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 .
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 11 June 2025.
CLAIMS UNDER EXAMINATION
Claims 44-50, 53-58, 60 and 64-69 have been examined on their merits.
PRIORITY
Provisional Application 62/336376, filed on 13 May 2016, is acknowledged.
REJECTIONS
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 44-50, 53-58, 60 and 64-69 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
Based on the claims as a whole, claims 44-50, 53-58, 60 and 64-69 are determined to be directed to a law of nature/natural principle. The rationale for the determination is explained below.
Claims 44, 49 and 64 are directed to methods of treating asthma or chronic obstructive pulmonary disease in a human subject.
Question 1: Is the claim to a process, machine manufacture or composition of matter? Yes, the invention recited in claims 44, 49 and 64 is a process.
Question 2A Prong 1: Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)? Yes, claims 44, 49 and 64 are directed to a law of nature.
(a) The limitations in the claim that set forth the law of nature is:
The 2019 PEG explains that the abstract idea exception includes the following groupings of subject matter:
Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations;
Certain methods of organizing human activity – fundamental economic principles or practices (including hedging, insurance, mitigating risk); commercial or legal interactions (including agreements in the form of contracts; legal obligations; advertising, marketing or sales activities or behaviors; business relations); managing personal behavior or relationships or interactions between people (including social activities, teaching, and following rules or instructions); and
Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion).
Regarding claim 44: Step (a) has been amended to recite the human subject has been “identified” as having asthma or chronic obstructive pulmonary disease (COPD). The specification does not disclose a definition for the term “identify”. Therefore a patient identified as having asthma or COPD is interpreted to have been diagnosed. The specification discloses imaging of the lungs has been utilized in the diagnosis of lung diseases ([0122 PG Pub). At [0131] the specification discloses diagnosis based on an overall score quantifying mucus plugging. At [0197] the specification discloses “determining, based at least on the quantification of mucus plugging, a diagnosis for the subject, the diagnosis comprising a detection of an airway mucus occlusion in at least one lung segment of the subject”. The specification discloses data and scans are “reviewed and discussed by” a “mucus score team” ([0278]). Visual imaging of the lungs to make a diagnosis is a mental observation (a judicial exception) based on a correlation (a natural phenomenon; judicial exception) between the presence of a mucus plug and a disease state.
Step (b) recites detecting airway mucus plugs with the MCT. The specification states mucus plugs are “discerned” using the scans based on areas of opacification ([0308] of PG Pub). Said discernment can be done visually by looking at a scan performed by MCT. This is a mental process (a judicial exception).
Step (c) recites a identifying a mucus score of the human subject based on the scans.
The specification discloses a visual scoring system ([0120] of PG Pub). The scoring system assigns a score of 1 to any lung segment occluded with mucus ([0120]).The specification states scoring is performed by radiologists that “review” the scans ([0250] of PG Pub). The specification states a mucus score is determined by the sum of plugs found in lung segments ([0247] of PG Pub). A sum is a mathematical calculation (a judicial exception). Identification based on a review is a mental process.
Such mental observations and evaluations fall within the “mental processes” grouping of abstract idea set forth in the 2019 PEG. 2019 PEG Section I, 84 Fed. Reg. at 52.
Step (d) recites administering to the human an effective amount of one of the recited therapeutics. As evidenced by the specification, these are all known mucolytic agents and type 2 inflammation inhibitors ([0058] [0070] of PG Pub). As evidenced by the specification, mucolytics are well known agents that reduce mucus ([0058] of PG Pub). As evidenced by the specification, type 2 inflammation inhibitors are well known agents that reduce inflammation ([0070] of PG Pub). The specification discloses administration of a mucolytic agent or a type 2 inflammation inhibitor is based on detection of an airway mucus occlusion ([0011]). The specification discloses patients with mucus plugs and inflammation are “likely” to respond to respond to treatment with mucolytic agent or a type 2 inflammation inhibitor ([0011] of PG Pub). Said likeliness is a natural correlation between the presence of mucus/inflammation and the ability of the recited agents to reduce these processes. The administration is based on looking at a scan, seeing a mucus plug, determining the patient is likely to respond and administering a well-known treatment for reducing mucus. The administration is recited at a high level of generality using therapies that are well known, routine and conventional.
Regarding claim 49: In addition to the limitations recited in claim 44, steps (b) and (c) of claim 49 recite using an identified threshold value. Identifying is interpreted to be a mental process. A threshold value is interpreted to be a mathematical equation. These are judicial exceptions.
The subject is identified as having “mucus high” asthma or “mucus high” COPD based on the number of mucus occlusions. The instant specification discloses the following at [0119]:
In embodiments, in applying the scoring methods of the present invention (score range: 0-20, or 0-19 or 1-18) to MDCT lung scans from patients with asthma and COPD, a subgroup with mucus scores >3 (e.g., at least 4) can be identified. These “mucus-high” patients are characterized by more severe airflow obstruction, high levels of airway and systemic type 2 inflammation, and relative resistance to usual asthma and COPD treatments. Notably, this “mucus-high” disease subtype is not revealed by mucus symptoms or by specific tests of lung function. Therefore, these asthmamucus-high and COPDmucus-high patient subgroups represent new disease phenotypes that require treatment interventions that specifically target mucus plugging of the airways.
This is a diagnosis based on a natural correlation between the amount of mucus and the disease phenotype (e.g., “mucus high” asthma/COPD). This correlation is a judicial exception.
Step (d) recites administering an effective amount of one of the mucolytics recited in step d. The remarks made above regarding administration of a well-known drug are reiterated.
Regarding claim 64: In addition to the limitations recited in claim 44, step (c) of claim 64 recites determining a number of lung segments with a mucus occlusion. This is performed by visually looking at the scans. As set forth above, this is a mental process (a judicial exception). Determining whether the number is larger than a threshold is a mental process based on a mathematical concept (the threshold value). Step (d) recites administering an effective amount of one of the mucolytics recited in step d. The remarks made above regarding administration of a well-known drug are reiterated.
Question 2A Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application? No.
While the claims perform scanning using multidetector computed tomography (MCT), this is interpreted to be an insignificant extra-solution activity because the scans are interpreted to be a necessary data gathering step that are required to perform the visual detection and identifying steps
As evidenced by the specification, type 2 inflammation inhibitors are well known agents that reduce inflammation ([0070] of PG Pub). The specification discloses administration of a mucolytic agent or a type 2 inflammation inhibitor is based on detection of an airway mucus occlusion ([0011]). The specification discloses patients with mucus plugs and inflammation are “likely” to respond to respond to treatment with mucolytic agent or a type 2 inflammation inhibitor ([0011] of PG Pub). Said likeliness is a natural correlation between the presence of mucus/inflammation and the ability of the recited agents to reduce these processes. The administration is recited at a high level of generality using therapies that are well known, routine and conventional.
Question 2B: Do the claims recite any additional elements? Yes.
With respect to Step 2B, limitations that were found to be enough to qualify as “significantly more” when recited in a claim with a judicial exception include:
Improvements to another technology or technical field.
Improvements to the functioning of the computer itself.
Applying the judicial exception with, or by use of, a particular machine.
Effecting a transformation or reduction of a particular article to a different state or thing
Adding a specific limitation other than what is well-understood, routine and conventional in the field, or adding unconventional steps that confine the claim to a particular useful application.
Other meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment.
With respect to Step 2B, limitations that were found not to be enough to qualify as “significantly more” when recited in a claim with a judicial exception include:
Adding the words ‘‘apply it’’ (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer
Simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, e.g., a claim to an abstract idea requiring no more than a generic computer to perform generic computer functions that are well understood, routine and conventional activities previously known to the industry
Adding insignificant extrasolution activity to the judicial exception, e.g., mere data gathering in conjunction with a law of nature or abstract idea
Generally linking the use of the judicial exception to a particular technological environment or field of use.
Does the additional element result in the claim amounting to significantly more?
No. Regarding claim 45: the claim recites the radiation dose of the MCT. The scans are considered an insignificant extra-solution activity because it is performed as a necessary data gathering step to make the identification (judicial exception).
Regarding claim 46: The claim recites the location of the mucus plugs. The scans are considered an insignificant extra-solution activity because it is performed as a necessary data gathering step to make the identification (judicial exception).
Claims 47-48 recite the patient has been identified as having asthma or COPD. As set forth above, the specification does not disclose a definition for the term “identify”. Therefore a patient identified as having asthma or COPD is interpreted to have been diagnosed. The specification discloses imaging of the lungs has been utilized in the diagnosis of lung diseases ([0122 PG Pub). At [0131] the specification discloses diagnosis based on an overall score quantifying mucus plugging. At [0197] the specification discloses “determining, based at least on the quantification of mucus plugging, a diagnosis for the subject, the diagnosis comprising a detection of an airway mucus occlusion in at least one lung segment of the subject”. The specification discloses data and scans are “reviewed and discussed by” a “mucus score team” ([0278]). Visual imaging of the lungs to make a diagnosis is a mental observation (a judicial exception) based on a correlation (a natural phenomenon; judicial exception) between the presence of a mucus plug and a disease state.
Regarding claim 49: While the claim recites scans of lung segments using multidetector computed tomography (MCT), the scans are interpreted to be a necessary data gathering step that are required to perform the judicial exception (visualization, counting, adding). Claim 49 recites the patient has been identified as having asthma or COPD. This is interpreted to mean the scans are performed on a patient with one the recited diseases. The disease state does not result in something more than the recited judicial exceptions (i.e., the recited mental processes and mathematical equations). Claim 49 recites administering a mucolytic or type 2 inflammation inhibitor. As set forth above, mucolytics are well known for treating conditions with increased mucus, such as asthma.
Regarding claim 50: The absence of hypersecretion symptoms does not result in some significantly more than the judicial exception (the abstract idea).
Regarding claims 54-55: As evidenced by the specification (supra), mucolytics including recombinant DNAse hypertonic saline and n-acetylcysteine are well known.
Regarding claim 57: the claim recites the radiation of the MCT. The scans are considered an insignificant extra-solution activity because it is performed as a necessary data gathering step to make the identification (judicial exception).
Claims 58 and 60 recite the patient has been identified as having asthma or COPD. The claims are rejected on the same grounds as claims 47-48 above.
Regarding claim 64: While the claim recites scans of lung segments using multidetector computed tomography (MCT), the scans are interpreted to be a necessary data gathering step that are required to perform the judicial exception (visualization, counting, adding). Claim 64 recites administering a mucolytic or type 2 inflammation inhibitor. As set forth above, mucolytics are well known for treating conditions with increased mucus, such as asthma.
Regarding claims 66-67: The claims recite the mucus score. This is interpreted to be a mathematical equation performed by visual assessment of the scans.
Regarding claim 68: The claim recite the threshold value. The threshold is performed as part of a mental assessment for identify the patient as having a “mucus-high” condition. This is a judicial exception.
Regarding claim 69: The claim recite the threshold value. As set forth above, a threshold value is a mathematical equation (a judicial exception).
APPLICANT’S ARGUMENTS
The arguments made in the response filed on 11 June 2025 are acknowledged. The arguments states the drugs recited in the base claims are particular treatments for asthma or COPD. The Applicant argues the claims are analogous to Example 43 of the USPTO guidance issued in the October 2019. The arguments state analysis under 35 USC 101 excludes consideration of whether the additional elements represent well-understood, routine, conventional activity.
EXAMINER’S RESPONSE
The arguments are not persuasive. The arguments do not address the judicial exceptions recited in the base claims. In claim 44 Steps (a), (b) and (c) recite judicial exceptions. While step (d) recites drug administration, the administration is based on looking at a scan, seeing a mucus plug, determining the patient is likely to respond and administering a treatment for reducing mucus. The administration is recited at a high level of generality using therapies that are well known, routine and conventional. Therefore administration does not result in something significantly more than the recited judicial exceptions.
Regarding Example 43 of the subject matter eligibility guidance: The Example relied upon by the Applicant states Step 2A Prong Two evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. Besides the abstract idea (step a of Example 43), the claim recites the additional element of “administering a treatment to the patient having a non-responder phenotype” in limitation (b). Although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated, or what the treatment is, but instead covers any possible treatment that a doctor decides to administer to the patient. The guidance states this limitation is recited at a high level of generality and is ineligible. While dependent claim 2 of Example 43 is eligible, it recites administering a non-steroidal agent capable of treating NAS-3. The guidance states the dependent claim is eligible because the abstract idea is used to identify the patient as being nonresponsive to glucocorticoids, and the patient is then administered a treatment that is particular to that identified phenotype.
Instant claim 44 recites any of the following compositions to treat either asthma or COPD:
n- acetylcysteine, carbocisteine, erdosteine, mecysteine, thioacetyl saccharide, methyl 6-thio-6- deoxy-a-D-galactopyranoside, 5-thiopentyl B-D-galactopyranoside, hypertonic saline, ambroxol, recombinant human Dnase, ivacaftor, lumacaftor, omalizumab, mepolizumab, benralizumab, reslizumab, lebrikizumab, tralokinumab, dupilumab, or fevipiprant.
Claims 49 and 64 recite administering any mucolytic agent or a type 2 inflammation inhibitor. These are not interpreted to be a “particular treatment or prophylaxis” for treating a particular phenotype or disease. Step 2B evaluates whether the claim as a whole amounts to significantly more than the recited judicial exceptions. The treatment step is recited at a high level of generality. The step is considered well-understood routine and conventional.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 49-50, 53-58, 60, 64-65 and 68-69 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 claims contain 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 49 and 64 have been amended to recite detecting a number of occlusions “greater than an identified threshold value” to identify a subject as having mucus-high asthma or mucus-high COPD. At [0131] the specification “mucus-high” subjects whose overall score exceeds a threshold value “(e.g., 3)” ([0131] [0138]). A score of 3 is exemplary. The specification also discloses the threshold can be 3.5 ([0255]). Therefore different thresholds can be used to identify a mucus-high subject. While the specification provides support for a threshold value, there is a lack of guidance from the specification on how to identify all of the threshold values that will diagnose a subject with “mucus high” asthma or COPD.
The written description requirement is in place to ensure that “when a patent claims a genus by its function or result, the specification recites sufficient materials to accomplish that function.” Ariad Pharms. Co. v. Eli Lilly & Co., 94 U.S.P.Q.2d 1161, 1172 (Fed. Cir. 2010) (en banc).
A consideration of the four corners of the specification does not reflect that applicants have actually invented the claimed invention, since the specification does not permit the skilled artisan to determine the conditions required by the claims.
APPLICANT’S ARGUMENTS
The arguments made in the response filed on 11 June 2025 are acknowledged. The arguments state [0255] of the specification discloses the median value of the mucus score in the ‘mucus present’ group was 3.5, and this value was used to divide asthmatics into three mucus subgroups based on mucus score. The arguments also state [0124-0137] describe a treatment system for asthma and COPD with an exemplary threshold of 3.
EXAMINER’S RESPONSE
Claims 49 and 64 require identifying a threshold value that diagnoses a mucus high subject. While the specification discloses a threshold value of 3, this is exemplary. As acknowledged by the Applicant, a threshold can also be a median of different mucus values, such as 3.5. The specification provides support for a threshold value, not does not provide guidance on how to determine the threshold values that can be used for diagnosing a mucus high subject.
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 45, 49-50, 53-58, 60 and 64-65 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 49 and 64 recite using a threshold value to diagnose a mucus-high subject. The specification discloses an exemplary threshold value of 3. The arguments filed on 11 June 2025 state a high mucus score is, for example, > 4. The specification does not define a threshold value. The metes and bounds of a threshold value able to diagnose a mucus-high subject are unclear. Appropriate correction is required. All dependent claims are included in this rejection.
APPLICANT’S ARGUMENTS
The arguments made in the response filed on 11 June 2025 are acknowledged. The arguments state claims 49 and 64 have been amended to recite “an identified threshold value”. The Applicant states it is clear whether or not the person is using an identified threshold value to identify a subject having a mucus-high asthma or COPD without the claim reciting a specific number.
EXAMINER’S RESPONSE
The arguments are not persuasive. The threshold value is required in order to identify a mucus-high human. While the specification discloses examples of threshold values that can be used for diagnosis, the claims are not limited to these values. The metes and bounds of a threshold value able to diagnose mucus-high asthma and COPD in a subject are unclear.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 44, 47-52, 54, 58-60, 63 and 66-68 are rejected under 35 U.S.C. 103 as being unpatentable over Odry et al. (previously cited; Automated Detection of Mucus Plugs within Bronchial Tree in MSCT Images. Proceedings of SPIE-The International Society for Optical Engineering 6511. 2007 pages 1-10), Busayarat et al. (previously cited; Detection of Bronchopulmonary Segments on High-Resolution CT – Preliminary Results. July 2007. Proceedings of the IEEE Symposium on Computer-Based Medical Systems, pages 1-7) and Oscarson et al. (previously cited; Thiosaccharide mucolytic agents. WO2014/153009).
Odry et al. teach pulmonary diseases characterized by chronic airway inflammation, such as Chronic Obstructive Pulmonary (COPD), result in abnormal bronchial wall thickening, lumen dilatation and mucus plugs. Multi-Slice Computed Tomography (MSCT) allows for assessment of these abnormalities, even in airways that are obliquely oriented to the scan plane (Abstract). As evidenced by the instant specification, Multi-Slice Computed Tomography is also known as “multidetector computed tomography (MDCT) ([0051]). Odry teaches MSCT is used to “scan” (supra). The art teaches a method to automatically detect the presence and location of mucus plugs within the peripheral airways (Abstract). Odry “developed a method to detect and locate mucus plugs that completely obstruct the airway tree (page 2, second full paragraph).
Odry teaches accurate assessment of the true extent and severity of disease optimally requires that all foci of mucoid obstruction be identified (see page 9, third paragraph). Mucus plugs play an important role in the natural history of airway disease since they cause chronic airway inflammation, and as such, mucus detection is of high clinical value (see page 10, first paragraph). Odry evaluates patients with known or suspected chronic airway disease (see Results section on page 6). Figure 5 illustrates mucus plugs (hence, occlusions) can be present throughout the bronchial tree of a subject. Examiner notes Figure 5 (bottom right panel), appears to disclose plugs in at least 4 segments of the bronchial tree. It is noted the art teaches “3D visualization allows the radiologists to quickly locate the mucoid foci and determine their extent” (see paragraph above Table 1). Therefore the art teaches (visual) detection of mucus plugs using MSCT scans.
Odry illustrates at least 4 mucus plugs. Therefore the art identifies a mucus score of the subject using the scans.
Claim 44 recite “wherein the subject who has asthma or COPD has no chronic mucus hypersecretion symptoms”. Examiner notes the Instant Specification discloses the following:
[0224] Understanding the role of mucus plugs as a mechanism of airflow obstruction in chronic severe asthma has been held back by methodologic difficulties. To date, imaging studies have not systematically examined the airways in patients with asthma for intraluminal mucus, and studies that have documented the relationship between mucus pathology and airflow have relied on chronic cough and sputum production, a symptom complex known as chronic mucus hypersecretion (CMH) (Vestbo et al., Am J Respir Crit Care Med 153, 1530-1535 (1996); Ulrik et al., Respir Med 99, 1576-1582 (2005)). Reliance on CMH symptoms to identify patients with airway mucus plugs is problematic, because CMH symptoms are often absent in patients with chronic obstructive pulmonary disease who have pathologically proven mucus plugs
[0316]
To determine whether asthmatics could have mucus plugs without CMH symptoms, the frequency of symptoms of CMH in the three mucus plug subgroups was examined. Among 121 patients who completed the cough and sputum questionnaire, 41 (34%) satisfied World Health Organization criteria for chronic mucus hypersecretion (CMH) (cough and sputum production on most days for at least 3 months a year for at least 2 consecutive years) (American Thoracic Society. Am Rev Respir Dis 85, 762-768 (1962)).
Odry does not teach any of the subjects with COPD used in the study has the symptoms identified in the instant specification.
While Odry teaches the bronchial tree is analyzed, it does not explicitly teach each lung segment.
While Odry teaches a patient with COPD, it does not teach administering an effective amount of one of the therapeutics recited in claim 44.
Busayarat segments the bronchial tree using high resolution computed tomography (Abstract). Busayarat et al. teaches “there are twenty bronchopulmonary segments (ten for each lung), which are named after the segmental bronchi that supply them as shown in Figure 1” (see page 1, third paragraph).
PNG
media_image1.png
473
480
media_image1.png
Greyscale
Examiner notes Figure 1 discloses the same segments recited in claim 1.Therefore the subject taught by Oscarson would be expected to have a lung with 20 segments.
Oscarson et al. teach a method of decreasing mucus elasticity or viscosity in a subject
in need thereof comprising administering an effective amount of a thiosaccharide
mucolytic agent ([0006]). In embodiments, the lung is specifically contemplated as the
target organ. In embodiments, the method includes administration of the thiosaccharide
mucolytic agent to the lung of a subject in need thereof ([0070]). The subject suffers a
condition of the lung including chronic obstructive pulmonary disease (COPD), cystic
fibrosis (CF), chronic asthma with airflow obstruction, chronic asthma in which mucus
obstruction is found, acute asthma in which mucus plugs are life threatening,
bronchiectasis, bronchiolitis, allergic bronchopulmonary aspergillosis, pneumonia, and
mechanical ventilator-associated lung injury where mucus pathology is prominent
([0071]). Examiner notes that while Oscarson discloses patients able to spontaneously expectorate sputum samples ([0271]), said patients have cystic fibrosis. The art does not teach patients with COPD or asthma that spontaneously expectorate sputum samples
It would have been obvious to use the method taught by Odry to scan 20 lung segments. One would have been motivated to do so since Odry uses CT to scan the lung and Busayarat teaches uses CT to analyze the lung and teaches the lung has 20 segments. One would have had a reasonable expectation of success since Busayarat teaches CT can be used with 20 lung segments. One would have expected similar results since both references use CT to analyze the lung.
It would have been obvious to combine the teachings of the prior art by treating a patient with COPD using hypertonic saline. One would have been motivated to do so since Odry teaches a patient with COPD and Oscarson teaches hypertonic saline is a known mucolytic used to treat chronic airway diseases ([0003]). The skilled artisan would use a mucolytic to treat a patient with mucus plugs. One would have had a reasonable expectation of success since Oscarson teaches it can be used to treat chronic airway diseases. One would have expected similar results since both references are directed to treating the same disorder. Therefore claim 44 is rendered obvious as claimed.
Claim 48 recites the patient has been identified as having asthma. Odry teaches patients with known or suspected chronic airway disease (supra). The art does not explicitly teach asthma.
As set forth above, Oscarson teaches patients with asthma and COPD have mucus plugs.
It would have been obvious to combine the teachings of the prior art by treating a patient with asthma. One would have been motivated to do so since Odry teaches a method of treating a with known or suspected chronic airway disease and mucus plugs, and Oscarson teaches asthma is characterized by mucus plugs. One would have expected similar results since both references are directed to treating chronic airway disease. Therefore claim 47 is included in this rejection.
Odry teaches a subject with COPD (supra). Therefore claim 48 is included in this rejection.
Regarding independent claim 49: the claim recites the limitations of claim 44 with the following exceptions:
It does not recite a mucus plug is a complete occlusion of a bronchus
It does not recite the therapeutics in step c of claim 44.
It does not recite the human subject does not have a chronic mucus hypersecretion symptom.
The claim recites the human is identified as having mucus-high asthma or mucus-high COPD based on the number being greater than the threshold value.
The teachings of Odry are reiterated.
Odry characterizes both “healthy” and mucus impacted lumens (see last paragraph of page 651110-4). Odry studies clear and mucus impacted airways. The art teaches clean means not filled with secretions (first paragraph of section 2.2.2). To detect mucus, the art teaches the use of a tolerance (first paragraph of page 651110-9). Mucus presence is validated if the correlation with the model is above the mucus tolerance for a number of consecutive sites along the branch (same cited section). The tolerance for a healthy lumen is broadly interpreted to be a threshold. As evidenced by the specification, mucus-high patients have mucus scores >3 ([0119]). Therefore the art visually identifies a patient that is mucus high.
While Odry teaches the bronchial tree is analyzed, it does not explicitly teach each lung segment.
While Odry teaches a patient with COPD, it does not teach administering an effective amount of one of the therapeutics recited in claim 49.
The teachings of Busayarat and Oscarson et al. are reiterated.
It would have been obvious to use the method taught by Odry to scan 20 lung segments. One would have been motivated to do so since Odry uses CT to scan the lung and Busayarat teaches uses CT to analyze the lung and teaches the lung has 20 segments. One would have had a reasonable expectation of success since Busayarat teaches CT can be used with 20 lung segments. One would have expected similar results since both references use CT to analyze the lung.
It would have been obvious to identify a mucus-high phenotype based on a threshold value. One would have been motivated to do so since Odry teaches the use of a healthy lumen tolerance (threshold) to determine mucus presence. One would treat patients with a tolerance above that of a healthy lumen since Odry teaches the disclosed method can be used to detect mucus impacted lumen.
It would have been obvious to combine the teachings of the prior art by treating a patient with COPD using hypertonic saline (hence, a mucolytic). One would have been motivated to do so since Odry teaches a patient with COPD and Oscarson teaches hypertonic saline is a known mucolytic used to treat chronic airway diseases([0003]). The skilled artisan would use a mucolytic to treat a patient with mucus plugs. One would have had a reasonable expectation of success since Oscarson teaches it can be used to treat chronic airway diseases. One would have expected similar results since both references are directed to treating the same disorder. Therefore claim 49 is rendered obvious as claimed.
As set forth above, Odry does not teach patients have chronic mucus hypersecretion symptoms. Therefore claim 50 is included in this rejection.
It would have been obvious to combine the teachings of the prior art by treating a patient with COPD using recombinant human DNAse. One would have been motivated to do so since Odry teaches a patient with COPD and Oscarson teaches DNAse is a known mucolytic used to treat chronic airway diseases ([0003]). The skilled artisan would use a mucolytic to treat a patient with mucus plugs. One would have had a reasonable expectation of success since Oscarson teaches it can be used to treat chronic airway diseases. One would have expected similar results since both references are directed to treating the same disorder. Therefore claim 54 is rendered obvious as claimed.
Claim 58 is rejected on the same grounds as claim 47 above.
Odry teaches a subject with COPD (supra). Therefore claim 60 is included in this rejection.
Odry discloses at least 4 plugs (supra). Therefore claims 66-68 are included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 49 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Odry et al. in view of Busayarat et al. and Sadwoska (Role of N-acetylcysteine in the management of COPD. Therapeutics and Clinical Risk Management 2006:2(1) 3–18).
The teachings of Odry as set forth above are reiterated.
Odry does not teach any of the subjects with COPD used in the study has the symptoms identified in the instant specification.
While Odry teaches the bronchial tree is analyzed, it does not explicitly teach each lung segment.
While Odry teaches a patient with COPD, it does not teach administering an effective amount of one of the therapeutics recited in claim 49.
The teachings of Busayarat as set forth above are reiterated.
Sadowska teaches N-acetylcysteine in the management of COPD. Current treatments for COPD are symptomatic and focus on the bronchodilatation. No effective medication currently exists that may influence the progress of the disease. Therefore, mucolytics like NAC may form an interesting therapeutic approach. Classical mucolytics, like NAC and other thiol reducing agents, degrade the three-dimensional network that forms the mucus by reducing the disulphide bonds (S-S) to a sulfhydryl (SH) bond (-SH) that no longer participates in the cross-linking. They may act on the mucus elasticity and viscosity as well as modulate its production and secretion (see page 427, right column, second paragraph).
It would have been obvious to use the method taught by Odry to scan 20 lung segments. One would have been motivated to do so since Odry uses CT to scan the lung and Busayarat teaches uses CT to analyze the lung and teaches the lung has 20 segments. One would have had a reasonable expectation of success since Busayarat teaches CT can be used with 20 lung segments. One would have expected similar results since both references use CT to analyze the lung.
It would have been obvious to combine the teachings of the prior art by treating a patient with COPD using a mucolytic. One would have been motivated to do so since Odry teaches a patient with COPD and Sadowska teaches N-acetylcysteine in the management of COPD. The skilled artisan would use a mucolytic to treat a patient with mucus plugs. One would have had a reasonable expectation of success since Sadowska teaches N-acetylcysteine can be used to treat COPD. One would have expected similar results since both references are directed to treating the same disorder. Therefore claim 49 is rendered obvious as claimed. Claim 55 recites N-acetylcysteine. Administration of recites N-acetylcysteine is rejected on the same grounds as claim 49. Therefore claim 55 is included in this rejection.
Therefore Applicant’s invention is rendered obvious as claimed.
Claims 49 and 56 are rejected under 35 U.S.C. 103 as being unpatentable over Odry et al. in view of Busayarat et al. and Page et al. (Bifunctional drugs for the treatment of asthma and chronic obstructive pulmonary disease. ERJ Express. Pages 1-8; 2014).
The teachings of Odry as set forth above are reiterated.
Odry does not teach any of the subjects with COPD used in the study has the symptoms identified in the instant specification.
While Odry teaches the bronchial tree is analyzed, it does not explicitly teach each lung segment.
While Odry teaches a patient with COPD, it does not teach administering an effective amount of one of the therapeutics recited in claim 49.
Page teaches dupilumab is a bifunctional drug which can be used to treat asthma or COPD (Table 1).
It would have been obvious to use the method taught by Odry to scan 20 lung segments. One would have been motivated to do so since Odry uses CT to scan the lung and Busayarat teaches uses CT to analyze the lung and teaches the lung has 20 segments. One would have had a reasonable expectation of success since Busayarat teaches CT can be used with 20 lung segments. One would have expected similar results since both references use CT to analyze the lung.
It would have been obvious to combine the teachings of the prior art by treating a patient with COPD using a type 2 inflammation inhibitor. One would have been motivated to do so since Odry teaches a patient with COPD and Page teaches dupilimab (type 2 inflammation inhibitor) can be used to treat asthma or COPD. The skilled artisan would use dupilimab since Odry teaches a patient with COPD and Page teaches dupilimab can be used to treat patients with COPD. One would have had a reasonable expectation of success since Page teaches dupilimab can be used to treat COPD. One would have expected similar results since both references are directed to treating the same disorder. Therefore claim 49 is rendered obvious as claimed. Claim 56 recites dupilimab. Administration of recites N-acetylcysteine is rejected on the same grounds as claim 49. Therefore claim 56 is included in this rejection.
Therefore Applicant’s invention is rendered obvious as claimed.
Claims 45 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Odry in view of Busayarat et al. and Oscarson as applied to claims 44 and 49 above, and further in view of Gomez-Cardona (Influence of radiation dose and reconstruction algorithm in MDCT assessment of airway wall thickness: A phantom study. Med Phys. 2015 Oct; 42(10): 5919–5927).
Claims 44 and 49 are rejected on the grounds set forth above. The teachings of the prior art are reiterated.
While Odry uses MDCT to detect airway mucus plugs. The art is silent regarding the use of low dose radiation MDCT.
Gomez-Cardona teaches wall thickness (WT) is an airway feature of great interest for the assessment of morphological changes in the lung parenchyma (Abstract). Patients with CF have very thick, tenacious airway mucus that impairs the normal mucociliary clearance of the pulmonary airways. This allows bacteria to flourish in the airways, causing recurrent infections. This in turn leads to airway damage, specifically increased wall thickness (WT) and increased diameter (bronchiectasis). Ultimately, this process results in progressive decrease in lung function and ultimately death. Other diseases that may also cause morphological changes in lung parenchyma include chronic obstructive pulmonary disease (COPD) and asthma (first paragraph of Introduction).
Multidetector computed tomography (MDCT) has recently been used to evaluate airway WT, but the potential risk of radiation-induced carcinogenesis—particularly in younger patients—might limit a wider use of MDCT in clinical practice (Abstract). Wall thickness measured from multidetector computed tomography (MDCT) has shown promise as an imaging biomarker for lung diseases such as CF, COPD, asthma, and as a predictor of pulmonary exacerbation. Automated and semiautomated methods of WT quantification from MDCT images offer the promise of improved accuracy and efficiency over existing expert reader scoring systems, particularly for mild disease. However, MDCT uses ionizing radiation that might increase the risk of carcinogenesis later in life,
and pediatric patients may be at two to three times greater risk than adults for a given amount of exposure. Furthermore, as patients’ life expectancy rises, the risk of radiation-induced carcinogenesis might also increase. To promote a wider clinical use of MDCT for the assessment of airway WT, it is highly desirable to reduce radiation dose in MDCT exams. See second paragraph of introduction.
The recent commercial implementation of the statistical model-based iterative reconstruction (MBIR) algorithm, instead of the conventional filtered back projection (FBP) algorithm, has enabled considerable radiation dose reduction in many other clinical applications of MDCT. (Abstract; see third paragraph of Introduction).
Compared with FBP, MBIR improved the contrast-to-noise ratio of the airways, particularly at low radiation dose levels (see Results section). Except for the smallest airway, MBIR enabled significant reduction in both the relative bias and angular standard deviation of the wall thickening, particularly at low radiation dose levels (see Results section).
It would have been obvious to try using low dose MDCT in the method taught by Odry. One would have been motivated to do so since Odry teaches the use of MDCT and Gomez-Cardona teaches using low dose radiation MDCT. One would do so reduce to risk of radiation-induced carcinogenesis as taught by Gomez-Cardona. One would have had a reasonable expectation of success since Gomez-Cardona teaches low dose radiation MDCT can successfully be used for imaging. One would have expected similar results since both references are directed to MDCT. Therefore claims 45 and 57 are included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 46 and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Odry in view of Busayarat et al. and Oscarson as applied to claims 44 and 49 above, and further in view of Gomez-Cardona as evidenced by Charalampidis et al. (Pleura space anatomy. J Thorac Dis 2015;7(S1):S27-S32).
Claims 44 and 49 are rejected on the grounds set forth above. The teachings of the prior art are reiterated.
While Odry uses MDCT to detect airway mucus plugs. The art does not teach the airway mucus plug is not within 2cm of the diaphragmatic pleura and costal pleura.
The teachings of Gomez-Cardona as set forth above are reiterated. Gomez-Cardona The smallest airway (Airway 8) was excluded from analysis since the spatial resolution of the MDCT system was not fine enough to resolve such a small feature (page 5921, right column, first paragraph). The art teaches airway 8 is a “Subsegmental bronchi” (see Table 1).
As evidenced by Charalampidis et al., the costal and diaphragmatic pleura art at the periphery of the lung (see Figure 10). As evidenced by Charalampidis et al. the terminal bronchiole are the smallest airways and are located closest to the pleura of the lung (see Figures 1, 4, 8 and 10).
It would have been obvious to use MDCT to detect airway plugs in areas that are not within 2cm of the diaphragmatic and costal pleura. One would have been motivated to do so since Odry uses MDCT to analyze the lungs and Gomez-Cardona teaches the smallest airways are excluded from analysis since the spatial resolution of the MDCT system was not fine enough to resolve such a small feature. As evidenced by Charalampidis et al., the smallest airways are closest to the costal and diaphragmatic pleura. The skilled artisan would avoid using MDCT to analyze areas closest to the diaphragmatic and costal pleura since Gomez-Cardona teaches MDCT does not have the spatial resolution of the MDCT to analyze these areas. While the art does not explicitly state within 2cm, the skilled artisan would avoid areas that are closest to the claimed pleura for the reasons set forth above. One would have had a reasonable expectation of success since Gomez-Cardona teaches MDCT can be used to analyze larger airways. One would have expected similar results since Odry and Gomez-Cardona are both directed to methods of using MDCT to analyze lungs. Therefore claims 46 and 53 are rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 64-65 and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Odry et al. in view of Rikxoort et al. (Automatic Segmentation of Pulmonary Segments From Volumetric Chest CT Scans. IEEE Transactions On Medical Imaging, Vol. 28 No. 4 2009) and Oscarson et al. (previously cited).
The teachings of Odry as set forth above are reiterated.
Odry et al. teach pulmonary diseases characterized by chronic airway inflammation, such as Chronic Obstructive Pulmonary (COPD), result in abnormal bronchial wall thickening, lumen dilatation and mucus plugs. Multi-Slice Computed Tomography (MSCT) allows for assessment of these abnormalities, even in airways that are obliquely oriented to the scan plane (Abstract). As evidenced by the instant specification, Multi-Slice Computed Tomography is also known as “multidetector computed tomography (MDCT) ([0051]). As set forth above, the art teaches MSCT is used to “scan”. Therefore the art scans using multidetector computed tomography. The art teaches a method to automatically detect the presence and location of mucus plugs within the peripheral airways (Abstract). Odry “developed a method to detect and locate mucus plugs that completely obstruct the airway tree (page 2, second full paragraph),
Odry teaches accurate assessment of the true extent and severity of disease optimally requires that all foci of mucoid obstruction be identified (see page 9, third paragraph). Mucus plugs play an important role in the natural history of airway disease since they cause chronic airway inflammation, and as such, mucus detection is of high clinical value (see page 10, first paragraph). Odry evaluates patients with known or suspected chronic airway disease (see Results section on page 6). Figure 5 illustrates mucus plugs (hence, occlusions) can be present throughout the bronchial tree of a subject. Examiner notes Figure 5 (bottom right panel), appears to disclose plugs in at least 4 segments of the bronchial tree. It is noted the art teaches “3D visualization allows the radiologists to quickly locate the mucoid foci and determine their extent (see paragraph above Table 1). Therefore the art teaches visual dete