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 .
Response to Amendments
Applicant’s amendments to the claims of October 3, 2025, in response to the Office Action of June 2, 2025, are acknowledged.
Response to Arguments
In view of Applicant’s arguments and declaration, the examiner notes that the definition of the claimed subject population is straightforward: a subject with RCC is defined to include: a subject that has a cough that lasts for at least 8 weeks despite treatment. This definition includes subjects with a lung disease, including IPF, COPD, emphysema, chronic bronchitis, asthma, and others with a cough that persists.
The examiner notes that in light of this, the claimed subject population is inclusive of a number of conditions, including but not limited to: asthma, COPD, emphysema, chronic bronchitis, idiopathic pulmonary fibrosis, asthma, and many others. The prior art teaches treating these same subjects with nalbuphine. As such, rejections are set forth below.
This action is a Non-final action. Rhame et al., (US2008/0207667) is applied; Jegga et al., (US2019/0247373) (filed July 13, 2017) is also applied which teaches treating idiopathic pulmonary fibrosis (IPF) with nalbuphine; Pavard et al., (The Lancet, Volume 371, Issue 9621, 1375 – 1384) and Ryan et al. (Expert Opinion on Pharmacotherapy, vol. 19, no. 7, p. 687-711, April 2018) are also applied.
Further, a Double Patenting Rejection is set forth over parent U.S. Pat. No. 11,660,296, which is directed to treating IPF with nalbuphine, as well as U.S. provisional application no. 19/270,674.
Also see the following noting the state of the art and the high prevalence of persistent chronic cough in claimed subjects. This is duplicative and is not used in a rejection at this time.
Lin, “Combined pulmonary fibrosis and emphysema (CPFE): an entity different from emphysema or pulmonary fibrosis alone,” J Thorac Dis. 2015 Apr;7(4):767-79. Those with IPF are noted to have cough in 73-86% of subjects in the late stage.
Status of the Claims
Claims 1-29 are pending and examined.
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.
Claims 1-28 are rejected under 35 U.S.C. 103 as being unpatentable over Jegga et al., (US2019/0247373) (filed July 13, 2017), in view of Rhame et al., (US2008/0207667), and in view of Pavard et al., (The Lancet, Volume 371, Issue 9621, 1375 – 1384), and in view of Ryan et al. (Expert Opinion on Pharmacotherapy, vol. 19, no. 7, p. 687-711, April 2018).
Jegga teaches a method for treating idiopathic pulmonary fibrosis (IPF) by administering an opioid receptor inhibitor including nalbuphine. See prior art claims 1 and 5. Nalbuphine can be administered orally to treat the following conditions: lung fibrosis, pulmonary fibrosis, cystic fibrosis, idiopathic pulmonary fibrosis (IPF), radiation-induced lung injury, and others. See prior art claims 13, 14, 20, and 21. Nalbuphine is listed as one of less than 50 agents in paragraph 45 and prior art claim 5. While there is some picking and choosing, a POSA would certainly read Jegga and understand that nalbuphine can be administered orally to treat IPF.
Claims 1, 2, and 5 of Jegga are shown/described below:
1. A method for treating an animal for fibrosis, comprising one or more administrations of one or more compositions comprising one or more opioid receptor inhibitors, wherein the compositions may be the same or different if there is more than one administration.
21. The method of any of claims 1-20, wherein the method is for treating lung fibrosis, pulmonary fibrosis, cystic fibrosis, idiopathic pulmonary fibrosis (IPF), radiation-induced lung injury, skin fibrosis, kidney fibrosis, heart fibrosis, atrial fibrosis, endomyocardial fibrosis, or myocardial infarction.
Claim 5 of Jegga is directed to a compound that can treat these conditions. The compound includes nalbuphine of approximately 50 agents.
While this is not anticipatory, Jegga et al. are persons of ordinary skill in the art (POSA) that would certainly understand that nalbuphine can be used to treat IPF.
Jegga does not explicitly select nalbuphine among the limited listing of active agent. Rhame is applied below because it strengthens the teachings of Jegga.
Rhame teaches treating respiratory diseases with nalbuphine. See par. 1. Nalbuphine is known to have a potency with respect to analgesia that is equivalent to morphine on a milligram basis. See par. 3. Controlled release formulations are known in the art. See par. 9. Rhame teaches nalbuphine for treating respiratory diseases. See par. 12. The ability to treat respiratory diseases was unexpected in view of the side effect of respiratory depression. See par. 15. A salt of nalbuphine can also be used and it this includes the hydrochloride form. See par. 21. Further, treatment includes treatment of respiratory diseases and their symptoms, including: “asthma, cough, cough with pruritis, chronic obstructive pulmonary disease, dyspnea, the symptoms of the listed diseases, and other respiratory diseases and their symptoms.” See par. 17. Conditions also include colds, flu, asthma, bronchitis, nasal congestion, lower respiratory symptoms, cough, and others. See par. 24. These conditions are chronic/persistent. Dosage can be optimized and frequency of administration “can be readily determined by one of ordinary skill in the art” using known techniques. See par. 37. Formulations can be in many forms including sustained release capsules, tablets, and more. See par. 54. Rhame claims treating symptoms associated with diseases affecting the respiratory or pulmonary system of humans and those symptoms include: cough with pruritis, COPD, dyspnea, pulmonary hypertension, or pulmonary symptoms, distress associated with cardiac disease, among others. See prior art claims 1 and 2. Dosages can range from 0.285 to 0.57 mg/kg per day and from a broad range of 0.1 to 1 mg/kg per day. This includes about 20 mg to 40 mg per day and from 7 mg to 70 mg per day. See par. 40. Magnesium stearate and other excipients are contemplated. Tablets, e.g., can be made to sustain release over time. See par. 56.
Rhame teaches nalbuphine for treating pulmonary conditions as the agent to be used.
Pavard teaches that chronic cough is a common symptom of almost all chronic respiratory conditions and is responsible for over a third of referrals to pulmonology:
Chronic cough is defined as cough lasting for more than 8 weeks.1 This definition is based on evidence that a cough lasting longer than this duration is unlikely to be due to a respiratory tract infection.2 Chronic cough is a common symptom of almost all chronic respiratory, and some non-respiratory conditions. Several recognisable causes of chronic cough, such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, lung cancer, an inhaled foreign body, pulmonary tuberculosis, sarcoidosis, idiopathic pulmonary fibrosis, and heart failure will be obvious after clinical assessment, spirometry, and chest radiography... Cough is the primary focus of referral in 38% and the sole focus in 10% of patients seen in a typical adult respiratory clinic.
See page 1375 (emphasis added).
Ryan teaches that chronic cough “that persists despite assessment and treatment according to an accepted guideline is termed refractory chronic cough, idiopathic chronic cough, or unexplained cough” (Ryan, page 687). Therefore, refractory chronic cough, idiopathic chronic cough, or unexplained cough are considered synonyms in the art. Additionally, Ryan teaches that morphine is useful in the treatment of refractory chronic cough (CC): “The primary available therapies for refractory CC include gabapentin, speech pathology, and morphine.” See p708.
Rhame teaches nalbuphine has similar effects to morphine in treating cough, and both Pavard and Ryan teach morphine will treat refractory chronic cough. Thus, even if Rhame and Jegga were somehow interpreted as not including RCC, the combination of prior art provides a proper nexus for treatment of the same. More particularly, the analgesic and respiratory potential of nalbuphine are noted to be similar to that of morphine. See par.’s 3, 6, 7, and others.
It would have been prima facie obvious prior to the filing of the instant application to arrive at the claimed methods in view of Jegga, Rhame, Pavard, and Ryan. One would be motivated to do so because Jegga and Rhame teach treating conditions, including IPF, COPD, and other chronic respiratory conditions with similar dosages of nalbuphine. This communicates that regardless of the mechanism by which cough is existing, there is a reasonable and predictable expectation that the claimed agent will treat the same. Further, a refractory cough would have a reasonable and predictable expectation of success in being treated because Rhame teaches treating cough caused by chronic persistent conditions and notes that Nalbuphine is similar to morphine in the analgesic and respiratory potential. Morphine is taught to treat RCC. Further, Baichwal teaches extended release formulations comprising the same components claimed for administration by the same route of administration. Moreover, Pavard teaches that most chronic respiratory conditions including many taught by Rhame include a cough that lasts for more than 8 weeks despite treatment. A POSA would understand from Rhame that a cough that is chronic and associated with an underlying condition is refractory and will remain despite treatment. Ryan provides additional explanation in this regard because morphine which is similar to nalbuphine is shown to treat RCC. This provides further reasonable and predictable expectation of success in view of the prior art that the claimed method will be successfully undertaken.
With regard to claims 24-26, it would appear that when an optimized dosage is administered to treat a chronic cough in a subject it would yield a claimed improvement. It appears that a level of improvement is a result of the claimed process steps that are positively recited and those steps are rendered obvious as described herein by the cited prior art. The burden is on Applicant to explain and show why the claimed levels of improvement do not result from the active steps taught and rendered obvious by the prior art. A cough monitoring device merely quantifies the result of existing treatment and this can include any mode of tracking or counting the same. This could include writing down the count with a pencil and paper, e.g.
Claims 1-29 are rejected under 35 U.S.C. 103 as being unpatentable over Rhame (US2008/0207667), in view of Pavard et al., (The Lancet, Volume 371, Issue 9621, 1375 – 1384), in view of Ryan et al. (Expert Opinion on Pharmacotherapy, vol. 19, no. 7, p. 687-711, April 2018), and in view of Baichwal et al., (U.S. Pat. No. 8,394,812) (applicant is co-inventor of the ‘812 patent).
Rhame teaches treating respiratory diseases with nalbuphine. See par. 1. Nalbuphine is known to have a potency with respect to analgesia that is equivalent to morphine on a milligram basis. See par. 3. Controlled release formulations are known in the art. See par. 9. Rhame teaches nalbuphine for treating respiratory diseases. See par. 12. The ability to treat respiratory diseases was unexpected in view of the side effect of respiratory depression. See par. 15. A salt of nalbuphine can also be used and it this includes the hydrochloride form. See par. 21. Further, treatment includes treatment of respiratory diseases and their symptoms, including: “asthma, cough, cough with pruritis, chronic obstructive pulmonary disease, dyspnea, the symptoms of the listed diseases, and other respiratory diseases and their symptoms.” See par. 17. Conditions also include colds, flu, asthma, bronchitis, nasal congestion, lower respiratory symptoms, cough, and others. See par. 24. These conditions are chronic/persistent. Dosage can be optimized and frequency of administration “can be readily determined by one of ordinary skill in the art” using known techniques. See par. 37. Formulations can be in many forms including sustained release capsules, tablets, and more. See par. 54. Rhame claims treating symptoms associated with diseases affecting the respiratory or pulmonary system of humans and those symptoms include: cough with pruritis, COPD, dyspnea, pulmonary hypertension, or pulmonary symptoms, distress associated with cardiac disease, among others. See prior art claims 1 and 2. Dosages can range from 0.285 to 0.57 mg/kg per day and from a broad range of 0.1 to 1 mg/kg per day. This includes about 20 mg to 40 mg per day and from 7 mg to 70 mg per day. See par. 40. Magnesium stearate and other excipients are contemplated. Tablets, e.g., can be made to sustain release over time. See par. 56.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Pavard teaches that chronic cough is a common symptom of almost all chronic respiratory conditions and is responsible for over a third of referrals to pulmonology:
Chronic cough is defined as cough lasting for more than 8 weeks.1 This definition is based on evidence that a cough lasting longer than this duration is unlikely to be due to a respiratory tract infection.2 Chronic cough is a common symptom of almost all chronic respiratory, and some non-respiratory conditions. Several recognisable causes of chronic cough, such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, lung cancer, an inhaled foreign body, pulmonary tuberculosis, sarcoidosis, idiopathic pulmonary fibrosis, and heart failure will be obvious after clinical assessment, spirometry, and chest radiography... Cough is the primary focus of referral in 38% and the sole focus in 10% of patients seen in a typical adult respiratory clinic.
See page 1375 (emphasis added).
Ryan teaches that chronic cough “that persists despite assessment and treatment according to an accepted guideline is termed refractory chronic cough, idiopathic chronic cough, or unexplained cough” (Ryan, page 687). Therefore, refractory chronic cough, idiopathic chronic cough, or unexplained cough are considered synonyms in the art. Additionally, Ryan teaches that morphine is useful in the treatment of refractory chronic cough (CC): “The primary available therapies for refractory CC include gabapentin, speech pathology, and morphine.” See p708.
Rhame teaches nalbuphine has similar effects to morphine in treating cough, and both Pavard and Ryan teach morphine will treat refractory chronic cough.
Rhame does not teach the claimed formulation of claim 29.
Baichwal teaches sustained release formulations of nalbuphine or salts therefor comprising oral unit dosages having locust bean gum, xanthan gum, mannitol, and calcium sulfate dihydrate. See col. 2, lines 43-47. Nalbuphine is present from 1 to 100 mg, or about 20 mg, or about 40 mg, or about 60 mg. See col. 5, lines 14-15. Further, hydroxypropyl celluloses can be used as exemplary hydrophilic compounds. Fumaric acid is taught for 180 mg formulations. See Examples 24-28.
It would have been prima facie obvious prior to the filing of the instant application to arrive at the claimed methods in view of Rhame, Pavard, and Ryan. One would be motivated to do so because Rhame teach treating conditions, including COPD, and other chronic respiratory conditions with similar dosages of nalbuphine. This communicates that regardless of the mechanism by which cough is existing, there is a reasonable and predictable expectation that the claimed agent will treat the same. Further, a refractory cough would have a reasonable and predictable expectation of success in being treated because Rhame teaches treating cough caused by chronic persistent conditions. Further, Baichwal teaches extended release formulations comprising the same components claimed for administration by the same route of administration. Moreover, Pavard teaches that most chronic respiratory conditions including many taught by Rhame include a cough that lasts for more than 8 weeks despite treatment. A POSA would understand from Rhame that a cough that is chronic and associated with an underlying condition is refractory and will remain despite treatment. Ryan provides additional explanation in this regard because morphine which is similar to nalbuphine is shown to treat RCC. This provides further reasonable and predictable expectation of success in view of the prior art that the claimed method will be successfully undertaken. A refractory cough would have a reasonable and predictable expectation of success in being treated because Rhame teaches treating cough caused by chronic persistent conditions and notes that Nalbuphine is similar to morphine in the analgesic and respiratory potential. Morphine is taught to treat RCC. Further, Baichwal teaches extended release formulations comprising the same components claimed for administration by the same route of administration. Moreover, Pavard teaches that most chronic respiratory conditions including many taught by Rhame include a cough that lasts for more than 8 weeks despite treatment. A POSA would understand from Rhame that a cough that is chronic and associated with an underlying condition is refractory and will remain despite treatment. Ryan provides additional explanation in this regard because morphine which is similar to nalbuphine is shown to treat RCC. This provides further reasonable and predictable expectation of success in view of the prior art that the claimed method will be successfully undertaken.
With regard to claims 24-26, it would appear that when an optimized dosage is administered to treat a cough in a subject it would yield a claimed improvement. It appears that a level of improvement is a result of the claimed process steps that are positively recited and those steps are rendered obvious as described herein by the cited prior art. The burden is on Applicant to explain and show why the claimed levels of improvement do not result from the active steps taught and rendered obvious by the prior art. A cough monitoring device merely quantifies the result of existing treatment and this can include any mode of tracking or counting the same. This could include writing down the count with a pencil and paper, e.g.
Claims 1-28 are rejected under 35 U.S.C. 103 as being unpatentable over Rhame (US2008/0207667), in view of Pavard et al., (The Lancet, Volume 371, Issue 9621, 1375 – 1384), in view of Ryan et al. (Expert Opinion on Pharmacotherapy, vol. 19, no. 7, p. 687-711, April 2018), and in view of Sciascia et al., (U.S. Pat. No. 8,637,538).
Rhame teaches treating respiratory diseases with nalbuphine. See par. 1. Nalbuphine is known to have a potency with respect to analgesia that is equivalent to morphine on a milligram basis. See par. 3. Controlled release formulations are known in the art. See par. 9. Rhame teaches nalbuphine for treating respiratory diseases. See par. 12. The ability to treat respiratory diseases was unexpected in view of the side effect of respiratory depression. See par. 15. A salt of nalbuphine can also be used and it this includes the hydrochloride form. See par. 21. Further, treatment includes treatment of respiratory diseases and their symptoms, including: “asthma, cough, cough with pruritis, chronic obstructive pulmonary disease, dyspnea, the symptoms of the listed diseases, and other respiratory diseases and their symptoms.” See par. 17. Conditions also include colds, flu, asthma, bronchitis, nasal congestion, lower respiratory symptoms, cough, and others. See par. 24. These conditions are chronic/persistent. Dosage can be optimized and frequency of administration “can be readily determined by one of ordinary skill in the art” using known techniques. See par. 37. Formulations can be in many forms including sustained release capsules, tablets, and more. See par. 54. Rhame claims treating symptoms associated with diseases affecting the respiratory or pulmonary system of humans and those symptoms include: cough with pruritis, COPD, dyspnea, pulmonary hypertension, or pulmonary symptoms, distress associated with cardiac disease, among others. See prior art claims 1 and 2. Dosages can range from 0.285 to 0.57 mg/kg per day and from a broad range of 0.1 to 1 mg/kg per day. This includes about 20 mg to 40 mg per day and from 7 mg to 70 mg per day. See par. 40. Magnesium stearate and other excipients are contemplated. Tablets, e.g., can be made to sustain release over time. See par. 56.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Pavard teaches that chronic cough is a common symptom of almost all chronic respiratory conditions and is responsible for over a third of referrals to pulmonology:
Chronic cough is defined as cough lasting for more than 8 weeks.1 This definition is based on evidence that a cough lasting longer than this duration is unlikely to be due to a respiratory tract infection.2 Chronic cough is a common symptom of almost all chronic respiratory, and some non-respiratory conditions. Several recognisable causes of chronic cough, such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, lung cancer, an inhaled foreign body, pulmonary tuberculosis, sarcoidosis, idiopathic pulmonary fibrosis, and heart failure will be obvious after clinical assessment, spirometry, and chest radiography... Cough is the primary focus of referral in 38% and the sole focus in 10% of patients seen in a typical adult respiratory clinic.
See page 1375 (emphasis added).
Ryan teaches that chronic cough “that persists despite assessment and treatment according to an accepted guideline is termed refractory chronic cough, idiopathic chronic cough, or unexplained cough” (Ryan, page 687). Therefore, refractory chronic cough, idiopathic chronic cough, or unexplained cough are considered synonyms in the art. Additionally, Ryan teaches that morphine is useful in the treatment of refractory chronic cough (CC): “The primary available therapies for refractory CC include gabapentin, speech pathology, and morphine.” See p708.
Rhame teaches nalbuphine has similar effects to morphine in treating cough, and both Pavard and Ryan teach morphine will treat refractory chronic cough.
Rhame does not teach the claimed formulation of claim 29.
Sciascia teaches oral compositions comprising 15 mg to 60 mg once or twice a day and then titrated at increments of 15 mg to 60 mg to an effective dose. See col. 1, lines 60-62.
“In certain embodiments, the anti-pruritus agent is administered in an oral extended release formulation comprising nalbuphine hydrochloride, mannitol, hydroxypropyl cellulose, locust bean gum, xanthan gum, calcium sulfate dihydrate and magnesium stearate.” Col. 3, lines 5-10.
It would have been prima facie obvious prior to the filing of the instant application to arrive at the claimed methods in view of Rhame and Sciascia. One would be motivated to do so because Rhame teaches similar dosages for the same route of administration to treat cough deriving from many pathologies and treating and preventing cough associated with and a symptom of many pathologies. This communicates that regardless of the mechanism by which cough is existing, there is a reasonable and predictable expectation that the claimed agent will treat the same. A refractory cough would have a reasonable and predictable expectation of success in being treated because Rhame teaches treating cough caused by chronic persistent conditions and notes that Nalbuphine is similar to morphine in the analgesic and respiratory potential. Morphine is taught to treat RCC. Moreover, Pavard teaches that most chronic respiratory conditions including many taught by Rhame include a cough that lasts for more than 8 weeks despite treatment. A POSA would understand from Rhame that a cough that is chronic and associated with an underlying condition is refractory and will remain despite treatment. Ryan provides additional explanation in this regard because morphine which is similar to nalbuphine is shown to treat RCC. This provides further reasonable and predictable expectation of success in view of the prior art that the claimed method will be successfully undertaken.
With regard to claims 24-26, it would appear that when an optimized dosage is administered to treat a cough in a subject it would yield a claimed improvement. It appears that a level of improvement is a result of the claimed process steps that are positively recited and those steps are rendered obvious as described herein by the cited prior art. The burden is on Applicant to explain and show why the claimed levels of improvement do not result from the active steps taught and rendered obvious by the prior art. A cough monitoring device merely quantifies the result of existing treatment and this can include any mode of tracking or counting the same. This could include writing down the count with a pencil and paper, e.g.
Claims 1-29 are rejected under 35 U.S.C. 103 as being unpatentable over Jegga et al., (US2019/0247373) (filed July 13, 2017), in view of Rhame et al., (US2008/0207667), and in view of Pavard et al., (The Lancet, Volume 371, Issue 9621, 1375 – 1384), in view of Ryan et al. (Expert Opinion on Pharmacotherapy, vol. 19, no. 7, p. 687-711, April 2018), in view of Baichwal et al., (U.S. Pat. No. 8,394,812) (applicant is co-inventor of the ‘812 patent), and in view of Sciascia et al., (U.S. Pat. No. 8,637,538).
Jegga teaches a method for treating idiopathic pulmonary fibrosis (IPF) by administering an opioid receptor inhibitor including nalbuphine. See prior art claim 1 and 5. Further, the agent can be administered orally and can be used to treat the following conditions: lung fibrosis, pulmonary fibrosis, cystic fibrosis, idiopathic pulmonary fibrosis (IPF), radiation-induced lung injury, and others. See prior art claims 13, 14, 20, and 21. Nalbuphine is listed as one of less than 50 agents in paragraph 45 and prior art claim 5. While there is some picking and choosing, a POSA would certainly read Jegga and understand that nalbuphine can be administered orally to treat IPF.
Claims 1, 2, and 5 are shown/described below:
1. A method for treating an animal for fibrosis, comprising one or more administrations of one or more compositions comprising one or more opioid receptor inhibitors, wherein the compositions may be the same or different if there is more than one administration.
21. The method of any of claims 1-20, wherein the method is for treating lung fibrosis, pulmonary fibrosis, cystic fibrosis, idiopathic pulmonary fibrosis (IPF), radiation-induced lung injury, skin fibrosis, kidney fibrosis, heart fibrosis, atrial fibrosis, endomyocardial fibrosis, or myocardial infarction.
Claim 5 of Jegga is directed to a compound that can treat these conditions. The compound includes nalbuphine of approximately 50 agents.
While this is not anticipatory, Jegga et al. are POSA that would certainly understand that nalbuphine can be used to treat IPF.
Jegga does not explicitly select nalbuphine among the limited listing of active agent. Rhame strengthens the teachings of Jegga.
Rhame teaches treating respiratory diseases with nalbuphine. See par. 1. Nalbuphine is known to have a potency with respect to analgesia that is equivalent to morphine on a milligram basis. See par. 3. Controlled release formulations are known in the art. See par. 9. Rhame teaches nalbuphine for treating respiratory diseases. See par. 12. The ability to treat respiratory diseases was unexpected in view of the side effect of respiratory depression. See par. 15. A salt of nalbuphine can also be used and it this includes the hydrochloride form. See par. 21. Further, treatment includes treatment of respiratory diseases and their symptoms, including: “asthma, cough, cough with pruritis, chronic obstructive pulmonary disease, dyspnea, the symptoms of the listed diseases, and other respiratory diseases and their symptoms.” See par. 17. Conditions also include colds, flu, asthma, bronchitis, nasal congestion, lower respiratory symptoms, cough, and others. See par. 24. These conditions are chronic/persistent. Dosage can be optimized and frequency of administration “can be readily determined by one of ordinary skill in the art” using known techniques. See par. 37. Formulations can be in many forms including sustained release capsules, tablets, and more. See par. 54. Rhame claims treating symptoms associated with diseases affecting the respiratory or pulmonary system of humans and those symptoms include: cough with pruritis, COPD, dyspnea, pulmonary hypertension, or pulmonary symptoms, distress associated with cardiac disease, among others. See prior art claims 1 and 2. Dosages can range from 0.285 to 0.57 mg/kg per day and from a broad range of 0.1 to 1 mg/kg per day. This includes about 20 mg to 40 mg per day and from 7 mg to 70 mg per day. See par. 40. Magnesium stearate and other excipients are contemplated. Tablets, e.g., can be made to sustain release over time. See par. 56.
Rhame teaches nalbuphine for treating pulmonary conditions as the agent used.
Pavard teaches that chronic cough is a common symptom of almost all chronic respiratory conditions and is responsible for over a third of referrals to pulmonology:
Chronic cough is defined as cough lasting for more than 8 weeks.1 This definition is based on evidence that a cough lasting longer than this duration is unlikely to be due to a respiratory tract infection.2 Chronic cough is a common symptom of almost all chronic respiratory, and some non-respiratory conditions. Several recognisable causes of chronic cough, such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, lung cancer, an inhaled foreign body, pulmonary tuberculosis, sarcoidosis, idiopathic pulmonary fibrosis, and heart failure will be obvious after clinical assessment, spirometry, and chest radiography... Cough is the primary focus of referral in 38% and the sole focus in 10% of patients seen in a typical adult respiratory clinic.
See page 1375 (emphasis added).
Ryan teaches that chronic cough “that persists despite assessment and treatment according to an accepted guideline is termed refractory chronic cough, idiopathic chronic cough, or unexplained cough” (Ryan, page 687). Therefore, refractory chronic cough, idiopathic chronic cough, or unexplained cough are considered synonyms in the art. Additionally, Ryan teaches that morphine is useful in the treatment of refractory chronic cough (CC): “The primary available therapies for refractory CC include gabapentin, speech pathology, and morphine.” See p708.
Rhame teaches nalbuphine has similar effects to morphine in treating cough, and both Pavard and Ryan teach morphine will treat refractory chronic cough.
Baichwal teaches sustained release formulations of nalbuphine or salts therefor comprising oral unit dosages having locust bean gum, xanthan gum, mannitol, and calcium sulfate dihydrate. See col. 2, lines 43-47. Nalbuphine is present from 1 to 100 mg, or about 20 mg, or about 40 mg, or about 60 mg. See col. 5, lines 14-15. Further, hydroxypropyl celluloses can be used as exemplary hydrophilic compounds. Fumaric acid is taught for 180 mg formulations. See Examples 24-28.
Sciascia teaches oral compositions comprising 15 mg to 60 mg once or twice a day and then titrated at increments of 15 mg to 60 mg to an effective dose. See col. 1, lines 60-62.
“In certain embodiments, the anti-pruritus agent is administered in an oral extended release formulation comprising nalbuphine hydrochloride, mannitol, hydroxypropyl cellulose, locust bean gum, xanthan gum, calcium sulfate dihydrate and magnesium stearate.” Col. 3, lines 5-10.
It would have been prima facie obvious prior to the filing of the instant application to arrive at the claimed methods in view of Rhame and Sciascia. One would be motivated to do so because Rhame teaches similar dosages for the same route of administration to treat cough deriving from many pathologies and treating and preventing cough associated with and a symptom of many pathologies. This communicates that regardless of the mechanism by which cough is existing, there is a reasonable and predictable expectation that the claimed agent will treat the same. A refractory cough would have a reasonable and predictable expectation of success in being treated because Rhame teaches treating cough caused by chronic persistent conditions and notes that Nalbuphine is similar to morphine in the analgesic and respiratory potential. Morphine is taught to treat RCC. Further, Baichwal teaches extended release formulations comprising the same components claimed for administration by the same route of administration. Moreover, Pavard teaches that most chronic respiratory conditions including many taught by Rhame include a cough that lasts for more than 8 weeks despite treatment. A POSA would understand from Rhame that a cough that is chronic and associated with an underlying condition is refractory and will remain despite treatment. Ryan provides additional explanation in this regard because morphine which is similar to nalbuphine is shown to treat RCC. This provides further reasonable and predictable expectation of success in view of the prior art that the claimed method will be successfully undertaken.
With regard to claims 24-26, it would appear that when an optimized dosage is administered to treat a cough in a subject it would yield a claimed improvement. It appears that a level of improvement is a result of the claimed process steps that are positively recited and those steps are rendered obvious as described herein by the cited prior art. The burden is on Applicant to explain and show why the claimed levels of improvement do not result from the active steps taught and rendered obvious by the prior art. A cough monitoring device merely quantifies the result of existing treatment and this can include any mode of tracking or counting the same. This could include writing down the count with a pencil and paper, e.g.
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 1-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,660,296, in view of Jegga et al., (US2019/0247373) (filed July 13, 2017), in view of Rhame et al., (US2008/0207667), and in view of Pavard et al., (The Lancet, Volume 371, Issue 9621, 1375 – 1384), and in view of Ryan et al. (Expert Opinion on Pharmacotherapy, vol. 19, no. 7, p. 687-711, April 2018). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘296 patent are directed to treating IPF and chronic cough associated therewith. Further, nalbuphine is taught by the cited prior art to treat chronic cough and refractory chronic cough in conditions including by not limited to IPF. Moreover, Pavard notes that chronic cough is associated with many conditions known to be treated by nalbuphine. Even further, morphine is similar to nalbuphine in its’ ability to treat cough and morphine is established as a treatment for RCC. As such, there is a reasonable and predictable expectation of success in arriving at the claimed invention in view of the ‘296 patent and the prior art.
Claims 1-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent Application No. 19/270,674, in view of Jegga et al., (US2019/0247373) (filed July 13, 2017), in view of Rhame et al., (US2008/0207667), and in view of Pavard et al., (The Lancet, Volume 371, Issue 9621, 1375 – 1384), and in view of Ryan et al. (Expert Opinion on Pharmacotherapy, vol. 19, no. 7, p. 687-711, April 2018). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘674 patent include interstitial lung disease (ILD) and claim 11 notes that IPF is a species of ILD. IPF and ILD are each conditions associated with chronic cough. Moreover, Pavard notes that chronic cough is associated with many conditions known to be treated by nalbuphine. Even further, morphine is similar to nalbuphine in its’ ability to treat cough and morphine is established as a treatment for RCC. As such, there is a reasonable and predictable expectation of success in arriving at the claimed invention in view of the ‘296 patent and the prior art.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
As such, no claim is allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D. BARSKY whose telephone number is (571)272-2795. The examiner can normally be reached on 9-5 M-F.
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/JARED BARSKY/Primary Examiner, Art Unit 1628