRC in order to expand the applications of the method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 9, and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/614,374 in view of Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892).
Claim 1 of the ‘374 recites a method for treating a subject suffering from cancer, the method comprising detecting, in a bodily sample from the test subject, the concentration of a signature compound; and administering a therapeutic agent to the test subject if there is an increase in the concentration of the signature compound detected in the bodily sample from the test subject relative to a reference for the concentration of the signature compound. Claim 19 of the ‘374 recites that the signature compound can be phenol. Claims of the ‘374 do not recite CRC and different concentration of a signature compound from a breath sample in CRC patient compared to reference.
As discussed above, Wang discloses a method of noninvasive detection of CRC by analysis of exhaled breath (title). Wang discloses that the VOCs in the exhalations shows significantly differences between CRC patients and healthy controls, and that the concentration of 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne decreases in the exhalations from CRC patients, compared to the control (abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘374 for treating a subject suffering from CRC utilizing a signature compound such as 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne, as taught by Wang. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Wang teaches such method can be used for treating CRC. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘374 for treating other cancers in order to expand the applications of the method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/614,374 in view of Wang et al. (Analytical and bioanalytical chemistry, 2014; cited on PTO-892) and de Boer et al. (Clinical Gastroenterology and Hepatology, 2014; cited on PTO-892).
Claims of the ‘374 are discussed above.
Wang is discussed above.
Claims of the ‘374 do not recite a method for determining the efficacy of treating a subject suffering from CRC with a therapeutic agent or a specialized diet.
As discussed above, de Boer discloses the potential of VOCs as fully noninvasive markers for the detection of neoplastic lesions of the colon (abstract). De Boer discloses that VOCs can be used to monitor therapeutic response in the treatment of CRC (abstract; page 1087, column 2, ¶ 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘374 for determining the efficacy of treating a subject suffering from CRC with a therapeutic agent as taught by Wang and de Boer. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Wang and de Boer teach such method can be used for determining the efficacy of treating a subject suffering from CRC. It is well established in clinical practice that tracking pre- and post-treatment biomarker levels provides direct feedback on therapeutic efficacy to guide ongoing treatment decisions. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘374 for determining the efficacy of treating a subject suffering from CRC in order to expand the applications of the method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Nissa M Westerberg/Primary Examiner, Art Unit 1618
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